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Adama Mickiewicza W Poznaniu.Budapesti Muszaki Es Gazdasagtudomanyi EgyetemThe Provost, Fellows, Foundation Scholars & The Other Members Of Board Of The College Of The Holy & Undivided Trinity Of Queen Elizabeth Near DublinThe University Of ManchesterTechnische Universiteit Delft%European Molecular Biology Laboratory$Universita Commerciale Luigi BocconiMasarykova Univerzita3Norges Teknisk-Naturvitenskapelige Universitet NtnuUniversite De Bordeaux^Institut Francais Des Sciences Et Technologies Des Transports, De L'Amenagement Et Des ReseauxInstituto Superior Tecnico5University Of Portsmouth Higher Education CorporationUniversitaet OsnabrueckUniversity Of BathAUniversity College Dublin, National University Of Ireland, DublinWAssociation Pour La Recherche Et Le Developpement Des Methodes Et Processus Industriels7Stichting Sron Netherlands Institute For Space ResearchUniversitat De ValenciaHelsingin YliopistoUniversidad Autonoma De MadridThe University Of LiverpoolUniversita Degli Studi Di PaviaUniversity Of LeedsAalborg UniversitetEcole Normale Superieure<Magyar Tudomanyos Akademia Tarsadalomtudomanyi KutatokozpontKFundacion De La Comunidad Valenciana Centro De Investigacion PrincipefelipeUniversitetet I BergenFundacion Imdea Materiales!Universidad Politecnica De MadridTechnische Universitaet Berlin!Norsk Institutt For Luftforskning-Eidgenoessische Technische Hochschule Zuerich#Friedrich-Schiller-Universitat JenaUniversiteit Antwerpen9Koninklijke Nederlandse Akademie Van Wetenschappen - Knaw'Heinrich-Heine-Universitaet DuesseldorfPhilipps Universitaet Marburg,Instytut Matematyczny Polskiej Akademii Nauk!Universita Degli Studi Di TriesteBilkent niversitesi-Technische Universitaet Bergakademie FreibergUniversity Of SussexUniversiteit Twente3Imperial College Of Science Technology And Medicine Tty-SaatioThe University Of StirlingEScuola Superiore Di Studi Universitari E Di Perfezionamento Sant'AnnaEotvos Lorand Tudomanyegyetem!Universitat Autonoma De Barcelona9Magyar Tudomanyos Akademia Energiatudomanyi Kutatokozpont7Fundacio Institut De Recerca De L'Energia De Catalunya Universitaet Stuttgart"Consiglio Nazionale Delle RicercheForschungszentrum Julich Gmbh$Universitat Politecnica De CatalunyaKing'S College LondonThe University Of ExeterJyvaskylan YliopistoUniversitaet Siegen:Fondazione Per La Ricerca E La Cura Dei Linfomi Nel TicinoUniversite De Fribourg Technische Universitaet MuenchenThe University Of Reading$Albert-Ludwigs-Universitaet FreiburgHeriot-Watt University4Friedrich Miescher Institute For Biomedical Research$Johannes Gutenberg-Universitat MainzUniversitat Des Saarlandes4Rheinisch-Westfaelische Technische Hochschule AachenBFrom longitudinal proteomics to dynamic individualized diagnosticsTaming non convexity?In many important areas and applications of science one has to solve non convex optimization problems and ideally and ultimately one would like to find the global optimum. However in most cases one is faced with NP-hard problems and therefore in practice one has been often satisfied with only a local optimum obtained with some ad-hoc (local) optimization algorithm. TAMING intends to provide a systematic methodology for solving hard non convex polynomial optimization problems in all areas of science. Indeed the last decade has witnessed the emergence of Polynomial Optimization as a new field in which powerful positivity certificates from real algebraic geometry have permitted to develop an original and systematic approach to solve (at global optimality) optimization problems with polynomial (and even semi-algebraic) data. The backbone of this powerful methodology is the moment-SOS approach also known as Lasserre hierarchy which has attracted a lot of attention in many areas (e.g., optimization, applied mathematics, quantum computing, engineering, theoretical computer science) with important potential applications. It is now a basic tool for analyzing hardness of approximation in combinatorial optimization and the best candidate algorithm to prove/disprove the famous Unique Games Conjecture. Recently it has also become a promising new method for solving the important Optimal Power Flow Problem in the strategic domain of Energy Networks (as the only meth< od that could solve to optimality certain types of such problems). However in its present form this promising methodology inherits a high computational cost and a (too) severe problem size limitation which precludes from its application many important real life problems of significant size. Proving that indeed this methodology can fulfill its promises and solve important practical problems in various areas poses major theoretical & practical challenges.KNew era of printed paper electronics based on advanced functional celluloselCultural Evolution of Kinship Diversity: Variation in Language, Cognition, and Social Norms Regarding FamilyWhy do human societies differ in whom they class as family? Why are cousins classed with siblings in some societies but not others? Accounting for the variable ways that cultures classify kin is an enduring puzzle. The VARIKIN project takes a cultural evolutionary approach to variety and unity and engages different fields cultural phylogenetics, corpus linguistics, and cross-cultural child development. VARIKIN-Evolution asks how and why does kinship diversity evolve across cultures and over time? Using comparative phylogenetic modeling of cultural evolution we investigate the dynamics of how kinship terminologies and family norms change in eight language families. Are there  universal patterns of change, or does local cultural history and context determine changes in family organisation? How do social norms drive change in kinship terminology? VARIKIN-Usage investigates how people use kinship language by using corpus linguistics, surveys, and interviews to quantify patterns of usage in spoken and written language. How frequently are kinship terms used in different contexts and what meanings are more prevalent? Do patterns vary between languages, and can the patterns of usage at the individual level be linked to historical processes of change? VARIKIN-Development investigates how children acquire and understand kinship across cultures. Using participant observation and elicitation tasks, we characterise children s social learning of kinship in a small-scale, non-Western community. Are there cross-cultural patterns of acquisition? Can socialisation produce constraints on the kinds of kinship children can learn? These three research directions are united by a coherent framework for the integration of macro- and micro-evolutionary processes. With a highly multidisciplinary background, the Applicant is uniquely positioned to direct this vanguard project towards a comprehensive understanding of diversity in how we classify our social worlds.$Information Aggregation in ElectionsNExploring the Plurality of New Worlds: Their Origins, Climate and Habitability^Design, manufacturing and control of INterfaces in THERMally conductive polymer nanocompositesThis proposal addresses the design, manufacturing and control of interfaces in thermally conductive polymer/graphene nanocomposites. In particular, the strong reduction of thermal resistance associated to the contacts between conductive particles in a percolating network throughout the polymer matrix is targeted, to overcome the present bottleneck for heat transfer in nanocomposites. The project includes the investigation of novel chemical modifications of nanoparticles to behave as thermal bridges between adjacent particles, advanced characterization methods for particle/particle interfaces and controlled processing methods for the preparations of nanocomposites with superior thermal conductivity. The results of this project will contribute to the fundamental understanding of heat transfer in complex solids, while success in mastering interfacial properties would open the way to a new generation of advanced materials coupling high thermal conductivity with low density, ease of processing, toughness and corrosion resistance. /The role of immune cells in Alzheimer's diseaseAlzheimer s disease is the most common form of dementia affecting more than 35 million people worldwide and its prevalence is projected to nearly double every 20 years with tremendous social and economical impact on the society. There is no cure for Alzheimer's disease and current drugs only temporarily improve disease symptoms. Alzheimer's disease is characterized by a progressive deterioration of cognitive functions, and the neuropathological features include amyloid beta deposition, aggregates of hyperphosphorylated tau protein, and the loss of neurons in the central nervous system (CNS). Research efforts in the past decades have been focused on neurons and other CNS resident cells, but this "neurocentric" view has not resulted in disease-modifying therapies. Growing evidence suggests that inflammation mechanisms are involved in Alzheimer's disease and our team has recently shown an unexpected role for neutrophils in Alzheimer's disease, supporting the innovative idea that circulating leukocytes contribute to disease pathogenesis. The main goal of this project is to study the role of immune cells in animal models of Alzheimer's disease<  focusing on neutrophils and T cells. We will first study leukocyte-endothelial interactions in CNS microcirculation in intravital microscopy experiments. Leukocyte trafficking will be then studied inside the brain parenchyma by using two-photon microscopy, which will allow us to characterize leukocyte dynamic behaviour and the crosstalk between migrating leukocytes and CNS cells. The effect of therapeutic blockade of leukocyte-dependent inflammation mechanisms will be determined in animal models of Alzheimer's disease. Finally, the presence of immune cells will be studied on brain samples from Alzheimer's disease patients. Overall, IMMUNOALZHEIMER will generate fundamental knowledge to the understanding of the role of immune cells in neurodegeneration and will unveil novel therapeutic strategies to address Alzheimer s disease. SAn Integrative Approach to Understanding Convergent Evolution in Ant-eating MammalsDespite its widespread occurrence across the tree of life, many questions still remain unanswered concerning the fascinating phenomenon of convergent evolution. Ant-eating mammals constitute a textbook example of morphological convergence with at least five independent origins in placentals (armadillos, anteaters, aardvarks, pangolins, and aardwolves). The large extent of convergent morphological evolution, the importance of molecular convergence, and the role of the host microbiome in diet adaptation are currently gaining acceptance. However, large-scale comparative studies combining morphology, host genomics, and metagenomics of the associated microbiome are still lacking. In the ConvergeAnt project, we propose taking advantage of the unique set of convergently evolved characters associated with the ant-eating diet to investigate the molecular mechanisms underlying phenotypical adaptation. By using state-of-the art phenotyping methods based on X-ray micro-computed tomography and Illumina sequencing technologies we will combine morphometric, genomic, and metagenomic approaches to evaluate the extent of convergent evolution in the skull of myrmecophagous placentals, in their genomes, and in their associated oral and gut microbiomes. With this ambitious research proposal, we aim at providing answers to longstanding but fundamental evolutionary questions pertaining to the mechanisms of convergent evolution. The ConvergeAnt project will be the first of its kind to apply such an integrative approach to investigate the complex interplay between the mammalian genome and its associated microbiome in a classical case of adaptive convergence driven by a highly specialized diet.#Spectral theory of random operatorsFThe theme of this proposal is the study of random operators associated with some geometric structure, and the influence of the geometry on the spectral properties of the operator. Such operators appear in problems from theoretical physics, and lead to new and interesting mathematical structures.One circle of questions is related to random operators, which describe the motion of a quantum particle in a disordered medium, such as random band matrices. The behaviour of the particle is influenced by the underlying geometry, as quantified by the (non-rigorous) Thouless criterion for localisation in terms of the mixing time of the classical random walk; in the context of random band matrices, the predictions of the Thouless criterion are supported by additional (non-rigorous) arguments. These predictions have so far not been rigorously justified; an exception is my own result, validating it at the spectral edges. One of our goals is to develop new methods, which would be applicable in the bulk of the spectrum, for random band matrices and other operators with geometric structure.Another circle of questions is given by random processes taking values in large random matrices. The spectral properties of the random matrix at every point of the underlying space are described by the random matrix theory; but how does the spectrum evolve along the underlying space? The richness of this question is apparent from the one-dimensional case of Dyson Brownian motion. We intend to study the local eigenvalue statistics of general matrix-valued random processes with multi-dimensional underlying space; to give a complete description of the random processes which appear in the limit, first for the spectral edges and then for the bulk of the spectrum, and to explore the appearance of these processes in a variety of basic questions of mathematical physics.Unravelling respiratory microflows in silico and in vitro: novel paths for targeted pulmonary delivery in infants and young children-New frontiers in numerical general relativity:The retinae as windows to the brain: An oscillatory visionSeveral sophisticated image processing circuits have been discovered in the animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, but electroretinography (ERG) has not been tapped to examine this potential in humans. Bolstered by our compelling results combining ERG with magnetoencephalography (MEG), this project will address several open questions with respect to human visual processing:1) Could variable retinal timing be linked to intrinsic image properties and pass on phase variance downstream to visual cortex? Our data suggests the retina responds to moving gratings and natural imagery with non-phase-locked high gamma oscillations (>65 Hz) just like visual cortex, and that slower ERG potentials exhibit strong phase-locking within stimuli but large phase variance across stimuli.2) Do such retinal gamma band responses, both evoked and induced, directly drive some cortical gamma responses? Pilot data suggests that it can, through retinocortical coherence, our novel ERG-MEG mapping technique.3) Several kinds of motion have now been shown to elicit massive synchrony in mammalian retina circuits. Does this also result in macroscopic high-frequency activity? If so, our experiments will finally reveal and characterize motion detection by the human retina.4) Do efferent pathways to the retina exist in humans? We discovered that the ERG exhibits eyes-closed alpha waves strikingly similar to the classic EEG phenomenon and, leveraging our retinocortical coherence technique, that this activity is likely driven by contralateral occipital cortex. Then, can retinal responses be influenced by ongoing cortical activity?Characterizing retinocortical interaction represents a complete paradigm shift that will be imperative for our understanding of neural synchrony in the human nervous system and enable several groundbreaking new avenues for research.>Synthesis Technologies for Reactive Systems Software EngineersThe design and development of open reactive systems, which compute by reacting to ongoing stimuli from their environment, and include, for example, mobile applications running on smart phone devices, web-based applications, industrial robotic systems, embedded software running on chips inside cars and aircraft, etc., is a complex and challenging task. Despite advancement from low-level assembly languages to higher-level languages with powerful abstraction mechanisms, and the use of automated testing and formal verification, reactive systems < software development is still a mostly manual and error-prone iterative activity of coding and debugging.A fundamentally different alternative approach to reactive systems development is synthesis, the automatic creation of correct-by-construction software from its specification. Synthesis has the potential to transform the way open reactive systems software is developed, making the process more effective and productive, and making its results more reliable and usable. However, while important advancements have been recently made on the algorithmic aspects of synthesis, no work has yet taken advantage of these achievements to change software engineering practices from  program centric to  specification centric . No effective end-to-end means to use synthesis are available to engineers, and the potential revolutionary impact of synthesis on the engineering of reactive systems software is far from being fully explored. The proposal targets four objectives: a new, rich specification language, tailored for synthesis and for use by software engineers; a set of new methods for specification centric development; tool implementations in  killer app application domains; and systematic evaluation with engineers. The research aims to unleash and evaluate the potential of synthesis to revolutionize reactive systems software development and to open the way for new directions in software engineering research and practice.&Dynamic Penetrating Peptide Adaptamers@Troy+ stomach stem cells in homeostasis, repair and pathogenesisThe adult mammalian stomach can be divided into three distinct parts: From the proximal fore-stomach over the corpus to the distal pylorus. Due to constant exposure to mechanical stress and to hostile contents of the lumen, highly specialized cell types have to be constantly reproduced in order to maintain the function of the gastrointestinal tract. Recently, the applicant identified Troy+ chief cells as a novel stem cell population in the corpus epithelium. Troy+ chief cells displayed a very low proliferation rate indicating their quiescent nature compared to other known gastro-intestinal tract stem cells. Interestingly, these stem cells can actively divide upon tissue damage, suggesting distinctive statuses under conditions of homeostasis and injury.As Troy+ stomach stem cells exhibit interconvertible characteristics i.e. quiescent and proliferative, they represent a unique model of adult stem cells with which we can study 1) the dynamics of stem cell propagation in homeostasis and regeneration and the underlying mechanism of this switch by analysing molecular and epigenetic profiles. Subsequently, by analysing mRNA expression profiles and epigenetic changes in Troy+ stem cells between homeostasis and injury repair, we will generate a list of genes with potentially interesting functions in cell fate decisions. We will therefore investigate 2) the stomach stem cell programme in homeostasis and regeneration using in vitro and in vivo functional genetics. Lastly, we will characterise 3) human stomach stem cells in normal and pathological conditions.Here we pursue three main aims:- Investigating Troy+ stem cell dynamics during homeostasis and injury repair- Unmasking the stomach stem cell programme using in vitro and in vivo functional genetics- Characterising human stomach stem cells>Epistasis analysis of angiogenes with high cellular definition|Blood and lymphatic vessels have been the subject of intense investigation due to their important role in cancer development and in cardiovascular diseases. The significant advance in the methods used to modify and analyse gene function have allowed us to obtain a much better understanding of the molecular mechanisms involved in the regulation of the biology of blood vessels. However, there are two key aspects that significantly diminish our capacity to understand the function of gene networks and their intersections in vivo. One is the long time that is usually required to generate a given double mutant vertebrate tissue, and the other is the lack of single-cell genetic and phenotypic resolution. We have recently performed an in vivo comparative transcriptome analysis of highly angiogenic endothelial cells experiencing different VEGF and Notch signalling levels. These are two of the most important molecular mechanisms required for the adequate differentiation, proliferation and sprouting of endothelial cells. Using the information generated from this analysis, the overall aim of the proposed project is to characterize the vascular function of some of the previously identified genes and determine how they functionally interact with these two signalling pathways. We propose to use novel inducible genetic tools that will allow us to generate a spatially and temporally regulated fluorescent cell mosaic matrix for quantitative analysis. This will enable us to analyse with unprecedented speed and resolution the function of several different genes simultaneously, during vascular development, homeostasis or associated diseases. Understanding the genetic epist< atic interactions that control the differentiation and behaviour of endothelial cells, in different contexts, and with high cellular definition, has the potential to unveil new mechanisms with high biological and therapeutic relevance. 4Algal Lipids: the Key to Earth Now and aNcient EarthAlkenones are algal lipids that have been used for decades to reconstruct quantitative past sea surface temperature. Although alkenones are being discovered in an increasing number of lake sites worldwide, only two terrestrial temperature records have been reconstructed so far. The development of this research field is limited by the lack of interdisciplinary research that combines modern biological and ecological algal research with the organic geochemical techniques needed to develop a quantitative biomarker (or molecular fossil) for past lake temperatures. More research is needed for alkenones to become a widely used tool for reconstructing past terrestrial temperature change. The early career Principal Investigator has discovered a new lake alkenone-producing species of haptophyte algae that produces alkenones in high abundances both in the environment and in laboratory cultures. This makes the new species an ideal organism for developing a culture-based temperature calibration and exploring other potential environmental controls. In this project, alkenone production will be manipulated, and monitored using state-of-the-art photobioreactors with real-time detectors for cell density, light, and temperature. The latest algal culture and isolation techniques that are used in microalgal biofuel development will be applied to developing the lake temperature proxy. The objectives will be achieved through the analysis of 90 new Canadian lakes to develop a core-top temperature calibration across a large latitudinal and temperature gradient ( latitude = 5,  spring surface temperature = 9C). The results will be used to assess how regional palaeo-temperature (Uk37), palaeo-moisture (Dwax) and palaeo-evaporation (Dalgal) respond during times of past global warmth (e.g., Medieval Warm Period, 900-1200 AD) to find an accurate analogue for assessing future drought risk in the interior of Canada.FReshaping society and space: home-based self-employment and businesses8The aim of WORKANDHOME is to develop a new framework for understanding fundamental changes currently taking place to work that situates individuals as economic actors within the context of their wider life domains, household, home and neighbourhood. This will break new ground in how we understand and classify economic activity, the home, the firm, places of economic activity, labour markets and  residential neighbourhoods. Significant and rising numbers of people work from home as a self-employed worker or business owner throughout Europe. This will be the first study that explores social, economic and spatial aspects of homeworking by self-employed workers and business owners including the role of new technologies and social media in dissolving the home-work boundary. This is an important new area for social science research since home-based self-employment and businesses vividly manifest the interconnection of  home and  work and of the  economic and the  social as part of an increasingly complex society. WORKANDHOME will integrate theoretical perspectives from economic geography, entrepreneurship and small business research, sociology, economics, housing and neighbourhood studies. In order to investigate new realities of how people work and live, this study will integrate analytical methods across the social sciences and computer sciences and create a new fusion of primary, secondary and  big social media data from the UK, the Netherlands, Germany, Europe and the world. WORKANDHOME offers a major step forward in understanding how people live, work, do business and shape space. Its integrated and international approach will stimulate considerable interdisciplinary exchange across disciplines in the social sciences for better understanding and tackling contemporary societal and economic changes and challenges.AAlgorithms for Complex Collective Decisions on Structured Domains< Algorithms for Complex Collective Decisions on Structured Domains. The aim of this proposal is to substantially advance the field of Computational Social Choice, by developing new tools and methodologies that can be used for making complex group decisions in rich and structured environments. We consider settings where each member of a decision-making body has preferences over a finite set of alternatives, and the goal is to synthesise a collective preference over these alternatives, which may take the form of a partial order over the set of alternatives with a predefined structure: examples include selecting a fixed-size set of alternatives, a ranking of the alternatives, a winner and up to two runner-ups, etc. We will formulate desiderata that apply to such preference aggregation procedures, design specific procedures that satisfy as many of these desiderata as possible, and develop efficient algorithms for computing them. As the latter step may be infeasible on general preference domains, we will focus on identifying the least restrictive domains that enable efficient computation, and use real-life preference data to verify whether the associated restrictions are likely to be satisfied in realistic preference aggregation scenarios. Also, we will determine whether our preference aggregation procedures are computationally resistant to malicious behavior. To lower the cognitive burden on the decision-makers, we will extend our procedures to accept partial rankings as inputs. Finally, to further contribute towards bridging the gap between theory and practice of collective decision making, we will provide open-source software implementations of our procedures, and reach out to the potential users to obtain feedback on their practical applicability.nReleasing Prisoners Of The Paradigm: Understanding How Cooperation Varies Across Contexts In The Lab And FieldCooperation is essential for mitigating conflict between individual and collective interests in relationships and groups, such as providing public goods and conserving resources. Most research testing psychological and economic theory of cooperation has applied a highly specific lab method (e.g., the prisoner s dilemma) that unnecessarily constrains the applicability of research findings. The discrepancies between cooperation observed in the lab and field can be due to variation in interdependence. Two limitations of lab studies to generalizing findings to the field are that (1) lab studies contain interdependence that differs from reality and (2) in the field people lack knowledge about their objective interdependence with others  and must infer their interdependence. I propose two inter-related research programs that test hypotheses derived from Functional Interdependence Theory on how objective and perceived interdependence affect cooperation. Project 1 applies meta-analysis to test hypotheses about how variation in objective interdependence across lab studies moderates the effectiveness of strategies to promote cooperation. Because Project 2 involves a pioneering effort to catalogue and analyze the 60 year history of research on cooperation, I will apply these efforts to develop an international, multidisciplinary institution and open access database for cataloguing studies in a way that facilitates scientific progress. Project 2 (a) develops a measure of perceived interdependence, (b) observes the interdependence people encounter in their daily lives, (c) tests two models of how people think about interdependence, and (d) innovates and applies a method to test hypotheses about factors that influence accuracy and bias in perceptions of interdependence. To maximize the ecological validity of research findings, I study cooperation in different samples (students, romantic couples, and employees) with the use of multiple methods (survey, experimental, and field).8At the roots of corruption: a behavioral ethics approachAFor many years, human cooperation has been praised as beneficial in organizational and personal settings. Indeed, cooperation allows people to develop trust, build meaningful relationships, achieve mutually beneficial outcomes, and strengthen bonding with one's group members. However, while the benefits of cooperation are clear, very little is known about its possible negative aspects. Such negative aspects include the potential emergence of unethical conduct among cooperating partners, or as termed here  corrupt collaboration. Such joint unethical efforts, benefiting (directly or indirectly) one or more of the involved parties, occur in business, sports, and even academia. Corrupt collaboration emerges when one party bends ethical rules (here: lie) to set the stage for another party to further bend ethical rules and get the job done, that is, secure personal profit based on joint unethical acts. We propose that corrupt collaborations most commonly occur when all involved parties gain from the corrupt behavior. The current proposal is aimed at unfolding the roots and nature of corrupt collaborations; their existence,<  the psychological and biological processes underlying them, and the settings most likely to make corrupt collaboration emerge and spread. Accordingly, the information gathered in the current proposal has the potential to change the commonly held conceptions regarding the unidimensional  positive  nature of cooperation. It will help create a comprehensive understanding of cooperation and, specifically, when it should be encouraged or, alternatively, monitored.]Localizing 4000 Years of Cultural History. Texts and Scripts from Elephantine Island in EgyptThe aim of this project is to write a cultural history of 4000 years, localized on Elephantine Island in Egypt.Elephantine was a militarily and strategically very important island in the river Nile on the southern borderof Egypt. No other settlement in Egypt is so well attested over such a long period of time. Its inhabitantsform a multi-ethnic, multicultural and multi-religious community that left us vast amounts of written sourcesdetailing their everyday lives from the Old Kingdom to beyond the Arab Conquest. Today, several thousandpapyri and other manuscripts from Elephantine are scattered in more than 60 institutions across Europe andbeyond. Their texts are written in different languages and scripts, including Hieroglyphs, Hieratic, Demotic,Aramaic, Greek, Coptic and Arabic. 80% of these manuscripts are still unpublished and unstudied. The greatchallenge of this project is to use this material to answer three key questions covering:1) Multiculturalism and identity between assimilation and segregation,2) Organization of family and society,3) Development of religions (Polytheism, Judaism, Christianity and Islam).Thus, access needs to be gained to these texts, making them publicly available in an open access onlinedatabase. Links are to be identified between papyrus fragments from different collections and aninternational  papyrus puzzle will be undertaken, incorporating cutting-edge methods from digitalhumanities, physics and mathematics (e.g. for the virtual unfolding of papyri). Using this database withmedical, religious, legal, administrative, even literary texts, the micro-history of the everyday life of the localand global (i.e.  glocal ) community of Elephantine will be studied within its socio-cultural setting in Egyptand beyond. It will be linked back to macro-historical questions and benefit from newly-introducedmethodologies of global history: Elephantine can thus be used as a case study and a model for the past,present and future.BDistributed Optimization Methods for Smart Cyber-Physical NetworksThe combination of embedded electronics and communication capability in almost any mobile or portable device has turned this century into the age of cyber-physical networks. Smart communicating devices with their sensing, computing and control capabilities promise to make our cities, transportation systems, factories and living environments more intelligent, energy-efficient, safe and secure. This extremely complex system has raised a number of new challenges involving ICT disciplines. In particular, a novel peer-to-peer distributed computational model is appearing as a new opportunity in which a service is built-up cooperatively by peers, rather than by a unique provider that knows and owns all data. The interdisciplinary  Optimization Community is facing this revolution sharing a common need: to find new theories, methodologies and tools to optimize over this complex network system. With this in mind, OPT4SMART has a twofold objective. First, to provide a comprehensive theoretical framework to solve distributed optimization problems over peer-to-peer networks. Second, to develop effective numerical tools, based on this framework, to solve estimation, learning, decision and control problems in cyber-physical networks. To achieve this twofold objective, we will take a systems-theory perspective. Specific problems from these four areas will be abstracted to a common mathematical set-up, and addressed by means of interdisciplinary methodologies arising from a synergic combination of optimization, controls, and graph theories. In particular, OPT4SMART will f< ace the challenge of solving optimization problems under severe communication limitations, very-large-scale problem and data size, and real-time computational constraints. The expected result will be a combination of strong theoretical methods and effective numerical toolboxes available to people in Engineering, Computer Science, Mathematics and other areas, who are facing optimization in cyber-physical networks.Dynamic interplay between DNA methylation, histone modifications and super enhancer activity in normal T cells and during malignant T cell transformationDynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human disease. The ultimate goal of this research proposal is to study the chromatin architecture during normal and malignant T cell differentiation in order to define how DNA methylation drives oncogenic gene expression as a novel concept in cancer research.T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric and 25% of adult ALL cases and was originally identified as a highly aggressive tumor entity. T-ALL therapy has been intensified leading to gradual improvements in survival. However, 20% of pediatric and 50% of adult T-ALL cases still relapse and ultimately die because of refractory disease. Research efforts have unravelled the complex genetic basis of T-ALL but failed to identify new promising targets for precision therapy. Recent studies have identified a subset of T-ALLs whose transcriptional programs resemble those of early T-cell progenitors (ETPs), myeloid precursors and hematopoietic stem cells. Importantly, these so-called ETP-ALLs are characterized by early treatment failure and an extremely poor prognosis. The unique ETP-ALL gene expression signature suggests that the epigenomic landscape in ETP-ALL is markedly different as compared to other genetic subtypes of human T-ALL.My project aims to identify genome-wide patterns of DNA methylation and histone modifications in genetic subtypes of human T-ALL as a basis for elucidating how DNA methylation drives the expression of critical oncogenes in the context of poor prognostic ETP-ALL. Given that these ETP-ALL patients completely fail current chemotherapy treatment, tackling this completely novel aspect of ETP-ALL genetics will yield new targets for therapeutic intervention in this aggressive haematological malignancy. VTransdiagnostic views on eating disorders and obesity and new approaches for treatmentrEating disorders such as Anorexia Nervosa (AN), Bulimia Nervosa (BN), Binge Eating Disorder (BED) and overweight/obesity are highly prevalent in the EU and worldwide. They cause tremendous suffering, elevate suicide rates, and account for multiple organic effects that increase all-cause mortality. Etiological and maintenance factors are not well understood and transdiagnostic theoretical models across eating and weight disorders are largely missing. The present project aims to develop an integrated theoretical framework by studying psychological factors that contribute to non-homeostatic eating across the full spectrum of eating-related disorders. It is proposed that high levels on psychological traits such as restraint eating (i.e., chronic dieting behaviour), emotional eating (i.e., eating in response to negative emotional events rather than hunger), craving/food addiction (i.e., intense and chronic urge to consume palatable foods), impulsivity (i.e., inadequate food consumption planning and low self-control), and low self-esteem influence neural systems that balance appetitive (mostly bottom-up) with regulatory (mostly top-down) processes. This model is tested in the four patient groups and healthy controls utilizing an integrated set of assessment methods, involving psychometric testing, smartphone based ambulatory assessment, and neurocognitive laboratory measurement. Derived from this model, novel behavioural interventions such as smartphone based stimulus control and cognitive inhibition training will be developed. Results will have implications for theoretical models of eating and weight disorders as well as for neuroaffective models of appetite regulation. Smartphone technology might usefully complement current interventions in supporting an effective transfer to daily life and help alleviate the burden for patients with eating-related mental and physical diseases.6Formal lexically informed logics for searching the webSemantic search engines use structured knowledge to improve traditional web search, e.g. by directly answering questions from users. Current approaches to semantic search rely on the unrealistic assumption that all true facts about a given domain are explicitly stated in their knowledge base or on the web. To reach their full potential, semantic search engines need the ability to reason about known facts. However, existing logics cannot adequately deal with the imperfect nature of knowledge from the web. One problem is that relevant information tends to be distributed over several heterogeneous knowledge bases that are inconsistent with each other. Moreover, domain theories are seldom complete, which means that a form of so-called plausible reasoning is needed. Finally, as relevant logical theories do not exist for many domains, reasoning may need to rely on imperfect probabilistic theories that have been learned from the web. To overcome these challenges, FLEXILOG will introduce a family of logics for robust reasoning with messy real-world knowledge, based on vector-space representations of natural language terms (i.e. of lexical knowledge). In particular, we will use lexical knowledge to estimate the plausibility of logical models, using conceptual simplicity as a proxy for plausibility (i.e. Occam s razor). This will enable us to implement various forms of commonsense reasoning, equipping classical logic with the ability to draw plausible conclusions based on regularities that are observed in a knowledge base. We will then generalise our approach to probabilistic logics, and show how we can use the resulting lexically informed probabilistic logics to learn accurate and comprehensive domain theories from the web. This project will enable a robust data-driven approach to logic-based se< mantic search, and more generally lead to fundamental progress in a variety of knowledge-intensive applications for which logical inference has traditionally been too brittle.[Genetic Mapping of Evolutionary Developmental Variation using Hybrid Mouse in vitro CrossesDiscovering the genetic changes underlying species differences is a central goal in evolutionary genetics. Most evolutionarily important traits affecting fitness are complex or quantitative traits, whose genetic bases are elusive. In mammals, dissecting the genetic basis of complex trait variation is particularly challenging, because efficient genetic mapping requires enormous pedigrees or specialized genetic panels that are typically beyond the resources of individual groups. Using a radically novel method to circumvent breeding limitations by  breeding mice in vitro, I propose to dissect the genetic basis of evolutionary developmental variation. This ground-breaking approach will allow me to create large genetic mapping panels of potentially any size from mouse interspecific hybrids of increasing evolutionary divergence. In vitro crosses promise a breakthrough in evolutionary biology: by bypassing hybrid sterility and inviability, we will ask which genetic changes underlie species differences. The proposed experiments address how genetic changes accumulate during evolution of new species to shape gene regulatory networks and cause phenotypic changes at the gene expression, fitness and organismal level. This research has the potential to revolutionize genetic mapping. If realized, its impact on personalized medicine, agricultural science and evolutionary research cannot be understated./The Power of Maternal Microbes on Infant HealthRecent reports suggest that early microbial colonization has an important role for in promoting health. This may contribute to reduce the risk of chronic diseases such as obesity, allergies and inflammatory conditions. Advances in understanding host-microbe interactions imply that maternal microbiota plays a crucial role on health programming. This process begins in utero and it is modulated by mode of delivery and diet. My research has shown that i) specific shifts in milk microbial composition are associated with lactation time and mode of delivery, ii) milk microbes drive the infant microbiota composition; iii) maternal microbiota dysbiosis may be transferred to the infant. However, factors defining maternal microbiota and its biological role upon infant s health are not yet fully understood. Hence, this project aims to characterize maternal microbes to be transferred to neonates and determine their function in infant health programming. The specific aims are:(1) understanding how the maternal microbiome is influenced by host and environmental factors;(2) characterizing the microbial core and bioactive compounds transmitted to the offspring mainly via breastfeeding and their key roles in the microbial modulation and host response;(3) understanding the interactions among breast milk bioactive compounds and their role in infant health;(4) shedding light on how maternal microbes influence the infant immune system & (5)development of new dietary strategies and therapies based on microbial replacement and modulation. To achieve these objectives, a systems biology approach by means of state-of-the-art techniques and new methodologies based on subpopulation enrichment by flow cytometer-sorter to study host microbe interactions will be used. Results obtained will demonstrate the interaction between infant nutrition, microbes and host response in early life and its key role in health programming, enabling new applications in the field of personalized nutrition & medicine.QAnimal coloration through deep time: evolutionary novelty, homology and taphonomyWhat does the fossil record tell us about the evolution of colour in animals through deep time? Evidence of colour in fossils can inform on the visual signalling strategies used by ancient animals. Research to date often has a narrow focus, lacks a broad phylogenetic and temporal context, and rarely incorporates information on taphonomy. This proposal represents a bold new holistic approach to the study of fossil colour: it will couple powerful imaging- and chemical analytical techniques with a rigorous programme of fossilisation experiments simulating decay, burial, and transport, and analysis of fossils and their sedimentary context, to construct the first robust models for the evolution of colour in animals through deep time. The research will resolve the original integumentary colours of fossil higher vertebrates, and the original colours of fossil hair; the fossil record of non-melanin pigments in feathers and insects; the biological significance of monotonal patterning i< n fossil insects; and the evolutionary history of scales and 3D photonic crystals in insects. Critically, the research will test, for the first time, whether evidence of fossil colour can solve broader evolutionary questions, e.g. the true affinities of enigmatic Cambrian chordate-like metazoans, and feather-like integumentary filaments in dinosaurs. The proposal entails construction of a dedicated experimental maturation laboratory for simulating the impact of burial on tissues. This laboratory will form the core of the world s first integrated  experimental fossilisation facility , consolidating the PI s team as the global hub for fossil colour research. The research team comprises the PI, three postdoctoral researchers, and three PhD students, and will form an extensive research network via collaborations with 13 researchers from Europe and beyond. The project will reach out to diverse scientists and will inspire a positive attitude to science among the general public and policymakers alike.CDEtermination of Orphan Receptor PHysiological Agonists and sigNals?The role of 5HT3a inhibitory interneurons in sensory processingHow do cortical circuits process sensory stimuli that leads to perception? Sensory input is encoded by complex interactions between principal excitatory neurons and a diverse population of inhibitory cells. Distinct inhibitory neurons control different subcellular domains of target principal neurons, suggesting specific roles of different cells during sensory processing. However, the individual contribution of these inhibitory subtypes to sensory processing remains poorly understood. This is mainly due to the technical challenges of recording the activity of identified cell types in-vivo, in response to quantified sensory stimuli. Therefore, I propose a novel approach based on four pillars: 1) An optically accessible circuit in the superficial layers of the cortex, comprised of inhibitory cells expressing the serotonin receptor 5HT3a, and the distal dendrites of pyramidal neurons. 2) A novel combination of electrophysiology and 3D two-photon imaging to simultaneously record the activity of morphologically identified 5HT3a cells and their dendritic targets. 3) A head-fixed perceptual decision task, whereby mice use their whiskers to determine the location of an object, allowing an accurate description of the sensory stimulus. 4) The integration of experimental data and computer models to gain mechanistic insights into circuit functions. The 5HT3a cells and the distal dendrites of pyramidal neurons receive  top-down contextual information from other cortical areas that is essential for constructing meaningful perceptions of sensory stimuli. Thus I hypothesize that 5HT3a cells influence sensory perceptions by controlling the excitability of the pyramidal cell distal dendrites that integrate top-down and sensory input. Thus, I will not only reveal novel functions of inhibitory neurons, I will also shed light on how top-down and sensory input is integrated, and I will provide novel methods to test the functions of other cell types in normal mice and disease models.2Structural studies of mammalian Cys-loop receptorsIn the brain, Cys-loop receptors mediate fast neurotransmission. They function as allosteric signal transducers across the plasma membrane: upon binding of one or more neurotransmitter molecules to an extracellular site, the receptors undergo complex conformational transitions that result in transient opening of an intrinsic ion channel. The Cys-loop family comprises receptors activated by serotonin, acetylcholine, glycine and GABA. Mammalian receptors are also the targets of a legion of psycho-active and therapeutic compounds (including nicotine, benzodiazepines, anti-emetics, general anaesthetics). Our structural knowledge is currently limited to invertebrate homologues. Atomic structures mammalian receptors are therefore acutely missing in order to understand their physiological role in molecular terms, and to be able to develop new drugs targeting them. The project proposes to decipher the operation mechanism, the pharmacology and conformational transitions of mammalian Cys-loop receptors. S< tarting with a solid body of preliminary results, we will obtain new high-resolution structures, taking advantage of antibody-based crystallization chaperones. We will try and record for the first time a  molecular movie of the gating conformational transition in cristallo. On the way, we will also investigate the potential of antibody-based modulators of Cys-loop receptors for biomedical applications.The applicant has solved in the past the structures of a bacterial Cys-loop receptor and of the mouse serotonin receptor. The proposed research will take place at the CNRS in Grenoble, France, in a very favourable environment for structural biology.2Functional 2D metamaterials at visible wavelengthsFor the last 15 years, optics has undergone a remarkable evolution towards ever decreasing sizes, better integration in complex systems, and more compact devices readily available to mass markets. Whereas traditional optics is at the centimeter scale, newly developed techniques use nanoscale objects to control, guide, and focus light. From the capability to shape metallic and dielectric nanostructures has emerged the field of nanophotonics. Advances in nanophotonics offer the possibility to control the material s optical properties to create artificial materials with electromagnetic properties not found in nature. Man-made 3D metamaterials have interesting fundamental aspects and present many advantages with respect to conventional devices. Unexpected effects have led to the development of interesting applications like high resolution lenses and cloaking devices. Inspired by this new technology, we have developed new 2D metamaterials. Our flat metamaterials (metasurfaces) are much simpler to manufacture than their 3D counterparts. By depositing a set of nanostructures at an interface, we can immediately control the light properties; unlike refractive optical components, the wavefront is modified without propagation. As of today, these interfaces are created using metallic nanostructures and work in the infrared. In this ERC, we plan to extend the concept of optical metasurfaces in the visible which is the most important wavelength range for applications. By combining with optically active semiconductors such as InGaAlN, we will add optical gain and modulation capability to the system to create new, efficient optoelectronic devices. The response of the metasurfaces is tunable by changing the environment surrounding the nanostructures. We will use this property to create ultrathin reconfigurable flat devices. Metasurfaces will be integrated with AlN/GaN to modulate light at high frequencies and further exploited to control polariton gases in solid state metasystems.:Hybrid Node Modes for Highly Efficient Light Concentrators~The meaning of solar energy for future decentralized power supply will largely depend on both efficiency and cost of solar to electrical power conversion. All kinds of conversion strategies including photovoltaics, concentrated solar power, solar to fuel and others would benefit from efficiently collecting solar power on large areas. For this reason luminescent solar concentrators have been developed for over thirty years, but due to waveguide losses their maximum size is still limited to a few centimeters.The proposed project suggests the exploitation of a new type of electromagnetic waveguide in order to realize passive planar concentrators of unsurpassed collection efficiency, size, concentration, lifetime and costs. A dielectric TE1-mode shows a node, a position in the waveguide where no intensity is found. A thin film placed in this node remains largely  invisible for the propagating mode. Such dielectric node modes (DNMs) have been investigated by the applicant in previous work, but only recently a silver island film (SIF) was for the first time placed in such a node. The resulting extremely low waveguide losses cannot be explained by our current understanding of waveguide modes and hint to a hybridization between the SIF-bound long-range surface plasmon polaritons (LRSPPs) and the DNMs into what we call hybrid node modes (HNMs). The SIFs strongly interact with inciden< t light. An appropriate nanopatterning of SIFs enables efficient excitation of low-loss HNMs modes collecting solar power over square meters and concentrating it. To achieve this goal new technological methods are used that enable patterning on the nanometer scale and low cost roll-to-roll processing at the same time. New measurement techniques and numerical simulation tools will be developed to investigate the HNMs  a novel kind of electromagnetic modes  and their exploitation in the passive solar concentrators.,Woven and 3D-Printed Thermoelectric TextilesImagine a world, in which countless embedded microelectronic components continuously monitor our health and allow us to seamlessly interact with our digital environment. One particularly promising platform for the realisation of this concept is based on wearable electronic textiles. In order for this technology to become truly pervasive, a myriad of devices will have to operate autonomously over an extended period of time without the need for additional maintenance, repair or battery replacement. The goal of this research programme is to realise textile-based thermoelectric generators that without additional cost can power built-in electronics by harvesting one of the most ubiquitous energy sources available to us: our body heat.Current thermoelectric technologies rely on toxic inorganic materials that are both expensive to produce and fragile by design, which renders them unsuitable especially for wearable applications. Instead, in this programme we will use polymer semiconductors and nanocomposites. Initially, we will focus on the preparation of materials with a thermoelectric performance significantly beyond the state-of-the-art. Then, we will exploit the ease of shaping polymers into light-weight and flexible articles such as fibres, yarns and fabrics. We will explore both, traditional weaving methods as well as emerging 3D-printing techniques, in order to realise low-cost thermoelectric textiles.Finally, within the scope of this programme we will demonstrate the ability of prototype thermoelectric textiles to harvest a small fraction of the wearer s body heat under realistic conditions. We will achieve this through integration into clothing to power off-the-shelf sensors for health care and security applications. Eventually, it can be anticipated that the here interrogated thermoelectric design paradigms will be of significant benefit to the European textile and health care sector as well as society in general.P375 Million Years of the Diversification of Life on Land: Shifting the Paradigm?Life on land today is spectacularly diverse, representing 75 95% of all species on Earth. However, it remains unclear how this extraordinary diversity has been acquired across deep geological time. This research project will address this major knowledge gap by reassessing the dominant paradigm of terrestrial diversification, an exponential increase in diversity over the last 375 million years, using the rich and well-studied fossil record of tetrapods (four-limbed vertebrates) as an exemplar group. Previous analyses of tetrapod diversification have been based on an outdated and problematic dataset that is likely to artificially inflate apparent diversity towards the present day. A major new dataset will be assembled, detailing the spatial and temporal distribution of terrestrial tetrapods across their entire fossil record in unprecedented detail. These data will be analysed using the latest approaches to sampling-standardisation in order to generate completely novel, rigorous curves of diversification through time. These will be compared within a cutting-edge statistical framework to alternate diversification models, as well as to changes in rock record sampling, global environments (e.g. sea level and atmospheric composition) and marine diversity. These comparisons will allow us to address the following key questions: (i) Does terrestrial diversification follow an exponential pattern over the last 375 million years? (ii) Is the terrestrial fossil record as complete as the marine fossil record? (iii) Are long-term patterns of terrestrial diversific< ation driven by physical changes in the Earth system such as climate change? (iv) Did marine and terrestrial biodiversity follow similar trajectories across geological time? (v) How severely did mass extinction events impact upon terrestrial tetrapod diversification? Our work will establish a new, rigorous paradigm for the long-term pattern of terrestrial diversification, and test and identify its drivers.OBig Splash: Efficient Simulation of Natural Phenomena at Extremely Large Scales3Unravelling cluster root development in white lupinMPlant development is continuous throughout their lifetime and reflects their ability to adapt to their environment. This developmental plasticity is very obvious in the development of the root system. Surprisingly, the fundamental mechanisms of root development have been studied into great detail but the effect of the environment on its plasticity is still largely unknown. I will use phosphate, since this nutrient has a very low mobility in soil, as a mean to study plant developmental adaptation in white lupin.This species has developed extreme adaptive mechanism to improve phosphate uptake by producing structures called  cluster roots . They are dense clusters of lateral roots with determi     !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcefghijklmnopqrstuvwxyz{|}~nate development and highly specific physiology. I will develop new tools to identify cluster root mutants in white lupin, sequence white lupin genome, perform tissues specific transcriptomics and perform full molecular characterization of selected genes. This project will also lead me to compare adaptive mechanisms between white lupin and narrow-leafed lupin, a closely related species that does not produce cluster roots. We will also test whether it is possible to transfer the ability to form cluster roots in this species. Altogether, this project will lead to a major advance in our capacity to understand how plants are able to sense and respond to their environment and how evolution has selected adaptive developmental mechanisms to improve their capacity to use limited resources.This project focuses on the most extreme developmental adaptation produced in response to phosphate starvation. It is ambitious, as it will necessitate the development of several tools. However, it is highly feasible since it builds on my previous experience and important outcome can be expected in term of crop improvement and means to reduce the use of phosphate fertilizers.6Towards a Self-Amplifying Carbon-Fixing Anabolic CycleHow can simple molecules self-organize into a growing synthetic reaction network like biochemical metabolism? This proposal takes a novel synthesis-driven approach to the question by mimicking a central self-amplifying CO2-fixing biochemical reaction cycle known as the reductive tricarboxylic acid cycle. The intermediates of this cycle are the synthetic precursors to all major classes of biomolecules and are built from CO2, an anhydride and electrons from simple reducing agents. Based on the nature of the reactions in the cycle and the specific structural features of the intermediates that comprise it, we propose that the entire cycle may be enabled in a single reaction vessel with a surprisingly small number of simple, mutually compatible catalysts from the recent synthetic organic literature. However, since one of the required reactions does not yet have an efficient synthetic equivalent in the literature and since those that do have not yet been carried out sequentially in a single reaction vessel, we will first independently develop the new reaction and sequences before attempting to combine them into the entire cycle. The new reaction and sequences will be useful green synthetic methods in their own right. Most significantly, this endeavour could provide the first experimental evidence of an exciting new alternative model for early biochemical evolution that finally illuminates the origins and necessity of biochemistry s core reactions.,Genuine Quantumness in Cooperative PhenomenaThe proposed research programme addresses issues of fundamental and technological importance in quantum information science and its interplay with complexity. The main aim of this project is to provide a new paradigmatic foundation for the characterisation of quantumness in cooperative phenomena and to develop novel platforms for its practical utilisation in quantum technology applications.To reach its main goal, this programme will target five specific objectives:O1. Constructing a quantitative theory of quantumness in composite systems;O2. Benchmarking genuine quantumness in information and communication protocols;O3. Devising practical solutions for quantum-enhanced metrology in noisy conditions;O4. Developing quantum thermal engineering for refrigerators and heat engines;O5. Establishing a cybernetics framework for regulative phenomena in the quantum domain.This project is deeply< driven by the scientific curiosity to explore the ultimate range of applicability of quantum mechanics. Along the route to satisfying such curiosity, this project will fulfill a crucial two-fold mission. On the fundamental side, it will lead to a radically new level of understanding of quantumness, in its various manifestations, and the functional role it plays for natural and artificial complex systems traditionally confined to a classical domain of investigation. On the practical side, it will deliver novel concrete recipes for communication, sensing and cooling technologies in realistic conditions, rigorously assessing in which ways and to which extent these can be enhanced by engineering and harnessing quantumness.Along with a skillful team which this grant will allow to assemble, benefitting from the vivid research environment at Nottingham, and mainly thanks to his creativity, broad mathematical and physical preparation and relevant inter-disciplinary expertise, the applicant is in a unique position to accomplish this timely and ambitious mission."Robots with animal-like resilienceDespite over 50 years of research in robotics, most existing robots are far from being as resilient as the simplest animals: they are fragile machines that easily stop functioning in difficult conditions. The goal of this proposal is to radically change this situation by providing the algorithmic foundations for low-cost robots that can autonomously recover from unforeseen damages in a few minutes. The current approach to fault tolerance is inherited from safety-critical systems (e.g. spaceships or nuclear plants). It is inappropriate for low-cost autonomous robots because it relies on diagnostic procedures, which require expensive proprioceptive sensors, and contingency plans, which cannot cover all the possible situations that an autonomous robot can encounter. It is here contended that trial-and-error learning algorithms provide an alternate approach that does not require diagnostic, nor pre-defined contingency plans. In this project, we will develop and study a novel family of such learning algorithms that make it possible for autonomous robots to quickly discover compensatory behaviors. We will thus shed a new light on one of the most fundamental questions of robotics: how can a robot be as adaptive as an animal? The techniques developed in this project will substantially increase the lifespan of robots without increasing their cost and open new research avenues for adaptive machines.>Control of contact interactions for robots acting in the worldWhat are the algorithmic principles that would allow a robot to run through a rocky terrain, lift a couch while reaching for an object that rolled under it or manipulate a screwdriver while balancing on top of a ladder? Answering this seemingly nave question resorts to understanding the fundamental principles for robot locomotion and manipulation, which is very challenging. However, it is a necessary step towards ubiquitous robots capable of helping humans in an uncountable number of tasks. The fundamental aspect of both locomotion and manipulation is that the dynamic interaction of the robot with its environment through the creation of physical contacts is at the heart of the tasks. The planning of such interactions in a general manner is an unsolved problem. Moreover, it is not clear how sensory information (e.g. tactile and force sensors) can be included to improve the robustness of robot behaviors. Most of the time, it is simply discarded. CONT-ACT has the ambition to develop a consistent theoretical framework for motion generation and control where contact interaction is at the core of the approach and an efficient use of sensory information drives the development of high performance, adaptive and robust planning and control methods. CONT-ACT develops an architecture based on real-time predictive controllers that fully exploit contact interactions. In addition, the structure of sensory information during contact interactions is experimentally analyzed to create sensor representations adapted for control. It is then possible to learn predictive models in sensor space that are used to create very reactive controllers. The robot constantly improves its performance as it learns better sensory models. It is a step towards a general theory for robot movement that can be used to control any robot with legs and arms for both manipulation and locomotion tasks and that allows robots to constantly improve their performances as they experience the world.5Josephson Junction Spectroscopy of Mesoscopic SystemsSpectroscopy is a powerful tool to probe matter. By measuring the spectrum of elementary excitations, one reveals the symmetries and interactions inherent in a physical system. Mesoscopic devices, which preserve quantum coherence over lengths larger than the atomic scale, offer a unique possibility to both engineer and investigate excitations at the single quanta level. Unfortunately, conventional spectroscopy techniques are inadequate for coupling radiation to mesoscopic systems and detecting their small absorption signals. I propose an on-chip, Josephson-junction based spectrometer which surpasses state-of-the-art instruments and is ideally suited for probing elementary excitations in mesoscopic systems. It has an original design providing uniform wideband coupling from 2-2000 GHz, low background noise, high sensitivity, and narrow linewidth.I describe the operating principle and design of the spectrometer, show preliminary results demonstrating proof-of-concept, and outline three experiments which exploit the spectrometer to address important issues in condensed matter physics. The experiments are: measuring the lifetime of single quasiparticle and excited Cooper pair states in superconductors, a topic relevant for quantum information processing; determining whether graphene has a bandgap, a fundamental yet unresolved question; and recording a clear spectroscopic signature of Majorana bound states in topological superconductor weak links.Various applications of the superconducting circuits developed for the spectrometer include a Josephson vector network analyzer, a cryogenic mixer, a THz camera, a detector for radioastronomy, and a scanning microwave impedance microscope. In itself the proposed JJ spectrometer is a general purpose tool that will benefit researchers studying mesoscopic systems. Ultimately, Josephson junction spectroscopy should not only be useful to detect existing elementary excitations but also to discover new ones.=Engineering a scaffold based therapy for corneal regenerationCorneal blindness resulting from disease, physical injury or chemical burns affects millions worldwide and has a considerable economic and social impact on the lives of people across Europe. In many cases corneal transplants can restore vision however the shortage of donor corneas suitable for transplantation has necessitated the development of alternative treatments. The aim of this project is to develop a new approach to corneal tissue regeneration. Previous approaches at engineering corneal tissue have required access to donor cells and lengthy culture periods in an attempt to grow tissue in vitro prior to implantation with only limited success and at great expense. Our approach will differ fundamentally from these in that we will design artificial corneal s< caffolds that do not require donated cells or in vitro culture but instead will recruit the patient s own cells to regenerate the cornea post-implantation. These biomaterial scaffolds will incorporate specific chemical and physical cues with the deliberate aim of attracting cells and inducing tissue formation. Studies will be undertaken to examine how different chemical, biochemical, physical and mechanical cues can be used to control the behaviour of corneal epithelial, stromal and endothelial cells. Once the optimal combination of these cues has been determined, this information will be incorporated into the design of the scaffold. Recent advances in manufacturing and material processing technology will enable us to develop scaffolds with organized nanometric architectures and that incorporate controlled growth factor release mechanisms. Techniques such as 3D bio-printing and nanofiber electrospinning will be used to fabricate scaffolds. The ability of the scaffold to attract cells and promote matrix remodelling will be examined by developing an in vitro bioreactor system capable of mimicking the ocular environment and by performing in vivo tests using a live animal model.,Theory of statistical topological insulatorsTopological insulators (TI) are a novel class of materials with insulating bulk and conducting surface. The conduction of the surface is protected by the topological properties of the bulk, as long as a fundamental symmetry is present (for instance time-reversal symmetry). My goal is to investigate to what limits does the protection hold in cases where the protecting symmetry is broken, and only present in statistical sense, after averaging over the disordered ensemble. In a pilot study I showed that materials that are protected by such average symmetry, which I have called  statistical topological insulators (STI) significantly extend the classification of topological phases of matter and promise new methods to robustly control the conducting surface properties. I plan to develop a general theory of STI for physically relevant symmetries, describe the observable properties of their protected surface states, invent ways to predict whether materials are expected to be STI, and explore the generalization of STIs to strongly interacting topological phases of matter. I expect that the outcome of my research will significantly extend our understanding of topological phases of matter, and provide new ways to design materials with robust properties.NModelling lianas as key drivers of tropical forest responses to climate changeTropical forests are essential components of the earth system. Yet, much uncertainty exists about the exact role of this biome in the global carbon cycle. Our limited understanding of tropical forest functioning is reflected in uncertain global vegetation model projections. A large source of uncertainty in these models is their representation of ecosystem demographic processes. Interestingly, fieldwork has revealed lianas as important components of tropical forests, which are apparently increasing in abundance. Liana proliferation might be a key adaptation mechanism of tropical forests to climate change, which has potentially large impacts on the long term tropical forest biome carbon balance. Nevertheless, no single terrestrial ecosystem model currently includes lianas. TREECLIMBERS will generate important insights into the mechanisms by which lianas influence the carbon balance of tropical forests, by building the first vegetation model that includes lianas. We will make the first integrative study of (1) the contribution of lianas to instantaneous carbon and water fluxes, (2) liana contribution and influence on canopy structure, (3) their role for long term demographic processes, and (4) of their role in forest responses to drought events. TREECLIMBERS will develop the first liana plant functional type (PFT) by combining a unique global meta-analysis of existing data with innovative terrestrial LiDAR 3D measurements of the canopy to study the contribution of lianas to the canopy structure. New and available data will be integrated in the Ecosystem Demography (ED) model, a forerunner of the next generation of vegetation models. By using model-data fusion we will, for the first time, integrate the large amount of available and emerging liana data, leading to an integrated insight into the role of lianas in tropical forest functioning. This project aims to show that shifts in floristic composition due to global change may have important impacts in tropical forests.hStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young studentsMounting evidence suggests that early life factors have an important impact on the occurrence of late-life neurological diseases. From a public health perspective this is of particular relevance for dementia, the prevalence of which is increasing drastically, with no available preventive treatment, and epidemiological data suggesting that pathological processes may begin many years before clinical diagnosis. MRI-defined structural brain phenotypes are powerful intermediate markers for dementia, and can already show measurable alterations in young and middle-aged adults. These include global and regional brain volumes, gray matter volume and cortical thickness, and markers of white matter integrity. The SEGWAY project aims to: (i) explore the heritability and genetic determinants of structural brain phenotypes in young adults in their early twenties participating in the i-Share study, the largest ongoing student cohort; (ii) take a lifetime perspective by examining the shared genetic contribution to structural brain alterations in young adulthood (i-Sha< re) and late-life, among participants of a large French population-based study (3C-Dijon); (iii) explore the interaction between genetic variants and vascular risk factors with established impact on structural brain phenotypes, in both age groups; (iv) examine the clinical significance of genetic risk variants for structural brain alterations by testing their association with cognitive performance in young and older adults. Replication and of our findings will be sought in the multigenerational Framingham Heart Study and other independent samples. Identifying common biological mechanisms underlying both early and late-life structural brain changes would provide important information on the mechanisms and timecourse of brain aging throughout a lifetime and could be of major importance for identifying of molecular drug targets and characterizing high risk populations most likely to benefit from early interventions.QA Multiscale and Multimodal Modelling Approach for Green Urban Traffic ManagementThe MAGnUM project aims to (i) create a consistent set of interrelated dynamic and multimodal traffic models able to capture driver behaviours at the different urban scales and (ii) apply this variety of models to design efficient and green traffic management strategies. Traffic flow dynamics is well reproduced at a local urban scale by the kinematic wave model and its numerous extensions. Even if this model is parsimonious compared to other modelling approaches, it can hardly be applied at larger urban scales for traffic control applications. Very recently, a new modelling approach has been proposed to represent congestion dynamics at large scales. It relates the total travel production to the vehicle accumulation in a traffic network with for now a restrictive condition about network homogeneity. This approach is very promising for designing new traffic management systems but heterogeneous situations should be handled by properly connecting with the local scale to account for the effects of the local distributions and variations of the driver behaviour (demand) and the network structure (supply). Investigating these relationships and proposing a full set of consistent models representing traffic dynamics at several relevant scales (successive spatial and temporal integration) is very challenging with high potential gains for traffic control applications. This is the primary goal of MAGnUM and will be achieved by mixing analytical investigations on idealized but insightful test cases with explanatory approaches based on data gained from dynamic simulations or serious game sessions on more realistic and complex cases. The second goal of the project concerns the design of innovative traffic management strategies at multiple urban scales. Breakthroughs will be achieved by considering multiple and competitive objectives when optimizing with a tight focus on environment issues and multi-modality.CMatter and strong-field gravity: New frontiers in Einstein s theoryGravity is the weakest but the most intriguing fundamental interaction in the Universe. In the last decades a formidable intellectual effort has shown that the full-fledged geometric nature of gravity offers much more than a beautiful description and understanding of all stellar and galactic. In the quest for the ultimate theory of gravity, new and spectacular connections between high-energy physics, astrophysics, cosmology and theoretical physics have emerged. Triggered by breakthroughs at the observational, experimental and conceptual levels, strong gravity physics is experiencing a Golden Age, making it one of the most active fields of research of the 21st century. My group in Lisbon has been involved in groundbreaking research into the nature of strong-field effects in curved spacetime with applications in various fields, thus establishing international leadership in the field. This proposal aims at understanding, via perturbative techniques and full-blown nonlinear evolutions, the strong-field regime of gravity, and includes challenging nonlinear evolutions describing gravitational collapse, compact binary inspirals and collisions in the presence of fundamental fields. The proposed programme will significantly advance our knowledge of Einstein's field equations and their role in fundamental questions (e.g. cosmic censorship, hoop conjecture, spacetime stability, no hair theorems), but also its interplay with high energy, astro and particle physics (testing the precise nature of the interaction between compact objects and matter --such as dark matter candidates or accretion disks-- and its imprint on gravitational wave emission, understanding gravitational-led turbulence,etc).This is a cross-cutting and multidisciplinary program with an impact on our understanding of gravity at all scales, on our perception of black hole-powered phenomena and on gravitational-wave and particle physics. :The symplectic geometry of anti-self-dual Einstein metrics#This project is founded on a new formulation of Einstein's equations in dimension 4, which I developed together with my co-authors. This new approach reveals a surprising link between four-dimensional Einstein manifolds and six-dimensional symplectic geometry. My project will exploit this interplay in both directions: using Riemannian geometry to prove results about symplectic manifolds and using symplectic geometry to prove results about Reimannian manifolds.Our new idea is to rewrite Einstein's equations using the language of gauge theory. The fundamental objects are no longer Riemannian metrics, but instead certain connections over a 4-manifold M. A connection A defines a metric g_A via its curvature, analogous to the relationship between the electromagnetic potential and field in Maxwell's theory. The total volume of (M,g_A) is an action S(A) for the theory, whose critical points give Einstein metrics. At the same time, the connection A also determines a symplectic structure \omega_A on an associated 6-manifold Z which fibres over M.My project has two main goals. The first is to classify the symplectic manifolds which arise this way. Classification of general symplectic 6-manifolds is beyond current techniques of symplectic geometry, making my aims here very ambitious. My second goal is to provide an existence theory both for anti-self-dual Poincar--Einstein metrics and for minimal surfaces in such manifolds. Again, my aims here go decisively beyond the state of the art. In all of these situations, a fundamental problem is the formation of singularities in degenerating families. What makes new progress possible is the fresh input coming from the symplectic manifold Z. I will combine this with techniques from Riemannian geometry and gauge theory to control the singularities which can occur. Cosmological Tests of GravityEinstein s theory of General Relativity (GR) is tested accurately within the local universe i.e., the solar system, but this leaves open the possibility that it is not a good description at the largest scales in the Universe. The standard model of cosmology assumes GR as a theory to describe gravity on all scales. In 1998, astronomers made a surprising discovery that the expansion of the Universe is accelerating, not slowing down. This late-time acceleration of the Universe has become the most challenging problem in theoretical physics. Within the framework of GR, the acceleration would originate from an unknown  dark energy. Alternatively< , it could be that there is no dark energy and GR itself is in error on cosmological scales. The standard model of cosmology is based on a huge extrapolation of our limited knowledge of gravity. This discovery of the late time acceleration of the Universe may require us to revise the theory of gravity and the standard model of cosmology based on GR. The main objective of my project is to develop cosmological tests of gravity and seek solutions to the origin of the observed accelerated expansion of the Universe by challenging conventional GR. Upcoming surveys will make cosmological tests of gravity a reality in the next five years. There are remaining issues in developing theoretical frameworks for probing gravitational physics on cosmological scales. We construct modified gravity theories as an alternative to dark energy and analyse  screening mechanisms to restore GR on scales where it is well tested. We then develop better theoretical frameworks to perform cosmological tests of gravity that include non-linear scales by exploiting our theoretical knowledge of the models and our state-of-the-art simulations.This grant will exploit and develop the world-leading position of the group initiated by Kazuya Koyama at the University of Portsmouth funded by the ERC starting grant (2008-2013).&Insect-inspired capillary nanostampingAim of the proposed project is a) development and establishment of insect-inspired capillary nanostamping (IICN) as next-generation contact nanolithography, b) replacing state-of-the-art lithographic and synthesis protocols requiring use of sacrificial templates or time-consuming self-assembly steps by IICN and c) significant IICN-driven acceleration and upscaling of the production of extended nanostructured systems. To meet these aims, IICN stamp design will be inspired by insect feet depositing small secretion droplets through arrays of hairy contact elements on counterpart surfaces. Monolithic IICN stamps extending cm2 will consist of spongy ink-filled substrates connected to extended arrays of spongy nanoscale dispensing elements with diameters in the 100 nm range (density up to ~130 dispensing elements per square micron). Ink supplied through the spongy pore systems forms capillary bridges between each dispensing element and counterpart surfaces, thus enabling massively parallel capillary bridge-guided nanorod synthesis. Capillary bridge rupture during stamp retraction leads to massively parallel lithographic deposition of ink nanodroplet arrays (target nanodroplet volume: a few 10 zeptolitres). IICN model applications include production of a) ultrathin nanoporous membranes for separation; b) ordered silicon nanostructures by IICN-supported metal-assisted etching; c) nearly-ergodic arrays of encapsulated liquid nanocontainers for massively parallel ensemble nanochemistry or ensemble tracing of single molecules; d) nearly-ergodic biochips for massively parallel analyte detection with single-molecule resolution. As example for substitution of time-consuming self-assembly in nanomaterial synthesis by IICN, IICN-accelerated production of ordered nanoporous alumina will be studied. To pave the way for upscaling and potential commercialization of IICN, high-throughput IICN devices for automated operation in batch and continuous roller modes will be constructed.5Externally Tuneable Separations for Membrane ReactorsWMultiscale Modelling of the Neuromuscular System for Closed Loop Deep Brain StimulationDeep brain stimulation (DBS) is an effective therapy for treating the symptoms of Parkinson s disease (PD). Despite its success, the mechanisms of DBS are not understood and there is a need to improve DBS to improve long-term stimulation in a wider patient population, limit side-effects, and extend battery life. Currently DBS operates in  open-loop , with stimulus parameters empirically set. Closed-loop DBS, which adjusts parameters based on the state of the system, has the potential to overcome current limitations to increase therapeutic efficacy while reducing side-effects, costs and energy. Several key questions need to be addressed before closed loop DBS can be implemented clinically. This research will develop a new multiscale model of the neuromuscular system for closed-loop DBS. The model will simulate neural sensing and stimulation on a scale not previously considered, encompassing the electric field around the electrode, the effect on individual neurons and neural networks, and generation of muscle force. This will involve integration across multiple temporal and spatial scales, in a complex system with incomplete knowledge of system variables. Experiments will be conducted to validate the model, and identify new biomarkers of neural activity that can used with signals from the brain to enable continuous symptom monitoring. The model will be used to design a new control strategy for closed-loop DBS that can accommodate the nonlinear nature of the system, and short- and long-term changes in system behavior. Though challenging, this research will provide new insights into the changes that take place in PD and the mechanisms by which DBS exerts its therapeutic influence. This k< nowledge will be used to design a new strategy for closed-loop DBS, ready for testing in patients, with the potential to significantly improve patient outcomes in PD and fundamentally change the way in which implanted devices utilise electrical stimulation to modulate neural activity.iMechanobiology of nuclear import of transcription factors modeled within a bioengineered stem cell niche.Many therapeutic applications of stem cells require accurate control of their differentiation. To this purpose there is a major ongoing effort in the development of advanced culture substrates to be used as  synthetic niches for the cells, mimicking the native ones. The goal of this project is to use a synthetic niche cell culture model to test my revolutionary hypothesis that in stem cell differentiation, nuclear import of gene-regulating transcription factors is controlled by the stretch of the nuclear pore complexes. If verified, this idea could lead to a breakthrough in biomimetic approaches to engineering stem cell differentiation.I investigate this question specifically in mesenchymal stem cells (MSC), because they are adherent and highly mechano-sensitive to architectural cues of the microenvironment. To verify my hypothesis I will use a combined experimental-computational model of mechanotransduction. I will a) scale-up an existing three-dimensional synthetic niche culture substrate, fabricated by two-photon laser polymerization, b) characterize the effect of tridimensionality on the differentiation fate of MSC cultured in the niches, c) develop a multiphysics/multiscale computational model of nuclear import of transcription factors within differentially-spread cultured cells, and d) integrate the numerical predictions with experimentally-measured import of fluorescently-labelled transcription factors.This project requires the synergic combination of several advanced bioengineering technologies, including micro/nano fabrication and biomimetics. The use of two-photon laser polymerization for controlling the geometry of the synthetic cell niches is very innovative and will highly impact the fields of bioengineering and biomaterial technology. A successful outcome will lead to a deeper understanding of bioengineering methods to direct stem cell fate and have therefore a significant impact in tissue repair technologies and regenerative medicine.[Localization in biomechanics and mechanobiology of aneurysms: Towards personalized medicineRupture of Aortic Aneurysms (AA), which kills more than 30 000 persons every year in Europe and the USA, is a complex phenomenon that occurs when the wall stress exceeds the local strength of the aorta due to degraded properties of the tissue. The state of the art in AA biomechanics and mechanobiology reveals that major scientific challenges still have to be addressed to permit patient-specific computational predictions of AA rupture and enable localized repair of the structure with targeted pharmacologic treatment. A first challenge relates to ensuring an objective prediction of localized mechanisms preceding rupture. A second challenge relates to modelling the patient-specific evolutions of material properties leading to the localized mechanisms preceding rupture. Addressing these challenges is the aim of the BIOLOCHANICS proposal. We will take into account internal length-scales controlling localization mechanisms preceding AA rupture by implementing an enriched, also named nonlocal, continuum damage theory in the computational models of AA biomechanics and mechanobiology. We will also develop very advanced experiments, based on full-field optical measurements, aimed at characterizing localization mechanisms occurring in aortic tissues and at identifying local distributions of material properties at different stages of AA progression. A first in vivo application will be performed on genetic and pharmacological models of mice and rat AA. Eventually, a retrospective clinical study involving more than 100 patients at the Saint-Etienne University hospital will permit calibrating estimations of AA rupture risk thanks to our novel approaches and infuse them into future clinical practice. Through the achievements of BIOLOCHANICS, nonlocal mechanics will be possibly extended to other soft tissues for applications in orthopaedics, oncology, sport biomechanics, interventional surgery, human safety, cell biology, etc.DTubular Supramolecular Polymers: A new class of therapeutic polymers{This research programme will establish a new class of materials and develop them into functional devices for biomedical applications. We will design tubular supramolecular polymers, supramolecular polymer brushes (SPBs), based on the self-assembly of cyclic peptide  polymer conjugates. The synergy between the cyclic peptide, which directs the formation of the SPBs and the polymer conjugate, which provides functionality, will open the route to a wealth of new functional structures. We will build on our initial work and expand our research to generate new synthetic routes for the ligation of polymers to peptides, develop new protocols for the characterisation of the materials, and establish the mechanism of supramolecular polymerisation. This research programme will open new horizons in the fundamental understanding and production of supramolecular polymers.< In particular, beyond the generation of new materials, the functionality of these systems may allow the development of supramolecular living polymers, a long-standing goal in polymer chemistry that is still elusive. The functionality and versatility of the SPBs obtained in this work open the route to a wealth of applications, and we will focus on one specific target: the fabrication of drug delivery vectors. We will exploit the unique combination of features presented by this new class of polymer therapeutics, such as multiple attachment points for one or more drug(s) / targeting ligands / markers, the ability to self-disassemble into smaller and easy-to-excrete components, and an elongated shape that enables diffusion and interaction with cells more efficiently than traditional globular delivery systems. We will study the pharmacology properties of the SPBs, including their stability, toxicity, mode of cell penetration and ability to deliver a single or a combination of bioactive agent(s) (in the case of concerted mechanisms).?Molecular and cellular determinants of cell monolayer mechanicsEpithelial monolayers are amongst the simplest tissues in the body, yet they play fundamental roles in adult organisms where they separate the internal environment from the external environment and in development when the intrinsic forces generated by cells within the monolayer drive tissue morphogenesis. The mechanics of these simple tissues is dictated by the cytoskeletal and adhesive proteins that interface the constituent cells into a tissue-scale mechanical syncitium. Mutations in these proteins lead to diseases with fragilised epithelia. However, a quantitative understanding of how subcellular structures govern monolayer mechanics, how cells sense their mechanical environment and what mechanical forces participate in tissue morphogenesis is lacking.To overcome these challenges, my lab devised a new technique to study the mechanics of load-bearing monolayers under well-controlled mechanical conditions while allowing imaging at subcellular, cellular and tissue resolutions. Using this instrument, my proposal aims to understand the molecular determinants of monolayer mechanics as well as the cellular behaviours that drive tissue morphogenesis. I will focus on four objectives: 1) discover the molecular determinants of monolayer mechanics, 2) characterise monolayer mechanics, 3) dissect how tension is sensed by monolayers, and 4) investigate the biophysics of individual cell behaviours participating in tissue morphogenesis.Together these studies will enable us to understand how monolayer mechanics is affected by changes in single cell behaviour, subcellular organisation, and molecular turnover. This multi-scale characterisation of monolayer mechanics will set the stage for new theoretical descriptions of living tissues involving both molecular-scale phenomena (cytoskeletal turnover, contractility, and protein unfolding) operating on short time-scales and rearrangements due to cell-scale phenomena (cell intercalation, cell division) acting on longer times.'Do intermediate-mass black holes exist?With this proposed project I will determine whether intermediate-mass black holes (IMBHs) exist. I propose to use ESA's new Gaia mission, the rich Hubble Space Telescope data archive, and state-of-the-art techniques to investigate systems predicted to exist but not yet found hitherto, such as recoiled hyper-compact stellar systems, red-supergiant mass donors to ultra-luminous X-ray sources, and white dwarf tidal disruption events. The latter can only be detected if black holes with masses less than 1E5 Msun are involved. Using these systems and events we can probe the sphere of influence of the IMBH and determine the black hole mass dynamically.Currently, there are strong indications for the existence of IMBHs, but dynamical evidence, the irrefutable proof of their existence, is still lacking. Whereas the unequivocal detection of an IMBH will be a breakthrough discovery in itself, it has also important consequences for searches of dark matter annihilation signals, it will provide a baseline for the rate predictions of gravitational wave radiation events involving IMBHs, and the properties of a population of IMBHs provides important constraints on the growth of supermassive black holes and galaxies. Finally, if we discover IMBHs in hyper-compact star clusters it validates numerical relativity simulations that predict that merging black holes receive a recoil kick.My membership of Gaia's Data Processing and Analysis Consortium gives me a distinct advantage in analysing and interpreting Gaia data that, through the superb angular resolution, immediate spectroscopic observations and all-sky coverage, provides unique capabilities ideally suited for answering the question whether IMBHs exist.My proposed project is the first to recognize the potential of Gaia (WP1&2) as well as the implications of having red supergiant mass donors in some ultra-luminous X-ray sources (WP3) for answering the question on the existence of IMBHs.[Size matters: scaling principles for the prediction of the ecological footprint of biofuelsThere is a major scientific and societal challenge in quantifying and reducing ecological footprints of products. Ecological footprint calculations suffer severely from a limited availability of data, such as the amount of energy and materials associated with the production, use and disposal of products. Furthermore, ecological footprints pertaining to biodiversity are typically biased towards a limited number of well-known species with a focus on relative species richness, leaving out ecosystem service attributes of biodiversity. As it is virtually impossible to collect all the empirical data required for all species, there is an urgent need to develop an operational framework to derive representative ecological footprints with limited data requirements. I propose to develop a novel framework based on a set of unifying scaling principles related to the production size of products and the body size of species. These scaling principles will be developed to predict key characteristics of biofuel production, such as energy return of investment, agricultural land requirements and greenhouse gas emissions, as well as global impact indicators, such as species extinction risks. The focus of the research is on (1) liquid biofuel production (bioethanol and biodiesel) from various first and second generation feedstock as an important but controversial renewable energy source (2) vascular plant diversity, as the common basis of all terrestrial ecosystems, and (3) habitat destruction and climate change, as important drivers of global change. Together with the PI, two PhD students, two Postdocs and a technical assistant will work on different components of the new predictive models, substantially enhancing the scientific understanding of how to provide reliable ecological footprints in practice.oA preparative approach to geometric effects in innovative solar cell types based on a nanocylindrical structureThe ERC Consolidator Grant project SOLACYLIN aims at providing experimental insight into the function of 'third-generation' photovoltaic systems by generating materials stacks structured in a well-defined, accurately tunable, nanocylindrical geometry. To this goal, we will develop and exploit advanced preparative methods based on two fundamental ingredients: (a) ordered 'anodic' porous oxides and (b) atomic layer deposition (ALD). The former solids will be generated as templates providing ordered arrays of straight, cyclindrical pores, the diameter and length of which can be varied between 20 nm and 300 nm and between 0.5 microns and 50 microns, respectively. The latter method will be used to coat the inner pore walls with one or several layers of the photovoltaic stack, each with a thickness set to values chosen between 1 nm and 30 nm. We will invent and characterize novel surface reaction schemes for the deposition in ALD mode (from the gas phase and from solutions) of functional materials (doped semiconductors and intrinsic light absorbers) with tailored chemical and physical p< roperties. We will investigate the experimental conditions in which they can be combined in a way that optimizes the quality of their interfaces. Finally, we will quantify the electrical and photovoltaic performance of p-i-n junctions prepared with our methods. We will have the unique capability of describing in a systematic, accurate manner how the experimental photovoltaic parameters depend on the individual thicknesses of the individual layers and on the length of the cylinders. This direct experimental handle on the amount of light absorbed, on the one hand, and the charge carrier transport distances to the electrical contacts, on the other hand, will be correlated with the relevant material parameters (absorption coefficients, carrier mobilities). This information will unveil the phenomena limiting the efficiency of each type of solar cell, and suggest avenues to remedy them.kA Chemical Approach to Molecular Spin Qubits: Decoherence and Organisation of Rare Earth Single Ion MagnetsxCoordination Chemistry and Molecular Magnetism are in an ideal position for the rational design of Single-Molecule Magnets which can be used as molecular spin qubits, the irreducible components of any quantum technology. Indeed, a major advantage of molecular spin qubits over other candidates stems from the power of Chemistry for a tailored and inexpensive synthesis of systems for their experimental study. In particular, the so-called Lanthanoid-based Single-Ion Magnets, which are currently the hottest topic in Molecular Magnetism, have the potential to be chemically designed, tuning both their single-molecule properties and their crystalline environment. This will allow the independent study of the different quantum processes that cause the loss of quantum information, collectively known as decoherence. The study of quantum decoherence processes in the solid state is necessary both to lay the foundations for next-generation quantum technologies and to answer some fundamental questions.The goals of this project are:#1 To unravel the mechanistic details of decoherence in molecular spin qubits based on mononuclear lanthanoid complexes. This study will stablish criteria for the rational design of single spin qubits.#2 To extend this study to the coupling between two or more spin qubits. This will allow us to explore the use of polynuclear lanthanoid complexes to achieve quantum gates or simple algorithms.#3 To extrapolate to infinite systems formed by the complex organization of spin qubits. This exploratory goal will permit us to move beyond zero-dimensional systems, thus facilitating the advance towards complex quantum functions.`Novel etiology of autoimmune disorders: the role of acquired somatic mutations in lymphoid cellsMolecular pathogenesis of most immune-mediated disorders, such as of autoimmune diseases, is poorly understood. These common maladies carry a heavy burden both on patients and on society. Current therapy is non-targeted and results in significant short- and long-term adverse effects.Large granular lymphocyte (LGL) leukemia is characterized by expansion of cytotoxic T- or NK-cells and represents an intriguing clinical continuum between a neoplastic and an autoimmune disorder. Patients suffer from autoimmune cytopenias and rheumatoid arthritis (RA), which are thought to be mediated by LGL cells targeting host tissues. My group recently discovered that 40-50% of LGL leukemia patients carry in their lymphoid cells acquired, activating mutations in the STAT3 gene  a key regulator of immune and oncogenic processes (Koskela et al, N Engl J Med, 2012). This breakthrough discovery gives insight to the pathogenesis of autoimmune disorders at large. I present here a hypothesis that a strong antigen-induced proliferation is a mutational driver, which causes somatic mutations in lymphoid cells. When mutations hit key activating pathways, autoreactive cells acquire functional advantage and expand. The target antigen of the expanded clone determines the clinical characteristics of the autoimmune disease induced. To prove this hypothesis, we will separate small lymphocyte clones from patients with autoimmune diseases and use sensitive next-generation sequencing methods to characterize the spectrum of somatic mutations in lymphoid cells. Further, we will study the function of mutated lymphocytes and examine the mechanisms of autocytotoxicity and end-organ/tissue damage. Finally, we aim to understand factors, which induce somatic mutations in lymphoid cells, such as the role of viral infections.The results will transform our understanding of molecular pathogenesis of autoimmune diseases and lead to accurate diagnostics and discovery of novel drug targets.OUnravelling Fragile 1D Quantum States of Matter Through Ultra-sensitive ImagingIn condensed matter physics there are several iconic predictions that have evaded experimental discovery for many decades. Well-known examples include the proposed fractionally-charged quasiparticles in one-dimension, the theorized quantum crystal of electrons, and the elusive Kondo cloud. These sought-after many-body states all share two key aspects underscoring why they are so hard to discover: They each involve a fragile quantum state of matter that is destroyed easily by disorder or elevated temperatures, and in each case the distinguishing fingerprint is encoded in their real-space structure, which is often difficult to probe directly. The discovery of such phases therefore requires two challenging experimental components: A superb material system in which these phases can be generated, and a novel real-space probe that can image their spatial structure, yet is minimally invasive as not to destroy them. Recently, we have developed a radically new approach for creating the state-of-the-art in both material systems and scanning probes, based on carbon nanotube devices of unprecedented complexity and cleanliness. With these components in place, we are poised to make the next quantum leap in technology by building a conceptually new experimental platform in which fragile quantum states of matter can be realized and studied microscopically: We will use a nanotube single-electron-transistor as a high-resol< ution, ultrasensitive scanning charge detector to non-invasively image an exotic quantum state within a second pristine nanotube. With this new platform we will thus be able to address several foundational questions in condensed matter physics (including those mentioned above) and unravel their underlying physics. $3D Bioprinting of JOINT ReplacementsThe world has a significant medical challenge in repairing injured or diseased joints. Joint degeneration and its related pain is a major socio-economic burden that will increase over the next decade and is currently addressed by implanting a metal prosthesis. For the long term, the ideal solution to joint injury is to successfully regenerate rather than replace the damaged cartilage with synthetic implants. Recent advances in key technologies are now bringing this  holy grail within reach; regenerative approaches, based on cell therapy, are already clinically available albeit only for smaller focal cartilage defects.One of these key technologies is three-dimensional (3D) bio-printing, which provides a greatly controlled placement and organization of living constructs through the layer-by-layer deposition of materials and cells. These tissue constructs can be applied as tissue models for research and screening. However, the lack of biomechanical properties of these tissue constructs has hampered their application to the regeneration of damaged, degenerated or diseased tissue.Having established a cartilage-focussed research laboratory in the University Medical Center Utrecht, I have addressed this biomechanical limitation of hydrogels through the use of hydrogel composites. Specifically, I have pioneered a 3D bio-printing technology that combines accurately printed small diameter thermoplast filaments with cell invasive hydrogels to form strong fibre-reinforced constructs. This, in combination with bioreactor technology, is the key to the generation of larger, complex tissue constructs with cartilage-like biomechanical resilience. With 3D-JOINT I will use my in-depth bio-printing and bioreactor knowledge and experience to develop a multi-phasic 3D-printed biological replacement of the joint. 7Modulation of RNA-based regulatory processes by virusesSmall and large non-coding RNAs are essential components at the heart of gene expression regulation. The past fifteen years have witnessed the emergence of a new field of research impacting diverse domains of biology. Among these, virology is no exception and discoveries such as the antiviral role of RNA silencing, virus-encoded microRNAs (miRNAs), or miRNA-based regulation of viruses have notably shifted our views of host-virus interactions. Although we know a lot about the mechanisms of action of ncRNAs, and their role in the context of viral infections, we know much less regarding the control of the regulatory RNAs themselves. In other words, how are the regulators regulated? To provide answers to this burning question, we propose to use different viruses as models to investigate the various levels where modulation of regulatory RNA can occur. Thus, we will study the importance of RNA secondary and tertiary structure as well as accessory proteins in the regulation of miRNA primary transcript processing. In a second axis, we propose to investigate how the functional, mature miRNAs can be controlled. To this end, we will focus on the mechanisms of target-mediated miRNA decay and the role of competing endogenous RNAs. We will finally turn to the regulation of antiviral RNA silencing. Although it seems that this kind of defence mechanism exist in mammalian cells, it is not yet clear how physiologically relevant it is and how it interfaces with other innate immune mechanisms. In this multidisciplinary project, we will use a combination of techniques ranging from bioinformatics to cellular biology to achieve our goal to get a comprehensive view of how RNA silencing processes are regulated during virus infection.%Unconventional Bifunctional CatalystsThe development of sustainable chemical processes is one of the most important features in modern chemistry. It has become a key research area worldwide providing solutions to important societal demands by optimizing the use of natural resources and minimizing waste and environmental impact. Among the relevant methods for achieving this goal, catalysis represents a key and central approach. Both Organocatalysis and Metal Catalysis have emerged as solutions to the problems in this context. In this field, the progress of a novel bifunctional organocatalyst that could increase the number of different activations, and therefore the synthesis of valuable enantio-enriched molecules, would be highly desirable. Especially important, but still unknown, are the bifunctional-catalysts based on a Neutral Coordinate Organocatalyst and Photo-Organocatalysts. This proposal aims to develop two new unconventional approaches for the synthesis of bifunctional organocatalysts. The first one is based on the development of new Bifunctional Neutral Coordinate Organocatalyst and their application to the synthesis of biologically relevant compounds. I propose to use these bifunctional catalysts to promote the dual activation of silyl reagents and suitable electrophiles. This approach constitutes an unconventional way to synthesize asymmetric molecules and has no precedent in the literature. The second section of this proposal explores the photo-activation-bifunctional organocatalyst. I propose the design and application of new metal-free Bifunctional Photo-Organocatalysts which are able to chemically and photo-activate the substrate simultaneously in an asymmetric manner. This project has the potential to change the general view of asymmetric Neutral Coordinate Organocatalyst and Photo-catalysis as we know it today. These unconventional bifunctional would be incorporated into the privileged catalyst library for its applications in new asymmetric transformations.TDirect Visualization of Light-Driven Atomic-Scale Carrier Dynamics in Space and TimeElectronics is rapidly speeding up. Ultimately, miniaturization will reach atomic dimensions and the switching speed will reach optical frequencies. This ultimate regime of lightwave electronics, where atomic-scale charges are controlled by few-cycle laser fields, holds promise to advance information pro< cessing technology from today s microwave frequencies to the thousand times faster regime of optical light fields. All materials, including dielectrics, semiconductors and molecular crystals, react to such field oscillations with an intricate interplay between atomic-scale charge displacements (polarizations) and collective carrier motion on the nanometer scale (currents). This entanglement provides a rich set of potential mechanisms for switching and control. However, our ability to eventually realize lightwave electronics, or even to make first steps, will critically depend on our ability to actually measure electronic motion in the relevant environment: within/around atoms. The most fundamental approach would be a direct visualization in space and time. This project, if realized, will offer that: a spatiotemporal recording of electronic motion with sub-atomic spatial resolution and sub-optical-cycle time resolution, i.e. picometers and few-femtoseconds/attoseconds. Drawing on our unique combination of expertise covering electron diffraction and few-cycle laser optics likewise, we will replace the photon pulses of conventional attosecond spectroscopy with freely propagating single-electron pulses at picometer de Broglie wavelength, compressed in time by sculpted laser fields. Stroboscopic diffraction/microscopy will provide, after playback of the image sequence, a direct visualization of fundamental electronic activity in space and time. Profound study of atomic-scale light-matter interaction in simple and complex materials will provide a comprehensive picture of the fundamental physics allowing or limiting the high-speed electronics of the future.GDetecting Local Adaptation with Climate-Informed Spatial Genetic ModelsLocal adaptation, whereby individuals of a population exhibit higher fitness in their local environment compared to that experienced by other populations, has the potential to shape the distribution of genetic diversity and influence speciation. However, detecting and quantifying the extent of local adaptation is challenging, since neutral demographic processes can leave signatures which are hard to distinguish from those of local selection. In this project, I propose to quantify the extent of local adaptation in Anatomically Modern Humans by using climate-informed spatial genetic models (CISGeM) to reconstruct past population sizes, local movements, and range expansions, and thus provide a null model against which the signature of geographically-localised selection can be detected.In CISGeM, demography is affected by local resource availability, which in turn is defined by paleoclimate and paleovegetation reconstructions. By using these additional lines of evidence, it is possible to generate accurate demographic reconstructions for any number of populations, as well as integrating information from both modern and ancient genomes. Such spatially-explicit reconstructions are key for defining the expected neutral patterns due to complex demography, and thus allow us to isolate the signals of selection from this noisy background with high fidelity. The availability of paleoclimate reconstructions also enables formally testing hypotheses about the drivers of selection, integrating the changes in the strength of selection through space and time.While this project will be focused on Anatomically Modern Humans, the framework that I will develop will be applicable to the investigation of local adaptation from genomic data in any species. Such tools are very timely, given the ever-increasing availability of large genetic datasets thanks to the decreasing cost of genotyping and sequencing in both model and non-model organisms.'Neural oscillations - a code for memoryEpisodic memory refers to the fascinating human ability to remember past events in a highly associative and information rich way. But how are these memories coded in human brains? Any mechanism accounting for episodic memory must accomplish at least two functions: to build novel associations, and to represent the information constituting the memory. Neural oscillations, regulating the synchrony of neural assemblies, are ideally suited to accomplish these two functions, but in opposing ways. On the one hand, neurophysiological work suggests that increased synchrony strengthens synaptic connections and thus forms the basis for associative memory. Neurocomputational work, on the other hand, suggests that decreased synchrony is necessary to flexibly express information rich patterns in a neural assembly. Therefore, a conundrum exists as to how oscillations code episodic memory. The aim of this project is to propose and test a new framework that has the potential to reconcile this conflict. The central idea is that synchronization and desynchronization cooperatively code episodic memories, with synchronized activity in the hippocampus in the theta (~4 Hz) and gamma (~ 40-60 Hz) frequency range mediating the building of associations, and neocortical desynchronization in the alpha (~10 Hz) and beta (~15 Hz) frequency range mediating the representation of mnemonic information. Importantly the two modules, with their respective synchronous/asynchronous behaviours, must interact during the formation and retrieval of episodic memories, but how and whether this is the case remains untested to date. I will test these fundamental questions using a multidisciplinary and multi-method approach, including human single cell recordings, neuroimaging, brain stimulation, and computational modelling. The results from these experiments have the potential to reveal the neural code that human episodic memory is based on, which is still one of the biggest mysteries of the human mind.;Nanoencapsulation for Energy Storage and Controlled ReleaseIThe main vision of the project ENERCAPSULE is the development of nanoencapsulation technologies based on switchable nanoscale barriers for novel generation of controlled energy storage and delivery systems. These systems will be based on the  smart nanocontainers (size below 200 nm) loaded with the energy-enriched active components: materials for thermal energy (b< oth latent and based on chemical reactions) storage and substances for bioenergy (ATP or its components) storage for synthetic biology platforms. First novelty of the proposed project is the protection of the nanoscaled energy-enriched materials against environment during storage and controlled release of the encapsulated energy on demand only using both inherent properties of nanocontainer shell or biomimetic nanovalves introduced as shell components. Another main objective of the project is to study the structure and surface-to-volume properties of the energy enriched materials dispersed and encapsulated on nanoscale. The questions of stability of energy nanomaterials, influence of the nanocontainer shell on their energy capacity, homogeneity and operation lifetime will be investigated. Polymer organic nanocapsules with hollow interior and mesoporous carbon nanoparticles are chosen in the project as main types of the nanocontainer scaffolds for energy-enriched materials due to their high loading capacity and potential to design their shells to attain them controlled permeability properties. At the end of the project, developed novel energy storage and delivery systems will be combined within one network having several mechanisms for release and uptake of energy, which can be activated depending on type and intensity of the external impact (demand). The potential applications of such multienergy storage systems will be tested by industrial companies supporting the project.*3-Dimensional Maps of the Spinning NucleonHow does the inside of the proton look like? What generates its spin?( 3DSPIN will deliver essential information to answer these questions at the frontier of subnuclear physics.At present, we have detailed maps of the distribution of quarks and gluons in the nucleon in 1D (as a function of their momentum in a single direction). We also know that quark spins account for only about 1/3 of the spin of the nucleon.3DSPIN will lead the way into a new stage of nucleon mapping, explore the distribution of quarks in full 3D momentum space and obtain unprecedented information on orbital angular momentum. Goals1. extract from experimental data the 3D distribution of quarks (in momentum space), as described by Transverse-Momentum Distributions (TMDs);2. obtain from TMDs information on quark Orbital Angular Momentum (OAM).Methodology3DSPIN will implement state-of-the-art fitting procedures to analyze relevant experimental data and extract quark TMDs, similarly to global fits of standard parton distribution functions. Information about quark angular momentum will be obtained through assumptions based on theoretical considerations. The next five years represent an ideal time window to accomplish our goals, thanks to the wealth of expected data from deep-inelastic scattering experiments (COMPASS, Jefferson Lab), hadronic colliders (Fermilab, BNL, LHC), and electron-positron colliders (BELLE, BABAR). The PI has a strong reputation in this field. The group will operate in partnership with the Italian National Institute of Nuclear Physics and in close interaction with leading experts and experimental collaborations worldwide.ImpactMapping the 3D structure of chemical compounds has revolutionized chemistry. Similarly, mapping the 3D structure of the nucleon will have a deep impact on our understanding of the fundamental constituents of matter. We will open new perspectives on the dynamics of quarks and gluons and sharpen our view of high-energy processes involving nucleons.eInterfacing spin waves with superconducting quantum circuits for single magnon creation and detectionCSocial Cognition in Adolescents: Brain Networks and Social NetworkskThe forming of social bonds is an evolutionary imperative, and a rich target for empirical research. Social scientists have scrutinized the structure of the elaborate social networks that characterize today s society. Neuroscientists have elucidated the brain mechanisms underlying our ability to navigate this social world. Yet, these research lines have been largely separated. This proposal aims to integrate social network research and social brain research, focusing on adolescence as the most dynamic phase shaping the interplay between social networks and the social brain. Social development in adolescents is clearly driven by maturation of specific social-cognitive functions; yet these functions are manifest in, and moulded by, interpersonal relationships within social networks. I aim to clarify how changes in the social brain relate to changes in social network position and structure during adolescent development. This can be achieved by using the quantitative tools of social network analysis in conjunction with the experimental approach of social neuroscience. I plan to investigate a cohort of approximately 1000 adolescents nested in 50 classes in a longitudinal design with 6 measurements over 3 years; fMRI investigating task-related func< tional activation and connectivity is conducted yearly in a subsample of 100. The neural and behavioural correlates of social cognition are investigated using experimental tasks tapping i) understanding others and ii) interacting with others; social behaviour is charted through ecological momentary assessment techniques; social networks are mapped using surveys and digital information acquired routinely via mobile phones (mobile sensing). This approach clarifies how during a crucial developmental phase the social brain shapes the social environment, and vice versa, the social environment influences maturation of the social brain.wRethinking Disability: the Global Impact of the International Year of Disabled Persons (1981) in Historical PerspectiveApproximately 10% of the world s population is estimated to be disabled and this number is expected to rise in the next few decades. People in different cultural settings ascribe different meanings to disability; consequently, its repercussions are both culturally contingent and universal. This project brings together the local and global dimensions of disability and examines the interaction, tension and conflict between these two aspects by undertaking the first comprehensive study of the far-reaching political, societal and cultural implications of the International Year of Disabled Persons (IYDP) which was organized under the auspices of the United Nations in 1981. A landmark event which appears to have gone virtually unrecognized in scholarship; the IYDP was the first occasion to place disability into a global context by endorsing it authoritatively as a human rights issue and thereby raising the question as to how the concept may be understood in a multicultural world. There will be four closely-related objectives: 1. to examine the IYDP s impact on human rights discourses and to scrutinize their applicability within global settings; 2. to document the IYDP s contribution to emancipation and social change and to consider the different trajectories of emancipation in various parts of the world; 3. to assess the ways in which the IYDP influenced everyday life experiences, galvanized identity formation and inspired the emergence of a distinct subculture; 4. to analyze the transnational exchanges and knowledge transfer in conjunction with the IYDP and to examine how the Western oriented discourses penetrating the developing world interacted with the local environment. The project s innovative contribution and academic impact lies in connecting the IYDP to broader political, social and cultural processes in the last quarter of the twentieth century and thereby bringing disability in a global context to the attention of mainstream historical scholarship.LHow the Brain Learns to Forget - The Neural Signature of Fear Memory ErasureCan fear memories be erased from the brain? While it sounds like science fiction, recent findings suggest that fear memories can be undone upon their retrieval, through either pharmacological or behavioural interventions. Still, whether such reconsolidation interference techniques genuinely result in permanent erasure of the original fear memory is a topic of considerable controversy. Purely behavioural work may never settle the debate, as it cannot be excluded that an apparent loss of fear memory reflects a long-lasting failure to retrieve the fear memory rather than its permanent erasure. We argue that a careful look at the brain memory circuits that control the reduced expression of fear after reconsolidation interference, through imaging studies in humans and inactivation studies in rats, does have the potential to resolve the controversy and decide between erasure and retrieval failure as mechanisms underlying reconsolidation interference [WP1]. To open up a memory trace for reconsolidation interference, it is important that retrieval of the memory is accompanied by surprise or prediction error (PE; a discrepancy between the memory and what actually happens), as we demonstrated in a break-through study in Science (Sevenster, Beckers, & Kindt, 2013). Here, we propose that subtle differences in the degree of PE generated during fear memory retrieval may be what demarcates memory erasure from impaired retrieval. To investigate that claim, we will pioneer an objective neural marker of PE in humans [WP2] and use optogenetics to directly trigger dopamine-based PE signals in the rat brain in order to establish the causal role of PE in enabling fear memory erasure. Along the way, we will investigate the generalization of fear to novel cues as both a problem and a potential target for fear memory modification [WP3] and test an innovative method to interfere with reconsolidation that circumvents limitations of current pharmacological and behavioural techniques [WP4].Quantum Metamaterials: A Theoretical and Computational Approach Towards Seamlessly Integrated Hybrid Classical/Quantum Nano-structuresThe overarching aim of this proposal is to initiate and advance an integrated theoretical and computational research programme in an emerging area of metamaterials research, namely Quantum Metamaterials. Thus, it is commonly believed that one of the most noteworthy developments witnessed in the last decade in physical sciences and engineering is the emergence of metamaterials. Unlike ordinary materials, which are assembled at the atomic level, metamaterials are composite materials built up from artificially engineered meta-atoms and meta-molecules. The fundamental idea in this area of research is that remarkable physical properties beyond those available in naturally occurring materials can be achieved by designing the meta-constituents of the metamaterial and structuring it at a scale comparable or smaller than the optical wavelength. In this context, a new paradigm in metamaterials research emerges when the building blocks of metamaterials are quantum resonators, e.g., quantum dots (QDs), QD molecules, graphene disks coupled to interacting QDs, and quantum nanowires, case in which the macroscopic properties of quantum metamaterials are determined by the quantum properties of their basic constituents. We have organised this research programme along< three broad, synergistically integrated themes. The first will focus on the development of a general theory of the effective, macroscopic properties of quantum metamaterials. The key challenge is to build a theoretical framework in which the macroscopic properties of quantum metamaterials are derived directly from those of their quantum building blocks. The second theme will be geared towards developing a set of numerical methods and software tools for ab initio simulations of fundamental physical properties quantum metamaterials. The foundational work pertaining to the first two themes will enable us to pursue the main objective of the third theme, which is the exploration of new science and novel applications.8In-situ produced nanoparticles for enhanced oil recovery The era of finding  easy oil is coming to an end, and future supply will become more reliant on fossil fuels produced from enhanced oil recovery (EOR) process. Many EoR methods have been used, including mechanical, chemical, thermal and biological approaches, but there are still 50~70% of the original oil trapped in reservoir rocks after the primary and secondary recovery. NanoEOR, i.e, injecting nanoparticles (NPs) together with flooding fluids, is an emerging field. However all proposed applications are based on pre-fabricated NPs, which encountered enormous problems in NP stabilization and transport under reservoir conditions. This project proposes a revolutionary concept, iNanoEOR: in-situ production of NPs inside the reservoir for enhanced oil recovery. Rather than pre-manufacturing, dispersing and stabilizing NPs in advance, NPs will be produced in the reservoir by controlled hydrothermal reactions, acting as sensors to improve reservoir characterisation, or as property modifiers to effectively mobilize the trapped oil. This project will validate the innovative iNanoEOR concept by answering three questions: i) how the concept works? ii) what kind of NPs should be produced that can effectively mobilize trapped oil? iii) what are desired NP properties to allow them flow through a reservoir? Three work programs are designed, and a number of breakthroughs beyond state-of-art research are expected, which include i) proof-of-concept of the innovative iNanoEOR, ii) developing a new methodology for temperature measurement inside a reservoir, iii) revelation of the influence of NPs on EOR under reservoir-like conditions, iv) understanding the controlling factors in NP transport at different scales. The project will not only contribute directly to iNanoEOR, but also transfers the PI s expertise in nanomaterials and multiphase flow into oil and gas sector and underpin many NP-related subsurface applications, which currently is non-existing in the Europe.BWIreLess LOWband communications: massive and ultra-reliable accessThe overall objective of WILLOW is to make wireless communication a true commodity by enabling lowband communications: low-rate links for massive number of devices and ultra-reliable connectivity. This research effort is a major endeavour in the area of wireless communications, taking a different path from the mainstream research that aims at  4G, but faster . Lowband communication is the key to enabling new applications, such as massive sensing, ultra-reliable vehicular links and wireless cloud connectivity with guaranteed minimal rate. The research in WILLOW is centred on two fundamental issues. First, it is the efficient communication with short packets, in which the data size is comparable to the size of the metadata, i.e. control information, which is not the case in broadband communication. Communication of short packets that come from a massive number of devices and/or need to meet a latency constraint requires fundamental rethinking of the packet structure and the associated communication protocols. Second is the system architecture in which graceful rate degradation, low latency and massive access can exist simultaneously with the broadband services. The principles from WILLOW will be applied to: (a) clean-slate wireless systems; (b) reengineer existing wireless systems. Option (b) is unique to lowband communication that does not require high physical-layer speed, but can reuse the physical layer of an existing system and redefine the metadata/data relationship to achieve massive/ultra-reliable communication. WILLOW carries high risk by conjecturing that it is possible to support an unprecedented number of connected devices and wireless reliability levels. C< onsidering the timeliness and the relevance, the strong track record of the PI and the rich wireless research environment at Aalborg University, WILLOW is poised to make a breakthrough towards lowband communications and create the technology that will enable a plethora of new wireless usage modes.bBehavioral and neural determinants of metacognition and self-awareness in human adults and infantsProposal summary. Understanding the psychological and neurobiological determinants of consciousness is fundamental. Yet, the main trend focusing on how the front of the brain (prefrontal cortex) interacts with the back (sensory cortex) for accessing perceptual contents limits our understanding of the information coding schemas underlying consciousness. Here, we explore these informational properties in adults and infants from 3 novel perspectives: sleep, self-consciousness and metacognition. First, we will study unconscious processes in the full absence of consciousness, including self-consciousness and metacognition, by focusing on the sleeping brain s ability to process and learn information from its environment. While most studies on subliminal perception measured unconscious processes intermixed with conscious ones, studying their impact in the sleeping brain will provide new insights on a broader and more natural type of unconscious. Secondly, we will explore the fundamental issue of whether multiple agents can share information and each other s conscious access mechanisms, without being aware of it. Using a novel approach called the  Reversed Perspective Paradigm , we will study if access to conscious content can be determined by another agent s actions and sensory processing while the agent is lured to believe she owns these access mechanisms. We aim at challenging the long-held conviction that consciousness is a paradigm of privacy, by breaking it using virtual reality and objective methods from psychology. Finally, we will attempt to answer the two fundamental issues of whether infants have a capacity for metacognition (do they know they know) and whether they experience self-consciousness (do they feel themselves as a unitary entity). Examining these self-reflection mechanisms, through behavioural and EEG techniques, will address the issue of whether humans in the initial state have a primitive self, or are actually unconscious about their own person.Large Discrete StructuresThe proposed project seeks to introduce novel methods to analyze and approximate large graphs and other discrete structures and to apply the developed methods to solve specific open problems. A need for such methods comes from computer science where the sizes of input structures are often enormous. Specifically, the project will advance the recently emerged theory of combinatorial limits by developing new insights in the structure of limit objects and by proposing a robust theory bridging the sparse and dense cases. The analytic methods from the theory of combinatorial limits will be used to analyze possible asymptotic behavior of large graphs and they will be applied in conjunction with structural arguments to provide solutions to specific problems in extremal combinatorics. The obtained insights will also be combined with methods from discrete optimization and logic to provide new algorithmic frameworks.^Optical nanoscopy at 1 nm resolution: far-field fluorescence control at cryogenic temperaturesOptical nanoscopy is a powerful technique used in biology to study subcellular structures and function via specifically targeted fluorescent labels. Localization microscopy in particular offers a much better resolution (~10-50 nm) than conventional microscopy (~250 nm) while being relatively undemanding on the experimental setup and the subsequent image analysis. The next revolution in imaging to 1 nm isotropic resolution in 3D must realize a big increase in the number of collected photons from single fluorescent emitters as well as in the labelling density. Only then can subcellular structures be imaged at the molecular level to study the molecular machinery of the cell. Notably observations of DNA conformation in 3D at such resolutions would be spectacular and enable investigation of biophysical models ranging from chromosomal DNA packaging to gene regulation.I propose a new imaging technique based on fluorescence control at cryogenic temperatures in combination with novel data driven super-resolution reconstruction schemes employing prior knowledge that promises this unprecedented optical far-field resolution. I introduce a twofold technical leap by i) much higher photon counts due to negligible photobleaching at cryogenic temperatures while maintaining the sparsity required for single emitter localization and ii) relaxing the required labelling density using a priori information and the averaging of many identical entities. Orientational blinking ensures single emitter localization via a combination of polarization sensitive excitation, detection and stimulated depletion and triplet state shelving.Biophysical models of cell structures and data driven priors mean that fewer samples are needed to fully describe a structure.In a larger perspective, the outcome of this research will enable the combination of structural cryo-electron microscopy imaging at subnanometer resolutions with functional fluorescent imaging at the nanometer scale.-Very fast Imaging by Broadband coherent RAmanThe VIBRA project aims at developing an innovative microscope for real-time non-invasive imaging of cells and tissues, which promises to have a revolutionary impact on several fields of biology and medicine. Chemically specific vibrational signatures of molecules enable their direct structural characterization. Reliable and quantitative endogenous bio-markers can be established, e.g., to follow cell differentiation and to identify crucial properties of tissues (malignant vs benign phenotype of a tumour). In this way neoplasms can be located and their borders with normal tissue traced for surgery. Spontaneous Raman spectroscopy demonstrated this capability, but it is intrinsically too slow for imaging. Coherent Raman microscopy, on the other hand, c< an reach extremely high speed (up to the video rate) but at the expense of poor chemical selectivity, being limited to a single vibrational frequency.The ground-breaking goal of VIBRA is to combine the most detailed molecular information over the entire vibrational spectrum with the highest acquisition speed. The PI will develop a complete coherent Raman microscope for near-video-rate broadband vibrational imaging. This high risk/high gain goal will be achieved by the combination of four key developments: improved pulsed laser source; optimized non-linear interaction, enhancing the signal; increase in acquisition speed, thanks to innovative spectrometers; parallel on-board data processing.In the final application phase, the VIBRA project will validate the performances of the novel vibrational imaging system studying two important bio-medical problems: cancerous cell differentiation and detection of neuronal tumours. This will pave the way towards future  virtual histopathology : intraoperative non-invasive evaluation of cancerous tissue. My vision is to allow researchers and doctors without a specific knowledge in lasers and optics to routinely visualize functional properties of cells and tissues in vivo.&REsistive-Switch CompUting bEyond CMOS:Digital computers rely today on CMOS (complementary metal-oxide-semiconductor) technology, which improves its performance every generation thanks to the Moore s law of downscaling. As CMOS transistor size approaches few nm, alternative logic switches with better scaling capability must be identified to prolong Moore s law beyond CMOS. Among the emerging switching concepts, resistive switching (RS) devices can change their resistance by electrically-induced redox reactions. RS provides the basis for the resistive memory (ReRAM) technology which is currently investigated as future computer memory and storage technology. The objective of this project is to design, develop and demonstrate a novel computing paradigm based on RS devices. The project will pursue this objective at 3 levels of increasing complexity, namely the device fabrication, the design of new logic gates and the demonstration of computing circuits. RS logic will be finally compared to CMOS and other approaches to identify the strength and the potential applications of RS logic in the computing scenario.^No Sword Bites So Fiercly as an Evil Tongue?Gossip Wrecks Reputation, but Enhances Cooperation,Social norms in general, and norms of cooperation in particular, are the cement of all human societies. For the difficult problems of the maintenance and enforcement of social norms and of cooperation, humans have developed surprisingly complex solutions. Reputation mechanisms and gossip are certainly among the compound informal solutions. According to common wisdom, gossip channels mainly negative and often fictitious information. If it is so, how can dishonest gossip and the resulting biased reputations legitimize social order and promote cooperation? This is the main puzzle we tackle in the proposed project exploiting a wide scale of instruments. We use analytical modeling and agent-based simulation to derive hypotheses. We test simple hypotheses in small group experiments. We develop new methodological tools to appropriately analyze the triadic nature of gossip embedded in network flows of information. We utilize dynamic network datasets from primary and secondary school classes, and we gather qualitative and quantitative information from organizations to test conditional hypotheses about the role that gossip plays in reputation and cooperation in different developmental and social contexts of life. In addition, we apply new communication technologies currently under development to explore the hidden world of gossip and the dynamics of reputations in dormitories and organizations. With the insights gained, we can overcome common stereotypes about gossip and highlight how gossip is related to credible reputational signals, cooperation, and social order. Expected results will help us to outline the conditions that can promote cooperativeness in work groups, and they will help to construct successful prevention strategies of social exclusion and other potentially harmful consequences of the evil tongue.tTowards the design of Personalised Polymer-based Combination Nanomedicines for Advanced Stage Breast Cancer PatientsResearch on anticancer therapies has provided little progress towards improved survival rates for patients with metastatic disease. The intrinsic advantages of polymer conjugates can be optimised to rationally design targeted combination therapies, concept I pioneered that allows enhanced therapeutic efficiency. Early clinical trials involving conjugates showed activity in chemotherapy refractory patients and reduced drug-related toxicity. However, there is a growing concern on patient variability regarding tumor patho-physiology that underlie successful therapeutic outcome. Specific biomarkers are required to select those patients most likely to show good clinical response to these therapies. The objective of MyNano is to engineer polymer-based combination therapies designed to treat metastatic breast cancer in a patient personalised manner. Therefore, novel multicomponent polymer conjugates with precise control over size, shape, solution conformation, multifunctionality and bioresponsiveness will be obtained while in parallel their structure activity relationships to underlying proposed mechanisms of action in clinically relevant models will be studied. Polyglutamates obtained by controlled polymerisation and self-assembly strategies will be the carriers. Primary breast cancer patient tissue will be used to generate cell and in vivo models representing different clinical molecular subtypes. MyNano will also investigate new combination strategies using current treatments together wit< h inhibitors of tumor-derived exosome release pathways, phenomenon related to metastasis and resistance mechanisms. The aim is to provide a novel methodological approach that would allow by reiterative design to optimise the design of the next generation nanoconjugates for the treatment of specific metastatic cancer clinical subtypes. MyNano will be a breakthrough as it introduces a paradigm shift in the strategy to design nanomedicines in areas of unmet clinical need.FStructure of paramagnetic integral membrane metalloproteins by MAS-NMRIntegral membrane metalloproteins are involved in the transport and homeostasis of metal ions, as well as in key redox reactions that have a tremendous impact on many fields within life sciences, environment, energy, and industry. Most of our understanding of fine details of biochemical processes derives from atomic or molecular structures obtained by diffraction methods on single crystal samples. However, in the case of integral membrane systems, single crystals large enough for X-ray diffraction cannot be easily obtained, and the problem of structure elucidation is largely unsolved. We have recently pioneered a breakthrough approach using Magic-Angle Spinning Nuclear Magnetic Resonance (MAS-NMR) for the atomic-level characterization of paramagnetic materials and complex biological macromolecules. The proposed project aims to leverage these new advances through a series of new concepts i) to improve the resolution and sensitivity of MAS-NMR from nuclei surrounding a paramagnetic metal ion, such as e.g. cobalt, nickel and iron, and ii) to extend its applicability to large integral membrane proteins in lipid membrane environments. With these methods, we will enable the determination of structure-activity relationships in integral membrane metalloenzymes and transporters, by combining the calculation of global structure and dynamics with measurement of the electronic features of metal ions. These goals require a leap forward with respect to today s protocols, and we propose to achieve this through a combination of innovative NMR experiments and isotopic labeling, faster MAS rates and high magnetic fields. As outlined here, the approaches go well beyond the frontier of current research. The project will yield a broadly applicable method for the structural characterization of essential cellular processes and thereby will provide a powerful tool to solve challenges at the forefront of molecular and chemical sciences today.=Synchronisation to enhance reliability of climate predictionsClimate prediction is the next frontier in climate research. Prediction of climate on timescales from a season to a decade has shown progress, but beyond the ocean skill remains low. And while the historical evolution of climate at global scales can be reasonably simulated, agreement at a regional level is limited and large uncertainties exist in future climate change. These large uncertainties pose a major challenge to those providing climate services and to informing policy makers.This proposal aims to investigate the potential of an innovative technique to reduce model systematic error, and hence to improve climate prediction skill and reduce uncertainties in future climate projections. The current practice to account for model systematic error, as for example adopted by the Intergovernmental Panel on Climate Change, is to perform simulations with ensembles of different models. This leads to more reliable predictions, and to a better representation of climate. Instead of running models independently, we propose to connect the different models in manner that they synchronise and errors compensate, thus leading to a model superior to any of the individual models  a super model. The concept stems from theoretical non-dynamics and relies on advanced machine learning algorithms. Its application to climate modelling has been rudimentary. Nevertheless, our initial results show it holds great promise for improving climate prediction. To achieve even greater gains, we will extend the approach to allow greater connectivity among multiple complex climate models to create a true super climate model. We will assess the approach s potential to enhance seasonal-to-decadal prediction, focusing on the Tropical Pacific and North Atlantic, and to reduce uncertainties in climate projections. Importantly, this work will improve our und< erstanding of climate, as well as how systematic model errors impact prediction skill and contribute to climate change uncertainties.1Bio-Imaging of Zoonotic and Emerging BunyavirusesWe aim to understand host cell entry of enveloped viruses at molecular level. A crucial step in this process is when the viral membrane fuses with the cell membrane. Similarly to cell cell fusion, this step is mediated by fusion proteins (classes I III). Several medically important viruses, notably dengue and many bunyaviruses, harbour a class II fusion protein. Class II fusion protein structures have been solved in pre- and post-fusion conformation and in some cases different factors promoting fusion have been determined. However, questions about the most important steps of this key pr     !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdeghijklmnopqrstuvwxyz{|}~ocess remain unanswered. I will focus on the entry mechanism of bunyaviruses by using cutting-edge, high spatial and temporal resolution bio-imaging techniques. These viruses have been chosen as a model system to maximise the significance of the project: they form an emerging viral threat to humans and animals, no approved vaccines or antivirals exist for human use and they are less studied than other class II fusion protein systems. Cryo-electron microscopy and tomography will be used to solve high-resolution structures (up to ~3 ) of viruses, in addition to virus receptor and virus membrane complexes. Advanced fluorescence microscopy techniques will be used to probe the dynamics of virus entry and fusion in vivo and in vitro. Deciphering key steps in virus entry is expected to contribute to rational vaccine and drug design. During this project I aim to establish a world-class laboratory in structural and cellular biology of emerging viruses. The project greatly benefits from our unique biosafety level 3 laboratory offering advanced bio-imaging techniques. Furthermore it will also pave way for similar projects on other infectious viruses. Finally the novel computational image processing methods developed in this project will be broadly applicable for the analysis of flexible biological structures, which often pose the most challenging yet interesting questions in structural biology.)Prosaposin and GPR37 in synucleinopathiesThe next breakthrough in the treatment of synucleinopathies, incl Parkinsons disease (PD), will be aimed at interference of disease progression based on insights into the underlying pathogenic process. The pathological hallmark of PD are Lewy bodies (LBs), in which -synuclein is the major constituent together with other PD-linked gene products (DJ-1, LRRK2, parkin, and GBA) and aggregated GPR37. GPR37 is exceptional among GPCRs having a high propensity for intracellular receptor accumulation and aggregation leading to neurotoxicity. However, unexpectedly, our results suggest that GPR37 is neuroprotective in dopaminergic when located at the plasma membrane. Consistently, prosaposin (PSAP), and its neurotrophic fragment prosaptide, were recently identified as agonists at GPR37. PSAP is a neuroprotective protein that regulates intracellular lysosomal enzyme function, with saposin C being a co-factor of GBA. In addition, we hypothesize that PSAP is secreted following cellular stress and, via membraneous GPR37, cue dopamine neurons to initiate survival pathways. Pivotal to this programme is modeling and analysis of the atomic structures of GPR37 in complex with prosaptide, which will grossly facilitate mechanistic understanding and drug development with potential use in diagnosis and treatment. Novel applications and technological advancements of fluorescence correlation spectroscopy will be implemented for single molecule trafficking of GPR37 and its ligands and will examine whether GPCR multimerization beyond dimer formation may be neurotoxic. Normal and cGPR37KO mice will be virally transduced by -synuclein to delineate in the relative contributions of improved lysosomal function versus GPR37 agonism for neuroprotection by prosaptides. Evolving from the autopsy studies that anti GPR37 label LBs and that prosaposin is released upon cellular injury, we will develop GPR37 ligands as PET tracers for LBs in synucleinopathies.The Materials Genome in ActionIt is now possible to make an enormous spe< ctrum of different, novel nanoporous materials simply by changing the building blocks in the synthesis of Metal Organic Frameworks (MOF) or related materials. This unique chemical tunability allows us to tailor-make materials that are optimal for a given application. The promise of finding just the right material seems remote however: because of practical limitations we can only ever synthesize, characterize, and test a tiny fraction of all possible materials. To take full advantage of this development, therefore, we need to develop alternative techniques, collectively referred to as Materials Genomics, to rapidly screen large numbers of materials and obtain fundamental insights into the chemical nature of the ideal material for a given application. The PI will tackle the challenge and promise posed by this unprecedented chemical tunability through the development of a multi-scale computational approach, which aims to reliably predict the performance of novel materials before synthesis. We will develop methodologies to generate libraries of representative sets of synthesizable hypothetical materials and perform large-scale screening of these libraries. These studies should give us fundamental insights into the common molecular features of the top-performing materials. The methods developed will be combined into an open access infrastructure in which our hypothetical materials are publicly accessible for data mining and big-data analysis. The project is organized in three Work Packages, each centered around finding better materials for carbon capture: (1) screen materials for gas separations and develop the tools to predict the best materials for carbon capture; (2) gain insights into and develop a computational methodology for screening the mechanical properties of nanoporous materials; (3) achieve an understanding of the amine-CO2 chemistry in diamine-appended MOFs and use this to predict their performance.LVirtual Design, Virtual Processing and Virtual Testing of Metallic MaterialsThe project VIRMETAL is aimed at developing multiscale modeling strategies to carry out virtual design, virtual processing and virtual testing of advanced metallic alloys for engineering applications so new materials can be designed, tested and optimized before they are actually manufactured in the laboratory. The focus of the project is on materials engineering i.e. understanding how the structure of the materials develops during processing (virtual processing), the relationship between this structure and the properties (virtual testing) and how to select materials for a given application (virtual design). Multiscale modeling will be tackled using a bottom-up, hierarchical, modeling approach. Modeling efforts will begin with ab initio simulations and bridging of the length and time scales will be accomplished through different multiscale strategies which will encompass the whole range of length and time scales required by virtual design, virtual processing and virtual testing. Nevertheless, not everything can or should be computed and critical experiments are an integral part of the research program for the calibration and validation of the multiscale strategies. The research will be focused on two cast metallic alloys from the Al-Si-Mg and Mg-Al-Zn systems. The expected breakthrough is precisely to demonstrate that the structure and properties of two standard engineering alloys of considerable industrial interest can be obtained from first principles by bridging a cascade of modeling tools at the different length scales. Once this is proven, further research will lead to the continuous expansion of both the number and the capability of multiscale simulation tools, leading to widespread application of Computational Materials Engineering in academia and industry. This will foster the implementation of this new revolutionary technology in leading European industries from aerospace, automotive, rail transport, energy generation and engineering sectors.@Microbiology of extremely acidic terrestrial volcanic ecosystemsTerrestrial mud volcanos are extreme environments with pH values below even 1, with temperatures up to 70 C. They represent  hotspots of greenhouse gas emissions. Despite the hostile conditions, mud volcanos harbour very unique microbial communities involved in the cycling of elements like carbon, hydrogen, sulfur, and nitrogen. Microbial communities in extreme environments are characterized by low biodiversity and as a consequence serve as good models to study linkages between genomic potential and environmental parameters. Metagenome studies have shown that most of the microorganisms in extreme environments are only distantly related to cultivated bacteria. Therefore, state-of the-art enrichment techniques using chemostat and sequencing batch cultivation with inocula from geothermal sites and driven by physiological information from metagenomic/metatranscriptomic data have a high potential to result in novel isolates. This was already demonstrated by our isolation of both mesophilic and thermophilic acid-loving methanotrophs. The aim of this project is to obtain a fundamental understanding of the microbial ecology of extremely acid terrestrial mud volcanos with special emphasis on the elemental cycles of sulfur, methane and nitrogen. After identification and isolation, the microbial key players will be investigated to unravel the molecular mechanisms by which they adapt to extreme (thermo)acidophilic conditions. To achieve this, several parallel and complementary state-of-the-art-approaches will be combined, e.g. meta-omics, microbial ecophysiology, cultivation techniques, cell biology/biochemistry, metabolism/gene expression studies. The project will profoundly increase the understanding of these natural hotspots of greenhouse gas production/degradation and newly isolated strains have a high potential for finding sustainable solutions for the most pressing grand challenges of the European society e.g. new green enzymatic catalyst and technologies for industry.YTowards a deepened understanding of combustion processes using advanced laser diagnostics.Coherent Structures in Wall-bounded Turbulence< Turbulence is a multiscale phenomenon for which control efforts have often failed because the dimension of the attractor is large. However, kinetic energy and drag are controlled by relatively few slowly evolving large structures that sit on top of a multiscale cascade of smaller eddies. They are essentially single-scale phenomena whose evolution can be described using less information than for the full flow. In evolutionary terms they are punctuated  equilibria for which chaotic evolution is only intermittent. The rest of the time they can be considered coherent and predictable for relatively long periods. Coherent structures studied in the 1970s in free-shear flows (e.g. jets) eventually led to increased understanding and to industrial applications. In wall-bounded cases (e.g. boundary layers), proposed structures range from exact permanent waves and orbits to qualitative observations such as hairpins or ejections. Although most of them have been described at low Reynolds numbers, there are reasons to believe that they persist at higher ones in the  LES sense in which small scales are treated statistically. Recent computational and experimental advances provide enough temporally and spatially resolved data to quantify the relevance of such models to fully developed flows. We propose to use mostly existing numerical data bases to test the various models of wall-bounded coherent structures, to quantify how often and how closely the flow approaches them, and to develop moderate-time predictions. Existing solutions will be extended to the LES equations, methods will be sought to identify them in fully turbulent flows, and reduced-order models will be developed and tested. In practical situations, the idea is to be able to detect large eddies and to predict them  most of the time . If simple enough models are found, the process will be implemented in the laboratory and used to suggest control strategies.Allocation Made PracticaL:Allocation Made PracticaLThe AMPLify project will lay the foundations of a new field, computational behavioural game theory that brings a computational perspective, computational implementation, and behavioural insights to game theory. These foundations will be laid by tackling a pressing problem facing society today: the efficient and fair allocation of resources and costs. Research in allocation has previously considered simple, abstract models like cake cutting. We propose to develop richer models that capture important new features like asynchronicity which occur in many markets being developed in our highly connected and online world. The mechanisms currently used to allocate resources and costs are limited to these simple, abstract models and also do not take into account how people actually behave in practice. We will therefore design new mechanisms for these richer allocation problems that exploit insights gained from behavioural game theory like loss aversion. We will also tackle the complexity of these rich models and mechanisms with computational tools. Finally, we will use computation to increase both the efficiency and fairness of allocations. As a result, we will be able to do more with fewer resources and greater fairness. Our initial case studies in resource and cost allocation demonstrate that we can improve efficiency greatly, offering one company alone savings of up to 10% (which is worth tens of millions of dollars every year). We predict even greater impact with the more sophisticated mechanisms to be developed during the course of this project.VMechanisms of alternative pre-mRNA splicing regulation in cancer and pluripotent cellsAlternative splicing of messenger RNA precursors is a prevalent form of gene regulation that greatly expands the coding capacity and regulatory opportunities of higher eukaryotic genomes. It contributes to cell differentiation and pluripotency and its deregulation promotes cancer progression, as evidenced by the frequent occurrence of cancer-associated mutations in splicing factors, which are also targets of anti-tumor drugs. Despite its prevalence and relevance, the underlying mechanisms of regulation remain poorly understood. This proposal aims to develop and apply systematic approaches that can allow us to carry out the equivalent of genetic analysis of splicing regulation in cancer and pluripotent cells. These technologies can help to unweave the complex network of functional interactions within the spliceosome and of the spliceosome with regulatory factors, exhaustively map the contribution of regulatory sequences and be used to investigate, with unprecedented detail, mechanisms of regulation for essentially any regulator or alternative splicing event operating in a particular cell line. Such approaches can offer a unique opportunity to address key unresolved mechanistic questions, including the molecular basis for positional effects of splicing regulatory factors (RNA Maps), the regulatory potential of the core spliceosome and the integration of alternative splicing with other cell regulatory programs. We will combine these approaches with biochemical and cellular assays to investigate detailed mechanisms of regulation relevant for the control of cell proliferation and/or pluripotency in cancer and induced pluripotent stem (iPS) cells. Progress in this area can contribute to reveal the molecular logic governing a key layer of gene regulation and has the potential to discover novel factors and regulatory circuits that trigger or modulate cell growth, differentiation and cancer progression.8Probing Physics beyond the Standard Model from MoleculesThe Standard Model of physics is incomplete. Gravity is not understood at the quantum level, dark matter and dark energy are not explained, and (string)-theories searching to cover these shortcomings are only consistent in higher-dimensional spaces, while only four of those dimensions are observed. The mystery of finely<  tuned strengths of the fundamental forces, providing us with a Universe of complexity, remains unexplained. This calls for new physics that can also be explored at the atomic scale in the low energy domain. That is the paradigm underlying the present proposal: Effects of new physics  either related to hitherto unknown particles or to symmetry-breaking phenomena  will manifest themselves as minute shifts in the quantum level structures of atoms and molecules, in minute drifts over time or dependencies on environmental conditions.I propose to perform precision metrology measurements on the H2 molecule in a search for new physics. Deviations between experimental results and QED-theory will scan unexplored territory beyond the Standard Model. Molecular metrology results of the fundamental ground tone vibration in H2 will be confronted with QED-theory calculations to search for the existence of new forces at the Angstrm length scale. If extra dimensions beyond the known 3+1 would be compactified at the same length scale of 1 , this would lead to strongly enhanced gravitational effects, measurable in a molecule. Our current research on experimental probes for varying constants on a cosmological time scale, is redirected into the investigation of chameleon scenarios: by studying H2 molecules in white dwarf stars by uv-astronomy, and by studying methanol molecules in our own galaxy by radio astronomy, searching for a possible dependence of fundamental constants on strong gravity or on density. If any of these targeted phenomena could be uncovered, it would have great impact on science as a whole, and on our view on the Universe and its origin.UDeveloping and delivering neurocomputational models to bridge between brain and mind.The promise of cognitive neuroscience is truly exciting  to link mind and brain in order to reveal the neural basis of higher cognitive functions. This is crucial, scientifically, if we are to understand the nature of mental processes and how they arise from neural machinery but also, clinically, if we are to establish the basis of neurological patients impairments, their clinical management and treatment. Cognitive-clinical neuroscience depends on three ingredients: (a) investigating complex mental behaviours and the underlying cognitive processes; (b) mapping neural systems and their function; and (c) methods and tools that can bridge the gap between brain and mental behaviour. Experimental psychology and behavioural neurology has delivered the first component. In vivo neuroimaging and other allied technologies allow us to probe and map neural systems, their connectivity and neurobiological responses. The principal aim of this ERC Advanced grant is to secure, for the first time, the crucial third ingredient  the methods and tools for bridging systematically between cognitive science and systems neuroscience.The grant will be based on two main activities: (i) convergence of methods  instead of employing each neuroscience and cognitive method independently, they will be planned and executed simultaneously to force a convergence of results; and (ii) development of a new type of neurocomputational model - to provide a novel formalism for bridging between brain and cognition. Computational models are used in cognitive science to mimic normal and impaired behaviour. Such models also have an as-yet untapped potential to connect neuroanatomy and cognition: latent in every model is a kind of brain-mind duality  each model is based on a computational architecture which generates behaviour. We will retain the ability to simulate detailed cognitive behaviour but simultaneously make the models architecture reflect systems-level neuroanatomy and function.JCamera Observation and Modelling of 4D Tracer Dispersion in the AtmosphereCOMTESSA will push back the limits of our understanding of turbulence and plume dispersion in the atmosphere by bringing together full four-dimensional (space and time) observations of a (nearly) passive tracer (sulfur dioxide, SO2), with advanced data analysis and turbulence and dispersion modelling.Observations will be made with six cameras sensitive to ultraviolet (UV) radiation and three cameras sensitive to infrared (IR) radiation. The UV cameras will be built specifically for this project where high sensitivity and fast sampling is important. The accuracy of UV and IR retrievals will be improved by using a state-of-the art-3D radiative transfer model. Controlled puff and plume releases of SO2 will be made from a tower, which will be<  observed by all cameras, yielding multiple 2D images of SO2 integrated along the line of sight. The simultaneous observations will allow - for the first time - a tomographic reconstruction of the 3D tracer concentration distribution at high space (< 1 m) and time (>10 Hz) resolution. An optical flow code will be used to determine the eddy-resolved velocity vector field of the plume. Special turbulent phenomena (e.g. plume rise) will be studied using existing SO2 sources (e.g. smelters, power plants, volcanic fumaroles).Analysis of the novel campaign observations will deepen our understanding of turbulence and tracer dispersion in the atmosphere. For instance, for the first time we will be able to extensively measure the concentration probability density function (PDF) in a plume not only near the ground but also at high-er altitudes; quantify relative and absolute dispersion; estimate the value of the Richardson-Obukhov constant, etc. We will also use the data to evaluate state-of-the-art LES and Lagrangian dispersion models and revise their underlying parameterizations.COMTESSA s vision is that the project results will lead to large improvements of tracer transport in all atmospheric models.RArtificial-Intelligence Driven Discovery and Synthesis of Polyoxometalate ClustersWe outline a 5 year programme that introduces a new platform for the preparation, understanding, and exploitation of precisely defined nano-molecules / materials based upon the assembly of molecular metal oxide precursors (polyoxometalates) under non-equilibrium conditions with well-defined physical properties using automated intelligent feedback. We will elucidate the mechanism of assembly of these gigantic molecules and devise a set of rules similar to the magic numbers found in gold nanoclusters, using these to break the 10 nm size barrier for a single molecule. Targeted properties include photochemical and electrochemical sensors, bistable molecules, doped traditional oxides with polyoxometalates, and new catalysts including water oxidation via a Universal Building Block (UBB) approach that links properties of the building blocks with emergent properties of the resulting clusters and materials for the first time. The new approach includes the conversion of batch to flow synthesis not only for automation, but to understand fundamental mechanistic aspects, and to use artificial intelligence algorithms to help move through the myriad of possible combinations (without needing to synthesise every possible molecule). The SMART-POM approach is therefore not merely automation of one-pot chemistry, but an entirely new paradigm building on our recent developments and will allow us to move through a vast combinatorial space effectively only locating areas of novelty via feedback control. This feedback will be used to discover, design, and develop complex, adaptive and functional metal oxide-based materials based upon sensory feedback from the physical properties measurements. Thus SMART-POM will open up a whole new synthetic space, give mechanistic understanding, and allow the discovery of molecules with potential real-world applications. Finally, we will aim to extend the SMART-POM paradigm to other areas of chemistry which will benefit from the search for novelty.wEfficient, Flexible Synthesis of Molecules with Tailored Shapes: from Photo-switchable Helices to anti-Cancer Compounds The creation of new molecular entities and subsequent exploitation of their properties is central to a broad spectrum of research disciplines from medicine to materials but progress has been limited by the difficulties associated with chemical synthesis. We are now proposing a fundamentally new strategy, which has the potential to revolutionise how we conduct complex organic synthesis. The basic C C bond-forming step involves the reaction of a lithiated carbamate with a boronic ester to give a homologated boronic ester with complete stereocontrol. Furthermore, the reaction shows >98% efficiency in most cases and can be conducted iteratively and in one pot (up to 9 iterations has been demonstrated with full stereocontrol). We will now extend this methodology to more functionalised carbamates as this will enable the rapid synthesis of polypropionates, which are amongst the most important classes of biologically active molecules. The robust methodology is now ripe for transfer to the solid phase as this will enable the preparation of libraries of these molecules. Through applying our assembly-line-synthesis methodology to complex molecules with diverse structures, we will demonstrate its scope, robustness, and full potential. The methodology enables stereochemistry to be  dialled in to a carbon chain, which in turn controls the conformation and we will exploit this feature in the shape-selective synthesis of molecules. We will explore how the sense of helical chirality of these molecules can be switched (M to P) just with light. We will target helical molecules with specific groups at specific places for optimum binding to disrupt protein protein interactions involved in cancer. Finally, our methodology provides ready access to a family of building blocks that repre< sent common repeat units found in polyketides. By combining these building blocks iteratively using lithiation-borylation, we should be able to rapidly and reliably prepare complex natural products.sNodding Syndrome: a trans-disciplinary approach to identify the cause and decrease the incidence of river epilepsyNodding syndrome (NS) is a neurological, incurable syndrome, currently affecting mainly children between 5 and 15 years of age in South Sudan, Uganda and Tanzania. Since 1950, when NS was first described, its cause has remained a mystery. NS is characterized by head-nodding (an atonic form of epilepsy), often followed by clonic - tonic seizures, developmental retardation and faltering growth. In the affected regions, NS is a major public health problem associated with severe socio-economic consequences. After exploratory missions to South Sudan, Uganda and the Democratic Republic of the Congo (DRC), we gathered epidemiological evidence that supports the hypothesis that NS is a disease caused by a pathogen transmitted by blackflies, the vectors that transmit the parasitic worm that causes onchocerciasis. This pathogen could be an unknown neurotropic virus or another pathogen that is transmitted either independently or as a symbiont of the worm. We postulate that this pathogen is able to cause typical NS, but also other forms of epidemic epilepsy. We hypothesise that the same disease is also endemic in other onchocerciasis hyper-endemic regions e.g. in the Mbam valley, Cameroon and the Orientale Province, DRC (where it is referred to as  river epilepsy ). In this project we aim to investigate our hypotheses in South Sudan, Uganda, Tanzania, Cameroon and the DRC with a trans-disciplinary approach including clinical-epidemiological, post-mortem, eco-entomological, and metagenomic studies. We will study the effect of vector control methods and ivermectin distribution on the incidence of river epilepsy. So far a multi-country study on NS was never done and nearly all previous studies were cross-sectional, carried out during short country visits. With this long term research plan we hope to finally discover the cause of NS and detect effective control strategies to decrease the incidence of epilepsy in onchocerciasis endemic areas.SInsomnia s Negative Sequelae On Mood: from Neuroscience to Intervention in the AgedMajor depression is among the most burdening health hazards. Its prevalence is 1-3%, an additional 8-16% have clinically significant symptoms, and prognosis is poor. Unfortunately, less than 20% of the cases are detected and treatment effectiveness is moderate. The Global Consortium for Depression Prevention stresses that our best chance to combat the global burden of depression is provide preventive intervention to identified people at risk. This project targets the strongest modifiable risk factor: insomnia. With prevalence estimates up to 40%, insomnia is among the most frequent disorders in the elderly population. Meta-analysis shows that no less than 13% of people with insomnia develop depression. This extreme risk and the very high prevalence of insomnia in the ageing population, shows the urgency and promise of: (1) early identification of these 13%, (2) finding mechanisms by quantification of how they differ from insomniacs that do not develop depression with respect to brain structure and function, psychological traits, behavioural habits and environmental exposures; and (3) enrolling them in intervention protocols aimed at sleep improvement and prevention of depression. The project extends recent findings emerging from the applicant s pioneering, unconventional and innovative approach to insomnia; the proposal that distinct subtypes exist and can be discriminated data-driven by means of multivariate trait analysis and brain imaging. Ignorance of this heterogeneity has obstructed progress in mechanistic understanding and rational treatment. In an unprecedented interdisciplinary way the project (1) identifies the insomnia subtype that develops depression; (2) profiles mechanisms involved; and (3) optimizes effectiveness of internet-supported home-applicable interventions to improve sleep and prevent depression. This approach will identify risks and mechanisms, and< facilitate immediate implementation of risk-based prevention strategies and policies.<hybridFRET - deciphering biomolecular structure and dynamicstTo understand and modulate biological processes, we need their spatiotemporal molecular models. In this project we propose to build these models by a holistic approach. The recent methodological and technical advances in fluorescence spectroscopy and microscopy as well as in multi-scale modelling of complex biochemical systems set the stage to tackle cross-fertilizing challenges in biophysics, biochemistry and cell biology. The applicant proposes to develop a novel integrative platform for a Molecular Fluorescence Microscope (MFM) to achieve ultimate resolution in space (sub-nanometer) and time (picoseconds) for characterizing structure and dynamics of proteins. MFM will combine Multi-parameter Fluorescence Detection with Computational Microscopy (molecular dynamics and coarse grained simulations) in a hybrid approach, first, to derive a complete molecular description of all fluorescence properties of the tailored dyes in proteins (objectives 1 and 2) and, second, to utilize this information in simulations to report on the protein properties (objective 3). In this hybrid approach high precision FRET measurements are the core experimental technique (hybridFRET). The MFM will allow us to tackle the central biophysical question of how intra- and intermolecular domain interactions modulate proteins' overall structure, dynamics, and thus ultimately function (objective 4). In this proposal we will apply MFM to two prototypic proteins of significant medical relevance. The combination with Multi-parameter Fluorescence Image Spectroscopy will exploit the ultimate resolution of the MFM for molecular protein imaging in live cells. To follow and ultimately understand biological processes, we need their spatiotemporal models of the integrative fluorescence spectroscopy platform. Until now, no holistic use of fluorescence spectroscopy for structural modelling of proteins has been reported.PCalibration and integration of peripheral and foveal information in human visionHuman visual perception is one of the best-studied areas of research on the human mind. However, 99% of that research is concentrated on the central region making up less than 1% of our visual field. This is the region that gets mapped onto the fovea, where vision is best. However, information from the peripheral parts of a scene is highly important. Mediated by attention and eye movements, it is essential for guiding us through our environment. In the brain, the foveal and peripheral parts of the visual field undergo vastly different processing regimes. Since objects normally do not change their appearance, whether we view them foveally or peripherally, our visual system must integrate and calibrate peripheral information before an eye movement with foveal information after an eye movement. We are planning to address these processes in four series of experiments. First, we will study the perception of basic visual features, such as orientation, numerosity and colour across the visual field and their integration in peripheral and foveal vision across eye movements. Second, we will investigate how this integration is supported by attention and memory resources. Third, since the integration requires learning and plasticity, we will track changes across the life span and study how healthy subjects can learn to compensate for artificial changes of peripheral and foveal vision. And fourth, we will explore whether we can manipulate the integration process for the optimal guidance of eye movements in complex natural search tasks. The project will provide insights how the brain achieves a stable and homogeneous representation of the visual environment despite the ever changing sensory input and the inhomogeneity of processing across the visual field. We will reveal the basic learning mechanisms that allow a continuous calibration of peripheral and foveal vision, and that could be used in the long run for behavioural training of patients suffering from vision impairments. cDust in the wind  a new paradigm for inflow and outflow structures around supermassive black holesActive galactic nuclei (AGN) represent the active growing phases of supermassive black holes. For the first time, we are able to resolve the dusty gas on parsec scales and directly test our standard picture of these objects. While this  unification scheme relates the parsec-scale IR emission with a geometrically-thick disk, I have recently found that the bulk of the dust emission comes from the polar region of the alleged disk where gas is blown out from the vicinity of the black hole. Along with these polar features, the compactness of the dust distribution seems to depend on the accretion state of the black hole. Neither of these findings have been predicted by current models and lack a physical explanation. To explain the new observations, I proposed a revision to the AGN unification scheme that involves a dusty wind driven by radiation pressure. Depending on their masses, velocities, and frequency, such dusty winds might play a major role in self regulating AGN activity and, thus, impact the interplay between host and black hole evolution. However, as of now we do not know if these winds are ubiquitous in AGN and how they would work physically. Upon completion of the research program, I want to " characterise the pc-scale mass distribution, its kinematics, and the connection to the accretion state of the AGN, " have a physical explanation of the dusty wind features and constrain its impacts on the AGN environment, and " have established dust parallax distances to several nearby AGN, as a multi-disciplinary application of the constraints on the dust distribution. For that, I will combine the highest angular resolution observations in the IR and sub-mm to create the first pc-scale intensity, velocity, and density maps of a sample of 11 AGN. I will develop a new model that combines hydrodynamic simulations with an efficient treatment of radiative transfer to simulate dusty winds. Finally, direct dista< nces to 12 AGN with a combined 3% precision will be measured.*Rigidity of groups and higher index theoryVCell intrinsic control of CD4 T cell differentiation by cytosolic DNA sensing pathwaysbINhomogenieties and fluctuations in quantum CohErent matter Phases by ultrafast optical TomographyWBiocompatible and Interactive Artificial Micro- and Nanoswimmers and Their ApplicationsMicroswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing. However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale. This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers. To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications. PDissecting active matter: Microscopic origins of macroscopic actomyosin activityA molecular interface science approach: Decoding single molecular reactions and interactions at dynamic solid/liquid interfacesqZebrafish vision in its natural context: from natural scenes through retinal and central processing to behaviour.OTerrestrial vertebrates and the evolutionary origins of morphological diversityExplaining the great disparity of organismal form is a central goal of biological research. However, despite many decades of inquiry, there is little understanding of how evolution gave rise to this disparity. Key hypotheses predict changes in macroevolutionary modes through geological time: rates of evolution may either have decreased as global niche space became crowded, or increased due to accumulation of key innovations that improve body plan versatility. The absence of data to test these hypotheses a major knowledge gap that severely limits our understanding of evolution on Earth. TEMPO is an ambitious project to quantify patterns of phenotypic evolution on an unprecedented scale (>300 million years), by generating a large, detailed morphological dataset. Using the evolutionary radiation of land vertebrates as a model system, TEMPO will address these fundamental, unresolved questions: (1) How have rates and constraints of phenotypic evolution varied through geological time? (2) Are these patterns consistent with the occurrence of global niche-filling? (3) Can evolutionary versatility enabled by key innovations explain these patterns? (4) What modes of lineage evolution generated observed trends of morphological disparity? Previous large-scale studies lacked the temporal and phenotypic scope to address these questions, analysing only body size in only extant taxa. TEMPO will overcome these limitations to provide a step-change in understanding, by: (1) Using 21st century 3D data-capture methods on specimens from the mammalian and bird/crocodile evolutionary lineages. (2) Combining living with fossil taxa to extend our knowledge far into deep time; and (3) Analysing multiple aspects of form in a multivariate framework, using cutting-edge phylogenetic model-fitting approaches. By doing this, TEMPO will unify palaeontology and evolutionary biology, transforming knowledge of how phenotype evolves and the processes generating animal disparity on geological timescales.rSex-limited experimental evolution of natural and novel sex chromosomes: the role of sex in shaping complex traitsThe origin and evolution of sexual reproduction and sex differences represents one of the major unsolved problems in evolutionary biology, and although much progress had been made both via theory and empirical research, recent data suggest that sex chromosome evolution may be more complex than previously thought. The concept of sexual antagonism (when there is a positive intersexual genetic correlation in trait expression but opposite fitness effects of the trait(s) in males and females) has become essential to our understanding of sex chromosome evolution. The goal of this proposal is to understand how the interacting effects of sexual antagonism, sex-linked genetic variation, and sex-specific selection shape the genetic architecture of complex traits. I will test the hypotheses that: 1) individual sexually antagonistic loci are common in the genome, both in separate-sexed species and in hermaphrodites, and drive patterns of sexual antagonism often seen on the trait level. 2) That the response to sex-specific selection in sex-linked loci is usually due to standing sexually antagonistic genetic variation. 3) That sexually antagonistic variation is primarily non-additive in nature. To accomplish this, I will use a combination of approaches, including sex-limited experimental evolution of the X chromosome and reciprocal sex chromosome introgression among distantly related populations of Drosophila, quantitative genetic analysis and experimental evolution mimicking the creation of a novel sex chromosome in the hermaphroditic flatworm Macrostomum, and analytical and simulation modeling. This project will serve to confirm or refute the assumption that trait-level sexual antagonism reflects the contributions of many individual sexually antagonistic loci, increase our understanding of the contribution of coevolution of the sex chromosomes to population divergence, and help provide us with a better general understanding of how genotype maps to phenotype.NRational Design of Photoreceptor Mutants with Desired Photochemical PropertiesVisual perception in Context_Understanding and manipulating the dynamics of chromosome topologies in transcriptional controlDMathematical aspects of three-dimensional water waves with vorticity,The goal of this project is to develop a mathematical theory for steady three-dimensional water waves with vorticity. The mathematical model consists of the incompressible Euler equations with a free surface, and vorticity is important for modelling the interaction of surface waves with non-uniform currents. In the two-dimensional case, there has been a lot of progress on water waves with vorticity in the last decade. This progress has mainly been based on the stream function formulation, in which the problem is reformulated as a nonlinear elliptic free boundary problem. An analogue of this formulation is not available in three dimensions, and the theory has therefore so far been restricted to irrotational flow. In this project we seek to go beyond this restriction using two different approaches. In the first approach we will adapt methods which have been used to construct three-dimensional ideal flows with vorticity in domains with a fixed boundary to the free boundary context (for example Beltrami flows). In the second approach we will develop methods w< hich are new even in the case of a fixed boundary, by performing a detailed study of the structure of the equations close to a given shear flow using ideas from infinite-dimensional bifurcation theory. This involves handling infinitely many resonances. XQuantifying the evolution of Earth's atmosphere with novel isotope systems and modellingAtmospheric oxygen is fundamental to life as we know it, but its concentration has changed dramatically over Earth s 4.5 billion year history. An amazing qualitative story has emerged, in which Earth s atmosphere was devoid of free oxygen for the first 2 billion years of planetary history, with two significant increases in concentration at ~2.4 and ~0.55 billion years ago. Both oxygenation events were accompanied by extreme climatic effects  the  snowball earth episodes  and paved the way for massive reorganization of biogeochemical cycles such as the Cambrian radiation of macroscopic life. Despite these profound influences on the Earth system, we currently lack fundamental quantitative constraints on Earth s atmospheric evolution. I am poised to add substantial quantitative rigor to Earth s atmospheric history, by constraining the concentrations of important gases (e.g., O2, O3, CO2, CH4, organic haze) in ancient atmospheres to unprecedented accuracy. I will accomplish this via an innovative interdisciplinary program focused on the unusual mass-independent isotope fractionations observed in sedimentary rocks containing sulfur and oxygen. These signals are direct remnants of ancient atmospheric chemistry, and contain far more information than can currently be interpreted. This project combines novel experimental and methodological approaches with state-of-the-art numerical modelling to significantly advance our ability to decipher the isotope records. A unique  early Earth UV lamp coupled to a custom-built photocell will enable direct production of isotope signals under Earth-like conditions, with time-dependent sampling. Groundbreaking analytical methodologies will vastly increase the global geochemical database. The experimental results and data will provide ground-truth for next-generation atmospheric models that will constrain atmospheric composition and its feedbacks with the Earth-biosphere-climate system during key points in our planetary history.GInformation-age microscopy for deep vision imaging of biological tissueModern biology could not exist without the optical microscope. Hundreds of years of research have seemingly developed microscopes to perfection, with one essential limitation: in turbid biological tissue, not even the most advanced microscope can penetrate deeper than a fraction of a millimetre. At larger depths light scattering prevents the formation of an image. DEEP VISION takes a radically new approach to microscopy in order to lift this final limitation. Microscopes are based on the idea that light propagates along a straight line. In biological tissue, however, this picture is naive: light is scattered by every structure in the specimen. Since the amount of  non-scattered light decreases exponentially with depth, a significant improvement of the imaging depth is fundamentally impossible, unless scattered light itself is used for imaging. In 2007, Allard Mosk and I pioneered the field of wavefront shaping. The game-changing message of wavefront shaping is that scattering is not a fundamental limitation for imaging: using a spatial light modulator, light can be focused even inside the most turbid materials, if  only the correct wavefront is known. DEEP VISION aims to initiate a fundamental change in how we think about microscopy: to use scattered light rather than straight rays for imaging. The microscope of the future is no longer based on Newtonian optics. Instead, it combines new insights in scattering physics, wavefront shaping, and compressed sensing to extract all useful information from a specimen. Whereas existing microscopes are ignorant to the nature of the specimen, DEEP VISION is inspired by information theory; imaging revolves around a model that integrates observations with statistical a-priori information about the tissue. This model is used to calculate the wavefronts for focusing deeper into the specimen. Simulations indicate that my approach will pe< netrate at least four times deeper than existing microscopes, without loss of resolution. TControl for Orbit Manoeuvring through Perturbations for Application to Space SystemsSpace benefits mankind through the services it provides to Earth. Future space activities progress thanks to space transfer and are safeguarded by space situation awareness. Natural orbit perturbations are responsible for the trajectory divergence from the nominal two-body problem, increasing the requirements for orbit control; whereas, in space situation awareness, they influence the orbit evolution of space debris that could cause hazard to operational spacecraft and near Earth objects that may intersect the Earth. However, this project proposes to leverage the dynamics of natural orbit perturbations to significantly reduce current extreme high mission cost and create new opportunities for space exploration and exploitation. The COMPASS project will bridge over the disciplines of orbital dynamics, dynamical systems theory, optimisation and space mission design by developing novel techniques for orbit manoeuvring by  surfing through orbit perturbations. The use of semi-analytical techniques and tools of dynamical systems theory will lay the foundation for a new understanding of the dynamics of orbit perturbations. We will develop an optimiser that progressively explores the phase space and, though spacecraft parameters and propulsion manoeuvres, governs the effect of perturbations to reach the desired orbit. It is the ambition of COMPASS to radically change the current space mission design philosophy: from counteracting disturbances, to exploiting natural and artificial perturbations. COMPASS will benefit from the extensive international network of the PI, including the ESA, NASA, JAXA, CNES, and the UK space agency. Indeed, the proposed idea of optimal navigation through orbit perturbations will address various major engineering challenges in space situation awareness, for application to space debris evolution and mitigation, missions to asteroids for their detection, exploration and deflection, and in space transfers, for perturbation-enhanced trajectory design.aObservation and Modelling of Radiocarbon in Atmospheric Methane for Methane Source Identification9III-Nitrides Nanostructures for Energy-Efficiency DevicesEnergy efficiency offers a vast and low-cost resource to address future energy demand while reducing carbon dioxide emissions. The unique properties of III-Nitride semiconductors make them the ideal material for future energy challenges. Their outstanding optical properties are revolutionizing the world with efficient LED light bulbs. Even greater impact is anticipated for power electronics. The much larger Baliga s figure of merit of GaN compared to SiC and Si enables drastically more efficient power switches, which are at the heart of any energy generation/management system. However, current III-Nitride device performance is far from the fundamental materials capabilities, and severe thermal management and reliability limitations hinder their full potential for energy-efficiency. The In-Need proposes a unique approach to address concurrently all current challenges based on advanced nanostructures designed to optimally exploit the superior properties of the new bulk GaN materials. Nanostructuring distinct regions of the device will allow a precise control over their intrinsic characteristics. To address reliability issues and yield unprecedented device performance, these nanostructures will be combined to the excellent properties of bulk GaN. This will open opportunities for new vertical devices, enabling smaller structures with larger voltages and higher efficiencies. Efficient thermal management will be achieved with ultra-near junction cooling. Nano/micro-channels filled with high thermal conductivity materials or coolants will be embedded inside the device. We believe our judicious nano-scale design of new high-performing materials will result in state-of-the-art devices, leading to a large-scale impact in energy efficiency. The miniaturization and large power density enabled by our approach will allow future integration of power devices into single power microchips. This will revolutionize energy use < much like Silicon microchips did for information processing.1BETTER UNDERSTANDING the METAPHYSICS of PREGNANCY9Tunable Photonic Structures via Photomechanical ActuationYResolving conflicts between food security and biodiversity conservation under uncertaintyVA Bidirectional MyoKinetic Implanted Interface for Natural Control of Artificial LimbsMYKI aims at developing and clinically evaluating a dexterous hand prosthesis with tactile sensing which is naturally controlled and perceived by the amputee. This will be possible by overcoming the conventional approaches based on recording electrical signals from the peripheral nervous system (nerves or skeletal muscles) through the development of a radically new Human-Machine Interface (HMI) based on magnetic field principles, both able to decode voluntary motor commands and to convey sensory feedback to the individual. Core of this system is a multitude of magnets implanted in independent muscles and external magnetic readers/drivers (MRDs) able to (i) continuously localize the movements of the magnets and, at specific times, (ii) induce subtle movements in specific magnets. In fact, as a magnet is implanted it will travel with the muscle it is located in, and its localization will provide a direct measure of the contraction/elongation of that muscle, which is voluntarily controlled by the central nervous system. In this way it will be possible to decode the efferent signals sent by the brain by observing a by-product of the muscle fibres recruitment. On the other hand, a movement induced in the implanted magnet by the external MRD, could provide a perceivable stimulus, conveyed to the brain by means of the peripheral sensory receptors present in the muscle (e.g. muscle spindles or Golgi tendon organ) or in the neighbouring skin (tactile mechanoreceptors). In this way we aim to provide tactile and/or proprioceptive sensory information to the brain, thus restoring the physiological sensorimotor control loop. Remarkably, with passive magnetic tags (that do not require to be powered-on) and wearable readers/drivers, it will be possible to implement a wireless, bidirectional HMI with dramatically enhanced capabilities with respect to the state of the art interfaces, as illustrated in this proposal.GSmart Monitoring, Inspection and Life-Cycle Assessment of Wind TurbinesvIntelligent functional glazing with self-cleaning properties to improve the energy efficiency of the built environmentThe latest forecast by the International Energy Agency predicts that the CO2 emissions from the built environment will reach 15.2Gt in 2050, double their 2007 levels. Buildings consume 40% of the primary energy in developed countries with heating and cooling alone accounting for 63% of the energy spent indoors. These trends are on an ascending trajectory - e.g. the average energy demand for air-conditioning has been growing by ~17% per year in the EU. Counterbalancing actions are urgently required to reverse them. The objective of this proposal is to develop intelligent window insulation technologies from sustainable materials. The developed technologies will adjust the amount of radiation escaping or entering a window depending upon the ambient environmental conditions and will be capable of delivering unprecedented reductions to the energy needed for regulating the temperature in commercial and residential buildings. Recognising the distinct requirements between newly built and existing infrastructure, two parallel concepts will be developed: i) A new class of intelligent glazing for new window installations, and, ii) a flexible, intelligent, polymer film to retrofit existing window installations. Both solutions will be enhanced with unique self-cleaning properties, bringing about additional economic benefits through a substantial reduction in maintenance costs. Overall, we aim to develop intelligent glazing technologies that combine: i) power savings of >250 W/m2 of glazing capable of delivering >25% of energy savings and efficiency improvements >50% compared with existing static solutions; ii) visible transparency of >60% to comply with the EU standards for windows ,and, iii) self-cleaning properties that introduce a cost balance. A number of technological breakthroughs are required to satisfy such ambitious targets which are delivered in this project by the seamless integration of nanotechnology engineering, novel photonics and advanced material synthesis.Cognitive Ageing in DogsThe aim of this project is to understand the causal factors contributing to the cognitive decline during senescence and to develop sensitive and standardized behaviour tests for early detection in order to increase the welfare of affected species. With the rapidly ageing population of Europe, related research is a priority in the European Union. We will focus both on characterising the ageing phenotype and the underlying biological processes in dogs as a well-established natural animal model. We develop a reliable and valid test battery applying innovative multidisciplinary methods (e.g. eye-tracking, motion path analysis, identification of behaviour using inertial sensors, EEG, fMRI, candidate gene, and epigenetics) in both longitudinal and cross-sectional studies. We expect to reveal specific environmental risk factors which hasten ageing and also protective factors which may postpone it. We aim to provide objective criteria (behavioural, physiological and genetic biomarkers) to assess and predict the ageing trajectory for specific individual dogs. This would help veterinarians to recognise the symptoms early, and initiate necessary counter actions. This approach establishes the framework for answering the broad question that how we can extend the healthy life of ageing dogs which indirectly also contributes to the welfare of the owner and decreases veterinary expenses. The detailed description of the ageing phenotype may also facilitate the use of dogs as a natural model for human senescence, including the development and application of pharmaceutical interventions. We expect that our approach offers the scientific foundation to delay the onset of cognitive ageing in dog populations by 1-2 years, and also increase the proportion of dogs that enjoy healthy ageing. 7SCALEFORES: Scaling Rules For Ecosystem Service MappingSNovel 2D quantum device concepts enabled by sub-nanometre precision nanofabrication?IIn today s electronics, the information storage and processing are performed by independent technologies. The information-processing is based on semiconductor (silicon) devices, while non-volatile data storage relies on ferromagnetic metals. Integrating these tasks on a single chip and within the same material technology would enable disruptively new device concepts opening the way towards ultra-high speed electronic circuits. Due to the unique versatility of its electronic and magnetic properties, graphene has a strong potential as a platform for the implementation of such devices. By engineering their structure at the atomic level, graphene nanostructures of metallic, semiconducting, as well as magnetic properties can be realized. Here we propose that the unmatched precision and full edge orientation control of our STM-based nanofabrication technique enables the relia< ble implementation of such graphene nanostructures, as well as their complex, functional networks. In particular, we propose to experimentally demonstrate the feasibility of (1) semiconductor graphene nanostructures based on the quantum confinement effect, (2) spin-based devices from graphene nanostructures with magnetic edges, as well as (3) novel operation principles based on the interplay of the electronic and spin-degrees of freedom. We propose to demonstrate the electrical control of magnetism in graphene nanostructures, as well as a novel switching mechanism for graphene field effect transistors induced by the transition between two magnetic edge configurations. Exploiting such novel operation mechanisms in graphene nanostructure engineered at the atomic scale is expected to lay the foundations of disruptively new device concepts combining electronic and spin-based mechanisms that can overcome some of the fundamental limitations of today s electronics.tBreaking the temperature limits of Solid Oxide Fuel Cells: Towards a new family of ultra-thin portable power sources2Strongly interacting Rydberg slow light polaritonsA fundamental property of optical photons is their extremely weak interactions, which can be ignored for all practical purposes and applications. This phenomena forms the basis for our understanding of light and is at the heart for the rich variety of tools available to manipulate and control optical beams. On the other hand, a controlled and strong interaction between individual photons would be ideal to generate non-classical states of light, prepare correlated quantum states of photons, and harvest quantum mechanics as a new resource for future technology. Rydberg slow light polaritons have recently emerged as a promising candidate towards this goal, and first experiments have demonstrated a strong interaction between individual photons. The aim of this project is to develop and advance the research field of Rydberg slow light polaritons with the ultimate goal to generate strongly interacting quantum many-body states with photons. The theoretical analysis is based on a microscopic description of the Rydberg polaritons in an atomic ensemble, and combines well established tools from condensed matter physics for solving quantum many-body systems, as well as the inclusion of dissipation in this non-equilibrium problem. The goals of the present project addresses questions on the optimal generation of non-classical states of light such as deterministic single photon sources and Schrdinger cat states of photons, as well as assess their potential for application in quantum information and quantum technology. In addition, we will shed light on the role of dissipation in this quantum many-body system, and analyze potential problems and fundamental limitations of Rydberg polaritons, as well as address questions on equilibration and non-equilibrium dynamics. A special focus will be on the generation of quantum many-body states of photons with topological properties, and explore novel applications of photonic states with topological properties.8Personalized oncolytic vaccines for cancer immunotherapyThis grant application proposes to develop a novel, customizable and personalized anti-cancer vaccine: peptide-coated conditionally replicating adenovirus (PeptiCrad). Anti-cancer vaccines represent a promising approach for cancer treatment because they elicit durable and specific immune response that destroys primary tumors and distant metastases. Oncolytic viruses (OVs) are of significant interest because in addition to cytolysis they stimulate anti-tumor immune responses, thereby functioning as anti-tumor vaccines. However, their efficacy among cancer patients has been modest. One reason for this shortcoming is that the immune responses generated by virus infection primarily target the virus rather than the tumor. In addition, tumors differ across patients. Specific and personalized approaches (rather than generic virus infection strategies) are required to optimize therapy. To this end we propose to develop a novel vaccine platform that combines the strengths of OVs with the specificity of vaccines. Our technology is called PeptiCrad. PeptiCrad is a virus  dressed as a tumor . It directly kills cancer cells (i.e., oncolytic viruses) and expresses immunomodulatory molecules (i.e., cytokines or the immune checkpoint inhibitors anti-CTLA4 or anti-PDL1); most importantly, it diverts immunity toward the tumor (i.e., the capsid becomes covered with MHC-I-restricted tumor-specific peptides). The method that we have developed to cover the virus with tumor peptides is novel and exceeds current state-of-the-art. Importantly, it is fast and does not require genetic or chemical manipulation of the virus; this feature has a significant impact on the translational capability of the project. Our preliminary results show great potential but significant questions regarding the development and the personalization of PeptiCrad remain to be studied. In this grant I propose two lines of research, one focused on the development and the other one on the personalization of PeptiCrad. Fa Theoretical chemistry Approach to tiME-resolved molecular Plasmonic< sUltrafast spectroscopy is a powerful tool able to disclose the atomistic real-time motion picture of the basic chemical events behind technology and Life, such as catalytic reactions or photosynthetic light harvesting. Nowadays, by cleverly harnessing the interaction of the studied molecules with plasmons (collective electron excitations supported, e.g., by metal nanoparticles) it is becoming possible to focus these investigations on specific nanoscopic regions, such as a portion of a catalytic surface or of a photosynthetic membrane. This coupling can also produce new quantum effects such as molecule-plasmon hybrid excitations. On the other hand, it makes the real-time molecular evolution and its perturbation by light more complex, and thus calls for new theoretical treatments. The available ones are unable to tackle this complexity, because they consist of phenomenological models focused on field enhancements or on generic features of the various plasmon-molecule coupling regimes. The goal of TAME-Plasmons is to develop a theoretical chemistry approach to directly simulate the real time evolution of molecules interacting with plasmons and light. Our approach lifts the current theoretical limitations by coupling a real-time quantum chemical description of the molecules with a time-dependent electromagnetic description of plasmons, rooted in our previous work on steady-state molecular plasmonics. We will implement this approach in an open-source software, accessible also to non-specialists. We will address current open issues such as the controversial nature of plasmon-aided frequency up-conversion by noble gases and the interpretation of sub-molecularly resolved photoemission induced by scanning tunneling microscopy. We will also anticipate questions that may arise along with progress in the field, for example how to engineer energy transfer paths in photosynthetic light harvesting proteins by exploiting the coupling to plasmons.iCross-Linguistic Acquisition of Sentence Structure: Integrating Experimental and Computational ApproachesHow children acquire their native language remains one of the key unsolved problems in Cognitive Science. This project will answer a question that lies at the heart of this problem: How do children acquire the abstract generalizations that allow them to produce novel sentences, while avoiding the ungrammatical utterances that result from across-the-board application of these generalizations (e.g., *The clown laughed the man)? Previous single-process theories (the entrenchment, preemption and verb semantics hypotheses) fail to explain all of the current English data, and do not begin to address the issue of how learners of other languages solve this learnability problem. The aim of the present project is to solve this problem by developing and testing a new unified cross-linguistic account of the development of sentence structure. In addition to the overarching theoretical question set out above, the research will address four key questions: (1) What do learners bring to the task in terms of cognitive-semantic universals?; (2) How do children form linguistic generalizations in the first place?; (3) Why are languages the way they are; would other types of systems be difficult or impossible to learn?; (4) What is the nature of development?. These questions will be addressed by means of four Work Packages (WPs). WP1 uses grammaticality judgment and elicited production paradigms developed by the PI to investigate the acquisition of basic transitive and intransitive sentence structure (e.g., The man broke the window/The window broke) across six typologically different languages: English, K iche Mayan, Japanese, Hindi, Hebrew and Turkish (at ages 3-4, 5-6, 9-10 and 18+ years). WP2 uses the same paradigms to investigate idiosyncratic language-specific generalizations within three of these languages. WP3 uses Artificial Grammar Learning to focus on the issue of language evolution. WP4 uses computational modeling to investigate and simulate development.RNovel approaches to determining the function of tissue-specific regulatory T cellsRegulatory T cells (Tregs) are formed through the expression of the transcription factor Foxp3 in T cells, resulting in the rewiring of the cell function into an immunosuppressive phenotype. Recently, it has been proposed that Tregs also have additional tissue-specific physiological roles when resident in different tissues. For example, tissue-specific Tregs residing in the muscle and adipose tissue possess immunological and non-immunological functions in these tissues, distinct from the generic Tregs in circulation. Currently, research into tissue-specific functions of Tregs, or any other migratory cell type, is limited by the available research tools. A vital part of immunological studies is cell depletion, yet a major limitation of all available methods is that they deplete target cells across the entire organism. This makes it extremely difficult to ascertain the function of tissue-resident Tregs, as systemic deletion results in severe autoimmunity, confounding the study of tissue-specific subsets. In order to assess these tissue-resident subsets new research tools are required to deplete the target cells in a specific anatomical region while leaving the same cell type unaffected in other organs. This project proposes to generate new synthetic biology tools for depleting tissue-resident cells and then to apply these tools to the study of tissue-resident Tregs in the brain, lung, liver, kidney and pancreas, thus creating a comprehensive atlas of tissue-specific functions. These studies will be extended by systematic molecular, cellular and kinetic analysis using existing innovative methods established in the laboratory. Finally, our tissue-specific deletion system will have a profound impact on immunology beyond the direct scope of the project, as the tools will be developed to allow flexible application to any cell type. In essence, this is a field of research currently held back by the absence of appropriate tools, waiting for the generation of a new toolkit.VDynamical magnetic excitations with spin-orbit interaction in realistic nanostructuresNano-spin-< orbitronics is an emerging and fast growing field that aims at combining three degrees of freedom " spin, charge and spin-orbit interaction " to explore new nanotechnologies stemming from fundamental physics. New magnetic phases of matter are investigated using, in particular, atomic design to tailor beneficial physical properties down to the atomic level. Storage, transport and manipulation of magnetic information within a small set of atoms does not only require a fundamental understanding of their ground-state properties from the perspective of quantum mechanics, but crucially also their dynamical excited states. We propose to go beyond the state of the art by investigating from first-principles the dynamical properties of chiral spin textures in nanostructures from 2-dimensions to 0-dimension with these nanostructures being deposited on different substrates where spin-orbit interaction plays a major role. Understanding their response to external dynamical fields (electric/magnetic) or currents will impact on the burgeoning field of nano-spin-orbitronics. Indeed, to achieve efficient manipulation of nano-sized functional spin textures, it is imperative to exploit and understand their resonant motion, analogous to the role of ferromagnetic resonance in spintronics. A magnetic skyrmion is an example of a spin-swirling texture characterized by a topological number that will be explored. This spin state has huge potential in nanotechnologies thanks to the low spin currents needed to manipulate it. Based on time-dependent density functional theory and many-body perturbation theory, our innovative scheme will deliver a paradigm shift with respect to existing theoretical methodologies and will provide a fundamental understanding of: (i) the occurrence of chiral spin textures in reduced dimensions, (ii) their dynamical spin-excitation spectra and the coupling of the different excitation degrees of freedom and (iii) their impact on the electronic structure.WEpithelial cell sheets as engineering materials: mechanics, resilience and malleabilityThe epithelium is a cohesive two-dimensional layer of cells attached to a fluid-filled fibrous matrix, which lines most free surfaces and cavities of the body. It serves as a protective barrier with tunable permeability, which must retain integrity in a mechanically active environment. Paradoxically, it must also be malleable enough to self-heal and remodel into functional 3D structures such as villi in our guts or tubular networks. Intrigued by these conflicting material properties, the main idea of this proposal is to view epithelial monolayers as living engineering materials. Unlike lipid bilayers or hydrogels, widely used in biotechnology, cultured epithelia are only starting to be integrated in organ-on-chip microdevices. As for any complex inert material, this program requires a fundamental understanding of the structure-property relationships. (1) Regarding their effective in-plane rheology, at short time-scales epithelia exhibit solid-like behavior while at longer times they flow as a consequence of the only qualitatively understood dynamics of the cell-cell junctional network. (2) As for material failure, excessive tension can lead to epithelial fracture, but as we have recently shown, matrix poroelasticity can also cause hydraulic fracture under stretch. However, it is largely unknown how adhesion molecules, membrane, cytoskeleton and matrix interact to give epithelia their robust and flaw-tolerant resilience. (3) Regarding shaping 3D epithelial structures, besides the classical view of chemical patterning, mechanical buckling is emerging as a major morphogenetic driving force, suggesting that it may be possible design 3D epithelial structures in vitro by mechanical self-assembly. Towards understanding (1,2,3), we will combine a broad range of theoretical, computational and experimental methods. Besides providing fundamental mechanobiological understanding, this project will provide a framework to manipulate epithelia in bioinspired technologies.HUnifying concepts in the topological design of non-crystalline materialsGlasses have traditionally been enabling materials to major societal challenges. Significant breakthroughs on many areas of technological progress have been very closely linked to the exploitation of glassy materials. It is strong consensus that this key role will persist in the emerging solutions to major global challenges in living, energy, health, transport and information processing, provided that the fundamental limitations of the presently available empirical or semi-empirical approaches to glass processing can be overcome. In the coming decade, it is therefore a major task to take the step towards ab initio exploitation of disordered materials through highly-adapted processing strategies. This requires pioneering work and in-depth conceptual developments which combine compositional design, structural evolution and the thermo-kinetics of material deposition into holistic tools. Only those would significantly contribute to solving some of the most urgent materials needs for glass applications in functional devices, be it in < the form of thin films, particles or bulk materials. The present project challenges today s engineering concepts towards the conception of such tools. For that, melt deposition, isothermal deposition from liquid phases, and gas-phase deposition of non-crystalline materials will be treated - within the class of inorganic glasses - in a generalist approach, unified by the understanding that glass formation represents the only strict deviation from self-organization, and that, hence, the evolution of structural complexity in glassy materials can be tailored on any length-scale through adequate processing. Providing a topological scheme for the quantification and chemical tailoring of structural complexity, UTOPES will answer to the challenge of finding order in disorder, and will thus break the grounds for the third generation of glasses with properties beyond what is presently thought as the limits of physical engineering. EDissecting the cellular mechanics of contact inhibition of locomotionOur aim is to dissect the mechanisms of contact inhibition of locomotion (CIL), a process whereby migrating cells collide and repel each other, as it is now clear that CIL is pivotal to understanding embryogenesis and pathologies such as cancer. We have developed an in vivo model using Drosophila macrophages (hemocytes), along with novel analytical tools, to examine the contact inhibition response in cells during development. We therefore have an unprecedented opportunity to address CIL in a genetically tractable organism within a physiologically relevant setting. This model has revealed that a precisely controlled CIL response is a significant driving force behind the acquisition of embryonic patterns, and recent data show that this precision requires a series of synchronized changes in cytoskeletal dynamics. Our central hypothesis is that key to this cellular  dance is mechanosensation of the collision, which integrates subsequent signaling mechanisms to choreograph the steps of the contact inhibition process. The first part of this proposal will elucidate the molecular mechanisms controlling CIL by exploiting our unique ability to live image and genetically dissect this process in Drosophila. We will also take an interdisciplinary approach to elucidate the mechanical aspects of the response, which will allow us to examine the feedback between signaling pathways and the physical forces of the CIL response. We will subsequently extend our detailed understanding of the CIL process, and our novel set of analytical tools, to mammalian cell types and model systems. This will allow us to develop new assays to directly probe the mechanics of CIL and begin to investigate the function of this underexplored process in other cell types. This in depth knowledge of the response places us in the best position to extend our understanding of CIL to new physiologically relevant scenarios that in the future will impact on human health.LQuantum Black Holes: A macroscopic window into the microstructure of gravityOPolicy, practice and patient experience in the age of intensified data sourcing_The physics of antibiotic resistance evolution in spatially-structured multicellular assembliesPA programming language bridging theory and practice for scientific data curation?Accretion, Winds, and Evolution of Spins and Magnetism of StarsThis project focuses on Sun-like stars, which possess convective envelopes and universally exhibit magnetic activity (in the mass range 0.1 to 1.3 MSun). The rotation of these stars influences their internal structure, energy and chemical transport, and magnetic field generation, as well as their external magnetic activity and environmental interactions. Due to the huge range of timescales, spatial scales, and physics involved, understanding how each of these processes relate to each other and to the long-term evolution remains an enormous challenge in astrophysics. To face this challenge, the AWESoMeStars project will develop a comprehensive, physical picture of the evolution of stellar rotation, magnetic activity, mass loss, and accretion. In doing so, we will (1) Discover how stars lose the vast majority of their angular momentum, which happens in the accretion phase (2) Explain the observed rotation-activity relationship and saturation in terms of the evolution of magnetic properties & coronal physics (3) Characterize coronal heating and mass loss across the full range of mass & age (4) Explain the Skumanich (1972) relationship and distributions of spin rates observed in young clusters & old field stars (5) Develop physics-based gyrochronology as a tool for using rotation rates to constrain stellar ages. We will accomplish these goals using a fundamentally new and multi-faceted approach, which combines the power of multi-dimensional MHD simulations with long-timescale rotational-evolution models. Specifically, we will develop a next generation of MHD simulations of both star-disk interactions and stellar winds, to model stars over the full range of mass & age, and to characterize how magnetically active stars impact their environments. Simultaneously, we will create a new class of rotational-evolution models that include external torques derived from our simulations, compute the evolution of spin rates of entir< e star clusters, & compare with observations.>Mumps VIRus EXploitation of the human adhesion receptor GPR125Mumps virus is a re-emerging pathogen that causes painful inflammatory symptoms, such as parotitis (salivary gland infection) and orchitis (testis infection). It is highly neurotropic with evidence of brain infection in half of cases and clinical evidence in up to 10%. It is a small RNA virus belonging to the family of paramyxoviridae that includes e.g. viruses for measles and pneumonia, all having a huge impact on global economics and human health. Current vaccine programs have not managed to eliminate mumps and infections occur also in vaccinated individuals. Seven transmembrane (7TM) receptors are important drug targets. Large DNA viruses (herpes- and pox-) assign large parts of their genomes to exploit 7TM receptors. No such mechanism has however yet been described for small viruses. Based on strong preliminary data, I will in this interdisciplinary project test the groundbreaking hypothesis that the adhesion 7TM receptor GPR125 is central for the organ damage caused by mumps virus via an interaction with the mumps virus-encoded short-hydrophobic (SH)-protein. I will do so by determining: 1 - The functional consequences of GPR125-SH-interaction at a single cell, organ and whole body level within the context of mumps virus infection 2 - The structural requirements for the GPR125-mumps virus interaction using NMR and resolution of crystal structure in preparation for future drug design The project is high risk and high gain, yet the gain clearly exceeds the risk. On account of my past expertise in pharmacology and virology, and that of several expert collaborators, the project is indeed feasible. It has tremendous perspectives as SH-proteins are present also in other viruses. The SH-GPR125 complex might thus represent a general principle for organ damage and a mode of action more generally amenable to therapeutic interference. In fact, novel approaches, mechanism-based, might be seen as more appealing to those who fear current vaccination 'modes'.ZBiogeochemical and ecosystem interactions with socio-economic activity in the global oceanThe global marine ecosystem is being deeply altered by human activity. On the one hand, rising concentrations of atmospheric greenhouse gases are changing the physical and chemical state of the ocean, exerting pressure from the bottom up. Meanwhile, the global fishery has provided large economic benefits, but in so doing has restructured ecosystems by removing most of the large animal biomass, a major top-down change. Although there has been a tremendous amount of research into isolated aspects of these impacts, the development of a holistic understanding of the full interactions between physics, chemistry, ecology and economic activity might appear impossible, given the myriad complexities. This proposal lays out a strategy to assemble a team of trans-disciplinary expertise, that will develop a unified, data-constrained, grid-based modeling framework to represent the most important interactions of the global human-ocean system. Building this framework requires solving a series of fundamental problems that currently hinder the development of the full model. If these problems can be solved, the resulting model will reveal novel emergent properties and open the doors to a range of previously unexplored questions of high impact across a range of disciplines. Key questions include the ways in which animals interact with oxygen minimum zones with implications for fisheries, the impacts fish harvesting may have on nutrient recycling, spatio-temporal interactions between managed and unmanaged fisheries, and fundamental questions about the relationships between fish price, fishing cost, and multiple markets in a changing world. Just as the first coupled ocean-atmosphere models revealed a wealth of new behaviours, the coupled human-ocean model proposed here has the potential to launch multiple new fields of enquiry. It is hoped that the novel approach will contribute to a paradigm shift that treats human activity as one component within the framework of the Earth System.dEpistemic Transitions in Islamic Philosophy, Theology and Science: From the 12th to the 19th CenturylElectron-lattice-spin correlations and many-body phenomena in 2D semiconductors and related heterostructuresTemporal Quantum CorrelationsBDual targeting of senescence and tumor immunity for cancer therapyWe have previously demonstrated that cellular senescence opposes tumorigenesis thereby opening up new potential opportunities for cancer treatment. Senescence and tumor immunity in cancer are tightly interconnected. Tumor-infiltrating immune cells promote the clearance of senescent tumor cells thereby contributing to the tumor suppressive function of senescence. Moreover, T lymphocytes can drive senescence in cancers by secreting different cytokines in the tumor microenvironment. We have also recently reported that GR1+ myeloid cells antagonize treatment-induced senescence (TIS) and that compounds that block the tumor recruitment of GR1+ cells enhance TIS. Major objective of this proposal is to characterize the immune landscape of different prostate cancer mouse models in order to develop novel treatment modalities that combine pro-senescence compounds with immunotherapy. Using proteomics and bioinformatics approaches, we will assess how the genetic background of prostate tumors, shapes the tumor microenvironment and immune response during TIS. Next, we will define the mechanisms that regulate the recruitment and activation of myeloid derived suppressive cells, macrophages and B-lymphocytes in Pten deficient prostate tumors by focusing on a novel class of secreted factors identified in these tumors. We will also assess in vivo whether the secretome of tumor cells can transmit senescence to TILs and compounds that interfere with the secretome can prevent immunosenescence. Finally, we will develop monoclonal antibodies directed towards senescent tumors cells that we will use as diagnostic and therapeutic tools. These antibodies will be used as biomarkers to detect senescent tumor cells in prostate cancers and will be tested in pre-clinical trials to assess whether they improve tumor clearance during TIS. Our findings will form the basis for future clinical trials in prostate cancer patients.$Principles of Graph Data IntegrationThe present proposal tackles fundamental problems in data management, leveraging expressive, large-scale and heterogeneous graph structures in order to integrate both unstructured (e.g., text) and structured (e.g., relational) content. Integrating heterogeneous content has become a key hurdle in the deployment of Big Data applications, due to the meteoric rise of both machine and user-generated data storing information in a variety of formats. Traditional integration techniques cleaning up, fusing and then mapping heterogeneous data onto rigid abstractions fall short of accurately capturing the complexity and wild heterogeneity of today s information. Having closely followed the emergence of heterogeneous information sources online, I am convinced that only an interdisciplinary approach drawing both from classical data management and from large-scale Web inform< ation processing techniques can solve the formidable data integration challenges that they pose. The following project proposes an ambitious overhaul of information integration techniques embracing the scale and heterogeneity of today s data. I propose the use of expressive and heterogeneous graphs of entities to continuously and dynamically interrelate disparate pieces of content while capturing their     !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefgijklmnopqrstuvwxyz{|}~ idiosyncrasies. The following project focuses on three core issues related to large-scale and heterogeneous information graphs: i) the effective extraction of fined-grained information from unstructured sources and their proper integration into large-scale heterogeneous and probabilistic graphs, ii) the creation of novel physical storage structures and primitives to durably and efficiently manage the profusion of data considered by such graphs using clusters of commodity machines, and iii) the development of logical data abstraction mechanisms facilitating the effective and efficient resolution of complex analytic and data integration queries on top of the physical layer.-Amorphous and Evolutionary DNA NanotechnologyOAmorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for the optimization of nucleic acid nanocomponents.Amorphous DNA nanotechnology first aims at the creation of cell-sized, DNA-programmed microgels  DNA cells  with sensor, computation, communication, and actuator functions. Interacting DNA cells will be arranged into chemical cell consortia and artificial tissues using microfluidics, micromanipulation and 3D bioprinting techniques. Spatially distributed chemical circuits will then be utilized to establish collective behaviors such as quorum sensing, pattern formation, and self-differentiation within these consortia and tissues. The approach will be further scaled up to produce multicomponent DNA gel compositions that become active and differentiate upon mixing. In evolutionary nanotechnology, techniques derived from directed molecular evolution experiments will be applied to optimize the arrangement of functional nucleic acids on DNA and RNA nanoscaffolds. Compartmentalization and microfluidics will be utilized to screen for nucleic acid nanostructures capable of superstructure formation, and also for the development of ligand-sensitive components for molecular programming. An evolutionary approach will then be applied to amorphous DNA cells, resulting in DNA cell populations which contain individuals with different molecular identities. The proposal will pave the way for the creation of macroscopic materials with DNA-programmed intelligence, resulting in novel applications for DNA nanotechnology and molecular programming in diverse fields such as environmental and biological sensing, biocatalysis, smart adaptive materials, and soft robotics.ABio-Inspired Self-Assembled Supramolecular Organic NanostructuresPeptide building blocks serve as very attractive bio-inspired elements in nanotechnology owing to their controlled self-assembly, inherent biocompatibility, chemical versatility, biological recognition abilities and facile synthesis. We have demonstrated the ability of remarkably simple aromatic peptides to form well-ordered nanostructures of exceptional physical properties. By taking inspiration from the minimal recognition modules used by nature to mediate coordinated processes of self-assembly, we have developed building blocks that form well-ordered nanostructures. The compact design of the building blocks, and therefore, the unique structural organization, resulted in metallic-like Young's modulus, blue luminescence due to quantum confinement, and notable piezoelectric properties. The goal of this proposal is to develop two new fronts for bio-inspired building block repertoire along with co-assembly to provide new avenues for organic nanotechnology. This will combine our vast experience in the assembly of aromatic peptides together with additional structural modules from nature. The new entities will be developed by exploiting the design principles of small aromatic building blocks to arrive at the smallest possible module that form super helical assembly based on the coiled coil motifs and establishing peptide nucleic acids based systems to combine the worlds of peptide and DNA nanotechnologies. The proposed research will combine extensive design and synthesis effort to provide a very diverse collection of novel buildings blocks and determination of their self-assembly process, followed by broad chemical, physical, and biological characterization of the nanostructures. Furthermore, effort will be made to establish supramolecular co-polymer systems to extend the morphological control of the assembly process. The result of the project will be a large and defined collection of novel chemical entities that will help reshape the field of bioorganic nanotechnology.:Global Change 2.0: Unlocking the past for a clearer futureThe terrestrial biosphere responds rapidly and sensitively to climate change and is important in mediating physical and biog< eochemical feedbacks to climate. There are still enormous uncertainties in our understanding of how the terrestrial biosphere will respond to changes in climate in the 21st century, and large uncertainties in predictions of the climate feedbacks. Many issues that limit our ability to predict the future of the terrestrial biosphere can be addressed by examining what happened in the recent geologic past  where the drivers of climate change are relatively well known and there is abundant globally-distributed, quantitative, well-dated and unambiguous evidence of the biospheric response. The goal of this project is to unleash the power of the palaeo-record to understand the interactions of climate and the terrestrial biosphere, and to explain how terrestrial systems (vegetation, fire, hydrology, biogeochemical cycles including the carbon, trace gas and dust cycles) respond and contribute to long-term (millennial) and rapid (decadal to centennial) climate changes. I will use process-based models with global palaeodata syntheses to address four specific challenges to our understanding of past and future climate and environmental change: (1) How does vegetation respond to rapid climate change and what are the consequences of this response for climate?(2) To what extent does increasing CO2 enhance tree growth or competitive fitness, and how does this translate into changes in ecosystems and ecosystem services?(3) How does the terrestrial biosphere respond to changes in climate variability and the prevalence of extreme events?(4) How does the land surface affect regional climates, and why do models persistently fail to predict these effects accurately?In addressing these challenges, I will deliver public-access data sets, model outputs and comparison tools so the strengths of the palaeorecord can be exploited by the wider global change communECoherent multidimensional spectroscopy of controlled isolated systemsFundamental quantum mechanical processes determine the properties of matter and their functionality. In order to understand complex processes such as light harvesting in photosynthesis and photovoltaics, a detailed knowledge of coherent effects in excitation and charge transfer processes and related dynamics is required. To a large extent, the complexity of the systems induces too many interactions and perturbations of the processes to isolate and understand individual mechanisms. Advanced experimental methods, capable of detecting quantum coherences, so far are not applicable to quantum state controlled molecular complexes isolated from the perturbing environment, due to the low density of such targets. In this project we will for the first time employ coherent femtosecond multidimensional spectroscopy to dilute isolated molecular complexes. For a specific heterogeneous synthesis we will use aggregation in superfluid helium at millikelvin temperatures. In order to reach the needed sensitivity we will setup a novel phase modulation technique including lock-in demodulation in combination with mass-resolved ionization and photoelectron detection. Advanced mathematical methods will furthermore be developed and applied, boosting efficient collection of multidimensional datasets. We will be able to (a) identify processes and coherent dynamics of excitation and charge transfer in fundamental heterogeneous complexes, in particular van der Waals bound donor acceptor complexes (b) elucidate coherence and dissipation effects in contact with tailored external baths, (c) investigate microsolvation, i.e. measure the evolution of dynamic properties as a function of attached solvent molecules, (d) determine collective effects like autoionization in dilute atomic gases or exciton annihilation in semiconductor systems, (e) implement compressed sensing in multidimensional data acquisition, (f) implement largely parallelized phase-cycling into real-time data acquisition."Synthesising Inductive Data Models-Inspired by recent successes towards automating highly complex jobs like programming and scientific experimentation, the ultimate goal of this project is to automate the task of the data scientist when developing intelligent systems, which is to extract knowledge from data in the form of models. More specifically, this project wants to develop the foundations of a theory and methodology for automatically synthesising inductive data models.An inductive data model (IDM) consists of 1) a data model (DM) that specifies an adequate data structure for the dataset (just like a database), and 2) a set of inductive models (IMs), that is, a set of patterns and models that have been discovered in the data. While the DM can be used to retrieve information about the dataset and to answer questions about specific data points, the IMs can be used to make predictions, propose values for missing data, find inconsistencies and redundancies, etc. The task addressed in this project is to automatically synthesise such IMs from past data and to use these to support the user when making decisions.It will be assumed that the data set consists of a set of tables, that the end-user interacts with the ID< M via a visual interface, and the data scientist via a unifying IDM language offering a number of core IMs and learning algorithms.The key challenges to be tackled in SYNTH are: 1) the synthesis system must  learn the learning task , that is, it should identify the right learning tasks and learn appropriate IMs for each of these; 2) the system may need to restructure the data set before IM synthesis can start; and 3) a unifying IDM language for a set of core patterns and models must be developed.The approach will be implemented in open source software and evaluated on two challenging application areas: rostering and sports analytics.4Microscale Processes Governing Global Sustainability:Exponential sums, translation invariance, and applicationsPTranscriptional and Epigenetic Regulation of Totipotency in Mouse Early Embryos.In mammals, fusion of two highly differentiated gametes gives rise to a totipotent zygote capable of developing into a whole organism. It coincides with translation and degradation of maternally provided transcripts, initiation of global transcription called zygotic genome activation (ZGA), and  epigenetic reprogramming of germline chromatin states into an embryonic state. The molecular mechanisms underlying this exquisite reprogramming of cell fate are barely understood. This research program has the ambitious goal to identify and characterize in a comprehensive way the transcription factors and chromatin regulators which initiate and regulate ZGA in a parental specific manner in early mouse embryos. We will utilize novel and highly sensitive genomic approaches to measure nascent transcription and determine open and modified chromatin landscapes in oocytes and early embryos, wild-type and conditionally deficient for major epigenetic modifiers. We will apply computational approaches to identify candidate TFs and histone modifiers controlling ZGA. We will use molecular and developmental biology approaches, combined with sensitive quantitative live-imaging, to interrogate the function of TFs and their binding sites for ZGA.We will further investigate the significance of possible paternal inheritance of nucleosomes at CpG islands for gene regulation during ZGA and later development by depleting nucleosomes from mature sperm by using sophisticated conditional deficiency and gain-of-function mouse models. By transferring nuclei of immature spermatid and mature sperm into oocytes, we will interrogate the relevance of nucleosome eviction during spermatogenesis, as a possibly truly epigenetic reprogramming process, for defining embryonic competence. ERC funding would represent a crucial contribution to dissecting the molecular mechanisms underlying acquisition of totipotency in mouse embryos and may impact on the use of Assisted Reproductive Technologies in human medPExperimental Searches for Oscillating and Transient effects from the Dark SectorThe objective of the proposed project is to pioneer a magnetometry-based experimental framework for the detection of time-varying signatures of the  dark sector . This novel approach will enable systematic searches for particles contributing to the dark matter and for dark-energy components.The nature of dark matter and that of dark energy are among the central open problems in modern physics. There are only few experimental bounds and so far no conclusive observations of dark-sector particles or fields. Experiments enabling a direct coupling to the dark sector and thus a systematic search for and study of the contributing particles and fields would open up new vistas for areas ranging from particle physics to astrophysics and cosmology, and would in particular provide insights into the physics beyond the Standard Model.Here, we propose a framework for such experimental searches based on high-precision magnetometers, and networks thereof. Our approach is distinct from existing efforts in two ways. First, it will enable searches for so-far unexplored couplings to ultra-light bosonic particles present in the Universe that could be components of dark matter and/or dark energy, in particular axions and axion-like particles (ALPs). Second, we will develop and use devices and methods tailored to search for oscillatin< g and transient, rather than time-independent, effects. Specifically, we will use nuclear magnetic resonance (NMR) techniques for detecting spin precession caused by background axion and ALP dark matter, and geographically separated magnetometers for identify transient effects, such as crossing domain walls of ALP fields, which have been proposed as a possible dark-energy component.The devices and methods developed in the framework of this project will provide the essential components for unique searches for a broad class of dark-matter and dark-energy candidates and might enable the key experiments to understanding the dark sector.Power to the People. Verified.Twenty years ago we were able to repair cars at home. Nowadays customer services repair coffee machines. By installing software updates. Soon you will no longer be able to repair your bike.Embedded software innovations boost our society; they help us tremendously in our daily life. But we do not understand what the software does, regardless of how well educated or smart we are. Proprietary embedded software has become an opaque layer between functionality and user. That layer is thick enough to possibly induce malicious or unintended behaviour. Proprietary embedded software locks us out of the products we own.We need a turn to open and hence customisable embedded software. However, a minor customisation might well have strong unexpected impact, for instance on the longevity of an embedded battery, or the safety of the battery charging process. We thus need means to detect, quantify and prevent such implications.The POWVER project lays the foundations. It provides quantitative verification technology for system-level correctness, safety, dependability, and performability. In this endeavour, POWVER takes up a hard scientific challenge, a challenge where discrete and continuous, real-time, stochastic as well as data- and user-dependent aspects are all deeply intertwined: embedded software for electric power management. Electric power is intricate to handle by software, is safety-critical, but vital for mobile devices and their longevity. Since ever more tools, gadgets, and vehicles run on batteries and use power harvesting, power management is a pivot of the future.POWVER will demonstrate that quantitative verification of open embedded software is feasible, and can ensure safe and dependable operation of safety-critical devices. A proof of concept will target the field of electric mobility, set up as a blueprint for other battery-powered appliances. As such, POWVER is the nucleus for a radical change in the way embedded software quality is assured in general.EThe origins of dendritic computation within mammalian neural circuitsIMulti-Scale Description of Non-Universal Behavior in Turbulent CombustionCombustion is an extremely important field for our society. The development of new, step-change technologies is essential and greatly benefits from computational design. However, turbulent combustion physics are complex, highly non-linear, of multi-scale and multi-physics nature, and involve interactions at many time-scales. This makes modeling quite challenging such that accurate predictive models, especially for the formation of pollutants, are not available. Today, the two major challenges for developing predictive simulations of turbulent combustion are first to account for its multi-scale nature by considering the non-universal behavior of small-scale turbulence, which is known to be critically important for turbulence-chemistry interactions, and second, to provide data in sufficient detail for rigorous analysis of model deficiencies and unambiguous model development. These two issues are addressed in the proposed work. The main overall objectives are: 1) Establish a new multi-scale framework to analyze and model turbulent combustion phenomena based on a new way to describe turbulence using so-called dissipation elements, which are space-filling regions in a scalar field allowing to capture its small-scale morphology and non-universality. 2) Create new unprecedented datasets using direct numerical simulations (DNS) and provide new analysis methods to develop and validate combustion models; this will include automatically reducing and optimizing chemical kinetic mechanisms for use in DNS and developing an on-the-fly chemistry reduction technique. 3) Apply new modeling approaches to complex and highly non-linear modeling questions, such as pollutant formation in turbulent spray combustion. The successful outcome of the project will provide new and unprecedented datasets, a quantitative description of the impact of non-universality in small-scale turbulence on different aspects of turbulent combustion, and the basis for an entirely new multi-scale closure.Oxidative stress, an excess of radical and other reactive oxygen species (ROS), has been suggested as a major disease mechanism. However, the major clinical trials using anti-oxidants have been failures, even suggesting serious side effects. Here, I propose completely different approaches: First, instead of letting radicals form and then scavenge them we will identify their diseases-relevant sources and prevent their formation or specifically repair the damage caused by ROS. Second, we will differentiate beneficial signalling roles of ROS. In combination, this will result in unprecedented precision and molecular specificity. In 2010, I submitted a somewhat related proposal to the ERC and received a comment as being  too focused on essential hypertension . This proposal has a much broader focus and impact beyond cardiovascular diseases. In the past months we achieved major breakthroughs by identifying a radical/ROS source (NOX4) as fundamental mechanism in stroke, the fastest growing and soon no 1 cause of death. We are also developing in phase II a radical formation inhibitor for neurotrauma. Moreover, our basic research facilitated the development of drug classes re-activating an oxidatively damaged signalling receptor, now in phase III. Further, we identified angiogenesis as a radical/ROS-dependent and protective (!) signalling event. This proposal is just the beginning: our basic science will open up new fields and leap forward in personalized medicine with groundbreaking technologies and approaches. We will contribute to the diagnosis and early identification of patients at risk and to monitor their successful treatment (in vitro/blood-based); to the localization of diseas< e processes (in vivo/molecular imaging) before the onset of symptoms; and to a new generation of more effective, predictable, and mechanism-based drugs. We also expect to later apply our findings and tools to neurobiology and oncology, where ROS also play physiological and pathological roles.-Radical Medicine: Redefining Oxidative Stress&Innovative Polymers for Energy Storage5Light-activatable ruthenium-based anticancer prodrugsROur proposal addresses theoretical and phenomenological properties of large distance ( Infra-Red , IR in the following) modifications of the gravitational interaction. Such modifications are motivated by two main reasons: firstly, to find alternative explanations to the presence of dark matter or dark energy in cosmology; secondly, to better understand the currently well accepted cosmological model, disentangling there what does from what does not depend on the large distance dynamics of gravity and extracting as much as possible new information on gravity from the latest cosmological observations. For the second goal, it matters to have at hand alternatives to the standard cosmological model based on general relativity, to serve as benchmarks. Very recently, new ideas have been proposed to modified gravity in the IR. First, a large class of scalar-tensor theories featuring the  k-mouflaging of the scalar has been proposed and partly classified. Second, new kinds of massive gravities which might be devoid of the standard pathologies of those models have been discovered. Third, models of non local gravity have been proposed with many interesting features. In this proposal, we intend to better understand those constructions, in which the works of the applicant played a major role, and whose properties are largely unexplored. As transversal goals, we also intend to propose new ways to modify gravity in the IR, as well as to develop schemes to tests IR modifications of gravity against cosmological and gravitational data. The project will be lead by the applicant, four postdocs and two students.3New paradigms for InfraRed modifications of GravitysWe propose to perform a wide spectrum of ionosphere-related research, from ionosphere seismology to ionospheric storms and GNSS/GPS performance during extreme ionospheric and space weather events. The main focus will be made on such rare subject as ionosphere seismology that aims to study ionosphere response to large earthquakes, to investigate the main properties of different kinds of ionospheric disturbances occurred due to seismic and seismic-like events, including tsunamis, volcano eruptions and explosions. The 11/03/2011 Tohoku megaquake has opened new challenges for modeling of co-seismic effects and has indicated new directions for further research. In particular, we found that the ionosphere is able of showing images of a seismic fault slip rupturing about ~8 minutes after an earthquake, which opens new opportunities for short-time tsunami warnings. In addition to the ionosphere seismology, the project includes fundamental multi-instrumental studies of the global dynamics of the ionosphere under geomagnetically disturbed and quiet conditions. Great attention will be paid on investigation of features of traveling ionospheric disturbances and on the ionosphere behavior during variations of interplanetary parameters such as magnetic field (IMF) and electric field (IEF). The latter is directly connected to the last subject of our proposal - solar- and ionosphere-induced GPS -failures. The main advantages for Europe coming with this project are: 1) a highly interdisciplinary project on a sufficiently new branch of the science and with rare applications; 2) extension of the fundamental ionosphere studies in Europe that will increase the competitiveness of Europe among other world-famous research schools on the Earth s ionosphere; 3) the results of our work on GNSS operation quality will be useful for the future Galileo mission as well, and would help to improve the system.mSeismology in the ionosphere? This is REAL! Ionosphere as a natural indicator of numerous geophysical events?Early Life Traces, Evolution, and Implications for AstrobiologyAlmost half of the human genome is made of Transposable Elements (TEs), whose ongoing activity continually impacts our genome. However, little is known about how the host regulates TEs and their genomic and epigenomic impacts. EpiPluriRetro will advance research in a new groundbreaking concept: that TEs are active in our pluripotent genome, and that epigenetic regulation is employed therein to regulate TE activity. LINE-1 retrotransposons comprise approximately 20% of the mammalian genome,< and L1 retrotransposition events can create genetic diversity by a variety of mechanisms. From acting as simple insertion mutagens to inducing other complex genomic alterations it is becoming increasingly evident that the activity of TEs is a major force driving human genome evolution. It has been demonstrated that the main mutagenic load associated with TE mobilization occurs during early human embryogenesis (i.e., our pluripotent genome). EpiPluriRetro will examine how epigenetic mechanisms influence LINE-1 retrotransposition in pluripotent cells. To do that, we will combine genetic, biochemical and genomics approaches to identify pluripotent host factors that influence the fate of LINE-1 retrotransposition. In addition, EpiPluriRetro will analyze the impact of LINE-1 insertions in our pluripotent genome and the Epimutagenic impact of new LINE-1 mobilization events in pluripotent cells. To do that, we have developed an innovative approach to analyze the effect of LINE-1 insertions within human genes without biases, including epigenetic alterations induced by a new L1 insertion. EpiPluriRetro will help to understand how the activity of TEs is controlled in our heritable genome, which will directly impact our knowledge in how new genetic diseases are generated in humans. In addition, EpiPluriRetro will allow us to describe a new concept in human biology, as we will analyze how new TE insertions can modify the chromatin status of flanking genomic regions where they insert.REpigenetic control and impact of mammalian retrotransposons in pluripotent genomes! This study investigates the mechanistic bases of human freeze-fight-flight reactions. The ability to control our social behavior is essential for almost every social interaction. It frequently fails in challenging situations when people fall back on basic defensive  freeze-fight-flight (FFF) reactions. It chronically fails in social motivational disorders, with social anxiety as one extreme, and aggression as another. Such disorders are notoriously resistant to therapy. Accordingly, it is essential that we obtain mechanistic insight into the psychological and neurobiological control of human FFF behavior. Upon a social challenge, an automatic attentive immobility, the freeze reaction, serves fast risk-assessment, needed to optimize subsequent fight-or-flight responses. Precise temporal tuning of FFF responses is critical to adequate coping with social challenges. It is orchestrated by complex neuroendocrine systems, utilizing the steroid hormone testosterone. Imbalances in the temporal dynamics and associated neuroendocrine control of FFF behaviors are highly predictive of animal fear and aggression. Testing these mechanisms in humans is critical to advance mechanistic insight in human FFF control, but has as of yet been foreclosed in the absence of the requisite tools to objectively measure human FFF. Recent innovations have enabled us to demonstrate that human freeze reactions to social threat mimic animal freeze responses (bodily immobility and fear bradycardia). These findings open up paths toward investigating the role of FFF reactions in social motivational disorders. The major aim of the proposed research program is to reveal the mechanistic basis of human FFF regulation through the use of three cutting-edge methods: First I intend to integrate body-postural and electroencephalographic measures to detect, for the first time, the temporal dynamics and neuroendocrine control of the full FFF sequence in healthy individuals and patients with social anxiety and aggressive disorders. Second, I will apply hormonal and neural interventions to directly manipulate human FFF control using testosterone administration and transcranial magnetic stimulation. Third, and most crucially, I will validate the predictive value of basic FFF tendencies prospectively in a large longitudinal study. I will test adolescents in a critical transition phase (age 14-17) when they are most vulnerable to social and hormonal influences and when most symptoms develop. The projected findings will advance core theoretical knowledge of the mechanistic basis of human emotion regulation. Moreover they are of critical importance for clinical treatment and society, breaking the grounds for early symptom detection and (preventive) intervention into social anxiety and aggressive disorders that form an ever-growing burden for society.+Neural control of human freeze-fight-flight#Diamond Quantum Devices and BiologyWe propose a new paradigm in materials science  heterostructures based on two-dimensional atomic crystals (and their hybrids with metallic and semiconducting quantum dots and nanostructures), and develop several devices which are based on such concept. Two-dimensional (2D) atomic crystals (such as graphene, monolayers of boron nitride, molybdenum disulphide, etc) possess a number of exciting properties, which are often un< ique and very different from those of their tree-dimensional counterparts. However, it is the combinations of such 2D crystals in 3D stacks that offer truly unlimited opportunities in designing the functionalities of such heterostructures. One can combine conductive, insulating, probably superconducting and magnetic 2D materials in one stack with atomic precision, fine-tuning the performance of the resulting material. Furthermore, the functionality of such stacks is  embedded in the design of such heterostructure. We will create several types of devices based on such heterostructures, including tunnelling transistors, charge and spin drag, photodetectors, solarcells, lasers and other optical and electronic components. As the range of available 2D materials broadens, so the possible functionality of the 2D-based heterostructures will cover larger and larger area. We will concentrate on creating and understanding of the prototypes of such hetersotructures and apply efforts in developing methods for their mass-production suitable for various applications. The development of such novel paradigm in material science will only by possible by bringing together a Synergy group of researchers with complementary skills, knowledge and resources.>Novel materials architecture based on atomically thin crystalsQuantum Chromodynamics at WorkjWe propose to develop new chemometric and high-throughput analytical methods to assess the effects of environmental and climate changes on target biological systems which are representative of ecosystems. This project will combine powerful chemometric and analytical high-throughput methodologies with toxicological tests to examine the effects of environmental stressors (like chemical pollution) and of climate change (like temperature, water scarcity or food shortage), on genomic and metabonomic profiles of target biological systems. The complex nature of experimental data produced by high-throughput analytical techniques, such as DNA microarrays, hyphenated chromatography-mass spectrometry or multi-dimensional nuclear magnetic resonance spectroscopy, requires powerful data analysis tools to extract, summarize and interpret the large amount of information that such megavariate data sets may contain. There is a need to improve and automate every step in the analysis of the data generated from genomic and metabonomic studies using new chemometric and multi- and megavariate tools. The main purpose of this project is to develop such tools. As a result of the whole study, a detailed report on the effects of global change and chemical pollution on the genomic and metabonomic profiles of a selected set of representative target biological systems will be delivered and used for global risk assessment. The information acquired, data sets and computer software will be stored in public data bases using modern data compression and data management technologies. And all the methodologies developed in the project will be published.CHEMometric and High-throughput Omics Analytical Methods for Assessment of Global Change Effects on Environmental and Biological SystemsDespite intensive abatement efforts, airborne particulate matter remains a major public health issue with costs across the European Union estimated at 600 billion euros in 2005. Road traffic remains one of the major sources of particulate matter, and diesel emissions are by far the largest source of atmospheric nanoparticles in urban areas. Semi-volatile organic compounds emitted largely in the condensed matter phase are a major component of diesel emissions, and as primary particles are advected from their road traffic source, the semi-volatile compounds vaporise and are oxidised, forming a greater mass of secondary organic aerosol (SOA). However, the semi-volatile compounds are extremely poorly characterised as they are not resolved by traditional gas chromatographic methods, presenting an unresolved complex mixture (UCM). For this reason, despite being a major precursor of SOA, such compounds are often poorly represented or completely omitted from atmospheric chemistry-transport models. This proposal is concerned with applying new two dimensional gas chromatographic methods to characterisation of the UCM at a molecular level which will be followed by studies of the physico-chemical properties of representative components of the semi-volatile emissions. The very abundant nucleation nanoparticle mode of diesel emissions is comprised almost entirely of semi-volatile organic material and hence these particles are progressively lost from the atmosphere by evaporation. Until now, there has been insufficient knowledge of the properties of the semi-volatile components to model this behaviour reliably. Such processes will be quantified through both controlled laboratory studies and carefully designed field measurements. Numerical models on both a street canyon and a neighbourhood (5x5 km) scale will be developed to simulate the key processes, such that spatial patterns and size distributions will be predicted, and compared with independent measurements.wFundamental Studies of the Sources, Properties and Environmental Behaviour of Exhaust Nanoparticles from Road Vehicles_A new window on the Universe: The formation and evolution of galaxy clusters and proto-clusters Vegetation forms a key interface between Earth surface and atmosphere. The important role of vegetation carbon, water and energy exchanges is well established, but the overall impact of plant trace gas (VOC) emission for large-scale Earth processes is poorly understood. Although it is widely accepted that VOCs play major roles in the formation of ozone, secondary organic aerosols (SOA) and cloud condensation nuclei (CNN) with potentially profound impacts on air quality and Earth radiative balance, the research has so far focused only on constitutive emissions from species considered  emitters . However, differently from constitutive VOCs emitted only by certain species, all plant species can be triggered to emit induced VOCs under abiotic and biotic stress. So far, induced high-reactivity VOCs are<  not considered in global VOC budget, and thus, this proposal tests the key assumption that VOC emissions worldwide have been vastly underestimated. As global change is resulting in higher level of stress in Earth ecosystems, the relevance of induced emissions is further expected to gain in importance. The current project has the overall objective to evaluate the effect of plant-generated VOC emissions on air composition and environment under global change, with particular emphasis on the role of VOCs induced in response to environmental stress. The study first quantifies the VOC production vs. stress severity relationships across species with differing stress tolerance and advances and parameterizes the qualitative induced VOC model developed by PI. The novel quantitative model is further verified by flux measurements and scaled up to regional and global scales to assess the contribution of induced emissions to overall VOC budget, and study the feedbacks between stress, ozone, SOA and CNN formation and the Earth climate using an hierarchy of available models. This highly cross-disciplinary project is expected to result in key contributions in two research fields of major significance: plant stress tolerance from molecules to globe and the role of vegetation component in atmospheric reactivity and Earth climate. The first part of the study provides fundamental insight into the stress responsiveness of plants with differing tolerance to environmental limitations, extending  leaf economics spectrum , a hotspot of current plant ecology research. The second part provides quantitative information on large-scale importance of plant VOCs in globally changing climates with major relevance for understanding the role of plants in the Earth s large scale processes.=Stress-Induced Plant Volatiles in Biosphere-Atmosphere SystemCD8+ T cells play a key role in the control of infections by intracellular pathogens. Recently, several top-notch studies provided ample evidence that NK cells are important in the regulation of CD8+ T cell response. NKG2D is an activating NK cell receptor which plays a role in the adaptive immune response by co-stimulating CD8+ T cells. Due to unique pattern of immune response, live attenuated CMVs are attractive candidates as vaccine vectors for a number of clinically relevant infections. The main idea behind this project stems from our preliminary data which suggest that a recombinant CMV vector expressing NKG2D ligand has a tremendous potential for subverting viral immunoevasion and boosting the efficiency of CD8 T cell response. During the project we plan to systematically investigate the impact of all major innate immunity players on the CD8+ T cell response. A special focus will be given in obtaining new knowledge on the maintenance of memory CD8+ T cells during latent infection. This study will also provide novel insights on the role of NKG2D in both NK and T cell immunity. In order to test our hypothesis in vivo, we will employ state-of-the-art technology used in herpesvirus genetics coupled with high-end immune monitoring. Ultimately, we will translate our results to a human CMV vector, in order to gauge the impact of NKG2D signaling on immune response in a humanized mouse model. We believe that the significance of the proposed study is enormous since stimulating CD8+ T cells has been widely recognized as a method of choice for vaccine development. There are relatively large number of pathogens for which the immunity acquired post-infection does not fully shelter against re-infection and disease. Therefore, we are in a desperate need for vaccines which offer superior protection compared to the one following natural infection. This study will provide groundbreaking information which will set the stage for the development of new vaccines and vaccine vectors.Strengthening adaptive immunity via innate immunity: enhancing the CD8 T cell response by using the NKG2D ligand expressed in a herpesvirus vectoruCis-regulatory variation: Using natural genetic variation to dissect cis-regulatory control of embryonic development.In mammals, the liver is the peripheral integrator of nutrient availability and energetic needs of the entire organism. We recently demonstrated that dietary amino acids (AA) activate liver Estrogen Receptors (ER) and that, in case of food scarcity, the lowered circulating AA decrease liver ER activity and reduce IGF-1 synthesis with the consequent blockage of the estrous cycle. Here, we hypothesize that in females liver ERa is also a sensor of the endogenous signalling induced by transitions among reproductive stages and a key organizer for the changes required to adapt energy metabolism to reproductive necessities. Thus, we propose that in mammals liver ERa is regulated by reproductive functions and that, in case of ovary malfunctioning, the altered estrogenic signalling causes metabolic impairment leading to local and perhaps systemic disruption of energy homeostasis. To demonstrate our theory, we will explore: i) the molecular pathways activating liver ERa and the related ERa transcriptome by genome-wide analytical tools; ii) the hepatic metabolism and the systemic consequences of liver ER pharmacological and genetic manipulations by means of metabolomic technologies; iii) the association between altered signalling on liver ER and the onset of metabolic disorders; iv) the molecular interactions between ER and PPAR activity and the effect of estrogens on liver autophagy. WAYS research is facilitated by a series of tools such as ER conditional KO, reporter mice, arrays of genes known as target of liver ERa, and others generated by our laboratory in collaboration with EU groups in previous EU programs. The vision of the liver as a functional unit with reproductive organs constitutes a paradigm shift in our understanding of woman physiology; thus, the full comprehension of liver ERa activity and regulation will be a critical step for the conception of new therapies for several diseases affecting women including the metabolic syndrome or the non-alcoholic steatosis.|Role of Liver Estrogen Receptor in female Energy Metabolism, Reproduction and Aging: What About Your Liver Sexual Functions?Humans are equipped with a variety of intrinsic immunity or host restriction factors. These evolved under positive selection pressure for diversification and represent a first line of def< ence against invading viruses. Unfortunately, however, many pathogens have evolved effective antagonists against our defences. For example, the capability of HIV-1 to counteract human restriction factors that interfere with reverse transcription, uncoating and virion release has been a prerequisite for the global spread of AIDS. We are just beginning to understand the diversity and induction of antiretroviral factors and how pandemic HIV-1 group M (major) strains evolved to counteract all of them. Here, I propose to use a genetics, proteomics and evolutionary approach to discover and define as-yet-unknown antiviral effectors and their inducers. To identify novel antiviral factors, we will examine the capability of all primate genes that are under strong positive selection pressure to inhibit HIV and its simian (SIV) precursors. This examination from the evolutionary perspective of the invading pathogen will also reveal which adaptations allowed HIV-1 to cause the AIDS pandemic. Furthermore, complex peptide-protein libraries representing essentially the entire human peptidome, will be utilized to identify novel specific inducers of antiviral restriction factors. My ultimate aim is to unravel the network of inducers and effectors of antiviral immunity - the "Anti-Virome" - and to use this knowledge to develop novel effective preventive and therapeutic approaches based on the induction of combinations of antiviral factors targeting different steps of the viral life cycle. The results of this innovative and interdisciplinary program will provide fundamental new insights into intrinsic immunity and may offer alternatives to conventional vaccine and therapeutic approaches because most restriction factors have broad antiviral activity and are thus effective against various pathogens.yA combined evolutionary and proteomics approach to the discovery, induction and application of antiviral immunity factorsThe expectation of a reward is known to be the driving force behind adaptive behaviour and learning. The effects of reward arise in dopaminergic reward circuitry at the centre of our primitive brain, which guides our goal-directed behaviour and fosters motivational control. A lot is known about the motivational effect of reward, but its effect on attention and perception has only marginally been explored. Recent studies from my lab suggest that such an effect of reward on perception is substantial and, crucially, arises instantly and is not related to a person s motivation or strategy. Rewarding experiences change our brain: objects associated with reward appear to be more strongly represented in the visual cortex. This makes these objects to stand out from the environment. It makes that we perceive them, and focus on them, even when we try to ignore these objects. The research plan presented here will examine the neural response in early visual brain areas to objects associated with high versus low reward. We will measure the response of the brain, specifically the dopaminergic reward circuitry, when a reward is delivered. To investigate how these effects depend on dopamine, we plan to conduct studies involving Parkinson s patients which allow us to directly manipulate the amount of dopamine in the brain. By means of deep brain stimulation, we link the effect even more tightly to the reward circuitry, by replacing reward by stimulation of this circuitry. As a final frontier we will relate individual reward sensitivity (a personality trait related to the mesolimbic dopamine system) to the development of addiction and risk seeking behaviour. The proposed research will have tremendous impact on the study of cognition, education, and (risky) decision making, as well as on a variety of clinical syndromes in which both attention and reward have been critically implicated, such as (drug) addiction and obesity.>What you get is what you see: How Reward Determines PerceptionmWe will use univariate and multivariate functional Magnetic Resonance Imaging (fMRI) techniques, surface and stereo EEG, and in depth single cell recording to investigate the role of human parietal lobe in the monocular or stereoscopic observation of actions performed by conspecifics either using their biological effectors or artificial implements (tools, spears, bicycle, microphone, etc). The fMRI techniques will provide evidence for segregated processing of different types of observed actions within the parietal cortex. The EEG techniques will provide the time course of the electric activity in the parietal regions in comparison to the events and dynamic changes in the video and the time course in other parts of the action observation network. The stereo EEG also provides a more precise localization than fMRI, serving as an important confirmation of the fMRI results. The single cell recordings are crucial to demonstrate the selectivity of the neuronal processes for actions observed, their postural or kinematic parameters or localization in the visual field. This selectivity is crucial to show the presence of mirror neurons for the different types of actions and the use of tools, to document the contribution of the parietal neurons to discrimination between actions, and to assess the benefits of stereoscopic viewing. This project should yield a comprehensive view of the role of parietal lobe in action planning and understanding, including using artificial implements, and pave the way for understanding how higher-order parietal cognitive processes are rooted in the simpler action planning and understanding capacities.The human Parietal Lobe>Against the backdrop of an ever-expanding world population and increasingly limited resources, progress in chemistry, and organic chemistry in particular, is essential for the future of humanity. In the last century, transition metal chemistry has completely changed the field of synthesis. Nevertheless, it is often based on rare and toxic metals. Traditional organic chemistry, on the other hand, makes use of cheap and innocuous organic molecules but at the cost of more limited reactivity. Herein, we propose to design new hypervalent iodine reagents, which will combine the high reactivity of metals with the lower toxicity and cost of main group elements while openin< g new horizons for the synthesis of organic molecules. The most important impact of the project will be to accelerate the innovative circle of progress, especially for research in medicinal chemistry. An extremely useful toolbox, an "iKit", will become available for medicinal chemists. The optimal outcome would be a "magic iodine bullet", which the chemist can use to install a chemical functional group on an organic molecule of his or her choice. An added impact of the project will be greater understanding of the reactivity of hypervalent iodine reagents and their interplay with metal catalysts, leading to unforeseen applications. This understanding can lead to the development of reactions catalytic in iodine, which can be useful not only for research, but also for the larger scale production of chemicals. Based on the successful outcome of this project, an unlimited number of organic transformations will be possible in the future. Applications will not be solely limited to synthetic chemistry, as there exists the possibility for emergent development of other well-defined reagents tailored to meet the needs of scientists in chemical biology and materials science.JHypervalent Iodine Reagents: A Tool Kit for Accessing Molecular ComplexityA renewed interest in Ge has been sparked by the prospects of exploiting its lower effective mass and higher hole mobility to improve the performance of transistors. Ge emerges also as a promising material in the field of spin qubits, as its coherence times are expected to be very long. Finally, it has been proposed that strained Ge nanowires show an unusually large spin orbit interaction, making them thus suitable for the realization of Majorana fermions. In view of these facts, one is able to envision a new era of Ge in information technology. The growth of Ge nanocrystals on Si was reported for the first time in 1990. This created great expectations that such structures could provide a valid route towards innovative, scalable and CMOS-compatible nanodevices. Two decades later the PI was able to realize the first devices based on such structures. His results show that Ge self-assembled quantum dots display a unique combination of electronic properties, i.e. low hyperfine interaction, strong and tunable spin-orbit coupling and spin selective tunneling. In 2012, the PI s group went a step further and realized for the first time Ge nanowires monolithically integrated on Si substrates, which will allow the PI to move towards double quantum dots and Majorana fermions. In view of their exceptionally small cross section, these Ge wires hold promise for the realization of hole systems with exotic properties. Within this project, these new wires will be investigated, both as spin as well as topological qubits. The objective of the present proposal is mainly to: a) study spin-injection by means of normal and superconducting contacts, b) study the characteristic time scales for spin dynamics and move towards electrical spin manipulation of holes, c) observe Majorana fermions in a p-type system. The PI s vision is to couple spin and topological qubits in one  technological platform enabling thus the coherent transfer of quantum information between them.OTowards spin qubits and Majorana fermions in Germanium self-assembled hut-wires!Function of Chemosensory CircuitsNeurons and blood vessels rely on common guidance signals to wire into elaborate neural and vascular networks that are closely juxtaposed and interdependent: vascular supply of oxygen and nutrients is essential to sustain the high metabolic rate of the nervous system, and conversely neural control of vascular tone is crucial for circulatory homeostasis. However, it remains unclear how the nervous and vascular systems establish an intimate physical and functional relationship. This proposal seeks to reveal the developmental mechanisms that link neuronal connectivity and vascularization of the nervous system, focusing on the interactions between vascular endothelial cells and spinal motor neurons that control locomotion, respiration and autonomic responses. Motor neuron diseases and a variety of other neurodegenerative conditions are precipitated by vascular abnormalities. Thus, understanding the molecular basis of neurovascular crosstalk may offer novel therapeutic opportunities. My group will use mutagenesis-based forward genetics in reporter mice combined with gene profiling of motor neurons and endothelial cells to screen for novel regulators of neurovascular interactions and pathfinding. Candidate genes will be further characterized using in vivo mouse and chick models, in addition to in vitro studies to uncover the mechanisms of action. Through this multi-disciplinary approach, the proposal will address these fundamental questions: (i) Do neurovascular interactions instruct the assembly of neural and vascular networks? (ii) What signaling pathways connect region-specific vascularization of the CNS to the local metabolic and functional demand of neuronal tissues? (iii) What mechanisms account for specificity, spatiotemporal control and integration of guidance signaling? In addition, this research plan will generate comprehensive transcriptional/proteomic datasets and novel mouse mutants for future studies of neurovascular communication and patterning.ENeurovascular Interactions and Pathfinding in the Spinal Motor System/The Higgs: A colored View from the Top at ATLAS:Interplay between influenza viruses and host SUMO pathwaysqMany picornaviruses are human pathogens that cause diseases varying in symptoms from common cold to life-threatening encephalitis. Currently there are no anti-picornavirus drugs approved for human use. We propose to study molecular structures of picornaviruses and their life cycle intermediates in order to identify new targets for anti-viral inhibitors and to lay the foundations for structure-based development of drugs against previously structurally uncharacterized picornaviruses. We will use X-ray crystallography to determine virion structures of representative viruses from Parechovirus, Kobuvirus, Cardiovirus, and Cosavirus genera and Human Rhinovirus-C species. We will use cryo-electron microscopy < to study picornavirus replication complexes in order to explain the mechanism of copy-choice recombination of picornavirus RNA genomes that leads to creation of new picornavirus species. We will determine whether picornavirus virions assemble from capsid protein protomers around the condensed genome or if the genome is packaged into a pre-formed empty capsid. Furthermore, we will investigate how picornaviruses initiate infection by analyzing genome release from virions and its translocation across lipid membrane. A major innovation in our approach will be the use of focused ion beam micromachining for sample preparation that will allow us to study macromolecular complexes within infected mammalian cells by cryo-electron tomography. Our analysis of virion structure, cell entry, genome replication, and particle assembly will identify molecular details and mechanism of function of critical picornavirus life-cycle intermediates.*Structural studies of human picornavirusesEarthquakes represent one of the deadliest and costliest natural disasters affecting our planet  and one of the hardest to predict. To improve seismic hazard evaluation in earthquake-prone regions, an understanding of earthquake nucleation and of the underlying microphysical and chemical processes is crucial. A better understanding of the processes that control earthquake nucleation is also of rapidly growing importance for mitigation of induced seismicity, caused by activities such as gas and oil production, and geological storage of CO2 or gas. The SEISMIC project is a multi-scale study aimed at understanding the parameters that control slip (in)stability in experiments and models addressing earthquake nucleation. A central question to be tackled is what controls the velocity-dependence of fault friction and hence the potential for accelerating, seismogenic slip, and on what length scales the processes operate. A novel acoustic imaging technique will be developed and applied in experiments to obtain direct information on the internal microstructural evolution of fault slip zones during deformation, and on how this evolution leads to unstable slip. The SEISMIC project will link experiments with sophisticated numerical models of grain-scale frictional processes. Using both experiments and grain scale modelling, the SEISMIC project will in turn directly test boundary element models for large scale fault slip. The coupling of experiments with grain-scale numerical models, based on in-situ imaging, will provide the first, integrated, multiscale physical basis for extrapolation and upscaling of lab friction parameters to natural conditions. Ultimately, the SEISMIC project will test and validate the resulting models for fault slip by simulating and comparing patterns of seismicity for two natural-laboratory cases: a) for the l Aquila region of Central Italy, and b) for a reservoir-scale case study involving induced seismicity in the Netherlands.xSlip and Earthquake Nucleation in Experimental and Numerical Simulations: a Multi-scale, Integrated and Coupled ApproachePlasma-assisted development and functionalization of electrospun mats for tissue engineering purposesFrom the twelfth to the seventeenth century, Aristotle s writings lay at the foundation of Western culture, providing a body of knowledge and a set of analytical tools applicable to all areas of human investigation. Scholars of the Renaissance have emphasized the remarkable longevity and versatility of Aristotelianism, but their attention has remained firmly, and almost exclusively, fixed on the transmission of Aristotle s works in Latin. Scarce attention has gone to works in the vernacular. Nonetheless, several important Renaissance figures wished to make Aristotle s works accessible and available outside the narrow circle of professional philosophers and university professors. They believed that his works could provide essential knowledge to a broad set of readers, and embarked on an intense programme of translation and commentary to see this happen. It is the argument of this project that vernacular Aristotelianism made fundamental contributions to the thought of the period, anticipating many of the features of early modern philosophy and contributing to a new encyclopaedia of knowledge. Our project aims to offer the first detailed and comprehensive study of the vernacular diffusion of Aristotle through a series of analyses of its main texts. We will thus study works that fall within the two main Renaissance divisions of speculative philosophy (metaphysics, natural philosophy, mathematics, and logic) and civil philosophy (ethics, politics, rhetoric, and poetics). We will give strong attention to the < contextualization of the texts they examine, as is standard practice in the best kind of intellectual history, focusing on institutional contexts, reading publics, the value of the vernacular, new visions of knowledge and eclecticism. With the work of the PI, two professors, 5 post-docs and two PhD students we aim to make considerable advances in the understanding of both speculative and civil philosophy within vernacular Aristotelianism.sAristotle in the Italian Vernacular: Rethinking Renaissance and Early-Modern Intellectual History (c. 1400 c. 1650)The ubiquity of arsenic resistant genes across all of life s variety suggests a close intimacy between arsenic biogeochemistry and evolution, over geological time scales. However, the behaviour of arsenic in past environments where life originated and its impact on our evolution is essentially unknown. Arsenic is of particular importance because of its toxic properties, prevalence in tight association with ubiquitous iron and sulfide minerals and as a major component of sulfide-rich waters, all common features of Precambrian oceans. Arsenic obstructs the synthesis of the building blocks of life, exhibiting both chronic and acute toxicity at very low concentrations. These properties make arsenic an agent capable of exerting strong selective pressure on the distribution, success and diversity of life. This is exemplified by when the release of arsenic into groundwater following rock-weathering processes results in widespread poisoning. Using the state of the art stable isotopes tools, coupled to biomass production, bacterial iron, arsenic and sulfur cycling under ancient oceanic conditions, this project will open a new discussion on the much debated relationship between ocean chemistry and evolution, by introducing a new arsenic framework. This will be achieved under three majors themes: 1) Does there exist a biogeochemical connection between arsenic and the timing and transition from the iron-rich to the hypothesized sulfide-rich oceans that are linked to the rise of atmospheric oxygen? 2) Does arsenic and sulfide show concomitant cyclicity during the Precambrian? 3) Could arsenic thus serve as a proxy for the calibration of key transitional steps in the timing of biological innovation?9The Coevolution of Life and Arsenic in Precambrian OceansThe objective of this project is to quantify the role of consumers behaviour on the design and assessment of policies aimed at enhancing energy efficiency and conservation and at promoting climate change mitigation. The project brings together different disciplines  namely energy policy, environmental and ecological economics, behavioral public finance, experimental economics, and technology policy- in an integrated fashion. COBHAM is designed to go beyond the standard analysis of energy and climate policies in the presence of environmental externalities, by accounting for the heterogeneity in consumers preferences, the role of social interactions, and the presence of behavioral tendencies and biases. The project seeks to: i) carry out innovative research in the theoretical understanding of the interplay between behavioral tendencies and environmental externalities; ii) generate new empirical data and research on individual preferences by means of original surveys and controlled experiments; iii) enhance integrated assessment models (IAMs) of economy, energy and climate with an advanced representation of consumers behavior. In doing so, the project will be able to provide a richer characterization of energy demand and of greenhouse gas emission scenarios, to better estimate consumers responsiveness to energy and climate policies, and to provide input to the design of new policy instruments aimed at influencing energy and environmental sustainable behavior. COBHAM is of high public policy relevance given Europe s legislation on energy efficiency and CO2 emissions, and can provide important insights also outside the sphere of energy and climate policymaking.kThe role of consumer behavior and heterogeneity in the integrated assessment of energy and climate policiescBeyond structure: integrated computational and experimental approach to Ensemble-Based Drug Design.Alterations of the intracellular space, including intracellular protein accumulation, organelle and cytoskeleton dislocation, and modifications in cell shape, are an early hallmark of many neurodegenerative processes. The ability to assess and quantify these alterations non-invasively would be of tremendous interest, not only in a clinical context, but also for preclinical research. However, no tool currently exists allowing such measurements. Diffusion-weigh< ted magnetic resonance spectroscopy (DW-MRS) gives access to the apparent diffusion coefficient (ADC) of brain metabolites in vivo, which is related to their average quadratic displacement. Since metabolites are purely intracellular, their ADC is solely governed by the properties of the intracellular space. The dependency of the ADC on the delay during which displacement is measured (the  diffusion time Td) tells how metabolite motion deviates from free diffusion, which can in theory help untangle and quantify the different factors governing motion. So far, DW-MRS has only been performed in a limited number of studies, for Td ranging from ~10 to ~100 milliseconds, and has not yet demonstrated its ability to quantitatively assess the intracellular space. In the present work, we will develop cutting-edge DW-MRS methods to probe brain metabolite motion for Td varying over several orders of magnitude (from ~0.1 milliseconds to ~10 seconds). The dependency of the ADC over Td will provide unique insights about the mechanisms governing metabolite motion at very different scales. Data will be modeled to quantitatively extract parameters such as the intracellular viscosity, the size of intracellular structures, and cell shape and size. Estimated parameter values will be compared to values derived from other techniques, such as microscopy. Finally, developed methods will be used to investigate early alterations of the intracellular space in animal models of neurodegeneration.UExploring brain intracellular space using diffusion-weighted NMR spectroscopy in vivooClinical ultrasound platform for the quantitative and longitudinal imaging of theranostics and cellular therapyDLate diagnosis and difficult treatment represent major obstacles in the fight against cancer. I propose here the development of self-regulated theranostic nanodevices supporting both early cancer diagnosis and targeted, tumor-cell-specific drug-release. Specifically, I will exploit the  designability of nucleic acids to design and optimize molecular nanodevices that undergo binding-induced conformational changes upon target binding and, in doing so, signal the presence of a specific tumor marker or release a toxic therapeutic cargo. The inspiration behind my approach is derived from nature, which employs similar nanometer-scale protein and nucleic-acid-based  switches as devices to detect  and respond to- specific molecules even against the complex background  noise of the physiological environment. Furthering on this  nature-inspired synthetic biology view I will also exploit naturally occurring regulatory mechanisms (e.g., allostery, cooperativity, etc.) to tune and edit the dose-response curve of these nanodevices, improve their analytical sensitivity, and optimize drug-release efficiency. In summary, I will use biomimetic  tricks taken directly from nature to move beyond the state-of-the-art of sensor design, with the goal being improved diagnostics and  smarter, more effective drug delivery. Achieving these goals will require multidisciplinary expertise in the field of analytical chemistry, biophysics, electrochemistry, bioengineering, computational chemistry and synthetic biology. In my career I have demonstrated skills and expertise in similarly complex projects and in each of these challenging fields. Finally, the development of the proposed nanodevices will significantly impact the safety, compliance and efficacy of therapies and medical procedures bringing to scientific, technological and socio-economic benefits.dNature-inspired theranostic nanodevices for tumor imaging, early diagnosis and targeted drug-releaseAn inescapable consequence of sex in eukaryotes is the evolution of a biphasic life cycle with alternating diploid and haploid phases. The occurrence of selection during both phases has far reaching consequences for fundamental evolutionary processes including the rate of adaptation, the extent of inbreeding depression and the load of deleterious mutations, as well as for applied research into assisted fertilization. It has been a long-standing dogma that, unlike in plants, selection at the haploid gametic level in animals is of no great importance. However, empirical evidence for postmeiotic haploid gene expression is increasing and with the recent recognition of the importance of epigenetic effects for evolutionary mechanisms it is paramount to revisit haploid selection in animals. The aim of the proposed project is to reconsider haploid selection in animals and to investigate the relative importance of genetic and epigenetic effects in sperm for the subsequent generation. The project consists of three logically connected parts, which tackle the question from different angles using the zebrafish Danio rerio as the main model system. In Part I, I will disentangle genetic from epigenetic eff< ects and identify epigenetic effects that affect sperm and offspring performance by combining experimental evolution with next-generation sequencing data. In Part II, I will pinpoint genes that are expressed at the postmeiotic haploid stage of spermatogenesis and determine which of these genes may be under haploid selection. In Part III, I will get to the core of the question and perform single-cell genotyping to explore possible links between sperm phenotype and the underlying sperm genotype. By combining aspects from evolutionary biology, mathematical modeling, genomics and developmental biology this project will advance our understanding of how epigenetic and genetic differences among gametes shape phenotypes and mediate evolutionary change in animals.eHaploid selection in animals: investigating the importance of genetic and epigenetic effects in spermIn spite of their small areal extent, inland waters play a vital role in the carbon cycle of the continents, as they emit significant amounts of the greenhouse gases (GHG) carbon dioxide (CO2) and methane (CH4) to the atmosphere, and simultaneously bury more organic carbon (OC) in their sediments than the entire ocean. Particularly in tropical hydropower reservoirs, GHG emissions can be large, mainly owing to high CH4 emission. Moreover, the number of tropical hydropower reservoirs will continue to increase dramatically, due to an urgent need for economic growth and a vast unused hydropower potential in many tropical countries. However, the current understanding of the magnitude of GHG emission, and of the processes regulating it, is insufficient. Here I propose a research program on tropical reservoirs in Brazil that takes advantage of recent developments in both concepts and methodologies to provide unique evaluations of GHG emission and OC burial in tropical reservoirs. In particular, I will test the following hypotheses: 1) Current estimates of reservoir CH4 emission are at least one order of magnitude too low, since they have completely missed the recently discovered existence of gas bubble emission hot spots; 2) The burial of land-derived OC in reservoir sediments offsets a significant share of the GHG emissions; and 3) The sustained, long-term CH4 emission from reservoirs is to a large degree fuelled by primary production of new OC within the reservoir, and may therefore be reduced by management of nutrient supply. The new understanding and the cross-disciplinary methodological approach will constitute a major advance to aquatic science in general, and have strong impacts on the understanding of other aquatic systems at other latitudes as well. In addition, the results will be merged into an existing reservoir GHG risk assessment tool to improve planning, design, management and judgment of hydropower reservoirs.mTowards a new understanding of carbon processing in freshwaters: methane emission hot spots and carbon burialResponding to climate change has profound implications for behaviour; yet policies to achieve this change have met with limited success. A key challenge for environmental social scientists is the need to move forward in understanding how to bring about change in consumption, community and political behaviours, which is commensurate to the scale of the climate change challenge. One promising area is  behavioural spillover , the notion that taking up a new behaviour (e.g., recycling) may lead to adoption of other, more environmentally beneficial, behaviours. Such a notion appears to hold the promise of changing a suite of behaviours in a cost-effective way. Yet despite robust theoretical principles (e.g., self-perception theory) underpinning behavioural spillover, there is little empirical research. The proposed research intends to produce a step-change in behavioural and sustainability science by undertaking a mixed-method, cross-cultural study of pro-environmental behavioural spillover in order to open up new ways of promoting sustainable lifestyle change and significantly broadening our understanding of behaviour within individuals and cultures. There are three objectives for the research: 1. To examine ways in which pro-environmental behaviour, lifestyles and spillover are understood and develop within different cultures; 2. To understand drivers of behavioural consistency and spillover effects across contexts, including home and work, and cultures; and 3. To develop a theoretical framework for behavioural spillover and test interventions to promote spillover across different contexts and cultures. Three Work Packages will address these objectives: 1. Defining and understanding spillover: Focus groups with biographical questions and card sorts [Years 1-2] 2. Examining drivers of spillover: Cross-national survey with factor, correlation and regression analyses [Years 2-3] 3. Developing theory and testing interventions: Laboratory and field experiments [Years 3-5]/Low-carbon Lifestyles and Behavioural SpilloverUncertainty is pervasive in all aspects of climate change. Although this is beyond dispute, the vast majority of research assessing climate ignores uncertainty, in large part because of the technical complexities involved. The present project aims at advancing substantially the way we conceptualize, model and frame the climate change policy making process, focusing on the central role of uncertainty. The first step is that of applying state of the art techniques from operation research (stochastic dynamic and approximate dynamic programming) to the realm of integrated assessment models (the conventional tool used to perform climate change analysis). These techniques enable us to capture a wide range of stochastic phenomena in the decision process. However, to really move forward the research edge one needs to shift the focus on to the way we, as individuals, perceive these uncertain phenomena. Indeed, the literature on decision making under uncertainty spans way beyond economics, statistics and operations research: Notably psychology and philosophy. These disciplines have had a major role in extending what we know about the process of decision making under uncertainty, and this project aims at reconciling this stran< d of literature with that on climate change policy design and assessment. The three main research questions are: 1) What are key risk and uncertainty perception issues and  biases when we face climate change and under what instances should they be included in normative analyses of climate change? 2) How can we map these  alternative representations of uncertainty and risk perception into integrated assessment models and how will these affect the normative predicaments of these models ? 3) How can we communicate and frame uncertainty itself, as well as results of stochastic analyses, in a way that help us reducing those biases that have no normative role, but arise from our limited attentional and information processing capacity?KRISk and uncertainty in developing and Implementing Climate change pOliciesOptical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in present nanoscopy. In this project, I propose a paradigm-shift in the field of advanced microscopy by developing optical nanoscopy based on a photonic integrated circuit. The project will take advantage of nanotechnology to fabricate an advance waveguide-chip, while fast telecom optical devices will provide switching of light to the chip, enhancing the speed of imaging. This unconventional route will change the field of optical microscopy, as a simple chip-based system can be added to a normal microscope. In this project, I will build a waveguide-based structured-illumination microscope (W-SIM) to acquire fast images (25 Hz or better) from a living cell with an optical resolution of 50-100 nm. I will use W-SIM to discover the dynamics (opening and closing) of fenestrations (100 nm) present in the membrane of a living liver sinusoidal scavenger endothelial cell. It is believed among the Hepatology community that these fenestrations open and close dynamically, however there is no scientific evidence to support this hypothesis because of the lack of suitable tools. The successful imaging of fenestration kinetics in a live cell during this project will provide new fundamental knowledge and benefit human health with improved diagnoses and drug discovery for liver. Chip-based nanoscopy is a new research field, inherently making this a high-risk project, but the possible gains are also high. The W-SIM will be the first of its kind, which may open a new era of simple, integrated nanoscopy. The proposed multiple-disciplinary project requires a near-unique expertise in the field of laser physics, integrated optics, advanced microscopy and cell-biology that I have acquired at leading research centers on three continents.KHigh-speed chip-based nanoscopy to discover real-time sub-cellular dynamics5Interfacing quantum states in carbon nanotube devicesBetterSense aims to solve the two main problems in current gas sensor technologies: the high power consumption and the poor selectivity. For the former, we propose a radically new approach: to integrate the sensing components and the energy sources intimately, at the nanoscale, in order to achieve a new kind of sensor concept featuring zero power consumption. For the latter, we will mimic the biological receptors designing a kit of gas-specific molecular organic functionalizations to reach ultra-high gas selectivity figures, comparable to those of biological processes. Both cutting-edge concepts will be developed in parallel an integrated together to render a totally new gas sensing technology that surpasses the state-of-the-art. As a matter of fact, the project will enable, for the first time, the integration of gas detectors in energetically autonomous sensors networks. Additionally, BetterSense will provide an integral solution to the gas sensing challenge by producing a full set of gas-specific sensors over the same platform to ease their integration in multi-analyte systems. Moreover, the project approach will certainly open opportunities in adjacent fields in which power consumption, specificity and nano/micro integration are a concern, such as liquid chemical and biological sensing. In spite of the promising evidences that demonstrate the feasibility of this proposal, there are still many scientific and technological issues to solve, most of them in the edge of what is known and what is possible today in nano-fabrication and nano/micro integration. For this reason, BetterSense also aims to contribute to the global challenge of making nanodevices compatible with scalable, cost-effective, microelectronic technologies. For all this, addressing this challenging proposal in full requires a funding scheme compatible with a high-risk/high-gain vision to finance the full dedication of a highly motivated research team with multidisciplinary skillCNanodevice Engineering for a Better Chemical Gas Sensing TechnologyThis proposal aims to advance a new general theory that links plasticity in prey responses to predation and biogeochemical processes to explain context-dependent variations in ecosystem functioning. The physiological reaction of prey to predation involves allocating resources from production to support emergency functions. An example of such a reaction is an increase in maintenance respiration concomitant with higher carbohydrate and lower N demand. Such changes in prey energy and elemental budget should alter the role prey play in regulating the quality of detrital inputs to soils. Nutrient content of detritus is an important determinant of the way soil communities regulate ecosystem processes. Thus, the physiological reaction of prey to predation can potentially explicate changes in ecosystem functioning. My first empirical examination of a few selected mechanisms of this theory has yielded very promising insights. The main objectives of this proposal are: (1) To systematically test whether prey reactions to predation are consistent with the proposed theory s predictions across species and ecosystems; (2) to examine the interface between stress physiology and anti-predatory behaviors in explaining predator induced die< t shift, and (3) to evaluate how predator induced responses at the individual level regulate ecosystem processes. To address these objectives, I propose combining manipulative field experiments, highly controlled laboratory and garden experiments, and stable-isotopes pulse chase approaches. I will examine individual prey responses and the emerging patterns across five food-chains that represent phylogenetically distant taxa and disparate ecosystems. The proposed study is expected to revolutionize our understanding of the mechanisms by which aboveground predators regulate ecosystem processes. Promoting such a mechanistic understanding is crucial to predict how human-induced changes in biodiversity will affect life-supporting ecosystem services.UPhysiological Reaction to Predation- A General Way to Link Individuals to Ecosystems%Wall-crossing and Birational GeometryHigh-throughput (HT) screening of live cells is crucial to accelerate both fundamental biological research and discovery of new drugs. Current methods for HT cell screenings, however, either require a large number of microplates, are prone to cross-contaminations and are limited to adherent cells (cell microarrays), or are not compatible with adherent cells as well as with spatial indexing (droplet microfluidics). We recently demonstrated the use of superhydrophobic-superhydrophilic microarrays to create high-density arrays of microdroplets or hydrogel micropads. We propose here to develop a new platform for HT cell screening experiments using the unique properties of the superhydrophilic microarrays separated by superhydrophobic thin barriers. The new technology will allow us to perform up to 300K cell experiments in parallel using a single chip. Individual cell experiments will be performed in thousands of completely isolated microdroplet at defined locations on the chip. This will enable spatial indexing, time-lapse measurements and screening of either adherent or non-adherent cells. Parallel manipulations within individual microreservoirs, such as washing, addition of chemical libraries, or staining will be developed to open new possibilities in the field of live cell studies. Superhydrophobic barriers will allow complete isolation of the microreservoirs, thus preventing cross-contamination and cell migration. We will also develop a technology for the HT screening of cells in 3D hydrogel micropads. We will use these methods to gain better understanding of how different parameters of the 3D cell microenvironment influence various aspects of cell behavior. The project will require the development of new technological tools which can later be applied to a wide range of cell screening experiments and biological problems. Our long term aim is to replace the outdated microplate technology with a more powerful and convenient method for cell screening experiments.TDropletMicroarrays: Ultra High-Throughput Screening of Cells in 3D MicroenvironmentsdBiological Membranes in Action: A Unified Approach to Complexation, Scaffolding and Active Transport3DAtacommunications based on NanophotoniC Resonators!Hierarchical Carbon NanomaterialsfTransforming Citizenship through Hybrid Governance: The Impacts of Public-Private Security AssemblagessThe hippocampus is an important structure for spatial memory in rodents and episodic memory in humans. The hippocampus uses a sparse coding scheme where a given environment is represented by the place selective firing of a small group of cells, (called place cells) among a larger population of silent neurons. Thus a given environment is not only coded by the firing rate and timing of active cells but also by the very identity of these cells that fire or stay silent in that environment. Similarly, in humans, specific items or episodes are coded by the selective firing of particular cells in the temporal lobe among a larger population of silent neurons. Thus understanding the mechanisms involved in the selection of which cells will be active in a particular environment is one of the most important to understand the formation of spatial memories in rodents and episodic memories in humans. This question is at the core of our research project. Place cells have been extensively studied at the system level using extracellular recording which can only record the spiking output of neurons but not the intracellular mechanisms leading to that spiking. This is why I recently contributed to the development of a new technique allowing intracellular recordings in freely behaving animals. Using this technique we found an important role for intrinsic neuronal properties in the distinction between place and silent cells. Intriguingly, these differences were observed even before the new exploration began. Based on these findings we will address three objectives: 1) determine the role of intrinsic excitability in the initial selection of place cells, 2) test whether a similar coding scheme are valid for the other major hippocampal area for spatial coding: the CA3 area and last 3) determine whether these intrinsic mechanisms play a role in another major function of the hippocampus the remapping.>An intracellular approach to spatial coding in the hippocampus-Optical Quantum Control of Magnetic MoleculesThe creation of new molecular entities and subsequent exploitation of their properties is central to a broad spectrum of research disciplines from medicine to materials. Most  if not all- of the efforts of organic chemists were directed to the development of creative strategies to built carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. But is the creation of new bonds the only approach that organic chemistry should follow? Could we design the synthesis of challenging molecular skeleton no more through the construction of carbon-carbon bonds but rather through selective cleavage of carbon-carbon bonds (C-C bond activation)? The goal of this work is to develop powerful synthetic approaches for the selective C-C bond activation and demonstrate that it has the potential to be a general principle in organic synthesis for the regio-, diastereo- and even enantiomerically enriched preparation of adducts despite that C-C single bonds belong among the least reactive functional groups in chemistry. The realization of this synthetic potential requires the ability to functionalize selectively one C-C bond in compounds containing many such bonds and an array of functional groups. This site selective C-C bond activation is one of the greatest challenges that must be met to be used widely in complex-molecular synthesis. To emphasize the practicality of C-C bond activation, we will prepare in a single-pot operation challenging mo< lecular framework possessing various stereogenic centers from very simple starting materials through selective C-C bond activation. Ideally, alkenes will be in-situ transformed into alkanes that will subsequently undergo the C-C activatio     !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghiklmnopqrstuvwxyz{|}~n even in the presence of functional group. This work will lead to ground-breaking advances when non-strained cycloalkanes (cyclopentane, cyclohexane) will undergo this smooth C-C bond activation with friendly and non toxic organometallic species.LSelective Carbon-Carbon Bond Activation: A Wellspring of Untapped ReactivityAdvances in transportation, energy harvesting, chemical processing, climatology, atmospheric and marine pollution are obstructed by the lack of understanding of turbulence. The turbulent energy transfer toward small-scales is characterized by highly non-Gaussian and out-of-equilibrium fluctuations that cannot be described by mean-field theories or traditional closure approximations. State-of-the-art computers and algorithms do not allow to perform brute-force direct numerical simulations of any realistic turbulent configuration: modelling is mandatory. On the other hand, turbulence models are often strongly limited by our lack of understanding of fundamental mechanisms. As a result, we have a deadlock: turbulence is thought of as  unsolvable theoretically and computationally  intensive . Indeed, progress by using conventional methods has been slow. Last year, however, something new happened. Two unconventional conceptual and numerical methodologies to study Navier-Stokes equations appeared based on: (i) a surgery of nonlinear interactions with different Energy and Helicity contents, (ii) a fractal-Fourier decimation. These unexplored tools are potential breakthroughs to unravel the basic mechanisms governing the turbulent transfer in isotropic, anisotropic and bounded flows, e.g. the mechanism behind the growth of small-scales vorticity and formation/stability of coherent structures, a challenge that has defeated all numerical and theoretical attempts, up to now. The ultimate goal of NewTURB is to integrate the fresh knowledge achieved by using these novel numerical instruments to push forward the frontiers of turbulence modelling, exploiting the possibility to reduce the number-of-degrees-of-freedom in an innovative way to deliver alternative frontier  multiscale eddy-simulations methodologies for both unbounded and bounded flows with smooth walls or with heterogeneous landscapes, e.g. flows over a rough surface.SNew eddy-simulation concepts and methodologies for frontier problems in TurbulenceThis proposal concerns open systems, i.e. systems interacting with the environment, and their fundamental role in natural sciences. The main objectives are: i) to develop theory of Brownian motion for molecules in biological environments; ii) to adapt classical many-body open systems such as kinetic or/and diffusion-aggregation models to the quantum domain; iii) to develop theory of open systems as quantum simulators; finally iv) to develop theory of quantum Brownian motion in inhomogeneous media. Although all these objectives may seem to be quite unrelated, our main goal will be to connect them in order to unambiguously asses the relevance of open systems in specific areas of physics, biology and beyond. Accordingly, objective i) will be explored in close collaboration with experimentalists in which the diffusion of biomolecules on cell membranes requires a description in terms of Brownian motion in correlated disordered potentials. In ii) we will search for many-body kinetic and growth models that provide the configurations that may serve as samples of random potentials desired in i). These models can be regarded as quantum models with non-Hermitian generators of evolution; in some situations they can be generalized to genuine quantum ones, described by a quantum master equation, linking ii) and iii). In iii) we will look for applications of quantum open systems as quantum simulators of condensed matter/high energy physics. We will also look at single particle interactions with quantum many body environment, linking the objectives iii) with iv) and i). Expected results are: a) understanding the relationship between biological function and the spatiotemporal dynamics of single molecules in living cells; b) understanding of the structure of classical many body stochastic models and their relation to quantum ones; c) concrete proposals for open systems quantum simulators; and d) development of tools to characterize and observe quantum Brownian motion.BOpen SYstems RevISited: From Brownian motion to quantum simulatorsGauge theories play a central role in particle and condensed matter physics. Heavy-ion collisions explore the strong dynamics of quarks and gluons, which also governs the deep interior of neutron stars, while strongly correlated electrons determine the physics of high-temperature superconductors and spin liquids. Numerical simulations of such systems are often hindered by sign problems. In quantum link models - an alternative formulation of gauge theories developed by the applicant - gauge fields emerge from discrete quantum variables. In the past year, in close collaboration with atomic physicists, we have established quantum link models as a framework for the atomic quantum simulation of dynamical gauge fields. Abelian gauge theories can be realized with Bose-Fermi mixtures of ultracold atoms in an optical lattice, while non-Abelian gauge fields arise from fermionic constituents embodied by alkaline-earth atoms. Quantum simulators, which do not suffer from the sign problem, shall be constructed to address non-trivial dynamics, including quantum phase transitions in spin liquids, the real-time dynamics of confining strings as well as of chiral symmetry restoration at finite temperature and baryon density, baryon superfluidity, or color-flavor locking. New classical simulation algorithms shall be developed in order to solve severe sign problems, to investigate confining gauge theories, and to validate the proposed quantum simulators. Starting from U(1) and SU(2) gauge theories, an atomic physics tool box shall be developed for quantum simulation of gauge theories of increa< sing complexity, ultimately aiming at 4-d Quantum Chromodynamics (QCD). This project is based on innovative ideas from particle, condensed matter, and computational physics, and requires an interdisciplinary team of researchers. It has the potential to drastically increase the power of simulations and to address very challenging problems that cannot be solved with classical simulation methods.bClassical and Atomic Quantum Simulation of Gauge Theories in Particle and Condensed Matter PhysicsCataract is the opacification of the crystalline lens of the human eye. It is usually related with age and is one of the leading causes of blindness. The increase in light scatter in the lens reduces the contrast in the retinal images severely degrading vision. The current solution is to perform surgery to remove the natural lens that is substituted by an artificial intraocular lens. This is a successful procedure restoring good quality of vision in most patients. However, in many situations it would be incredible advantageous to actually  see through a cataractous eye. The optics of the eye is affected by two factors: aberrations and scatter. In the last decade, correcting optical aberrations in the eye was accomplished by using adaptive optics techniques. This permitted to obtain high resolution images of the retina and also to improve vision. However, the possibility of correcting scatter in the eye was never considered before. We propose here the use of spatial and temporal advanced photonics techniques for imaging through the turbid media of the cataractous lens. We envision two direct applications of this technology: a dedicated fundus camera to register images of the retina in patients affected by cataracts and a novel type of opto-electronics spectacles restoring some vision in cataract patients. The fundus camera would offer clinicians the unique opportunity to determine if there is any retinal pathology underneath the cataractous eye. The scatter-correcting goggles would be useful in those cases where surgery were not possible for any reason or as a temporarily relieve until the surgery is performed. The same type of technology could be applied in the case of normal eyes with lower levels of scatter but desiring to achieve a better than normal vision for some specific tasks. This proposal presents a completely new and disruptive idea, which if successful would render immediate and significant benefits to patients worldwide.0Seeing through cataracts with advanced photonicsMFoundations for Temporal Retrieval, Exploration and Analytics in Web ArchivesOur ambition is to probe the influence of non-proportional multiaxial straining on the multiscale aspects of metal plasticity with focus on three deformation mechanisms: dislocation plasticity in bcc metals, mechanical twinning in fcc metals and the martensitic phase transformation. These mechanisms play a key role in modern TWIP and TRIP steels, yet about their response to multiaxial loading not much is known. The underlying hypothesis of this research project is that by performing biaxial deformation tests at the micro-, meso- and macro-scale meanwhile following the microstructure insitu, ground-breaking insight can be obtained on how a second strain path, a change in strain path with or without prior unloading affects the operation of the deformation mechanism, the defect accumulation and as a consequence, the evolving microstructure. The expected outcome of the research will help the formulation of criteria to be implemented in micromechanical models, for which constitutive equations are now relying solely on a knowledgebase derived from uniaxial testing. Operationally, the project contains a development phase and a research phase. First a micro- and meso-scale biaxial test rig will be developed, allowing deforming small samples in two orthogonal directions independently, compatible to be installed at various Xray beamlines of synchrotron facilities in Europe and in SEMs. The research phase will be multiscale: the response of each deformation mechanism will be investigated at the level of the mechanism itself, at the level of an oligocrystal focusing on transmission of strain across grain boundaries and at the macrosopic level focussing on the evolution of the microstructure. Experimental research will be accompanied by synergetic computational simulations.7MULTIAX: Multiaxial and Multiscale Plasticity in Metals-Physics of Atoms with Attosecond Light PulsesUnderstanding how organisms regulate size is one of the most fascinating open questions in biology. The aim of the AMAIZE project is to unravel how growth of maize leaves is controlled. Maize leaf development offers great opportunities to study the dynamics of growth regulatory networks, essentially because leaf development is a linear system with cell division at the leaf basis followed by cell expansion and maturation. Furthermore, the growth zone is relatively large allowing easy access of tissues at different positions. Four different perturbations of maize leaf size will be analyzed with cellular resolution: wild-type and plants having larger leaves (as a consequence of GA20OX1 overexpression), both grown under either well-watered or mild drought conditions. Firstly, a 3D cellular map of the growth zone of the fourth leaf will be made. RNA-SEQ of three different tissues (adaxial- and abaxial epidermis; mesophyll) obtained by laser dissection with an interval of 2.5 mm along the growth zone will allow for the analysis of the transcriptome with high resolution. Additionally, the composition of fifty selected growth regulatory protein complexes and DNA targets of transcription factors will be determined with an interval of 5 mm along the growth zone. Computational methods will be used to construct comprehensive integrative maps of the cellular and molecular processes occurring along the growth zone. Finally, selected regulatory nodes of the growth regulatory networks will be further functionally analyzed using a transactivation system in maize. AMAIZE opens up new perspectives for the identification of optimal growth regulatory networks that can be selected for by advanced breeding or for which more robust variants (e.g.< reduced susceptibility to drought) can be obtained through genetic engineering. The ability to improve the growth of maize and in analogy other cereals could have a high impact in providing food security2Atlas of leaf growth regulatory networks in MAIZECurrent radar tracking technology to monitor insect movements in space allows us to catch only glimpses of their spatial movements  it is severely constrained by the restricted range that can be covered, the fact that individuals can only be tracked one at a time, and the lack of a height dimension. Here we propose ground-breaking technology advances to make insect telemetry fit for the 21st century, to answer multiple fundamental questions in pollinator space use and its implications for the plants they pollinate. We will work towards transponder miniaturisation to make application to a large number of insect species viable; we will develop radar technology to allow coverage of areas of up to 10km2 and the exploration of the 3rd dimension of insect flight, and we will adapt the equipment so that multiple individuals can be traced simultaneously. We will identify the rules of bee movements at the landscape scale, and the extent to which they use familiar landmarks and learnt vectors to link multiple locations. We will explore whether speed-accuracy tradeoffs are relevant in landmark navigation. Natural resource exploration and exploitation will be monitored over the entire foraging career of select individuals, and we will quantify individual differences in space use. Tracking bees in three dimensions will allow us to ask whether looking at the landscape from above aids efficient navigation. The tracking of multiple bees simultaneously will allow us to monitor competitive interactions as well as the possibility of social learning in space use. For the first time we will also track the spatial movement strategies of queens and males to see how they interface the search for mates with the need to forage efficiently. Our findings will have wide-ranging applications not just for the understanding of pollinator space use, but also for the conservation, management, and the understanding of mating patterns in the plants they pollinate.QSpace use by bees radar tracking of spatial movement patterns of key pollinators/Towards the NEXT generation of bb0nu experimetstIn a modern society, metallic materials are crucially important (e.g. energy, safety, infrastructure, transportation, health, medicine, life sciences, IT). Contemporary examples with inherent challenges to be overcome are the design of ultrahigh specific strength materials. There is a critical need for successful developments in this area in particular for reduced energy consumption, reduction of pollutant emissions and passenger safety. Alternative approaches include improved thermal stability and creep resistance of high-temperature alloys for energy conversion, which are generally used in power plants and turbine engines, high temperature process technology, and fossil-fuel driven engines. The ageing European society makes biomedical materials for implant and stent design also crucially important. A drawback of nearly all current high strength metallic materials is that they lack ductility (i.e. are brittle and hard to form)- or on the opposite side, they may be highly ductile but lack strength. The key concept behind INTELHYB is to define new routes for creation of tailored metallic materials based on scale-bridging intelligent hybrid structures enabling property as well as function optimization. The novelty of this proposal as compared to conventional ideas is that they apply to monolithic amorphous materials or bulk microcrystalline. The basis will be founded on innovative strategies for the design, synthesis and characterization of intrinsic length-scale modulation and phase transformation under highly non-equilibrium conditions. This will include the incorporation of dispersed phases which are close to or beyond their thermodynamic and mechanical stability limit thus forming a hierarchically structured hybrid and ductile/tough alloys. Alternatively, the material itself will be designed in a manner such that it is at the verge of its thermodynamic/mechanical stability.PNext generation of complex metallic materials with intelligent hybrid structuresAThis proposal aims at the discovery of robust transition-metal catalyzed transformations that can take place in aqueous media and cellular lysates, and are susceptible of being exported to living cells. Specifically, we will exploit the special coordination and activation ability of different metal complexes towards pi-systems to induce chemo-selective reactions of designed, abiotic, unsaturated substrates. Moreover, and importantly, the metal catalysts will be conjugated to designed ligands or biopolymers so that the catalytic power of the metal complex can be transferred to specific  in vivo locations. Initial designs in this latter  high risk endeavor will be guided by the current knowledge on metal-catalyzed bio-orthogonal chemistry as well as by some precedents on catalysis-based metal-sensing tactics. Ultimately, we want to install catalytic power in specific cellular sites and/or endow cata< lytic properties to any selected bio-molecular target. The catalytic activity could then be used to trigger the amplified generation of fluorescent signals or boost the production of bioactive drugs from inert, non-toxic precursors. This will set the basis for the development of efficient bio-sensing and imaging tools, and  in cellulo diagnosis tactics, and of novel target-directed therapeutic strategies. With the crescent identification of disease-related biomarkers, the development of biomarker-associated diagnosis and therapy protocols is becoming one of the more urgent challenges in modern life sciences. Advances in early diagnosis can have a profound impact in public health, and boost new technology developments. The transversal expertise of my group in synthesis, metal catalysis, molecular recognition and chemical biology (see PI profile) places us in a rather unique position to tackle this type of interdisciplinary project.cMetal catalysis in biological habitats: New strategies for optical bio-sensing and targeted therapyOThree-dimensional molecular resolution mapping of soft matter-liquid interfacesxMesenchymal cells (MCs) of the intestinal lamina propria refer to a variety of cell types, most commonly intestinal myofibroblasts, fibroblasts, pericytes, and mesenchymal stromal cells, which show many similarities in terms of origin, function and molecular markers. Understanding the physiological significance of MCs in epithelial and immunological homeostasis and the pathophysiology of chronic intestinal inflammatory and neoplastic disease remains a great challenge. In this proposal, we put forward the challenging hypothesis that, especially during acute or chronic inflammatory and tumorigenic conditions, MCs play important physiological roles in intestinal homeostasis regulating key processes such as epithelial damage, regeneration and tumorigenesis, intestinal inflammation and lymphoid tissue formation. We further posit that a unifying principle underlying such functions would be the innate character of MCs, which we hypothesize are capable of directly sensing and metabolizing innate signals from microbiota or cytokines in order to exert homeostatic epithelial and immunological regulatory functions in the intestine. We will be using genetic approaches to target innate pathways in MCs and state of the art phenotyping to discover the physiologically important signals orchestrating intestinal homeostasis in various animal models of intestinal pathophysiology. We will also study MC lineage relations and plasticity during disease and develop ways to interfere therapeutically with MC physiology to achieve translational added value for intestinal diseases, as well as for a range of other pathologies sharing similar characteristics._Mesenchymal Cells of the Lamina Propria in Intestinal Epithelial and Immunological Homeostasis.Centrioles are critical for the formation of cilia, flagella and centrosomes, as well as for human health. The mechanisms governing centriole formation constitute a long-standing question in cell biology. We will pursue an innovative multidisciplinary research program to gain further insight into these mechanisms, using human cells, C. elegans and Trichonympha as model systems. This program is expected to also have a major impact by contributing a novel cell free assay to the field, thus paving the way towards making synthetic centrioles. Six specific aims will be pursued: 1) Deciphering HsSAS-6/STIL distribution and dynamics. We will use super-resolution microscopy, molecular counting, photoconversion and FCS to further characterize these two key components required for centriole formation in human cells. 2) The SAS-6 ring model as a tool to redirect centriole organization. Utilizing predictions from the SAS-6 ring model, we will assay the consequences for centrioles and cilia of altering the diameter and symmetry of the structure. 3) Determining the architecture of C. elegans centrioles. We will conduct molecular counting and cryo-ET of purified C. elegans centrioles to determine if they contain a spiral or a cartwheel, as well as identify SAS-6-interacting components. 4) Comprehensive 3D map and proteomics of Trichonympha centriole. We will obtain a ~35 3D map of the complete T. agilis centriole, perform proteomic analysis to identify its constituents and test their function using RNAi. 5) Regulation of cartwheel height and centriole length. We will explore whether cartwheel height is set by SAS-6 proteins and perform screens in human cells to identify novel components regulating cartwheel height and centriole length. 6) Novel cell free assay for cartwheel assembly and centriole formation. Using SAS-6 proteins on a lipid monolayer as starting point, we will develop and utilize a cell-free assay to reconstitute cartwheel assembly and centriole format7Dissecting the mechanisms governing centriole formationWModuli of curves with symmetries:determine the stable irreducible components of the moduli space of curves of genus g with an action of a finite group G, using a new homological invariant. Stable means: for g sufficiently large, or for sufficiently large numerical branching function. Higher homological stabilization for these moduli spaces. Faithful actions of the absolute Galois group on moduli spaces of marked varieties, triangle curves, varieties isogenous to a product, Beauville surfaces. Change of fundamental group. Fields of definitions of triangle curves and the scheme representing triangle curves. Uniformization: characterization of proj. var. whose universal cover is a given bounded symmetric domain (Catanese-Di Scala did the case of tube domains). Orbifold Uniformization: where we have a quotient of a non free action, or a noncompact such quotient. Classification of surfaces with genus 0 having the bidisk as universal cover. Symmetric differentials and fundamental groups of some ball quotients. Topological methods in Moduli Theory: strong, weak and pseudo rigidity for the Inoue type varieties of Bauer and Catanese (free quotients of ample divisors on projective varieties which are K(\pi, 1)). With Lonne and Wajnryb, using methods by Auroux and Katzarkov: study canonical symplectic structures and deformation types of some simply connected algebraic surfaces, determining braid group factorizations associated to subcanonical projections. More general bicoloured braid factorizations associated to general projections. Teichmueller space of certain algebraic surfaces. Classification and Moduli of surfaces with low invariants. Surfaces of geometric genus 0: new construction techniques, structure of fundamental groups, moduli spaces, existence questions for surfaces with certain invariants, for homotopy quadrics, structure of fake quadrics.PTopological, Algebraic, Differential Methods in Classification and Moduli TheorycNanostructuring graphene and graphitic substrates for controlled and reproducible functionalizationQRisk and uncertainty are inherent in any decision-making procedure, but while a substantial body of work on the governance of international migration focuses on challenges posed to governance systems, we know remarkably little about the impact of risk and uncertainty<  on: (i) the cognitive biases of actors within migration governance systems; (ii) the susceptibility of these biases to change; (iii) the relationship between cognitive bias and broader questions of systemic resilience, vulnerability and adaptation and (iv) the similarities and differences in migration governance between major world regions. Each of these is a significant gap in our knowledge of international migration governance. To address this gap this project will focus on the context of decision to ask: what are the causes and consequences of the cognitive biases concerning risk and uncertainty held by actors in migration governance systems? The project will: (i) test the causes and consequences of the  frames held by actors in migration governance systems, specify the scope for these frames to change and to analyse the likely systemic effects of change on migration governance systems in four major world regions. (ii) develop a comparative regional analysis of the micro-political foundations of migration governance and their implications for system adaptation and change. (iii) significantly advance conceptual and methodological understanding of international migration governance through the use of concepts of systemic adaptation, vulnerability and resilience that bridge behavioural theories of choice with theories of institutional and organisational change. (iv) disseminate the results effectively through a range of appropriate outlets and through engagement with a range of users of the results of this work in academia, policy-making communities, NGOs and the wider public.0Prospects for International Migration GovernanceRADICAL explores the idea that consciousness is something that the brain learns to do rather than a static property of certain neural states vs. others. Here, considering that consciousness is extended both in space and in time, I adopt a resolutely dynamical perspective that mandates an experimental approach focused on change, at different time scales. I suggest that consciousness arises as a result of the brain's continuous attempts at predicting not only the consequences of its actions on the world and on other agents, but also the consequences of activity in one cerebral region on activity in other regions. By this account, the brain continuously and unconsciously learns to redescribe its own activity to itself, so developing systems of metarepresentations that characterise and qualify the target first order representations. Such learned redescriptions form the basis of conscious experience. Learning and plasticity are thus constitutive of consciousness. This is what I call the  Radical Plasticity Thesis . In a sense, this is the enactive perspective, but turned both inwards and (further) outwards. Consciousness involves  signal detection on the mind ; the conscious mind is the brain's (non-conceptual, implicit) theory about itself. Theoretically, RADICAL offers the possibility of unifying Global Workspace Theory with higher-order Thought Theory by showing how the former can be built through mechanisms that flesh out the latter. Empirically, RADICAL aims at testing these ideas in three domains: (1) the perception action loop, (2) the self-other loop, and (3) the inner loop. 20 experiments leveraging behavioural experimentation, brain imaging, and computational modeling are proposed to test and further develop RADICAL. The overarching goal of the project is to characterize the computational principles that differentiate conscious from unconscious cognition, based on a bold, original, and innovative theory in which learning and plasticity play central roles.;The Radical Plasticity Thesis: How we learn to be consciousCutting went through a revolution in the 1990s when high-speed milling (HSM) was introduced: the sculpture-like workpieces produced with high precision and efficiency resulted in one order of magnitude less parts in cars/aircrafts, which kept this traditional technology competitive at the turn of the century. This has been followed by an incremental development when not just the cutting speeds, but depths of cut and feed rates are pushed to limits,<  too. The limits are where harmful vibrations occur. Cutting is subject to a special one called chatter, which is originated in a time delay: the cutting edge interferes with its own past oscillation recorded on the wavy surface cut of the workpiece. In 1907, the 3rd president of ASME, Taylor wrote:  Chatter is the most obscure and delicate of all problems facing the machinist . In spite of the development of the theory of delay-differential equations and nonlinear dynamics, Taylor s statement remained valid 100 years later when HSM appeared together with a new kind of chatter. The applicant has been among those leading researchers who predicted these phenomena; the experimental/numerical techniques developed in his group are widely used to find parameters, e.g. where milling tools with serrated edges and/or with varying helix angles are advantageous. The SIREN project aims to find isolated parameter islands with 3-5 times increased cutting efficiency. The work-packages correspond to points of high risk: (1) validated, delay-based nonlinear modelling of the dynamic contact problem between chip and tool; (2) fixation of the tool that is compatible with a dynamically reliable mathematical model of the contact between tool and tool-holder; (3) up-to-date dynamic modelling of the spindle at varying speeds. High risk originates in the attempt of using distributed delay models, but high gain is expected with robust use of parameter islands where technology reaches a breakthrough in cutting efficiency for the 21st century.6Stability Islands: Performance Revolution in MachiningvFrom cell biology to polymer photovoltaics, (self-)assembly processes that give rise to morphology and functionality result from non-equilibrium processes, which are driven by both, external forces, such as flow due to pressure gradients, inserting energy, or manipulation on a local molecular level, or internal forces, such as relaxation into a state of lower free energy. The resulting material is arrested in a metastable state. Most previous work has focused on the relationship between structure and properties, while insight into the guiding principles governing the formation of a (new) material, has been lacking. However, a comprehensive molecular level understanding of non-equilibrium assembly would allow for control and manipulation of material processes and their resulting properties. This lag of knowledge can be traced to the formidable challenge in obtaining a molecular picture of non-equilibrium assembly. Non-equilibrium processes have been studied extensively on a macroscopic level by non-equilibrium thermodynamics. We take a novel route approaching the challenge from a molecular point of view. Recent advances in experimental, but especially computational modeling, now allow to follow (supra-) molecular structural evolution across the range of length and time scales necessary to comprehend, and ultimately control and manipulate macroscopic functional properties of soft matter at the molecular level. Soft matter is particularly suited for that approach, as it is  slow and easy to manipulate. We take the computational physics route, based on simulations on different levels of resolution (all atom, coarse grained, continuum) in combination with recent multiscale and adaptive resolution techniques. This work will initiate the way towards a paradigm change from conventional Structure Property Relations (SPR) to molecularly based Structure Process Property Relations (SPPR).qFrom Structure Property to Structure Process Property Relations in Soft Matter  a Computational Physics ApproachPlasmon-based nanophotnics, an explosively growing research field concerned with surface-plasmon waveguides and circuitry, is oriented towards exploiting unique perspectives opened for radiation guiding along metal surfaces: extreme mode confinement (i.e., far beyond the diffraction limit) and seamless interfacing of electronic and photonic circuits (that both utilize the same metal circuitry). At the same time, unavoidable radiation absorption by metals results in the fundamental trade-off between the mode confinement and propagation loss, so that the problem of making the most of the above unique features becomes of paramount importance. The proposal encompasses two ground-breaking research directions in plasmonics that explore and utilize extremely confined plasmon-waveguide modes for functional and quantum nanophotonics. These directions of in-depth investigations concentrate within two interrelated and largely unexplored research areas within plasmonics: development of ultra-compact plasmonic configurations e< xhibiting unique functionalities and realization of strong coupling between extremely confined plasmonic modes and individual quantum emitters. Fundamental studies of ultimate mode confinement and coupling to quantum emitters would evolve into investigations carried out within forefront topics including (i) dynamic control of plasmon-waveguide modes using the same metal circuitry for both radiation guiding and its control with electrical signals; (ii) moulding the radiation flow by gradually varying waveguide cross sections in order to realize efficient nanofocusing of radiation, miniature ultra-dispersive wavelength-selective components and table-top models of plasmonic black holes, and (iii) quantum plasmonics with individual quantum emitters being strongly coupled to deep subwavelength surface plasmon modes, targeting the realization of a saturable waveguide mirror, single-photon transistor and long-distance entanglement of two remote quantum emitters.2Plasmon-based Functional and Quantum NanophotonicsThe project is aimed at uncovering new links between integrable systems, string theory and quantum field theory. The goal is to study non-perturbative phenomena in strongly-coupled field theories, and to understand relationship between gauge fields and strings at a deeper level.-Integrable Systems in Gauge and String TheoryX-ray crystallography yields atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes constituting the macromolecular machinery of life. Life is not static, and many of the most important reactions in chemistry and biology are light induced and occur on ultrafast timescales. These have been studied with high time resolution primarily by ultrafast laser spectroscopy, but they reduce the vast complexity of the process to a few reaction coordinates. Here we develop attosecond serial crystallography and spectroscopy, to give a full description of ultrafast processes atomically resolved in real space and on the electronic energy landscape, from co-measurement of X-ray and optical spectra, and X-ray diffraction. This technique will revolutionize our understanding of structure and function at the atomic and molecular level and thereby unravel fundamental processes in chemistry and biology. We apply a fully coherent attosecond X-ray source based on coherent inverse Compton scattering off a free-electron crystal, developed in this project, to outrun radiation damage effects due to the necessary high X-ray irradiance required to acquire diffraction signals [A. Cho, "Breakthrough of the year", Science 388, 1530 (2012)]. Our synergistic project will optimize the entire instrumentation towards fundamental measurements of the mechanism of light absorption and excitation energy transfer. The multidisciplinary team optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size, and advanced X-ray detectors. We will apply our new capabilities to one of the most important problems in structural biology, which is to elucidate the dynamics of light reactions, electron transfer and protein structure in photosynthesis. Also, the attosecond source can provide a coherent seed and will help to overcome peak flux limitations of X-ray FELs by introducing chirped pulse amplification to FEL technology.?Frontiers in Attosecond X-ray Science: Imaging and SpectroscopyThe classical view of genomes as linear sequences has been replaced by a vision of nuclear organization that is both dynamic and complex, with chromosomes and genes non-randomly positioned in the nucleus. Process compartmentalization and spatial location of genes modulate the transcriptional output of the genomes. However, how the interplay between genome structure and gene regulation is established and maintained is still unclear. The aim of this project is to explore whether the genome 3D structure acts as an information source for modulating transcription in response to external stimuli. With a genuine interdisciplinary team effort, we will study the conformation of the genome at various integrated levels, from the nucleosome fiber to the distribution of chromosomes territories in the nuclear space. We will generate high-resolution 3D models of the spatial organization of the genomes of distinct eukaryotic cell types in interphase to identify differences in the chromatin landscape. We will follow the time course of structural changes in response to cues that affect gene expression either permanently or transiently. We will analyze the changes in genome structure during the stable trans-differentiation of immortalized B cells to macrophages and during the transient hormonal responses of differentiated cells. We plan to establish novel functional strategies, based on targeted and high-throughput reporter assays, to assess the relevance of the spatial environment on gene regulation. Using sophisticated modeling and computational approaches, we will combine high-resolution data from chromosome interactions, super-resolution images and omics information. Our long-term plan is to implement a 3D browser for the comprehensive mapping of chromatin properties and genomic features, to better understand how external signals are integrated at the genomic, epigenetic and structural level to orchestrate changes in gene expression that are cell specific and dynamic.UDynamics of human genome architecture in stable and transient gene expression changesP is an earthbound and finite element and the prospect of constrained access to mineable P resources has already triggered geopolitical disputes. In contrast to P, availabilities of carbon (C) and nitrogen (N) to ecosystems are rapidly increasing in most areas of the globe. The resulting imminent change in the stoichiometry of available elements will have no equivalent in the Earth s history and will bear profound, yet, unknown consequences for life, the Earth System and human society. The ongoing shifts in C:N:P balances in ecosystems will necessarily affect the structure, function and diversity of the Earth system. P-market crises might put pressure on the global food system and create environmental ripple effects ranging from expansion of agricultural land to P-price-induced changes in land management exacerbating the stoichiometric resource imbalance. Yet, the impacts of this unprecedented human disturbance of elemental stoichiometry remain a research enigma. The IMBALANCE-P-team, that gathers four leading researchers in the fields of ecosystem diversity and ecology, biogeochemistry, Earth System modelling, and global agricultural and resource economics, is formidably positioned to address this Earth System management challenge by providing improved understanding and quantitative foresight needed to formulate a range of policy options tha< t will contain the risks and mitigate the consequences of stoichiometric imbalances. IMBALANCE-P will integrate some of Europe's leading integrated assessment and Earth system models, calibrated using ecosystem nutrient limitation data obtained from field experiments. The project will establish an international process of science-based P-diplomacy.CEffects of phosphorus limitations on Life, Earth system and SocietyMany current theories implicate brain oscillations in perception, attention, consciousness or memory. This, however, has one critical implication that is often overlooked in cognitive sciences: if a perceptual function relies on an oscillatory basis, then it should operate periodically, as a sequence of successive episodes or 'snapshots', with more or less favourable moments recurring at a well-defined periodicity. The present project aims to explore the validity and the consequences of this groundbreaking notion of "rhythmic perception". Whereas current research links perceptual functions to relatively slow changes of oscillatory amplitude, we propose to investigate the perceptual consequences of brain rhythms at the rapid time scale of the oscillatory cycle  the notion of "perceptual cycles". In work-package (WP) 1, we will explore the range of perceptual and cognitive operations that depend on oscillatory neural implementations, and reveal their cyclic behaviour. In WP2, we will relate these perceptual and cognitive cycles to the underlying neural activities by means of brain imaging techniques (EEG, fMRI, TMS); a key innovation is a proposed novel fMRI method to visualize the spatio-temporal propagation of perceptual cycles. In WP3, we will utilize this knowledge to control the power, frequency and phase of perceptual rhythms and thus dynamically manipulate, improve or prevent perception. In WP4, we will bridge the gap between lower- and higher-frequency perceptual cycles (from ~2 to ~100Hz) by experimental studies of cross-frequency coupling and computational models of visual information multiplexing. The project as a whole will characterize the rhythmic dynamics of perception, their neural basis and their functional implications, bringing us closer to understanding perception itself. The idea that sensory perception and cognition might follow a succession of snapshots rather than a continuous stream could spark a major transformation in cognitive sciences.YPerceptual Cycles: Exploring and controlling the perceptual consequences of brain rhythmsThe main objective of COMOTION is to enable novel experiments for the investigation of the intrinsic properties of large molecules, including biological samples like proteins, viruses, and small cells -X-ray free-electron lasers have enabled the observation of near-atomic-resolution structures in diffraction- before-destruction experiments, for instance, of isolated mimiviruses and of proteins from microscopic crystals. The goal to record molecular movies with spatial and temporal atomic-resolution (femtoseconds and picometers) of individual molecules is near. -The investigation of ultrafast, sub-femtosecond electron dynamics in small molecules is providing first results. Its extension to large molecules promises the unraveling of charge migration and energy transport in complex (bio)molecules. -Matter-wave experiments of large molecules, with currently up to some hundred atoms, are testing the limits of quantum mechanics, particle-wave duality, and coherence. These metrology experiments also allow the precise measurement of molecular properties. The principal obstacle for these and similar experiments in molecular sciences is the controlled production of samples of identical molecules in the gas phase. We will develop novel concepts and technologies for the manipulation of complex molecules, ranging from amino acids to proteins, viruses, nano-objects, and small cells: We will implement new methods to inject complex molecules into vacuum, to rapidly cool them, and to manipulate the motion of these cold gas-phase samples using combinations of external electric and electromagnetic fields. These external-field handles enable the spatial separation of molecules according to size, shape, and isomer. The generated controlled samples are ideally suited for the envisioned precision experiments. We will exploit them to record atomic-resolution molecular movies using the European XFEL, as well as to investigate the limits of quantum mechanics using matter-wave interferometry.9Controlling the Motion of Complex Molecules and ParticlesTOR and Cellular Homeostasis7Fungal diseases represent a significant and growing threat to human health, particularly since the AIDS pandemic and increasing use of immunosuppressive drugs has produced a massive population of people with impaired immunity who are vulnerable to fungal infections. A great challenge in medical mycology is to understand how fungal virulence evolves. The vast majority of fungal species are not human pathogens and, for those that are, virulence appears to have evolved independently on many different occasions. Identifying the step(s) that convert an environmental fungus into a human pathogen, as well as subsequent changes in virulence within a pathogenic lineage, is therefore of fundamental importance. Based on a number of lines of evidence, I hypothesise that a critical regulator of fungal virulence in animal hosts is the activity of the fungal mitochondrion, an energy-generating organelle present in almost all eukaryotes. I propose to test this hypothesis comprehensively by combining genetic and cell biological approaches with high-resolution imaging methods..Mitochondria as regulators of fungal virulenceInflammatory diseases affect over 80 million people worldwide and accompany many diseases of industrialized countries, being the majority of them infection-free conditions. There are few efficient anti-inflammatory drugs to treat chronic inflammation and thus, there is an urgent need to validate novel targets. We now know that innate immunity is the main coordinator and driver of inflammation. Recently, we and others have shown that the activation of purinergic P2X7 receptors (P2X7R)<  in immune cells is a novel and increasingly validated pathway to initiate inflammation through the activation of the NLRP3 inflammasome and the release of IL-1 and IL-18 cytokines. However, how NLRP3 sense P2X7R activation is not fully understood. Furthermore, extracellular ATP, the physiological P2X7R agonist, is a crucial danger signal released by injured cells, and one of the most important mediators of infection-free inflammation. We have also identified novel signalling roles for P2X7R independent on the NLRP3 inflammasome, including the release of proteases or inflammatory lipids. Therefore, P2X7R has generated increasing interest as a therapeutic target in inflammatory diseases, being drug like P2X7R antagonist in clinical trials to treat inflammatory diseases. However, it is often questioned the functionality of P2X7R in vivo, where it is thought that extracellular ATP levels are below the threshold to activate P2X7R. The overall significance of this proposal relays to elucidate how extracellular ATP controls host-defence in vivo, ultimately depicting P2X7R signalling through and beyond inflammasome activation. We foresee that our results will generate a leading innovative knowledge about in vivo extracellular ATP signalling during the host response to infection and sterile danger.{Regulation of inflammatory response by extracellular ATP and P2X7 receptor signalling: through and beyond the inflammasome.The last decades are characterized by an upsurge of research on the impacts of global environmental changes on forests. Climate warming, atmospheric deposition of acidifying and eutrophying pollutants and land-use change are three of the most important threats to biodiversity in temperate forests. However, most studies focused on the effects of single factors over short time periods, such that our ability to predict the combined effects of multiple global change drivers over longer time periods remains rudimentary. The lack of knowledge on effects of global change drivers on forest herb layer communities is particularly striking, since the herb layer contains the largest part of vascular plant diversity in temperate forests and provides key ecosystem services. Therefore PASTFORWARD will build an integrative understanding of the interactive effects of land-use change, atmospheric deposition and climate warming on forest herb layer communities, starting from the insight that changes in herb layer communities are driven primarily by past land use, but can be modulated by atmospheric deposition, climate warming and forest management. Indeed, it is still largely ignored that sensible predictions of herb layer development trajectories under global change can only be made by taking the forest s land-use history into account, as legacies of past land use can leave century-long imprints on forest herb layer communities. Three complementary data sources (a database with resurveyed vegetation plots, field measurements in a pan-European network of resurvey plots, and a multi-factor experiment) combined with an ecosystem model will be used. Furthermore, concepts and tools from different disciplines, ranging from history over sylviculture to community and ecosystem ecology will be applied. The results of PASTFORWARD will help forest managers and policy makers in taking more informed decisions on how to combine resource extraction with biodiversity conservation.Development trajectories of temperate forest plant communities under global change: combining hindsight and forecasting (PASTFORWARD)An established dogma is that insulin is absolutely required for survival. This notion has been supported by the fact that the sole life-saving intervention available to the millions affected by type 1 diabetes mellitus (T1DM; an illness caused by pancreatic -cell loss and hence insulin deficiency) is insulin therapy. This treatment however does not restore normal metabolic homeostasis. In fact, the life-expectancy and -quality of T1DM people is worse compared to normal subjects. In part, this is due to challenging morbidities of T1DM, as for example heart disease and hypoglycemia, both of which are thought to be caused by insulin therapy itself. Indeed, owing to insulin s li< pogenic actions, this treatment likely contributes to the ectopic lipid deposition (i.e.: in non-adipose tissues) and extremely high incidence of coronary artery disease seen in T1DM subjects. Also, due to insulin s potent, fast-acting, glycemia-lowering action, this therapy significantly increases the risk of hypoglycemia; a disabling and life threatening event. Because insulin therapy does not restore metabolic homeostasis in T1DM subjects, better intervention is urgently needed. To these ends, we and others have shown that the hyperglycemic and lethal consequences of insulin deficiency can be rescued by administration of the adipocyte-secreted hormone leptin. Not only these results challenge an established view, they also raise a fundamental biological and medical question: what are the mechanisms by which leptin improves hyperglycemia and permits survival in the context of insulin deficiency? This proposal aims at identifying the critical cellular and molecular components underlying the beneficial effects of leptin in the context of insulin deficiency. Once identified, manipulation of these components has the potential to improve life-expectancy and -quality of the millions affected by insulin deficiency (e.g.: T1DM and also some late-stage type 2 diabetics).HMetabolic actions of brain leptin receptors signaling in type 1 diabetesColloidal inorganic nanocrystals (NCs) are among the most investigated nanomaterials in Nanoscience due to their high versatility. Research on NCs went through much advancement lately, especially on synthesis, assembly and on the study of their transformations, most notably via cation exchange (all fields in which the PI has contributed already). However, the integration of NCs with fabrication tools that employ conditions such as irradiation, etching and annealing is at a very early stage since we do not have a systematic knowledge of what transformations are triggered in the NCs under those conditions. Also, an issue related to the incorporation of NCs in materials/devices is whether, over time, the NCs will remain as they are, or they will transform into other structures. Plus, these transformations in NCs are poorly studied as they require fast recording techniques. This proposal will embark on an ambitious investigation of post-synthetic transformations in solution-grown NCs: by advancing the understanding of various aspects of chemical, structural and surface transformation of NCs, we will uncover new fabrication techniques that will employ such nanostructures as the key ingredients. This in turn will have a strong impact in opto-electronics, as several electronic components entirely made of NCs will be delivered. Four objectives are targeted: i) developing radically new sets of experimental tools for the investigation of chemical transformations in NCs, above all the ability to monitor in real time these transformations; ii) developing solution-grown nanostructures able to undergo programmed transformations under a defined stimulus; iii) understanding the role of irradiation on the fate of surface ligands and on cation exchange reactions in NCs; iv) combining chemical, structural and surface transformations towards NC-based opto-electronics. The success of the proposal hinges on the proven capabilities of the PI, with ample support from the host Institution.aAdvancing the Study of Chemical, Structural and Surface Transformations in Colloidal NanocrystalsGalactic stellar nuclei are very common in all types of galaxies and are marked by the presence of nuclear star clusters, the densest and most massive star clusters in the present-day Universe. Their formation is still an unresolved puzzle. The centre of the Milky Way contains a massive black hole and a stellar nucleus and is orders of magnitude closer than any comparable target. It is the only galactic nucleus and the most extreme astrophysical environment that we can examine on scales of milli-parsecs. It is therefore a crucial laboratory for studying galactic nuclei and their role in the context of galaxy evolution. Yet, suitable data that would allow us to examine the stellar component of the Galactic Centre exist for less than 1% of its projected area. Moreover, the well-explored regions are extraordinary, like the central parsec around the massive black hole, and therefore probably not representative for the overall environment. Fundamental questions on the stellar population, structure and assembly history of the Galactic Centre remain therefore unanswered. This project aims at addressing the open questions by obtaining accurate, high-angular resolution, multi-wavelength near-infrared photometry for an area of several 100 pc^2, a more than ten-fold increase compared to the current state of affairs. The Galactic Centre presents unique observational challenges because of a combination of high extinction and extreme stellar crowding. It is therefore not adequately covered by existing or upcoming imaging surveys. I present a project that is specifically tailored to overcome these observational challenges. In particular, I have developed a key technique to obtain the necessary sensitive, high-angular resolution images with a stable point spread function over large, crowded fields. It works with a range of existing ground-based instruments and will serve to complement existing data to provide a global and detailed picture of the stellar nucleus of the Milky Way.The Fingerprint of a Galactic Nucleus: A Multi-Wavelength, High-Angular Resolution, Near-Infrared Study of the Centre of the Milky WayNHarmonic Analysis, Partial Differential Equations and Geometric Measure TheorydMICROMACHINED OPTOMECHANICAL DEVICES: looking at cells, tissues, and organs ... with a gentle touch.EVariational Methods for Dynamic Inverse Problems in the Life SciencesThis project aims at producing a fully functional light energy conversion system that is inspired by, but does not necessarily mimic, the fundamental solar energy conversion unit of natural photosynthesis  the photosystem. This is a formidable challenge that can be met with thorough understanding of biological energy and electron transfer processes, and the growing capabilities of computational protein design. Here, this knowledge and capabilities will be further developed and utilized for the design and construction of multi-cofactor,< multi-subunit protein complexes with photosystem functionality. These will be designed to efficiently capture light in the visible and near infrared range, exploit it for driving the oxidation of a molecular redox carrier at one end, and providing highly reducing electrons at the other end. Our general goal will be achieved by designing protein-cofactor complexes that will facilitate light-driven electron- and excitation energy-transfer that will make up the reaction center, and light harvesting modules, respectively. Constructing protein scaffolds that will assemble and organize arrays of multiple pigments, and chains of redox cofactors are significant challenges at the forefront of the field of protein de novo design, and current theories of biological energy and electron transfer. Success will set a new standard, well beyond the current state of the art, for our ability to use computational protein design methods for assembling functional protein-cofactor complexes. These can be used as benchmarks to test and validate the engineering principles of biological energy conversion systems, as well as new ideas about their evolution. Practically, it will open new and exciting technological possibilities for constructing artificial solar energy conversion systems from biological building blocks, which may enable their introduction into living systems and the construction of novel bioreactors for light driven fuel production.9An artificial water-soluble photosystem by protein designThe gastrointestinal tract hosts the microbiome, one of the highest microbial densities on earth. Diverse host-microbiome interactions influence a multitude of physiological and pathological processes, yet the basic mechanisms regulating host-microbiome interactions remain unknown. Deciphering the codes comprising the host-microbiome communication network and factors initiating loss of homeostasis (termed dysbiosis) will enable the recognition of pathways and signals critically important to initiation and progression of common immune and metabolic disorders. We recently identified the NLRP6 inflammasome as a critical innate immune regulator of colonic microbial ecology, with its disruption resulting in auto-inflammation and tumorigenesis. We will use this unique system, coupled with innovative robotic high-throughput modalities, gnotobiotics, metagenomics and multiple genetically altered mouse models to generalize our studies and decipher the critical principles governing host-microbiome interactions. We will elucidate the host-derived microbiome recognition signaling pathway at its entirety, from its upstream activators to the downstream effector molecules controlling microbial ecology; uncover the principles generating a stable microbiota composition; and develop and apply computational modelling to dissect the general mechanisms disrupting microbiome stability leading to dysbiosis. Using this innovative experimental and computational toolbox we will study the impact of dysbiosis on key components of the metabolic syndrome, and apply our findings to devise the first rational proof-of-concept approach for individualized microbiome-based treatment for these common disorders. At the basic science level, unraveling the principles of host-microbiota interactions will lead to a conceptual leap forward in our understanding of physiology and disease. Concomitantly, it may generate a platform for microbiome-based personalized therapy against common idiopathic illnesses.uDeciphering the molecular language orchestrating host-microbiome interactions and their effects on health and diseaseAInnovative Catalyst Design for Large-Scale, Sustainable ProcessesAFormalizing Subjective Interestingness in Exploratory Data MiningModern historiography produced in Asia belongs to the history-paradigm of the European humanities and it is from within these epistemological confines that Western as well as Eastern scholars of Asian studies view the Asian writing of the past. While source criticism and historicism have today become key parts of historical consciousness in Asia, Asian historical representations are nonetheless firmly embedded in pre-modern Asian literary traditions via specific uses in historical writing of traditional rhetorical structures of narrative, emplotment, tropes, and literary imagery. Taking such linkage between present and past Asian traditions of historiography as its premise, project NAMO  with four team members consisting of the PI and three Postdocs  will examine the literary features of Asian historiography in India, China, and Tibet across the longue dure of the classical, medieval, and modern periods. First, a new method for the study of the literary forms that characterize historiography in Asia will be established by adapting basic analytical principles from Asian literary theories drawn from twelve classical Indian and Chinese works on poetics. Next, the team will determine the specific literary characteristics of narrative, plot, tropes, and historical explanation found in seventeen classical and medieval histories composed in China, India, and Tibet. Finally, it will be examined to which extent those traditional literary features still function as constitutive rhetorical elements in modern Asian history writing. This will be done by analyzing the literary forms used in a selection of twenty representative histories written in the People's Republic of China and the Republic of India during the period 1980-2010. The outcome will be a novel approach for the empirical study of Asian history that will open up a new level of comparative work in the theory of history across non-Western and Western traditions./Narrative Modes of Historical Discourse in AsiaThis project will be the first to engage in a comprehensive study of the role of genes and gene-environment (GxE) interaction on reproductive behaviour. Until now, social science research has focussed on socio-environmental explanations, largely neglecting the role of genes. Due to unprecedented advances in molecular genetics over the last two decades, for the first time in history we are able to examine whether there is a genetic component to reproductive outcomes, including age at first birth, number of ch< ildren and infertility. Building on my substantive empirical research, I first develop a multifactor theoretical and measurement model isolating socio-environmental and lifestyle factors. Second, I apply the most cutting-edge techniques in genetics to examine the genetic architecture of reproductive behaviour, including: the first genome-wide association study (GWAS) of reproductive choice; polygenic risk scores; and, genome-wide complex trait analysis (GCTA). Third, I focus on gene-environment interactions (GxE) to test different mechanisms of how the environment moderates genetic influences. Fourth, I propose to use genetic markers as instrumental variables (IVs) in a bi-directional Mendelian randomization (MR) analysis to determine causality and address the endogeneity of lifestyle and education in reproductive outcomes. This transdisciplinary project will produce fundamentally different results, overturn established links and deliver major breakthroughs in fertility research and beyond. This project is not only ground breaking by setting a new research agenda, but due to the inclusion of new genetic variables and techniques to study the causal effects of genes and their interaction with environment, will yield major innovations useful within demography and beyond. Research builds on the proven expertise and existing collaboration with geneticists, and is carefully costed to include 2 postdocs and 2 PhDs.]Unravelling the genetic influences of reproductive behaviour and gene-environment interaction Exploding stars, or supernovae, impact upon many diverse areas of astrophysics, from galaxy formation, to stellar evolution, to cosmology and studies of dark energy. I am playing a leading role in new, wide-field, high-cadence optical surveys that are revolutionising the study of supernovae, searching vast volumes of space, locating hundreds of events to study their demographics in detail, and uncovering new and bizarre types of explosions. In concert with a major European Southern Observatory public spectroscopic survey, PESSTO, these imaging surveys will provide an extraordinary dataset for understanding all facets of the supernova and explosive transient population. My work will perform several tests of the progenitors and physics of the classical type Ia supernovae in an attempt to understand how these crucial standard candles depend on their progenitor stellar populations. I will use these results to inform a new generation of models of type Ia supernovae. I will this distill these results to make a detailed measurement of the dark energy that powers the accelerating universe in which we live, greatly improving upon existing measurements of the variation of dark energy over the last ten billion years. A final aspect of my research is an innovative search for superluminous supernovae: a new class of supernova explosion a hundred times brighter than traditional supernovae, capable of being studied in the very distant universe. These objects may become cosmology's new standard candle, visible far beyond the reach of type Ia supernovae. My new search will significantly increase both the quantity and quality of superluminous supernova observations, allowing us to further our understanding of these enigmatic objects and use them in a cosmological setting for the first time.4Supernovae: Physics and Cosmology in the Next DecadeAs far as we know, our solar system is unique. It could, in principle, be the only planetary system in the Universe to harbor intelligent life or, indeed, life at all. As such, attempting to reconstruct its history is one of the most fundamental pursuits in the natural sciences. Whereas astronomical observations of star- forming regions provide a framework for understanding the formation of low-mass stars and the early evolution of planetary systems in general, direct information about the earliest solar system can only come from primitive meteorites and their components and some differentiated meteorites that record the birth of the solar system. The main objective of this proposal is to investigate the timescales and processes  including the role of supernovas  leading to the formation of the solar system by measurement of isotopic variations in meteorites. To achieve our objectives, we will integrate long-lived and short-lived radioisotope chronometers with the presence/absence of nucleosynthetic anomalies in various meteorites and meteoritic components. Our isotopic measurements will be obtained using state-of-the-art technologies such as second-generation mass spectrometers housed in laboratories directed by the PI and fully dedicated to cosmochemistry. This will allow us to: 1) define the mechanism and timescale for the collapse of the protosolar molecular cloud and emergence of the protoplanetary disk, 2) constrain the source and locale of chondrule-forming event(s) as well as the nature of the mechanism(s) required to transport chondrules to the accretion regions of chondrites, and 3) provide robust estimates of the timing and mechanism of asteroidal differentiation. We aim to understand how the variable initial conditions imposed by the range of possible stellar environments and protoplanetary disk properties regulated the formation and assemblage of disk solids into asteroidal and planetary bodies comprising our solar system.cStardust to asteroids: Unravelling the formation and earliest evolution of a habitable solar systemThe aim of this project is to forge a physical understanding of the transitions and of the turbulent flow of semi-dilute/dense non-colloidal suspensions, for different particle features and suspending fluids. It is estimated that 10% of the world energy consumption is due to the transport and handling of granular materials of which particle suspensions are an important part. A deep understanding of the mechanisms underlying the flow of particle suspensions, the transition to turbulence and the turbulence characteristics is crucial for many important practical applications involving engineered complex fluids, such as pastes and paper pulp. A better prediction and control of the flow of suspensions will therefore have a huge impact. Complex fluids are multiscale by nature w< here the physics at the microscale affects the macroscopic behaviour of the flow and vice versa giving rise to surprising and spectacular phenomena as well as making this one of the most important practical problem still to solve. Investigating the mechanisms by which the system microstructure determines the macroscopic flow properties and vice versa will not only give valuable insights into the nature of flowing suspensions but also will also lead to new ways to model and control it. Future generations of engineering CFD tools will have to contain models for complex suspensions. The fundamental approach proposed here, combined with challenging scientific and engineering examples backed up by experimental evidence, will make this possible and demonstrate it to a wider engineering community. The proposed project is based on highly accurate simulations of multiphase flow systems and state-of-the-art experiments. Such a holistic approach will enable us to understand the underlying mechanisms of instabilities and suspension turbulence and to develop accurate criteria for their prediction far in advance of what we could achieve with either approach separately.1TRansItions and Turbulence Of complex SuspensionsIn the last 10 years, power electronics has moved significantly towards the electric grid, making it more flexible and decentralized. Still important challenges remain. One of the most thrilling is re-inventing the distribution transformer after more than 125 years since its first use in the electrification of a city. In fact, actual distribution transformers can no longer fulfill the requirements of a modern electric grid highly dominated by distributed sources and new sizable loads, like heat pumps and electric vehicles. This project proposes the invention of a novel  Smart Transformer (ST), based on a modular architecture of units made by power electronics converters, that will be able to manage the energy and the information flows among sources and loads in the distribution area with the goal of decoupling it from the rest of the bulk power system. Actual proposals of Smart Transformers cannot compete in terms of cost, efficiency and reliability with traditional transformers. This project has decided to take this challenge with a paradigm shift in how to approach it and a new set of methodologies. The breakthrough results of this research will be obtained taking the following high-risk high-gain bet: significantly influence the efficiency and the reliability of the Smart Transformer by routing the energy flows among its power converter units. A new understanding of how the energy flows are managed by the modular connection of power converter units will guide the design of new architectures for the ST allowing different routes for the energy. Graph theory will be used to find optimal paths for the energy flows with the goal of maximizing efficiency and reliability. The energy flows will be managed by relying on information coming from the electric distribution system sensors (requirements) and from the power module sensors (constraints). The holy grail of this research is to provide a new durable heart to the electric distribution system.mThe Highly Efficient And Reliable smart Transformer (HEART), a new Heart for the Electric Distribution SystemUnderstanding the origin of the remarkable biodiversity in nature is an important goal in biological studies. Despite recent advances in evolutionary developmental biology, our understanding of the interaction between developmental genetic processes and the ecological environment in shaping the phenotype remains largely fragmented. This is mainly because of the difficulty to transfer molecular genetic tools to natural systems where we have a good understanding of the ecology. In this proposal, we combine original natural systems, water-walking insects, with state of the art tools of functional and developmental genetics, to study the interplay between developmental genetic pathways and the ecological environment, and how this interaction can shape adaptive phenotypic change. About 200 million years ago, the common ancestor of water-walking insects (Heteroptera, Gerromorpha) invaded water surface and radiated into a diverse array of niches, from shorelines to open oceans. This ecological transition and specialization is associated with an array of adaptive changes that enabled these insects to support their body weight and generate efficient propulsion on the water surface. In this project, we aim to develop a multilevel functional approach that combines developmental and evolutionary genetics, ecology, and comparative genomics and transcriptomics, to study a set of key morphological traits directly associated with the initial event of trans< ition to water surface life, and the diversification that followed. To achieve this, we chose three water-walking insects, along with a terrestrial and under-water outgroups, based on their morphology, ecology, and amenability for laboratory culturing and functional experiments. We will identify the genes and genetic changes responsible for the development and evolution of the hydrophobic bristles  a key trait that was instrumental in the transition from terrestrial to water surface life. In addition, we will identify the genetikWater-walking insects: marrying evo-devo with ecology for a better understanding of morphological evolution/Individual Robustness in Development and CancerThe fundamental limitation in our ability to dissect human diseases is the scarce availability of human tissues at relevant disease stages, which is particularly salient for neural disorders. Somatic cell reprogramming is overcoming this limitation through the derivation of patient-specific induced pluripotent stem cells (iPSC) that can be differentiated into disease-relevant cell-types. Despite these tantalizing possibilities, there are critical issues to be addressed in order to secure iPSC-modeling as a robust platform for the interrogation of disease aetiology and the development of new therapies. These concern the taming of human genetic variation, the identification of differentiation stages in which to uncover and validate phenotypes, and finally their translational into drug discovery assays. This project confronts these challenges focusing on the paradigmatic case of two rare but uniquely informative disorders caused by symmetric gene dosage imbalances at 7q11.23: Williams Beuren Syndrome and the subset of autism spectrum disorders associated to 7q11.23 microduplication. The hallmark of WBS is a unique behavioral-cognitive profile characterized by hypersociability and intellectual disability in the face of comparatively well-preserved language abilities. Hence, the striking symmetry in genotype and phenotype between WBS and 7dupASD points to the 7q11.23 cluster as a surprisingly small subset of dosage-sensitive genes affecting social behaviour and cognition. We build on a large panel of iPSC lines that we already reprogrammed from a unique cohort of WBS and 7dupASD patients and whose characterization points to specific derangements at the level of transcriptional/epigenetic control, protein synthesis and synaptic dysfunction. Through the integration of transcriptomic and epigenomic profiling with targeted mass spectrometry and gene network prediction we propose an innovative drug discovery pipeline for the identification of new therapeutic leads.Modeling Disease through Cell Reprogramming: a Translational Approach to the Pathogenesis of Syndromes Caused by Symmetrical Gene Dosage Imbalances!3D Euler, Vortex Dynamics and PDEiLarge Deviations and Non Equilibrium Phase Transitions for Turbulent Flows, Climate, and the Solar System[Non-Invasive In-Vivo Histology in Health and Disease Using Magnetic Resonance Imaging (MRI)The mammalian Target Of Rapamycin (mTOR) is a master regulator of growth. mTOR is a protein kinase that exists in two distinct complexes in the cell and transduces virtually all anabolic signals from the environment: nutrients, such as glucose and amino acids, growth factor peptides, such as insulin and insulin like growth factors, oxygen, mitochondrial metabolites, energy status. mTOR is required to sustain cell responses to nutrient availability including cell growth, proliferation, macromolecule biosynthesis, and suppress autophagy. During the past ten years we have generated and characterized a wide panel of mouse mutants in the mTOR pathway. We were involved in revealing specific phenotypes that increased our knowledge of mTOR roles in pathophysiology: mutants with small cells, mutants resistant to tumorigenesis in specific tissues and after specific oncogenic insults, mutants mimicking caloric restriction and promoting longevity, mutants with muscle dystrophy, mutants with altered insulin action. The overall goal of our research proposal for the next five years is twofold. From one hand we want to better understand fundamental processes including cell size control and organismal longevity. To this end we want to determine the molecular targets of the mTORC1/S6 kinase cassette that may explain the alterations in cell size and lifespan when these kinases are deregulated (project 1). From the other hand we want to understand and cure rare human genetic diseases that arise from pathological changes in the activity of the mTOR pathway in children or that may benefit from therapeutical intervention on this pathway. These diseases include Tuberous Sclerosis Complex, PEComas and hemangiomas (project 2), metabolic diseases (projects 3), lysosomal storage diseases (project 4). The translational approaches in this proposal will stem from a close interaction with multiple Medical Dept. in our shared research campus of the Necker Children Hospital.+mTOR pathophysiology in rare human diseasesbCancer is a devastating disease affecting 1 in 3 people in their lifetime. The incidence is rising because of our aging population and causes a huge economic impact on our society because of hospitalization and lost productivity. Radiotherapy alone or in combination with surgery and/or chemotherapy is used in ~50% of all patients and uses ionizing radiation to induce DNA breaks that are lethal to cells. While significant progress has been made, radiotherapy is often limited because of side-effects in normal tissues and tumor control often fails because of resistance and metastases. Novel treatment paradigms are urgently needed. Among the key classical biological factors that determine radiation response in normal and tumor cells are the 4R; Reoxygenation, Repopulation, Redistribution and Repair. They are determined by intrinsic (genetic) as well as extrinsic factors from the tumor microenvironment and underlie tumor heterogeneity a hallmark of cancers and a decisive factor in clinical response. Yet, standard cancer treatments are largely based on the flawed assumption that tumors are homogenous within and between patients. We hypothesized that NOTCH signaling and tumor hypoxia cause tumor heterogeneity and are tumor selective therapeutic targets. First we will study key biological mechanisms that determine intra tumor heterogeneity, second we will establish their role in therapy response and third we will exploit this knowledge to enhance radiotherapy and provide proof of concept of a highly innovative approach to selectively activate cancer therapeutics targeting the NOTCH stem cell pathway in therapy resistant tumor cells without adverse effects in normal tissues. DIRECT interrogates the molecular details of key cancer therapy response parameters providing opportunities for the next generation of tumor cell specific treatments that improve disease outcome.5Disabling Radiotherapy resistance in Cancer TreatmentIt is now accepted that exoplanets are ubiquitous. However little is known about those planets we have detected beyond the fact they exist and their location. For a minority, we know their weight, size and orbital parameters. For less than twenty, we have some clues about their atmospheric temperature and composition.<  How do we progress from here? We are still far from a hypothetical Hertzsprung Russell diagram for planets and we do not even know whether there ever will be such classification for planets. The planetary parameters mass, radius and temperature alone do not explain the diversity revealed by current observations. The chemical composition of these planets is needed to trace back their formation history and evolution, as was the case for the Solar System. Pioneering results were obtained through transit spectroscopy with Hubble, Spitzer and ground-based facilities, enabling the detection of ionic, atomic and molecular species and of the planet s thermal structure. With the arrival of improved or dedicated instruments in the coming decade, planetary science will expand beyond the narrow boundaries of our Solar System to encompass our whole Galaxy. In the next five years, ExoLights will address the following fundamental questions:  Why are exoplanets as they are?  What are the causes for the observed diversity?  Can their formation history be traced back from their current composition and evolution? New spectroscopic observations of a select sample of exoplanets atmospheres (~ 20 out of the 150 observable today) will be analysed with state-of-the art statistical techniques and interpreted through a comprehensive set of spectral retrieval models, developed by the PI and her team. This programme, together with the homogeneous re-analysis of archive observations of a larger sample of exoplanets, will allow us to use the chemical composition as a powerful diagnostic of the history, formation mechanisms and evolution of gaseous and rocky exoplanets."Decoding Lights from Exotic WorldsMaterials with strong electronic Coulomb correlations present unique electronic properties such as exotic magnetism, charge or orbital order, or unconventional optical or transport properties, including superconductivity, thermoelectricity or metal-insulator transitions. The concerted behavior of the electrons in these ``correlated materials" moreover leads to an extreme sensitivity to external stimuli such as changes in temperature, pressure, or external fields. This tuneability of even fundamental properties is both a harbinger for technological applications and a challenge to currently available theoretical methods: Indeed, these properties are the result of strong electron-electron interactions and subtle quantum correlations, and cannot be understood without a proper description of excited states. The aim of the present project is to elaborate, implement and test new approaches to investigate the spectral and optical properties of correlated materials ``from first principles", that is, without adjustable parameters. I will build on the success of state-of-the-art dynamical mean field-based electronic structure techniques, but aim at developing them into truly first-principles methods, where a full treatment of the long-range Coulomb interactions replaces the current practice of purely local Hubbard interaction parameters. My target materials are among the most interesting for modern technologies, such as transition metal oxides (with potential applications ranging from oxide electronics to battery materials) and rare earth compounds used as environmentally-responsible pigments. Establishing first-principles techniques with truly predictive power for these classes of materials will bring us closer to the final goal of tailoring correlated materials with preassigned properties.Predictive electronic structure calculations for materials with strong electronic correlations: long-range Coulomb interactions and many-body screeningControl of cell migration is crucial for many biological processes. Cells sense mechanical cues to guide their migration. As opposed to passive materials, living cells actively respond to the mechanical stimuli of their environment through the transduction of mechanical information into biochemical signaling events. These responses, particularly to rigidity, include differentiation, migration and alterations in cell-matrix and cell-cell adhesion and thus occur over a wide range of time and length scales. I propose to address the effect of substrate mechanical properties on cell migration using quantitative in vitro methods based on micro-fabrication and micro-mechanical techniques. My main objectives are to: 1/ Discover specific mechanisms that guide single cells toward stiffer substrates (a process known as durotaxis), investigate the range of stiffness-sensitive responses and determine the molecular mechanisms based on actin dynamics and cell adhesion assembly. 2/ Characterize the emergence of coordinated cell movements and thus how cells move in concert under external mechanical constraints. In addition to cell-substrate interactions, the role of cell-cell junctions is crucial in the transmission of mechanical signals over the cell population. By analyzing tissue dynamics at both mesoscopic and molecular scales, we hope to unravel how epithelial cell sheets mechanically integrate multiple adhesive cues to drive collective cell migration.3/ Elucidate the role of 3D mechanical environments in collective cell migration. In contrast to migration in 2D, cells in 3D must overcome the biophysical resistance of their surrounding milieu. Based on optical and innovative micro-fabrication techniques to modify the stiffness of 3D scaffolds, we will study its influence on cell migration modes and invasion. The goal of this interdisciplinary project is to understand how cells integrate mechanical adhesive signals to adapt their internal organization and ensure tissue integrity+Cell Migration under Mechanical ConstraintsExperience with adeno-associated virus (AAV) vector-mediated gene transfer in human trials has unveiled the therapeutic potential of this approach, with some of the most exciting results coming from clinical studies of gene transfer for hemophilia B, congenital blindness, and the recent market approval of the first AAV-based gene therapy in Europe. Follow-up data of subjects treated with AAV vectors is showing sustained correction of the disease phenotype for several years after gene transfer, and recent data confirmed that AAV vectors can drive expression of a transgene in humans for >10 years. With clinical development, however, some of the limitations of the approach, not entirely identified in preclinical studies, became obvious; in particular it is well established that the host immune system represents an< important obstacle to be overcome in terms of both safety and efficacy of gene transfer in vivo with AAV vectors. The overall goal of this proposal is to gain critical, missing knowledge on the interactions between AAV vectors and the immune system in order to develop strategies to achieve safe, effective, and long-lasting gene transfer in humans. In this proposal we will: 1) Define the molecular signatures of the immune system in humans undergoing gene transfer with AAV vectors using cutting-edge, high-content immunophenotyping technologies; 2) Study the role of anti-AAV antibodies as determinants of AAV capsid immunogenicity using both in vitro and in vivo systems; 3) Identify novel pharmacological and cellular approaches to overcome T cell immunity to AAV; 4) Develop novel strategies to overcome pre-existing antibody responses to AAV. This proposal exploits the knowledge and the skills available in our lab to develop new tools and to provide novel, basic insights into the human immune responses to AAV that will have a direct impact on the quality of life of patients affected by inherited disorders.QMolecular signatures and Modulation of immunity to Adeno-Associated Virus vectorsIBy far, most evolutionary research has focused on the changes that occur in the germline of individuals across generations, within and between species. For different reasons, much less attention has been given to the process of change within the somatic line of a multicellular individual. The formation of cancer tumors due to uncontrolled cell proliferation is one of the most prominent forms of somatic evolution. The evolution of cancer tumors in a body can be likened with the evolution of populations in more or less fragmented habitats. The tumor is usually a expanding population of clonal cells, which may differentiate to a bigger or lesser extent (population structure) and disperse to contiguous (range expansion) or more distant tissues (long distance colonization). During tumor progression, this population of cells is subject to distinct somatic evolutionary processes like mutation, drift, selection or migration, which can act at different points in time and geographical space. Very recently, the discovery of extensive intratumor heterogeneity, together with the rise of single cell genomics, has created an unique opportunity to study the phylogeography of cancer tumor cells. So far evolutionary inferences drawn from cancer genomes have been mostly qualitative. Here we propose to study a thousand single cell genomes from different regions in primary tumors and matched metastases. We will develop and apply state-of-the-art statistical and computational techniques from phylogenetics, phylogeography and population genomics to understand the tempo and mode of evolution of cell lineages within and between cancer tumors. By doing so we aim to construct a robust theoretical and methodological evolutionary framework that can contribute to a better understanding of the process of somatic evolution and shed light into the biology of cancer.:Phylogeography and somatic evolution of cancer tumor cellsHairy Cell Leukemia (HCL), a chronic B-cell neoplasm, is initially sensitive to chemotherapy with purine analogs, but ~40% of patients eventually relapses and becomes less responsive to these drugs. Furthermore, purine analogs may cause myelotoxicity, immune-suppression and severe opportunistic infections. Therefore, molecularly-targeted less toxic drugs are highly desirable in HCL. However, its low incidence and the initial efficacy of purine analogs has made HCL an orphan in the world of cancer research and has spoiled the academic and industrial interest in developing better treatments for this disease. But recently we identified the V600E activating mutation in the BRAF kinase as the key genetic lesion of HCL (similar to BCR-ABL1 in chronic myeloid leukemia). Orally available specific BRAF inhibitors (e.g., Vemurafenib) have in the meantime showed remarkable efficacy in melanoma patients harboring the BRAF-V600E mutation, although resistance to such drugs eventually develops in this malignancy through reactivation of MEK (the downstream target of BRAF). The ground-breaking objective of this project is to introduce for the first time in HCL, by means of phase-2 investigator-driven pilot clinical trials, the concept of BRAF and/or MEK inhibition as an oral, non chemotherapy-based, entirely out-patient, genetics-driven and rationally designed treatment strategy, first in patients with active disease despite (or severe toxicity from) previous chemotherapy with purine analogs, and then, potentially, in the frontline setting. In comparison to melanoma, deeper and longer effect of BRAF inhibition may be expected in HCL, due to its much lower genetic complexity and proliferation rate. Anyway, potential mechanisms of resistance will be searched for to identify other genes recurrently mutated or aberrantly expressed in HCL patients developing resistance to BRAF inhibition (if any), and the clinical feasibility of combined BRAF and MEK inhibition will be addressed.7Genetics-driven targeted therapy of Hairy Cell LeukemiaITransport, mixing and reaction of solutes and particles in natural media are of central importance in many fields of science and engineering, ranging from contaminant dispersion in geophysical flows to diffusion in living cells. Transport in these intrinsically heterogeneous media is characterized by early and late solute and particle arrivals, tailed spatial distributions, and scale effects in measured parameters. These behaviors cannot be explained by available models based on Fick s law and are called anomalous despite their ubiquity. The origin of such phenomena lies in heterogeneity-induced mixing processes that lead to fluctuations in chemical concentration, or, in other words, to physical non-equilibrium. Current transport formulations based on the advection-dispersion-reaction equation or phenomenological non-equilibrium models lack the relation to the heterogeneity controls, fail to describe mixing and concentration variability and thus are not suited for the quantification of chemical reactions. The main objective of this proposal is to establish a global predictive framework that quantifies mixing across scales, anomalous transport and reaction, and dynamic uncertainty for heterogeneous media. We propose an integrated approach that links the interrelated phenomena of mixing, anomalous transport and chemical reaction. In     !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijkmnopqrstuvwxyz{|}~ short, the idea consists in quantifying microscale heterogeneity-induced mixing in terms of the flow kinematics and heterogeneity structure and linking it to transp< ort through its relation to Lagrangian particle dynamics. These dynamics will be quantified stochastically by a novel generalized continuous time random walk approach and used to model chemical reactions under physical non-equilibrium in order to obtain a new solid approach for simulating reactive and conservative transport through natural media.Mixing in Heterogeneous Media Across Spatial and Temporal Scales: From Local Non-Equilibrium to Anomalous Chemical Transport and Dynamic UncertaintyThe expansion of a dilute gas through a gasdynamics convergent-divergent nozzle can occur in three different regimes, depending on the inlet and discharge conditions and on the gas: via a fully subsonic expansion, via a subsonic-supersonic or via a subsonic-supersonic-subsonic expansion embedding a compression shock wave within the divergent portion of the nozzle. I devised an exact solution procedure for computing nozzle flows of real gases, which allowed me to discover that in molecularly complex fluids eighteen additional different flow configurations are possible, each including multiple compression classical shocks as well as non classical rarefaction ones. Modern thermodynamic models indicate that these exotic regimes can possibly occur in nozzle flows of molecularly complex fluids such as hydrocarbons, siloxanes or perfluorocarbons operating close to the liquid-vapour saturation curve and critical point. The experimental observation of one only of these eighteen flow configurations would be sufficient to prove for the first time that non classical gasdynamics phenomena are indeed possible in the vapour region of a fluid with high molecular complexity To this purpose, a modification to the blow-down wind tunnel for dense gases at Politecnico di Milano is proposed to use mixtures of siloxane fluids. Measurements are complemented by numerical simulations of the expected flow field and by state-of-the-art uncertainty quantification techniques. The distinctive feature of the proposed experiment is the adoption of mixture of siloxanes as working fluids. Mixtures of siloxanes are well known to exhibit an higher stability limit than their pure components, due to the redistribution process occurring at high temperature. The increased understanding of real-gas dynamics will enable to improve the design of Organic Rankine Cycle Engines, to be used in small scale energy production from biomasses, binary geothermal systems and concentrating solar thermal power plants.DNon classical rarefaction shock-waves in molecularly complex vapoursCell-to-cell communication pathways coordinate cellular functions in multicellular organisms. Cells that are nearest neighbours can communicate through specific interactions between ligand and receptor proteins present in their respective cell membranes. The objective of this research program is to address the hypothesis that the physical context of the ligand/receptor interaction contributes to defining the fundamental mechanisms of action of cell-to-cell communication pathways and their cellular outcomes. The research program relies on the development of tools that provide well-defined physical inputs to cells, not confounded by simultaneous changes in chemical inputs. Therefore, beyond state-of-the-art developments in nanotechnology are here integrated with cell biology. In particular, DNA origami technology is applied to the development of ligand nanoclusters with customized spatial organization and mechanical properties. These ligand nanoclusters are used to probe the roles of physical properties of the ligand presentation on the activation of intracellular signalling pathways. We will focus on the ephrin/Eph cell-to-cell communication pathway, which regulates embryonic development and the homeostasis of adult organs. ephrin/Eph signalling is commonly disrupted in cancer, showing tumour suppressing or tumour promoting character. The mechanisms that generate the diversity of outcomes of the ephrin/Eph pathway are largely unknown. We will use DNA origami/ephrin ligand nanoclusters to investigate whether the spatial organization and mechanical properties of ephrin ligand assemblies impact Eph receptor function and contribute to generating diversity in the pathway. Our novel approach is readily transferrable to the study of other signalling pathways. We aim to generate a knowledge foundation for the roles of mechanotransduction, the conversion of physical to biochemical signals, in cell-to-cell communication mediated by membrane-bound ligands and receptors.1Mechanotransduction in Cell-to-Cell CommunicationlThis project explores the relationship between climate change and human behaviour. During the harshest conditions of the last ice age European human populations abandoned northern latitudes, with their range contracting to southern regions. By the time ice sheets retreated and large areas of land became available for resettlement there had been a hiatus of at least 7000 years. This project examines the recolonisation of these Northern regions which took place during a period of rapid climate change, the last major global warming event on earth. As people move eastwards and northwards increasing diversification is seen in their stone and bone tool industries which indicate human development. This project examines whether climate a) drove the human dispersal and development, b) played a more indirect role, or c) was of little significance to humans at this time. State-of-the-art scientific techniques (radiocarbon dating, DNA, stable isotope, clumped isotope and charcoal ring width analyses) will be used to create integrated chronological, palaeoclimatic and palaeoecological frameworks that are directly linked to the Late and Final Palaeolithic archaeological record. Temporal and spatial trends in climate change, prey abundance and behaviour, and technological development will be compared and considered in light of regional and global climate trends and archaeological evidence for hunting strategies, human mobility and landscape use. Such data will provide an insight into the conditions Palaeolithic people experienced and how this influenced their perceptions of the landscape they inhabited and the decisions they made.BCOLONISATION AND CULTURAL DIVERSIFICATION IN UNFAMILIAR LANDSCAPES^Molecular Subtype Specific Stem Cell Dynamics in Developing and Established Colorectal CancersUltra-sensitive NMR in liquidsThe nuclear magnetic resonance spectroscopy (NMR) is a versatile and powerful tool, especially in chemistry and in biology. However, its limited sensitivity and small amount of suitable probe nuclei pose severe constraints on the systems that may be explored.This project aims at overcoming the above limitations by giving NMR an ultra-high sensitivity and by enlarging the NMR "toolbox" to dozens of nuclei across the periodic table. This will be achieved by applying the -NMR method to the soft matter samples. The method relies on anisotropic emission of  particles in the decay of highly spin-polarized nuclei. This feature results in 10 orders of magnitude more sensitivity compared to conventional NMR and makes it applicable to elements which are otherwise difficult to investigate spectroscopically. -NMR has been successfully applied in nuclear physics and material < science in solid samples and high-vacuum environments, but never before to liquid samples placed in atmospheric pressure. With this novel approach I want to create a new universal and extremely sensitive tool to study various problems in biochemistry.The first questions which I envisage addressing with this ground-breaking and versatile method concern the interaction of essential metal ions, which are spectroscopically silent in most techniques, Mg2+, Cu+, and Zn2+, with proteins and nucleic acids. The importance of these studies is well motivated by the fact that half of the proteins in our human body contain metal ions, but their interaction mechanism and factors influencing it are still not fully understood. In this respect NMR spectroscopy is of great help: it provides information on the structure, dynamics, and chemical properties of the metal complexes, by revealing the coordination number, oxidation state, bonding situation and electronic configuration of the interacting metal.My long-term aim is to establish a firm basis for -NMR in soft matter studies in biology, chemistry and physics.aMonitoring bone healing around endosseous implants: from multiscale modeling to the patient s bedImplants are often employed in orthopaedic and dental surgeries. However, risks of failure, which are difficult to anticipate, are still experienced and may have dramatic consequences. Failures are due to degraded bone remodeling at the bone-implant interface, a multiscale phenomenon of an interdisciplinary nature which remains poorly understood. The objective of BoneImplant is to provide a better understanding of the multiscale and multitime mechanisms at work at the bone-implant interface. To do so, BoneImplant aims at studying the evolution of the biomechanical properties of bone tissue around an implant during the remodeling process. A methodology involving combined in vivo, in vitro and in silico approaches is proposed. New modeling approaches will be developed in close synergy with the experiments. Molecular dynamic computations will be used to understand fluid flow in nanoscopic cavities, a phenomenon determining bone healing process. Generalized continuum theories will be necessary to model bone tissue due to the important strain field around implants. Isogeometric mortar formulation will allow to simulate the bone-implant interface in a stable and efficient manner. In vivo experiments realized under standardized conditions will be realized on the basis of feasibility studies. A multimodality and multi-physical experimental approach will be carried out to assess the biomechanical properties of newly formed bone tissue as a function of the implant environment. The experimental approach aims at estimating the effective adhesion energy and the potentiality of quantitative ultrasound imaging to assess different biomechanical properties of the interface. Results will be used to design effective loading clinical procedures of implants and to optimize implant conception, leading to the development of therapeutic and diagnostic techniques. The development of quantitative ultrasonic techniques to monitor implant stability has a potential for industrial transfer. Over the past years, carbon nanomaterial such as graphene and carbon nanotubes (CNTs) have attracted the interest of scientists, because some of their properties are unlike any other engineering material. Individual graphene sheets and CNTs have shown a Youngs Modulus of 1 TPa and a tensile strength of 100 GPa, hereby exceeding steel at only a fraction of its weight. Further, they offer high currents carrying capacities of 10^9 A/cm, and thermal conductivities up to 3500 W/mK, exceeding diamond. Importantly, these off-the-chart properties are only valid for high quality individualized nanotubes or sheets. However, most engineering applications require the assembly of tens to millions of these nanoparticles into one device. Unfortunately, the mechanical and electronic figures of merit of such assembled materials typically drop by at least an order of magnitude in comparison to the constituent nanoparticles. In this ERC project, we aim at the development of new techniques to create structured assemblies of carbon nanoparticles. Herein we emphasize the importance of controlling hierarchical arrangement at different length scales in order to engineer the properties of the final device. The project will follow a methodical approach, bringing together different fields of expertise ranging from macro- and microscale manufacturing, to nanoscale material synthesis and mesoscale chemical surface modification. For instance, we will pursue combined top-down microfabrication and bottom-up self-assembly, accompanied with surface modification through hydrothermal processing. This research will impact scientific understanding of how nanotubes and nanosheets interact, and will create new hierarchical assembly techniques for nanomaterials. Further, this ERC project pursues applications with high societal impact, including energy storage and water filtration. Finally, HIENA will tie < relations with EU s rich CNT industry to disseminate its technologic achievements.We will use modern techniques in algebraic geometry, originating from string theory and mirror symmetry, to study fundamental problems of classical flavour. More concretely, we apply wall-crossing in the derived category to the birational geometry of moduli spaces. Bridgeland stability is a notion of stability for complexes in the derived category. Wall-crossing describes how moduli spaces of stable complexes change under deformation of the stability condition, often via a birational surgery occurring in its minimal model program (MMP). This relates wall-crossing to the most basic question of algebraic geometry, the classification of algebraic varieties. Our previous results additionally provide a very direct connection between Bridgeland stability conditions and positivity of divisors, the main tool of modern birational geometry. This makes the above link significantly more effective, precise and useful. We will exploit this in the following long-term projects: 1. Prove a Bogomolov-Gieseker type inequality for threefolds that we conjectured previously. This would provide a solution in dimension three to well-known open problems of seemingly completely different nature: the existence of Bridgeland stability conditions, Fujita's conjecture on very ampleness of adjoint line bundles, and projective normality of toric varieties. 2. Study the birational geometry of moduli space of sheaves via wall-crossing, adding more geometric meaning to their MMP. 3. Prove that the MMP for local Calabi-Yau threefolds is completely induced by deformation of Bridgeland stability conditions. The motivation is a derived version of the Kawamata-Morrison cone conjecture, classical questions on Chern classes of stable bundles, and mirror symmetry. 4. Answer major open questions on the birational geometry of the moduli space of genus zero curves (for example, the F-conjecture) using exceptional collections in the derived category and wall-crossing.Longitudinal omics data hold great promise to improve biomarker detection and enable dynamic individualized predictions. Recent technological advances have made proteomics an increasingly attractive option but clinical longitudinal proteomic datasets are still rare and computational tools for their analysis underdeveloped. The objective of this proposal is to create a roadmap to detect clinically feasible protein markers using longitudinal data and effective computational tools. A biomedical focus is on early detection of Type 1 diabetes (T1D). Specific objectives are: 1) Novel biomarker detector using longitudinal data. DynaOmics introduces novel types of multi-level dynamic markers that are undetectable in conventional single-time cross-sectional studies (e.g. within-individual changes in abundance or associations), develops optimization methods for their robust and reproducible detection within and across individuals, and validates their utility in well-defined samples. 2) Individualized disease risk prediction dynamically. DynaOmics develops dynamic individualized predictive models using the multi-level longitudinal proteome features and novel statistical and machine learning methods that have previously not been used in this context, including joint models of longitudinal and time-to-event data, and one-class classification type techniques. 3) Dynamic prediction of T1D. DynaOmics builds a predictive model of dynamic T1D risk to assist early detection of the disease, which is crucial for developing future therapeutic and preventive strategies. T1D typically involves a relatively long symptom-free period before clinical diagnosis but current tools to predict early T1D risk have restricted power. The objectives involve innovative and unconventional approaches and address major unmet challenges in the field, having high potential to open new avenues for diagnosis and treatment of complex diseases and fundamentally novel insights towards precision medicine.Fully recyclable and low cost electronic goods are still far from reality. My interest is in creating environmental friendly advanced functional materials and processes able to result in new class of paper based electronic products. This represents a reborn of the paper millenary industry for a plethora of low cost, recyclable and disposable electronics, putting Europe in the front line of a new era of consumer electronics. While the vision of the proposal is a very ambitious one, my ground-breaking research work to date related with oxide based transistors on paper (from which I am one of the co-inventors) has contributed to the basic technological breakthroughs needed to create the key elements to establish a new era of paper electronics. Field effect transistors (FETs), memory and CMOS devices, with excellent electronic performance and using paper as substrate and dielectric have resulted from my recent work. What I am proposing now is to reinvent the concept of paper electronics. In NEW_FUN I want to develop a completely new and disruptive approach where functionalized cellulose fibers will be used not only as dielectric but also as semiconductor and conductor able to coexist in a multilayer paper structure. That is, assembling paper that can have different functionalities locally, on each face or even along its entire thickness/bulk. This way issues such as failure under bending, mechanical robustness and stability can be minimized. Doing so, electronic and electrochemical devices can be produced not only on paper but also from paper. The outputs of NEW_FUN will open the door to turn paper into a real electronic material making possible disposable/recyclable electronic products, such as smart labels/packages (e.g. food and medicine industry), sensors for air quality control (car, house and industry environments); disposable electronic devices such as bio-detection platforms, lab-on-paper systems, among others. Elections are the foundation for democratic decision making. This research program will examine the effects of biased and privately informed entities election organizers on the ability of elections to aggregate information: Existing theory demonstrates that large electorates can reach correct decisions by aggregating information dispersed among many voters. However, existing theory does not account for the ubiquitous presence of biased organizers who intend to affect the election outcome. Examples of biased organizers may include a CEO holding a shareholder vote, a regional government holding a referendum, and political parties in general elections. This project will develop and analyze new models of voting that account for the effects of biased organizers on information aggregation. One of the examples I consider is an election organizer who can increase voter participation at some cost (e.g., through advertising). Preliminary work suggests that the presence of biased organizers has significant impact. As increasing participation becomes cheap, equilibria < exist where the election organizer recruits a large number voters and yet the majority votes almost surely for the organizer s favorite policy. This failure of information aggregation contrasts starkly with existing results for elections in which the number of voters is exogenously large. I will study the effectiveness of institutional safeguards against such manipulation, including supermajority rules, publicity requirements, and the regulation of communication to voters, and I will apply the theory in the context of shareholder voting and corporate control. Thus, this research program has important implications for the design of elections in realistic voting scenarios. Recent surveys have revealed an amazing, and yet unexplained, diversity of planets orbiting other stars. The key to understanding and exploiting this diversity is to study their atmospheres. This is because exoplanets atmospheres are unique laboratories that hold the potential to transform our understanding of planet formation, physics, and habitability. This is a new opportunity to place the Solar System and the Earth s ecosystem in a broader context; one of the main goals of modern astrophysics. The aim of this proposal is to leverage exoplanet detections, as well as observational capabilities and theoretical frameworks, to deepen and broaden our understanding of planetary physics. This project will transform the field of exoplanet atmospheres by contributing to three major advances. We will: i) push exoplanet characterization new frontiers by providing the largest in-depth study of atmospheres through the measurements of precise spectra, and the retrieval of their composition, in order to constrain their origins; ii) reveal for the first time global exo-climate through a novel method to probe atmospheric structure and dynamics; and iii) pioneer an innovative approach that uses robotic small telescopes to estimate the impact of stellar radiation on atmospheres, with a particular focus on their habitability. Theses objectives will be achieved via an ambitious portfolio of cutting-edge observations, combined with state-of-the-art modelling for their interpretation. Their accomplishment would be a major breakthrough, culminating in a comprehensive comparative exoplanetology, which in turn will open up new key discoveries in planetary formation and evolution. Our expertise will also enable predictions on conditions for habitability and direct the search atmospheric biosignatures with upcoming capabilities. The impact of our discoveries will go well beyond the scientific community since the quest of our origins is of interest to mankind. Fundamental research on respiratory transport phenomena, quantifying momentum and mass transfer in the lung depths, is overwhelmingly focused on adults. Yet, children are not just miniature adults; their distinct lung structures and heterogeneous ventilation patterns set them aside from their parents. In RespMicroFlows, we will break this cycle and unravel the complex microflows characterizing alveolar airflows in the developing pulmonary acini. Our discoveries will foster ground-breaking transport strategies to tackle two urgent clinical needs that burden infants and young children. The first challenge relates to radically enhancing the delivery and deposition of therapeutics using inhalation aerosols; the second involves targeting liquid bolus installations in deep airways for surfactant replacement therapy. By developing advanced in silico numerical simulations together with microfluidic in vitro platforms mimicking the pulmonary acinar environment, our efforts will not only deliver a gateway to reliably assess the outcomes of inhaling aerosols and predict deposition patterns in young populations, we will furthermore unravel the fundamentals of liquid bolus transport to achieve optimal surfactant delivery strategies in premature neonates. By recreating cellular alveolar environments that capture underlying physiological functions, our advanced acinus-on-chips will deliver both at true scale and in real time the first robust and reliable in vitro screening platforms of exogenous therapeutic materials in the context of inhaled aerosols and surfactant-laden installations. Combining advanced engineering-driven flow visualization solutions with strong foundations in transport phenomena, fluid dynamics and respiratory physiology, RespMicroFlows will pave the way to a new and unprecedented level in our understanding and quantitative mapping of respiratory flow phenomena and act as catalyst for novel targeted pulmonary drug delivery strategies in young children. bIn recent years general relativity (GR) has become an increasingly important new tool in areas of physics beyond its traditional playground in astrophysics. The main motivation for this comes from the AdS/CFT correspondence which conjectures an equivalence between gravity in anti-de Sitter (AdS) spaces and certain conformal field theories (CFT s). Via this correspondence, GR now plays a key role in improving our understanding of non-gravitational physics < at strong coupling. The AdS/CFT correspondence naturally leads to the study of GR in dimensions greater than four and/or in AdS spaces. Our current understanding of GR in these new settings is rather limited but it has been realized that the physics of gravity can be significantly different than in the 4d asymptotically flat case. Moreover, to access these new gravitational phenomena numerical methods have been and will be essential. However, the use of numerical GR beyond the traditional 4d asymptotically flat case is still in its infancy. The goal of this project is to improve our understanding of GR in higher dimensions and/or AdS spaces using numerical techniques. To achieve this goal, we will focus on the study of the following topics: 1. Develop stable codes for doing numerical GR in AdS and higher dimensions. We will use numerical GR and the AdS/CFT correspondence to study out of equilibrium phenomena in strongly coupled CFT s. We will also use numerical GR to understand the endpoint of the various black hole instabilities and thereby address long standing conjectures in GR. 2. New types of stationary black holes. We will use numerical GR to numerically construct new types of black holes in higher dimensions and in AdS, with novel topologies and fewer symmetries than the known ones. We shall apply them to the study of equilibrium configurations in strongly coupled gauge theories at finite temperature.The aim of this proposal is to identify, at the molecular level, the minimal topological and structural motifs that govern the membrane translocation of short peptides. A covalent reversible bond strategy will be developed for the synthesis of self-adaptive penetrating peptides (adaptamers) for targeted delivery. It is known that the recently developed therapeutic technologies (i.e. gene therapy, chemotherapy, hyperthermia, etc.) cannot reach their expected potential due to limitations in the current delivery strategies, which hinder the efficient targeting of the appropriate tissues, cells and organelles. Despite the enormous therapeutic potential of short penetrating peptides, these molecules suffer from drawbacks such as toxicity, instability to protease digestion and lack of specificity. Dynamic covalent chemistry has significant synthetic advantages. In the proposed research, peptide scaffolds with clickable reversible groups (e.g. hydrazide) will be conjugated with collections of aldehydes to afford self-adaptive biomimetic transporters, whose secondary structure and penetrating properties will be systematically characterized by biophysical, cell-biology and pattern recognition techniques. The versatility of dynamic supramolecular  peptide adaptamers with precisely positioned protein ligands will be explored for multivalent specific recognition, protein transport, cell targeting of drugs and probes and membrane epitoping. Additionally, we propose to synthesise dynamic and environmentally sensitive fluorescent probes for biocompatible membrane labelling and uptake signalling. The resulting discoveries of this research will allow the formulation of novel transfecting reagents for gene therapy, selective platforms for drug-delivery and the development of dynamic fluorescent membrane probes. The potential results of this proposal will shake the fields of drug-delivery and non-viral gene transfection and will resolve the limitations of the current approaches.The field of attosecond science is now entering the second decade of its existence, with good prospects for breakthroughs in a number of areas. We want to take the next step in this development: from mastering the generation and control of attosecond pulses to breaking new marks starting with the simplest systems, atoms. The aim of the present application is to advance the emerging new research field  Ultrafast Atomic Physics , where one- or two-electron wave packets are created by absorption of attosecond pulse(s) and analyzed or controlled by another short pulse. Our project can be divided into three parts: 1. Interferometric measurements using tunable attosecond pulses H< ow long time does it take for an electron to escape its potential? We will measure photoemission time delays for several atomic systems, using a tunable attosecond pulse source. This type of measurements will be extended to multiple ionization and excitation processes, using coincidence measurements to disentangle the different channels and infrared ionization for analysis. 2. XUV pump/XUV probe experiments using intense attosecond pulses How long does it take for an atom to become an ion once a hole has been created? Using intense attosecond pulses and the possibility to do XUV pump/ XUV probe experiments, we will study the transition between nonsequential double ionization, where the photons are absorbed simultaneously and all electrons emitted at the same time and sequential ionization where electrons are emitted one at a time. 3. "Complete" attosecond experiments using high-repetition rate attosecond pulses We foresee a paradigm shift in attosecond science with the new high repetition rate systems based on optical parametric chirped pulse amplification which are coming to age. We want to combine coincidence measurement with angular detection, allowing us to characterize (two-particle) electronic wave packets both in time and in momentum and to study their quantum-mechanical properties.4A systematic and novel, multi-scale model based catalyst design methodology will be developed. The fundamental nature of the models used is unprecedented and will represent a breakthrough compared to the more commonly applied statistical, correlative relationships. The methodology will focus on the intrinsic kinetics of (potentially) large-scale processes for the conversion of renewable feeds into fuels and chemicals. Non-ideal behaviour, caused by mass and heat transfer limitations or particular reactor hydrodynamics, will be explicitly accounted for when simulating or optimizing industrial-scale applications. The selected model reactions are situated in the area of biomass upgrading to fuels and chemicals: fast pyrolysis oil stabilization, glycerol hydrogenolysis and selective oxidation of (bio)ethanol to acetaldehyde. For the first time, a systematic microkinetic modelling methodology will be developed for oxygenates conversion. In particular, stereochemistry in catalysis will be assessed. Two types of descriptors will be quantified: kinetic descriptors that are catalyst independent and catalyst descriptors that specifically account for the effect of the catalyst properties on the reaction kinetics. The latter will be optimized in terms of reactant conversion, product yield or selectivity. Fundamental relationships will be established between the catalyst descriptors as determined by microkinetic modelling and independently measured catalyst properties or synthesis parameters. These innovative relationships allow providing the desired, rational feedback in from optimal descriptor values towards synthesis parameters for a new catalyst generation. Their fundamental character will guarantee adequate extrapolative properties that can be exploited for the identification of a groundbreaking next catalyst generation.Annually 1.2 million new cases of colorectal cancer (CRC) are seen worldwide and over 50% of patients die of the disease making it a leading cause of cancer-related mortality. A crucial contributing factor to these disappointing figures is that CRC is a heterogeneous disease and tumours differ extensively in the clinical presentation and response to therapy. Recent unsupervised classification studies highlight that only a proportion of this heterogeneity can be explained by the variation in commonly found (epi-)genetic aberrations. Hence the origins of CRC heterogeneity remain poorly understood. The central hypothesis of this research project is that the cell of origin contributes to the phenotype and functional properties of the pre-malignant clone and the resulting malignancy. To study this concept I will generate cell of origin- and mutation-specific molecular profiles of oncogenic clones and relate those to human CRC samples. Furthermore, I will quantitatively investigate how mutations and the cell of origin act in concert to determine the functional characteristics of the pre-malignant clone that ultimately develops into an invasive intestinal tumour. These studies are paralleled by the investigation of stem cell dynamics within established human CRCs by means of a novel marker independent lineage tracing strategy in combination with mathematical analysis techniques. This will provide critical and quantitative information on the relevance of the cancer stem cell concept in CRC and on the degree of inter-tumour variation with respect to the frequency and functional features of stem-like cells within individual CRCs and molecular subtypes of the disease. I am convinced that a better and quantitative understanding of the dynamical properties of stem cells during tumour development and within established CRCs will be pivotal for an improved classification, prevention and treatment of CRC. The rate at which research labs, enterprises and governments accumulate data is high and fast increasing. Often, these data are collected for no specific purpose, or they turn out to be useful for unanticipated purposes: Companies constantly look for new ways to monetize their customer databases; Governments mine various databases to detect tax fraud; Security agencies mine and cross-associate numerous heterogeneous information streams from publicly accessible and classified databases to understand and detect security threats. The objective in such Exploratory Data Mining (EDM) tasks is typically ill-defined, i.e. it is unclear how to formalize how interesting a pattern extracted from the data is. As a result, EDM is often a slow process of trial and error. During this fellowship we aim to develop the mathematical principles of what makes a pattern interesting in a very subjective sense. Crucial in this endeavour will be research into automatic mechanisms to model and duly consider the prior beliefs and expectations of the user for whom the EDM patterns are intended, thus relieving the users of the complex task to attempt to formalize themselves what makes a pattern interesting to them. This project will represent a radical change in how EDM research is done. Currently, researchers typically imagine a specific purpose for the patterns, try to formalize interestingness of such patterns given that purpose, and design an algorithm to mine them. However, given the variety of users, this strategy has led to a multitude of algorithms. As a result, users need to be data mining experts to understand which algorithm applies to their situation. To resolve this, we will develop a theoretically solid framework for the design of EDM systems that model the user's beliefs and expectations as much as the data itself, so as to maximize the amount of useful information transmitted to the user. This will ultimately bring the power of EDM within reach of the non-expert. Tracking the early traces of life preserved in very old rocks and reconstructing the major steps of its evolution is an exciting and most challenging domain of research. How amazing it is to have a cell that is 1.5 or 3.2 billion years old under a microscope! From these and other disseminated fragments of life preserved along the geological timescale, one can build the puzzle of biosphere evolution and rising biological complexity. The possibility that life may exist beyond Earth on other habitable planets lies yet at another scale of scientific debates and popular dreams. We have the chance now to live at a time when technology enable us to study in the finest details the very old record of life, or to land on planets with microscope and analytical tools, mimicking a geologist exploring extraterrestrial rocky outcrops to find traces of water and perhaps life. There is still a lot to be done however, to solve major questions of life evolution on Earth, and to look for unambiguous life traces, on Earth or beyond. The project ELiTE aims to provide key answers to some of these fundamental questions. Astrobiology studies the origin, e< volution and distribution of life in the Universe, starting with life on Earth, the only biological planet known so far. The ambitious objectives of the project ELiTE are the following: 1) The identification of Early traces of life and their preservation conditions, in Precambrian rocks of established age 2) The characterization of their biological affinities, using innovative approaches comprising micro to nanoscale morphological, ultrastructural and chemical analyses of fossil and recent analog material 3) The determination of the timing of major steps in evolution. In particular, the project ELiTE aims to decipher two major and inter-related steps in early life evolution and the rise of biological complexity: the evolution of cyanobacteria, responsible for Earth oxygenation and ancestor of the chloroplast, influencing drastically the evolution of life and the planet Earth, and the evolution of the domain Eucarya since LECA (Last Eucaryotic Universal Ancestor). 4) The determination of causes of observed pattern of evolution in relation with the environmental context (oxygenation, impacts, glaciations, tectonics, nutrient availability in changing ocean chemistry) and biological innovations and interactions (ecosystems evolution). Objective 1 has implications for the search for unambiguous traces of life on Earth and beyond Earth. Objectives 2 to 4 have implications for the understanding of causes and patterns of biological evolution and rise of complexity in Earth life. Providing answers to these most fundamental questions will have major impact on our understanding of early life evolution, with implications for the search for life beyond Earth.Biological systems are robust to perturbations, with many genetic, stochastic and environmental challenges having no or little phenotypic consequence. However, the extent of this robustness varies across individuals, for example the same mutation or treatment may only affect a subset of individuals. The overall objective of this project is to understand the cellular and molecular mechanisms that confer this robustness and why it varies across individuals. We will address three specific questions: 1. Why do inherited mutations have different outcomes in different individuals, even when they are genetically identical and share a common environment? 2. What are the mechanisms during development that confer robustness to mechanical deformation? 3. How can the loss of robustness be exploited to specifically kill cancer cells? To address the first two questions, we will use live imaging procedures that we have developed that make the C. elegans embryo a unique animal system to link early inter-individual variation in gene expression and cellular behaviour to later variation in phenotypes. To address the third question, we will apply our understanding of genetic robustness and genetic interaction networks in model organisms to the comprehensive analysis of cancer genome datasets. The predictions from these hypothesis-driven computational analyses will then be evaluated using wet-lab experiments. Understanding and predicting variation in robustness is both a fundamental challenge for biology and one that is central to the development of personalised and predictive medicine. A patient does not want to know the typical outcome of a mutation or treatment; they want to know what will actually happen to them. The work outlined here will contribute to our basic understanding of robustness and its variation among individuals, and it will also directly tackle the problem of predicting and targeting variation in robustness as a strategy to kill tumour cells.G protein-coupled receptors make up both the largest membrane protein and drug target families. DE-ORPHAN aims to determine the close functional context; specifically physiological agonists and signaling pathways; and provide the first research tool compounds, of orphan peptide receptors. Determination of physiological agonists (aka de-orphanization), by high-throughput screening has largely failed. We will introduce a new research strategy: 1) developing highly innovative bioinformatics methods for handpicking of all orphan receptor targets and candidate ligand screening libraries; and 2) employing a screening technique that can measure all signaling pathways simultaneously. The first potent and selective pharmacological tool compounds will be identified by chemoinformatic design of focused screening libraries. We will establish the ligands structure-activity relationships important for biological activity and further optimization towards drugs. The first potent and selective Gs- and G12/13 protein inhibitors will be designed by structure-based re-optimization from a recent crystal structure of a Gq-inhibitor complex, and applied to determine orphan receptor signaling pathways and ligand pathway-bias. They will open up for efficient dissection of important signaling networks and development of drugs with fewer side effects. DE-ORPHANs design hypotheses are based on unique computational methods to analyze protein and ligand similarities and are founded on genomic and protein sequences, structural data and ligands. The interdisciplinary research strategy applies multiple ligands acting independently but in concert to provide complementary receptor characterization. The results will allow the research field to advance into studies of receptor functions and exploitation of druggable targets, ligands and mechanisms. Which physiological insights and therapeutic breakthroughs will we witness when these receptors find their place in human pharmacology and medicine?Graphene is a new class of promising material with exceptional properties and thus warrants a plethora of potential applications in various domains of science and technology. However, due to intrinsic zero bandgap and inherently low solubility, a prerequisite for the use of graphene i< n several applications is its controlled and reproducible functionalization in a nanostructured fashion. Being a  surface-only nanomaterial, its properties are extremely sensitive not only to chemical modification but also to noncovalent interactions with simple organic molecules. A systematic knowledge base for targeted functionalization of graphene still eludes the scientific community. The present experimental protocols suffer from important shortcomings. Firstly, graphene functionalization occurs randomly in solution based methods and there is scarcity of methods that can exert precise control over how and where the reactions/interactions occur. Secondly, due to random functionalization, producing reproducible samples of structurally uniform graphene and graphitic materials remains a major challenge. Lastly, a molecular level understanding of the functionalization process is still lacking which precludes systematic strategies for manipulation of graphene and graphitic materials. NANOGRAPH@LSI aims to develop systematic experimental protocols for controlled and reproducible (covalent, non-covalent as well as the combination of both) functionalization of graphene and graphitic materials in a nanostructured fashion at the liquid-solid interface (LSI), along with the implementation of new nanoscale characterisation tools, targeting a broad range of applications in the fields of electronics, i.e. graphene bandgap engineering, sensing, and separation. Supramolecular self-assembly of organic building blocks at the liquid-solid interface will be employed as a basic strategy. In view of the above mentioned applications, also upscaling protocols will be developed and implemented.The origin of Harmonic Analysis goes back to the study of the heat diffusion, modeled by a differential equation, and the claim made by Fourier that every periodic function can be represented as a series of sines and cosines. In this statement we can find the motivation to many of the advances that have been made in this field. Partial Differential Equations model many phenomena from the natural, economic and social sciences. Existence, uniqueness, convergence to the boundary data, regularity of solutions, a priori estimates, etc., can be studied for a given PDE. Often, Harmonic Analysis plays an important role in such problems and, when the scenarios are not very friendly, Harmonic Analysis turns out to be fundamental. Not very friendly scenarios are those where one lacks of smoothness either in the coefficients of the PDE and/or in the domains where the PDE is solved. Some of these problems lead to obtain the boundedness of certain singular integral operators and this drives one to the classical and modern Caldern-Zygmund theory, the paradigm of Harmonic Analysis. When studying the behavior of the solutions of the given PDE near the boundary, one needs to understand the geometrical features of the domains and then Geometric Measure Theory jumps into the picture. This ambitious project lies between the interface of three areas: Harmonic Analysis, PDE and Geometric Measure theory. It seeks deep results motivated by elliptic PDE using techniques from Harmonic Analysis and Geometric Measure Theory.This project is built upon results obtained by the applicant in these three areas. Some of them are very recent and have gone significantly beyond the state of the art. The methods to be used have been shown to be very robust and therefore they might be useful towards its applicability in other regimes. Crucial to this project is the use of Harmonic Analysis where the applicant has already obtained important contributions.Neutrinoless double beta decay is a hypothetical, very slow radioactive process whose observation would establish unambiguously that massive neutrinos are Majorana particles --- that is to say, identical to their antiparticles ---, which implies that a new physics scale beyond the Standard Model must exist. Furthermore, it would prove that total lepton number is not a conserved quantity, suggesting that this new physics could also be the origin of the observed asymmetry between matter and antimatter in the Universe. In recent years, many innovative ideas have been put forward to improve the sensitivity of \bbonu\ experiments. In general, these propositions have sought to increase the number of experimental signatures available to reject backgrounds while attempting to use isotopes and detector techniques which can be more easily scaled to large masses. The objective of this project is to realize the NEXT experiment, an innovativedetector based on a high-pressure xenon gas (HPXe) TPC that will run at the Laboratorio Subterr\'aneo de Canfranc (LSC), in Spain. Our primary goal is to complete the construction and commissioning of a 150 kg HPXe TPC (NEXT-100) by 2014, and start a physics run in 2015 that can improve the present bound set by the EXO experiment and perhaps discover the Majorana nature of neutrinos. In addition, we will carry out an R\&D program focused in demonstrating the scalability of the technology to the ton scale.The success of modern medical treatments such as cellular therapy and targeted treatments requires appropriate tools for in vivo monitoring. Imaging modalities, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) are key candidates due to their noninvasive nature. However, these imaging techniques are extremely expensive and can involve radiation, both of which hinder their longitudinal and repetitive use. Ultrasound has so far been unsuitable due to the absence of a label to differentiate regions of interest from tissue background, the main problem being that current ultrasound contrast agents (CAs) have active lifetimes in the order of minutes. The CoNQUeST platform (Clinical Nanoparticles for Quantitative Ultrasound with high STability) proposed here is an entirely new type of ultrasound CA that is extremely stable (lifetime of a year) and is not affected by insonation. This mechanism of contrast generation appears completely novel: The polymeric particles are under 200nm in diameter and must contain a soluble metal (M.Srinivas et al., patent pending, filed 09/2012). Based on the current state of the art, these particles are too small and do not contain the requisite gaseous component for ultrasound contrast. CoNQUeST particles are applicable to longitudinal and repeated imaging, as is necessary for< cell tracking, due to their stability. Furthermore, these particles can be chemically bound to targeting agents, dyes and drugs, and are suitable for multimodal imaging, including MRI (both 1H and 19F), fluorescence and SPECT. Finally, the CoNQUeST agents are suitable for clinical use. I propose the application of the CoNQUeST agents to a clinical trial for tracking dendritic cell therapy in melanoma patients, longitudinal theranostic imaging in preclinical models and thorough characterisation of this novel mechanism of ultrasound contrast generation.Influenza viruses cause a significant seasonal disease burden and continually threaten to initiate human pandemics. Antivirals are available for treatment of influenza, however drug-resistant viruses often emerge. Thus, there is urgent need to develop new antivirals with lower chances of selecting resistance. As viruses rely extensively on cellular functions, one way to minimise resistance is to target new antivirals against host factors. This concept requires a fundamental understanding of mechanisms underpinning the interplay between influenza viruses and their hosts. In this project, we will investigate the role that host SUMO pathways play during influenza virus replication. SUMO proteins are important regulators of cell signalling, and are covalently linked to other proteins in order to alter structure, localization or function. As such, SUMO conjugation regulates many diverse aspects of biology. Our own work shows that global cellular SUMOylation increases during influenza virus infection, and that virus replication is severely impaired when cells are depleted of key enzymes and components required for general SUMO conjugation. Here, we will determine what viral components trigger SUMOylation, and which specific cellular enzymes are involved. We will characterize where in the cell SUMO conjugates accumulate, and for the first time apply large-scale affinity-based quantitative proteomics to the identification of proteins that become SUMO modified during infection. A key aim will be to correlate changes to the SUMO sub-proteome with the function of specific host SUMO-modifying enzymes, thereby establishing the mechanistic role of these modifications during virus replication. Understanding basic mechanisms underlying SUMOylation during influenza virus infection will provide new insights into the fundamental biology of these important pathogens. The work could also lead to identification of key cellular pathways that can be exploited as novel therapeutic targetsThis project will develop novel techniques for solving inverse problems in life sciences, in particular related to dynamic imaging. Major challenges in this area are efficient four- dimensional image reconstruction under low SNR conditions and further the quantification of image series as obtained from molecular imaging or life microscopy techniques. We will tackle both of them in a rather unified framework as inverse problems for time-dependent (systems of) partial differential equations. In the solution of these inverse problems we will investigate novel approaches for the following aspects specific to the above-mentioned problems in the life sciences: 1. Solution of inverse problems for PDEs in complex time-varying geometries 2. Development of appropriate variational regularization models for dynamic images, including noise and motion models 3. Improved forward and inverse modelling of cellular and intracellular dynamics leading to novel inverse problems for nonlinear partial differential equations 4. Construction and implementation of efficient iterative solution methods for the arising 4D inverse problems and their variational formulation All tasks will be driven by concrete applications in biology and medicine and their success will be evaluated in applications to real problems and data. This is based on interdisciplinary work related to electrocardiology and developmental biology. The overall development of methods will however be carried out in a flexible and modular way, so that they become accessible for larger problem classes.WIn recent breakthrough publications, the effect of fluctuations on the affinity of membrane-confined molecules has been evaluated, and a quantitative model for the time evolution of small adhesion domains has been developed under my leadership. Now I propose to bring my research to a new level by tackling the problem of active and passive organisation of proteins into macromolecular structures on fluctuating fluid membranes, using a physicist s approach across established disciplinary boundaries. The formation and transport of supramolecular complexes in membranes is ubiquitous to nearly all functions of biological cells. Today, there is a variety of experiments suggesting that macromolecular complexes act as scaffolds for free proteins, overall yielding obstructed diffusion, counterbalanced by active transport by molecular motors. However, an integrative view connecting complexation and transport is largely missing. Furthermore, the effects of membrane mediated interactions and (non)-thermal fluctuations were so far overlooked. Gaining a quantitative insight into these processes is key to understanding the fundamental functioning of cells. Together with my carefully selected team, I will address these intrinsically biological problems, by means of theoretical physics. Phenomena such as active and anomalous transport, as well as complexation are also currently subject to intense research in the statistical and soft matter physics communities. In this context, the aim of this proposal is to bridge the divide between the two worlds and significantly contribute to both physics and the life sciences by developing general principles that can be applied to processes in cells. Resolving these issues is of fundamental importance since it would identify how interactions on the cell surface arise, and may translate directly into pharmaceutical applications.Although protein dynamics plays an essential role in function, it is rarely considered explicitly in current structure-based approaches to drug design. Here I propose the computer-aided design of ligands by modulation of protein dynamics, or equivalently, protein structural ensembles. The detailed understanding of ligand-induced per< turbations of protein dynamics that will result from this study is crucial not just to accurately predicting binding affinities and tackling "undruggable" targets, but also to understanding protein allostery. Three major aims will be pursued during this project. First, I will combine concepts from chemoinformatics and non-equilibrium thermodynamics to detect cryptic "druggable" small molecule binding sites in computed structural ensembles. New computational methods will be developed to predict how binding at these putative sites is likely to influence protein function. This will enable rational approaches to allosteric control of protein function. Second, new classes of non-equilibrium sampling algorithms will be developed to improve by 2-3 orders of magnitude the speed of computation of protein/ligand structural ensembles by molecular simulations. This will enable routine consideration of protein flexibility in ligand optimisation problems. Third, I will address with the above methods a frontier problem in molecular recognition: the rational design of protein isoform-specific ligands. To achieve this goal, I will integrate computation with experiments and focus efforts on the therapeutically relevant cyclophilin protein family. Experimental work will involve the use of purchased or custom-synthesized competitive and allosteric ligands in enzymatic assays, calorimetry and crystal structure analyses. Overall, this project proposes fundamental advances in our ability to quantify and engineer protein-ligand interactions, therefore expanding opportunities for the development of future small molecule therapeutics.-A key challenge for the 21st century is, therefore to provide billions of people with the means to access, move and manipulate, what has become, huge volumes of information. The environmental and economic implications becoming serious, making energy efficient data communications key to the operation of today s society. In this project, the Principal Investigator will develop a new framework for optical interconnects and provide a common platform that spans Fibre-to-the-home to chip-to-chip links, even as far as global on-chip interconnects. The project is based on the efficient coupling of the Photonic Crystal resonators with the outside world. These provide the ultimate confinement of light in both space and time allowing orders of magnitude improvements in performance relative to the state of the art, yet in a simpler simple system- the innovator s dream. New versions of the key components of optical links- light sources, modulators and photo-detectors- will be realised in this new framework providing a new paradigm for energy efficient communication.tIn this project, I will explore the unique combination of two fascinating research themes: electrospinning and plasma technology. Electrospun nanofibrous matrices (so-called mats) are an exciting class of materials with a wide range of possible applications. Nevertheless, the development and functionalization of these electrospun materials remain very challenging tasks. Atmospheric pressure plasma technology will be utilized by my research group to create advanced biodegradable electrospun mats with unprecedented functionality and performance. To realise such a major breakthrough, plasma technology will be implemented in different steps of the manufacturing process: pre-electrospinning and post-electrospinning. My group will focus on four cornerstone research lines, which have been carefully chosen so that all critical issues one could encounter in creating advanced biodegradable electrospun mats are tackled. Research cornerstone A aims to develop biodegradable electrospun mats with appropriate bulk properties, while in research cornerstone B pre-electrospinning polymer solutions will be exposed to non-thermal atmospheric plasmas. This will be realized by probing unexplored concepts such as discharges created inside polymer solutions. In a third cornerstone C, an in-depth study of the interactions between an atmospheric pressure plasma and an electrospun mat will be carried out. Finally, the last cornerstone D will focus on plasma-assisted surface modification of biodegradable electrospun mats for tissue engineering purposes. Realization of these four cornerstones would result in a major breakthrough in their specific field which makes this proposal inherently a relatively high risk/very high gain proposal. I therefore strongly believe that this research program will open a whole new window of opportunities for electrospun materials with a large impact on science and society.Every time we grab an object to look at its geometrical details or to feel if it is hard or soft, we are ineluctably confronted with the limits of our senses. Behind its appearances, the object may still hide information that, encrypted in its microscopic features, remains undetected to our macroscopic assessment. In life sciences, those limits are more than just frustrating: they are an obstacle to study and detect life threatening conditions. Many different instruments may overcome those limits, but the vast majority of them rely either on  sight (optics) or  touch (mechanics) separately. On the contrary, I believe that it is from the combination of those two  senses that we have more chances to tackle the future challenges of cell biology, tissue engineering, and medical diagnosis. Inspired by this tantalizing perspective, and supported by a technology that I have brought from blackboard to market, I have now designed a scientific program to breach into the microscopic scale via an unbeaten path. The program develops along three projects addressing the three most relevant scales in life sciences: cells, tissues, and organs. In the first project, I will design and test a new optomechanical probe to investigate how a prolonged mechanical loa< d on a brain cell of a living animal may trigger alterations in its Central Nervous System. With the second project, I will develop an optomechanical tactile instrument that can assess how subsurface tissues deform in response to a mechanical stroke  a study that may change the way physicians look at tissue classification. For the third project, I will deliver an acousto-optical gas trace sensors so compact that can penetrate inside the lungs of an adult patient, where it could be used for early detection of pulmonary life threatening diseases. Each project represents an opportunity to open an entire new field, where optics and micromechanics are combined to extend our senses well beyond their natural limits.Coherent control and sensitive detection of quantum states in condensed matter are among the most topical challenges of modern physics. They drive the development of novel materials, theoretical concepts, and experimental methods to advance our understanding of fundamental laws of quantum mechanics and to create transformative technologies for future applications. During the past decades carbon has emerged as a new material platform to address these challenges: graphene and carbon nanotubes have been created as paradigm systems with exceptional physical properties. As atomically-thin cylinders carbon nanotubes combine ultra-low mass with extreme mechanical stiffness. This identifies them as perfect candidates for the realization of ultra-high quality mechanical resonators with applications in quantum metrology and sensing. Their crystalline lattice can be made free of nuclear spins by material engineering to ensure ultra-long electron spin coherence times for quantum information processing and coherent spintronics. In addition, semiconducting single-wall carbon nanotubes exhibit optical resonances with unprecedented tunability in color for quantum communication and cryptography. These outstanding material properties form the basis for our scientific research proposal. Our vision is to realize up-conversion schemes interfacing light with spin, mechanical, and spin-mechanical degrees of freedom in carbon nanotube devices. In particular, we will study spin dynamics in carbon nanotubes with an isotopically engineered nuclear spin lattice and we will suspend individual carbon nanotubes in high-fidelity optical micro-cavities to detect and control mechanical motion down to the quantum ground state. Ultimately, our devices will realize entirely novel regimes of quantum states by hybridizing light with magnetic or mechanical excitations and explore the foundations of emerging technologies at the quantum limit.This proposal deals with a collection of problems in PDE arising from fluid mechanics.The primary motivation is the understanding of the evolution of isolated vortex lines for 3D Euler. The importance of the evolution of vorticity in incompressible fluid mechanics is very well known. To date, only nonrigorous approaches are known to try to obtain an evolution equation for isolated vortex lines. Two desingularization procedures are carried out (including a time renormalization) to obtain an evolution equation (the binormal equation). While an isolated vortex line does not fit any known concept of solution (given the singularity of the velocity), and there has been significant recent activity on the nonuniqueness of solutions of Euler (De Lellis & Szekelyhidi, and recently Isett) it is expected that the geometric assumptions made about the solution will still make it possible to find a suitable concept of solution. In the proposal I describe an approach that should help to rigorously understand vortex lines. It is motivated by a programme developed for the Surface Quasi-Geostrophic (SQG) equation with C. Fefferman and for some related desingularized models with my student Zoe Atkins (Nov 2012 PhD). SQG has been of great interest in the PDE community due to the striking similarities it exhibits with 3D Euler. In particular, the evolution of sharp fronts for SQG corresponds to the evolution of vortex lines. In recent years I have developed an approach that overcomes the divergences known to exist for the velocity field (as in 3D Euler). The positive results obtained for SQG motivate the methodology and tools described in the proposal, including the construction of solutions with very large gradients and simple geometry and the use of a measure-theoretic approach to identify fundamental curves within these objects. Surprising connections with other equations motivate some other directions and linked projects, for example with Prandtl and boundary layer ther theory.Chemotherapy is, after surgery, the second most efficient therapy against cancer. However, it has many side effects for cancer patients because anticancer drugs kill cancer cells but also healthy ones. My project aims at synthesizing new metal-containing compounds that 1) are poorly toxic in the dark; 2) can be attached via a light-sensitive bond to liposomes that will carry them into cancer cells; and 3) detach from their carriers and become toxic upon light irradiation, thus killing cancer cells. These new compounds contain ruthenium, a metal combining photochemical and anticancer properties. I will replace the weakly bound chloride ligands of known cytotoxic ruthenium compounds by strongly bound sulfur ligands. By doing so, the DNA- and protein-binding ability of the ruthenium compounds will be lowered, which will lower their toxicity in the dark. Thioether-lipid conjugates will be used to attach the ruthenium prodrugs to liposomes carriers that are well taken up by cancer cells. Techniques to irradiate tumors in vivo are nowadays available in the clinics. By shining light onto the ruthenium-enriched cancer cells photochemical cleavage of the Ru-S bond will take place, thus detaching the metal complex from its carrier and allowing it for binding to biological molecules. Thus, the ruthenium prodrug will be transformed inside cancer cells into a highly toxic molecule that will kill the cells. I will study mononuclear compounds and molecules containing several ruthenium centres; visible light activation and near infrared light activation. The final aim is to obtain ruthenium-functionalized liposomes that are poorly toxic in the dark, preferentially go into cancer cells, and become toxic at the place of irradiation, using light that penetrates well into biological tissues. Because of this unique combination of properties my new light-activatable ruthenium prodrugs will ultimately lead to selective anticancer treatment showing low side effects for cancer patients.Computational simulations of natural phenomena are essential in science, engineering, product design, architecture, and computer graphics applications. However, despite progress in numerical algorithms and computational power, it is still unfeasible to compute detailed simulations at large scales. To make matters worse, important phenomena like turbulent splashing liquids and fracturing solids rely on delicate coupling between small-scale details and large-scale behavior. Brute-force computation of such phenomena is intractable, and current adaptive techniques are too fragile, too costly, or too crude to capture subtle instabilities at small scales. Increases in computational power and parallel algorithms will improve the situation, but progress will only be incremental until we address the problem at its source. I propose two main app< roaches to this problem of efficiently simulating large-scale liquid and solid dynamics. My first avenue of research combines numerics and shape: I will investigate a careful de-coupling of dynamics from geometry, allowing essential shape details to be preserved and retrieved without wasting computation. I will also develop methods for merging small-scale analytical solutions with large-scale numerical algorithms. (These ideas show particular promise for phenomena like splashing liquids and fracturing solids, whose small-scale behaviors are poorly captured by standard finite element methods.) My second main research direction is the manipulation of large-scale simulation data: Given the redundant and parallel nature of physics computation, we will drastically speed up computation with novel dimension reduction and data compression approaches. We can also minimize unnecessary computation by re-using existing simulation data. The novel approaches resulting from this work will undoubtedly synergize to enable the simulation and understanding of complicated natural and biological processes that are presently unfeasible to compute. iPes project aims to provide adequate support to Dr. David Mecerreyes (DM) who is at the stage of consolidating an independent research team. During his scientific career, DM has demonstrated creative thinking and excellent capacity to carry out research and going beyond the state of the art. His meritorious record of research, scientific publications (128 ISI articles, h index = 33), project conception, private sector experience, networking ability (participated in 10 European collaborative projects) and capacity for supervising and coordinating a research team are presented in detail in the initial part of the proposal. He recently moved from the private sector to create a new research group at the University of the Basque Country. He is now in an excellent academic position and research environment to commit and be devoted to an ERC frontier research project. DM s proposal passed to the second stage in the ERC starting grant call of last year. This year the research project has been re-built taking into account his group directions and the detected weak points of last year s proposal. This is his last opportunity for participating to the ERC starting-grant call. iPes proposes an innovative research programme at the forefront of polymer chemistry. The proposal goes in depth into the topic of energetic polymers. iPes activities will fully develop the field of polymers for energy storage by using an innovative macromolecular engineering approach generating the ground for future innovations. The main S&T goal is to obtain new polymeric materials, to get an insight into their unique electronic properties, to model the new energetic polymers and to investigate their application in innovative battery prototypes. These technologies are currently dominated by inorganic electrode materials. iPes aims at bringing polymer chemistry to a next level and developing basic knowledge about innovative polymeric materials which may open up new opportunities for Energy Storage.Understanding of the normal and diseased brain crucially depends on reliable knowledge of its microstructure. Important functions are mediated by small cortical units (columns) and even small changes in the microstructure can cause debilitating diseases. So far, this microstructure can only be determined using invasive methods such as, e.g., ex-vivo histology. This limits neuroscience, clinical research and diagnosis. My research vision is to develop novel methods for high-resolution magnetic resonance imaging (MRI) at 3T-9.4T to reliably characterize and quantify the detailed microstructure of the human cortex. This MRI-based histology will be used to investigate the cortical microstructure in health and focal cortical degeneration. Structure-function relationships in visual cortex will be elucidated in-vivo, particularly, ocular dominance columns and stripes. Specific microstructural changes in focal cortical degeneration due to Alzheimer s disease and monocular blindness will be determined, including amyloid plaque imaging. To resolve the subtle structures and disease related changes, which have not previously been delineated in-vivo by anatomical MRI, unprecedented isotropic imaging resolution of up to 250 m is essential. Methods for high-resolution myelin and iron mapping will be developed from novel quantitative MRI approaches that I have previously established. Super-resolution diffusion and susceptibility imaging will be developed to capture the neuropil microstructure. Anatomical imaging will be complemen< ted by advanced high-resolution functional MRI. The multi-modal MRI data will be integrated into a unified model of MRI contrasts, cortical anatomy and tissue microstructure. My ambitious goal of developing in vivo MRI-based histology can only be achieved by an integrative approach combining innovations in MR physics, modelling and tailored (clinical) neuroscience experiments. If successful, the project will transform research and clinical imaging.Quantum Chromodynamics (QCD) is one of the cornerstones of the Standard Model of particle physics. It describes the world of quarks, anti-quarks and gluons (partons) making up the protons and neutrons and therewith the ordinary matter in our universe. Collisions of protons and heavy nuclei at unprecedented energies in the Large Hadron Collider (LHC) at CERN enable experiments that will uncover mechanisms and symmetries underlying the Standard Model. In experiments at the LHC, as in many other high-energy physics experiments, QCD plays a crucial role as a toolbox. It employs the property that at very high energies, or equivalently very short distances, the transition of protons to partons is a long distance phenomenon that can be encoded through parton probabilities and decay functions, which incorporate the complex structure of the proton itself. Earlier I have revealed a new element in QCD: specific momentum-spin correlations can also be encoded in terms of (polarized) parton probabilities, collectively known as transverse momentum dependent (TMD) distribution and fragmentation functions. Experimental results have confirmed the applicability and the necessity of including the novel correlations in QCD in order to cope with current and upcoming experimental results. This proposal outlines my ambitions to develop the next generation of the QCD toolbox. I want to break with the restrictions of the collinear approximation for partons in high-energy processes and develop the full QCD dynamics underlying the novel correlations, study their universality and make them into workable tools that enable a full manipulation of spins and momenta of the partons for understanding experimental results at all frontiers, energy and precision. The results of this enterprise will affect the entire field of high-energy/nuclear physics and open up new windows to reveal the fundaments of the Standard Model through dedicated experiments at present-day and future facilities.YThe formation and evolution of clusters and proto-clusters of galaxies will be studied using unique diagnostic tools provided by the new pan-European radio telescope LOFAR and the APERTIF phased arrays on WSRT radio telescope. Combined with new ultra low frequency antennas (an extension to LOFAR here proposed), these new facilities will for the first time enable sensitive observations from the lowest possible frequencies accessible from the ground (~15 MHz) up to 1400 MHz. The guaranteed time projects (PI HR) to carry out ultra deep pointed observations and to survey the entire northern sky will be unique in terms of angular resolution, depth, and extremely large frequency range. This enables a coherent study of clusters of galaxies over the entire history of the universe up to the formation of the first proto-clusters. Studies of the associated shock waves produced by cluster mergers and the magnetic field properties of the cluster gas will constrain models of the formation of galaxy clusters.The large field of views of both LOFAR will enable the detection of radio emission from millions of star-forming galaxies up to z=2-3, at the epoch at which the bulk of galaxy formation is believed to have occurred. In combination with infrared surveys, the first significant sample of proto-clusters of galaxies will be obtained. This will enable the first complete study of the overall properties of proto-clusters and their galaxy contents.With LOFAR s ability to pinpoint radio sources with extremely steep radio spectra, we will detect radio galaxies at unprecedented distances. As our previous radio and optical investigations have established that distant radio galaxies are often located in proto-clusters, the most distant LOFAR radio galaxies would be excellent targets to locate and study the first proto-clusters close to or even at the epoch of reionisation.This project is an anthropological study of how citizenship is being reconfigured through hybrid forms of governance. It will research these transformations by focusing on public-private  security assemblages , with particular emphasis on the role of the private security industry. Much recent scholarly debate has focused on shifting modes of governance in a context of neoliberal globalization. Specific attention has focused on how governance is increasingly achieved through networks or assemblages of state, corporate and voluntary actors. Such assemblages of state and non-state actors blur the lines between public and private, and between local, national and transnational. This research will extend this debate by investigating the implications this form of governance has for how different groups enact and experience citizenship, concentrating on public-private security assemblages as hybrid, multi-scalar governance structures. It will examine how forms of  differentiated citizenship are produ< ced, and how political subjectivities shift, as a result of these forms of security governance. These transformations in citizenship will be analyzed through a multi-sited, comparative analysis of security assemblages in Jerusalem (Israel), Kingston (Jamaica) and Nairobi (Kenya). The project will research the composition, operation and regulation of public-private security assemblages, with special attention to the global mobilities of security experts and expertise. In each setting, the project will study the practices and discourses that structure relations between state and non-state security providers, clients and those seen as threats. It will focus on the  security encounter between these different actors, in which new social relationships and subjectivities are produced. The project is expected to lead to the development of an anthropological theory of security governance with both theoretical and applied relevance.A revolution is underway, as molecular magnets are establishing a fundamental link between spintronics, molecular electronics and quantum computation. On the other hand, we know almost nothing on how a magnetic molecule is affected by electrons flowing through it or by the excitation of a molecular group. OptoQMol will investigate these uncharted waters by developing innovative, ultra-clean methods that will provide information inaccessible to established procedures. This will allow an unprecedented study of the interplay of electronic and spin degrees of freedom in magnetic molecules and of its possible use for quantum logic. OptoQMol is a strongly multidisciplinary project, and makes use of an innovative mix of chemical and physical methods to overcome present experimental limitations, both in terms of time resolution and cleanliness. Instead of placing a magnetic molecule between bulk electrodes, we will directly grow photoactive groups on the molecule, so that electrons will flow through or close to the spin centers after a light pulse. This affords an ultra-clean system that can be studied in bulk, with a perfectly defined geometry of the magnetic and electronic elements. We will then combine optical and electron paramagnetic resonance techniques with ns time resolution, so as to observe the effect of electron flow on the spins in real time and measure the spin quantum coherence. Eventually we will use these innovative methods to control the interactions among spins and perform quantum logic operations. The success of OptoQMol will answer two fundamental questions: How do molecular spins interact with flowing electrons? How can we use electronic excitations to perform quantum logic operations between multiple electron spins? The results will open a totally new area of experimental and theoretical investigation. Moreover they will redefine the limits and possibilities of molecular spintronics and allow quantum logic operations among multiple electron spins.The aim of this project is to predict and compute extremely rare but essential trajectories in complex physical systems. We will compute rare transitions trajectories, first between two different turbulent attractors in models of planetary jet dynamics, and second between two configurations of ocean currents for a model of the thermohaline circulation. We will compute the dynamics and the probability for collisions between two planets in the solar system, on time scales of order of billions of years. We will evaluate rare events that lead to extremely large drags or torques on objects embedded in turbulent flows, directly from the dynamics. Because of the huge range of time scales, all those trajectories are not accessible through direct numerical simulations. The project's unity stems from the methodology based on large-deviations theory. Large deviation rate functions generalize the concept of entropy or free energy in non-equilibrium extended systems: they provide a global characterization of their most probable state, their large fluctuations and their phase transitions. Impressive explicit computations of large deviation rate functions have been recently performed in simple non-equilibrium systems. The main aim of this project is to bridge the gap between those extremely interesting new concepts and algorithms, and complex dynamical systems such as turbulent flows, semi-realistic models of fluids related to climate dynamics, or the long time behavior of the solar system. In order to achieve this goal, we will use macroscopic fluctuation theory, instanton theory, and other analytical methods in order to compute explicitly large deviation rate functions for essential macroscopic quantities (the velocity or density fields). We will also develop and use algorithms specifically dedicated at computing the statistics of extremely rare trajectories, based on the generalization of importance sampling implemented through cloning or multilevel splitting methods.The Target Of Rapamycin (TOR) proteins are ser/thr kinases conserved in Eukarya. They nucleate two distinct multiprotein complexes, named TORC1 and TORC2, which regulate many, widely varying, aspects of cell and organism physiology. TOR inhibitors, such as rapamycin and derivatives, are used clinically to treat cancer, cardio-vasculature disease and to prevent organ rejection. We recently reported that both TORC1/2 are wired in feedback loops, where their downstream cellular effectors are at the same time upstream regulators. It is this feedback loop that ultimately mediates the intrinsic role of TORC1/2 in cellular homeostasis: TORC1/2 detects deviations from a steady-state condition and by means of these feedback loops returns the cell to its homeostatic situation. We propose to systematically identify the TORC1/2 homeostatic signalling loops. Subsequent characterization will focus on the signalling networks controlling intermediary metabolism. Our ultimate goal is to comprehensively unravel the TORC1/2-dependent metabolic networks composed of regulatory feedback loops which will reveal the fundamental role of the TOR Complexes as molecular devices to achieve cellular homeostasis.Significant parts of our cultural heritage are produced on the Web, yet only insufficient opportunities exist for accessing and exploring the past of the Web. The ALEXANDRIA project aims to develop models, tools and techniques necessary to archive and index relevant parts of the Web, and to retrieve and explore this information in a meaningful way. While the easy accessibility to the current Web is a good baseline, optimal access to Web archives requires new models and algorithms for retrieval, exploration, and analytics which go far beyond what is needed to access the current state of the Web. This includes taking into account the unique temporal dimension of Web archives, structured semantic information already available on the Web, as well as social media and network information. Within ALEXANDRIA, we will significantly advance semantic and time-based indexing for Web archives using human-compiled knowledge available on the Web, to efficiently index, retrieve and explore information about entities and events from the past. In doing so, we will focus on the concurrent evolution of this knowledge and the Web content to be inde< xed, and take into account diversity and incompleteness of this knowledge. We will further investigate mixed crowd- and machine-based Web analytics to support long- running and collaborative retrieval and analysis processes on Web archives. Usage of implicit human feedback will be essential to provide better indexing through insights during the analysis process and to better focus harvesting of content. The ALEXANDRIA Testbed will provide an important context for research, exploration and evaluation of the concepts, methods and algorithms developed in this project, and will provide both relevant collections and algorithms that enable further research on and practical application of our research results to existing archives like the Internet Archive, the Internet Memory Foundation and Web archives maintained by European national libraries.With the ground-breaking discovery of a new, Higgs-like boson on July 4th, 2012, by the CMS and ATLAS collaborations at CERN, a new era of particle physics has begun. The discovery is the first step in answering an unsolved problem in particle physics, the question how fundamental bosons and fermions acquire their mass. One of the major goals in collider physics in the next few years will be the deeper insight into the nature of the new particle, its connection to the known fundamental particles and possible extensions beyond the standard model (SM) of particle physics. My project aims at a particular interesting field to study, the relation of the new particle with the heaviest known elementary particle, the top quark. I aim to develop new, innovative techniques and beyond state-of-the-art methods to extract the Yukawa coupling between the top quark and the Higgs boson, which is expected to be of the order of one - much higher than that of any other quark. I will analyse the only process where the top-Higgs Yukawa coupling can be measured, in associated production of top quark pairs and a Higgs boson. The Higgs boson mainly decays into a pair of b-quarks. This is one of the most challenging channels at the LHC, as huge background processes from gluon splitting contribute. In particular, I will develop and study color flow variables, which provide a unique, powerful technique to distinguish color singlet Higgs bosons from the main background, color octet gluons. The ultimate goal of the project is the first measurement of the top-Higgs Yukawa coupling and its confrontation with SM and beyond SM Higgs boson models, resulting in an unprecedented insight into the fundamental laws of nature. The LHC will soon reach a new energy frontier of 13 TeV starting in 2014. This new environment will provide never seen opportunities to study hints of new physics and precisely measure properties of the newly found particle. This sets the stage for the project.|Smell and taste are the least studied of all senses. Very little is known about chemosensory information processing beyond the level of receptor neurons. Every morning we enjoy our coffee thanks to our brains ability to combine and process multiple sensory modalities. Meanwhile, we can still review a document on our desk by adjusting the weights of numerous sensory inputs that constantly bombard our brains. Yet, the smell of our coffee may remind us that pleasant weekend breakfast through associative learning and memory. In the proposed project we will explore the function and the architecture of neural circuits that are involved in olfactory and gustatory information processing, namely habenula and brainstem. Moreover we will investigate the fundamental principles underlying multimodal sensory integration and the neural basis of behavior in these highly conserved brain areas. To achieve these goals we will take an innovative approach by combining two-photon calcium imaging, optogenetics and electrophysiology with the expanding genetic toolbox of a small vertebrate, the zebrafish. This pioneering approach will enable us to design new types of experiments that were unthinkable only a few years ago. Using this unique combination of methods, we will monitor and perturb the activity of functionally distinct elements of habenular and brainstem circuits, in vivo. The habenula and brainstem are important in mediating stress/anxiety and eating habits respectively. Therefore, understanding the neural computations in these brain regions is important for comprehending the neural mechanisms underlying psychological conditions related to anxiety and eating disorders. We anticipate that our results will go beyond chemical senses and contribute new insights to the understanding of how brain circuits work and interact with the sensory world to shape neural activity and behavioral outputs of animals.I will develop an all new type of reactor for pharmaceutical and chemical process applications  the  tuneable membrane reactor . These contain ground-breaking conducting polymer composite membranes that will allow in-situ tuning of the molecular selectivity for both neutral and charged species through them. This is revolutionary: current state-of-the-art membranes can be electrically tuned for charged species only. The project is timely, developing a new technology that can give the EU a competitive advantage for our declining pharmaceutical and (petro)chemical manufacturing base and builds on my recent research innovations. To do this, my team of 3 PDRAs, 3 PhDs and I will develop unique stable polymer-polymer acid-nanoparticle composite membranes that can be externally electrically tuned to different pore sizes and/or molecular selectivity, uniquely tuning for neutral and charged species. We will characterise the chemical, physical and transport mechanisms responsible for the membrane tuneablity and relate these to transport models. We will then determine the feasibility of applying these unique tuneable membranes into membrane reactors, to allow in-situ external control of two key reactor parameters currently not possible: (1) Membrane fouling - membrane pore size/free volume and charge will be changed by applied potential allowing the fouling layer to be pushed off/through the membrane. (2) Precise external control of the reactant and product spectrum in the reactor by modifying species retention. By doing this, these tuneable membranes can be used to control the reaction rate, emissions and catalyst retention to maximise reaction rate and selectivity. This increases energy efficiency and emission co< ntrol, helping the EU 20-20-20 environmental targets to be met. The overall impact applies beyond the project  we will be able to increase the control of membrane separations used worldwide, helping industries including food, water, healthcare and chemicals. The proposed project will experimentally interface ferromagnets with superconducting quantum circuits to study dynamics within the magnet. To this end, magnonic elements made up by thin, structured magnetic films will be strongly coupled to the qubit. Superconducting qubits are ideal detectors due to their quantum limited back-action on the measured object and energy resolution. Spectroscopy and coherence measurements on the hybrid system will be made in order to address fundamental aspects such as spin wave generation, detection, coherence, or wave propagation down to mK temperatures and at ultra-low power (atto-watts). Amplitude and phase noise of spin wave resonators will be determined. At the final stage of the project, the quantum limited resolution of qubits will facilitate single magnon creation and detection. Quantum states are swapped between qubit and magnon, and superpositioned and entangled states will be explored. Monitoring the qubit response to its magnetic environment the low and high-frequency flux noise spectrum of spin waves will be inferred. The research methodology employs junctions, resonators, and qubits as research objects and detectors. The samples will be characterized at cryogenic temperatures by transport, magnetometry, resonator and qubit setups. Magnetic materials will be deposited and structured beneath or ontop the superconducting quantum circuits. Exploring spin wave dynamics in thin films by coupling to a superconducting qubit complements conventional measurement techniques based on photon, electron or neutron scattering methods, which require highly populated excitations. The project connects to and extends research objects of ground-breaking nature to open up new horizons for quantum, magnon and spin electronics. Magnetic material physics is enhanced by new research concepts such as quantum resolved spectroscopy and coherence measurements on intrinsic dynamic states.The field of combustion is of utmost societal/industrial importance while at the same time posing outstanding scientific challenges. In order to handle these, it is extremely important to develop and apply non-intrusive laser-diagnostic techniques with high spatial and temporal resolution for measurements of key parameters such as species concentrations and temperatures. Such techniques have been developed and applied by the PI for more than thirty-five years and the home institute has one of the most advanced instrumentations in academia world-wide. The proposal activities will be divided into two areas including five main Work packages: 1. Development of new diagnostic techniques. We will concentrate on concepts based on structured illumination which will add a new dimension to present diagnostics based on temporal, intensity and spectral properties. It will allow for multiscalar measurements and efficient suppression of background light. Furthermore, we will work with femto/picosecond lasers for investigating the diagnostic applicability of filamentation, new aspects of non-linear techniques, and diagnostic aspects of photodissociation phenomena. 2. Phenomenological combustion studies using advanced laser diagnostics. A very important aspect of the project is to use the developed and available diagnostic techniques to assure experimental data in extremely challenging environments and together with modeling experts enhance the understanding of combustion phenomena. Studies will be carried out on three different topics: - Flame structures in laminar flames at high pressure as well as turbulent flames at atmospheric/high pressure. - Biomass gasification, where complex fuels require new techniques to measure nitrogen, alkali, chlorine and sulfur compounds, as well as for measurements inside fuel particles. - Combustion improvement by electric activation which can be introduced to handle flame oscillations and instabilities. The Atiyah-Singer index theorem was one of the most spectacular achievements of mathematics in the XXth century, connecting the analytic and topological properties of manifolds. The Baum-Connes conjecture is a hugely successful approach to generalizing the index theorem to a much broader setting. It has remarkable applications in topology and analysis. For instance, it implies the Novikov conjecture on the homotopy invariance of higher signatures of a closed manifold and the Kaplansky-Kadison conjecture on the existence of non-trivial idempotents in the reduced group C*-algebra of a torsion-free group. At present, the Baum-Connes conjecture is known to hold for a large class of groups, including groups admitting metrically proper isometric actions on Hilbert spaces and Gromov hyperbolic groups. The Baum-Connes conjecture with certain coefficients is known to fail for a class of groups, whose Cayley graphs contain coarsely embedded expander graphs. Nevertheless, the conjecture in full generality remains open and there is a growing need for new examples of groups and group actions, that would be counterexamples to the Baum-Connes conjecture. The main objective of this project is to exhibit such examples. Our approach relies on strengthening Kazhdan s property (T), a prominent cohomological rigidity property, from its original setting of Hilbert spaces to much larger classes of Banach spaces. Such properties are an emerging d     !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmopqrstuvwxyz{|}~irection in the study of cohomological rigidity and are not yet well-understood. They lie at the intersection of geometric group theory, non-commutative geometry and index theory. In their study we will implement novel approaches, combining geometric and analytic techniques with variety of new cohomological constructions. vThis proposal aims to investigate the role of cytosolic DNA sensing pathways in CD4 T cell differentiation. Cellular host defense to pathogens relies on the detection of pathogen-associated molecular patterns including deoxyribonucleic acid (DNA), wh< ich can be recognized by host myeloid cells through Toll-like receptor (TLR) 9 binding. Recent evidence however suggests that innate immune cells can also perceive cytoplasmic DNA from infectious or autologous origin through cytosolic DNA sensors triggering TLR9-independent signaling. Activation of cytosolic DNA sensor-dependent signaling pathways has been clearly shown to trigger innate immune responses to microbial and host DNA, but the contribution of cytosolic DNA sensors to the differentiation of CD4 T cells, an essential event for shaping adaptive immune responses, has not been documented. This proposal aims to fill this current knowledge gap. We aim to decipher the molecular series of transcriptional events triggered by DNA in CD4 T cells that ultimately result in altered T cell differentiation. This aim will be addressed by combining in vitro and in vivo approaches such as advanced gene expression analysis of CD4 T cells and use of transgenic and gene-deficient mice. Structure activity relationship and biophysical studies will also be performed to unravel novel immunomodulators able to affect CD4 T cell differentiation. Standard time domain experiments measure the time evolution of the reflected/transmitted mean number of photons in the probe pulses. The evolution of the response of a material is typically averaged over the illuminated area as well as over many pump and probe measurements repeated stroboscopically. The aim of this project is to extend time domain optical spectroscopy beyond mean photon number measurements by performing a full Time Resolved Quantum State Reconstruction (TRQSR) of the probe pulses as a function of the pump and probe delay. The nature of the light matter interaction and the transient light-induced states of matter will be imprinted into the probe quantum state after the interaction with the material and can be uncovered with unprecedented detail with this new approach to time domain studies. TRQSR will be implemented by combining pump and probe experiments resolving single light pulses with balanced homodyne detection quantum tomography in the pulsed regime. We will apply and exploit the unique capabilities of TRQSR to address two different unresolved problems in condensed matter. Firstly, we will investigate the coherent and squeezed nature of low energy photo-induced vibrational states. We will use TRQSR with probe pulses shorter than the phonon timescale to interrogate the time evolution of the vibrational state induced by the pump pulse. Secondly, we will address inhomogeneities in photo-induced phase transformations. With TRQSR we can perform time domain measurements with a very small photon number per pulse which will give information on the interaction between the material (as prepared by the pump pulse) and individual photons. In this limit, TRQSR will allow us to retrieve rich statistics. While the average will deliver the information of a standard pump and probe experiment, higher order moments will give information on the time evolution of spatial inhomogenieties in the transient state. Biological motion and forces originate from mechanically active proteins operating at the nanometer scale. These individual active elements interact through the surrounding cellular medium, collectively generating structures spanning tens of micrometers whose mechanical properties are perfectly tuned to their fundamentally out-of-equilibrium biological function. While both individual proteins and the resulting cellular behaviors are well characterized, understanding the relationship between these two scales remains a major challenge in both physics and cell biology. We will bridge this gap through multiscale models of the emergence of active material properties in the experimentally well-characterized actin cytoskeleton. We will thus investigate unexplored, strongly interacting nonequilibrium regimes. We will develop a complete framework for cytoskeletal activity by separately studying all three fundamental processes driving it out of equilibrium: actin filament assembly and disassembly, force exertion by branched actin networks, and the action of molecular motors. We will then recombine these approaches into a unified understanding of complex cell motility processes. To tackle the cytoskeleton's disordered geometry and many-body interactions, we will design new nonequilibrium self consistent methods in statistical mechanics and elasticity theory. Our findings will be validated through simulations and close experimental collaborations. Our work will break new ground in both biology and physics. In the context of biology, it will establish a new framework to understand how the cell controls its achitecture and mechanics through biochemical regulation. On the physics side, it will set up new paradigms for the emergence of original out-of-equilibrium collective behaviors in an experimentally well-characterized system, addressing the foundations of existing macroscopic "active matter" approaches.After decades of truly transformative advancements in single molecule (bio)physics and surface science, it is still no more than a vision to predict and control macroscopic phenomena such as adhesion or electrochemical reaction rates at solid/liquid interfaces based on well-characterized single molecular interactions. How exactly do inherently dynamic and simultaneous interactions of a countless number of interacting  crowded molecules lead to a concerted outcome/property on a macroscopic scale? Here, I propose a unique approach that will allow us to unravel the scaling of single molecule interactions towards macroscopic properties at adhesive and redox-active solid/liquid interfaces. Combining Atomic Force Microscopy (AFM) based single molecule force spectroscopy and macroscopic Surface Forces Apparatus (SFA) experiments CSI.interface will (1) derive rules for describing nonlinearities observed in complex, crowded (water and ions) and chemically diverse adhesive solid/liquid interfaces; (2) uniquely characterize all relevant kinetic parameters (interaction free energy and transition states) of electrochemical and adhesive reactions/interactions of single molecules at chemically defined surfaces as well as electrified single crystal facets and step edges. Complementary, (3) my team and I will build a novel molecular force apparatus in order to measure single-molecule steady-state dynamics of both redox cycles as well as binding unbinding cycles of specific interactions, and how these react to environmental triggers. CSI.interface goes well beyond present applications < of AFM and SFA and has the long-term potential to revolutionize our understanding of interfacial interaction under steady state, responsive and dynamic conditions. This work will pave the road for knowledge based designing of next-generation technologies in gluing, coating, bio-adhesion, materials design and much beyond. All visual systems are specialised to best serve an animal s sensory niche, yet how such specialisations are achieved through phylogenetic and developmental adaptations of the  common vertebrate visual system blueprint are poorly understood. I will study these adaptations in the visual system of zebrafish. I will use two-photon functional imaging and computational modelling to investigate how the visual system of zebrafish samples and processes behaviourally meaningful stimuli in the natural world. I will then use optogenetic manipulations while zebrafish navigate a virtual reality environment to directly probe the role of visual circuits in driving behaviour. Specifically, I will pursue four Aims: 1. What is the zebrafish eye designed to see? 2. How does the fish retina form feature selective output channels? 3. What does the fish s eye tell the fish s brain? 4. How does visual input to the brain lead to behaviour? Visual specialisations begin in the optics and movements of the eyes, and are subsequently deeply rooted in every step of neuronal computation. Therefore, I will study visual processing at these different organisational levels. Here, the highly  visual zebrafish present a powerful model. They (i) offer exquisite genetic tools to record and manipulate neurons, (ii) have transparent larval stages permitting optical access to the entire nervous system and (iii) there is a large array of well-studied and easily quantifiable visual behaviours. In addition, zebrafish undergo two distinct life-stages, from larva to adult - with distinct lifestyles in different visual environments and hence different feature-detection requirements. Comparison of processing strategies employed by the (a) larval and (b) adult zebrafish visual system with that of other species, including a complementary database already recorded in mice (c), will lead to an increasingly generalised understanding of biological vision. From a technological viewpoint photoreceptor proteins, the light-sensitive proteins involved in the sensing and response to light in a variety of organisms, represent biological light converters. Hence they are successfully utilized in a number of technological applications, e.g. the green-fluorescent protein used to visualize spatial and temporal information in cells. However, despite the ground-breaking nature of this utilization in life science and other disciplines, the attempts to design a photoreceptor for a particular application by protein mutation remains an open challenge. This is exactly the scope of my research proposal: the application of multi-scale modelling for the systematic design of biological photoreceptor mutants. With this target in mind I will study representatives of two prominent photoreceptor proteins subfamilies which are of towering interest to experimentalists: proteorhodopsins and cyanobacteriochromes. Computer models of these proteins will be constructed using accurate multi-scale modeling. Their excitation energies and other properties (e.g. excited-state reactivity and efficiency) will be calculated using multireference methods that were shown to have an accuracy of <3 kcal/mol. The insights gained from simulations of the wild-type proteins will provide the basis for proposing mutations with altered photochemical properties: in essence to predict absorption and emission spectra, excited-state lifetime and quantum yields. This research requires interactions across the disciplines, as the best candidates will be synthesized and characterized experimentally by collaborators. The outcome of these experiments will provide feedback to improve both the properties of the mutants and the simulation methodology. Ultimately this high-risk/high gain project should derive a comprehensive understanding that would result in novel biotechnological applications, e.g. optogenetic tools, fluorescent probes and biosensors.WEverything occurs in a context. We see a car in the context of a street scene and a stove in the context of a kitchen. Context greatly helps the processing of individual objects. Surprisingly however, context hardly plays a role in most models of visual perception, which treat perception as a largely bottom-up categorization process. In this research proposal, I will examine how context changes the cortical computations that give rise to visual perception, focusing on contextual modulations in space and time. Moreover, I will translate this research to a clinical condition that is marked by aberrant context modulations in perception. Firstly, I will examine the influence of spatial context from the surround on cortical processing of individual elements. I aim to uncover the neural mechanisms responsible for the contextual facilitation of features and objects. I hypothesize that spatial context constrains sensory input by changing sensory representations at earlier stages in line with expectations at highe< r-order stages of perceptual analysis. Secondly, I will examine the influence of temporal context from past history. I hypothesize that temporal contexts trigger cortical waves of neural  preplay activity, setting up time-varying templates of expected incoming visual input. Thirdly, I will test the clinical significance of this framework to understand perceptual atypicalities in Autism Spectrum Disorder (ASD). I will empirically test the hypothesis that ASD is marked by deficient processing of contextual information, in both the spatial and temporal domain. This integrative approach has the potential to significantly advance theoretical models of perception, based on underlying neurobiology, and underline the importance of context for understanding perception. Moreover, the knowledge gleaned can have significant societal and clinical impact. Transcriptional regulation of genes in eukaryotic cells requires a complex and highly regulated interplay of chromatin environment, epigenetic status of target sequences and several different transcription factors. Eukaryotic genomes are tightly packaged within nuclei, yet must be accessible for transcription, replication and repair. A striking correlation exists between chromatin topology and underlying gene activity. According to the textbook view, chromatin loops bring genes into direct contact with distal regulatory elements, such as enhancers. Moreover, we and others have shown that genomes are organized into discretely folded megabase-sized regions, denoted as topologically associated domains (TADs), which seem to correlate well with transcription activity and histone modifications. However, it is unknown whether chromosome folding is a cause or consequence of underlying gene function. To better understand the role of genome organization in transcription regulation, I will address the following questions: (i) How are chromatin configurations altered during transcriptional changes accompanying development? (ii) What are the real-time kinetics and cell-to-cell variabilities of chromatin interactions and TAD architectures? (iii) Can chromatin loops be engineered de novo, and do they influence gene expression? (iv) What genetic elements and trans-acting factors are required to organize TADs? To address these fundamental questions, I will use a combination of novel technologies and approaches, such as Hi-C, CRISPR knock-ins, ANCHOR tagging of DNA loci, high- and super-resolution single-cell imaging, genome-wide screens and optogenetics, in order to both study and engineer chromatin architectures. These studies will give groundbreaking insight into if and how chromatin topology regulates transcription. Thus, I anticipate that the results of this project will have a major impact on the field and will lead to a new paradigm for metazoan transcription control. Observation and Modelling of Radiocarbon in Atmospheric Methane for Methane Source Identification Greenhouse gas emissions are the primary cause of global climate change, and methane (CH4) is the second most important contributor after carbon dioxide (CO2). Major sources of methane are both natural (wetlands) and anthropogenic (agriculture, landfills and fossil fuels). Current efforts to assess the anthropogenic CH4 influence on climate change and the effectiveness of mitigation policies for CH4 are limited by large uncertainties in estimates of total methane emissions and their attribution to various sources by accounting-based techniques. This project will pioneer and apply innovative techniques for atmospheric observation and modelling of radiocarbon in CH4 that will enable unique quantification of fossil fuel vs. biogenic CH4 sources at regional and global scales, thereby improving the estimation and attribution of CH4 emissions of different types. The proposed work will significantly advance the frontier of current research on atmospheric methane and the characterization of anthropogenic sources on policy-relevant scales, and it has the potential to influence climate policy and industrial practices over the next 10-20 years.Every single human is the product of a pregnancy: an approximately nine-month period during which a foetus develops within its mother s body. Yet pregnancy has not been a traditional focus in philosophy. That is remarkable, for two reasons: First, because pregnancy presents fascinating philosophical problems: what, during the pregnancy, is the nature of the relationship between the foetus and the maternal organism? What is the relationship between the pregnant organism and the later baby? And when does one person or organism become two? Second, because so many topics immediately adjacent to or involved in pregnancy have taken centre stage in philosophical enquiry. Examples include questions about personhood, foetuses, personal identity and the self. This project launches the metaphysics of pregnancy as an important and fundamental area of philosophical research. The core aims of the project are: (1) to develop a philosophically sophisticated account of human pregnancy and birth, and the entities involved in this, that is attentive to our best empirical understanding of human reproductive biology; (2) to articulate the metaphysics of organisms, persons and selves in a way that acknowledges the details of how we come into existence; and (3) to start the process of rewriting the legal, social and moral language we use to classify ourselves and our actions, so that it is compatible with and can accommodate the nature of pregnancy. The project will investigate these questions in the context of a range of philosophical sub disciplines, including analytic metaphysics, philosophy of biology and feminist phil< osophy, and in close dialogue with our best empirical understanding of the life sciences  most notably physiology. The next frontier in photonics is to achieve dynamic and externally tunable materials that allow for real-time, on-demand control over optical responses. Light is in many ways an ideal stimulus for achieving such control, and PHOTOTUNE aims at devising a comprehensive toolbox for the fabrication of light-tunable solid-state photonic structures. We harness light to control light, by making use of photoactuable liquid-crystal elastomers, which display large light-induced deformations through coupling between anisotropic liquid-crystal order and elasticity brought about by the polymer network. We will take liquid-crystal elastomers into a new context by intertwining photomechanics and photonics. Specifically, PHOTOTUNE is built around the following two objectives: (i) Tunable photonic bandgaps and lasing in photoactuable layered structures: The aim is to take photomechanical materials into the scale of optical wavelengths and utilize them in thickness-tunable liquid-crystal elastomer films. Such films will be further integrated into layered structures to obtain photonic crystals and multilayer distributed feedback lasers whose properties can be tuned by light. (ii) Photomechanical control over plasmonic enhancement on nanostructured elastomeric substrates: Fabrication of metal nanostructures on substrates that can contract and expand in response to light comprises a perfect, yet previously unexplored, nanophotonic platform with light-tunable lattice parameters. We will apply such tunable photoelastomeric substrates for surface-enhanced Raman scattering and phototunable nonlinear plasmonics. We expect to present a wholly new technological toolbox for tunable optical components and sensing platforms and beyond: The horizons of PHOTOTUNE are as far-reaching as in studying distance-dependent physical phenomena, controlling the speed of light in periodic structures, and designing actively-tunable optical metamaterials. _Resolving conflicts between food security and biodiversity conservation under uncertainty Conflicts between food security and biodiversity conservation are increasing in scale and intensity and have been shown to be damaging for both biodiversity and human livelihoods. Uncertainty, for example from climate change, decreases food security, puts further pressure on biodiversity and exacerbates conflicts. I propose to develop a novel model that predicts solutions to conflicts between biodiversity conservation and food security under uncertainty. ConFooBio will integrate game theory and social-ecological modelling to develop new theory to resolve conservation conflicts. ConFooBio will implement a three-tiered approach 1) characterise and analyse 7 real-world conservation conflicts impacted by uncertainty; 2) develop new game theory that explicitly incorporates uncertainty; and 3) produce and test a flexible social-ecological model, applicable to any real-world conflict where stakeholders operate under conditions of extreme uncertainty. The project has importance for society at large because ecosystems and their services are central to human wellbeing. Managing a specific natural resource often results in conflict between those stakeholders focussing on improving food security and those focussed on biodiversity conversation. ConFooBio will illuminate resolutions to such conflicts by showing how to achieve win-win scenarios that protect biodiversity and secure livelihoods. In this project, I will develop a practical, transparent and flexible model for the sustainable future of natural resources that is also robust to uncertainty (e.g., climate change); this model will be highly relevant for environmental negotiations among stakeholders with competing objectives, e.g., the negotiations to set the United Nations Sustainable Development Goals in September 2015. The excessive energy consumption that Europe is faced with, calls for sustainable resource management and policy-making. Amongst renewable sources of the global energy pool, wind energy holds the lead. Nonetheless, wind turbine (WT) facilities are conjoined with a number of shortcomings relating to their short life-span and the lack of efficient management schemes. With a number of WTs currently reaching their design span, stakeholders and policy makers are convinced of the necessity for reliable life-cycle assessment methodologies. However, existing tools have not yet caught up with the maturity of the WT technology, leaving visual inspection and offline non-destructive evaluation methods as the norm. This proposal aims to establish a smart framework for the monitoring, inspection and life-cycle assessment of WTs, able to guide WT operators in the management of these assets from cradle-to-grave. Our project is founded on a minimal intervention principle, coupling easily deployed and affordable sensor technology with state-of-the-art numerical modeling and data processing tools. An integrated approach is proposed comprising: (i) a new monitoring paradigm for WTs relying on fusion of structural response information, (ii) simulation of influential, yet little explored, factors affecting structural response, such as structure-foundation-soil interaction and fatigue (ii) a stochastic framework for detecting anomalies in both a short- (damage) and long-term (deterioration) scale. Our end goal is to deliver a  protection-suit for WTs comprising a hardware (sensor) solution and a modular readily implementable software package, titled ETH-WINDMIL. The suggested kit aims to completely redefine the status quo in current Supervisory Control And Data Acquisition systems. This pursuit is well founded on background work of the PI within the area of structural monitoring, with a focus in translating the value of information into quantifiable terms and engineering practice.It is now widely recognized that sustainably managing ecosystem services  the b< enefits humans obtain from nature  is essential for humanity s prospects in the 21st century and beyond. However, at present there is little data on the distribution of most services in most places. To date, the discipline of ecosystem service mapping has tried overcome this lack of data by using proxies to map ecosystem services based on our perceived understanding of ecosystem services from small-scale studies. However, the most commonly used proxies have been shown to be inaccurate, particularly for understanding policy-relevant trade-offs and win-wins between ecosystem services. The challenge therefore remains - how do we reliably map such relationships between multiple ES, thereby enabling multifunctional, ES-based management of our landscapes? In the SCALEFORES project, I will address this challenge head-on by developing and testing a novel methodological framework that enables the use of existing data to produce accurate maps of the relationships between ES in previously unmapped regions. The overarching idea underpinning SCALEFORES is that we can use information on the scale-dependency of relationships between existing social and ecological datasets (e.g. land cover, soil type, human population density) to create maps of trade-offs and win-wins between ecosystem services. The SCALEFORES project will systematically examine the scale-dependency of relationships between ecosystem services and the social and ecological variables that underpin them. It will then use this knowledge to enable a step change increase in our ability to accurately map both relationships between ES and the distributions of ecosystem services themselves. The methodology developed in SCALEFORES will be validated against existing maps of ecosystem services in Europe, as this is the region with the best data on ecosystem services globally.Solid Oxide Fuel Cells (SOFCs) are one of the most efficient and fuel flexible power generators. However, a great limitation on their applicability arises from temperature restrictions. Operation approaching room temperature (RT) is forbidden by the limited performance of known electrolytes and cathodes while typical high temperatures (HT) avoid their implementation in portable applications where quick start ups with low energy consumption are required. The ULTRASOFC project aims breaking these historical limits by taking advantage of the tremendous opportunities arising from novel fields in the domain of the nanoscale (nanoionics or nano photochemistry) and recent advances in the marriage between micro and nanotechnologies. From the required interdisciplinary approach, the ULTRASOFC project addresses materials challenges to (i) reduce the operation to RT and (ii) technological gaps to develop ultra-low-thermal mass structures able to reach high T with extremely low consumption and immediate start up. A unique SOFC technology fully integrated in ultrathin silicon will be developed to allow operation with hydrogen at room temperature and based on hydrocarbons at high temperature. Stacking these SOFCs will bring a new family of ultrathin power sources able to provide 100 mW at RT and 5W at high T in a size of a one-cent coin. A stand-alone device fuelled with methane at HT will be fabricated in the size of a dice. Apart from breaking the state-of-the-art of power portable generation, the ULTRASOFC project will cover the gap of knowledge existing for the migration of high T electrochemical devices to room temperature and MEMS to high T. Therefore, one should expect that ULTRASOFC will open up new horizons and opportunities for research in adjacent fields like electrochemical transducers or chemical sensors. Furthermore, new technological perspectives of integration of unconventional materials will allow exploring unknown devices and practical applications. The thermodynamic behavior of black holes is a precious clue in unravelling the microscopic structure of quantum gravity. High precision computations of quantum black hole entropy provide a new window into the fundamental microscopic theory of gravity and its deviations from classical general relativity. Traditional methods of quantum field theory have proved to be not well-suited to perform these computations. Two breakthroughs in my recent work establish new ground for progress. On one front, a new method to sum up al< l perturbative quantum contributions to the entropy of a large class of black holes has been developed. This gives rise to the first exactly solvable model of a quantum black hole. On a second front, a longstanding theoretical obstacle called the wall-crossing problem has been cleared in my recent work on the microscopic description of black holes in string theory. The newly-developed field of mock modular forms is shown to be the correct framework to address questions of exact black hole entropy. This makes a large class of microscopic models amenable to analytic control, many of which were previously beyond reach. These developments open up a new line of research that I propose to pursue along two intersecting avenues. First, I aim to extend the computations of exact quantum black hole entropy towards models of realistic black holes. Second, I aim to advance the theoretical understanding of quantum black holes by investigating the deeper origins of mock modular symmetry. As a concrete application, I aim to establish that newfound group-theoretical structures called  moonshine symmetries are physically realized in quantum black holes, thus opening up connections between two exciting fields of research previously thought to be distinct. Together, the broad goal is to explain black hole microstructure through systematic computations of exact quantum entropy, and to investigate its consequences on the fundamental microscopic theory of gravity.The European healthcare services have begun collecting tissue samples and healthcare data from patients on an unprecedented scale. With POLICYAID we suggest the term 'intensified data sourcing' to describe these attempts at getting more data, on more people, of better quality while simultaneously making the data available for multiple uses. Data are used for research, for financial remuneration purposes, for quality assurance, to attract capital and even for police work. POLICYAID investigates how the diverse agendas interact in the making of a new infrastructure for healthcare. POLICYAID ambitiously aims to understand the drivers for and implications of intensified data sourcing in the biomedical realm across three levels: 1) policymaking, 2) everyday clinical practices, and 3) citizen experiences of health, illness, rights and duties. To achieve this aim we compare four different forms of intensified data sourcing, and analyze the regulatory frameworks guiding the data procurement and use in Denmark, the EU and beyond. Based on PI s strong inter-disciplinary background and experience, we fuse legal, sociological, anthropological and public health scholarship and develop new methodologies for policy analysis by combining document analysis, interviews, participant observation and register-based methodologies. Instead of simply assuming that data sourcing can be reduced to matters of surveillance, we open up the black box of data sourcing by describing how data are selected; financed; what they are used for; how data practices relate to the involved stakeholders' hopes and concerns, and; who gains which rights to the data. We can thereby explore how intensified data sourcing affects clinical routines and patient experience, as well as understand how Big Data for medical research emerges. POLICYAID thereby arrives at novel understandings of both policy making and what it means to be patient in the age of intensified data sourcing. The rise in bacterial infections that are resistant to antibiotic treatment poses a major global health challenge. Addressing this challenge is not just a clinical issue: understanding bacterial resistance evolution calls for an interdisciplinary approach, in which the development of new physics, in coordination with biology, chemistry and engineering, has a central role to play. In particular, statistical physics, to predict the stochastic emergence of drug-resistant mutants, must be integrated with soft matter and chemical physics, to understand the spatial organization of the bacterial populations within which this happens. Bacterial infections are very often spati< ally heterogeneous. This is known to influence the outcome of antibiotic treatment  for example bacterial biofilms, which form on the surfaces of medical implants, are notoriously hard to remove. However, much less attention has been paid to the role of spatial structure in the evolution of drug resistance, i.e. the emergence and spread of genetically drug-resistant bacterial strains. I will lead a research programme which will for the first time uncover the two-way link between the emergence of spatial structure in bacterial multicellular assemblies and the evolution of drug resistance. The programme builds on my current theoretical, simulation and experimental work. I will first determine the basic principles of evolution in drug gradients using theoretical models, combined with experiments in a controlled, 1D geometry. I will then explore how these principles translate to the more realistic scenario of bacterial biofilms, where spatial structure and drug gradients are emergent properties, using advanced computer simulation methods and both confocal microscopy and evolution experiments. In the final part of the programme, I will use these insights to reveal optimization principles for the design of evolution-resistant surface coatings for applications in medical devices.Science is increasingly data-driven. Scientific research funders now routinely mandate open publication of publicly-funded research data. Safely reusing such data currently requires labour-intensive curation. Provenance recording the history and derivation of the data is critical to reaping the benefits and avoiding the pitfalls of data sharing. There are hundreds of curated scientific databases in biomedicine that need fine-grained provenance; one important example is GtoPdb, a pharmacological database developed by colleagues in Edinburgh. Currently there are no reusable methodologies or practical tools that support provenance for curated databases, forcing each project to start from scratch. Research on provenance for scientific databases is still at an early stage, and prototypes have so far proven challenging to deploy or evaluate in the field. Also, most techniques to date focus on provenance within a single database, but this is only part of the problem: real solutions will have to integrate database provenance with the multiple tiers of web applications, and no-one has begun to address this challenge. I propose research on how to build support for curation into the programming language itself, building on my recent research on the Links Web programming language and on data curation. Links is a strongly-typed language that provides state-of-the-art support for language-integrated query and Web programming. I propose to build on Links and other recent language designs for heterogeneous meta-programming to develop a new language, called Skye, that can express modular, reusable curation and provenance techniques. To keep focus on the real needs of scientific databases, Skye will be evaluated in the context of GtoPdb and other scientific database projects. Bridging the gap between curation research and the practices of scientific database curators will catalyse a virtuous cycle that will increase the pace of breakthrough results from data-driven science.Not very long ago, it was still common to hold that little of interest took place in Islamic philosophy, theology and science after the death of the Peripatetic commentator Averroes in 1198. Recent research has produced increasing evidence against this view, and experts now commonly agree that texts from the so-called post-classical period merit serious analysis. That evidence, however, is still fragmentary, and we lack a clear understanding of the large scale and long run development in the various fields of Islamic intellectual culture after the twelfth century. This project will investigate debates concerning the nature and methods of knowledge in four of the most ambitious strands of Islamic theoretical thought, that is, philosophy, theology, natural science, and philosophically inclined Sufism. Its temporal scope extends from the end of the twelfth century to the beginning of the colonial era, and it focuses on foundational epistemological questions (how knowledge is defined, what criteria are used to distinguish it from less secure epistemic attitudes, what methods are identified as valid in the acquisition of knowledge) as well as questions concerning knowledge as the goal of our existence (in particular, whether perceptual experience is inherently valuable). Our study of the four strands is based on the hypothesis that the post-classical period is witness to a sophisticated discussion of knowledge, in which epistemic realism, intuitionism, phenomenalism, and subjectivism are pitted against each other in a nuanced manner. Hence, the project will result in a well-founded reassessment of the common view according to which post-classical Islamic intellectual culture is authoritarian and stuck to an epistemic paradigm that stifles insight and creativity. Thereby it will provide new ingredients for projects of endogenous reform and reorientation in Islam, and corroborate the view that our future histories of philosophy should incorporate the Islamic tradition. Two-dimensional crystalline materials exhibit exceptional physical properties and offer fascinating potential as fundamental building blocks for future two-dimensional electronic and optoelectronic devices. Transition metal dichalcogenides (TMDCs) are of particular interest as they show a variety of many-body phenomena and correlation effects. Key properties are: i) additional internal degrees of freedom of the electrons, described as valley pseudospin and layer pseudospin, ii) electronic many-body effects like strongly-bound excitons and trions, and iii) electron-lattice correlations like polarons. While these phenomena represent intriguing fundamental solid state physics problems, they are of great practical importance in view of the envisioned nanoscopic devices based on two-dimensional materials. The experimental research project FLATLAND will address the exotic spin-valley-layer correlations in few-layer thick TMDC crystals and TMDC-based heterostructures. The latter comprise other 2D materials, organic crystals, metals and phase change materials as second constituent. Microscopic coupling and correlation effects, both within pure materials as well as across the interface of heterostructures, will be accessed by time- and angle-resolved extreme ultraviolet-photoelectron spectroscopy, femtosecond electron diffraction, and time-resolved optical spectroscopies. The project promises unprecedented insight into the microscopic coupling mechanisms governing the performance of van der Waals-bonded devices. ~Correlations are central for our modern view on the foundations of quantum theory and applications lik< e quantum information processing. So far, research concentrated on correlations between two or more particles. Indeed, for this situation it is well established that spatial quantum correlations are a useful resource for tasks like quantum cryptography and quantum metrology. There are, however, other types of correlations in quantum mechanics, which arise if a sequence of measurements on a single quantum system is made. These temporal quantum correlations have recently attracted attention, because they are central for the understanding of some differences between the quantum and the classical world. Moreover, due to experimental progress their observation has become feasible with trapped ions, polarized photons, or other quantum optical systems. This project aims at a full understanding and characterization of temporal quantum correlations. For that, we will derive criteria and measures for temporal quantum correlations and investigate their connection to information theory. Then, we will elucidate to which extent temporal correlations can be used to prove that a system is quantum and not classical. Finally, we consider implementations of temporal quantum correlations using continuous variable systems like nanomechanical oscillators and applications in quantum information processing.Reactive transport modelling is a key tool in understanding the extremely complex interplay of flow, transport and reactions occurring over various temporal and spatial scales in the subsurface. The most difficult challenge in reactive transport is the capture of scale dependence, and upscaling reactive transport will ultimately only be successful if there is a detailed understanding of fundamental mechanisms at the pore level and the supporting data are available. State-of-the-art tools (e.g. X-ray microtomography and on-chip porous media) are not sufficient to understand reactive flow, as they do not provide real-time mapping of propagation of fronts (e.g. temperature, pressure, concentration) that are critical to refine and validate simulations. The ambition is to progress beyond the state of the art via additive manufacturing tools to print 3D replicas of porous cores that enable monitoring the properties within the pores. Our unique approach is to develop for the first time three-dimensional instrumented replicas of porous structures, so we can gain much needed dynamic data at the pore scale that can be incorporated into validated simulations coupling flow and reactive transport processes. We combine expertise and integrating ground-breaking work in: (i) additive manufacturing to produce three dimensional replicas of porous structures; (ii) tools to embed sensors to determine in-vivo propagation of fronts (pressure, temperature, pH) within complex structures; and (iii) novel high-fidelity in-silico pore models coupling relative permeability functions and critical saturations with compositional changes and validated using virtual reality tools. The ERC MILEPOST project will transform our ability to analyse and predict the behaviour of a wide range of pore-scale processes governing the macroscopic behaviour of complex subsurface systems and open up new horizons for science in other areas, e.g porosity controlled in polymers and bioprinting.Title: Exponential Sums, Translation Invariance, and Applications. Short Summary: Exponential sums are fundamental throughout (analytic) number theory, and are key to the robustness of applications in theoretical computer science, cryptography, and so on. They are the primary tool for testing equidistribution (apparent  randomness ) of number theoretic sequences. For a century, bounds for such sums of degree 3 or more have fallen far short of those conjectured to hold. The landscape for exponential sums changed decisively in late 2010, when the proposer devised the  efficient congruencing method. As a result, mean value estimates associated with translation invariant systems are now within a whisker of the main conjectures. Very significant progress has resulted in such Diophantine applications as Waring's problem, the validity of the Hasse principle for systems of diagonal equations, and equidistribution of polynomial sequences mod 1. It is little understood in the wider community that efficient congruencing offers a fundamentally new approach to estimating moments of Fourier coefficients of wide generality, with hitherto inaccessible applications. We propose: (i) to generalise efficient congruencing to approximately translation invariant systems, and explore consequent applications to Diophantine problems such as Waring's problem, restriction problems from discrete Fourier analysis, and bounds for the Riemann zeta function within the critical strip; (ii) to extend the method to the multidimensional setting relevant to the investigation of local-global principles for spaces of rational morphisms from rational curves to diagonal hypersurfaces; (iii) to explore the application of efficient congruencing over function fields where the ground field is a finite field, in particular as a vehicle for establishing estimates of use in randomness extractors; (iv) to investigate the potential use of higher degree translation invariance in generalising Gowers norms.This proposal aims to address a simple question: what is the fundamental unit of computation in the brain? Answering this question is crucial not only for understanding how the brain works, but also if we are to build accurate models of brain function, which require abstraction based on identification of the essential elements for carrying out computations relevant to behaviour. In this proposal, we will build on recent work demonstrating that dendrites are highly electrically excitable to test the possibility that single dendritic branches may act as individual computational units during behaviour, challenging the classical view that the neuron is the fundamental unit of computation. We will address this question using a combination of electrophysiolgical, anatomical, imaging, molecular, and modeling approaches to probe dendritic integration in pyramidal cells and Purkinje cells in mouse cortex and cerebellum. We will first define the c< omputational rules for integration of synaptic input in single and multiple dendrites by examining the somatic and dendritic responses to different spatiotemporal patterns of excitatory and inhibitory inputs in brain slices. Next, we will determine how these rules are engaged by patterns of sensory stimulation in vivo, by using various strategies to map the spatiotemporal patterns of synaptic inputs onto single dendrites. To understand how physiological patterns of activity in the circuit engage these dendritic computations, we will use anatomical approaches to map the wiring diagram of synaptic inputs to individual dendrites. Finally, we will perturb the dendritic computational rules by manipulating dendritic function using molecular and optogenetic tools, in order to provide causal links between specific dendritic computations and sensory processing relevant to behaviour. These experiments will provide us with deeper insights into how single neurons act as computing devices.xOptical, electron and probe microscopes are enabling tools for discoveries and knowledge generation in nanoscale sicence and technology. High resolution  nanoscale or molecular-, noninvasive and label-free imaging of three-dimensional soft matter-liquid interfaces has not been achieved by any microscopy method. Force microscopy (AFM) is considered the second most relevant advance in materials science since 1960. Despite its impressive range of applications, the technique has some key limitations. Force microscopy has not three dimensional depth. What lies above or in the subsurface is not readily characterized. 3DNanoMech proposes to design, build and operate a high speed force-based method for the three-dimensional characterization soft matter-liquid interfaces (3D AFM). The microscope will combine a detection method based on force perturbations, adaptive algorithms, high speed piezo actuators and quantitative-oriented multifrequency approaches. The development of the microscope cannot be separated from its applications: imaging the error-free DNA repair and to understand the relationship existing between the nanomechanical properties and the malignancy of cancer cells. Those problems encompass the different spatial  molecular-nano-mesoscopic- and time  milli to seconds- scales of the instrument. In short, 3DNanoMech aims to image, map and measure with picoNewton, millisecond and angstrom resolution soft matter surfaces and interfaces in liquid. The long-term vision of 3DNanoMech is to replace models or computer animations of bimolecular-liquid interfaces by real time, molecular resolution maps of properties and processes.Embryonic development is very robust: In the midst of segregating mutations and fluctuating environments, a fertilized egg has the remarkable capacity to give rise to a precisely patterned embryo. The stereotypic progression of development is driven by tightly regulated programs of gene expression. However, this deterministic view from genetics is at odds with an emerging view of transcription from genomics as a  noisy process, variable and changing both within and between individuals. How variable transcriptional programs can regulate robust embryonic development remains a long-standing question, which this proposal aims to address. By combining population genetics, genomics, and developmental genetics in Drosophila we will dissect the relationship between DNA sequence variation, transcription factor (TF) occupancy, and the regulatory control of developmental gene expression. The backdrop for this work is extensive information generated by my lab on the location and function of over 12,000 developmental cis-regulatory elements, including accurate, predictive models of their spatio-temporal activity. To understand the impact of variation on transcription and development, we will make use of a powerful experimental resource  192 sequenced Drosophila strains, collected from a highly genetically diverse wild population. The proposed research has three Specific Aims: 1) Perform the first high-resolution study associating SNPs and structural variants (eQTLs) with gene expression variation during embryonic development, 2) Quantify in vivo the relationship between cis-regulatory variation, TF occupancy, and gene expression, 3) Incorporate these data into an integrated, predictive model of transcription. These Aims, together with our cis-regulatory data, will offer unique, mechanistic insights into how cis-regulatory variation impacts developmental gene regulation, and into the molecular bases of robustness in developmental re<gulatory networks.Many of the most remarkable contributions of modern science to society have arisen from interdisciplinary work of scientists enabling novel imaging and sensing technologies (NMR, X-ray diffraction, electron microscopy). BioQ will revolutionize the state of the art to create novel sensing technologies for the broad field of life sciences research that provide unprecedented access and insight into structure and function of individual bio-molecules under physiological conditions and apply these to the observation of biological processes down to the quantum level and with atomic resolution. At this level quantum properties are predicted to play an important role for the function of biological systems subject to environmental noise. BioQ will unravel the interplay of quantum coherent dynamics, molecular vibrations and environmental noise due to molecular vibrations in biological processes and design and carry out experimental tests of its predictions. BioQ will achieve new levels of understanding and control of biological systems, culminating in new ways to interface biological systems with quantum devices. To this end BioQ will exploit the ability of biological systems to arrange themselves into highly ordered structures to form novel hybrid materials of functionalized nano-diamonds that are capable of harnessing complex quantum dynamics at room temperature. A deeper understanding of biological processes will open new roads towards drug design and bio-imaging. The elucidation of energy transport processes and dynamics may pave the way towards the design of more efficient light harvesting systems. Self-assembled hybrid bio-quantum devices provide a novel perspective towards quantum nanotechnology. The broad challenges that this ambitious programme present will be solved by an interdisciplinary team led by three PIs from experimental solid-state physics, theoretical quantum physics and bio-chemistry whose combination of expertise is essential for the success of BioQ.2Molecular and Structural Biology and Biochemistry 7Genetics, Genomics, Bioinformatics and Systems Biology #Cellular and Developmental Biology .Physiology, Pathophysiology and Endocrinology #Neurosciences and Neural Disorders Immunity and Infection .Diagnostic Tools, Therapies and Public Health 3Evolutionary, Population and Environmental Biology 4Applied life Sciences and Non-Medical Biotechnology Mathematics Earth System Science #Fundamental Constituents of Matter Condensed Matter Physics *Physical and Analytical Chemical Sciences "Synthetic Chemistry and Materials !Computer Science and Informatics &Systems and Communication Engineering #Products and Processes Engineering Universe Sciences %Markets, Individuals and Institutions,Institutions, Values, Beliefs and Behaviour "Environment, Space and Population "The Human Mind and Its Complexity !Cultures and Cultural Production The Study of the Human Past Synergy Panel Name;`Gl;`pey:ERC project numberS 7W 7+Fundacion Publica Andaluza Progreso Y Salud<Academisch Medisch Centrum Bij De Universiteit Van Amsterdam*European Organization For Nuclear Research:Centro De Investigacion Ecologica Yaplicaciones Forestalesv 7yvXd 7%Fundacio Centre De Regulacio Genomica 7OXbUSMO 7"6 8T9X/:q;<=>0@H DA B C DEiG&IhI@ZKLMN'O+Xm)p! Ss}XQh  g[,K}[Ld9mL.wYtg(e\Al <1Y#eD!^t ~ ]:h{A( Zy MF< bj7 Y`.aL rE \ /- De v  C  D ' U} m   @r % L (b X @ zv ccB ɀ  z dMbP?_*+%&ffffff?'ffffff?(?)?M\\192.168.208.145\Pantum P3000 4dXXA4PRIVdQSndeo Watermark]Times New Roman6d22C:\Users\Public\Pantum\form\Times New Roman " dXX333333?333333?&<3U} m7} m     AD A D @~ E@ B~ F@ B~ F*@ B~ F3@ B ~ F@ B~ F2@ B~ F.@ B ~ F"@ H~ F,@ B~ F4@ B~ F@ B~ F*@ H ~ F@ H~ F? B~ F&@ B~ F@ B~ F@ B~ F(@ B~ F @ B~ F@@ B~ F@ B~ F3@ B~ F0@ B ~ F3@ B~ F@ B~ F"@ C~ GPr@>l0> pencƉh1penc                     ;pey:ERC project number     O& &:H@&  &:H@& &:H@!pencƉh1H ddpencƉh1d dAdd3d dd dd d>@7ggD ɀ 8&E-9DP[/gr?~ljO dMbP?_*+%;?&C&"[SO,R|"&20 Tac6e-NVxvzNXTv'kvyvnUS&jZ?'jZ?(~?)~?M\\192.168.208.145\Pantum P3000 4=XXA4PRIVdQSndeo Watermark]Times New Roman6d22C:\Users\Public\Pantum\form\Times New Roman " =XX BP(? BP(?&\(U} IK} 2} ;K} 2Kt.t &;I;J;J;J;J;J;J;J;J ;J ;J ;J ;J;J;J;J;J;J;J;J;J;J;J;J;J;J;J;J;J;J;J;J L M M M N~ O? 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Garcia-Perez EPIPLURETROjlgp@genyo.esfcEpigenetics Retrotransposons, pluripotent genome, mutataion, genomic instability, Stem cell biology96Transposable Elements, Stem cell biology, Epiogenetics.+FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUDESLS1 ERC-2012-StGUREpigenetic control and impact of mammalian retrotransposons in pluripotent genomesAlmost half of the human genome is made of Transposable Elements (TEs), whose ongoing activity continually impacts our genome. However, little is known about how the host regulates TEs and their genomic and epigenomic impacts. EpiPluriRetro will advance r@Jv#A HuguesNury Pentabrainhugues.nury@ibs.fr52membrane protein, crystallography, cryoEM, channel41Centre National De La Recherche Scientifique CnrsFRLS1 ERC-2014-StG52Structural studies of mammalian Cys-loop receptorsIn the brain, Cys-loop receptors mediate fast neurotransmission. They function as allosteric signal transducers across the plasma membrane: upon binding of one or more neurotransmitter molecules to an extracellular site, the receptors undergo complex conf@0"A Robbie LoewithTORCHRobbie.Loewith@unige.ch\YTarget of Rapamycin, kinase, signaling, metabolism, complex, mass spec, phosphoproteomicsIFstructure biology, signaling, biochemistry, mass spectrometry, cryo-emUniversite De GeneveCHLS1 ERC-2013-CoGTOR and Cellular HomeostasisThe Target Of Rapamycin (TOR) proteins are ser/thr kinases conserved in Eukarya. They nucleate two distinct multiprotein complexes, named TORC1 and TORC2, which regulate many, widely varying, aspects of cell and organism physiology. TOR inhibitors, such @APavel PlevkaPicoStructurepavel.plevka@ceitec.muni.czvirus, structure, cryo, electron, microscopy, crystallography, bacteriophage, infection, cell, entry, molecular, mechanism, picornavirus, enterovirus, human, pathogen, honeybee, tomography, protein, expression, purificationkhstructure, molecular, biology, cloning, protein, expression, purification, virus, programming, scriptingMasarykova UniverzitaCZLS1 ERC-2013-StG-*Structural studies of human picornavirusesMany picornaviruses are human pathogens that cause diseases varying in symptoms from common cold to life-threatening encephalitis. Currently there are no anti-picornavirus drugs approved for human use. We propose to study molecular structures of picornavi@#AJuha HuiskonenBIZEBjuha@strubi.ox.ac.ukemerging disease, viral infection, rift valley fever virus, arbovirus, bunyavirus, virus entry, bio-imaging, electron microscopy, light microscopy, cryo-EM, cryo-electron microscopy, electron cryomicroscopy, tomography, membrane fusion, endocytosis, recepC@The Chancellor, Masters And Scholars Of The University Of OxfordUKLS1 ERC-2014-CoG41Bio-Imaging of Zoonotic and Emerging BunyavirusesWe aim to understand host cell entry of enveloped viruses at molecular level. A crucial step in this process is when the viral membrane fuses with the cell membrane. Similarly to cell cell fusion, this step is mediated by fusion proteins (classes I III). @s$A Juan AlbertoValcrcel JurezMASCPjuan.valcarcel@crg.euB?alternative splicing, cancer, pluripotency, regulatory networks85structural biology, bioinformatics, molecular biology(%Fundacio Centre De Regulacio GenomicaESLS1 ERC-2014-ADGYVMechanisms of alternative pre-mRNA splicing regulation in cancer and pluripotent cellsAlternative splicing of messenger RNA precursors is a prevalent form of gene regulation that greatly expands the coding capacity and regulatory opportunities of higher eukaryotic genomes. It contributes to cell differentiation and pluripotency and its der@"A Benjamin LehnerIR-DCben.lehner@crg.euKHGenomics, epigenetics, C. elegans, yeast, cancer, evolution, developmentKHGenomics, epigenetics, C. elegans, yeast, cancer, evolution, development(%Fundacio Centre De Regulacio GenomicaESLS2 ERC-2013-CoG2/Individual Robustness in Development and CancerBiological systems are robust to perturbations, with many genetic, stochastic and environmental challenges having no or little phenotypic consequence. However, the extent of this robustness varies across individuals, for example the same mutation or trea @A Eileen Furlong CisRegVarfurlong@embl.deTranscriptional regulation, population genetics. QTL, developmental enhancers, computational biology, genomics, genome regulation, epigenetics, chromatingdBioinformatics, computational biology, genomics, genome regulation, chromatin, developmental biology(%European Molecular Biology LaboratoryDELS2 ERC-2012-ADGxuCis-regulatory variation: Using natural genetic variation to dissect cis-regulatory control of embryonic development.Embryonic development is very robust: In the midst of segregating mutations and fluctuating environments, a fertilized egg has the remarkable capacity to give rise to a precisely patterned embryo. The stereotypic progression of development is driven by ti"@$A Thomas SextonCHROMTOPOLOGYsexton@igbmc.fr@=Nuclear organisation; chromatin topology; Hi-C; TAD; enhancer[XImage analysis; Live microscopy; Nuclear organisation; chromatin topology; TAD; enhancer74Centre Europeen De Recherche En Biologie Et MedecineFRLS2 ERC-2015-STGb_Understanding and manipulating the dynamics of chromosome topologies in transcriptional controlTranscriptional regulation of genes in eukaryotic cells requires a complex and highly regulated interplay of chromatin environment, epigenetic status of target sequences and several different transcription factors. Eukaryotic genomes are tightly packaged $@ A Pierre Gonczy CENFORpierre.gonczy@epfl.chcentriole, assembly'$cryo-electron tomography, biophysics+(Ecole Polytechnique Federale De LausanneCHLS3 ERC-2013-ADG:7Dissecting the mechanisms governing centriole formationCentrioles are critical for the formation of cilia, flagella and centrosomes, as well as for human health. The mechanisms governing centriole formation constitute a long-standing question in cell biology. We will pursue an innovative multidisciplinary res&@s#A BenjaminPERET LUPIN ROOTSbenjamin.peret@supagro.fr=:Plant development, cluster roots, white lupin, adaptation."Curious, motivated, passionate.41Centre National De La Recherche Scientifique CnrsFRLS3 ERC-2014-StG63Unravelling cluster root development in white lupinPlant development is continuous throughout their lifetime and reflects their ability to adapt to their environment. This developmental plasticity is very obvious in the development of the root system. Surprisingly, the fundamental mechanisms of root devel(@$#A Guillaume CharrasMolCellTissMechg.charras@ucl.ac.uk=:Cell Biophysics, Epithelia, Tissue mechanics, cytoskeletonLIBiophysicist, Epithelial Biologist, Developmental Biologist, cytoskeletonUniversity College LondonUKLS3 ERC-2014-CoGB?Molecular and cellular determinants of cell monolayer mechanicsEpithelial monolayers are amongst the simplest tissues in the body, yet they play fundamental roles in adult organisms where they separate the internal environment from the external environment and in development when the intrinsic forces generated by cel*@$ABrian Stramer CIL2015brian.m.stramer@kcl.ac.ukMJcell migration, contact inhibition of locomotion, drosophila morphogenesis*'cell migration, biophysics, developmentKing'S College LondonUKLS3 ERC-2015-CoGHEDissecting the cellular mechanics of contact inhibition of locomotionOur aim is to dissect the mechanisms of contact inhibition of locomotion (CIL), a process whereby migrating cells collide and repel each other, as it is now clear that CIL is pivotal to understanding embryogenesis and pathologies such as cancer. We have d,@7%A Antoine Peters Totipotencyantoine.peters@fmi.chhezygotic genome activation, mouse early embryonic development, gene regulation, chromatin, inheritanceQNmicro-manipulation of mouse embryos, molecular biology, computational biology 74Friedrich Miescher Institute For Biomedical ResearchCHLS3 ERC-2015-AdGSPTranscriptional and Epigenetic Regulation of Totipotency in Mouse Early Embryos.In mammals, fusion of two highly differentiated gametes gives rise to a totipotent zygote capable of developing into a whole organism. It coincides with translation and degradation of maternally provided transcripts, initiation of global transcription cal.@#A Bon-KyoungKooTroy Stem Cellskoobk77@gmail.com[XAdult stem cells, stomach, intestine, organoids, CRISPR, mouse genetics, lineage tracing[XAdult stem cells, stomach, intestine, organoids, CRISPR, mouse genetics, lineage tracingFCThe Chancellor, Masters And Scholars Of The University Of CambridgeUKLS4 ERC-2014-StGC@Troy+ stomach stem cells in homeostasis, repair and pathogenesisThe adult mammalian stomach can be divided into three distinct parts: From the proximal fore-stomach over the corpus to the distal pylorus. Due to constant exposure to mechanical stress and to hostile contents of the lumen, highly specialized cell types h0@x#ARui Benedito AngioGenesHDRui.benedito@cnic.esa^Angiogenesis, Vascular Biology, Heart, Notch, VEGF, signalling, cell and developmental biologya^Angiogenesis, Vascular Biology, Heart, Notch, VEGF, signalling, developmental biology, imagingKHFundacion Centro Nacional De Investigaciones Cardiovasculares Carlos IiiESLS4 ERC-2014-StGA>Epistasis analysis of angiogenes with high cellular definitionBlood and lymphatic vessels have been the subject of intense investigation due to their important role in cancer development and in cardiovascular diseases. The significant advance in the methods used to modify and analyse gene function have allowed us to1@y#ALouis VermeulenCRCStemCellDynamicsl.vermeulen@amc.uva.nl41colorectal cancer, molecular subtypes, stem cells(%bioinformatics, imaging, biochemistry?<Academisch Medisch Centrum bij de Universiteit van AmsterdamNLLS4 ERC-2014-StGa^Molecular Subtype Specific Stem Cell Dynamics in Developing and Established Colorectal CancersAnnually 1.2 million new cases of colorectal cancer (CRC) are seen worldwide and over 50% of patients die of the disease making it a leading cause of cancer-related mortality. A crucial contributing factor to these disappointing figures is that CRC is a h2@~"A Roberto CoppariLIfewithoutinsulinroberto.coppari@unige.chA>diabetes, hypothalamus, life without insulin, new therapeuticsYVhard worker, smart individual, strong drive to pursue an independent scientific careerUniversite De GeneveCHLS4 ERC-2013-CoGKHMetabolic actions of brain leptin receptors signaling in type 1 diabetesAn established dogma is that insulin is absolutely required for survival. This notion has been supported by the fact that the sole life-saving intervention available to the millions affected by type 1 diabetes mellitus (T1DM; an illness caused by pancreat3@P#A PieterVan Vlierberghe EpiTALL!pieter.vanvlierberghe@ugent.be$!DNA methylation, T-cell leukemia bioinformaticianUniversiteit GentBELS4 ERC-2014-StGDynamic interplay between DNA methylation, histone modifications and super enhancer activity in normal T cells and during malignant T cell transformationDynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human disease. The ultimate go4@"AMarioPende RariTORmario.pende@inserm.frdagrowth, signal transduction, metabolism, animal models, disease, nutrition, insulin, mTOR, ageingdagrowth, signal transduction, metabolism, animal models, disease, nutrition, insulin, mTOR, ageingEBInstitut National De La Sante Et De La Recherche Medicale (Inserm)FRLS4 ERC-2013-CoG.+mTOR pathophysiology in rare human diseasesThe mammalian Target Of Rapamycin (mTOR) is a master regulator of growth. mTOR is a protein kinase that exists in two distinct complexes in the cell and transduces virtually all anabolic signals from the environment: nutrients, such as glucose and amino a5@A AdrianaMaggiWaysadriana.maggi@unimi.ita^hormone action, estrogen, women health, transcription regulation, energy metabolism, microgliaEBmolecular biology, cell biology, animal biology, molecular imaging# Universita Degli Studi Di MilanoITLS4 ERC-2012-ADG|Role of Liver Estrogen Receptor in female Energy Metabolism, Reproduction and Aging: What About Your Liver Sexual Functions?In mammals, the liver is the peripheral integrator of nutrient availability and energetic needs of the entire organism. We recently demonstrated that dietary amino acids (AA) activate liver Estrogen Receptors (ER) and that, in case of food scarcity, the l6@$A Andrea AlimontiImmune-senescence therapyandrea.alimonti@ior.iosi.ch:7Prostate cancer, mouse models, senescence, immunology, _\mouse models, B cells, T cells, innate immune compartment, flow cytometry, molecular biology=:Fondazione Per La Ricerca E La Cura Dei Linfomi Nel TicinoCHLS4 ERC-2015-CoGEBDual targeting of senescence and tumor immunity for cancer therapyWe have previously demonstrated that cellular senescence opposes tumorigenesis thereby opening up new potential opportunities for cancer treatment. Senescence and tumor immunity in cancer are tightly interconnected. Tumor-infiltrating immune cells promote7@P#AKoen VervaekeSurfaceInhibitionkoenv@medisin.uio.no|In-vivo Ca2+ imaging, sensorimotor integration, barrel cortex, neural inhibition, mouse behavior, computational neurosciencenkin-vivo patch clamp recordings, neural tracing, in-vivo imaging, extracellular recordings, mouse behaviour.Universitetet I OsloNOLS5 ERC-2014-StGB?The role of 5HT3a inhibitory interneurons in sensory processingHow do cortical circuits process sensory stimuli that leads to perception? Sensory input is encoded by complex interactions between principal excitatory neurons and a diverse population of inhibitory cells. Distinct inhibitory neurons control different su8@{A Dario BonanomiNEVAIbonanomi.dario@hsr.it_\Neurobiology of axon guidance and development; Neurovascular Crosstalk, Motor Neuron Disease|cellular/molecular neurobiology; axon guidance and signaling; vascular biology; motor system disorders; ES models of diseaseOspedale San RaffaeleITLS5 ERC-2013-StGHENeurovascular Interactions and Pathfinding in the Spinal Motor SystemNeurons and blood vessels rely on common guidance signals to wire into elaborate neural and vascular networks that are closely juxtaposed and interdependent: vascular supply of oxygen and nutrients is essential to sustain the high metabolic rate of the ne9@"A Nikolaus WeiskopfHMRIweiskopf@cbs.mpg.deNKQuantitative magnetic resonance imaging (MRI); in-vivo histology using MRI vsExpert in MR physics, or ultra-high resolution fMRI, or advanced diffusion imaging, or multi-modal image processingUniversity College LondonUKLS5 ERC-2013-CoG^[Non-Invasive In-Vivo Histology in Health and Disease Using Magnetic Resonance Imaging (MRI)Understanding of the normal and diseased brain crucially depends on reliable knowledge of its microstructure. Important functions are mediated by small cortical units (columns) and even small changes in the microstructure can cause debilitating diseases. :@tA Jerome Epsztein Intraspacejerome.epsztein@inserm.frolspatial coding; hippocampus; spatial coding and memory; patch-clamp recordings; virtual reality; place cellsFCcomputational models, virus tracing, optogenetics, pharmacogeneticsEBInstitut National De La Sante Et De La Recherche Medicale (Inserm)FRLS5 ERC-2013-StGA>An intracellular approach to spatial coding in the hippocampusThe hippocampus is an important structure for spatial memory in rodents and episodic memory in humans. The hippocampus uses a sparse coding scheme where a given environment is represented by the place selective firing of a small group of cells, (called pl;@${AEmre YaksiChemosensoryCircuitsemre.yaksi@ntnu.noolzebrafish, neural circuits, systems neuroscience, neural computations, stress, learning, olfaction, habenula]Zcomputational, theoretical, optics, physics, engineering, neural circuits, neurophysiology63Norges Teknisk-Naturvitenskapelige Universitet NtnuNOLS5 ERC-2013-StG$!Function of Chemosensory CircuitsSmell and taste are the least studied of all senses. Very little is known about chemosensory information processing beyond the level of receptor neurons. Every morning we enjoy our coffee thanks to our brains ability to combine and process multiple sensor<@n$ATomBaden VisNeuroEcot.baden@sussex.ac.uk=:vision, retina, 2photon imaging, zebrafish, visual ecology2/optical imaging, statistical modeling, geneticsUniversity Of SussexUKLS5 ERC-2015-STGtqZebrafish vision in its natural context: from natural scenes through retinal and central processing to behaviour.All visual systems are specialised to best serve an animal s sensory niche, yet how such specialisations are achieved through phylogenetic and developmental adaptations of the  common vertebrate visual system blueprint are poorly understood. I will study=@:;%A Michael HausserDENDRITECIRCUITSm.hausser@ucl.ac.ukkhdendrites, neural computation, cortex, synaptic transmission, pyramidal cell, computational neuroscience?<optics, electrophysiology, imaging, multiphoton, microscopy University College LondonUKLS5 ERC-2015-AdGHEThe origins of dendritic computation within mammalian neural circuitsThis proposal aims to address a simple question: what is the fundamental unit of computation in the brain? Answering this question is crucial not only for understanding how the brain works, but also if we are to build accurate models of brain function, wh>@D;%A Gabriela ConstantinImmunoalzheimergabriela.constantin@univr.itjgAlzheimer's disease, neuroinflammation, neuroimmunology, leukocyte trafficking, multi-photon microscopyimmunologist, neuroscientist, neuroimmunologist, neuroimmunology, neuroscience, neuroinflammation, cell biology, immunology, imaging# Universita Degli Studi Di VeronaITLS6 ERC-2015-AdG2/The role of immune cells in Alzheimer's diseaseAlzheimer s disease is the most common form of dementia affecting more than 35 million people worldwide and its prevalence is projected to nearly double every 20 years with tremendous social and economical impact on the society. There is no cure for Alzhe?@"A Federico Mingozzi MoMAAVFederico.mingozzi@gmail.com30AAV, gene therapy, immunology, T cells, antibody gene therapy, AAV, immunology-*Universite Pierre Et Marie Curie - Paris 6FRLS6 ERC-2013-CoGTQMolecular signatures and Modulation of immunity to Adeno-Associated Virus vectorsExperience with adeno-associated virus (AAV) vector-mediated gene transfer in human trials has unveiled the therapeutic potential of this approach, with some of the most exciting results coming from clinical studies of gene transfer for hemophilia B, cong@@A George Kollias MCs-inTESTkollias@fleming.gr`]Chronic inflammation, tumorigenesis, intestinal homeostasis, animal models, mesenchymal cells85Biomedical Sciences Research Center Alexander FlemingELLS6 ERC-2013-ADGb_Mesenchymal Cells of the Lamina Propria in Intestinal Epithelial and Immunological Homeostasis.Mesenchymal cells (MCs) of the intestinal lamina propria refer to a variety of cell types, most commonly intestinal myofibroblasts, fibroblasts, pericytes, and mesenchymal stromal cells, which show many similarities in terms of origin, function and molecu@@lAFrank Kirchhoff Anti-Viromefrank.kirchhoff@uni-ulm.deC@HIV, AIDS, restriction factors, human peptidome, viral evolution85Creative, ambitious, molecular virology, cell biologyUniversitaet UlmDELS6 ERC-2012-ADG|yA combined evolutionary and proteomics approach to the discovery, induction and application of antiviral immunity factorsHumans are equipped with a variety of intrinsic immunity or host restriction factors. These evolved under positive selection pressure for diversification and represent a first line of defence against invading viruses. Unfortunately, however, many pathogenA@d"APablo Pelegrin DangerATPpablo.pelegrin@ffis.esGDInflammation, NLRP3, inflammasome, P2X7, macrophage, cytokines, IL-1PMFundacion Para La Formacion E Investigacion Sanitarias De La Region De MurciaESLS6 ERC-2013-CoG~{Regulation of inflammatory response by extracellular ATP and P2X7 receptor signalling: through and beyond the inflammasome.Inflammatory diseases affect over 80 million people worldwide and accompany many diseases of industrialized countries, being the majority of them infection-free conditions. There are few efficient anti-inflammatory drugs to treat chronic inflammation and A@A BenjaminHale SUMOFLUhale.ben@virology.uzh.chc`influenza, virus, SUMO, ubiquitin, interferon, immunity, RNA, virus-host interaction, proteomicsUniversitaet ZuerichCHLS6 ERC-2013-StG=:Interplay between influenza viruses and host SUMO pathwaysInfluenza viruses cause a significant seasonal disease burden and continually threaten to initiate human pandemics. Antivirals are available for treatment of influenza, however drug-resistant viruses often emerge. Thus, there is urgent need to develop newB@"AEran Elinav METABIOMEeran.elinav@weizmann.ac.il>;microbiome; microbiota; innate immunity; metabolic syndrome Weizmann Institute Of ScienceILLS6 ERC-2013-CoGxuDeciphering the molecular language orchestrating host-microbiome interactions and their effects on health and diseaseThe gastrointestinal tract hosts the microbiome, one of the highest microbial densities on earth. Diverse host-microbiome interactions influence a multitude of physiological and pathological processes, yet the basic mechanisms regulating host-microbiome iB@A Stipan Jonjic StAdvInnstipan.jonjic@medri.uniri.hr41NK cells, CD8 T cells, NKG2D, protective immunityYVimmunology, virology, biotechnology; NK cells, CD8 T cells, NKG2D, protective immunity,)Sveuciliste U Rijeci, Medicinski FakultetHRLS6 ERC-2012-ADGStrengthening adaptive immunity via innate immunity: enhancing the CD8 T cell response by using the NKG2D ligand expressed in a herpesvirus vectorCD8+ T cells play a key role in the control of infections by intracellular pathogens. Recently, several top-notch studies provided ample evidence that NK cells are important in the regulation of CD8+ T cell response. NKG2D is an activating NK cell receptoC@D"ARobinMay MitoFunr.c.may@bham.ac.uk=:pathogen, innate immunity, macrophage, Cryptococcus, fungiB?Immunologist, microbiologist, cell biologist, fungal geneticistThe University Of BirminghamUKLS6 ERC-2013-CoG1.Mitochondria as regulators of fungal virulenceFungal diseases represent a significant and growing threat to human health, particularly since the AIDS pandemic and increasing use of immunosuppressive drugs has produced a massive population of people with impaired immunity who are vulnerable to fungal C@v#ASatu MustjokiM-IMMsatu.mustjoki@helsinki.fi1.autoimmune disease, genetics, T-cell clonalityXUimmunology, bioinformatics, next-generation sequencing, autoimmune diseases, geneticsHelsingin YliopistoFILS6 ERC-2014-CoGc`Novel etiology of autoimmune disorders: the role of acquired somatic mutations in lymphoid cellsMolecular pathogenesis of most immune-mediated disorders, such as of autoimmune diseases, is poorly understood. These common maladies carry a heavy burden both on patients and on society. Current therapy is non-targeted and results in significant short- aD@>#A Sbastien Pfeffer RegulRNAspfeffer@unistra.frC@RNA silencing; microRNA; virus; innate immunity; Gene regulationOLMolecular biology, virology, RNA, high-throughput techniques, bioinformatics41Centre National De La Recherche Scientifique CnrsFRLS6 ERC-2014-CoG:7Modulation of RNA-based regulatory processes by virusesSmall and large non-coding RNAs are essential components at the heart of gene expression regulation. The past fifteen years have witnessed the emergence of a new field of research impacting diverse domains of biology. Among these, virology is no exceptionD@$A Lionel Apetoh CD4DNASPlionel.apetoh@inserm.frEBInstitut National De La Sante Et De La Recherche Medicale (Inserm)FRLS6 ERC-2015-STGYVCell intrinsic control of CD4 T cell differentiation by cytosolic DNA sensing pathwaysThis proposal aims to investigate the role of cytosolic DNA sensing pathways in CD4 T cell differentiation. Cellular host defense to pathogens relies on the detection of pathogen-associated molecular patterns including deoxyribonucleic acid (DNA), which cE@:$A Adrian Liston Tissue-Tregsadrian.liston@vib.be/,Tregs, immune, synthetic biology, immunology molecular biology, immunologyVibBELS6 ERC-2015-CoGURNovel approaches to determining the function of tissue-specific regulatory T cellsRegulatory T cells (Tregs) are formed through the expression of the transcription factor Foxp3 in T cells, resulting in the rewiring of the cell function into an immunosuppressive phenotype. Recently, it has been proposed that Tregs also have additional tE@n$ALauraElo DynaOmicslaura.elo@utu.fi~computational biomedicine, bioinformatics, statistical data mining, machine learning, longitudinal data analysis, biomarkers, Turun YliopistoFILS7 ERC-2015-STGEBFrom longitudinal proteomics to dynamic individualized diagnosticsLongitudinal omics data hold great promise to improve biomarker detection and enable dynamic individualized predictions. Recent technological advances have made proteomics an increasingly attractive option but clinical longitudinal proteomic datasets are F@$A Josu SznitmanRespMicroFlowssznitman@bm.technion.ac.il pmLungs, aerosols,children, therapy, flows, Drug delivery, Lungs, Inhalation Therapy, Particle Transport, FlowsspNanotechnology, particles, theragnostics, drug delivery, Drug Delivery, Nanotechnology, Functionalized Particles,)Technion - Israel Institute Of TechnologyILLS7 ERC-2015-STGUnravelling respiratory microflows in silico and in vitro: novel paths for targeted pulmonary delivery in infants and young childrenFundamental research on respiratory transport phenomena, quantifying momentum and mass transfer in the lung depths, is overwhelmingly focused on adults. Yet, children are not just miniature adults; their distinct lung structures and heterogeneous ventilatF@lAHarald H.H.W. Schmidt RADMED$!h.schmidt@maastrichtuniversity.nloxidative stress, drug discovery, stroke, diabetic complications, reactive oxygen species, diabetes, oxidative stress, cyclic GMP~phage display, antibodies, in vivo pharmacology, stroke models, drug discovery, stroke, diabetes, oxidative stress, cyclic GMPUniversiteit MaastrichtNLLS7 ERC-2011-ADG0-Radical Medicine: Redefining Oxidative StressOxidative stress, an excess of radical and other reactive oxygen species (ROS), has been suggested as a major disease mechanism. However, the major clinical trials using anti-oxidants have been failures, even suggesting serious side effects. Here, I propoG@"A Enrico TiacciHairy Cell Leukemiaenrico.tiacci@unipg.it$!Universita Degli Studi Di PerugiaITLS7 ERC-2013-CoG:7Genetics-driven targeted therapy of Hairy Cell LeukemiaHairy Cell Leukemia (HCL), a chronic B-cell neoplasm, is initially sensitive to chemotherapy with purine analogs, but ~40% of patients eventually relapses and becomes less responsive to these drugs. Furthermore, purine analogs may cause myelotoxicity, imG@"A GiuseppeTestaDISEASEAVATARSgiuseppe.testa@unimi.itmjdisease modeling; stem cells; epigenetics; transcriptomics; iPSC; autism spectrum disorder; bioinformaticsgraduate degree in bioinformatics / computational biology / informatics; PhD in molecular biology / neurobiology; experience in the analysis of -omics data; excellent track record# Universita Degli Studi Di MilanoITLS7 ERC-2013-CoGModeling Disease through Cell Reprogramming: a Translational Approach to the Pathogenesis of Syndromes Caused by Symmetrical Gene Dosage ImbalancesThe fundamental limitation in our ability to dissect human diseases is the scarce availability of human tissues at relevant disease stages, which is particularly salient for neural disorders. Somatic cell reprogramming is overcoming this limitation througH@A Francesco RicciNature Nanodevicesfrancesco.ricci@uniroma2.itDNA nanotechnology, synthetic biology, biosensors, nanodevices, nanomachines, supramolecular chemistry, bioengineering, Aptamers, Conformation switching probes, Smart drug-release, Electrochemical sensors.DNA nanotechnology, synthetic biology, biosensors, nanodevices, nanomachines, supramolecular chemistry, bioengineering, Aptamers, Conformation switching probes, Smart drug-release, Electrochemical sensors.,)Universita Degli Studi Di Roma TorvergataITLS7 ERC-2013-StGgdNature-inspired theranostic nanodevices for tumor imaging, early diagnosis and targeted drug-releaseLate diagnosis and difficult treatment represent major obstacles in the fight against cancer. I propose here the development of self-regulated theranostic nanodevices supporting both early cancer diagnosis and targeted, tumor-cell-specific drug-release. SH@*#ADavid Gloriam DE-ORPHANdavid.gloriam@sund.ku.dkGPCR, drug design, computational chemistry, pharmacology, medicinal chemistry, virtual screening, database development, programming, receptor functionGPCR, drug design, computational chemistry, pharmacology, medicinal chemistry, virtual screening, database development, programming, receptor functionKobenhavns UniversitetDKLS7 ERC-2014-StGFCDEtermination of Orphan Receptor PHysiological Agonists and sigNalsG protein-coupled receptors make up both the largest membrane protein and drug target families. DE-ORPHAN aims to determine the close functional context; specifically physiological agonists and signaling pathways; and provide the first research tool compoI@A Mangala Srinivas CONQUEST!Mangala.Srinivas@Radboudumc.nl96imaging, nanoparticles, MRI, ultrasound, cell tracking<9nanoparticles, ultrasound, photoacoustics, nanotechnology$!Stichting Katholieke UniversiteitNLLS7 ERC-2013-StGroClinical ultrasound platform for the quantitative and longitudinal imaging of theranostics and cellular therapyThe success of modern medical treatments such as cellular therapy and targeted treatments requires appropriate tools for in vivo monitoring. Imaging modalities, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) aI@,A Julien Valette INCELLjulien.valette@cea.frPMMagnetic resonance; spectroscopy; brain; diffusion; cell morphology; modelingmodeling; magnetic resonance; spectroscopy; diffusion; singlet state; long-lived state; carbon 13; 13C; chemical shift imaging; spectroscopic imaging; CSIA>Commissariat A L Energie Atomique Et Aux Energies AlternativesFRLS7 ERC-2013-StGXUExploring brain intracellular space using diffusion-weighted NMR spectroscopy in vivoAlterations of the intracellular space, including intracellular protein accumulation, organelle and cytoskeleton dislocation, and modifications in cell shape, are an early hallmark of many neurodegenerative processes. The ability to assess and quantify thJ@"AMarc Vooijs DIRECT&#marc.vooijs@maastrichtuniversity.nl[XNOTCH, HYPOXIA, CANCER, STEM CELL, RESISTANCE, PRODRUGS, SECRETASE INHIBITOR, METABOLISMC@BIOCHEMISTRY, ENZYMES, TUMOR METABOLISM, HIGH RESOLUTION IMAGINGUniversiteit MaastrichtNLLS7 ERC-2013-CoG85Disabling Radiotherapy resistance in Cancer TreatmentCancer is a devastating disease affecting 1 in 3 people in their lifetime. The incidence is rising because of our aging population and causes a huge economic impact on our society because of hospitalization and lost productivity. Radiotherapy alone or in J@pAPabloArtal SeeCat pablo@um.es,)Optics, Photonics, Biomedicine, CataractsURApplied physics, Optics, Photonics, Biomedical engineering, Electrical engineeringUniversidad De MurciaESLS7 ERC-2013-ADG30Seeing through cataracts with advanced photonicsCataract is the opacification of the crystalline lens of the human eye. It is usually related with age and is one of the leading causes of blindness. The increase in light scatter in the lens reduces the contrast in the retinal images severely degrading vK@"AAna Teixeira MECHCOMMana.teixeira@ki.seC@receptor, clustering, nanotechnology, omics, membrane biophysicsFCbiophysics, cell signalling, nanotechnology, omics, superresolutionKarolinska InstitutetSELS7 ERC-2013-CoG41Mechanotransduction in Cell-to-Cell CommunicationCell-to-cell communication pathways coordinate cellular functions in multicellular organisms. Cells that are nearest neighbours can communicate through specific interactions between ligand and receptor proteins present in their respective cell membranes. K@#A Stphanie Debette SEGWAY"stephanie.debette@u-bordeaux.frbrain imaging genomics; lifetime approach; next generation sequencing; cutting-edge MRI markers; large scale genomic studies in population-based setting; meta-analyses of genomic studies in context of international consortiaVSstatistical genetics; genetic epidemiology; brain imaging genomics; bioinformatics Universite De BordeauxFRLS7 ERC-2014-StGkhStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young studentsMounting evidence suggests that early life factors have an important impact on the occurrence of late-life neurological diseases. From a public health perspective this is of particular relevance for dementia, the prevalence of which is increasing drasticaL@#AJosMalda 3D-JOINTj.malda@umcutrecht.nlQNcartilage, regenerative medicine, 3D printing, biofabrication, electrospinning52biology, tissue engineering, robotics, bioreactors'$Universitair Medisch Centrum UtrechtNLLS7 ERC-2014-CoG'$3D Bioprinting of JOINT ReplacementsThe world has a significant medical challenge in repairing injured or diseased joints. Joint degeneration and its related pain is a major socio-economic burden that will increase over the next decade and is currently addressed by implanting a metal prosthL@8#APer Svenningsson PROGSYper.svenningsson@ki.se-*GPCR, Protein folding, Parkinsons disease-*GPCR, Protein folding, Parkinsons diseaseKarolinska InstitutetSELS7 ERC-2014-CoG,)Prosaposin and GPR37 in synucleinopathiesThe next breakthrough in the treatment of synucleinopathies, incl Parkinsons disease (PD), will be aimed at interference of disease progression based on insights into the underlying pathogenic process. The pathological hallmark of PD are Lewy bodies (LBsM@z$A robert colebunders NSETHIO$!robert.colebunders@uantwerpen.be KHnodding syndrome, epilepsy, onchocerciasis, burdan of disease, etiology ROepidemiology, mathematical modeling, neurology, tropical diseases, parasitologyUniversiteit AntwerpenBELS7 ERC-2014-ADGvsNodding Syndrome: a trans-disciplinary approach to identify the cause and decrease the incidence of river epilepsyNodding syndrome (NS) is a neurological, incurable syndrome, currently affecting mainly children between 5 and 15 years of age in South Sudan, Uganda and Tanzania. Since 1950, when NS was first described, its cause has remained a mystery. NS is characteriM@$A Vincenzo Cerullo PeptiCradvincenzo.cerullo@helsinki.fikhImmunotherapy, virotherapy, oncolytic adenovirus, peptides, tumour-specific peptides, Ligandome analysisjgLigandome analysis, peptides discovery, neoantigens, oncolytic herpes virus, oncolytic vaccinia virus, Helsingin YliopistoFILS7 ERC-2015-CoG;8Personalized oncolytic vaccines for cancer immunotherapyThis grant application proposes to develop a novel, customizable and personalized anti-cancer vaccine: peptide-coated conditionally replicating adenovirus (PeptiCrad). Anti-cancer vaccines represent a promising approach for cancer treatment because they eN@j$A Mette M. RosenkildeVIREXrosenkilde@sund.ku.dk]ZG protein-coupled receptors (GPCRs), adhesion GPCRs, blood brain barrier, virus infections|yG protein-coupled receptors (GPCRs), drug development, mouse models for infection and metabolism, novel antiviral therapyKobenhavns UniversitetDKLS7 ERC-2015-CoGA>Mumps VIRus EXploitation of the human adhesion receptor GPR125Mumps virus is a re-emerging pathogen that causes painful inflammatory symptoms, such as parotitis (salivary gland infection) and orchitis (testis infection). It is highly neurotropic with evidence of brain infection in half of cases and clinical evidenceN@$A Frederic Delsuc ConvergeAnt"Frederic.Delsuc@umontpellier.frzwEvolutionary genomics - Convergent molecular evolution - Microbiomes - Phylogenomics - Mammals , Evolutionary genomics ebMammalian comparative genomics - Microbiome evolution , Comparative genomics - Molecular evolution41Centre National De La Recherche Scientifique CnrsFRLS8 ERC-2015-CoGVSAn Integrative Approach to Understanding Convergent Evolution in Ant-eating MammalsDespite its widespread occurrence across the tree of life, many questions still remain unanswered concerning the fascinating phenomenon of convergent evolution. Ant-eating mammals constitute a textbook example of morphological convergence with at least fiO@"ADavid Posada PHYLOCANCERdposada@uvigo.es.+cancer evolution, cancer genomics, CRC, CLL96computational biologist, cancer genomicist, oncologistUniversidad De VigoESLS8 ERC-2013-CoG=:Phylogeography and somatic evolution of cancer tumor cellsBy far, most evolutionary research has focused on the changes that occur in the germline of individuals across generations, within and between species. For different reasons, much less attention has been given to the process of change within the somatic lO@LALars ChittkaSpaceRadarPollinatorl.chittka@qmul.ac.uk]Zentomology, behavior, navigation, sensory systems, insects, pollination, flowers, networksjgbehavior, navigation, sensory systems, insects, pollination, flowers, networks, neuroscience, cognition"Queen Mary University Of LondonUKLS8 ERC-2013-ADGQSpace use by bees radar tracking of spatial movement patterns of key pollinatorsCurrent radar tracking technology to monitor insect movements in space allows us to catch only glimpses of their spatial movements  it is severely constrained by the restricted range that can be covered, the fact that individuals can only be tracked one P@4"A AbderrahmanKhila WaterWalking abderrahman.khila@ens-lyon.frDAEvo-Devo, Adaptation, Evolution, Hemiptera, Genetics, Development30Evolution, Genomics, Bioinformatics, development41Centre National De La Recherche Scientifique CnrsFRLS8 ERC-2013-CoGnkWater-walking insects: marrying evo-devo with ecology for a better understanding of morphological evolutionUnderstanding the origin of the remarkable biodiversity in nature is an important goal in biological studies. Despite recent advances in evolutionary developmental biology, our understanding of the interaction between developmental genetic processes and t@P@A Simone Immler HapSelAsimone.immler@ebc.uu.se85evolution, genetics, genomics, epigenetics, zebrafish-*evolution, genetics, genomics, epigeneticsUppsala UniversitetSELS8 ERC-2013-StGheHaploid selection in animals: investigating the importance of genetic and epigenetic effects in spermAn inescapable consequence of sex in eukaryotes is the evolution of a biphasic life cycle with alternating diploid and haploid phases. The occurrence of selection during both phases has far reaching consequences for fundamental evolutionary processes inclP@#AYingguang FrankChan HybridMiXfrank.chan@tue.mpg.de;8Evolutionary Genetics, Mouse, Stem Cell, Genetic mappingVSTissue engineer; Evolutionary Geneticist; System biologist; Quantitative Geneticist>;Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften EvDELS8 ERC-2014-StG^[Genetic Mapping of Evolutionary Developmental Variation using Hybrid Mouse in vitro CrossesDiscovering the genetic changes underlying species differences is a central goal in evolutionary genetics. Most evolutionarily important traits affecting fitness are complex or quantitative traits, whose genetic bases are elusive. In mammals, dissecting tP@ADror Hawlena ECOSTRESSdror.hawlena@mail.huji.ac.il[Xfood-web, inducible defenses, ecosystem functioning, nutritional ecology, predation riskheecosystem modelling, soil ecology, microbial ecology, nutritional ecology, predator-prey interactions%"The Hebrew University Of JerusalemILLS8 ERC-2013-StGXUPhysiological Reaction to Predation- A General Way to Link Individuals to EcosystemsThis proposal aims to advance a new general theory that links plasticity in prey responses to predation and biogeochemical processes to explain context-dependent variations in ecosystem functioning. The physiological reaction of prey to predation involvesQ@u#AMaria McNamara ANICOLEVOmaria.mcnamara@ucc.ieYVfossil colour, taphonomy, fossil insects, fossil feathers, pigments, structural colourfossil colour, taphonomy, fossil insects, fossil feathers, pigments, structural colour, phylogenetics, morphometrics, SAXS, biomarkers, organic geochemistry, inorganic geochemistry, palaeomicsB?University College Cork - National University Of Ireland, CorkIELS8 ERC-2014-StGTQAnimal coloration through deep time: evolutionary novelty, homology and taphonomyWhat does the fossil record tell us about the evolution of colour in animals through deep time? Evidence of colour in fossils can inform on the visual signalling strategies used by ancient animals. Research to date often has a narrow focus, lacks a broad @Q@Alo Niinemets SIP-VOL+ylo.niinemets@emu.eestress volatiles, biogenic volatiles, plant trace gases, climate change, secondary organic aerosols, biosphere-atmosphere feedbacks, ozone, climate modelling, global changeGC-MS, plant stress physiology, volatile emissions, climate modelling, cloud modelling, aerosol modelling, trace gas eddy flux measurements, global changeEesti MaaulikoolEELS8 ERC-2012-ADG@=Stress-Induced Plant Volatiles in Biosphere-Atmosphere SystemVegetation forms a key interface between Earth surface and atmosphere. The important role of vegetation carbon, water and energy exchanges is well established, but the overall impact of plant trace gas (VOC) emission for large-scale Earth processes is pooQ@u#AHans Verbeeck TREECLIMBERShans.verbeeck@ugent.beEBvegetation modelling, lianas, tropical forest, lidar, carbon cylceB?modelling, programming, lidar scanning, ecology, biogeochemstryUniversiteit GentBELS8 ERC-2014-StGQNModelling lianas as key drivers of tropical forest responses to climate changeTropical forests are essential components of the earth system. Yet, much uncertainty exists about the exact role of this biome in the global carbon cycle. Our limited understanding of tropical forest functioning is reflected in uncertain global vegetationQ@#A Andrea ManicaLocalAdaptationam315@cam.ac.ukKHHuman demography, population genetics, natural selection, climate modelsVSPopulation genetics, computation modelling, climate modelling, vegetation modellingFCThe Chancellor, Masters And Scholars Of The University Of CambridgeUKLS8 ERC-2014-CoGJGDetecting Local Adaptation with Climate-Informed Spatial Genetic ModelsLocal adaptation, whereby individuals of a population exhibit higher fitness in their local environment compared to that experienced by other populations, has the potential to shape the distribution of genetic diversity and influence speciation. However, R@vm$AHuub Op den Camp VOLCANOh.opdencamp@science.ru.nlLImicrobiology, methanotrophy, acidic volcanic ecosystems, elemental cycles$!Stichting Katholieke UniversiteitNLLS8 ERC-2014-ADGC@Microbiology of extremely acidic terrestrial volcanic ecosystemsTerrestrial mud volcanos are extreme environments with pH values below even 1, with temperatures up to 70 C. They represent  hotspots of greenhouse gas emissions. Despite the hostile conditions, mud volcanos harbour very unique microbial communities inv@R@$ARoger BensonTEMPOroger.benson@earth.ox.ac.ukC@vertebrate; morphology; macroevolution; osteology; palaeontologyQNdigital osteology; phylogenetic comparative methods; macroevolution; tetrapodsC@The Chancellor, Masters And Scholars Of The University Of OxfordUKLS8 ERC-2015-STGROTerrestrial vertebrates and the evolutionary origins of morphological diversityExplaining the great disparity of organismal form is a central goal of biological research. However, despite many decades of inquiry, there is little understanding of how evolution gave rise to this disparity. Key hypotheses predict changes in macroevolutR@$A Jessica Abbott ComplexSexjessica.abbott@biol.lu.semjevolutionary genetics, sexual conflict, sexual antagonism, experimental evolution, drosophila, macrostomumLunds UniversitetSELS8 ERC-2015-STGurSex-limited experimental evolution of natural and novel sex chromosomes: the role of sex in shaping complex traitsThe origin and evolution of sexual reproduction and sex differences represents one of the major unsolved problems in evolutionary biology, and although much progress had been made both via theory and empirical research, recent data suggest that sex chromoR@b"ADrorNoyPS3drorn@migal.org.ilROartificial photosynthesis; protein design; light harvesting; electron transportOLprotein chemistry; protein expression and purification; biophysical methods;'$Migal Galilee Technology Center, LtdILLS9 ERC-2013-CoG<9An artificial water-soluble photosystem by protein designThis project aims at producing a fully functional light energy conversion system that is inspired by, but does not necessarily mimic, the fundamental solar energy conversion unit of natural photosynthesis  the photosystem. This is a formidable challenge S@#AMaria Carmen ColladoMAMImcolam@iata.csic.esROfood, nutrition, diet, microbiome, health, mother-infant, early life, lactationURmetagenome, microbiome, metabolome, transcriptomics, bioinformatics, biostatisticsA>Agencia Estatal Consejo Superior Deinvestigaciones CientificasESLS9 ERC-2014-StG2/The Power of Maternal Microbes on Infant HealthRecent reports suggest that early microbial colonization has an important role for in promoting health. This may contribute to reduce the risk of chronic diseases such as obesity, allergies and inflammatory conditions. Advances in understanding host-micro@S@n"AKris Verheyen PASTFORWARDkris.verheyen@ugent.beWTglobal change, forest ecosystems, long-term community dynamcis, ecoystem functioningROcommunity ecologist, ecosystem modeller, forest ecologist, historical ecologistUniversiteit GentBELS9 ERC-2013-CoGDevelopment trajectories of temperate forest plant communities under global change: combining hindsight and forecasting (PASTFORWARD)The last decades are characterized by an upsurge of research on the impacts of global environmental changes on forests. Climate warming, atmospheric deposition of acidifying and eutrophying pollutants and land-use change are three of the most important thS@4ADirkInze AMAIZEdiinz@psb.vib-ugent.bePlant growth - maize,)Leaf growth - maize - Regulatory networksVibBELS9 ERC-2013-ADG52Atlas of leaf growth regulatory networks in MAIZEUnderstanding how organisms regulate size is one of the most fascinating open questions in biology. The aim of the AMAIZE project is to unravel how growth of maize leaves is controlled. Maize leaf development offers great opportunities to study the dynamiS@$AEniko Kubinyi EVOLOReniko.kubinyi@ttk.elte.huB?cognition, social behaviour, genetics, neuroscience, aging, dogURbioinformatics, theoretical and practical background in animal behaviour/cognition Eotvos Lorand TudomanyegyetemHULS9 ERC-2015-STGCognitive Ageing in DogsThe aim of this project is to understand the causal factors contributing to the cognitive decline during senescence and to develop sensitive and standardized behaviour tests for early detection in order to increase the welfare of affected species. With thT@41%AEhudGazitBISONEhudg@post.tau.ac.il spNanotechnology, molecular self-assembly, peptides, peptide nucleic acids, biotechnology, bio-inspired materials gdorganic chemistry, supramolecular chemistry, biochemistry, biophysics, protein and peptide chemistryTel Aviv UniversityILLS9 ERC-2015-AdGDABio-Inspired Self-Assembled Supramolecular Organic NanostructuresPeptide building blocks serve as very attractive bio-inspired elements in nanotechnology owing to their controlled self-assembly, inherent biocompatibility, chemical versatility, biological recognition abilities and facile synthesis. We have demonstrated  @T@<AArendBayer WallXBirGeomarend.bayer@ed.ac.ukOLWall-crossing, birational geometry, stability conditions, derived categoriesThe University Of EdinburghUKPE1 ERC-2013-StG(%Wall-crossing and Birational GeometryWe will use modern techniques in algebraic geometry, originating from string theory and mirror symmetry, to study fundamental problems of classical flavour. More concretely, we apply wall-crossing in the derived category to the birational geometry of mod T@#ASashaSodin SPECTRUMsasha.sodin@gmail.com74random operators, random matrices, spectral theory, 0-mathematical physics, analysis, probability, Tel Aviv UniversityILPE1 ERC-2014-StG&#Spectral theory of random operatorsThe theme of this proposal is the study of random operators associated with some geometric structure, and the influence of the geometry on the spectral properties of the operator. Such operators appear in problems from theoretical physics, and lead to new T@"A Jose Maria Martel HAPDEGMTchema.martell@icmat.esNKHarmonic Analysis, Partial Differential Equations, Geometric Measure TheoryA>Agencia Estatal Consejo Superior Deinvestigaciones CientificasESPE1 ERC-2013-CoGQNHarmonic Analysis, Partial Differential Equations and Geometric Measure TheoryThe origin of Harmonic Analysis goes back to the study of the heat diffusion, modeled by a differential equation, and the claim made by Fourier that every periodic function can be represented as a series of sines and cosines. In this statement we can find U@`"A Martin Burger LifeInversemartin.burger@wwu.deIFInverse Problems, Mathematical Imaging, Dynamic Imaging in Biomedicine/,Westfaelische Wilhelms-Universitaet MuensterDEPE1 ERC-2013-CoGHEVariational Methods for Dynamic Inverse Problems in the Life SciencesThis project will develop novel techniques for solving inverse problems in life sciences, in particular related to dynamic imaging. Major challenges in this area are efficient four- dimensional image reconstruction under low SNR conditions and further the @U@A Fabrizio Catanese TADMICAMT$!Fabrizio.Catanese@uni-bayreuth.deMJModuli spaces, surfaces, uniformization, topology of algebraic varieties, Universitaet BayreuthDEPE1 ERC-2013-ADGSPTopological, Algebraic, Differential Methods in Classification and Moduli TheoryModuli of curves with symmetries:determine the stable irreducible components of the moduli space of curves of genus g with an action of a finite group G, using a new homological invariant. Stable means: for g sufficiently large, or for sufficiently large U@"AJose Rodrigo Vort3DEulerJ.Rodrigo@warwick.ac.uk(%PDE, Euler Equations, vortex dynamics(%PDE, Euler Equations, vortex dynamicsThe University Of WarwickUKPE1 ERC-2013-CoG$!3D Euler, Vortex Dynamics and PDEThis proposal deals with a collection of problems in PDE arising from fluid mechanics.The primary motivation is the understanding of the evolution of isolated vortex lines for 3D Euler. The importance of the evolution of vorticity in incompressible fluid  U@#AJoelFineSymplecticEinsteinjoel.fine@ulb.ac.beDifferential geometry, Riemannian geometry, symplectic geometry, Einstein manifolds, gauge theory, holomorphic curves, asymptotically hyperbolic manifoldsAny of the following: Riemannian geometry, symplectic geometry, Einstein manifolds, gauge theory, holomorphic curves, asymptotically hyperbolic manifolds Universite Libre De BruxellesBEPE1 ERC-2014-CoG=:The symplectic geometry of anti-self-dual Einstein metricsThis project is founded on a new formulation of Einstein's equations in dimension 4, which I developed together with my co-authors. This new approach reveals a surprising link between four-dimensional Einstein manifolds and six-dimensional symplectic geom V@z#A DanielKral LADISTd.kral@warwick.ac.uka^graph limits, combinatorial limits, extremal combinatorics, graph theory, discrete mathematicsSPextremal combinatorics, probabilistic method, graph theory, discrete mathematicsThe University Of WarwickUKPE1 ERC-2014-CoGLarge Discrete StructuresThe proposed project seeks to introduce novel methods to analyze and approximate large graphs and other discrete structures and to apply the developed methods to solve specific open problems. A need for such methods comes from computer science where the s @V@$APiotrNowakINDEXpnowak@impan.pl63index theory; geometric group theory; property (T);63index theory; geometric group theory; property (T);/,Instytut Matematyczny Polskiej Akademii NaukPLPE1 ERC-2015-STG-*Rigidity of groups and higher index theoryThe Atiyah-Singer index theorem was one of the most spectacular achievements of mathematics in the XXth century, connecting the analytic and topological properties of manifolds. The Baum-Connes conjecture is a hugely successful approach to generalizing th V@T$AErik Wahln 3DWATERWAVESerik.wahlen@math.lu.seurmathematical analysis, nonlinear partial differential equations, fluid mechanics, free boundaries, nonlinear wavesLunds UniversitetSEPE1 ERC-2015-STGGDMathematical aspects of three-dimensional water waves with vorticityThe goal of this project is to develop a mathematical theory for steady three-dimensional water waves with vorticity. The mathematical model consists of the incompressible Euler equations with a free surface, and vorticity is important for modelling the i V@n7%A Trevor WooleyESTIAmatdw@bristol.ac.ukqnAnalytic Number Theory, Diophantine Problems, Discrete Harmonic Analysis, Function Fields, Arithmetic GeometryAnalytic Number Theory, Hardy-Littlewood method, Diophantine Problems, Discrete Harmonic Analysis, Algebraic Geometry, Function Fields, Arithmetic Geometry, Arithmetic CombinatoricsUniversity Of BristolUKPE1 ERC-2015-AdG=:Exponential sums, translation invariance, and applicationsTitle: Exponential Sums, Translation Invariance, and Applications. Short Summary: Exponential sums are fundamental throughout (analytic) number theory, and are key to the robustness of applications in theoretical computer science, cryptography, and so o W@\#APau Figueras NewNGRp.figueras@qmul.ac.uk_\numerical general relativity, black holes, AdS/CFT, numerical relativity, higher dimensionsMJnumerical general relativity, black holes, AdS/CFT, numerical relativity "Queen Mary University Of LondonUKPE2 ERC-2014-StG0-New frontiers in numerical general relativityIn recent years general relativity (GR) has become an increasingly important new tool in areas of physics beyond its traditional playground in astrophysics. The main motivation for this comes from the AdS/CFT correspondence which conjectures an equivalenc @W@A Konstantin Zarembo INTEGRALzarembo@nordita.orgStockholms UniversitetSEPE2 ERC-2013-ADG0-Integrable Systems in Gauge and String TheoryThe project is aimed at uncovering new links between integrable systems, string theory and quantum field theory. The goal is to study non-perturbative phenomena in strongly-coupled field theories, and to understand relationship between gauge fields and st W@ԴAAnne L'HuillierPALPanne.lhuillier@fysik.lth.se_\attosecond physics, ultrafast optics, lasers, atomic physics, high-order harmonic generationQNatomic physics, spectroscopy, nonlinear optics, high order harmonic generationLunds UniversitetSEPE2 ERC-2013-ADG0-Physics of Atoms with Attosecond Light PulsesThe field of attosecond science is now entering the second decade of its existence, with good prospects for breakthroughs in a number of areas. We want to take the next step in this development: from mastering the generation and control of attosecond puls W@,A Juan JoseGomez CadenasNEXTgomez@mail.cern.ch:7high pressure xenon TPC, neutrinoless double beta decayROinstrumentation, time projection chambers, low background, deep neural networksA>Agencia Estatal Consejo Superior Deinvestigaciones CientificasESPE2 ERC-2013-ADG2/Towards the NEXT generation of bb0nu experimetsNeutrinoless double beta decay is a hypothetical, very slow radioactive process whose observation would establish unambiguously that massive neutrinos are Majorana particles --- that is to say, identical to their antiparticles ---, which implies that a ne X@xA Cedric DeffayetNIRGdeffayet@iap.frModified gravity, cosmologyHEModified and Einstein Gravity, Cosmology, Relativistic Field Theories41Centre National De La Recherche Scientifique CnrsFRPE2 ERC-2012-StG63New paradigms for InfraRed modifications of GravityOur proposal addresses theoretical and phenomenological properties of large distance ( Infra-Red , IR in the following) modifications of the gravitational interaction. Such modifications are motivated by two main reasons: firstly, to find alternative expl @X@A Maciej Lewenstein OSYRISmaciej.lewenstein@icfo.esopen systems, anomalous diffusion, Brownian motion, quantum Brownian motion, classical many body stochastic processes, quantum many body stochastic processes, quantum simulators, quantum annealkers classical stochastic processes, quantum stochastic processes, statistical physics, non-equilibrium classical and quantum dynamics, quantum simulation, quantum annealers+(Fundacio Institut De Ciencies FotoniquesESPE2 ERC-2013-ADGEBOpen SYstems RevISited: From Brownian motion to quantum simulatorsThis proposal concerns open systems, i.e. systems interacting with the environment, and their fundamental role in natural sciences. The main objectives are: i) to develop theory of Brownian motion for molecules in biological environments; ii) to adapt cla X@APiet MuldersQWORKp.j.g.mulders@vu.nlebQuantum Chromodynamics (QCD) ; transverse momentum dependent parton distribution functions (TMDs);FCQCD; PDFs; Standard Model of particle physics; Structure of hadrons Stichting VuNLPE2 ERC-2012-ADG!Quantum Chromodynamics at WorkQuantum Chromodynamics (QCD) is one of the cornerstones of the Standard Model of particle physics. It describes the world of quarks, anti-quarks and gluons (partons) making up the protons and neutrons and therewith the ordinary matter in our universe. Col X@Ps#A Gerardo AdessoGQCOP"gerardo.adesso@nottingham.ac.ukQuantum information, quantum foundations, quantum correlations, quantumness, complex systems, entanglement, quantum communication, quantum metrology, quantum technologies, mathematical physics, quantum computing, quantum algorithmsQuantum information, quantum foundations, quantum correlations, quantumness, complex systems, entanglement, quantum communication, quantum metrology, quantum technologies, mathematical physics, quantum computing, quantum algorithmsThe University Of NottinghamUKPE2 ERC-2014-StG/,Genuine Quantumness in Cooperative PhenomenaThe proposed research programme addresses issues of fundamental and technological importance in quantum information science and its interplay with complexity. The main aim of this project is to provide a new paradigmatic foundation for the characterisati Y@PA Uwe-JensWieseAtomicGaugeSimulatorwiese@itp.unibe.chROQuantum simulation of gauge theories, sign problem, strongly correlated systemsZWcomputational condensed matter physics, strongly correlated systems, quantum simulatorsUniversitaet BernCHPE2 ERC-2013-ADGebClassical and Atomic Quantum Simulation of Gauge Theories in Particle and Condensed Matter PhysicsGauge theories play a central role in particle and condensed matter physics. Heavy-ion collisions explore the strong dynamics of quarks and gluons, which also governs the deep interior of neutron stars, while strongly correlated electrons determine the ph @Y@@}AReinhild Yvonne Peters COLORTTH!Yvonne.Peters@manchester.ac.uk"top, Higgs, Yukawa, colour, QCDtop, Higgs, BSMThe University Of ManchesterUKPE2 ERC-2013-StG2/The Higgs: A colored View from the Top at ATLASWith the ground-breaking discovery of a new, Higgs-like boson on July 4th, 2012, by the CMS and ATLAS collaborations at CERN, a new era of particle physics has begun. The discovery is the first step in answering an unsolved problem in particle physics, th Y@ #A Magdalena Kowalska betaDropNMRkowalska@cern.chultrasensitive NMR on metal ions, liquid NMR, metal ion interaction with biomolecules, chemical shift and relaxation time calculations, laser spin polarization, radioactive ion beams,physical chemist, bio-physicist or bio-chemist with expertise in experimental or theoretical NMR studies; familiar or interested with liquid NMR of metal ions; NMR expert interested in new NMR methods; laser spectrostroscopist working with optical pumping-*EUROPEAN ORGANIZATION FOR NUCLEAR RESEARCHCHPE2 ERC-2014-StG!Ultra-sensitive NMR in liquidsThe nuclear magnetic resonance spectroscopy (NMR) is a versatile and powerful tool, especially in chemistry and in biology. However, its limited sensitivity and small amount of suitable probe nuclei pose severe constraints on the systems that may be explo Y@#AVitor Cardoso MaGRaThvitor.cardoso@ist.utl.ptLIBlack holes; gravitational radiation; dark matter; high energy collisionsRONumerical Relativity; astrophysics; gravitational radiation; black hole physicsInstituto Superior TecnicoPTPE2 ERC-2014-CoGCMatter and strong-field gravity: New frontiers in Einstein s theoryGravity is the weakest but the most intriguing fundamental interaction in the Universe. In the last decades a formidable intellectual effort has shown that the full-fledged geometric nature of gravity offers much more than a beautiful description and unde Z@#APeterBaumDIVIpeter.baum@lmu.de41ultrafast electron microscopy, attosecond physics41ultrafast electron microscopy, attosecond physics+(Ludwig-Maximilians-Universitaet MuenchenDEPE2 ERC-2014-CoGWTDirect Visualization of Light-Driven Atomic-Scale Carrier Dynamics in Space and TimeElectronics is rapidly speeding up. Ultimately, miniaturization will reach atomic dimensions and the switching speed will reach optical frequencies. This ultimate regime of lightwave electronics, where atomic-scale charges are controlled by few-cycle lase @Z@Z#A Alessandro Bacchetta 3DSPIN Alessandro.bacchetta@unipv.it0-Hadrons, quantum chromodynamics, quark, gluon!Subnuclear theoretical physics"Universita Degli Studi Di PaviaITPE2 ERC-2014-CoG-*3-Dimensional Maps of the Spinning NucleonHow does the inside of the proton look like? What generates its spin?( 3DSPIN will deliver essential information to answer these questions at the frontier of subnuclear physics.At present, we have detailed maps of the distribution of quarks and gluons in t Z@N#ADarioPolliVIBRAdario.polli@polimi.itgdCoherent Raman Sectroscopy and Microscopy, CARS, SRS (Stimulated Raman Scattering), ultrafast lasersb_Biologist with expertise in linear and non-linear microscopy. Laser scientist. Spectroscopist. Politecnico Di MilanoITPE2 ERC-2014-CoG0-Very fast Imaging by Broadband coherent RAmanThe VIBRA project aims at developing an innovative microscope for real-time non-invasive imaging of cells and tissues, which promises to have a revolutionary impact on several fields of biology and medicine. Chemically specific vibrational signatures of m Z@s$AWim UbachsNEWPHYS-MOLECULESw.m.g.ubachs@vu.nl.+precision spectroscopy - lasers - molecules85lasers - spectroscopy - molecules - physics/chemistry Stichting VuNLPE2 ERC-2014-ADG;8Probing Physics beyond the Standard Model from MoleculesThe Standard Model of physics is incomplete. Gravity is not understood at the quantum level, dark matter and dark energy are not explained, and (string)-theories searching to cover these shortcomings are only consistent in higher-dimensional spaces, while [@$A Hans Peter Bchler SIRPOL)&buechler@theo3.physik.uni-stuttgart.dejgquantum many body systems, quantum optics, strongly interacting photons, novel phases of quantum matterjgquantum many body systems, quantum optics, strongly interacting photons, novel phases of quantum matterUniversitaet StuttgartDEPE2 ERC-2015-CoG52Strongly interacting Rydberg slow light polaritonsA fundamental property of optical photons is their extremely weak interactions, which can be ignored for all practical purposes and applications. This phenomena forms the basis for our understanding of light and is at the heart for the rich variety of too @[@h$A Sameer MurthyQBHmurthy.sameer@gmail.com,)String theory, black holes, modular formsKing'S College LondonUKPE2 ERC-2015-CoGOLQuantum Black Holes: A macroscopic window into the microstructure of gravityThe thermodynamic behavior of black holes is a precious clue in unravelling the microscopic structure of quantum gravity. High precision computations of quantum black hole entropy provide a new window into the fundamental microscopic theory of gravity and [@$A OtfriedGhne TempoQotfried.guehne@uni-siegen.deDAquantum optics, quantum information theory, temporal correlations-*quantum optics, quantum information theoryUniversitaet SiegenDEPE2 ERC-2015-CoG Temporal Quantum CorrelationsCorrelations are central for our modern view on the foundations of quantum theory and applications like quantum information processing. So far, research concentrated on correlations between two or more particles. Indeed, for this situation it is well esta [@8%A Dmitry Budker Dark-OSTbudker@uni-mainz.deROUltralight dark matter, axions, axion-like particles, NMR, atomic magnetometers'$Johannes Gutenberg-Universitat MainzDEPE2 ERC-2015-AdGSPExperimental Searches for Oscillating and Transient effects from the Dark SectorThe objective of the proposed project is to pioneer a magnetometry-based experimental framework for the detection of time-varying signatures of the  dark sector . This novel approach will enable systematic searches for particles contributing to the dark m \@""A Benoit Ladoux DURACELLbenoit.ladoux@ijm.frpmcell mechanics, mechanobiology, cell migration, cytoskeleton, biophysics, collective behaviour, active matterdacell mechanics, mechanobiology, cell migration, cytoskeleton, collective cell migration, adhesion%"Universite Paris Diderot - Paris 7FRPE3 ERC-2013-CoG.+Cell Migration under Mechanical ConstraintsControl of cell migration is crucial for many biological processes. Cells sense mechanical cues to guide their migration. As opposed to passive materials, living cells actively respond to the mechanical stimuli of their environment through the transductio @\@"ASilke Biermann CORRELMAT!biermann@cpht.polytechnique.frkhCorrelated electron materials. Electronic structure calculations. Dynamical mean field theory and beyondSPElectronic structure theory, many-body perturbation theory, correlated materialsEcole PolytechniqueFRPE3 ERC-2013-CoGPredictive electronic structure calculations for materials with strong electronic correlations: long-range Coulomb interactions and many-body screeningMaterials with strong electronic Coulomb correlations present unique electronic properties such as exotic magnetism, charge or orbital order, or unconventional optical or transport properties, including superconductivity, thermoelectricity or metal-insula \@$zA Georgios Katsaros Spajoranageorgios.katsaros@ist.ac.atb_low temperature electronic transport, quantum dots, hybrid superconductor-semiconductor devicesdalow temperature physics, semiconductor nanodevices, superconductivity, high frequency electronics.+Institute Of Science And Technology AustriaATPE3 ERC-2013-StGROTowards spin qubits and Majorana fermions in Germanium self-assembled hut-wiresA renewed interest in Ge has been sparked by the prospects of exploiting its lower effective mass and higher hole mobility to improve the performance of transistors. Ge emerges also as a promising material in the field of spin qubits, as its coherence tim \@ A Ana SuncanaSmith MembranesActsmith@physik.fau.de+(modeling cell adhesion and tissue growthKHexperiments on tissue growth, modeling using stochastic dynamics methods63Friedrich-Alexander-Universitaet Erlangen NuernbergDEPE3 ERC-2013-StGgdBiological Membranes in Action: A Unified Approach to Complexation, Scaffolding and Active TransportIn recent breakthrough publications, the effect of fluctuations on the affinity of membrane-confined molecules has been evaluated, and a quantitative model for the time evolution of small adhesion domains has been developed under my leadership. Now I prop ]@AKurt Kremer MOLPROCOMPkremer@mpip-mainz.mpg.demjMultiscale Modeling of Soft Matter, Non-Equilibrium Processes, Polymers, Formation of Functional MaterialsPMComputational Physics, Non-Equilibrium Physics, Soft Matter Materials Science>;Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften EvDEPE3 ERC-2013-ADGqFrom Structure Property to Structure Process Property Relations in Soft Matter  a Computational Physics ApproachFrom cell biology to polymer photovoltaics, (self-)assembly processes that give rise to morphology and functionality result from non-equilibrium processes, which are driven by both, external forces, such as flow due to pressure gradients, inserting energy @]@A Alexander Hoegele QuantumCANDIalexander.hoegele@lmu.de|optical spectroscopy, solid-state quantum optics, carbon nanotubes, transition metal dichalcogenides, layered semicondcutors|optical spectroscopy, solid-state quantum optics, carbon nanotubes, transition metal dichalcogenides, layered semicondcutors+(Ludwig-Maximilians-Universitaet MuenchenDEPE3 ERC-2013-StG85Interfacing quantum states in carbon nanotube devicesCoherent control and sensitive detection of quantum states in condensed matter are among the most topical challenges of modern physics. They drive the development of novel materials, theoretical concepts, and experimental methods to advance our understand ]@A Sergey Bozhevolnyi PLAQNAPseib@iti.sdu.dk>;plasmonics, plasmon-based nanophotonics, quantum plasmonics)&plasmonics, nano-optics, nanophotonicsSyddansk UniversitetDKPE3 ERC-2013-ADG52Plasmon-based Functional and Quantum NanophotonicsPlasmon-based nanophotnics, an explosively growing research field concerned with surface-plasmon waveguides and circuitry, is oriented towards exploiting unique perspectives opened for radiation guiding along metal surfaces: extreme mode confinement (i.e. ]@HALapo Bogani OptoQMol!lapo.bogani@materials.ox.ac.ukmjspintronics, molecular magnetism, electron spin resonance, time resolved experiments, donor-acceptor dyadsmjspintronics, molecular magnetism, electron spin resonance, time resolved experiments, donor-acceptor dyadsC@The Chancellor, Masters And Scholars Of The University Of OxfordDEPE3 ERC-2013-StG0-Optical Quantum Control of Magnetic MoleculesA revolution is underway, as molecular magnets are establishing a fundamental link between spintronics, molecular electronics and quantum computation. On the other hand, we know almost nothing on how a magnetic molecule is affected by electrons flowing th ^@"A Freddy Bouchet TRANSITIONFreddy.Bouchet@ens-lyon.frc`Statistical physics, Climate Dynamics, Large deviation theory, Turbulence, Rare event algorithms@=Theoretical physics /applied mathematics or climate scientist41Centre National De La Recherche Scientifique CnrsFRPE3 ERC-2013-CoGliLarge Deviations and Non Equilibrium Phase Transitions for Turbulent Flows, Climate, and the Solar SystemThe aim of this project is to predict and compute extremely rare but essential trajectories in complex physical systems. We will compute rare transitions trajectories, first between two different turbulent attractors in models of planetary jet dynamics, a @^@n#AalarGiritJSPEC$!caglar.girit@college-de-france.frEBsuperconductors, Josephson junctions, andreev states, spectroscopy/,topological materials, synthesis, semimetalsCollege De FranceFRPE3 ERC-2014-StG85Josephson Junction Spectroscopy of Mesoscopic SystemsSpectroscopy is a powerful tool to probe matter. By measuring the spectrum of elementary excitations, one reveals the symmetries and interactions inherent in a physical system. Mesoscopic devices, which preserve quantum coherence over lengths larger tha ^@P~#AAnton Akhmerov STATOPINSa.r.akhmerov@tudelft.nl,)Topological insulators, Majorana fermionsROQuantum transport, superconductivity, topological insulators, Majorana fermions Technische Universiteit DelftNLPE3 ERC-2014-StG/,Theory of statistical topological insulatorsTopological insulators (TI) are a novel class of materials with insulating bulk and conducting surface. The conduction of the surface is protected by the topological properties of the bulk, as long as a fundamental symmetry is present (for instance time-r ^@#A shahalilaniSee-1D-Qmattershahal.ilani@weizmann.ac.il;8nanotube graphene scanning probe stm transport many-body Weizmann Institute Of ScienceILPE3 ERC-2014-CoGROUnravelling Fragile 1D Quantum States of Matter Through Ultra-sensitive ImagingIn condensed matter physics there are several iconic predictions that have evaded experimental discovery for many decades. Well-known examples include the proposed fractionally-charged quasiparticles in one-dimension, the theorized quantum crystal of elec _@#A Martin WeidesQuantumMagnonicsmartin.weides@kit.eduGDquantum technology, superconducting qubits, spin waves, ferromagnetsURcryogenic measurements, spectroscopy, time domain dependence, quantum manipulation'$Karlsruher Institut Fuer TechnologieDEPE3 ERC-2014-CoGheInterfacing spin waves with superconducting quantum circuits for single magnon creation and detectionThe proposed project will experimentally interface ferromagnets with superconducting quantum circuits to study dynamics within the magnet. To this end, magnonic elements made up by thin, structured magnetic films will be strongly coupled to the qubit. Sup @_@$A Daniele Fausti INCEPTdaniele.fausti@elettra.eu?<non-equilibrium properties, complex material, quantum opticsquantum optics$!Universita Degli Studi Di TriesteITPE3 ERC-2015-STGebINhomogenieties and fluctuations in quantum CohErent matter Phases by ultrafast optical TomographyStandard time domain experiments measure the time evolution of the reflected/transmitted mean number of photons in the probe pulses. The evolution of the response of a material is typically averaged over the illuminated area as well as over many pump and  _@8$A MartinLenz MicMactinmartin.lenz@u-psud.fr.+ theory; active matter; cytoskeleton; actinB?Physics; Theory; Soft Matter; Biophysics; Statistical Mechanics41Centre National De La Recherche Scientifique CnrsFRPE3 ERC-2015-STGSPDissecting active matter: Microscopic origins of macroscopic actomyosin activityBiological motion and forces originate from mechanically active proteins operating at the nanometer scale. These individual active elements interact through the surrounding cellular medium, collectively generating structures spanning tens of micrometers w _@$A Levente Tapaszto NanoFab2Dtapaszto@mfa.kfki.hu96 Graphene, Scanning Tunneling Microscopy, 2D Materials852D Materials, Graphene, Scanning Tunneling Microscopy<9Magyar Tudomanyos Akademia Energiatudomanyi KutatokozpontHUPE3 ERC-2015-STGVSNovel 2D quantum device concepts enabled by sub-nanometre precision nanofabricationIIn today s electronics, the information storage and processing are performed by independent technologies. The information-processing is based on semiconductor (silicon) devices, while non-volatile data storage relies on ferromagnetic metals. Integrating  `@z$ASamir Lounis DYNASOREs.lounis@fz-juelich.deChiral low-dimensional magnets;Dynamical magnetic excitations;Spin-orbit interaction;Time-dependent density functional theory;Many-body perturbation theory;Magnetic nanodevices;skyrmionsA>ab-initio;supercomputing;method development;magnetism;dynamics Forschungszentrum Julich GmbhDEPE3 ERC-2015-CoGYVDynamical magnetic excitations with spin-orbit interaction in realistic nanostructuresNano-spin-orbitronics is an emerging and fast growing field that aims at combining three degrees of freedom " spin, charge and spin-orbit interaction " to explore new nanotechnologies stemming from fundamental physics. New magnetic phases of matter are in  `@$A RosalindAllen EVOSTRUCrosalind.allen@ed.ac.uk52antibiotic resistance, biofilms, spatial structuredaBiological physics, microbiology, evolutionary biology, computer simulations, statistical physicsThe University Of EdinburghUKPE3 ERC-2015-CoGb_The physics of antibiotic resistance evolution in spatially-structured multicellular assembliesThe rise in bacterial infections that are resistant to antibiotic treatment poses a major global health challenge. Addressing this challenge is not just a clinical issue: understanding bacterial resistance evolution calls for an interdisciplinary approach @`@$ARalph Ernstorfer FLATLANDernstorfer@fhi-berlin.mpg.deJG2D materials, heterostructures, ultrafast dynamics, structural dynamicsiftime-resolved spectroscopy, photoemission spectroscopy, time-resolved diffraction, 2D heterostructures>;MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EVDEPE3 ERC-2015-CoGolElectron-lattice-spin correlations and many-body phenomena in 2D semiconductors and related heterostructuresTwo-dimensional crystalline materials exhibit exceptional physical properties and offer fascinating potential as fundamental building blocks for future two-dimensional electronic and optoelectronic devices. Transition metal dichalcogenides (TMDCs) are of ``@"A Jochen Kpper COMOTIONjochen.kuepper@cfel.decontrol; biomolecule; nanoparticle; laser control; cooling; imaging; diffraction; atomic resolution ultrafast; cryogenic; buffer gaslibiophysics; molecular physics; physical chemistry; laser physics; computer science; computational physics1.Stiftung Deutsches Elektronen-Synchrotron DesyDEPE4 ERC-2013-CoG<9Controlling the Motion of Complex Molecules and ParticlesThe main objective of COMOTION is to enable novel experiments for the investigation of the intrinsic properties of large molecules, including biological samples like proteins, viruses, and small cells -X-ray free-electron lasers have enabled the observati `@A Steven De FeyterNanograph@lsisteven.defeyter@kuleuven.be,)graphene, graphite, self-assembly, device!Katholieke Universiteit LeuvenBEPE4 ERC-2013-ADGfcNanostructuring graphene and graphitic substrates for controlled and reproducible functionalizationGraphene is a new class of promising material with exceptional properties and thus warrants a plethora of potential applications in various domains of science and technology. However, due to intrinsic zero bandgap and inherently low solubility, a prerequi `@ARoma Tauler CHEMAGEBroma.tauler@idaea.csic.esHigh-throughput Omics Analytical Methods, Metabonomics, Genomics, Chemometrics, Global Change, Effects on Environmental and Biological Systems, OLOmics Analytical Methods, Environmental and Biological Systems, ChemoemtricsA>Agencia Estatal Consejo Superior Deinvestigaciones CientificasESPE4 ERC-2012-ADGCHEMometric and High-throughput Omics Analytical Methods for Assessment of Global Change Effects on Environmental and Biological SystemsWe propose to develop new chemometric and high-throughput analytical methods to assess the effects of environmental and climate changes on target biological systems which are representative of ecosystems. This project will combine powerful chemometric and `@A Julien MichelEBDDjulien.michel@ed.ac.ukEBmolecular simulations, protein dynamics, drug design, free energy DAcomputational chemist, biophysical chemist, bioNMR spectroscopistTHE UNIVERSITY OF EDINBURGHUKPE4 ERC-2013-StGfcBeyond structure: integrated computational and experimental approach to Ensemble-Based Drug Design.Although protein dynamics plays an essential role in function, it is rarely considered explicitly in current structure-based approaches to drug design. Here I propose the computer-aided design of ligands by modulation of protein dynamics, or equivalently, `@DA Ricardo Garcia 3DNANOMECHr.garcia@cisc.esHEsolid-liquid interfaces; force microscopy; nanomechanics; soft matterHEforce microscopy; solid-liquid interfaces; nanomechanics; soft matterA>Agencia Estatal Consejo Superior Deinvestigaciones CientificasESPE4 ERC-2013-ADGROThree-dimensional molecular resolution mapping of soft matter-liquid interfacesOptical, electron and probe microscopes are enabling tools for discoveries and knowledge generation in nanoscale sicence and technology. High resolution  nanoscale or molecular-, noninvasive and label-free imaging of three-dimensional soft matter-liquid i a@#AGuido Pintacuda P-MEM-NMRguido.pintacuda@ens-lyon.frNuclear Magnetic Resonance (NMR); Magic-Angle Spinning (MAS); membrane proteins; paramagnetic ions; protein structure; protein dynamics; metal transporters; metalloenzymes=:Structural biology; biophysics; biochemistry; spectroscopy41Centre National De La Recherche Scientifique CnrsFRPE4 ERC-2014-CoGIFStructure of paramagnetic integral membrane metalloproteins by MAS-NMRIntegral membrane metalloproteins are involved in the transport and homeostasis of metal ions, as well as in key redox reactions that have a tremendous impact on many fields within life sciences, environment, energy, and industry. Most of our understandi  a@{$AClaus Seidel hybridFRETcseidel@hhu.deResolving the structure and dynamics of biomolecular systems by fluorescence spectroscopy and imaging with multi-parameter detection and super-resolution (STED). In vitro and live cell studies combined with computer simulations (coarse grained and all-atoSuper-resolution fluorescence microscopy, integrative modeling, computer simulations, structural promiscuous biomolecular systems, expression of proteins with unnatural amino acids that can be used for labeling.*'Heinrich-Heine-Universitaet DuesseldorfDEPE4 ERC-2014-ADG?<hybridFRET - deciphering biomolecular structure and dynamicsTo understand and modulate biological processes, we need their spatiotemporal molecular models. In this project we propose to build these models by a holistic approach. The recent methodological and technical advances in fluorescence spectroscopy and micr @a@$A GiovanniVolpeComplexSwimmersgiovanni.volpe@physics.gu.seolmicroswimmers, experimental, active brownian motion, soft matter, stochastic phenomena, optical manipulationvsstatistical physics, microswimmers, active brownian motion, soft matter, stochastic phenomena, optical manipulationBilkent niversitesiSEPE4 ERC-2015-STGZWBiocompatible and Interactive Artificial Micro- and Nanoswimmers and Their ApplicationsMicroswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equi `a@>$A Markus ValtinerCSI.interface(%Markus.Valtiner@chemie.tu-freiberg.de_\interface science, single molecule physics, force probe experiments, solid/liquid interfaceszwsolid/liquid interface simulations, ambient pressure XPS, single molecule physics, interface science, peptide materials0-Technische Universitaet Bergakademie FreibergDEPE4 ERC-2015-STGA molecular interface science approach: Decoding single molecular reactions and interactions at dynamic solid/liquid interfacesAfter decades of truly transformative advancements in single molecule (bio)physics and surface science, it is still no more than a vision to predict and control macroscopic phenomena such as adhesion or electrochemical reaction rates at solid/liquid inter a@2$AIgor Schapiro PhotoMutant igor.schapiro@mail.huji.ac.ilWTPhotoreceptor, Rhodopsin, Retinal, Cyanobacteriochrome, Computational Photochemistry~{Spectroscopy, Photoreceptor, Rhodopsin, Phytochrome, Retinal, Mutant, Extremophiles, Photolyase, Cryptochrome, UV, Bacteria%"The Hebrew University Of JerusalemILPE4 ERC-2015-STGQNRational Design of Photoreceptor Mutants with Desired Photochemical PropertiesFrom a technological viewpoint photoreceptor proteins, the light-sensitive proteins involved in the sensing and response to light in a variety of organisms, represent biological light converters. Hence they are successfully utilized in a number of technol a@$A StefanoCorniTAME-Plasmonsstefano.corni@nano.cnr.itTQmolecular plasmonics, quantum chemistry, theory of ultrafast optical spectroscopyZWquantum chemistry, computational chemistry or physics, classical electromagnetic theory%"Consiglio Nazionale Delle RicercheITPE4 ERC-2015-CoGIFa Theoretical chemistry Approach to tiME-resolved molecular PlasmonicsUltrafast spectroscopy is a powerful tool able to disclose the atomistic real-time motion picture of the basic chemical events behind technology and Life, such as catalytic reactions or photosynthetic light harvesting. Nowadays, by cleverly harnessing the a@j5%AFrank Stienkemeier COCONISstienkemeier@uni-freiburg.de&#2-dimensional coherent spectroscopyEBexperimental femtosecond spectroscopy, molecular and cluster beams'$Albert-Ludwigs-Universitaet FreiburgDEPE4 ERC-2015-AdGHECoherent multidimensional spectroscopy of controlled isolated systemsFundamental quantum mechanical processes determine the properties of matter and their functionality. In order to understand complex processes such as light harvesting in photosynthesis and photovoltaics, a detailed knowledge of coherent effects in excitata@4$A Javier MontenegroDYNAPjavier.montenegro@usc.esSupramolecular chemistry, Organic chemistry, Peptide Chemistry, Cell Transport, Membrane Chemistry, Fluorescent Probes, Imaging, Supramolecular chemistry, Organic chemistry, Peptide Chemistry, Cell Transport, Membrane Chemistry, Fluorescent Probes, Imaging., (%Universidad De Santiago De CompostelaESPE5 ERC-2015-STG)&Dynamic Penetrating Peptide AdaptamersThe aim of this proposal is to identify, at the molecular level, the minimal topological and structural motifs that govern the membrane translocation of short peptides. A covalent reversible bond strategy will be developed for the synthesis of self-adaptib@AIlanMarekCMetCchilanm@tx.technion.ac.il<9C-C bond cleavage, organic synthesis, stereoselectivity, Synthetic organic chemist,)Technion - Israel Institute Of TechnologyILPE5 ERC-2013-ADGOLSelective Carbon-Carbon Bond Activation: A Wellspring of Untapped ReactivityThe creation of new molecular entities and subsequent exploitation of their properties is central to a broad spectrum of research disciplines from medicine to materials. Most  if not all- of the efforts of organic chemists were directed to the development b@\A Jos LuisMascareas Cid METBIOCATjoseluis.mascarenas@usc.es$!Metal catalysis, Chemical biology$!Metal catalysis, Chemical biology(%Universidad De Santiago De CompostelaESPE5 ERC-2013-ADGfcMetal catalysis in biological habitats: New strategies for optical bio-sensing and targeted therapyThis proposal aims at the discovery of robust transition-metal catalyzed transformations that can take place in aqueous media and cellular lysates, and are susceptible of being exported to living cells. Specifically, we will exploit the special coordinati@b@"A LiberatoManna TRANS-NANOliberato.manna@iit.it`]nanocrystals, nanoparticles, transformations, electron microscopy, optoelectronics, synthesisDAsynthesis, materials science, device fabrication, optoelectronics-*Fondazione Istituto Italiano Di TecnologiaITPE5 ERC-2013-CoGdaAdvancing the Study of Chemical, Structural and Surface Transformations in Colloidal NanocrystalsColloidal inorganic nanocrystals (NCs) are among the most investigated nanomaterials in Nanoscience due to their high versatility. Research on NCs went through much advancement lately, especially on synthesis, assembly and on the study of their transforma`b@pu#A Christian Mller ThermoTexchristian.muller@chalmers.seB?organic thermoelectrics, 3D printing, textile, plastic, polymerb_thermoelectrics, electrical engineering, graphene, carbon nanotube, polymer, 3D printing, fiber!Chalmers Tekniska Hoegskola AbSEPE5 ERC-2014-StG/,Woven and 3D-Printed Thermoelectric TextilesImagine a world, in which countless embedded microelectronic components continuously monitor our health and allow us to seamlessly interact with our digital environment. One particularly promising platform for the realisation of this concept is based on wb@A Sylvestre Bonnet RuProLightbonnet@chem.leidenuniv.nlxuphototherapy, photodynamic, metallodrugs, bioinorganic chemistry, photochemistry, hypoxic tumours, PACT, chemotherapyFCtumour spheroids, cancer biology, hypoxic tumours, tumour targetingUniversiteit LeidenNLPE5 ERC-2012-StG85Light-activatable ruthenium-based anticancer prodrugsChemotherapy is, after surgery, the second most efficient therapy against cancer. However, it has many side effects for cancer patients because anticancer drugs kill cancer cells but also healthy ones. My project aims at synthesizing new metal-containing b@(ADavid MecerreyesiPESdavid.mecerreyes@ehu.es%"polymers, batteries, ionic liquidsMJpolymer scientist, materials scientist, electrochemist, battery technology<9Universidad Del Pais Vasco/ Euskal Herriko UnibertsitateaESPE5 ERC-2012-StG)&Innovative Polymers for Energy StorageiPes project aims to provide adequate support to Dr. David Mecerreyes (DM) who is at the stage of consolidating an independent research team. During his scientific career, DM has demonstrated creative thinking and excellent capacity to carry out research b@#A JosephMoran CARBONFIXmoran@unistra.fr52prebiotic chemistry; metabolism; reaction networks30analytical chemistry; reaction networks; geology@=Centre International De Recherche Aux Frontieres De La ChimieFRPE5 ERC-2014-StG96Towards a Self-Amplifying Carbon-Fixing Anabolic CycleHow can simple molecules self-organize into a growing synthetic reaction network like biochemical metabolism? This proposal takes a novel synthesis-driven approach to the question by mimicking a central self-amplifying CO2-fixing biochemical reaction cyclb@oA JeromeWaser iTools4MCjerome.waser@epfl.chTQsynthetic organic chemistry, hypervalent iodine, catalysis, C-H functionalizationKHsynthetic organic chemist, expertise in catalysis and method development+(Ecole Polytechnique Federale De LausanneCHPE5 ERC-2013-StGMJHypervalent Iodine Reagents: A Tool Kit for Accessing Molecular ComplexityAgainst the backdrop of an ever-expanding world population and increasingly limited resources, progress in chemistry, and organic chemistry in particular, is essential for the future of humanity. In the last century, transition metal chemistry has completc@#A Martin Steinhart INCANAMartin Steinhart`]Capillary nanostamping, nanostructures, lithography, nanodroplet arrays, nanoporous materialsUniversitaet OsnabrueckDEPE5 ERC-2014-CoG)&Insect-inspired capillary nanostampingAim of the proposed project is a) development and establishment of insect-inspired capillary nanostamping (IICN) as next-generation contact nanolithography, b) replacing state-of-the-art lithographic and synthesis protocols requiring use of sacrificial te c@#A Sebastien Perrier TUSUPOs.perrier@warwick.ac.uk<9supramolecular, nano materials, nanotechnology, materials<9supramolecular, nano materials, nanotechnology, materialsThe University Of WarwickUKPE5 ERC-2014-CoGGDTubular Supramolecular Polymers: A new class of therapeutic polymersThis research programme will establish a new class of materials and develop them into functional devices for biomedical applications. We will design tubular supramolecular polymers, supramolecular polymer brushes (SPBs), based on the self-assembly of cycl@c@#A Julien Bachmann Solacylinjulien.bachmann@fau.deMJphotovoltaics, atomic layer deposition, 3D nanomaterials, porous materials photovoltaics, semiconductors63Friedrich-Alexander-Universitaet Erlangen NuernbergDEPE5 ERC-2014-CoGroA preparative approach to geometric effects in innovative solar cell types based on a nanocylindrical structureThe ERC Consolidator Grant project SOLACYLIN aims at providing experimental insight into the function of 'third-generation' photovoltaic systems by generating materials stacks structured in a well-defined, accurately tunable, nanocylindrical geometry. To `c@ #A Alejandro Gaita-Ario DECRESIM gaita@uv.esb_Molecular Spin Qubits, Quantum Decoherence, Pulsed EPR, http://www.uv.es/gaita/decresim.htmlGDSolid-state physicist, Theoretical physicist, Open quantum systemsUniversitat De ValenciaESPE5 ERC-2014-CoGnkA Chemical Approach to Molecular Spin Qubits: Decoherence and Organisation of Rare Earth Single Ion MagnetsCoordination Chemistry and Molecular Magnetism are in an ideal position for the rational design of Single-Molecule Magnets which can be used as molecular spin qubits, the irreducible components of any quantum technology. Indeed, a major advantage of molecc@#AJose Aleman UNBICATjose.aleman@uam.es"Organocatalysis, Photocatalysis&#photocatalysis, catalytic-materials!Universidad Autonoma De MadridESPE5 ERC-2014-CoG(%Unconventional Bifunctional CatalystsThe development of sustainable chemical processes is one of the most important features in modern chemistry. It has become a key research area worldwide providing solutions to important societal demands by optimizing the use of natural resources and minimc@B#A Dzmitry Shchukin ENERCAPSULEd.shchukin@liverpool.ac.uk&#energy nanomaterials, encapsulation/,nanomaterials, energy storage, encapsulationThe University Of LiverpoolUKPE5 ERC-2014-CoG>;Nanoencapsulation for Energy Storage and Controlled ReleaseThe main vision of the project ENERCAPSULE is the development of nanoencapsulation technologies based on switchable nanoscale barriers for novel generation of controlled energy storage and delivery systems. These systems will be based on the  smart nanocc@#A Maria Jesus Vicent MyNanomjvicent@cipf.esBiological chemistry; New materials; Intelligent materials; Polymer Chemistry; Polymer Therapeutics; Nanomedicine; Targeted drug delivery; Advanced Breast Cancer; Exosomes; MetastasisVSExosomes; Patient Derived xenografts; organoids; Metastasis; Biomarkers; PredictorsNKFundacion De La Comunidad Valenciana Centro De Investigacion PrincipefelipeESPE5 ERC-2014-CoGwtTowards the design of Personalised Polymer-based Combination Nanomedicines for Advanced Stage Breast Cancer PatientsResearch on anticancer therapies has provided little progress towards improved survival rates for patients with metastatic disease. The intrinsic advantages of polymer conjugates can be optimised to rationally design targeted combination therapies, concepc@v$ALeroy Cronin SMART-POMlee.cronin@glasgow.ac.ukinorganic chemistry; artificial intelligence; self-assembly; self-organisation; deep learning; big data; supramolecular echemistrymjinorganic chemist; computer scientist; robotics; computer vision; synthetic chemistry; interdisciplinary; University Of GlasgowUKPE5 ERC-2014-ADGURArtificial-Intelligence Driven Discovery and Synthesis of Polyoxometalate ClustersWe outline a 5 year programme that introduces a new platform for the preparation, understanding, and exploitation of precisely defined nano-molecules / materials based upon the assembly of molecular metal oxide precursors (polyoxometalates) under non-equid@w$A Varinder Aggarwal FRESCOV.AGGARWAL@BRISTOL.AC.UKURorganic synthesis, boron, stereoselective, coupling, catalysis, natural products, 1.organic synthesis, catalysis, natural productsUniversity Of BristolUKPE5 ERC-2014-ADGzwEfficient, Flexible Synthesis of Molecules with Tailored Shapes: from Photo-switchable Helices to anti-Cancer Compounds The creation of new molecular entities and subsequent exploitation of their properties is central to a broad spectrum of research disciplines from medicine to materials but progress has been limited by the difficulties associated with chemical synthesis. d@1%A Simmel FriedrichAEDNAsimmel@tum.dec`Molecular programming, in vitro synthetic biology, bionanotechnology, artificial cells & tissues`]Microfluidics, cell-free gene expression, molecular evolution, 3D printing, pattern formation# Technische Universitaet MuenchenDEPE5 ERC-2015-AdG0-Amorphous and Evolutionary DNA NanotechnologyAmorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for th@d@Z$A Jean Bernard LASSERRE TAMINGlasserre@laas.fr<9Applied Mathematics - Optimization, Scientific computing;8 Applied Mathematics; Optimization & Computer Scientist41Centre National De La Recherche Scientifique CnrsFRPE6 ERC-2014-ADGTaming non convexity?In many important areas and applications of science one has to solve non convex optimization problems and ideally and ultimately one would like to find the global optimum. However in most cases one is faced with NP-hard problems and therefore in practice`d@x#A ShaharMaoz SYNTECHmaoz@cs.tau.ac.ilEBSoftware engineering, reactive synthesis, modeling, Formal Methods2/software engineering, formal methods, ModelingTel Aviv UniversityILPE6 ERC-2014-StGA>Synthesis Technologies for Reactive Systems Software EngineersThe design and development of open reactive systems, which compute by reacting to ongoing stimuli from their environment, and include, for example, mobile applications running on smart phone devices, web-based applications, industrial robotic systems, embd@#A Edith Elkind ACCORDelkind@cs.ox.ac.ukcomputational social choice/,algorithms, preferences, voting, game theoryC@The Chancellor, Masters And Scholars Of The University Of OxfordUKPE6 ERC-2014-StGDAAlgorithms for Complex Collective Decisions on Structured DomainsAlgorithms for Complex Collective Decisions on Structured Domains. The aim of this proposal is to substantially advance the field of Computational Social Choice, by developing new tools and methodologies that can be used for making complex group decisiond@"ATijl De Bie FORSIEDtijl.debie@ugent.beKHData science, data mining, exploratory data analysis, information theorynkData science, data mining, algorithms, machine learning, probabilistic graphical models, information theoryUniversiteit GentUKPE6 ERC-2013-CoGDAFormalizing Subjective Interestingness in Exploratory Data MiningThe rate at which research labs, enterprises and governments accumulate data is high and fast increasing. Often, these data are collected for no specific purpose, or they turn out to be useful for unanticipated purposes: Companies constantly look for new d@r#A Steven Schockaert FLEXILOGSchockaertS1@cardiff.ac.ukpmentity embeddings, interpretable machine learning, knowledge representation and reasoning, description logicsCardiff UniversityUKPE6 ERC-2014-StG96Formal lexically informed logics for searching the webSemantic search engines use structured knowledge to improve traditional web search, e.g. by directly answering questions from users. Current approaches to semantic search rely on the unrealistic assumption that all true facts about a given domain are expld@y#AChris Wojtan Big Splashwojtan@ist.ac.athePhysics based animation, fluid simulation, liquid simulation, fracture simulation, computer graphics,computer graphics, animation, fluid simulation, physics based animation, applied mathematics, high performance computing, discrete differential geometry, geometric integration.+Institute Of Science And Technology AustriaATPE6 ERC-2014-StGROBig Splash: Efficient Simulation of Natural Phenomena at Extremely Large ScalesComputational simulations of natural phenomena are essential in science, engineering, product design, architecture, and computer graphics applications. However, despite progress in numerical algorithms and computational power, it is still unfeasible to coe@(x#AJean-Baptiste Mouret ResiBots jean-baptiste.mouret@inria.frrobotics, machine-learning?<Institut National De Recherche Eninformatique Et AutomatiqueFRPE6 ERC-2014-StG%"Robots with animal-like resilienceDespite over 50 years of research in robotics, most existing robots are far from being as resilient as the simplest animals: they are fragile machines that easily stop functioning in difficult conditions. The goal of this proposal is to radically change t e@A WolfgangNejdl ALEXANDRIAnejdl@kbs.uni-hannover.de@=temporal retrieval, exploration and analytics in web archives>;information retrieval, social networks, scalable algorithms2/Gottfried Wilhelm Leibniz Universitaet HannoverDEPE6 ERC-2013-ADGPMFoundations for Temporal Retrieval, Exploration and Analytics in Web ArchivesSignificant parts of our cultural heritage are produced on the Web, yet only insufficient opportunities exist for accessing and exploring the past of the Web. The ALEXANDRIA project aims to develop models, tools and techniques necessary to archive and ind@e@r$ATobyWalsh AMPLifytoby.walsh@data61.csiro.auOLsocial choice, fair division, resource allocation, optimisation, game theoryOLsocial choice, fair division, resource allocation, optimisation, game theory!Technische Universitaet BerlinDEPE6 ERC-2014-ADGAllocation Made PracticaLAllocation Made PracticaLThe AMPLify project will lay the foundations of a new field, computational behavioural game theory that brings a computational perspective, computational implementation, and behavioural insights to game theory. These foundations w`e@$AJames CheneySkyejcheney@inf.ed.ac.uk>;programming languages; databases; web programming; curationPMprogramming languages; databases; query languages; scientific data managementThe University Of EdinburghUKPE6 ERC-2015-CoGSPA programming language bridging theory and practice for scientific data curationScience is increasingly data-driven. Scientific research funders now routinely mandate open publication of publicly-funded research data. Safely reusing such data currently requires labour-intensive curation. Provenance recording the history and derivatioe@$A PhilippeCudre-Mauroux GraphIntphil@exascale.info2/Big Data; Semantic Integration; NLP; Graph Data"Big Data; NLP; Machine LearningUniversite De FribourgCHPE6 ERC-2015-CoG'$Principles of Graph Data IntegrationThe present proposal tackles fundamental problems in data management, leveraging expressive, large-scale and heterogeneous graph structures in order to integrate both unstructured (e.g., text) and structured (e.g., relational) content. Integrating heteroge@5%ALuc De RaedtSYNTHluc.deraedt@cs.kuleuven.beartificial intelligence, data science, automating data science, data mining, constraints, probabilistic programming, inductive programmingspartificial intelligence researchers working on symbolic methods in data mining / data science / machine learning!Katholieke Universiteit LeuvenBEPE6 ERC-2015-AdG%"Synthesising Inductive Data ModelsInspired by recent successes towards automating highly complex jobs like programming and scientific experimentation, the ultimate goal of this project is to automate the task of the data scientist when developing intelligent systems, which is to extract ke@|:%A Holger Hermanns POWVERhermanns@cs.uni-saarland.deZWembedded software, quantitative verification, power management, light electric vehiclesolformal verification, stochastic models, power management, supervisory control, motor and charge electronics Universitat Des SaarlandesDEPE6 ERC-2015-AdG!Power to the People. Verified.Twenty years ago we were able to repair cars at home. Nowadays customer services repair coffee machines. By installing software updates. Soon you will no longer be able to repair your bike.Embedded software innovations boost our society; they help us treme@ #A Giuseppe Notarstefano OPT4SMART&#giuseppe.notarstefano@unisalento.itVSDistributed optimization, distributed control, multi-agent systems, cptimal controlGDOptimization, Control Theory, Signal Processing, distributed controlUniversita Del SalentoITPE7 ERC-2014-StGEBDistributed Optimization Methods for Smart Cyber-Physical NetworksThe combination of embedded electronics and communication capability in almost any mobile or portable device has turned this century into the age of cyber-physical networks. Smart communicating devices with their sensing, computing and control capabilitief@TA Juan DanielPrades Garca BetterSensedprades@el.ub.edu<9low power devices, sensors, gas sensors, chemical sensors+(electrical characterization, device testUniversitat De BarcelonaESPE7 ERC-2013-StGFCNanodevice Engineering for a Better Chemical Gas Sensing TechnologyBetterSense aims to solve the two main problems in current gas sensor technologies: the high power consumption and the poor selectivity. For the former, we propose a radically new approach: to integrate the sensing components and the energy sources intima f@ #A Patrice Genevet FLATLIGHTpg@crhea.cnrs.frMetasurfaces, metamaterials?<nano-fabrication, nano-structuration, semiconductor physics 41Centre National De La Recherche Scientifique CnrsFRPE7 ERC-2014-StG52Functional 2D metamaterials at visible wavelengthsFor the last 15 years, optics has undergone a remarkable evolution towards ever decreasing sizes, better integration in complex systems, and more compact devices readily available to mass markets. Whereas traditional optics is at the centimeter scale, new@f@ALiam O'Faolain DANCERliam.ofaolain@tyndall.ieLInanophotonics, photonic crystal, silicon photonics, optical interconnectsLInanophotonics, photonic crystal, silicon photonics, optical interconnectsCork Institute Of TechnologyUKPE7 ERC-2013-StG63DAtacommunications based on NanophotoniC ResonatorsA key challenge for the 21st century is, therefore to provide billions of people with the means to access, move and manipulate, what has become, huge volumes of information. The environmental and economic implications becoming serious, making energy effic`f@"A Davide Iannuzzi DIDYMUSd.iannuzzi@vu.nlNKOptical fiber sensors, Mechanobiology, Neuroscience, Instrument development Stichting VuNLPE7 ERC-2013-CoGgdMICROMACHINED OPTOMECHANICAL DEVICES: looking at cells, tissues, and organs ... with a gentle touch.Every time we grab an object to look at its geometrical details or to feel if it is hard or soft, we are ineluctably confronted with the limits of our senses. Behind its appearances, the object may still hide information that, encrypted in its microscopicf@0"Amarco liserreHEARTml@tf.uni-kiel.dC@power electronics, power system, WBG semiconductors, reliabilityC@power electronics, power system, WBG semiconductors, reliability,)Christian-Albrechts-Universitaet Zu KielDEPE7 ERC-2013-CoGpmThe Highly Efficient And Reliable smart Transformer (HEART), a new Heart for the Electric Distribution SystemIn the last 10 years, power electronics has moved significantly towards the electric grid, making it more flexible and decentralized. Still important challenges remain. One of the most thrilling is re-inventing the distribution transformer after more thanf@w#A Ludovic Righetti CONT-ACT$!ludovic.righetti@tuebingen.mpg.de;8robotics, optimal control, contact interaction, learning<9learning control, reinforcement learning, optimal control>;Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften EvDEPE7 ERC-2014-StGA>Control of contact interactions for robots acting in the worldWhat are the algorithmic principles that would allow a robot to run through a rocky terrain, lift a couch while reaching for an object that rolled under it or manipulate a screwdriver while balancing on top of a ladder? Answering this seemingly nave quesf@0A Balpreet Ahluwalia Nanoscopy"balpreet.singh.ahluwalia@uit.noPMSuper-resolution optical microscopy, Nanoscopy, Integrated optics, Waveguides/,Microscopy, Optics, Waveguides, Bio-imaging Universitetet I TromsoeNOPE7 ERC-2013-StGNKHigh-speed chip-based nanoscopy to discover real-time sub-cellular dynamicsOptical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in f@#A Madeleine Lowery DBSModelmadeleine.lowery@ucd.ieNeural Engineering, deep brain stimulation, computational neuroscience, neural modelling, parkinson's disease, electromyographyebelectrophysiology, parkinson's disease, deep brain stimulation, neuromodulation, neural prosthesesDAUniversity College Dublin, National University Of Ireland, DublinIEPE7 ERC-2014-CoGZWMultiscale Modelling of the Neuromuscular System for Closed Loop Deep Brain StimulationDeep brain stimulation (DBS) is an effective therapy for treating the symptoms of Parkinson s disease (PD). Despite its success, the mechanisms of DBS are not understood and there is a need to improve DBS to improve long-term stimulation in a wider patieng@#A Nicolae PanoiuQUANTUMMETALINKn.panoiu@ucl.ac.ukQuantum metamaterials"Computational quantum mechanicsUniversity College LondonUKPE7 ERC-2014-CoGQuantum Metamaterials: A Theoretical and Computational Approach Towards Seamlessly Integrated Hybrid Classical/Quantum Nano-structuresThe overarching aim of this proposal is to initiate and advance an integrated theoretical and computational research programme in an emerging area of metamaterials research, namely Quantum Metamaterials. Thus, it is commonly believed that one of the most  g@|#APetar Popovski WILLOWpetarp@es.aau.dkURwireless communications, machine-to-machine communication, ultra-reliable wireless=:Internet of Things, data mining, UAV, blockchain, wirelessAalborg UniversitetDKPE7 ERC-2014-CoGEBWIreLess LOWband communications: massive and ultra-reliable accessThe overall objective of WILLOW is to make wireless communication a true commodity by enabling lowband communications: low-rate links for massive number of devices and ultra-reliable connectivity. This research effort is a major endeavour in the area of w@g@#ABernd RiegerOptonanoATcryob.rieger@tudelft.nlsuper-resolution microscopy, image processing, fluorescence at cryogenic temperature, polarization optics, registration of point cloudsWTphysics, (computational) microscopy, optics, electrical engineering, computer vision Technische Universiteit DelftNLPE7 ERC-2014-CoGa^Optical nanoscopy at 1 nm resolution: far-field fluorescence control at cryogenic temperaturesOptical nanoscopy is a powerful technique used in biology to study subcellular structures and function via specifically targeted fluorescent labels. Localization microscopy in particular offers a much better resolution (~10-50 nm) than conventional micros`g@v#A Daniele Ielmini RESCUEdaniele.ielmini@polimi.itMemristor, resistive switching memory, memristive computing, neuromorphic hardware, spin-transfer torque magnetic memory, crosspoint architectureMemristor, resistive switching memory, memristive computing, neuromorphic hardware, spin-transfer torque magnetic memory, crosspoint architecturePolitecnico Di MilanoITPE7 ERC-2014-CoG)&REsistive-Switch CompUting bEyond CMOSDigital computers rely today on CMOS (complementary metal-oxide-semiconductor) technology, which improves its performance every generation thanks to the Moore s law of downscaling. As CMOS transistor size approaches few nm, alternative logic switches withg@$AIvo Vellekoop DEEPVISIONi.m.vellekoop@utwente.nlSPnonlinear microscopy, wavefront shaping, light scattering, computational imagingSPnonlinear microscopy, wavefront shaping, light scattering, computational imagingUniversiteit TwenteNLPE7 ERC-2015-STGJGInformation-age microscopy for deep vision imaging of biological tissueModern biology could not exist without the optical microscope. Hundreds of years of research have seemingly developed microscopes to perfection, with one essential limitation: in turbid biological tissue, not even the most advanced microscope can penetratg@$A Elison Matioli In-Needelison.matioli@epfl.chTQGaN, power electronics, ballistic devices, semiconductor physics, quantum devicesTQGaN, power electronics, ballistic devices, semiconductor physics, quantum devices+(Ecole Polytechnique Federale De LausanneCHPE7 ERC-2015-STG<9III-Nitrides Nanostructures for Energy-Efficiency DevicesEnergy efficiency offers a vast and low-cost resource to address future energy demand while reducing carbon dioxide emissions. The unique properties of III-Nitride semiconductors make them the ideal material for future energy challenges. Their outstandingg@$A Christian Cipriani MYKIch.cipriani@sssup.it Upper limb prostheses, artificial hand, grasping, manipulation, human machine interfaces, sensory feedback, myoelectric control, emg, Artificial sensors, bioengineering Upper limb prostheses, artificial hand, grasping, manipulation, human machine interfaces, sensory feedback, myoelectric control, emg, Artificial sensors, bioengineering, biomechanics, hand surgeryHEScuola Superiore Di Studi Universitari E Di Perfezionamento Sant'AnnaITPE7 ERC-2015-STGYVA Bidirectional MyoKinetic Implanted Interface for Natural Control of Artificial LimbsMYKI aims at developing and clinically evaluating a dexterous hand prosthesis with tactile sensing which is naturally controlled and perceived by the amputee. This will be possible by overcoming the conventional approaches based on recording electrical sig@,A Michael De VolderHIENAmfld2@cam.ac.ukspcarbon nanotubes, hierarchical materials, energy storage, water filtration, CNT, graphene, battery, biomimeticWTCNT, carbon nanotubes, graphene, battery, hierarchical, biomimetic, water filtrationFCThe Chancellor, Masters And Scholars Of The University Of CambridgeUKPE8 ERC-2013-StG$!Hierarchical Carbon NanomaterialsOver the past years, carbon nanomaterial such as graphene and carbon nanotubes (CNTs) have attracted the interest of scientists, because some of their properties are unlike any other engineering material. Individual graphene sheets and CNTs have shown a Yh@A HelenaVan Swygenhoven MULTIAXHelena.vanswygenhoven@psi.ch?<multiaxial, deformation, alloys, microstructure, mechanicalPaul Scherrer InstitutCHPE8 ERC-2013-ADG:7MULTIAX: Multiaxial and Multiscale Plasticity in MetalsOur ambition is to probe the influence of non-proportional multiaxial straining on the multiscale aspects of metal plasticity with focus on three deformation mechanisms: dislocation plasticity in bcc metals, mechanical twinning in fcc metals and the marte h@#ALuis Pereira NewFunlmnp@fct.unl.ptPaper electronics, cellulose nanocomposites, electronic and electrochemical devices, cellulose nanofibers/oxides nanocomposites, cellulose templates for electronics and photonicsCellulose based electronics and photonics, Cellulose Photonics, Cellulose modification, electronic and electrochemical devices based on biomaterials and cellulose derivatives.DANova Id Fct - Associacao Para A Inovacao E Desenvolvimento Da FctPTPE8 ERC-2014-StGNKNew era of printed paper electronics based on advanced functional celluloseFully recyclable and low cost electronic goods are still far from reality. My interest is in creating environmental friendly advanced functional materials and processes able to result in new class of paper based electronic products. This represents a rebo@h@#A AlbertoFina INTHERMalberto.fina@polito.itOLThermal conductivity of polymer nanocomposites, graphene functionalization, OLgraphene functionalization, phonon spectra, molecular dynamics, DFTB, SThM, Politecnico Di TorinoITPE8 ERC-2014-StGa^Design, manufacturing and control of INterfaces in THERMally conductive polymer nanocompositesThis proposal addresses the design, manufacturing and control of interfaces in thermally conductive polymer/graphene nanocomposites. In particular, the strong reduction of thermal resistance associated to the contacts between conductive particles in a pe`h@A Jrgen Eckert INTELHYBjuergen.eckert@oeaw.ac.atTQ Next generation of complex metallic materials with intelligent hybrid structuressolid background in materials science, physics, metastable phase formation and transformation, mechanical and functional propertiesIFLeibniz-Institut Fuer Festkoerper- Und Werkstoffforschung Dresden E.V.DEPE8 ERC-2013-ADGSPNext generation of complex metallic materials with intelligent hybrid structuresIn a modern society, metallic materials are crucially important (e.g. energy, safety, infrastructure, transportation, health, medicine, life sciences, IT). Contemporary examples with inherent challenges to be overcome are the design of ultrahigh specific h@@"AJoris Thybauti-CaDJoris.Thybaut@UGent.be30catalysis, reaction engineering, rational designC@catalyst synthesis and characterization, high throughput testingUniversiteit GentBEPE8 ERC-2013-CoGDAInnovative Catalyst Design for Large-Scale, Sustainable ProcessesA systematic and novel, multi-scale model based catalyst design methodology will be developed. The fundamental nature of the models used is unprecedented and will represent a breakthrough compared to the more commonly applied statistical, correlative relah@ԒAPavel LevkinDropCellArraylevkin@kit.edu96cell screening, droplet microarray, HTS, microfluidics'$Karlsruher Institut Fuer TechnologieDEPE8 ERC-2013-StGWTDropletMicroarrays: Ultra High-Throughput Screening of Cells in 3D MicroenvironmentsHigh-throughput (HT) screening of live cells is crucial to accelerate both fundamental biological research and discovery of new drugs. Current methods for HT cell screenings, however, either require a large number of microplates, are prone to cross-contamh@"A Alberto Guardon NSHOCKalberto.guardone@polimi.itFluid mechanics, Non-ideal compressible-fluid flows, non-classical flows, themordynamics, binary mixtures, siloxane fluids, turbomachineryFluid mechanics, Non-ideal compressible-fluid flows, non-classical flows, themordynamics, binary mixtures, siloxane fluids, turbomachineryPolitecnico Di MilanoITPE8 ERC-2013-CoGGDNon classical rarefaction shock-waves in molecularly complex vapoursThe expansion of a dilute gas through a gasdynamics convergent-divergent nozzle can occur in three different regimes, depending on the inlet and discharge conditions and on the gas: via a fully subsonic expansion, via a subsonic-supersonic or via a subsonh@N"AMarcoDentz MHetScalemarco.dentz@csic.esfcmixing, dispersion, reaction, flow, groundwater, heterogenous media, anomalous transport, upscalingA>Agencia Estatal Consejo Superior Deinvestigaciones CientificasESPE8 ERC-2013-CoGMixing in Heterogeneous Media Across Spatial and Temporal Scales: From Local Non-Equilibrium to Anomalous Chemical Transport and Dynamic UncertaintyTransport, mixing and reaction of solutes and particles in natural media are of central importance in many fields of science and engineering, ranging from contaminant dispersion in geophysical flows to diffusion in living cells. Transport in these intrinsi@A Nathalie De Geyter PLASMATSnathalie.degeyter@ugent.beJGnon-thermal plasma, electrospinning, surface modification, biomaterials63electrospinning, surface modification, biomaterialsUniversiteit GentBEPE8 ERC-2013-StGhePlasma-assisted development and functionalization of electrospun mats for tissue engineering purposesIn this project, I will explore the unique combination of two fascinating research themes: electrospinning and plasma technology. Electrospun nanofibrous matrices (so-called mats) are an exciting class of materials with a wide range of possible applicatio i@ns#A PatrickGrrn HyMoCogoerrn@uni-wuppertal.de63optics, plasmonics, thin films, light concentrators+(optics, plasmonics, thin film technology$!Bergische Universitaet WuppertalDEPE8 ERC-2014-StG=:Hybrid Node Modes for Highly Efficient Light ConcentratorsThe meaning of solar energy for future decentralized power supply will largely depend on both efficiency and cost of solar to electrical power conversion. All kinds of conversion strategies including photovoltaics, concentrated solar power, solar to fuel @i@"ALuca Brandt TRITOSluca@mech.kth.seheparticle-laden flows, multiphase turbulent flows, numerical simulations, heat transfer in suspensionsifparticle-laden flows, experimental particle-laden flows, computational algorithms for multiphase flowsKungliga Tekniska HoegskolanSEPE8 ERC-2013-CoG41TRansItions and Turbulence Of complex SuspensionsThe aim of this project is to forge a physical understanding of the transitions and of the turbulent flow of semi-dilute/dense non-colloidal suspensions, for different particle features and suspending fluids. It is estimated that 10% of the world energy c`i@dAGbor StpnSIRENstepan@mm.bme.huspTime delayed mechanical systems, chatter, modelling of cutting, modelling of dynamic contacts,damping, frictionchip-formation, finite element modelling, dissipation, friction, contact force distribution, electric resistance, rotating spindle, bearing stiffness and damping, contactless measurement, semi-virtual machining, hardware-in-the-loop1.Budapesti Muszaki Es Gazdasagtudomanyi EgyetemHUPE8 ERC-2013-ADG96Stability Islands: Performance Revolution in MachiningCutting went through a revolution in the 1990s when high-speed milling (HSM) was introduced: the sculpture-like workpieces produced with high precision and efficiency resulted in one order of magnitude less parts in cars/aircrafts, which kept this traditii@(t#AMark Ahearne EYEREGENahearnm@tcd.ie+(tissue engineering, cornea, biomaterialsThe Provost, Fellows, Foundation Scholars & The Other Members Of Board Of The College Of The Holy & Undivided Trinity Of Queen Elizabeth Near DublinIEPE8 ERC-2014-StG@=Engineering a scaffold based therapy for corneal regenerationCorneal blindness resulting from disease, physical injury or chemical burns affects millions worldwide and has a considerable economic and social impact on the lives of people across Europe. In many cases corneal transplants can restore vision however thei@`ALuca Biferale NewTURBbiferale@roma2.infn.itVSturbulence, direct numerical simulations, large eddy simulations, atmospheric flowsturbulence, direct numerical simulations, large eddy simulations, dynamical systems, atmospheric flows, magnetohydrodynamics, out-of-equilibrium statistical mechanics, turbulent diffusion,)Universita Degli Studi Di Roma TorvergataITPE8 ERC-2013-ADGVSNew eddy-simulation concepts and methodologies for frontier problems in TurbulenceAdvances in transportation, energy harvesting, chemical processing, climatology, atmospheric and marine pollution are obstructed by the lack of understanding of turbulence. The turbulent energy transfer toward small-scales is characterized by highly non-Gi@#A Darrell Patterson TUNEMEMd.patterson@bath.ac.ukmembrane reactor, stimuli responsive materials, homogeneous catalysis, pharma synthesis, membrane separations, nanofiltration, smart materialsmembrane reactor, stimuli responsive materials, homogeneous catalysis, pharma synthesis, membrane separations, nanofiltration, smart materialsUniversity Of BathUKPE8 ERC-2014-CoG85Externally Tuneable Separations for Membrane ReactorsI will develop an all new type of reactor for pharmaceutical and chemical process applications  the  tuneable membrane reactor . These contain ground-breaking conducting polymer composite membranes that will allow in-situ tuning of the molecular selectivi@#AManuela Teresa Raimondi NICHOIDmanuela.raimondi@polimi.itfcmechanobiology, two-photon polymerization, nanofabrication, stem cell, bioengineering, biomechanics;8live imaging, confocal, molecular biology, biotechnologyPolitecnico Di MilanoITPE8 ERC-2014-CoGliMechanobiology of nuclear import of transcription factors modeled within a bioengineered stem cell niche.Many therapeutic applications of stem cells require accurate control of their differentiation. To this purpose there is a major ongoing effort in the development of advanced culture substrates to be used as  synthetic niches for the cells, mimicking the j@6#A StephaneAVRIL BIOLOCHANICSavril@emse.frZWmechanobiology, aneurysms, computational modelling, predictive/personnalized medecine, bioengineeringZWAssociation Pour La Recherche Et Le Developpement Des Methodes Et Processus IndustrielsFRPE8 ERC-2014-CoG^[Localization in biomechanics and mechanobiology of aneurysms: Towards personalized medicineRupture of Aortic Aneurysms (AA), which kills more than 30 000 persons every year in Europe and the USA, is a complex phenomenon that occurs when the wall stress exceeds the local strength of the aorta due to degraded properties of the tissue. The state o j@n#A DongshengWen iNanoEORd.wen@leeds.ac.ukLInanotechnology, oil and gas, nanoparticle synthesis, controlled delivery 30nanomaterials, oil and gas, chemical engineeringUniversity Of LeedsUKPE8 ERC-2014-CoG;8In-situ produced nanoparticles for enhanced oil recovery The era of finding  easy oil is coming to an end, and future supply will become more reliant on fossil fuels produced from enhanced oil recovery (EOR) process. Many EoR methods have been used, including mechanical, chemical, thermal and biological appr@j@Z$A BerendSmitMaGicberend.smit@epfl.chDAMolecular simulations, metal organic frameworks, materials genome@=molecular dynamics, monte carlo simulations, materials genome+(Ecole Polytechnique Federale De LausanneCHPE8 ERC-2014-ADG!The Materials Genome in ActionIt is now possible to make an enormous spectrum of different, novel nanoporous materials simply by changing the building blocks in the synthesis of Metal Organic Frameworks (MOF) or related materials. This unique chemical tunability allows us to tailor-ma`j@k$A Javier LLORCA VIRMETALjavier.llorca@imdea.org Multiscale materials modeling;8multiscale materials modeling; physical metallurgy; ICMEFundacion Imdea MaterialesESPE8 ERC-2014-ADGOLVirtual Design, Virtual Processing and Virtual Testing of Metallic MaterialsThe project VIRMETAL is aimed at developing multiscale modeling strategies to carry out virtual design, virtual processing and virtual testing of advanced metallic alloys for engineering applications so new materials can be designed, tested and optimized j@4n$A MarcusAldnTUCLAMarcus.Alden@forbrf.lth.serocombustion, laser diagnostics, laser-induced fluorescence, plasma assisted combustion, high pressure combustionrocombustion, laser diagnostics, laser-induced fluorescence, plasma assisted combustion, high pressure combustionLunds UniversitetSEPE8 ERC-2014-ADG\YTowards a deepened understanding of combustion processes using advanced laser diagnosticsThe field of combustion is of utmost societal/industrial importance while at the same time posing outstanding scientific challenges. In order to handle these, it is extremely important to develop and apply non-intrusive laser-diagnostic techniques with hij@n$A Javier Jimenez Coturb jimenez@torroja.dmt.upm.es?<turbulence theory, turbulence control, large scale computingB?turbulence researcher with a physics or computation background $!Universidad Politecnica De MadridESPE8 ERC-2014-ADG1.Coherent Structures in Wall-bounded TurbulenceTurbulence is a multiscale phenomenon for which control efforts have often failed because the dimension of the attractor is large. However, kinetic energy and drag are controlled by relatively few slowly evolving large structures that sit on top of a multj@\$A Camilla Colombo COMPASScamilla.colombo@polimi.itOrbit perturbations, space trajectory design, optimisation, spacecraft dynamics, space debris, asteroids, astrodynamics, manifold dynamics, dynamical system theory in astrdynamics, semi-analytical methods, space missionsebapplied mathematics, dynamical system theory, computer science, space engineer, physics, astronomyPolitecnico Di MilanoITPE8 ERC-2015-STGWTControl for Orbit Manoeuvring through Perturbations for Application to Space SystemsSpace benefits mankind through the services it provides to Earth. Future space activities progress thanks to space transfer and are safeguarded by space situation awareness. Natural orbit perturbations are responsible for the trajectory divergence from thj@$AArri Priimgi PHOTOTUNEarri.priimagi@tut.fiifphotoactuation, photomechanics, azobenzene, liquid crystals, tunable plasmonics, SERS, organic lasers ifphotoactuation, photomechanics, azobenzene, liquid crystals, tunable plasmonics, SERS, organic lasers Tty-SaatioFIPE8 ERC-2015-STG<9Tunable Photonic Structures via Photomechanical ActuationThe next frontier in photonics is to achieve dynamic and externally tunable materials that allow for real-time, on-demand control over optical responses. Light is in many ways an ideal stimulus for achieving such control, and PHOTOTUNE aims at devising a k@F$AEleni Chatzi WINDMILchatzi@ibk.baug.ethz.chwind turbines, sustainability, life cycle assessment, structural health monitoring, structural identification, multi fidelity modeling, decision support tools, infrastructure managementwind turbines, life cycle assessment, structural health monitoring, structural identification, multi fidelity modeling, decision support tools0-Eidgenoessische Technische Hochschule ZuerichCHPE8 ERC-2015-STGJGSmart Monitoring, Inspection and Life-Cycle Assessment of Wind TurbinesThe excessive energy consumption that Europe is faced with, calls for sustainable resource management and policy-making. Amongst renewable sources of the global energy pool, wind energy holds the lead. Nonetheless, wind turbine (WT) facilities are conjoin k@$A IoannisPapakonstantinou IntelGlazingi.papakonstantinou@ucl.ac.uktransition metal oxides, vanadium dioxide, tuneable plasmonics, thermochromic windows, smart windows, smart materials, superhydrophobic surfaces, antireflection coatings, nanotechnology, nanophotonicsnanotechnology, nanophotonics, metamaterials, plasmonics, nanofabrication, finite difference time domain, heat transport, radiative cooling, thermochromic materials, transition metal oxides, superhydrophobic surfaces, thermodynamicsUniversity College LondonUKPE8 ERC-2015-STGyvIntelligent functional glazing with self-cleaning properties to improve the energy efficiency of the built environmentThe latest forecast by the International Energy Agency predicts that the CO2 emissions from the built environment will reach 15.2Gt in 2050, double their 2007 levels. Buildings consume 40% of the primary energy in developed countries with heating and cool@k@t$A Albert Tarancn ULTRASOFCatarancon@irec.cat:7Fundacio Institut De Recerca De L'Energia De Catalunya ESPE8 ERC-2015-CoGwtBreaking the temperature limits of Solid Oxide Fuel Cells: Towards a new family of ultra-thin portable power sourcesSolid Oxide Fuel Cells (SOFCs) are one of the most efficient and fuel flexible power generators. However, a great limitation on their applicability arises from temperature restrictions. Operation approaching room temperature (RT) is forbidden by the limit`k@$A Marino Arroyo EpiMechmarino.arroyo@upc.edu^[cell and tissue mechanics, epithelia, computational mechanics, mechanobiology, biomembranes'$Universitat Politecnica De CatalunyaESPE8 ERC-2015-CoGZWEpithelial cell sheets as engineering materials: mechanics, resilience and malleabilityThe epithelium is a cohesive two-dimensional layer of cells attached to a fluid-filled fibrous matrix, which lines most free surfaces and cavities of the body. It serves as a protective barrier with tunable permeability, which must retain integrity in a k@h$A Lothar Wondraczek UTOPES Lothar.wondraczek@uni-jena.de.+glass; photonics; optical materials; energy.+glass; photonics; optical materials; energy&#Friedrich-Schiller-Universitat JenaDEPE8 ERC-2015-CoGKHUnifying concepts in the topological design of non-crystalline materialsGlasses have traditionally been enabling materials to major societal challenges. Significant breakthroughs on many areas of technological progress have been very closely linked to the exploitation of glassy materials. It is strong consensus that this key k@<6%A Mercedes Maroto-Valer MILEPOSTm.maroto-valer@hw.ac.ukSPReactive transport, Porous media, Chemical rates, Pore modelling, 3D micromodels74flow in porous media, 3D printing, embedding sensorsHeriot-Watt UniversityUKPE8 ERC-2015-AdG74Microscale Processes Governing Global SustainabilityReactive transport modelling is a key tool in understanding the extremely complex interplay of flow, transport and reactions occurring over various temporal and spatial scales in the subsurface. The most difficult challenge in reactive transport is the cak@;%AHeinz Pitsch MILESTONEH.Pitsch@itv.rwth-aachen.dea^Turbulent Combustion, Dissipation Elements, Direct Numerical Simulation, Large Eddy Simulation74Rheinisch-Westfaelische Technische Hochschule AachenDEPE8 ERC-2015-AdGLIMulti-Scale Description of Non-Universal Behavior in Turbulent CombustionCombustion is an extremely important field for our society. The development of new, step-change technologies is essential and greatly benefits from computational design. However, turbulent combustion physics are complex, highly non-linear, of multi-scale k@"$A GuillaumeHaiat BoneImplant$!guillaume.haiat@univ-paris-est.frBone, Implant, Biomechanics, ultrasound, modeling, simulation, osseointegration, acoustics, mechanical engineering, Medical engineering and technology, mechanical engineering, signal processing, mechanotransduction, micromechanics, orthopedic surgery, denBone, Implant, Biomechanics, ultrasound, modeling, simulation, osseointegration, acoustics, mechanical engineering, Medical engineering and technology, mechanical engineering, signal processing, mechanotransduction, micromechanics, orthopedic surgery, den41CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRSFRPE8 ERC-2015-CoGaMonitoring bone healing around endosseous implants: from multiscale modeling to the patient s bedImplants are often employed in orthopaedic and dental surgeries. However, risks of failure, which are difficult to anticipate, are still experienced and may have dramatic consequences. Failures are due to degraded bone remodeling at the bone-implant interl@$A Jean-Michel Desert EXO-ATMOSdesert@uva.nlAstronomy, Planetary Systems Sciences, Exoplanets, Exoplanets atmospheres, Observations, exoplanets, exoplanet atmospheres, bio-signatures, planets, starsExoplanets, planet atmospheres, exoplanet characterization, stellar astrophysics, astrobiology, biosignatures, exoplanets, exoplanet atmospheres, bio-signatures, planets, starsUniversiteit Van AmsterdamNLPE9 ERC-2015-STGQNExploring the Plurality of New Worlds: Their Origins, Climate and Habitability Recent surveys have revealed an amazing, and yet unexplained, diversity of planets orbiting other stars. The key to understanding and exploiting this diversity is to study their atmospheres. This is because exoplanets atmospheres are unique laboratories l@"AMark SullivanSPCNDm.sullivan@soton.ac.ukFCastrophysics; cosmology; supernovae; dark energy; stellar evolutionUniversity Of SouthamptonUKPE9 ERC-2013-CoG74Supernovae: Physics and Cosmology in the Next DecadeExploding stars, or supernovae, impact upon many diverse areas of astrophysics, from galaxy formation, to stellar evolution, to cosmology and studies of dark energy. I am playing a leading role in new, wide-field, high-cadence optical surveys that are rev@l@>"A Giovanna Tinetti ExoLightsg.tinetti@ucl.ac.uk@=Exoplanets, atmospheric physics, spectroscopy, space missions>;Exoplanets, big data analysis techniques, planetary scienceUniversity College LondonUKPE9 ERC-2013-CoG%"Decoding Lights from Exotic WorldsIt is now accepted that exoplanets are ubiquitous. However little is known about those planets we have detected beyond the fact they exist and their location. For a minority, we know their weight, size and orbital parameters. For less than twenty, we have`l@"A Rainer SchoedelGALACTICNUCLEUSrainer@iaa.esgdNear infrared observational astronomy; stellar populations, Galactic Center, high angular resolutionwtNear infrared observational astronomy; stellar populations, Galactic Center, high angular resolution, image analysisA>Agencia Estatal Consejo Superior Deinvestigaciones CientificasESPE9 ERC-2013-CoGThe Fingerprint of a Galactic Nucleus: A Multi-Wavelength, High-Angular Resolution, Near-Infrared Study of the Centre of the Milky WayGalactic stellar nuclei are very common in all types of galaxies and are marked by the presence of nuclear star clusters, the densest and most massive star clusters in the present-day Universe. Their formation is still an unresolved puzzle. The centre of l@ܛA Hubertus  Rottgering  NewClusters rottgering@strw.leidenuniv.nlspradio astronomy, merging clusters, protoclusters, distant radio galaxies, epoch of deionisation, radio feedback spradio astronomy, merging clusters, protoclusters, distant radio galaxies, epoch of deionisation, radio feedback Universiteit LeidenNLPE9 ERC-2012-ADGb_A new window on the Universe: The formation and evolution of galaxy clusters and proto-clustersThe formation and evolution of clusters and proto-clusters of galaxies will be studied using unique diagnostic tools provided by the new pan-European radio telescope LOFAR and the APERTIF phased arrays on WSRT radio telescope. Combined with new ultra low l@\#A Kazuya Koyama CosTesGravKazuya.Koyama@port.ac.ukB?cosmology, dark energy, modified gravity, large scale structure/,postdoctoral researcher, lecturer, professor85University Of Portsmouth Higher Education CorporationUKPE9 ERC-2014-CoG Cosmological Tests of GravityEinstein s theory of General Relativity (GR) is tested accurately within the local universe i.e., the solar system, but this leaves open the possibility that it is not a good description at the largest scales in the Universe. The standard model of cosmolol@P#APeter JonkerIMBHp.jonker@sron.nl;8Intermediate-mass black holes, super-massive black holes# Astronomer, post-doc, researcher:7Stichting Sron Netherlands Institute For Space ResearchNLPE9 ERC-2014-CoG*'Do intermediate-mass black holes exist?With this proposed project I will determine whether intermediate-mass black holes (IMBHs) exist. I propose to use ESA's new Gaia mission, the rich Hubble Space Telescope data archive, and state-of-the-art techniques to investigate systems predicted to exil@$A Sebastian HoenigDUST-IN-THE-WINDs.hoenig@soton.ac.uk=:astronomy, astrophysics, active galactic nuclei, cosmology=:astronomy, astrophysics, active galactic nuclei, cosmologyUniversity Of SouthamptonUKPE9 ERC-2015-STGcDust in the wind  a new paradigm for inflow and outflow structures around supermassive black holesActive galactic nuclei (AGN) represent the active growing phases of supermassive black holes. For the first time, we are able to resolve the dusty gas on parsec scales and directly test our standard picture of these objects. While this  unification schemem@2$ASeanMatt AWESoMeStarss.matt@exeter.ac.uklow-mass stars, stellar rotation, stellar magnetic activity, stellar winds, accretion, stellar evolution, angular momentum, MHD, numerical simulationsThe University Of ExeterUKPE9 ERC-2015-CoGB?Accretion, Winds, and Evolution of Spins and Magnetism of StarsThis project focuses on Sun-like stars, which possess convective envelopes and universally exhibit magnetic activity (in the mass range 0.1 to 1.3 MSun). The rotation of these stars influences their internal structure, energy and chemical transport, and m m@"A Martin BizzarroStardust2asteroidsbizzarro@snm.ku.dkKobenhavns UniversitetDKPE10 ERC-2013-CoGfcStardust to asteroids: Unravelling the formation and earliest evolution of a habitable solar systemAs far as we know, our solar system is unique. It could, in principle, be the only planetary system in the Universe to harbor intelligent life or, indeed, life at all. As such, attempting to reconstruct its history is one of the most fundamental pursuits @m@pA Ernest Chi FruCLAPOChiFruE@cardiff.ac.ukOLarsenic, Precambrian oceans, marine biogeochemical cycles, evolution of lifeURisotopic geochemist, sedimentologist, geochemist, biogeochemist, geomicrobiologistStockholms UniversitetSEPE10 ERC-2013-StG<9The Coevolution of Life and Arsenic in Precambrian OceansThe ubiquity of arsenic resistant genes across all of life s variety suggests a close intimacy between arsenic biogeochemistry and evolution, over geological time scales. However, the behaviour of arsenic in past environments where life originated and its`m@A SebastianSobek HYDROCARBsebastian.sobek@ebc.uu.serobiogeochemistry, limnology, aquatic science, sedimentology, ecosystem ecology, carbon cycling, greenhouse gases,)biogeochemistry, sedimentology, modeling Uppsala UniversitetSEPE10 ERC-2013-StGpmTowards a new understanding of carbon processing in freshwaters: methane emission hot spots and carbon burialIn spite of their small areal extent, inland waters play a vital role in the carbon cycle of the continents, as they emit significant amounts of the greenhouse gases (GHG) carbon dioxide (CO2) and methane (CH4) to the atmosphere, and simultaneously bury mm@v#AJaimeToney ALKENoNEjaime.toney@glasgow.ac.ukURbiomarkers, lakes, temperature, environment, algae, alkenone, lipids, paleoclimateUniversity Of GlasgowUKPE10 ERC-2014-StG74Algal Lipids: the Key to Earth Now and aNcient EarthAlkenones are algal lipids that have been used for decades to reconstruct quantitative past sea surface temperature. Although alkenones are being discovered in an increasing number of lake sites worldwide, only two terrestrial temperature records have beem@ԔARoy Harrison FASTERr.m.harrison@bham.ac.ukmjDiesel exhaust; atmospheric aerosol; hydrocarbon analysis; atmospheric modelling; atmospheric measurementsatmospheric scientistThe University Of BirminghamUKPE10 ERC-2012-ADGzwFundamental Studies of the Sources, Properties and Environmental Behaviour of Exhaust Nanoparticles from Road VehiclesDespite intensive abatement efforts, airborne particulate matter remains a major public health issue with costs across the European Union estimated at 600 billion euros in 2005. Road traffic remains one of the major sources of particulate matter, and diem@A Emmanuelle JavauxELITEej.javaux@ulg.ac.beearly life, evolution, microfossils, paleobiology, precambrian, eukaryotes, cyanobacteria, microanalyzes, astrobiology, biosignaturesdamicrospectroscopist, precambrian sedimentologist, geochemist, astrobiologist, micropaleontologistUniversite De LiegeBEPE10 ERC-2012-StGB?Early Life Traces, Evolution, and Implications for AstrobiologyTracking the early traces of life preserved in very old rocks and reconstructing the major steps of its evolution is an exciting and most challenging domain of research. How amazing it is to have a cell that is 1.5 or 3.2 billion years old under a microscm@AAndre Niemeijer SEISMICa.r.niemeijer@uu.nl0-friction, earthquakes,seismic cycle, faulting2/Faulting modeler, field geologist, seismologistUniversiteit UtrechtNLPE10 ERC-2013-StG{xSlip and Earthquake Nucleation in Experimental and Numerical Simulations: a Multi-scale, Integrated and Coupled ApproachEarthquakes represent one of the deadliest and costliest natural disasters affecting our planet  and one of the hardest to predict. To improve seismic hazard evaluation in earthquake-prone regions, an understanding of earthquake nucleation and of the undn@xA Elvira Astafyeva SIREALastafyeva@ipgp.frURionosphere, earthquakes, ionospheric seismology, geomagnetic storms, space weatherURionosphere, earthquakes, ionospheric seismology, geomagnetic storms, space weather)&Institut De Physique Du Globe De ParisFRPE10 ERC-2012-StGpmSeismology in the ionosphere? This is REAL! Ionosphere as a natural indicator of numerous geophysical eventsWe propose to perform a wide spectrum of ionosphere-related research, from ionosphere seismology to ionospheric storms and GNSS/GPS performance during extreme ionospheric and space weather events. The main focus will be made on such rare subject as ionosp n@Vt#A Richard ButlerTERRAbutler.richard.j@gmail.comvsPalaeontology, species richness, biodiversity, fossil record, terrestrial, Tetrapoda, Cenozoic, Mesozoic, databasesGDBiodiversity analysis, biogeography, species richness, fossil recordThe University Of BirminghamUKPE10 ERC-2014-StGSP375 Million Years of the Diversification of Life on Land: Shifting the Paradigm?Life on land today is spectacularly diverse, representing 75 95% of all species on Earth. However, it remains unclear how this extraordinary diversity has been acquired across deep geological time. This research project will address this major knowledge g@n@,#ANoel Keenlyside STERCPnoel.keenlyside@uib.noClimate prediction, Interactive Ensemble, Climate Change Projections, Model Systematic Error, Machine Learning, Dynamical System, Data assimilation, Multi-model ensemblesjgClimate modeller, Climate dynamics, Seasonal to decadal prediction, Machine Learning, Data assimilationUniversitetet I BergenNOPE10 ERC-2014-CoG@=Synchronisation to enhance reliability of climate predictionsClimate prediction is the next frontier in climate research. Prediction of climate on timescales from a season to a decade has shown progress, but beyond the ocean skill remains low. And while the historical evolution of climate at global scales can be re`n@u$A AndreasStohl COMTESSA ast@nilu.no1.turbulence, atmosphere, dispersion, tomographyeither interest in the experimental activities of COMTESSA (camera observations of SO2), or a theoretician/modeller interested in aspects of atmospheric turbulence and tracer dispersion$!Norsk Institutt For LuftforskningNOPE10 ERC-2014-ADGMJCamera Observation and Modelling of 4D Tracer Dispersion in the AtmosphereCOMTESSA will push back the limits of our understanding of turbulence and plume dispersion in the atmosphere by bringing together full four-dimensional (space and time) observations of a (nearly) passive tracer (sulfur dioxide, SO2), with advanced data ann@8$AMark Claire OXYGENmc229@st-andrews.ac.ukyvEarth System Science, atmospheric evolution, mass-independent isotope fractionation (MIF), oxygen, sulfur, early earthZWNumerical modelling, experimentalist, photochemistry, isotope geochemist, field geology74The University Court Of The University Of St AndrewsUKPE10 ERC-2015-STG[XQuantifying the evolution of Earth's atmosphere with novel isotope systems and modellingAtmospheric oxygen is fundamental to life as we know it, but its concentration has changed dramatically over Earth s 4.5 billion year history. An amazing qualitative story has emerged, in which Earth s atmosphere was devoid of free oxygen for the first 2n@~$A Heather Graven METHIDh.graven@imperial.ac.ukURAtmospheric methane, Radiocarbon, Carbon cycle, Observations, Modelling, EmissionsURAtmospheric methane, Radiocarbon, Carbon cycle, Observations, Modelling, Emissions63Imperial College Of Science Technology And MedicineUKPE10 ERC-2015-STGdaObservation and Modelling of Radiocarbon in Atmospheric Methane for Methane Source IdentificationObservation and Modelling of Radiocarbon in Atmospheric Methane for Methane Source Identification Greenhouse gas emissions are the primary cause of global climate change, and methane (CH4) is the second most important contributor after carbon dioxide (CO2n@$AEric Galbraith BIGSEAeric.galbraith@icrea.cat30ocean model biogeochemistry ecosystem fisheries 63model marine ecology economics behaviour governance$!Universitat Autonoma De BarcelonaESPE10 ERC-2015-CoG]ZBiogeochemical and ecosystem interactions with socio-economic activity in the global oceanThe global marine ecosystem is being deeply altered by human activity. On the one hand, rising concentrations of atmospheric greenhouse gases are changing the physical and chemical state of the ocean, exerting pressure from the bottom up. Meanwhile, the gn@1%ASandra (Sandy) Harrison1.GC2.0: Unlocking the past for a clearer futures.p.harrison@reading.ac.ukwtpalaeoclimate; biosphere feedbacks; climate impacts on vegetation; vegetation modelling; abrupt climate change; PMIPmjpalaeodata synthesis; climate reconstruction; climate modelling; environmental modelling; model evaluationThe University Of ReadingUKPE10 ERC-2015-AdG=:Global Change 2.0: Unlocking the past for a clearer futureThe terrestrial biosphere responds rapidly and sensitively to climate change and is important in mediating physical and biogeochemical feedbacks to climate. There are still enormous uncertainties in our understanding of how the terrestrial biosphere will o@Fy#A Stephan LauermannInfoAggregations.lauermann@uni-bonn.de`]economic theory, game theory, voting, Economic Theory, Auctions, Elections, Political Economyeconomic theorists, 1.Rheinische Friedrich-Wilhelms-Universitat BonnDESH1 ERC-2014-StG'$Information Aggregation in ElectionsElections are the foundation for democratic decision making. This research program will examine the effects of biased and privately informed entities election organizers on the ability of elections to aggregate information: Existing theory demonstrates th o@8A Andrew Geddes MIGPROSPa.geddes@shef.ac.ukinternational migration, governance, politics, international relations, Asia-Pacific, South America, North America, Europe, regional integration.international migration, governance, politics, international relations, Asia-Pacific, South America, North America, Europe, regional integration.The University Of SheffieldUKSH2 ERC-2013-ADG30Prospects for International Migration GovernanceRisk and uncertainty are inherent in any decision-making procedure, but while a substantial body of work on the governance of international migration focuses on challenges posed to governance systems, we know remarkably little about the impact of risk and@o@ؠARivkeJaffe SECURCITr.k.jaffe@uva.nlTQsecurity, privatization, cities, citizenship, governance, neoliberalism, policingjgpolicing, security, assemblages, STS, materiality, cities, citizenship, infrastructure, urban, violenceUniversiteit Van AmsterdamNLSH2 ERC-2013-StGifTransforming Citizenship through Hybrid Governance: The Impacts of Public-Private Security AssemblagesThis project is an anthropological study of how citizenship is being reconfigured through hybrid forms of governance. It will research these transformations by focusing on public-private  security assemblages , with particular emphasis on the role of the `o@#A Kroly Takcs EVILTONGUEtakacs.karoly@tk.mta.hugossip; reputation; cooperation; social norms; informal communication; social networks; status competition; honesty; indirect reciprocity; text analysisb_agent-based models; network dynamics; statistical models for networks; semantics; text analysis?<Magyar Tudomanyos Akademia Tarsadalomtudomanyi KutatokozpontHUSH2 ERC-2014-CoGa^No Sword Bites So Fiercly as an Evil Tongue?Gossip Wrecks Reputation, but Enhances CooperationSocial norms in general, and norms of cooperation in particular, are the cement of all human societies. For the difficult problems of the maintenance and enforcement of social norms and of cooperation, humans have developed surprisingly complex solutions.o@$AKlaus Hoeyer POLICYAIDklho@sund.ku.dkZWScience and technology studies (STS), anthropology, Big Data, data politics, healthcare?<Science and technology studies (STS), anthropology, Big DataKobenhavns UniversitetDKSH2 ERC-2015-CoGROPolicy, practice and patient experience in the age of intensified data sourcingThe European healthcare services have begun collecting tissue samples and healthcare data from patients on an unprecedented scale. With POLICYAID we suggest the term 'intensified data sourcing' to describe these attempts at getting more data, on more peopo@lA Massimo Tavoni CobhamMassimo.tavoni@polimi.itQNBehavioural economics. climate change. energy economics. Environmental scienceSPBehavioural economist. climate change economist. integrated assessment modeler. Politecnico Di MilanoITSH3 ERC-2013-StGnkThe role of consumer behavior and heterogeneity in the integrated assessment of energy and climate policiesThe objective of this project is to quantify the role of consumers behaviour on the design and assessment of policies aimed at enhancing energy efficiency and conservation and at promoting climate change mitigation. The project brings together different o@V#ADarja Reuschke WORKANDHOMEd.reuschke@soton.ac.ukbusiness, homeworking, networks, commuting, coworking, neighbourhoods, cities, growth, inclusion, entrepreneurship, enterprise, GIS!geography, geoinformatics, GIS74The University Court Of The University Of St AndrewsUKSH3 ERC-2014-StGIFReshaping society and space: home-based self-employment and businessesThe aim of WORKANDHOME is to develop a new framework for understanding fundamental changes currently taking place to work that situates individuals as economic actors within the context of their wider life domains, household, home and neighbourhood. This o@f"A MelindaMills SOCIOGENOME"Melinda.mills@nuffield.ox.ac.ukB?Fertility, genetics, life course, biosocial, assortative matingjgCombining social science and genetics, demography, life course, fertility, statistics, polygenic scoresC@The Chancellor, Masters And Scholars Of The University Of OxfordUKSH3 ERC-2013-CoG`]Unravelling the genetic influences of reproductive behaviour and gene-environment interactionThis project will be the first to engage in a comprehensive study of the role of genes and gene-environment (GxE) interaction on reproductive behaviour. Until now, social science research has focussed on socio-environmental explanations, largely neglectinp@dA Lorraine WhitmarshCASPIwhitmarshle@cardiff.ac.ukc`Low-carbon, lifestyles, behaviour change, spillover, rebound effect, sustainable, cross-cultural:7Environmental psychologist, cross-cultural psychologistCardiff UniversityUKSH3 ERC-2013-StG2/Low-carbon Lifestyles and Behavioural SpilloverResponding to climate change has profound implications for behaviour; yet policies to achieve this change have met with limited success. A key challenge for environmental social scientists is the need to move forward in understanding how to bring about chp@A valentina bosetti risico"valentina.bosetti@unibocconi.itLIuncertainty perception; climate change uncertainty; science communication96behavioral economics; decision science; climate cahnge'$Universita Commerciale Luigi BocconiITSH3 ERC-2013-StGNKRISk and uncertainty in developing and Implementing Climate change pOliciesUncertainty is pervasive in all aspects of climate change. Although this is beyond dispute, the vast majority of research assessing climate ignores uncertainty, in large part because of the technical complexities involved. The present project aims at adva p@#A Ludovic Leclercq MAGnUMludovic.leclercq@ifsttar.frtransportation systems ; Aggregated Traffic modelling, Drivers behaviour, Traffic Flow Theory, Multimodal, Multiscale, Urban Road Networks, Sustainable Traffic Management, Congestion, Behavioural studies85Transportation ; Optimization ; Data Mining ; Controla^Institut Francais Des Sciences Et Technologies Des Transports, De L'Amenagement Et Des ReseauxFRSH3 ERC-2014-CoGTQA Multiscale and Multimodal Modelling Approach for Green Urban Traffic ManagementThe MAGnUM project aims to (i) create a consistent set of interrelated dynamic and multimodal traffic models able to capture driver behaviours at the different urban scales and (ii) apply this variety of models to design efficient and green traffic manage0p@p#AMark HuijbregtsSIZEm.huijbregts@science.ru.nlifbiodiversity impacts, biofuels, environmental footprints, global scale analysis, environmental scaling=:natural or technological science, environmental modeling, $!Stichting Katholieke UniversiteitNLSH3 ERC-2014-CoG^[Size matters: scaling principles for the prediction of the ecological footprint of biofuelsThere is a major scientific and societal challenge in quantifying and reducing ecological footprints of products. Ecological footprint calculations suffer severely from a limited availability of data, such as the amount of energy and materials associated @p@ƽ$ANils Bunnefeld ConFooBionils.bunnefeld@stir.ac.ukWTbiodiversity, food security, conflict, ecosystem services, social-ecological systemsbiodiversity, food security, decision theory, game theory, behavioural games, environmental psychology, conflict, social-ecological systemsThe University Of StirlingUKSH3 ERC-2015-STG\YResolving conflicts between food security and biodiversity conservation under uncertaintyResolving conflicts between food security and biodiversity conservation under uncertainty Conflicts between food security and biodiversity conservation are increasing in scale and intensity and have been shown to be damaging for both biodiversity and humaPp@$AFelix Eigenbrod SCALEFORESf.eigenbrod@soton.ac.ukSPecosystem services, scale, landscape ecology, ecological modelling, macroecology>;DGVM modeller, land system modeller, earth systems modellerUniversity Of SouthamptonUKSH3 ERC-2015-STG:7SCALEFORES: Scaling Rules For Ecosystem Service MappingIt is now widely recognized that sustainably managing ecosystem services  the benefits humans obtain from nature  is essential for humanity s prospects in the 21st century and beyond. However, at present there is little data on the distribution of most `p@v#AFiona Jordan VARIKINfiona.jordan@bristol.ac.ukcultural phylogenetics, language diversity, corpus linguistics, cross-cultural child development, interdisciplinary approaches to kinship, @=cognitive modelling, ethnography, anthropological fieldwork, University Of BristolUKSH4 ERC-2014-StGolCultural Evolution of Kinship Diversity: Variation in Language, Cognition, and Social Norms Regarding FamilyWhy do human societies differ in whom they class as family? Why are cousins classed with siblings in some societies but not others? Accounting for the variable ways that cultures classify kin is an enduring puzzle. The VARIKIN project takes a cultural evopp@#A SarangDalalOscillatoryVisionsarang@cfin.au.dk~{retina, vision, cognitive neuroscience, magnetoencephalography, electroencephalography, retina, vision, neural oscillationsretinal neurophysiology, vision, cognitive neuroscience, magnetoencephalography, electroencephalography, source localization, neural oscillationsAarhus UniversitetDKSH4 ERC-2014-StG=:The retinae as windows to the brain: An oscillatory visionSeveral sophisticated image processing circuits have been discovered in the animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, p@XAGuyOrbanParietalactionguy.orban@kuleuven.beGDaction observation; parietal cortex, intra-cerebral recordings; fMRIPMvision, electrophysiology, computational skills, human and non human primates"Universita Degli Studi Di ParmaITSH4 ERC-2012-ADGThe human Parietal LobeWe will use univariate and multivariate functional Magnetic Resonance Imaging (fMRI) techniques, surface and stereo EEG, and in depth single cell recording to investigate the role of human parietal lobe in the monocular or stereoscopic observation of actip@Ⱦ"ARufin VanRullen P-CYCLES$!rufin.vanrullen@cerco.ups-tlse.frYVbrain rhythms, perception, oscillations, awareness, perceptual framing, EEG, TMS, fMRIWTcognitive neuroscience, computational neuroscience, brain imaging, signal processing41Centre National De La Recherche Scientifique CnrsFRSH4 ERC-2013-CoG\YPerceptual Cycles: Exploring and controlling the perceptual consequences of brain rhythmsMany current theories implicate brain oscillations in perception, attention, consciousness or memory. This, however, has one critical implication that is often overlooked in cognitive sciences: if a perceptual function relies on an oscillatory basis, thenp@AAxel Cleeremans RADICALaxcleer@ulb.ac.beQNconsciousness, unconscious information processing, learning, neural plasticityhecomputational modeling, cognitive neuroscience, philosophy of mind, experimental psychology, learning Universite Libre De BruxellesBESH4 ERC-2013-ADG>;The Radical Plasticity Thesis: How we learn to be consciousRADICAL explores the idea that consciousness is something that the brain learns to do rather than a static property of certain neural states vs. others. Here, considering that consciousness is extended both in space and in time, I adopt a resolutely dynamp@c#A Daniel Balliet COOPERATIONd.p.balliet@vu.nlheCooperation, Social Dilemmas, Meta-analysis, Behavioral Economics, Social Psychology, InterdependenceOLevolutionary dynamics, evolutionary psychology, economics, social psychology Stichting VuNLSH4 ERC-2014-StGqnReleasing Prisoners Of The Paradigm: Understanding How Cooperation Varies Across Contexts In The Lab And FieldCooperation is essential for mitigating conflict between individual and collective interests in relationships and groups, such as providing public goods and conserving resources. Most research testing psychological and economic theory of cooperation has ap@w#AShaul ShalviCorruption Rootss.shalvi@uva.nla^Corruption; Decision Making; Ethics; Moral Psychology; Social Psychology; Behavioral Economics@=Decision Making; Behavioral Economics; Experimental EconomicsUniversiteit Van AmsterdamNLSH4 ERC-2014-StG;8At the roots of corruption: a behavioral ethics approachFor many years, human cooperation has been praised as beneficial in organizational and personal settings. Indeed, cooperation allows people to develop trust, build meaningful relationships, achieve mutually beneficial outcomes, and strengthen bonding withp@#AJens Blechert NewEatjens.blechert@sbg.ac.at}zemotional eating, eating disorders, neuro-cognitive correlated of food image responses, ambulatory assessment, food choiceMethodologically oriented researchers with expertise in statistical analysis of ambulatory monitoring data, EEG data analysis, food choice modelling$!Paris-Lodron-Universitat SalzburgATSH4 ERC-2014-StGYVTransdiagnostic views on eating disorders and obesity and new approaches for treatmentEating disorders such as Anorexia Nervosa (AN), Bulimia Nervosa (BN), Binge Eating Disorder (BED) and overweight/obesity are highly prevalent in the EU and worldwide. They cause tremendous suffering, elevate suicide rates, and account for multiple organicp@TA Johannes Theeuwes REWARDVIEWJ.Theeuwes@vu.nlWTexperimental psychology, cognitive neuroscience, reward processing, visual selection@=attention, eye movements, reward processing, visual selection Stichting VuNLSH4 ERC-2012-ADGA>What you get is what you see: How Reward Determines PerceptionThe expectation of a reward is known to be the driving force behind adaptive behaviour and learning. The effects of reward arise in dopaminergic reward circuitry at the centre of our primitive brain, which guides our goal-directed behaviour and fosters mop@T&AKarin Roelofs Neurodefensek.roelofs@donders.ru.nlYVNeural circuits, steroid hormones, stress, defensive responses; Anxiety and aggressionqnCognitive Neuroscience; Computational modelling; Motivation and Emotion; Neuroendocrine mechanisms; Psychiatry$!Stichting Katholieke UniversiteitNLSH4 ERC-2012-StG.+Neural control of human freeze-fight-flightThis study investigates the mechanistic bases of human freeze-fight-flight reactions. The ability to control our social behavior is essential for almost every social interaction. It frequently fails in challenging situations when people fall back on basicq@$#ASimon Hanslmayr Code4Memorys.hanslmayr@bham.ac.uk\YEpisodic memory, brain oscillations, human single unit recordings, combined EEG-fMRI, MEGvsmemory, oscillations, EEG/MEG, intracranial EEG recordings, computational modelling of neural networks, hippocampusThe University Of BirminghamUKSH4 ERC-2014-CoG*'Neural oscillations - a code for memoryEpisodic memory refers to the fascinating human ability to remember past events in a highly associative and information rich way. But how are these memories coded in human brains? Any mechanism accounting for episodic memory must accomplish at least two fq@$#ALydia KrabbendamSCANSlydia.krabbendam@vu.nlJGsocial cognition, adolescence, social networks, functional neuroimaging[Xexpertise in (social) cognitive neuroscience, interest in development during adolescence Stichting VuNLSH4 ERC-2014-CoGFCSocial Cognition in Adolescents: Brain Networks and Social NetworksThe forming of social bonds is an evolutionary imperative, and a rich target for empirical research. Social scientists have scrutinized the structure of the elaborate social networks that characterize today s society. Neuroscientists have elucidated the b q@#ATom Beckers WipeOutFeartom.beckers@kuleuven.beKHEmotional memory; fear learning; post-retrieval amnesia; reconsolidation!Katholieke Universiteit LeuvenBESH4 ERC-2014-CoGOLHow the Brain Learns to Forget - The Neural Signature of Fear Memory ErasureCan fear memories be erased from the brain? While it sounds like science fiction, recent findings suggest that fear memories can be undone upon their retrieval, through either pharmacological or behavioural interventions. Still, whether such reconsolidati0q@@#ASid Kouider METAWAREsid.kouider@ens.frOLNeuroscience; consciousness; human adults; human infants; EEG; psychophysics30Neuroscience; consciousness; EEG ; psychophysicsEcole Normale SuperieureFRSH4 ERC-2014-CoGebBehavioral and neural determinants of metacognition and self-awareness in human adults and infantsProposal summary. Understanding the psychological and neurobiological determinants of consciousness is fundamental. Yet, the main trend focusing on how the front of the brain (prefrontal cortex) interacts with the back (sensory cortex) for accessing perce@q@u$A Matthew Lambon RalphBRAIN2MIND_NEUROCOMP%"matt.lambon-ralph@manchester.ac.ukjgcognitive neuroscience; semantics and language; aphasia; computational modelling; fMRI; MR tractography85cognitive neuroscience; imaging analyses; aphasiologyThe University Of ManchesterUKSH4 ERC-2014-ADGXUDeveloping and delivering neurocomputational models to bridge between brain and mind.The promise of cognitive neuroscience is truly exciting  to link mind and brain in order to reveal the neural basis of higher cognitive functions. This is crucial, scientifically, if we are to understand the nature of mental processes and how they arise Pq@z$AEus Van Someren INSOMNIAe.van.someren@nin.knaw.nlFCInsomnia, depression, mood, MRI, HD-EEG, RCT, multivariate analysis%"multivariate analysis, MRI, HD-EEG<9Koninklijke Nederlandse Akademie Van Wetenschappen - KnawNLSH4 ERC-2014-ADGSInsomnia s Negative Sequelae On Mood: from Neuroscience to Intervention in the AgedMajor depression is among the most burdening health hazards. Its prevalence is 1-3%, an additional 8-16% have clinically significant symptoms, and prognosis is poor. Unfortunately, less than 20% of the cases are detected and treatment effectiveness is mod`q@d$A Alexander Schtz PERFORMa.schuetz@uni-marburg.de/,Visual perception; Neuroscience; Psychology;/,Visual perception; Neuroscience; Psychology; Philipps Universitaet MarburgDESH4 ERC-2015-STGSPCalibration and integration of peripheral and foveal information in human visionHuman visual perception is one of the best-studied areas of research on the human mind. However, 99% of that research is concentrated on the central region making up less than 1% of our visual field. This is the region that gets mapped onto the fovea, whepq@$A Floris de LangeCONTEXTVISIONflorisdelange@gmail.comPMVision, perception, expectation, attention, context, fMRI, MEG, psychophysicsMJtop-down, attention, predictive coding, perception, neuroimaging, modeling$!Stichting Katholieke UniversiteitNLSH4 ERC-2015-STGVisual perception in ContextEverything occurs in a context. We see a car in the context of a street scene and a stove in the context of a kitchen. Context greatly helps the processing of individual objects. Surprisingly however, context hardly plays a role in most models of visual pq@$ABen AmbridgeCLASSBen.Ambridge@Liverpool.ac.ukFCpsychology; linguistics; language acquisition; language developmentFCpsychology; linguistics; language acquisition; language developmentThe University Of LiverpoolUKSH4 ERC-2015-CoGliCross-Linguistic Acquisition of Sentence Structure: Integrating Experimental and Computational ApproachesHow children acquire their native language remains one of the key unsolved problems in Cognitive Science. This project will answer a question that lies at the heart of this problem: How do children acquire the abstract generalizations that allow them to pq@4AMarco Sgarbi Aristotlemarco.sgarbi@unive.it0-renaissance, intellectual history, philosophy.+reseachers, teachers, professors, post-docs!Universita Ca' Foscari VeneziaITSH5 ERC-2013-StGsAristotle in the Italian Vernacular: Rethinking Renaissance and Early-Modern Intellectual History (c. 1400 c. 1650)From the twelfth to the seventeenth century, Aristotle s writings lay at the foundation of Western culture, providing a body of knowledge and a set of analytical tools applicable to all areas of human investigation. Scholars of the Renaissance have emphasq@,"A Ulrich TimmeKraghNAMOutkragh@gmail.commjThe structures and use of narrative in Asian history writing with focus on China, India, Tibet, and PersiaWTspecialists of theory of history, Asian studies, and/or literary theory of narrative/,Uniwersytet Im. Adama Mickiewicza W PoznaniuDKSH5 ERC-2013-CoG2/Narrative Modes of Historical Discourse in AsiaModern historiography produced in Asia belongs to the history-paradigm of the European humanities and it is from within these epistemological confines that Western as well as Eastern scholars of Asian studies view the Asian writing of the past. While sourq@D$A Elselijn KingmaBUMPe.m.kingma@soton.ac.uk.+Philosophy, Pregnancy, Biology, Metaphysics=:Philosophy, Pregnancy, Biology, Metaphysics, PhenomenologyUniversity Of SouthamptonUKSH5 ERC-2015-STG41BETTER UNDERSTANDING the METAPHYSICS of PREGNANCYEvery single human is the product of a pregnancy: an approximately nine-month period during which a foetus develops within its mother s body. Yet pregnancy has not been a traditional focus in philosophy. That is remarkable, for two reasons: First, becausq@6$AJari KaukuaETIjari.kaukua@jyu.figdIslamic philosophy, Islamic theology, medieval philosophy, history of philosophy, history of sciencegdIslamic philosophy, Islamic theology, medieval philosophy, history of philosophy, history of scienceJyvaskylan YliopistoFISH5 ERC-2015-CoGgdEpistemic Transitions in Islamic Philosophy, Theology and Science: From the 12th to the 19th CenturyNot very long ago, it was still common to hold that little of interest took place in Islamic philosophy, theology and science after the death of the Peripatetic commentator Averroes in 1198. Recent research has produced increasing evidence against this viq@b"A Rhiannon Stevens UP-Northrhiannon.stevens@ucl.ac.ukArchaeology, isotopes, ancient DNA, radiocarbon, environment, climate, colonisation, Palaeolithic, hunter gatherers, Palaeolithic, Archaeology, bioarchaeology, palaeoclimate, palaeoecology, climate change, colonization,demography, archaeological sciencearchaeology, geochemistry, palaeoclimate, palaeoecology palaeobiology, climate change, archaeological science, isotopes, ancient dna, University College LondonUKSH6 ERC-2013-CoGEBCOLONISATION AND CULTURAL DIVERSIFICATION IN UNFAMILIAR LANDSCAPESThis project explores the relationship between climate change and human behaviour. During the harshest conditions of the last ice age European human populations abandoned northern latitudes, with their range contracting to southern regions. By the time icq@u#A Verena Lepper ELEPHANTINEv.lepper@smb.spk-berlin.dePMCultural History, Global History, Papyri, Ancient Egypt, Physics, MathematicspmIn any of the following fields: Cultural History, Global History, Papyri, Ancient Egypt, Physics, Mathematics%"Stiftung Preussischer KulturbesitzDESH6 ERC-2014-StG`]Localizing 4000 Years of Cultural History. Texts and Scripts from Elephantine Island in EgyptThe aim of this project is to write a cultural history of 4000 years, localized on Elephantine Island in Egypt.Elephantine was a militarily and strategically very important island in the river Nile on the southern borderof Egypt. No other settlement in Egq@f#A MonikaBaar DISABILITYm.k.baar@hum.leidenuniv.nl nkdisabilty, welfare state, global health, development policies, social movements, human rights, vulnerabiltydaglobal health, human rights, disabilty, international organizations, global history, anthropologyUniversiteit LeidenNLSH6 ERC-2014-CoGzwRethinking Disability: the Global Impact of the International Year of Disabled Persons (1981) in Historical PerspectiveApproximately 10% of the world s population is estimated to be disabled and this number is expected to rise in the next few decades. People in different cultural settings ascribe different meanings to disability; consequently, its repercussions are both cr@"A MiguelBeato del Rosal 4D-GENOMEmiguel.beato@crg.euyvgene regulation, chromatin dynamics, steroid hormones, breast cancer cells, 3D genome structure, nucleosome dynamics _\epigenomics, gene regulation, protein structure, chromatin remodelling, cell reprogramming (%FUNDACIO CENTRE DE REGULACIO GENOMICAESSYG6 ERC-2013-SyGXUDynamics of human genome architecture in stable and transient gene expression changesThe classical view of genomes as linear sequences has been replaced by a vision of nuclear organization that is both dynamic and complex, with chromosomes and genes non-randomly positioned in the nucleus. Process compartmentalization and spatial location r@|A Andrea Ferrari Hetero2Dacf26@eng.cam.ac.ukNKgraphene, layered materials, optoelectronics, Raman spectroscopy, PhotonicsNKgraphene, layered materials, optoelectronics, Raman spectroscopy, PhotonicsTHE UNIVERSITY OF MANCHESTERUKSYG6 ERC-2012-SyGA>Novel materials architecture based on atomically thin crystalsWe propose a new paradigm in materials science  heterostructures based on two-dimensional atomic crystals (and their hybrids with metallic and semiconducting quantum dots and nanostructures), and develop several devices which are based on such concept. T r@؝"A Michael Obersteiner IMBALANCE-Poberstei@iiasa.ac.at2/phosphorus limitations, Earth System managementwtecosystem diversity and ecology, biogeochemistry, Earth System modelling, global agricultural and resource economics=:CENTRO DE INVESTIGACION ECOLOGICA YAPLICACIONES FORESTALESESSYG6 ERC-2013-SyGFCEffects of phosphorus limitations on Life, Earth system and SocietyP is an earthbound and finite element and the prospect of constrained access to mineable P resources has already triggered geopolitical disputes. In contrast to P, availabilities of carbon (C) and nitrogen (N) to ecosystems are rapidly increasing in most 0r@؝"AJosepPeuelas i Reixach IMBALANCE-Pjosep.penuelas@uab.catmjphosphorus, nitrogen, nutrients, global change, ecology, earth system models, integrated assessment models*'dynamic, multidisciplinary, ecologist, =:CENTRO DE INVESTIGACION ECOLOGICA YAPLICACIONES FORESTALESESSYG6 ERC-2013-SyGFCEffects of phosphorus limitations on Life, Earth system and SocietyP is an earthbound and finite element and the prospect of constrained access to mineable P resources has already triggered geopolitical disputes. In contrast to P, availabilities of carbon (C) and nitrogen (N) to ecosystems are rapidly increasing in most @r@hzA Martin Bodo PlenioBioQmartin.plenio@uni-ulm.deJGQuantum Technologies, Quantum Physics, Quantum Sensing, Quantum Biology96Quantum Technologies, Quantum Sensing, Quantum BiologyUNIVERSITAET ULMDESYG6 ERC-2012-SyG&#Diamond Quantum Devices and BiologyMany of the most remarkable contributions of modern science to society have arisen from interdisciplinary work of scientists enabling novel imaging and sensing technologies (NMR, X-ray diffraction, electron microscopy). BioQ will revolutionize the state oPr@"AFranz KrtnerAXSISfranz.kaertner@cfel.deXUTHz accelerator, attosecond table-top FEL, X-ray diffractive imaging and spectroscopyC@high energy and high power lasers, THz generation, FEL-physics, 1.STIFTUNG DEUTSCHES ELEKTRONEN-SYNCHROTRON DESYDESYG6 ERC-2013-SyGB?Frontiers in Attosecond X-ray Science: Imaging and SpectroscopyX-ray crystallography yields atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes constituting the macromolecular machinery of life. Life is not static, and many of the most import SummaryInformation(DocumentSummaryInformation8,CompObj o Oh+'0@Hl MARINI Massimiliano (ERCEA)nsfcfile@nsfc.gov.cn@]**j@A@wk\q՜.+,0HP X`hpx  Sheet1ChinaChina!Print_AreaChina!Print_Titles  Χ F#Microsoft Office Excel 2003 Biff8Excel.Sheet.89q