ERC FUNDED PROJECTS

"Here, we propose a novel design for a significantly improved detector for the emerging field of coherent two-dimension infrared (2DIR) spectroscopy, which is an optical analog of Nuclear Magnetic Resonance spectroscopy (NMR). 2DIR is a cutting edge technique which is rapidly growing and has applications in subjects as diverse as energy sciences, biophysics, biomedical research and physical chemistry. Currently, the single most important technical problem that is generally agreed to limit applications of the methodology is the sensitivity with which the signals are measured. Having worked on multiple stabilisation techniques during the ERC funded research it was realised that a straightforward design alteration of the infrared detector will improve the sensitivity very significantly, theoretically by more than one order of magnitude. Here, the technical principles are explained, and a plan for commercialising the instrument in collaboration with the current market leader - Infrared System Development Corp. (ISDC) -. We apply for funding to develop the prototype."

149 999 €

Start date: 2013-11-01, End date: 2014-10-31

At the end of their life, stars spread their inner material into the diffuse interstellar medium. This diffuse medium gets locally denser and form dark clouds (also called dense or molecular clouds) whose innermost part is shielded from the external UV field by the dust, allowing for molecules to grow and get more complex. Gravitational collapse occurs inside these dense clouds, forming protostars and their surrounding disks, and eventually planetary systems like (or unlike) our solar system. The formation and evolution of molecules, minerals, ices and organics from the diffuse medium to planetary bodies, their alteration or preservation throughout this cosmic chemical history set the initial conditions for building planets, atmospheres and possibly the first bricks of life. The current view of interstellar chemistry is based on fragmental works on key steps of the sequence that are observed. The objective of this proposal is to follow the fractionation of the elements between the gas-phase and the interstellar grains, from the most diffuse medium to protoplanetary disks, in order to constrain the chemical composition of the material in which planets are formed. The potential outcome of this project is to get a consistent and more accurate description of the chemical evolution of interstellar matter. To achieve this objective, I will improve our chemical model by adding new processes on grain surfaces relevant under the diffuse medium conditions. This upgraded gas-grain model will be coupled to 3D dynamical models of the formation of dense clouds from diffuse medium and of protoplanetary disks from dense clouds. The computed chemical composition will also be used with 3D radiative transfer codes to study the chemical tracers of the physics of protoplanetary disk formation. The robustness of the model predictions will be studied with sensitivity analyses. Finally, model results will be confronted to observations to address some of the current challenges.

1 166 231 €

Start date: 2013-09-01, End date: 2018-08-31

The 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.

12 272 645 €

Start date: 2014-06-01, End date: 2019-05-31

"High-energy observations of our Galaxy offer a good, albeit not complete, picture of the X-ray source populations, in particular the accreting binary sources. Recent ability to study accreting binaries in nearby galaxies has shown that we would be short-sighted if we restricted ourselves to our Galaxy or to a few nearby ones. I propose an ambitious project that involves a comprehensive study of all the galaxies within 10 Mpc for which we can study in detail their X-ray sources and stellar populations. The study will combine data from a unique suite of observatories (Chandra, XMM-Newton, HST, Spitzer) with state-of-the-art theoretical modelling of binary systems. I propose a novel approach that links the accreting binary populations to their parent stellar populations and surpasses any current studies of X-ray binary populations, both in scale and in scope, by: (a) combining methods and results from several different areas of astrophysics (compact objects, binary systems, stellar populations, galaxy evolution); (b) using data from almost the whole electromagnetic spectrum (infrared to X-ray bands); (c) identifying and studying the different sub-populations of accreting binaries; and (d) performing direct comparison between observations and theoretical predictions, over a broad parameter space. The project: (a) will answer the long-standing question of the formation efficiency of accreting binaries in different environments; and (b) will constrain their evolutionary paths. As by-products the project will provide eagerly awaited input to the fields of gravitational-wave sources, γ-ray bursts, and X-ray emitting galaxies at cosmological distances and it will produce a heritage multi-wavelength dataset and library of models for future studies of galaxies and accreting binaries."

1 242 000 €

Start date: 2014-04-01, End date: 2019-03-31

"The A2C2 project treats two major challenges in climate and atmospheric research: the time dependence of the climate attractor to external forcings (solar, volcanic eruptions and anthropogenic), and the attribution of extreme climate events occurring in the northern extra-tropics. The main difficulties are the limited climate information, the computer cost of model simulations, and mathematical assumptions that are hardly verified and often overlooked in the literature. A2C2 proposes a practical framework to overcome those three difficulties, linking the theory of dynamical systems and statistics. We will generalize the methodology of flow analogues to multiple databases in order to obtain probabilistic descriptions of analogue decompositions. The project is divided into three workpackages (WP). WP1 embeds the analogue method in the theory of dynamical systems in order to provide a metric of an attractor deformation in time. The important methodological step is to detect trends or persisting outliers in the dates and scores of analogues when the system yields time-varying forcings. This is done from idealized models and full size climate models in which the forcings (anthropogenic and natural) are known. A2C2 creates an open source toolkit to compute flow analogues from a wide array of databases (WP2). WP3 treats the two scientific challenges with the analogue method and multiple model ensembles, hence allowing uncertainty estimates under realistic mathematical hypotheses. The flow analogue methodology allows a systematic and quasi real-time analysis of extreme events, which is currently out of the reach of conventional climate modeling approaches. The major breakthrough of A2C2 is to bridge the gap between operational needs (the immediate analysis of climate events) and the understanding long-term climate changes. A2C2 opens new research horizons for the exploitation of ensembles of simulations and reliable estimates of uncertainty."

1 491 457 €

Start date: 2014-03-01, End date: 2019-02-28

We propose to elucidate the structural design principles of naturally occurring antibody complementarity-determining regions (CDRs) and to computationally design novel antibody functions. Antibodies represent the most versatile known system for molecular recognition. Research has yielded many insights into antibody design principles and promising biotechnological and pharmaceutical applications. Still, our understanding of how CDRs encode specific loop conformations lags far behind our understanding of structure-function relationships in non-immunological scaffolds. Thus, design of antibodies from first principles has not been demonstrated. We propose a computational-experimental strategy to address this challenge. We will: (a) characterize the design principles and sequence elements that rigidify antibody CDRs. Natural antibody loops will be subjected to computational modeling, crystallography, and a combined in vitro evolution and deep-sequencing approach to isolate sequence features that rigidify loop backbones; (b) develop a novel computational-design strategy, which uses the >1000 solved structures of antibodies deposited in structure databases to realistically model CDRs and design them to recognize proteins that have not been co-crystallized with antibodies. For example, we will design novel antibodies targeting insulin, for which clinically useful diagnostics are needed. By accessing much larger sequence/structure spaces than are available to natural immune-system repertoires and experimental methods, computational antibody design could produce higher-specificity and higher-affinity binders, even to challenging targets; and (c) develop new strategies to program conformational change in CDRs, generating, e.g., the first allosteric antibodies. These will allow targeting, in principle, of any molecule, potentially revolutionizing how antibodies are generated for research and medicine, providing new insights on the design principles of protein functional sites.

1 499 930 €

Start date: 2013-09-01, End date: 2018-08-31

Antibody detection assays are used in many fields of biomedicine including the diagnosis of infectious diseases, autoimmune diseases and allergies. Current analytical techniques for antibody detection come with intrinsic limitations such as the requirement for multiple time-consuming incubation steps, multiple reagents, and/or sophisticated equipment. Supported by an ERC consolidator grant we have developed a highly modular sensor concept for antibody-responsive reporter enzymes (AbSens) that addresses many of these challenges. Key advantages include the ability to monitor antibodies directly in solution, easy read-out based on a simple color reaction, adaptability to target any antibody of interest, and high affinity and specificity. We believe that this generic sensor platform could find applications in low-cost point-of-care diagnostics, clinical research, and the development of therapeutic antibodies. The goal of AbSens is to identify those opportunities in the huge market of antibody-based diagnostics where our sensor platform provides unique advantages over existing technologies, both in terms of analytical performance and economics. To enable the next step towards commercialization, the analytical performance of our technology will be compared to current gold standards using relevant clinical samples in collaboration with commercial parties and clinicians. Other commercially important parameters are the long-term stability of the assay components and the development of a yeast-based production system to lower the cost of enzyme production. Based on an in-depth market analysis and the feedback we receive from external stakeholders on the performance of our technology, a realistic strategy will be developed for the further commercialization. In anticipation of exploring the commercialization of our AbSens technology we filed a US provisional patent application in Sept. 2012 on the key underlying technology, which was recently continued via the PCT route.

150 000 €

Start date: 2014-09-01, End date: 2015-08-31

"Many of today's and tomorrow's computer systems are built on top of large-scale networks such as, e.g., the Internet, the world wide web, wireless ad hoc and sensor networks, or peer-to-peer networks. Driven by technological advances, new kinds of networks and applications have become possible and we can safely assume that this trend is going to continue. Often modern systems are envisioned to consist of a potentially large number of individual components that are organized in a completely decentralized way. There is no central authority that controls the topology of the network, how nodes join or leave the system, or in which way nodes communicate with each other. Also, many future distributed applications will be built using wireless devices that communicate via radio. The general objective of the proposed project is to improve our understanding of the algorithmic and theoretical foundations of decentralized distributed systems. From an algorithmic point of view, decentralized networks and computations pose a number of fascinating and unique challenges that are not present in sequential or more standard distributed systems. As communication is limited and mostly between nearby nodes, each node of a large network can only maintain a very restricted view of the global state of the system. This is particularly true if the network can change dynamically, either by nodes joining or leaving the system or if the topology changes over time, e.g., because of the mobility of the devices in case of a wireless network. Nevertheless, the nodes of a network need to coordinate in order to achieve some global goal. In particular, we plan to study algorithms and lower bounds for basic computation and information dissemination tasks in such systems. In addition, we are particularly interested in the complexity of distributed computations in dynamic and wireless networks."

1 148 000 €

Start date: 2013-11-01, End date: 2018-10-31

"An important driver of scientific progress has always been the envisioning of applications far beyond existing technological capabilities. Such thinking creates new challenges for physicists, driven by the groundbreaking nature of the anticipated application. In the case of laser physics, one of these applications is laser wake-field particle acceleration and possible future uses thereof, such as in collider experiments, or for medical applications such as cancer treatment. To accelerate electrons and positrons to TeV-energies, a laser architecture is required that allows for the combination of high efficiency, Petawatt peak powers, and Megawatt average powers. Developing such a laser system would be a challenging task that might take decades of aggressive research, development, and, most important, revolutionary approaches and innovative ideas. The goal of the ACOPS project is to develop a compact, efficient, scalable, and cost-effective high-average and high-peak power ultra-short pulse laser concept. The proposed approach to this goal relies on the spatially and temporally separated amplification of ultrashort laser pulses in waveguide structures, followed by coherent combination into a single train of pulses with increased average power and pulse energy. This combination can be realized through the coherent addition of the output beams of spatially separated amplifiers, combined with the pulse stacking of temporally separated pulses in passive enhancement cavities, employing a fast-switching element as cavity dumper. Therefore, the three main tasks are the development of kW-class high-repetition-rate driving lasers, the investigation of non-steady state pulse enhancement in passive cavities, and the development of a suitable dumping element. If successful, the proposed concept would undoubtedly provide a tool that would allow researchers to surpass the current limits in high-field physics and accelerator science."

1 881 040 €

Start date: 2014-02-01, End date: 2019-01-31

Computer models based on known physical laws are our primary tool for predicting climate change. Yet the state-of-the-art models exhibit a disturbingly wide range of predictions of future climate change, especially when examined at the regional scale, which has not decreased as the models have become more comprehensive. The reasons for this are not understood. This represents a basic challenge to our fundamental understanding of climate. The divergence of model projections is presumably related to systematic model errors in the large-scale fluxes of heat, moisture and momentum that control regional aspects of climate. That these errors stubbornly persist in spite of increases in the spatial resolution of the models suggests that they are associated with errors in the representation of unresolved processes, whose effects must be parameterised. Most attention in climate science has hitherto focused on the thermodynamic aspects of climate. Dynamical aspects, which involve the atmospheric circulation, have received much less attention. However regional climate, including persistent climate regimes and extremes, is strongly controlled by atmospheric circulation patterns, which exhibit chaotic variability and whose representation in climate models depends sensitively on parameterised processes. Moreover the dynamical aspects of model projections are much less robust than the thermodynamic ones. There are good reasons to believe that model bias, the divergence of model projections, and chaotic variability are somehow related, although the relationships are not well understood. This calls for studying them together. My proposed research will focus on this problem, addressing these three aspects of the atmospheric circulation response to climate change in parallel: (i) diagnosing the sources of model error; (ii) elucidating the relationship between model error and the spread in model projections; (iii) understanding the physical mechanisms of atmospheric variability.

2 489 151 €

Start date: 2014-03-01, End date: 2020-02-29

Actanthrope intends to promote a neuro-robotics perspective to explore original models of anthropomorphic action. The project targets contributions to humanoid robot autonomy (for rescue and service robotics), to advanced human body simulation (for applications in ergonomics), and to a new theory of embodied intelligence (by promoting a motion-based semiotics of the human action). Actions take place in the physical space while they originate in the –robot or human– sensory-motor space. Geometry is the core abstraction that makes the link between these spaces. Considering that the structure of actions inherits from that of the body, the underlying intuition is that actions can be segmented within discrete sub-spaces lying in the entire continuous posture space. Such sub-spaces are viewed as symbols bridging deliberative reasoning and reactive control. Actanthrope argues that geometric approaches to motion segmentation and generation as promising and innovative routes to explore embodied intelligence: - Motion segmentation: what are the sub-manifolds that define the structure of a given action? - Motion generation: among all the solution paths within a given sub-manifold, what is the underlying law that makes the selection? In Robotics these questions are related to the competition between abstract symbol manipulation and physical signal processing. In Computational Neuroscience the questions refer to the quest of motion invariants. The ambition of the project is to promote a dual perspective: exploring the computational foundations of human action to make better robots, while simultaneously doing better robotics to better understand human action. A unique “Anthropomorphic Action Factory” supports the methodology. It aims at attracting to a single lab, researchers with complementary know-how and solid mathematical background. All of them will benefit from unique equipments, while being stimulated by four challenges dealing with locomotion and manipulation actions.

2 500 000 €

Start date: 2014-01-01, End date: 2018-12-31

The two biggest challenges in solving practical optimization problems are computational intractability, and the presence of uncertainty: most problems are either NP-hard, or have incomplete input data which makes an exact computation impossible. Recently, there has been a huge progress in our understanding of intractability, based on spectacular algorithmic and lower bound techniques. For several problems, especially those with only local constraints, we can design optimum approximation algorithms that are provably the best possible. However, typical optimization problems usually involve complex global constraints and are much less understood. The situation is even worse for coping with uncertainty. Most of the algorithms are based on ad-hoc techniques and there is no deeper understanding of what makes various problems easy or hard. This proposal describes several new directions, together with concrete intermediate goals, that will break important new ground in the theory of approximation and online algorithms. The particular directions we consider are (i) extend the primal dual method to systematically design online algorithms, (ii) build a structural theory of online problems based on work functions, (iii) develop new tools to use the power of strong convex relaxations and (iv) design new algorithmic approaches based on non-constructive proof techniques. The proposed research is at the cutting edge of algorithm design, and builds upon the recent success of the PI in resolving several longstanding questions in these areas. Any progress is likely to be a significant contribution to theoretical computer science and combinatorial optimization.

1 519 285 €

Start date: 2014-05-01, End date: 2019-04-30

Relative to other species, humans are characterised by considerable biological diversity despite genetic homogeneity. This diversity is reflected in skeletal variation, but we lack sufficient understanding of the underlying mechanisms to adequately interpret the archaeological record. The proposed research will address problems in our current understanding of the origins of human variation in the past by: 1) documenting and interpreting the pattern of global hunter-gatherer variation relative to genetic phylogenies and climatic variation; 2) testing the relationship between environmental and skeletal variation among genetically related hunter-gatherers from different environments; 3) examining the adaptability of living humans to different environments, through the study of energetic expenditure and life history trade-offs associated with locomotion; and 4) investigating the relationship between muscle and skeletal variation associated with locomotion in diverse environments. This will be achieved by linking: a) detailed study of the global pattern of hunter-gatherer variation in the Late Pleistocene and Holocene with; b) ground-breaking experimental research which tests the relationship between energetic stress, muscle function, and bone variation in living humans. The first component tests the correspondence between skeletal variation and both genetic and climatic history, to infer mechanisms driving variation. The second component integrates this skeletal variation with experimental studies of living humans to, for the first time, directly test adaptive implications of skeletal variation observed in the past. ADaPt will provide the first links between prehistoric hunter-gatherer variation and the evolutionary parameters of life history and energetics that may have shaped our success as a species. It will lead to breakthroughs necessary to interpret variation in the archaeological record, relative to human dispersals and adaptation in the past.

1 911 485 €

Start date: 2014-07-01, End date: 2019-06-30

"The proposed research program has three main objectives. The first and second objectives are to seek extreme precisions in optical atomic spectroscopy and optical clocks, and to use this quest as a mean of exploration in atomic physics. The third objective is to explore new possibilities that stem from extreme precision. These goals will be pursued via three complementary activities: #1: Search for extreme precisions with an Hg optical lattice clock. #2: Explore and exploit the rich Hg system, which is essentially unexplored in the cold and ultra-cold regime. #3: Identify new applications of clocks with extreme precision to Earth science. Clocks can measure directly the gravitational potential via Einstein’s gravitational redshift, leading to the idea of “clock-based geodesy”. The 2 first activities are experimental and build on an existing setup, where we demonstrated the feasibility of an Hg optical lattice clock. Hg is chosen for its potential to surpass competing systems. We will investigate the unexplored physics of the Hg clock. This includes interactions between Hg atoms, lattice-induced light shifts, and sensitivity to external fields which are specific to the atomic species. Beyond, we will explore the fundamental limits of the optical lattice scheme. We will exploit other remarkable features of Hg associated to the high atomic number and the diversity of stable isotopes. These features enable tests of fundamental physical laws, ultra-precise measurements of isotope shifts, measurement of collisional properties toward evaporative cooling and quantum gases of Hg, investigation of forbidden transitions promising for measuring the nuclear anapole moment of Hg. The third activity is theoretical and is aimed at initiating collaborations with experts in modelling Earth gravity. With this expertise, we will identify the most promising and realistic approaches for clocks and emerging remote comparison methods to contribute to geodesy, hydrology, oceanography, etc."

1 946 432 €

Start date: 2014-04-01, End date: 2019-03-31

This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.

2 310 884 €

Start date: 2014-11-01, End date: 2019-10-31

"AEROCAT aims at the elucidation of the potential of nanoparticle derived aerogels in catalytic applications. The materials will be produced from a variety of nanoparticles available in colloidal solutions, amongst which are metals and metal oxides. The evolving aerogels are extremely light, highly porous solids and have been demonstrated to exhibit in many cases the important properties of the nanosized objects they consist of instead of simply those of the respective bulk solids. The resulting aerogel materials will be characterized with respect to their morphology and composition and their resulting (electro-)catalytic properties examined in the light of the inherent electronic nature of the nanosized constituents. Using the knowledge gained within the project the aerogel materials will be further re-processed in order to exploit their full potential relevant to catalysis and electrocatalysis. From the vast variety of possible applications of nanoparticle-based hydro- and aerogels like thermoelectrics, LEDs, pollutant clearance, sensorics and others we choose our strictly focused approach (i) due to the paramount importance of catalysis for the Chemical Industry, (ii) because we have successfully studied the Ethanol electrooxidation on a Pd-nanoparticle aerogel, (iii) we have patented on the oxygen reduction reaction in fuel cells with bimetallic aerogels, (iv) and we gained first and extremely promising results on the semi-hydrogenation of Acetylene on a mixed Pd/ZnO-nanoparticle aerogel. With this we are on the forefront of a research field which impact might not be overestimated. We should quickly explore its potentials and transfer on a short track the knowledge gained into pre-industrial testing."

2 194 000 €

Start date: 2014-02-01, End date: 2019-01-31

"By 2040, the European population aged over 60 will rise to 290 million, with those estimated to have dementia to 15.9 million. These dramatic demographic changes will pose huge challenges to health care systems, hence a detailed understanding of age-related cognitive and neurobiological changes is essential for helping elderly populations maintain independence. However, while existing research into cognitive ageing has carefully characterised developmental trajectories of functions such as memory and processing speed, one key cognitive ability that is particularly relevant to everyday functioning has received very little attention: In surveys, elderly people often report substantial declines in navigational abilities such as problems with finding one’s way in a novel environment. Such deficits severely restrict the mobility of elderly people and affect physical activity and social participation, but the underlying behavioural and neuronal mechanisms are poorly understood. In this proposal, I will take a new approach to cognitive ageing that will bridge the gap between animal neurobiology and human cognitive neuroscience. With support from the ERC, I will create a team that will characterise the mechanisms mediating age-related changes in navigational processing in humans. The project will focus on three structures that perform key computations for spatial navigation, form a closely interconnected triadic network, and are particularly sensitive to the ageing process. Crucially, the team will employ an interdisciplinary methodological approach that combines mathematical modelling, brain imaging and innovative data analysis techniques with novel virtual environment technology, which allows for rigorous testing of predictions derived from animal findings. Finally, the proposal also incorporates a translational project aimed at improving spatial mnemonic functioning with a behavioural intervention, which provides a direct test of functional relevance and societal impact."

1 318 990 €

Start date: 2014-01-01, End date: 2018-12-31

"In our largely unchanging radio Universe, a highly dynamic component was recently discovered: flashes of bright radio emission that last only milliseconds but appear all over the sky. Some of these radio bursts can be traced to intermittently pulsating neutron stars. Other bursts however, apparently originate far outside our Galaxy. Due to great observational challenges, the evolution of the neutron stars is not understood, while more importantly, the nature of the extragalactic bursts remains an outright mystery. My overall aim is to understand the physics that drives both kinds of brief and luminous bursts. My primary goal is to identify the highly compact astrophysical explosions powering the extragalactic bursts. My previous surveys are the state of the art in fast-transient detection; I will now increase by a factor of 10 this exploration volume. In real-time I will provide arcsec positions, 10,000-fold more accurate than currently possible, to localize such extragalactic bursts for the first time and understand their origin. My secondary goal is to unravel the unexplained evolution of intermittently pulsating neutron stars (building on e.g., my recent papers in Science, 2013), by doubling their number and modeling their population. To achieve these goals, I will carry out a highly innovative survey: the Apertif-LOFAR Exploration of the Radio Transient Sky. ALERT is over an order of magnitude more sensitive than all current state-of-the art fast-transient surveys. Through its novel, extremely wide field-of-view, Westerbork/Apertif will detect many tens of extragalactic bursts. Through real-time triggers to LOFAR I will next provide the precise localisation that is essential for radio, optical and high-energy follow-up to, for the first time, shed light on the physics and objects driving these bursts – evaporating primordial black holes; explosions in host galaxies; or, the unknown?"

1 999 823 €

Start date: 2014-12-01, End date: 2019-11-30

One of the fundamental goals of theoretical computer science is to understand the possibilities and limits of efficient computation. This quest has two dimensions. The theory of algorithms focuses on finding efficient solutions to problems, while computational complexity theory aims to understand when and why problems are hard to solve. These two areas have different philosophies and use different sets of techniques. However, in recent years there have been indications of deep and mysterious connections between them. In this project, we propose to explore and develop the connections between algorithmic analysis and complexity lower bounds in a systematic way. On the one hand, we plan to use complexity lower bound techniques as inspiration to design new and improved algorithms for Satisfiability and other NP-complete problems, as well as to analyze existing algorithms better. On the other hand, we plan to strengthen implications yielding circuit lower bounds from non-trivial algorithms for Satisfiability, and to derive new circuit lower bounds using these stronger implications. This project has potential for massive impact in both the areas of algorithms and computational complexity. Improved algorithms for Satisfiability could lead to improved SAT solvers, and the new analytical tools would lead to a better understanding of existing heuristics. Complexity lower bound questions are fundamental but notoriously difficult, and new lower bounds would open the way to unconditionally secure cryptographic protocols and derandomization of probabilistic algorithms. More broadly, this project aims to initiate greater dialogue between the two areas, with an exchange of ideas and techniques which leads to accelerated progress in both, as well as a deeper understanding of the nature of efficient computation.

1 274 496 €

Start date: 2014-03-01, End date: 2019-02-28

"The first decade of Algorithmic Mechanism Design (AMD) concentrated, very successfully, on the design of truthful mechanisms for the allocation of resources among agents with private preferences. Truthful mechanisms are ones that incentivize rational users to report their preferences truthfully. Truthfulness, however, for all its theoretical appeal, suffers from several inherent limitations, mainly its high communication and computation complexities. It is not surprising, therefore, that practical applications forego truthfulness and use simpler mechanisms instead. Simplicity in itself, however, is not sufficient, as any meaningful mechanism should also have some notion of fairness; otherwise agents will stop using it over time. In this project I plan to develop an innovative AMD theoretical framework that will go beyond truthfulness and focus instead on the natural themes of simplicity and fairness, in addition to computational tractability. One of my primary goals will be the design of simple and fair poly-time mechanisms that perform at near optimal levels with respect to important economic objectives such as social welfare and revenue. To this end, I will work toward providing precise definitions of simplicity and fairness and quantifying the effects of these restrictions on the performance levels that can be obtained. A major challenge in the evaluation of non-truthful mechanisms is defining a reasonable behavior model that will enable their evaluation. The success of this project could have a broad impact on Europe and beyond, as it would guide the design of natural mechanisms for markets of tens of billions of dollars in revenue, such as online advertising, or sales of wireless frequencies. The timing of this project is ideal, as the AMD field is now sufficiently mature to lead to a breakthrough and at the same time young enough to be receptive to new approaches and themes."

1 394 600 €

Start date: 2013-11-01, End date: 2018-10-31

Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.

2 176 000 €

Start date: 2014-02-01, End date: 2020-01-31

"Recent technological evolutions, including the cloud, the multicore, the social and the mobiles ones, are turning computing ubiquitously distributed. Yet, building high-assurance distributed programs is notoriously challenging. One of the main reasons is that these systems usually seek to achieve several goals at the same time. In short, they need to be efficient, responding effectively in various average-case conditions, as well as reliable, behaving correctly in severe, worst-case conditions. As a consequence, they typically intermingle different strategies: each to cope with some specific condition, e.g., with or without node failures, message losses, time-outs, contention, cache misses, over-sizing, malicious attacks, etc. The resulting programs end up hard to design, prove, verify, implement, test and debug. Not surprisingly, there are anecdotal evidences of the fragility of the most celebrated distributed systems. The goal of this project is to contribute to building high-assurance distributed programs by introducing a new dimension for separating and isolating their concerns, as well as a new scheme for composing and reusing them in a modular manner. In short, the project will explore the inherent power and limitations of a novel paradigm, Adversary-Oriented Computing (AOC). Sub-programs, each implementing a specific strategy to cope with a given adversary, modelling a specific working condition, are designed, proved, verified, implemented, tested and debugged independently. They are then composed, possibly dynamically, as black-boxes within the same global program. The AOC project is ambitious and it seeks to fundamentally revisit the way distributed algorithms are designed and distributed systems are implemented. The gain expected in comparison with today's approaches is substantial, and I believe it will be proportional to the degree of difficulty of the distributed problem at hand."

2 147 012 €

Start date: 2014-06-01, End date: 2019-05-31

The proposal is built on the core idea to use an ensemble of multiple level self-organization processes to create a next generation photocatalytic platform that provides unprecedented property and reactivity control. As a main output, the project will yield a novel highly precise combined catalyst/photocatalyst assembly to: 1) provide a massive step ahead in photocatalytic applications such as direct solar hydrogen generation, pollution degradation (incl. CO2 decomposition), N2 fixation, or photocatalytic organic synthesis. It will drastically enhance efficiency and selectivity of photocatalytic reactions, and enable a high number of organic synthetic reactions to be carried out economically (and ecologically) via combined catalytic/photocatalytic pathways. Even more, it will establish an entirely new generation of “100% depoisoning”, anti-aggregation catalysts with substantially enhanced catalyst life-time. For this, a series of self-assembly processes on the mesoscale will be used to create highly uniform arrays of single-catalyst-particle-in-a-single-TiO2-cavity; target is a 100% reliable placement of a single <10 nm particle in a 10 nm cavity. Thus catalytic features of, for example Pt nanoparticles, can ideally interact with the photocatalytic properties of a TiO2 cavity. The cavity will be optimized for optical and electronic properties by doping and band-gap engineering; the geometry will be tuned to the range of a few nm.. This nanoscopic design yields to a radical change in the controllability of length and time-scales (reactant, charge carrier and ionic transport in the substrate) in combined photocatalytic/catalytic reactions. It is of key importance that all nanoscale assembly principles used in this work are scalable and allow to create square meters of nanoscopically ordered catalyst surfaces. We target to demonstrate the feasibility of the implementation of the nanoscale principles in a prototype macroscopic reactor.

2 427 000 €

Start date: 2014-03-01, End date: 2019-02-28

APPLAUSE’s aim is to produce a body of evidence that illustrates how young people with mental health problems currently interact with both formal mental health services and informal social and familial support structures. Careful analysis of data gathered in the UK and Brazil will allow formulation of globally relevant insights into mental health care delivery for young people, which will be presented internationally as a resource for future health care service design. APPLAUSE will allow the collection of an important data set that does not currently exist in this field, and will look to other disciplines for innovative approaches to data analysis. Whist standard analysis may allow for snapshots of health service use, using innovative life course methods will allow us to to characterise patterns of complete service use of each individual participant’s experience of accessing mental health care and social support. Adolescence is a critical period in mental health development, which has been largely neglected by public health efforts. Psychiatric disorders rank as the primary cause of disability among individuals aged 10-24 years, worldwide. Moreover, many health risk behaviours emerge during adolescence and 70% of adult psychiatric disorders are preceded by mental health problems during adolescent years. However, delays to receiving care for psychiatric disorders, following disorder onset, avreage more than ten years and little is known about factors which impede access to and continuity of care among young people with mental health problems. APPLAUSE will analyse current access models, reports of individual experiences of positive and negative interactions with health care services and the culturally embedded social factors that impact on such access. Addressing this complex problem from a global perspective will advance the development of a more diverse and innovative set of strategies for improving earlier access to care.

1 499 948 €

Start date: 2014-01-01, End date: 2018-12-31