ERC FUNDED PROJECTS

Evidence of a growing disengagement of citizens from politics is multiplying. Electoral turnout reaches historically low levels. Anti-establishment and populist parties are on the rise. Fewer and fewer Europeans trust their representative institutions. In response, we have observed a multiplication of institutional reforms aimed at revitalizing representative democracy. Two in particular stand out: the delegation of some political decision-making powers to (1) selected citizens and to (2) selected experts. But there is a paradox in attempting to cure the crisis of representative democracy by introducing such reforms. In representative democracy, control over political decision-making is vested in elected representatives. Delegating political decision-making to selected experts/citizens is at odds with this definition. It empowers the non-elected. If these reforms show that politics could work without elected officials, could we really expect that citizens’ support for representative democracy would be boosted and that citizens would re-engage with representative politics? In that sense, would it be a cure for the crisis of representative democracy, or rather a curse? Our central hypothesis is that there is no universal and univocal healing (or harming) effect of non-elected politics on support for representative democracy. In order to verify it, I propose to collect data across Europe on three elements: (1) a detailed study of the preferences of Europeans on how democracy should work and on institutional reforms towards non-elected politics, (2) a comprehensive inventory of all actual cases of empowerment of citizens and experts implemented across Europe since 2000, and (3) an analysis of the impact of exposure to non-elected politics on citizens’ attitudes towards representative democracy. An innovative combination of online survey experiments and of panel surveys will be used to answer this topical research question with far-reaching societal implication.

1 981 589 €

Start date: 2018-09-01, End date: 2023-08-31

"In the past few decades, the disciplines of textual scholarship and genetic criticism have insisted on their respective differences. Nonetheless, a rapprochement would be mutually beneficial. The proposed research endeavours to innovate scholarly editing with the combined forces of these two disciplines. Since genetic criticism has objected to the subservient role of manuscript research in textual criticism, the proposed research suggests a reversal of roles: instead of employing manuscript research with a view to making an edition, an electronic edition can be designed in such a way that it becomes a tool for manuscript research and genetic criticism. The research hypothesis is that such a rapprochement can be achieved by means of an approach to textual variants that values creative undoing (ways of de-composing a text as an integral part of composition and literary invention) more than has hitherto been the case in textual scholarship. This change of outlook will be tested by means of the marginalia, notes and manuscripts of an author whose work is paradigmatic for genetic criticism: Samuel Beckett. His manuscripts will serve as a case study to determine the functions of creative undoing in the process of literary invention and its theoretical and practical implications for electronic scholarly editing and the genetic analysis of modern manuscripts. Extrapolating from this case study, the results are employed to tackle a topical issue in European textual scholarship. The envisaged rapprochement between the disciplines of genetic criticism and textual scholarship is the core of this proposal’s endeavour to advance the state of the art in these disciplines by giving shape to a new orientation within scholarly editing."

1 147 740 €

Start date: 2013-01-01, End date: 2017-12-31

Understanding the coordination of attitudes in societies is vitally important for many disciplines and global social challenges. Network opinion dynamics are poorly understood, especially in hybrid networks where automated (bot) agents seek to influence economic or political processes (e.g. USA: Trump vs Clinton; UK: Brexit). A dynamic fixing theory of attitudes is proposed, premised on three features of attitudes demonstrated in ethnomethodology and social psychology; that people: 1) simultaneously hold a repertoire of multiple (sometimes ambivalent) attitudes, 2) express attitudes to enact social identity; and 3) are accountable for attitude expression in interaction. It is proposed that interactions between agents generate symbolic links between attitudes with the emergent social-symbolic structure generating perceived ingroup similarity and outgroup difference in a multilayer network. Thus attitudes can become dynamically fixed when constellations of attitudes are locked-in to identities via multilayer networks of attitude agreement and disagreement; a process intensified by conflict, threat or zero-sum partisan processes (e.g. elections/referenda). Agent-based simulations will validate the theory and explore the hypothesized channels of bot influence. Network experiments with human and hybrid networks will test theoretically derived hypotheses. Observational network studies will assess model fit using historical Twitter data. Results will provide a social-psychological-network theory for attitude dynamics and vulnerability to computational propaganda in hybrid networks. The theory will explain: (a) when and how consensus can propagate rapidly through networks (since identity processes fix attitudes already contained within repertoires); (b) limits of identity-related attitude propagation (since attitudes outside of repertoires will not be easily adopted); and (c) how attitudes can often ‘roll back’ after events (since contextual changes ‘unfix’ attitudes).

1 499 925 €

Start date: 2018-12-01, End date: 2023-11-30

"Mutation and recombination are fundamental biological processes that determine adaptability of populations. The mutation rate reflects the equilibrium between the need to adapt, the burden of mutation load, the “cost of fidelity”, and random drift that determines a lower limit in achievable fidelity. Recombination fulfills an essential mechanistic role during meiosis, ensuring proper chromosomal segregation. Recombination affects the rate of creation and loss of favorable haplotypes, imposing 2nd-order selection pressure on modifiers of recombination. It is becoming apparent that recombination and mutation rates vary between individuals, and that these differences are in part inherited. Both processes are therefore “evolvable”, and amenable to genomic analysis. Identifying genetic determinants underlying these differences will provide insights in the regulation of mutation and recombination. The mutational load, and in particular the number of lethal equivalents per individual, remains poorly defined as epidemiological and molecular data yield estimates that differ by one order of magnitude. A relationship between recombination and fertility has been reported in women but awaits confirmation. Population structure (small effective population size; large harems), phenotypic data collection (systematic recording of > 50 traits on millions of cows), and large-scale SNP genotyping (for genomic selection), make cattle populations uniquely suited for genetic analysis. DAMONA proposes to exploit these unique resources, combined with recent advances in next generation sequencing and genotyping, to: (i) quantify and characterize inter-individual variation in male and female mutation and recombination rates, (ii) map, fine-map and identify causative genes underlying QTL for these four phenotypes, (iii) test the effect of loss-of-function variants on >50 traits including fertility, and (iv) study the effect of variation in recombination on fertility."

2 258 000 €

Start date: 2013-03-01, End date: 2018-02-28

Wireless and mobile communication systems have become an important part of our daily environment. Since the introduction of the GSM-network in the early nineties, different wireless applications such as WiFi, Bluetooth, GPS, etc. have been brought into the market. This has become possible due to the high integration of integrated circuits in relatively cheap technologies. Besides the digital signal processing, those wireless applications require complex analog circuits operating at very high frequencies (RF circuits). In the early days these were implemented as discrete components or standalone ICs in expensive technologies such as GaAs, InP and SiGe. Due to the research towards nanometer CMOS technologies, and due to improved RF circuit techniques, RF-CMOS has been introduced since the mid nineties. The intention of this research project is to take the next big leap forward in wireless applications, i.e. the exploration and research, based on the vast RF-CMOS knowledge already existing, towards the Extremely High Frequencies which is above 70 GHz up to 300GHz, with wavelengths close to 1 mm. The research project is a logical evolution of the RF-CMOS research knowledges of the team. For that the "natural evolution" acronym DARWIN (Deep mm-Wave RF CMOS Integrated Circuits (with the M of CMOS inverted (W)) is choosen. Implementing circuit techniques in standard CMOS technologies at those frequencies is again an enormous challenge and will open a lot of new opportunities and applications towards the future due to possibilities in safety monitoring, e.g. collision radar detection for automobiles at 77 GHz, the need for high data-rate telecommunication systems, with capacity of 1-10 Gbps, and imaging for medical and security systems. The goal of the proposed project is to perform the necessary fundamental basic research to be able to implement these 70-300 GHz applications in CMOS technology (45 nm and below).

2 042 640 €

Start date: 2009-01-01, End date: 2013-12-31

A new immunoregulatory axis has emerged in recent years demonstrating that cellular metabolism is crucial in controlling immune responses. This regulatory axis is acutely sensitive to nutrients that fuel metabolic pathways and support nutrient sensitive signalling pathways. My recent research demonstrates that nutrients are dynamically controlled and are not equally available to all immune cells. The data shows that activated T cells, clustered around a dendritic cell (DC), can consume the available nutrients, leaving the DC nutrient deprived in vitro. This local regulation of the DC nutrient microenvironment by neighbouring cells has profound effects on DC function and T cell responses. Nutrient deprived DC have altered signalling (decreased mTORC1 activity), increased pro-inflammatory functions (IL12 and costimulatory molecule expression) and induce enhanced T cell responses (proliferation, IFNγ production). However, proving this, particularly in vivo, is a major challenge as the tools to investigate nutrient dynamics within complex microenvironments have not yet been developed. This research programme will generate innovative new technologies to measure the local distribution of glucose, glutamine and leucine (all of which control mTORC1 signalling) to be visualised and quantified. These technologies will pioneer a new era of in vivo nutrient analysis. Nutrient deprivation of antigen presenting DC will then be investigated (using our new technologies) in response to various stimuli within the inflammatory lymph node and correlated to CD8 T cell responses. We will generate state-of-the-art transgenic mice to specifically knock-down nutrient transporters for glucose, glutamine, or leucine in DC to definitively prove that the availability of these nutrients to antigen presenting DC is a key mechanism for controlling CD8 T cells responses. This would be a paradigm shifting discovery that would open new horizons for the study of nutrient-regulated immune responses.

1 995 861 €

Start date: 2018-05-01, End date: 2023-04-30

Somatically acquired loss-of-heterozygosity (LOH) is extremely common in cancer; deletions of recessive cancer genes, miRNAs, and regulatory elements, can confer selective growth advantage, whereas deletions over fragile sites are thought to reflect an increased local rate of DNA breakage. However, most LOHs in cancer genomes remain unexplained. Here we plan to combine a TALEN technology and the experimental models of cell transformation derived from primary human cells to delete specific chromosomal regions that are frequently lost in cancer samples. The development of novel strategies to introduce large chromosomal rearrangements into the genome of primary human cells will offer new perspectives for studying gene function, for elucidating chromosomal organisation, and for increasing our understanding of the molecular mechanisms and pathways underlying cancer development.Using this technology to genetically engineer cells that model cancer-associated genetic alterations, we will identify LOH regions critical for the development and progression of human cancers, and will investigate the cooperative effect of loss of genes, non-coding RNAs, and regulatory elements located within the deleted regions on cancer-associated phenotypes. We will assess how disruption of the three-dimensional chromosomal network in cells with specific chromosomal deletions contributes to cell transformation. Isogenic cell lines harbouring targeted chromosomal alterations will also serve us as a platform to identify compounds with specificity for particular genetic abnormalities. As a next step, we plan to unravel the mechanisms by which particular homozygous deletions contribute to cancer-associated phenotypes. If successful, the results of these studies will represent an important step towards understanding oncogenesis, and could yield new diagnostic and prognostic markers as well as identify potential therapeutic targets.

1 498 764 €

Start date: 2012-10-01, End date: 2017-09-30

This proposal seeks support for a research group led by James Heckman of the Geary Institute at University College Dublin to produce an integrated developmental approach to health that studies the origins and the evolution of health inequalities over the lifecourse and across generations, and the role played by cognition, personality, genes, and environments. Major experimental and nonexperimental international datasets will be analyzed. A practical guide to implementing related policy will be produced. We will build a science of human development that draws on, extends, and unites research on the biology and epidemiology of health disparities with medical economics and the economics of skill formation. The goal is to develop an integrated framework to jointly model the economic, social and biological mechanisms that produce the evolution and the intergenerational transmission of health and of the capabilities that foster health. The following tasks will be undertaken: (1) We will quantify the importance of early-life conditions in explaining the existence of health disparities across the lifecourse. (2) We will understand how health inequalities are transmitted across generations. (3) We will assess the health benefits from early childhood interventions. (4) We will examine the role of genes and environments in the aetiology and evolution of disease. (5) We will analyze how health inequalities emerge and evolve across the lifecourse. (6) We will give biological foundations to both our models and the health measures we will use. The proposed research will investigate causal channels for promoting health. It will compare the relative effectiveness of interventions at various stages of the life cycle and the benefits and costs of later remediation if early adversity is not adequately eliminated. It will guide the design of current and prospective experimental and longitudinal studies and policy formulation, and will train young scholars in frontier methods of research

2 505 222 €

Start date: 2011-05-01, End date: 2016-04-30

The possibility to chronically monitor the brain 24/7 in daily-life activities would revolutionize human-machine interactions and health care, e.g., in the context of neuroprostheses, neurological disorders, and brain-computer interfaces (BCI). Such chronic systems must satisfy challenging energy and miniaturization constraints, leading to modular designs in which multiple networked miniature neuro-sensor modules form a ‘neuro-sensor network’ (NSN). However, current multi-channel neural signal processing (NSP) algorithms were designed for traditional neuro-sensor arrays with central access to all channels. These algorithms are not suited for NSNs, as they require unrealistic bandwidth budgets to centralize the data, yet a joint neural data analysis across NSN modules is crucial. The central idea of this project is to remove this algorithm bottleneck by designing novel scalable, distributed NSP algorithms to let the modules of an NSN jointly process the recorded neural data through in-network data fusion and with a minimal exchange of data. To guarantee impact, we mainly focus on establishing a new non-invasive NSN concept based on electroencephalography (EEG). By combining multiple ‘smart’ mini-EEG modules into an ‘EEG sensor network’ (EEG-Net), we compensate for the lack of spatial information captured by current stand-alone mini-EEG devices, without compromising in ‘wearability’. Equipping such EEG-Nets with distributed NSP algorithms will allow to process high-density EEG data at viable energy levels, which is a game changer towards high-performance chronic EEG for, e.g., epilepsy monitoring, neuroprostheses, and BCI. We will validate these claims in an EEG-Net prototype in the above 3 use cases, benefiting from ongoing collaborations with the KUL university hospital. In addition, to demonstrate the general applicability of our novel NSP algorithms, we will validate them in other emerging NSN types as well, such as modular or untethered neural probes.

1 489 656 €

Start date: 2019-01-01, End date: 2023-12-31

Evolutionary change of gene copy number through gene duplication is a relatively pervasive phenomenon in eukaryotic genomes. However, for a subset of genes such changes are deleterious because they result in imbalances in the cell. Such dosage-sensitive genes have been increasingly implicated in disease, particularly through the association of copy number variants (CNVs) with pathogenicity. In my lab we have previously discovered that many genes in the human genome which were retained after whole genome duplication (WGD) are refractory to gene duplication both over evolutionary timescales and within populations. These are expected characteristics of dosage-balanced genes. Many of these genes are implicated in human disease. I now propose to take a computational (dry-lab) approach to examine the evolution of dosage-balanced genes further and to develop a sophisticated model of evolutionary constraint of copy number. These models will enable the identification of dosage-balanced genes and their consideration as novel candidate disease loci. Recognising and interpreting patterns of constraint is the cornerstone of molecular evolution. Through careful analysis of genome sequences with respect to gene duplication over evolutionary times and within populations, we will develop a formal and generalised model of copy-number evolution and constraint. We will use these models to identify candidate disease loci within pathogenic CNVs. We will also study the characteristics of known disease genes in order to identify novel candidate loci for dosage-dependent disease. This is an ambitious and high impact project that has the potential to yield major insights into gene copy-number constraint and its relationship to complex disease.

1 358 534 €

Start date: 2013-01-01, End date: 2018-12-31

Thousands of species are polyploid. However, the long-term establishment of organisms that have undergone ancient whole genome duplications (WGDs) has been exceedingly rare and when we analyse the genomes of plants and animals, we can, at most, find evidence for a very limited number of WGDs that survived on the longer term. The paucity of (established) ancient genome duplications and the existence of so many species that are currently polyploid provides a fascinating paradox. There is growing evidence that the majority of ancient WGDs were established at specific times in evolution, for instance during periods of environmental change and periods of mass-extinction. The reason for this ‘stress’-polyploidy relationship has been the subject of considerable speculation and several hypotheses have been put forward to explain this observation: (a) stressful conditions promote polyploid formation; (b) polyploidisation causes a niche shift allowing polyploids to grow in conditions that are unsuitable for their non-polyploid ancestors; and (c) polyploids have an increased evolvability and consequently adapt faster to a changing environment. Here, we want to unravel the mechanistic underpinnings of why and how polyploids can outcompete non-polyploids. We will address these questions by replaying the ‘genome duplication tape of life’ in two different model systems, namely Chlamydomonas and Spirodela. We will run long-term evolutionary (and resequencing) experiments. We will complement these experiments with in-silico experiments based on so-called digital organisms running on artificial genomes. Complementary modelling approaches will also be employed to study the effects of polyploidy from an eco-evolutionary dynamics perspective. By integrating the results obtained from these in vivo and in silico experiments, we will obtain important novel insights in the adaptive potential of polyploids under stressful conditions or during times of environmental and/or climate change.

2 500 000 €

Start date: 2020-01-01, End date: 2024-12-31

Contemporary microprocessors seek at improving performance through thread-level parallelism by co-executing multiple threads on a single microprocessor chip. Projections suggest that future processors will feature multiple tens to hundreds of threads, hence called many-thread processors. Many-thread processors, however, lead to non-dependable performance: co-executing threads affect each other s performance in unpredictable ways because of resource sharing across threads. Failure to deliver dependable performance leads to missed deadlines, priority inversion, unbalanced parallel execution, etc., which will severely impact the usage model and the performance growth path for many important future and emerging application domains (e.g., media, medical, datacenter). DPMP envisions that performance introspection using a cycle accounting architecture that tracks per-thread performance, will be the breakthrough to delivering dependable performance in future many-thread processors. To this end, DPMP will develop a hardware cycle accounting architecture that estimates single-thread progress during many-thread execution. The ability to track per-thread progress enables system software to deliver dependable performance by assigning hardware resources to threads depending on their relative progress. Through this cooperative hardware-software approach, this project addresses a fundamental problem in multi-threaded ad multi/many-core processing.

1 389 000 €

Start date: 2010-10-01, End date: 2016-09-30

Droughts cause agricultural loss, forest mortality and drinking water scarcity. Their predicted increase in recurrence and intensity poses serious threats to future global food security. Several historically unprecedented droughts have already occurred over the last decade in Europe, Australia and the USA. The cost of the ongoing Californian drought is estimated to be about US$3 billion. Still today, the knowledge of how droughts start and evolve remains limited, and so does the understanding of how climate change may affect them. Positive feedbacks from land have been suggested as critical for the occurrence of recent droughts: as rainfall deficits dry out soil and vegetation, the evaporation of land water is reduced, then the local air becomes too dry to yield rainfall, which further enhances drought conditions. Importantly, this is not just a 'local' feedback, as remote regions may rely on evaporated water transported by winds from the drought-affected region. Following this rationale, droughts self-propagate and self-intensify. However, a global capacity to observe these processes is lacking. Furthermore, climate and forecast models are immature when it comes to representing the influences of land on rainfall. Do climate models underestimate this land feedback? If so, future drought aggravation will be greater than currently expected. At the moment, this remains largely speculative, given the limited number of studies of these processes. I propose to use novel in situ and satellite records of soil moisture, evaporation and precipitation, in combination with new mechanistic models that can map water vapour trajectories and explore multi-dimensional feedbacks. DRY-2-DRY will not only advance our fundamental knowledge of the mechanisms triggering droughts, it will also provide independent evidence of the extent to which managing land cover can help 'dampen' drought events, and enable progress towards more accurate short-term and long-term drought forecasts.

1 465 000 €

Start date: 2017-02-01, End date: 2022-01-31

Future data-driven modelling is increasingly challenging for many systems due to higher complexity levels, such as in energy systems, environmental and climate modelling, traffic and transport, industrial processes, health, safety, and others. This requires powerful concepts and frameworks that enable the design of high quality predictive models. In this proposal E-DUALITY we will explore and engineer the potential of duality principles for future data-driven modelling. An existing example illustrating the important role of duality in this context is support vector machines, which possess primal and dual model representations, in terms of feature maps and kernels, respectively. Within this project, besides using existing notions of duality that are relevant for data-driven modelling (e.g. Lagrange duality, Legendre-Fenchel duality, Monge-Kantorovich duality), we will also explore new ones. Duality principles will be employed for obtaining a generically applicable framework with unifying insights, handling different system complexity levels, optimal model representations and designing efficient algorithms. This will require taking an integrative approach across different research fields. The new framework should be able to include e.g. multi-view and multiple function learning, multiplex and multilayer networks, tensor models, multi-scale and deep architectures as particular instances and to combine several of such characteristics, in addition to simple basic schemes. It will include both parametric and kernel-based approaches for tasks as regression, classification, clustering, dimensionality reduction, outlier detection and dynamical systems modelling. Higher risk elements are the search for new standard forms in modelling systems with different complexity levels, matching models and representations to system characteristics, and developing algorithms for large scale applications within this powerful new framework.

2 492 500 €

Start date: 2018-10-01, End date: 2023-09-30

For a number of reasons, in particular their proximity and the abundant range of diagnostics to determine their characteristics, outflows from young stellar objects (YSOs) offer us the best opportunity of discovering how astrophysical jets are generated and the nature of the link between outflows and their accretion disks. Models predict that the jet is initially launched from within 0.1 to a few au of the star and focused on scales at most ten times larger. Thus, even for the nearest star formation region, we need high spatial resolution to image the “central engine” and test current models. With these ideas in mind, and the availability of a whole new set of observational and computational resources, it is proposed to investigate the origin of YSO jets, and the jet/accretion zone link, using a number of highly novel approaches to test magneto-hydrodynamic (MHD) models including: (a) Near-infrared interferometry to determine the spatial distribution and kinematics of the outflow as it is launched as a way of discriminating between competing models. (b) A multi-epoch study of the strength and configuration of the magnetic field of the parent star to see whether model values and geometries agree with observations and the nature of its variability. (c) Examining, through high spatial resolution radio observations, how the ionized component of these jets are collimated very close to the source and how shocks in the flow can give rise to low energy cosmic rays. (d) Use the James Webb Space Telescope (JWST) and, in particular, the Mid-Infrared Instrument (MIRI) and Near-Infrared Spectrograph (NIRSpec) to investigate with high spatial resolution atomic jets from protostars that are still acquiring most of their mass. In addition, we will study how accretion is affected by metallicity by studying young solar-like stars in the low metallicity Magellanic Clouds. In all cases the required observational campaigns have been approved.

1 853 090 €

Start date: 2017-10-01, End date: 2022-09-30

Current anti-angiogenesis based anti-tumor therapy relies on starving tumors by blocking their vascular supply via inhibition of growth factors. However, limitations such as resistance and toxicity, mandate conceptually distinct approaches. We will explore an entirely novel and long-overlooked strategy to discover additional anti-angiogenic candidates, based on the following innovative concept: ¿rather than STARVING TUMORS BY BLOCKING THEIR VASCULAR SUPPLY, we intend TO STARVE BLOOD VESSELS BY BLOCKING THEIR METABOLIC ENERGY SUPPLY¿, so that new vessels cannot form and nourish the growing tumor. This project is a completely new research avenue in our group, but we expect that it will offer refreshing long-term research and translational opportunities for the field. Because so little is known on endothelial cell (EC) metabolism, we will (i) via a multi-disciplinary systems-biology approach of transcriptomics, proteomics, computational network modeling, metabolomics and flux-omics, draw an endothelio-metabolic map in angiogenesis. This will allow us to identify metabolic regulators of angiogenesis, which will be further validated and characterized in (ii) loss and gain-of-function studies in various angiogenesis models in vitro and (iii) in vivo in zebrafish (knockdown; zinc finger nuclease mediated knockout), providing prescreen data to select the most promising candidates. (iv) EC-specific down-regulation (miR RNAi) or knockout studies of selected candidates in mice will confirm their relevance for angiogenic phenotypes in a preclinical model; and ultimately (v) a translational study evaluating EC metabolism-targeted anti-angiogenic strategies (pharmacological inhibitors, antibodies, small molecular compounds) will be performed in tumor models in the mouse.

2 365 224 €

Start date: 2011-05-01, End date: 2016-04-30

In ELECTRIC, I will integrate electrically powered optical frequency combs on mass manufacturable silicon chips. This will allow for making use of all the advantageous properties of these light sources in real-life situations. Optical frequency combs are light sources with a spectrum consisting of millions of laser lines, equally spaced in frequency. This equifrequency spacing provides a link between the radio frequency band and the optical frequency band of the electromagnetic spectrum. This property has literally revolutionized the field of frequency metrology and precision laser spectroscopy. Recently, their application field has been extended. Amongst others, their unique properties have been exploited in precision distant measurement experiments as well as optical waveform and microwave synthesis demonstrators. Moreover, so called “dual-comb spectroscopy” experiments have demonstrated broadband Fourier Transform Infrared spectroscopy with ultra-high resolution and record acquisition speeds. However, most of these demonstrations required large bulky experimental setups which hampers wide deployment. I will build frequency combs on optical chips that can be mass-manufactured. Unlike the current chip scale Kerr comb based solutions they do not need to be optically pumped with a powerful continuous wave laser and can have a narrower comb spacing. The challenge here is two-fold. First, we need to make electrically powered integrated low noise oscillators. Second, we need to lower the threshold of current on-chip nonlinear optical interactions by an order of magnitude to use them in on-chip OFC generators. Specifically I will achieve this goal by: • Making use of ultra-efficient nonlinear optical interactions based on soliton compression in dispersion engineered III-V waveguides and plasmonic enhanced second order nonlinear materials. • Enhance the performance of ultra-low noise silicon nitride mode locked lasers with these nonlinear components.

1 391 250 €

Start date: 2018-02-01, End date: 2023-01-31

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, evolution 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.

1 470 736 €

Start date: 2013-01-01, End date: 2018-12-31

Asian monsoon is a spectacular occurrence in the climate system. What make it so powerful are the combination of thermal contrast between the World s largest landmass (Eurasian continent) and ocean basin (the Indo-Pacific Ocean) and the presence of the World s largest ridge, the Tibetan Plateau. Climatologically, monsoon regions are the most convectively active areas and account for the majority of global atmospheric heat and moisture transport. Moreover, the economy, culture and rhythms of life of 60% of humanity are critically influenced by the evolution and variability of the Asian monsoon. The need to better understand the monsoon leads inevitably to the close inspection of its activity during the geological times to provide a long-term perspective from which any future change may be more effectively assessed. Our research proposal aims to understand the seeming paradox of the exceptionally intense East Asian summer monsoon (actually the strongest over the last one million years) which occurred during the relatively cool interglacial (MIS-13), 500,000 years ago. This will be done using first a model of intermediate complexity (LOVECLIM) to achieve a number of sensitivity experiments to the astronomical forcing, the Eurasian and North American ice sheets, the Tibetan Plateau and the Ocean. Ocean-atmosphere coupled general circulation models will then be used to confirm the main processes underlined by LOVECLIM, in particular those related to the wave train topographically induced by the Eurasian ice sheet, to the Tibetan Plateau, to the sea-surface temperature and to their role in reinforcing the East Asian summer monsoon. This monsoon of MIS-13 will be compared with the monsoon which occurred during the other interglacials of the upper Pleistocene and Holocene (about the last 700,000 years). All simulation results will be compared with the available proxy records, in particular-but not exclusively-those coming from the loess-soil sequences in China.

893 880 €

Start date: 2008-11-01, End date: 2013-10-31

The incidence of autoimmune diseases in developed societies is increasing at high rates, but the underlying cause for this phenomenon has not been elucidated yet. Since the genetic architect remains considerably stable, this increase is likely associated with changes in the environment. Autoimmunity is linked to an imbalance of pro-inflammatory Th17 cells and anti-inflammatory Foxp3+ regulatory T cells (Treg). However, little is known regarding environmental factors that influence the Th17/Treg balance. We recently discovered that a sodium-rich diet severely exacerbates experimental autoimmune encephalomyelitis (EAE) through an increased induction of pathogenic Th17 cells. Surprisingly, our preliminary data indicate that high-salt conditions also significantly impair Treg function, resembling a phenotype observed in several human autoimmune diseases. In addition, we have evidence that a high-salt diet affects the gut microbiota, implicating possible indirect effects on immune cells in vivo. Based on these findings we hypothesize that excess dietary salt represents an environmental risk factor for autoimmune diseases by modulating the Th17/Treg balance by several direct and indirect mechanisms. To address this hypothesis we will 1) examine the underlying mechanisms of high-salt induced Treg dysfunction and effects on the Treg/Th17 balance by molecular and functional analysis in vitro and compare it to known risk variants of human autoimmune diseases, and 2) define direct and indirect effects of excess dietary salt on the Th17/Treg balance and autoimmunity in vivo and explore potential novel pathways for targeted interventions. Thus, the proposed study will uncover the impact of a newly discovered environmental modulator of the immune cell balance and will ultimately pave the way for new approaches in therapy and prevention of autoimmune diseases.

1 499 041 €

Start date: 2015-08-01, End date: 2020-07-31

One of the most ambitious goals of modern astrophysics is to characterise the physical and chemical properties of rocky planets orbiting in the habitable zone of nearby Sun-like stars. Although the observation of planetary transits could in a few limited cases be used to reach such a goal, it is widely recognised that only direct imaging techniques will enable such a feat on a statistically significant sample of planetary systems. Direct imaging of Earth-like exoplanets is however a formidable challenge due to the huge contrast and minute angular separation between such planets and their host star. The proposed EPIC project aims to enable the direct detection and characterisation of terrestrial planets located in the habitable zone of nearby stars using ground-based high-contrast imaging in the thermal infrared domain. To reach that ambitious goal, the project will focus on two main research directions: (i) the development and implementation of high-contrast imaging techniques and technologies addressing the smallest possible angular separations from bright, nearby stars, and (ii) the adaptation of state-of-the-art machine learning techniques to the problem of image processing in high-contrast imaging. While the ultimate goal of this research can likely only be reached with the advent of giant telescopes such as the Extremely Large Telescope (ELT) around 2025, the EPIC project will lay the stepping stones towards that goal and produce several high-impact results along the way, e.g. by re-assessing the occurrence rate of giant planets in direct imaging surveys at the most relevant angular separations (i.e., close to the snow line), by conducting the deepest high-contrast imaging search for rocky planets in the alpha Centauri system, by preparing the scientific exploitation of the ELT, and by providing the first open-source high-contrast image processing toolbox relying on supervised machine learning techniques.

2 178 125 €

Start date: 2019-05-01, End date: 2024-04-30

Heart failure (HF) affects 15 million Europeans and entails higher mortality and health care costs than cancer. EPLORE addresses this issue by prospective epidemiological research in 4 European countries and by a proof-of-concept clinical trial. WP1 will for the first time at the population level document the incidence and progression of subclinical LV dysfunction and clarify whether asymptomatic LV dysfunction, as picked up by the newest echocardiographic techniques, predicts cardiovascular (CV) outcomes, including HF. WP2 will investigate the contribution of ventricular-arterial coupling disease and mechanical LV dyssynchrony to subclinical LV dysfunction. WP3 will identify a set of urinary polypeptides that signify early LV dysfunction and validate these biomarkers by showing that they predict deterioration of LV function, progression to HF and the incidence of CV complications over and beyond established risk factors. WP3 will also search for novel panels of circulating biomarkers, of which combined measurement will add information (accuracy, sensitivity and specificity) to established biomarkers (e.g., NT-proBNP) and identify genetic variants involved in the progression of LV dysfunction, either causally or as biomarker. WP4 consists of a randomised clinical trial to translate in a high-risk high-gain setting the results of WPs 1-3 into clinical practice and to identify a new treatment modality that potentially slows progression of diastolic LV dysfunction. Dissemination in WP5 will contribute to new guidelines for the prevention and treatment of HF. WP6 includes governance, monitoring research strategies and output, and protection of IPR. In conclusion, EPLORE will advance risk stratification and the early diagnosis of subclinical HF. The project will potentially result into specific treatments for diastolic LV dysfunction and inform guidelines for prevention and treatment of HF. It will benefit 20% of Europeans who currently have subclinical LV dysfunction.

2 391 440 €

Start date: 2012-07-01, End date: 2017-06-30

Although a gap in educational performance of migrant children compared to children without a migration background is to be observed in most industrialized countries, it is particularly big in countries as Belgium, Germany, Austria and the Netherlands, as has been attested by the PISA-data. Social and ethnic segregation, which is particularly high in these educational systems, seems to be one of the important explanatory factors. This project wants to disentangle what are the crucial factors by which this high level of segregation impacts on unequal opportunities for immigrant children. Going beyond the classic composition effect model (looking at peer group effects, i.e. positive or negative influences of pupils on each other), this project wants to also examine the potential impact of differentiated teacher profiles on group performance. The project wishes to test the hypothesis that the link between school composition and educational performance is a (partly) spurious effect, caused by mediating effect of teacher characteristics. We hypothesize that better skilled and more positively oriented teachers are overrepresented in schools with an 'easier' school population, while so-called 'difficult' schools (populated by working-class immigrant children) have difficulty in attracting and - especially - keeping competent and motivated staff. In order to examine this hypothesis a mixed methods approach will be used, combining quantitative statistical analysis (on new and existing data, for instance multi-level analysis of the PISA-data set and other eligible datasets), qualitative case studies and focus groups. Secondary analysis of existing data-sets (PISA, TIMMS, PIRLS) will be undertaken and new data will be collected (taking the Flemish and Francophone educational systems in Belgium as case-studies).

1 276 071 €

Start date: 2012-01-01, End date: 2017-06-30

My overall aim is to understand the physiologic and medical importance of lung dendritic cells (DC) and to define the suitability of inhibitors of their function for the treatment of inflammatory lung diseases like asthma and COPD. Lung dendritic cells (DC) play crucial roles in the regulation of lung immunity. We still do not fully understand how they get activated in response to different types of environmental triggers like allergens, cigarette smoke and pathogens. Although recognition of conserved motifs by pattern recognition receptors on DCs could be a key event, these stimuli are also accompanied by accumulation of unfolded proteins in the endoplasmic reticulum (ER). Cells respond by mounting the unfolded protein response (UPR) that acts to ameliorate protein folding, but intersects with metabolism, induction of alarm signals and cellular suicide mechanisms. I hypothesize that the presence of unfolded proteins and ER stress in DCs is a crucial endogenous danger signal that is vital to understanding their biology and their involvement in inflammatory lung diseases. My specific aims are to : 1.define the fine tuning of ER stress pathways in various lung DC subsets in health and disease 2. define the specific role of ER stress proteins XBP1, JIK and ORMDL3 in DCs 3. test if interfering with ER stress pathways alters the course of inflammatory lung disease To approach these aims, I have developed mouse models of lung disease that are centered around lung DCs and where ER stress pathways can be genetically deleted. Using a combination of cell biological and immunological techniques I hope to achieve definitive answers as to how ER stress pathways regulate the function of DCs. Manipulation of ER stress pathways by drugs will have a major impact on very common diseases like diabetes, cardiovascular and neurodegenerative disease. Through the current proposal, I hope to extend this exciting field to lung biology.

1 499 580 €

Start date: 2010-12-01, End date: 2015-11-30

Supranational legal regimes are increasingly enforced by multi-level, non-hierarchical court systems, in which judges at the upper, supranational echelon do not have the power to reverse domestic court decisions. Yet the incentives and dynamics that shape the complex patterns of conflict and cooperation observed in the most important of all such court structures, the EU legal system, are still poorly understood. To what extent are domestic courts able to negotiate the terms of their cooperation with the Court of Justice? How do national courts differ in that respect? Are the non-compliance threats issued by domestic courts all equally credible? Do the rare cases where these threats have been put to execution pose a systemic risk to the authority of EU law? How are the domestic courts’ incentives to cooperate with EU judges affected by the sort of political backsliding witnessed in Hungary and Romania in recent years? Our interdisciplinary research project addresses these puzzles of legal integration with the avowed aim of helping judges and policy-makers make more informed choices when faced with compliance problems in the judicial realm. Grounded in a general theory of judicial behaviour, our generic hypothesis is that the authority of EU law at domestic level is determined by domestic politics as well as by judicial attitudes towards integration. EUTHORITY seeks to refine this hypothesis using game theoretic modelling to analyse strategic interactions among the Court of Justice and domestic courts and politicians. Theory-building combines with a large-scale data-collection effort. We undertake to compile longitudinal data on the institutional characteristics and doctrinal responses to legal integration of 68 domestic apex courts across the EU 28 Member States. With a view to construct an annual, court-specific index of legal integration, we also conduct an expert survey asking academic lawyers and practitioners to assess their courts' attitudes towards EU law.

1 475 150 €

Start date: 2015-09-01, End date: 2020-08-31

Every 30 seconds a person suffers an osteoporosis-related bone fracture in Europe, resulting in significant morbidity, mortality and healthcare costs estimated at €36billion annually. Current anti-catabolic therapeutics are associated with severe side effects and are purely preventative, while the only anabolic treatment plateaus at 6 months. This has resulted in a crisis in osteoporosis treatment. Therefore, the aim of EVERBONE is to develop and commercialise a new anabolic multitargeted medicinal product for bone regeneration that mimics the beneficial effects of physical exercise, by recruiting endogenous cells to promote angiogenesis, osteogenesis and bone formation. Building on the discovery that osteocyte-derived mechanically activated extracellular vesicles (MAEVs) mediate the anabolic bone forming response to physical exercise, this project will develop novel bioreactor systems to increase MAEV yield in vitro and scale up for clinical use. Secondly, it will identify a standard mechanical conditioning procedure to generate optimised angiogenically and osteogenically primed MAEVs. Finally, preclinical evaluation of MAEV treatment will be performed in a model of osteoporosis and bone healing, whereby it is expected that MAEVs will localize to bone and mobilise endogenous endothelial and stem cell populations to enhance bone regeneration in osteoporosis and improved healing rates in bone defects. This regrowth of bone will overcome current limitations of anti-resorptive treatments, reducing the risk of fracture and thus the financial burden of treatment. The project will leverage the applicants experience in bone mechanobiology to develop a new product with significant commercial potential. Therefore, the impact of EVERBONE will be multifaceted: it will transform how osteoporosis is treated, it will create economic value through the commercialisation of IP, and most importantly it will improve patient experience and their long-term health and well-being.

149 891 €

Start date: 2019-01-01, End date: 2020-06-30

The 21st century is expected to develop towards a society depending ever and ever more on (bio-)chemical measurements of fluids and matrices that are so complex they are well beyond the current analytical capabilities. Incremental improvements can no longer satisfy the current needs of e.g. the proteomics field, requiring the separation of tens of thousands of components. The pace of progress in these fields is therefore predominantly determined by that of analytical tools, whereby liquid chromatography is the most prominent technique to separate small molecules as well as macromolecules, based on differential interaction of each analyte with support structures giving it a unique migration velocity. To improve its performance, a faster transport between these structures needs to be generated. Unfortunately the commonly pursued strategy, relying on diffusion and reducing the structure size, has come to its limits due to practical limitations related to packing and fabrication of sub-micron support structures, pressure tolerance and viscous heating. A ground-breaking step to advance chromatographic performance to another level would be to accelerate mass transport in the lateral direction, beyond the rate of diffusion only. To meet this requirement, an array of microstructures and local electrodes can be defined to create lateral electroosmotic vortices in a pressure-driven column, aiming to accelerate the local mass transfer in an anisotropic fashion. The achievement of ordered arrays of vortices is intimately linked to this requirement, which is also of broader importance for mixing, anti-fouling of membrane and reactor surfaces, enhanced mass transfer in reactor channels, emulsification, etc. Understanding and implementing anisotropic vortex flows will therefore not only revolutionize analytical and preparative separation procedures, but will also be highly relevant in all flow systems that benefit from enhanced mass transfer.

1 460 688 €

Start date: 2016-03-01, End date: 2021-02-28

This five-year project aims to generate a paradigm shift in the understanding of Graeco-Roman and Late Antique communication. Non-literary, ‘documentary’ texts from Ancient Egypt such as letters, petitions and contracts have provided and continue to provide a key witness for our knowledge of the administration, education, economy, etc. of Ancient Egypt. This project argues that since documentary texts represent originals, their external characteristics should also be brought into the interpretation: elements such as handwriting, linguistic register or writing material transmit indirect social messages concerning hierarchy, status, and power relations, and can therefore be considered ‘semiotic resources’. The project’s driving hypothesis is that communicative variation – variation that is functionally insignificant but socially significant (e.g. there are ~ there’s ~ it’s a lot of people) – enables the expression of social meaning. The main aim of this project is to analyse the nature of this communicative variation. To this end, a multidisciplinary team of six researchers (one PI, one post-doc, and four PhD’s) will apply recent insights form socio-semiotic and socio-linguistic theory to a corpus of Graeco-Roman and Late Antique documentary texts (I – VIII AD) by means of a three-level approach: (i) an open-access database of annotated documentary texts will be created; (ii) the ‘semiotic potential’ of the different semiotic resources that play a role in documentary writing will be analysed; (iii) the interrelationships between the different semiotic resources will be studied. The project will have a significant scientific impact: (i) it will be the first to offer a holistic perspective towards the ‘meaning’ of documentary texts; (ii) the digital tool will open up new ways to investigate Ancient texts; (iii) it will make an important contribution to current socio-semiotic and socio-linguistic research; (iv) it will provide new insights about humans as social beings.

1 476 250 €

Start date: 2018-06-01, End date: 2023-05-31

Corneal 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 scaffolds 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.

1 498 734 €

Start date: 2015-07-01, End date: 2020-06-30

Obesity has reached epidemic proportions globally. At least 2.8 million people die each year as a result of being overweight or obese, the biggest burden being obesity-related diseases. It is now clear that inflammation is an underlying cause or contributor to many of these diseases, including type 2 diabetes, atherosclerosis, and cancer. Recognition that the immune system can regulate metabolic pathways has prompted a new way of thinking about diabetes and weight management. Despite much recent progress, most immunometabolic pathways, and how to target them, are currently unknown. One such pathway is the cross-talk between invariant natural killer (iNKT) cells and neighboring adipocytes. iNKT cells are the innate lipid-sensing arm of the immune system. Since our discovery that mammalian adipose tissue is enriched for iNKT cells, we have identified a critical role for iNKT cells in regulating adipose inflammation and body weight. The goal of this project is to use a multi-disciplinary approach to identify key signals and molecules used by iNKT cells to induce metabolic control and weight loss in obesity. Using immunological assays and multi-photon intravital microscopy, cells and pathways that control the unique regulatory functions of adipose iNKT cells will be identified and characterised. Novel lipid antigens in adipose tissue will be identified using a biochemical approach, perhaps explaining iNKT cell conservation in adipose depots, and providing safe tools for iNKT cell manipulation in vivo. Finally, using proteomics and whole body metabolic analysis in vivo, novel ‘weight-loss inducing’ factors produced by adipose iNKT cells will be identified. This ambitious and high impact project has the potential to yield major insights into immunometabolic interactions at steady state and in obesity. The ability to activate or induce adipose iNKT cells holds remarkable potential as an entirely new therapeutic direction for treating obesity and type 2 diabetes.

1 804 052 €

Start date: 2016-09-01, End date: 2021-08-31

‘Almost three centuries later, it is past time to rethink Montesquieu’s holy trinity’ (Ackerman, 2010). As Ackerman (and many others) have observed, political reality has long left the traditional model of the separation of powers behind. The problems posed by this gap between constitutional theory and political practice have recently acquired fresh urgency as developments in Hungary, Poland, Turkey, Russia, the UK, US, Bolivia and elsewhere place the separation of powers under strain. These include the emergence of authoritarian leaders; personalisation of political authority; recourse to non-legal plebiscites; and the capture or de-legitimisation of other constitutional bodies. This project argues that these difficulties are rooted in a deeper problem with constitutional thinking about institutional power: a constitution-as-law approach that equates the conferral of legal power with the authority to exercise it. This makes it possible for a gap to emerge between legal accounts of authority and its diverse –and potentially conflicting (Cotterrell)– sociological foundations. Where that gap exists, the practical authority of an institution (or constitution) may be vulnerable to challenge from rival and more socially-resonant claims (Scheppele (2017)). It is this gap between legal norms and social facts that the project aims to investigate – and ultimately bridge. How is authority established? How is it maintained? How might it fail? And how does the constitution (as rule? representation (Saward)? mission statement (King)?) shape, re-shape and come to be shaped by those processes? By investigating these questions across six case studies, the project will produce a multi-dimensional account of institutional authority that takes seriously the sociological influence of both law and culture. The results from these cases provide the evidential foundation for the project’s final outputs: a new model and new evaluative measures of the separation of powers.

1 997 628 €

Start date: 2020-01-01, End date: 2024-12-31

Most fire deaths are not caused by burns, but by smoke inhalation. Toxic gases in smoke are beside heat and lack of oxygen the major lethal factor in uncontrolled fires. Drones are considered more and more as the ultimate assistants during firefighting operations. Drones or Unmanned Aerial Vehicles (UAV) provide critical top-down perspectives on dangerous areas. This is helpful in dealing with most fires, and especially important and effective when dealing with fires at high risk sites. There is an urgent need for small, low-weight, low power, real-time gas sensors with a high specificity that can be integrated in UAVs. Availability of such sensors could save lives as UAVs might detect and map toxic gas fields in fireplaces and evaluate how they spread. Besides integration in UAVs, such sensors can be integrated in firefighter’s cloths or installed in fire prone places. In FireSpec, we propose the concept of an integrated wavelength modulation spectroscopic sensor for real time hazardous gas detection based on a silicon photonics integrated chip comprising a series of InP lasers, a gasprobe and an InP detector. The wavelengths of the lasers are matched with the mid-infrared (MIR) absorption lines of the gasses to be detected. The concept directly builds upon knowledge and technology developed in the ERC-project Miracle (Mid-InfraRed Active photonic integrated Circuits for Life sciences and Environment). In Miracle, we are investigating and developing the field of photonic integrated circuits for the MIR wavelength band based on high-index contrast waveguide structures. To extend the functionality of the photonic integrated circuit, heterogeneous integration of other materials such as III-V dies, on the high index contrast waveguide system for particular optical functions, such as lasers and detectors is pursued. FireSpec technology is expected to be a game changer in mobile real time toxic gas detection applications.

149 685 €

Start date: 2016-03-01, End date: 2017-08-31

Thin-film transistor technologies are present in many products today that require an active transistor backplane e.g. flat-panel displays and flat-panel photodetector arrays. Unipolar n-type transistors based on amorphous Indium-Gallium-Zinc-Oxide (a-IGZO) as semiconductor is currently the most promising technology for next generation products demanding a high-performant, low power transistor, manufacturable on flexible substrates enabling curved, bendable and even rollable displays. a-IGZO is a wide bandgap material characterized by extremely low off-state leakage currents and electron mobility of ~20 cm2/Vs. IGZO transistors fabricated on flexible substrates will also find their use in applications that require flexible integrated circuits. The goal of this FLICs proposal is to develop disruptive technology and ground-breaking design innovations with amorphous oxide TFTs on plastic substrates, targeting large scale or very large scale flexible integrated circuits with unprecedented characteristics in terms of power consumption, supply voltage and operating speed, for applications in IoT and wearable healthcare sensor patches. We introduce a new logic style, “quasi-CMOS”, which is based on unipolar, oxide dual-gate thin-film transistors. This logic style will drastically decrease the power consumption of unipolar logic gates in a novel way by taking advantage of dynamic backgate driving and of the transistor’s unique low off-state leakage current, without compromising on switching speed. In addition, we also introduce downscaling of the transistor’s dimensions, while remaining compatible with upscaling to large-area manufacturing platforms. Finally, we will investigate novel ultralow-power design techniques on system-level, while exploiting the quasi-CMOS logic gates. We will demonstrate the power of this innovation with circuits for item-level Internet-of-Things, UHF RFID, and wearable health sensor patches.

1 499 155 €

Start date: 2017-01-01, End date: 2021-12-31

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. The disease is highly prevalent in countries of the Mediterranean basin, the Caucasus and the Middle East, with 1:1000 up to 1:500 inhabitants being affected in countries like Turkey and Armenia. FMF has further spread to other regions of the world with migrations of these populations in modern history and today. Colchicine therapy is the gold standard for FMF patients, but given the risks involved, correct FMF diagnosis is desired before onset of therapy. Diagnosis of FMF is currently based on clinical presentation, and is further supported by review of ethnic origin, family history and genetic analysis of disease-associated MEFV alleles. However, clinical and genetic diagnosis of FMF are complicated by significant overlap of the clinical picture with other autoinflammatory diseases, and over 280 FMF alleles of MEFV have been described. Common genetic tests focus on the most common mutations in exons 2 and 10 of MEFV, but mutations may also occur in other parts of the MEFV gene. Consequently, genetic analysis of FMF is sometimes inconclusive, and correct diagnosis of FMF may sometimes be delayed for years. Here, we describe an immunological assay that for the first time allows selective identification of FMF patients based on the differential inflammasome activation response of their blood monocytes. The availability of a single robust, affordable and convenient assay that immunologically stratifies FMF patients from other autoinflammatory disease patients will be instrumental for improving timely and correct identification of FMF patients for colchicine therapy, and (where desired) will enable more cost-effective selection of patients for genetic confirmation of MEFV mutations.

148 413 €

Start date: 2016-10-01, End date: 2018-03-31

"Linear programming has proved to be an invaluable tool both in theory and practice. Semidefinite programming surpasses linear programming in terms of expressivity while remaining tractable. This project proposal investigates the modeling power of linear and semidefinite programming, in the context of combinatorial optimization. Within the emerging framework of extended formulations (EFs), I seek a decisive answer to the following question: Which problems can be modeled by a linear or semidefinite program, when the number of constraints and variables are limited? EFs are based on the idea that one should choose the ""right"" variables to model a problem. By extending the set of variables of a problem by a few carefully chosen variables, the number of constraints can in some cases dramatically decrease, making the problem easier to solve. Despite previous high-quality research, the theory of EFs is still on square one. This project proposal aims at (i) transforming our current zero-dimensional state of knowledge to a truly three-dimensional state of knowledge by pushing the boundaries of EFs in three directions (models, types and problems); (ii) using EFs as a lens on complexity by proving strong consequences of important conjectures such as P != NP, and leveraging strong connections to geometry to make progress on the log-rank conjecture. The proposed methodology is: (i) experiment-aided; (ii) interdisciplinary; (iii) constructive."

1 455 479 €

Start date: 2014-09-01, End date: 2019-08-31

"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."

1 549 315 €

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

In the future, even the most mundane objects will contain electronic circuitry allowing them to gather, process, display and transmit information. The resulting vast network, often called the Internet of Things, will revolutionise society. To realise this will require the ability to produce electronic circuitry extremely cheaply, often on unconventional substrates. This will be achieved through printed electronics, by the assembly of devices from solution (i.e. ink) using methods adapted from printing technology. However, while printed electronics has been advancing rapidly, the development of new, nano-materials-based inks is required for this area to meet its true potential. We believe recent developments in liquid exfoliation of 2D nanosheets have given us the ideal family of materials to revolutionise electronic ink production. Liquid exfoliation can transform layered crystals into suspensions of nanosheets in very large quantities. In this way we can produce liquid-dispersed nanosheets of a wide range of types including conducting (e.g. graphene, MXenes, TiB2 etc), semiconducting (e.g. MoS2, WSe2, GaS, Black phosphorous etc), insulating (e.g. BN, talc) or electrochemically active (e.g. MoO3, Ni(OH)2, MnO2 etc). These nanosheets can be deposited from liquid to form porous networks of defined electronic type. While these networks have huge applications potential, a large amount of work must be done to translate them into working printed devices. In this project, we will develop methods to transform large volume suspensions of exfoliated nanosheets into bespoke 2D inks with properties engineered for a range of specific printed device applications. We will learn to use this 2D ink to print patterned or large area 2D nanosheet networks with controlled structure, allowing us to tune the electrical properties of the network during printing. We will combine networks of different nanosheet types into complex heterostructures. This will allow us to print all device components (electrodes, active layers, dielectrics, energy storage layers) from one contiguous, multi-component network. In this way we will produce 2D network transistors, solar cells, displays and energy storage systems. FUTURE-PRINT will revolutionise electronic inks and will offer a new path forward for printed electronics.

2 213 317 €

Start date: 2016-11-01, End date: 2021-10-31

This project is the first comprehensive study of the demographic consequences of a major recent development in Europe: while men have always received more education than women in the past, this gender balance in education has now turned around. For the first time in history, there are more highly educated women than men reaching the reproductive ages and looking for a partner. I expect that this will have profound consequences for the demography of reproduction because mating practices have always implied that men are the majority in higher education. These traditional practices are no longer compatible with the new gender distribution in education. The objective of my project is to study in depth the consequences of this historically new situation for reproductive behaviour. The first step of the project is to reconstruct country-specific time series charting the shifting gender balance in education across time and space at different ages. These can then be used as contextual information in subsequent multilevel analyses of reproductive behaviour. In the second part, I will investigate how the reversal of the gender balance is influencing patterns of assortative mating by level of education. Third, I will study how the shifting gender balance is connected to the timing and probability of marriage versus unmarried cohabitation and to the timing and quantum of fertility. Finally, I will investigate the consequences for divorce and separation. Existing data sources will be used that cover a wide range of European countries. This project will not only be ground breaking by setting the research agenda for a new era in the European reproductive landscape. It will also introduce methodological innovations. First, agent based modelling will be used as a method to study assortative mating. Second, I propose a new way to study the causal effect of the gender balance in education. These methodological innovations will prove useful for many other social science projects.

1 489 000 €

Start date: 2013-01-01, End date: 2017-12-31

Thoracic aortic aneurysm and dissection (TAAD) is an important cause of morbidity and mortality in the western world. As 20% of all affected individuals have a positive family history, the genetic contribution to the development of TAAD is significant. Over the last decade dozens of genes were identified underlying syndromic and non-syndromic forms of TAAD. Although mutations in these disease culprits do not yet explain all cases, their identification and functional characterization were essential in deciphering three key aortic aneurysm/dissection patho-mechanisms: disturbed extracellular matrix homeostasis, dysregulated TGFbeta signaling and altered aortic smooth muscle cell contractility. Owing to the recent advent of next-generation sequencing technologies, I anticipate that the identification of additional genetic TAAD causes will remain quite straightforward in the coming years. Importantly, in many syndromic and non-syndromic families, significant non-penetrance and both inter- and intra-familial clinical variation are observed. So, although the primary genetic underlying mutation is identical in all these family members, the clinical spectrum varies widely from completely asymptomatic to sudden death due to aortic dissection at young age. The precise mechanisms underlying this variability remain largely elusive. Consequently, a better understanding of the functional effects of the primary mutation is highly needed and the identification of genetic variation that modifies these effects is becoming increasingly important. In this project, I carefully selected four different innovative strategies to discover mother nature’s own modifying capabilities in human and mouse aortopathy. The identification of these genetic modifiers will advance the knowledge significantly beyond the current understanding, individualize current treatment protocols to deliver true precision medicine and offer promising new leads to novel therapeutic strategies.

1 987 860 €

Start date: 2019-01-01, End date: 2023-12-31

Most biotechnological therapeutics used in the clinic today and under current development, are of protein nature. Eukaryotic expression systems (such as yeasts and mammalian cells) for these therapeutic proteins add carbohydrate moieties (glycans) to the proteins, and these glycans strongly modulate the protein's in vivo biodistribution and therapeutic efficacy. Until recently, no adequate tools were available to accurately control glycosylation structure in these expression systems, but bio-engineering research in our lab and elsewhere has now largely overcome this problem. In the GlycoTarget ERC Consolidator grant project, we aim at exploring the relation between the structure of the glycans on therapeutic proteins and the in vivo targeting properties of these modified proteins to different tissues/cells/subcellular organelles. As highly medically relevant test cases for this exploration, we have selected three diseases with strong unmet therapeutic need, that could potentially be treated with glyco-targeted biopharmaceuticals through three different routes of protein delivery: progressive liver disease (intravenous), allergic asthma (subcutaneous immunization) and active tuberculosis (intrapulmonary delivery).

1 994 760 €

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

The project includes Proof-of-Concept research, as well as preparation and submission of a new patent application. The intention of the current proposal is to develop a novel gas-solid reactor that drastically reduces the limitations of these reactors. Moreover, novel fields of applications will be sought. This new Intellectual Property of UGent will be a subject of its following licensing.

149 900 €

Start date: 2015-06-01, End date: 2016-11-30

Not only does the writer’s hand hold the pen, it manipulates pictures as well. Writers touch, hoard, cut, copy, pin and paste various kinds of pictures and these actions integrate literature in visual culture in many ways that have never been tackled as a whole before. Some writers spent their life surrounded by pictures taken from magazines, creating an inspirational environment; yet others nurtured their imagination with touristic leaflets and visual advertisements; others created fictional characters based on collected portraits. What do writers do with pictures? How does literature stage the pictures handled? From very concrete and banal uses of pictures will emerge a new vision of literature as intermediality in action. This investigation applies the tool set of visual anthropology and visual studies to writers for a deeper understanding of visual ecosystems. Covering a large period, from the beginning of mass reproduction in the 1880s and the digital practices of today, HANDLING focuses on the French and French-speaking field and stands as a laboratory to refashion a broader model for relationships between image and text. Its main challenge is to get to the root of contemporary iconographic practices. HANDLING is unconventional because literary studies usually focus on the text: contrary to the norm, it sets the image at the very centre of the literary act. This approach might yield promising results for the visibility of literature in the future, especially in exhibitions. Making these practices visible will make literature itself more visible. As an internationally recognized specialist of text-image relationships with an in-depth knowledge of French/Belgian literature and photography, I will build a team and lead this 5-year ambitious project. Grounded in interdisciplinarity, it will show the significant and unexpected role of literature in material visual culture.

1 500 000 €

Start date: 2019-07-01, End date: 2024-06-30

Heart failure affects about 2% of the European population with an annual mortality rate of 10%. Cardiac Resynchronization Therapy (CRT) has been proven to reduce morbidity and mortality and has become a recommended treatment. Optimal lead placement for CRT not only requires exact anatomically mapped information on the mechanical activation sequence to be corrected but also tissue viability and performance maps. Unfortunately, to date, no imaging technique allows building such maps non-invasively in a single examination in CRT patients. In this project, a new ultrasound imaging approach is proposed that will not only allow mapping all of these characteristics in a single examination but that will actually do this in a single heart beat. Hereto, real-time segmentation of the left ventricle will be used to limit the data acquisition to the spatial regions that contain myocardium. In this way unnecessary spatial sampling can be avoided which combined with new beam forming strategies will allow imaging the entire left ventricle at frame rates above 1000Hz. This very high temporal resolution will be used to accurately measure the onset of local deformation of the left ventricle in order to construct a mechanical activation map. Subsequently, cardiac motion estimates will be used to track anatomical regions throughout the cardiac cycle in order to construct a temporally averaged backscatter intensity map. As scar tissue is known to be more reflective than normal myocardium, this should allow mapping of scar. Finally, the automatic segmentation process will allow to locally measure wall thickness and curvature from which the mechanical load distribution within the ventricle can be derived. This, combined with estimates of regional myocardial deformation will produce a map of myocardial performance. The proposed system will thus provide important new diagnostic and therapeutic information and will therefore allow better CRT planning for the individual heart failure patient.

1 602 401 €

Start date: 2012-02-01, End date: 2018-01-31

Over one million finite element analyses are preformed in engineering offices every day and finite elements come with the price of mesh generation. This proposal aims at creating two breakthroughs in the art of mesh generation that will be directly beneficial to the finite element community at large. The first challenge of HEXTREME is to take advantage of the massively multi-threaded nature of modern computers and to parallelize all the aspects of the mesh generation process at a fine grain level. Reducing the meshing time by more than one order of magnitude is an ambitious objective: if minutes can become seconds, then success in this research would definitively radically change the way in which engineers deal with mesh generation. This project then proposes an innovative approach to overcoming the major difficulty associated with mesh generation: it aims at providing a fast and reliable solution to the problem of conforming hexahedral mesh generation. Quadrilateral meshes in 2D and hexahedral meshes in 3D are usually considered to be superior to triangular/tetrahedral meshes. Even though direct tetrahedral meshing techniques have reached a level of robustness that allow us to treat general 3D domains, there may never exist a direct algorithm for building unstructured hex-meshes in general 3D domains. In HEXTREME, an indirect approach is envisaged that relies on recent developments in various domains of applied mathematics and computer science such as graph theory, combinatorial optimization or computational geometry. The methodology that is proposed for hex meshing is finally extended to the difficult problem of boundary layer meshing. Mesh generation is one important step of the engineering analysis process. Yet, a mesh is a tool and not an aim. A specific task of the project is dedicated to the interaction with research partners that are committed to beta-test the results of HEXTREME. All the results of HEXTREME will be provided as an open source in Gmsh.

2 244 238 €

Start date: 2016-10-01, End date: 2021-09-30

This project concerns the creative agency of religious minorities in the transformation of Central and Eastern Europe societies in the 20th century. It constitutes the first comparative research on the secret police archives in the region from the perspective of the history and anthropology of religion and offers a radical perspectival shift on the value and uses of the secret police archives away from questions of justice and truth to questions of creative agency and cultural patrimony. Interdisciplinary in nature it combines archival, anthropological and cultural studies approaches to provide a re-examination and re-contextualization of the holdings of secret police archives in three states; Romania, Moldova and Hungary. The secret police archives, in addition to containing millions of files on individuals monitored by the state, also constitute a hidden repository of confiscated religious art and publications of religious minorities that were persecuted in the 20th century under fascism and communism. The investigation of these materials will be complemented by ethnographic research and the impact of the research will be extended through a public exhibition of previously hidden materials. The project has three principal stages: 1) copy/retrieve and catalogue examples of this creative material from the archives; 2) engage in ethnographic research with the communities that produced this material in order to explore the meaning and power of these artistic creations at the time of their production and in the context of post-socialism; 3) curate and stage a touring exhibition that re-presents the narratives and experiences of religious groups through their own artistic creations in order to conduct research in real time on questions of religious pluralism and intolerance in contemporary society. Through these three steps, this project will shed fresh light on the role that minority religious groups played in challenging the hegemonic order and in extending pluralism.

990 087 €

Start date: 2016-09-01, End date: 2020-08-31

HIGHWAVE is an interdisciplinary project at the frontiers of coastal/ocean engineering, earth system science, statistics and fluid mechanics that will explore fundamental open questions in wave breaking. Why do waves break, how do they dissipate energy and why is this important? A central element of the work builds on recent international developments in the field of wave breaking and wave run-up led by the PI that have provided the first universal criterion for predicting the onset of breaking of water waves in uniform water depths from deep to intermediate. This work has also shown that the run-up of nonlinear waves impinging on a vertical wall can exceed up to 12 times the far-field amplitude of the incoming waves. These results have now opened up the possibility for more accurate operational wave models. They have practical and economic benefits in determining structural loads on ships and coastal/offshore infrastructure, evaluating seabed response to extreme waves, and optimizing operational strategies for maritime and marine renewable energy enterprises. This is a tremendous advance comparable to the introduction of wave prediction during World War II, and the PI aims to be at the forefront of this research effort to take research in wave breaking into fundamentally new directions. The objectives of the project are: (i) to develop an innovative approach to include accurate wave breaking physics into coupled sea state and ocean weather forecasting models; (ii) to obtain improved criteria for the design of ships and coastal/offshore infrastructure; (iii) to quantify erosion by powerful breaking waves, and (iv) to develop new concepts in wave measurement with improved characterization of wave breaking using real-time instrumentation. This highly interdisciplinary project will involve an ambitious and unconventional combination of computational simulation/theory, laboratory experiments, and field measurements of sea waves, closely informed by application needs.

2 499 946 €

Start date: 2019-09-01, End date: 2024-08-31

String theory provides with a consistent framework which combines quantum mechanics and gravity. Two grand challenges of fundamental physics - building realistic models of black holes and cosmologies - can be addressed in this framework thanks to novel holographic methods. Recent astrophysical evidence indicates that some black holes rotate extremely fast, as close as 98% to the extremality bound. No quantum gravity model for such black holes has been formulated so far. My first objective is building the first model in string theory of an extremal black hole. Taking on this challenge is made possible thanks to recent advances in a remarkable duality known as the gauge/gravity correspondence. If successful, this program will pave the way to a description of quantum gravity effects that have been conjectured to occur close to the horizon of very fast rotating black holes. Supernovae detection has established that our universe is starting a phase of accelerated expansion. This brings a pressing need to better understand still enigmatic features of de Sitter spacetime that models our universe at late times. My second objective is to derive new universal properties of the cosmological horizon of de Sitter spacetime using tools inspired from the gauge/gravity correspondence. These results will contribute to understand its remarkable entropy, which, according to the standard model of cosmology, bounds the entropy of our observable universe.

1 020 084 €

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

Mimesis is one of the most influential concepts in Western thought. Originally invoked to define humans as the “most imitative” creatures in classical antiquity, mimesis (imitation) has recently been at the centre of theoretical debates in the humanities, social sciences, and the neurosciences concerning the role of “mimicry,” “identification,” “contagion,” and “mirror neurons” in the formation of subjectivity. And yet, despite the growing confirmations that imitation is constitutive of human behaviour, mimesis still tends to be confined to the sphere of realistic representation. The HOM project combines approaches that are usually split in different areas of disciplinary specialization to provide a correction to this tendency. Conceived as a trilogy situated at the crossroads between literary criticism, cinema studies, and critical theory, HOM’s outcomes will result in two monographs and accompanying articles that explore the aesthetic, affective, and conceptual implications of the mimetic faculty. The first, radically reframes a major proponent of anti-mimetic aesthetics in modern literature, Oscar Wilde, by looking back to the classical foundations of theatrical mimesis that inform his corpus; the second considers the material effects of virtual simulation by looking ahead to new digital media via contemporary science-fiction films; and the third establishes an interdisciplinary dialogue between philosophical accounts of mimesis and recent discoveries in the neurosciences. Together, these new perspectives on homo mimeticus reconsider the aesthetic foundations of a major literary author, open up a new line of inquiry in film studies, and steer philosophical debates on mimesis in new interdisciplinary directions.

1 044 000 €

Start date: 2016-11-01, End date: 2021-10-31

The chemical, pharmaceutical, and materials industries rely heavily upon chemicals from oil and natural gas feed-stocks (saturated hydrocarbons) that require considerable functionalisation prior to use. Catalytic oxidative functionalisation (e.g. CH4 + [O] + cat. → CH3OH), using first row transition metal catalysts, is potentially a sustainable, cheap, and green route to these high-commodity chemicals. However, catalytic oxidation remains a great modern challenge because such hydrocarbons contain remarkably strong inert C–H bonds that can only be activated with potent catalysts. We will take a Nature-inspired approach to designing and preparing powerful oxidation catalysts: we will interrogate the active oxidant, a metal-oxo (M=O) species, to guide our catalyst design. Specifically, we will prepare unprecedented Late first-row transition Metal-Oxo complexes (LM=O’s, LM = Co, Ni, Cu) that will activate the strongest of C–H bonds (e.g. CH4). This will be accomplished using a family of novel low coordinate ligands that will support LM=O’s. Due to their expected potent reactivity we will prepare LM=O’s under unique oxidatively robust, low-temperature conditions to ensure their stabilisation. The poorly understood factors (thermodynamics, metal, d-electron count) that control the reactivity of M=O’s will be thoroughly investigated. Based on these investigations LM=O reactivity will be manipulated and optimised. We expect LM=O’s will be significantly more reactive than any early transition metal-oxo’s (EM=O’s), because they will display a greater thermodynamic driving force for C–H activation. It is thus expected that LM=O’s will be capable of the activation of the strongest of C–H bonds (i.e. CH4). Driven by the knowledge acquired from these investigations, we will design and prepare the next generation of molecular oxidation catalysts - a family of late first-row transition metal compounds capable of catalysing hydrocarbon functionalisation under ambient conditions.

1 499 865 €

Start date: 2016-03-01, End date: 2021-02-28