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  • 2021-2021
  • European Commission
  • OA Publications Mandate: Yes
  • 2016
  • 2022

10
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  • Funder: EC Project Code: 694122
    Overall Budget: 2,461,090 EURFunder Contribution: 2,461,090 EUR

    Light fields technology holds great promises in computational imaging. Light fields cameras capture light rays as they interact with physical objects in the scene. The recorded flow of rays (the light field) yields a rich description of the scene enabling advanced image creation capabilities from a single capture. This technology is expected to bring disruptive changes in computational imaging. However, the trajectory to a deployment of light fields remains cumbersome. Bottlenecks need to be alleviated before being able to fully exploit its potential. Barriers that CLIM addresses are the huge amount of high-dimensional (4D/5D) data produced by light fields, limitations of capturing devices, editing and image creation capabilities from compressed light fields. These barriers cannot be overcome by a simple application of methods which have made the success of digital imaging in past decades. The 4D/5D sampling of the geometric distribution of light rays striking the camera sensors imply radical changes in the signal processing chain compared to traditional imaging systems. The ambition of CLIM is to lay new algorithmic foundations for the 4D/5D light fields processing chain, going from representation, compression to rendering. Data processing becomes tougher as dimensionality increases, which is the case of light fields compared to 2D images. This leads to the first challenge of CLIM that is the development of methods for low dimensional embedding and sparse representations of 4D/5D light fields. The second challenge is to develop a coding/decoding architecture for light fields which will exploit their geometrical models while preserving the structures that are critical for advanced image creation capabilities. CLIM targets ground-breaking solutions which should open new horizons for a number of consumer and professional markets (photography, augmented reality, light field microscopy, medical imaging, particle image velocimetry).

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  • Funder: EC Project Code: 681630
    Overall Budget: 1,999,010 EURFunder Contribution: 1,999,010 EUR

    Homologous recombination plays a crucial role to repair DNA strand breaks that may occur spontaneously upon replication fork collapse, during the course of radio- or chemotherapy or in a programmed manner during meiosis. Understanding the molecular mechanisms of re-combinational repair is thus very important not only from a basic research viewpoint, but it is also highly relevant for human health. Here, we will define the function of nucleases in homol-ogous recombination. First, we will study the initial steps in this pathway. We could show previously that the S. cerevisiae Sae2 protein promotes the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex near protein blocked DNA ends. This initiates nucleolytic resection of DNA breaks and activates homologous recombination. Our biochemical setup will be instrumental to define how is the activity of Sae2 regulated by phosphorylation on a mech-anistic level and how physiological protein blocks direct the Mre11 endonuclease. We will ex-tend the study to the human system, and attempt to apply the gained knowledge to improve the efficiency of genome editing by activating recombination in conjunction with the CRISPR-Cas9 nuclease system. Second, we will study how homologous recombination promotes gen-eration of genetic diversity during sexual reproduction. DNA strand breaks are introduced in-tentionally during the prophase of the first meiotic division. They are then processed by the recombination machinery into Holliday junction intermediates. These joint molecules are preferentially converted into crossovers in meiosis, resulting in exchange of genetic infor-mation between the maternal and paternal DNA molecules. This is dependent on the Mlh1-Mlh3 nuclease through a yet unknown mechanism. We will study how Mlh1-Mlh3 in complex with other proteins guarantee crossover outcome to promote diversity of the progeny.

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  • Funder: EC Project Code: 692775
    Overall Budget: 2,497,980 EURFunder Contribution: 2,497,980 EUR

    The discovery of novel sustainable catalytic reactions is a major current goal. Based on recent discoveries in our group, we plan to develop unprecedented sustainable catalytic reactions with special emphasis on reactions catalyzed by complexes of earth-abundant metals. We have recently discovered an intriguing reaction, namely the oxidation of organic compounds using water, with no added oxidant, evolving H2. This simple, selective reaction, offers now a novel, conceptually new, environmentally benign approach in the field of oxidation of organic compounds, which we will explore. We recently discovered a new mode of activation of multiple bonds by metal-ligand cooperation, including activation of CO2 and nitrile triple bonds, in which reversible C-C bond formation with the ligand is involved. Based on that, activation of nitriles has resulted in unprecedented C-C bond formation involving addition of simple aliphatic nitriles to various α,β-unsaturated carbonyl compounds. This mode of multiple bond activation may open a new approach to catalysis, “template catalysis”, which we plan to explore. In addition, the highly desirable, catalytic activation of the kinetically very stable, potent greenhouse gas N2O for the (so far elusive), efficient oxygen transfer to organic compounds, will be pursued. The use of CO2 in organic synthesis is an important timely topic. Based on its activation by metal ligand cooperation, new catalytic reactions of CO2 will be pursued, including unprecedented carbonylation of non-activated C-H bonds. Most reactions catalysed by metal complexes involve noble metals. Development of sustainable catalysis based on complexes of earth-abundant metals is of great interest. In all topics described above, catalysis by complexes of such metals will be emphasized. Moreover, based on recent results in our group, we plan to develop an unprecedented family of complexes of earth-abundant metals, and pursue novel sustainable catalysis, based on it.

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  • Funder: EC Project Code: 723770
    Overall Budget: 15,270,000 EURFunder Contribution: 5,039,100 EUR

    Nanomedicine is the application of nanotechnology to medicine and healthcare. The field takes advantage of the physical, chemical and biological properties of materials at the nanometer scale to be used for a better understanding of the biological mechanisms of diseases at the molecular level, leading to new targets for earlier and more precise diagnostics and therapeutics. Nanomedicine, rated among the six most promising Key Enabling Technologies, is one of the most important emerging areas of health research expected to contribute to one of the strategic challenges that Europe has to face in the future: Provide effective and affordable health care and assure the wellbeing of an increasingly aged population. EuroNanoMed III (ENM III) builds on the foundations of ENM I & II, which launched 7 successful joint calls for proposals since 2009, funded 51 transnational research projects involving 269 partners from 25 countries/regions, and allocated € 45,5 million to research projects from ENM funding agencies. ENM III consortium, reinforced with 12 new partners from Europe, Canada and Taiwan, is committed to fostering the competiveness of European nanomedicine actors taking into account recent changes in the landscape and new stakeholders and challenges, as identified in the SRIA in nanomedicine. The first joint call for proposals will be co-funded by ENM III partners and the EC. After the co-funded call, three additional joint transnational calls will be organized and strategic activities will be accomplished in collaboration with key initiatives in the field. ENM III actions focus on translatability of project results to clinical and industry needs.

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  • Funder: EC Project Code: 694888
    Overall Budget: 2,212,050 EURFunder Contribution: 2,212,050 EUR

    The aim of this project is to develop the next generation of compressive and computational sensing and processing techniques. The ability to identify and exploit good signal representations is pivotal in many signal and data processing tasks. During the last decade sparse representations have provided stunning performance gains for applications such as: imaging coding, computer vision, super-resolution microscopy and most recently in MRI, achieving many-fold acceleration through compressed sensing (CS). However in most real world sensing it is generally not possible to fully adopt the random sampling strategies advocated by CS. Systems are often nonlinear, measurements have limited dynamic range, noise is rarely Gaussian and reconstruction is not always the final goal. Furthermore, iterative reconstruction techniques are often not adopted in commercial imaging systems as they typically incur at least an order of magnitude more computation than traditional techniques. Thus there is a real need for a new framework for generalized computationally accelerated sensing and processing techniques. The research proposed here will build on the PIs recent work in this area and will develop and analyse a much richer class of hierarchical low dimensional signal models, accommodating everything from physical laws to data-driven models such as deep neural networks. It will provide quantitative guidance for system design and address sensing tasks beyond reconstruction including detection, classification and statistical estimation. It will also exploit low dimensional structure to reduce computational cost as well as estimation accuracy, challenging the notion that exploiting prior information must come at a computational cost. This research will result in a new generation of data-driven, physics-aware and task-orientated sensing systems in application domains such as advanced radar, CT and MR imaging and emerging sensing modalities such as multispectral time-of-flight cameras.

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  • Funder: EC Project Code: 679175
    Overall Budget: 1,970,000 EURFunder Contribution: 1,970,000 EUR

    Understanding how the mammalian brain network acquires its ability during development to process information and interact with the environment is one of the fundamental challenges in modern biology. The brain originates from a sheet of neural progenitors during embryogenesis but rapidly develops into distinct functional areas such as primary sensory and the highly associative cortices. Although all cortical areas consist of the same main neuronal elements, excitatory and inhibitory cells, their functions are markedly distinct. Unlike others, primary sensory cortical regions receive direct inputs from the environment through the respective thalamic nuclei starting at an early stage in development and are therefore likely to be shaped by incoming activity from sensory modalities. Despite the plethora of data on the arealization of the cortex by early signaling centers and the critical period plasticity mechanisms which take place after the basic elements of the circuit have been laid out, very little is known about the important period in between and how individual elements bind together to construct a functional circuit. This proposal is aimed at bridging this gap in knowledge, by addressing the long-standing question of how genes and activity interact during development to establish the correct wiring of excitatory and inhibitory cells in cortical sensory areas. As the primary role of inhibitory cells is to shape the flow of information transfer in the brain, they are well positioned to contribute significantly to the distinct modes of information processing performed in different cortical areas. Considering that dysfunction of cortical inhibitory circuits has been proposed as a major contributor to the etiology of neuropsychiatric-neurodevelopmental disorders, it is my hope that this approach will not only provide insights into the making of the healthy brain, but also into clinically relevant pathologies.

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  • Funder: EC Project Code: 717194
    Overall Budget: 3,321,160 EURFunder Contribution: 1,750,000 EUR

    AMATHO (A.dditive MA.nufacturing T.iltrotor HO.using) is aimed to design, assess and manufacture a novel tiltrotor drive system housing exploiting the features of additive manufacturing techniques. Preliminarily, functional, structural and technological peculiarities of rotorcraft main gearbox housings are analysed and relevant requirements are issued. In the meantime, viable AM processes are reviewed, on the basis of specific suitability, technological potential and degree of maturity. In particular, powder feed direct energy deposition techniques (Direct Laser Deposition - DLD) and powder bed fusion techniques (Selective Laser Melting - SLM and Electron Beam Meelting - EBM) are considered. The powder precursors are investigated as well, in terms of chemical nature (magnesium, aluminium, titanium alloy, stainless steel), particles granulometry and morphology. Static, fatigue, fracture mechanics, damage tolerance, corrosion endurance, chemical compatibility, machinability, weldability and heat-treatability testing are worked out and final trade-off process accomplished for choosing optimal materials and processes. Characterisation methodologies and NDI techniques are assessed as well. In addition to test activity on dedicated specimens, smaller, but fully representative, full-scale gearbox housing components (to be considered as proof of concept) are manufactured through the traded-off technologies and tested to check the compliance with general functional aspects of r/c drive system housing. In parallel, design rules and methodologies for detail design, optimisation and structural substantiation of AM components are defined and supporting numerical tools are set-up. Full-scale housing is manufactured and structural and functional tests are performed to support flight clearance on the NextGenCTR Demonstrator and procedures (engineering cost and industrial capability assessment) for the start-up of high-volume production are defined

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  • Funder: EC Project Code: 694307
    Overall Budget: 2,383,620 EURFunder Contribution: 2,383,620 EUR

    The endo-lysosomal system is critical to diverse processes, including protein homeostasis, signaling and antigen presentation. The vesicular compartment is organized as a collective unit wherein the bulk of endosomes derived from disparate origins resides in a cloud in the perinuclear region and extends outwards to include quickly moving vesicles in the periphery. At this busy intersection between the endocytic and biosynthetic pathways, lies the late endosomal compartment, responsible for protein degradation and antigen processing. In dendritic and other immune cells, this major constituent of the perinuclear cloud serves as a hub for MHC class II antigen loading. Previous work by us and others has elucidated key elements of MHC class II biology through the study of late endosomal transport to and from the cell periphery. It is clear that cell biology of endosomes is modulated by their proximity to other membrane compartments during transport, maturation, cargo selection and delivery and even during cytokinesis in cell division. However, how endosomal positioning in the perinuclear cloud and how their release for further transport is controlled remains largely unknown. The aim of this proposal is to define the molecular basis for endosomal positioning and then to interrogate the relationship between spatial regulation of the endocytic compartment and its functions with respect to i) MHC class II antigen presentation, ii) bacterial infection and iii) mitotic resolution. From a genome-wide siRNA screen for factors influencing MHC class II biology, we have identified a unique and previously uncharacterized ubiquitin ligase that resides in the ER membrane, from where it controls endosomal positioning and times their arrivals and departures as a function of its catalytic activity. On this basis, the work proposed herein is poised to resolve an entirely new molecular network in control of endosomal biology with implications for diverse biological processes.

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    downloaddownloads15
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  • Funder: EC Project Code: 677289
    Overall Budget: 1,493,780 EURFunder Contribution: 1,493,780 EUR

    Cancers are the leading cause of death in the developed world, with populations facing a 30% chance of developing the disease by the age of 75. As part of a concerted effort to open up new treatments and improve patients’ experiences with existing ones, the concept of drug delivery – using non-toxic carriers to transport medicines directly to the location of disease – has emerged. Metal-organic frameworks (MOFs), porous materials comprised of organic linkers and metal joints, show considerable promise as drug delivery vectors due to their high storage capacities, amenability to functionalization and the ability to prepare entirely non-toxic nanoparticulate derivatives. This proposal will use the PI’s expertise in advanced MOF synthetic methods to facilitate dramatic technological breakthroughs through unprecedented control of MOF self-assembly and surface chemistry. Management of MOF surface chemistry will allow installation of stimuli responsive release mechanisms and offer control over the trapping and release of cargo within MOFs, ensuring drugs are released only at the site of disease in the body. Surface incorporation of sophisticated biotargeting units such as peptides and aptamers will facilitate selective uptake of the MOFs by diseased tissues only. Rapid clean microwave syntheses will allow metal radionuclides to be incorporated for PET imaging, offering a novel alternative to traditional chelates. Comprehensive in vitro and in vivo testing will ensure that this multidisciplinary streamlining of materials, supramolecular and medicinal chemistries with the biosciences will generate highly efficient theranostic devices, offering more efficient, targeted drug delivery to improve treatment efficiency, mitigate side effects and open up new therapeutic avenues such as siRNA delivery. The fundamental advances required to generate these novel materials will also impact across the many applications of MOFs, from molecular storage and separations to catalysis.

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  • Funder: EC Project Code: 714693
    Overall Budget: 1,295,060 EURFunder Contribution: 1,295,060 EUR

    In the last several decades, it has been extensively studied how strategic behavior of economic agents could affect the outcomes of various institutions. Game theory and mechanism design theory play key roles in understanding economic agents' possible behavior in those institutions, its welfare consequences, and how we should design economic institutions to achieve desired social objectives even if the agents behave strategically for their own interests. However, existing studies mostly focus on somewhat narrow classes of economic environments by imposing restrictive assumptions. The proposed projects aim at providing novel theoretical frameworks which enable us to study agents' behavior and desirable institutions under much less assumptions. I believe that the projects have significant relevance in policy recommendation in practice and empirical studies, even though the proposed projects are primarily theoretical. In mechanism design, most papers in the literature focus on environments with independently distributed private information. We propose two novel (robustness-based) approaches to analyze mechanism design in correlated environments, motivated by their practical and empirical relevance. The robustness brought by my approach can be useful to mitigate certain types of misspecifications in mechanism design in practice. Moreover, the desirable robust mechanisms I obtain appear to be more sensible, and hence, can be useful for empirical studies of auction and other mechanism design problems. In game theory, it is often assumed that the game to be played is common knowledge, or even with uncertainty, uncertain variables are assumed to follow a common-knowledge prior .However, in many situations in reality, those do not seem to be satisfied. Our goal is to provide a novel theoretical framework to predict players' behavior in such incompletely specified games, and to identify conditions for (monotone) comparative statics. Both could be useful in empirical studies.

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500 Projects
  • Funder: EC Project Code: 694122
    Overall Budget: 2,461,090 EURFunder Contribution: 2,461,090 EUR

    Light fields technology holds great promises in computational imaging. Light fields cameras capture light rays as they interact with physical objects in the scene. The recorded flow of rays (the light field) yields a rich description of the scene enabling advanced image creation capabilities from a single capture. This technology is expected to bring disruptive changes in computational imaging. However, the trajectory to a deployment of light fields remains cumbersome. Bottlenecks need to be alleviated before being able to fully exploit its potential. Barriers that CLIM addresses are the huge amount of high-dimensional (4D/5D) data produced by light fields, limitations of capturing devices, editing and image creation capabilities from compressed light fields. These barriers cannot be overcome by a simple application of methods which have made the success of digital imaging in past decades. The 4D/5D sampling of the geometric distribution of light rays striking the camera sensors imply radical changes in the signal processing chain compared to traditional imaging systems. The ambition of CLIM is to lay new algorithmic foundations for the 4D/5D light fields processing chain, going from representation, compression to rendering. Data processing becomes tougher as dimensionality increases, which is the case of light fields compared to 2D images. This leads to the first challenge of CLIM that is the development of methods for low dimensional embedding and sparse representations of 4D/5D light fields. The second challenge is to develop a coding/decoding architecture for light fields which will exploit their geometrical models while preserving the structures that are critical for advanced image creation capabilities. CLIM targets ground-breaking solutions which should open new horizons for a number of consumer and professional markets (photography, augmented reality, light field microscopy, medical imaging, particle image velocimetry).

    more_vert
  • Funder: EC Project Code: 681630
    Overall Budget: 1,999,010 EURFunder Contribution: 1,999,010 EUR

    Homologous recombination plays a crucial role to repair DNA strand breaks that may occur spontaneously upon replication fork collapse, during the course of radio- or chemotherapy or in a programmed manner during meiosis. Understanding the molecular mechanisms of re-combinational repair is thus very important not only from a basic research viewpoint, but it is also highly relevant for human health. Here, we will define the function of nucleases in homol-ogous recombination. First, we will study the initial steps in this pathway. We could show previously that the S. cerevisiae Sae2 protein promotes the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex near protein blocked DNA ends. This initiates nucleolytic resection of DNA breaks and activates homologous recombination. Our biochemical setup will be instrumental to define how is the activity of Sae2 regulated by phosphorylation on a mech-anistic level and how physiological protein blocks direct the Mre11 endonuclease. We will ex-tend the study to the human system, and attempt to apply the gained knowledge to improve the efficiency of genome editing by activating recombination in conjunction with the CRISPR-Cas9 nuclease system. Second, we will study how homologous recombination promotes gen-eration of genetic diversity during sexual reproduction. DNA strand breaks are introduced in-tentionally during the prophase of the first meiotic division. They are then processed by the recombination machinery into Holliday junction intermediates. These joint molecules are preferentially converted into crossovers in meiosis, resulting in exchange of genetic infor-mation between the maternal and paternal DNA molecules. This is dependent on the Mlh1-Mlh3 nuclease through a yet unknown mechanism. We will study how Mlh1-Mlh3 in complex with other proteins guarantee crossover outcome to promote diversity of the progeny.

    visibility83
    visibilityviews83
    downloaddownloads31
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  • Funder: EC Project Code: 692775
    Overall Budget: 2,497,980 EURFunder Contribution: 2,497,980 EUR

    The discovery of novel sustainable catalytic reactions is a major current goal. Based on recent discoveries in our group, we plan to develop unprecedented sustainable catalytic reactions with special emphasis on reactions catalyzed by complexes of earth-abundant metals. We have recently discovered an intriguing reaction, namely the oxidation of organic compounds using water, with no added oxidant, evolving H2. This simple, selective reaction, offers now a novel, conceptually new, environmentally benign approach in the field of oxidation of organic compounds, which we will explore. We recently discovered a new mode of activation of multiple bonds by metal-ligand cooperation, including activation of CO2 and nitrile triple bonds, in which reversible C-C bond formation with the ligand is involved. Based on that, activation of nitriles has resulted in unprecedented C-C bond formation involving addition of simple aliphatic nitriles to various α,β-unsaturated carbonyl compounds. This mode of multiple bond activation may open a new approach to catalysis, “template catalysis”, which we plan to explore. In addition, the highly desirable, catalytic activation of the kinetically very stable, potent greenhouse gas N2O for the (so far elusive), efficient oxygen transfer to organic compounds, will be pursued. The use of CO2 in organic synthesis is an important timely topic. Based on its activation by metal ligand cooperation, new catalytic reactions of CO2 will be pursued, including unprecedented carbonylation of non-activated C-H bonds. Most reactions catalysed by metal complexes involve noble metals. Development of sustainable catalysis based on complexes of earth-abundant metals is of great interest. In all topics described above, catalysis by complexes of such metals will be emphasized. Moreover, based on recent results in our group, we plan to develop an unprecedented family of complexes of earth-abundant metals, and pursue novel sustainable catalysis, based on it.

    visibility19
    visibilityviews19
    downloaddownloads86
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    more_vert
  • Funder: EC Project Code: 723770
    Overall Budget: 15,270,000 EURFunder Contribution: 5,039,100 EUR

    Nanomedicine is the application of nanotechnology to medicine and healthcare. The field takes advantage of the physical, chemical and biological properties of materials at the nanometer scale to be used for a better understanding of the biological mechanisms of diseases at the molecular level, leading to new targets for earlier and more precise diagnostics and therapeutics. Nanomedicine, rated among the six most promising Key Enabling Technologies, is one of the most important emerging areas of health research expected to contribute to one of the strategic challenges that Europe has to face in the future: Provide effective and affordable health care and assure the wellbeing of an increasingly aged population. EuroNanoMed III (ENM III) builds on the foundations of ENM I & II, which launched 7 successful joint calls for proposals since 2009, funded 51 transnational research projects involving 269 partners from 25 countries/regions, and allocated € 45,5 million to research projects from ENM funding agencies. ENM III consortium, reinforced with 12 new partners from Europe, Canada and Taiwan, is committed to fostering the competiveness of European nanomedicine actors taking into account recent changes in the landscape and new stakeholders and challenges, as identified in the SRIA in nanomedicine. The first joint call for proposals will be co-funded by ENM III partners and the EC. After the co-funded call, three additional joint transnational calls will be organized and strategic activities will be accomplished in collaboration with key initiatives in the field. ENM III actions focus on translatability of project results to clinical and industry needs.

    visibility182
    visibilityviews182
    downloaddownloads133
    Powered by Usage counts
    more_vert
  • Funder: EC Project Code: 694888
    Overall Budget: 2,212,050 EURFunder Contribution: 2,212,050 EUR

    The aim of this project is to develop the next generation of compressive and computational sensing and processing techniques. The ability to identify and exploit good signal representations is pivotal in many signal and data processing tasks. During the last decade sparse representations have provided stunning performance gains for applications such as: imaging coding, computer vision, super-resolution microscopy and most recently in MRI, achieving many-fold acceleration through compressed sensing (CS). However in most real world sensing it is generally not possible to fully adopt the random sampling strategies advocated by CS. Systems are often nonlinear, measurements have limited dynamic range, noise is rarely Gaussian and reconstruction is not always the final goal. Furthermore, iterative reconstruction techniques are often not adopted in commercial imaging systems as they typically incur at least an order of magnitude more computation than traditional techniques. Thus there is a real need for a new framework for generalized computationally accelerated sensing and processing techniques. The research proposed here will build on the PIs recent work in this area and will develop and analyse a much richer class of hierarchical low dimensional signal models, accommodating everything from physical laws to data-driven models such as deep neural networks. It will provide quantitative guidance for system design and address sensing tasks beyond reconstruction including detection, classification and statistical estimation. It will also exploit low dimensional structure to reduce computational cost as well as estimation accuracy, challenging the notion that exploiting prior information must come at a computational cost. This research will result in a new generation of data-driven, physics-aware and task-orientated sensing systems in application domains such as advanced radar, CT and MR imaging and emerging sensing modalities such as multispectral time-of-flight cameras.

    more_vert
  • Funder: EC Project Code: 679175
    Overall Budget: 1,970,000 EURFunder Contribution: 1,970,000 EUR

    Understanding how the mammalian brain network acquires its ability during development to process information and interact with the environment is one of the fundamental challenges in modern biology. The brain originates from a sheet of neural progenitors during embryogenesis but rapidly develops into distinct functional areas such as primary sensory and the highly associative cortices. Although all cortical areas consist of the same main neuronal elements, excitatory and inhibitory cells, their functions are markedly distinct. Unlike others, primary sensory cortical regions receive direct inputs from the environment through the respective thalamic nuclei starting at an early stage in development and are therefore likely to be shaped by incoming activity from sensory modalities. Despite the plethora of data on the arealization of the cortex by early signaling centers and the critical period plasticity mechanisms which take place after the basic elements of the circuit have been laid out, very little is known about the important period in between and how individual elements bind together to construct a functional circuit. This proposal is aimed at bridging this gap in knowledge, by addressing the long-standing question of how genes and activity interact during development to establish the correct wiring of excitatory and inhibitory cells in cortical sensory areas. As the primary role of inhibitory cells is to shape the flow of information transfer in the brain, they are well positioned to contribute significantly to the distinct modes of information processing performed in different cortical areas. Considering that dysfunction of cortical inhibitory circuits has been proposed as a major contributor to the etiology of neuropsychiatric-neurodevelopmental disorders, it is my hope that this approach will not only provide insights into the making of the healthy brain, but also into clinically relevant pathologies.

    visibility115
    visibilityviews115
    downloaddownloads126
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    more_vert
  • Funder: EC Project Code: 717194
    Overall Budget: 3,321,160 EURFunder Contribution: 1,750,000 EUR

    AMATHO (A.dditive MA.nufacturing T.iltrotor HO.using) is aimed to design, assess and manufacture a novel tiltrotor drive system housing exploiting the features of additive manufacturing techniques. Preliminarily, functional, structural and technological peculiarities of rotorcraft main gearbox housings are analysed and relevant requirements are issued. In the meantime, viable AM processes are reviewed, on the basis of specific suitability, technological potential and degree of maturity. In particular, powder feed direct energy deposition techniques (Direct Laser Deposition - DLD) and powder bed fusion techniques (Selective Laser Melting - SLM and Electron Beam Meelting - EBM) are considered. The powder precursors are investigated as well, in terms of chemical nature (magnesium, aluminium, titanium alloy, stainless steel), particles granulometry and morphology. Static, fatigue, fracture mechanics, damage tolerance, corrosion endurance, chemical compatibility, machinability, weldability and heat-treatability testing are worked out and final trade-off process accomplished for choosing optimal materials and processes. Characterisation methodologies and NDI techniques are assessed as well. In addition to test activity on dedicated specimens, smaller, but fully representative, full-scale gearbox housing components (to be considered as proof of concept) are manufactured through the traded-off technologies and tested to check the compliance with general functional aspects of r/c drive system housing. In parallel, design rules and methodologies for detail design, optimisation and structural substantiation of AM components are defined and supporting numerical tools are set-up. Full-scale housing is manufactured and structural and functional tests are performed to support flight clearance on the NextGenCTR Demonstrator and procedures (engineering cost and industrial capability assessment) for the start-up of high-volume production are defined

    visibility108
    visibilityviews108
    downloaddownloads94
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    more_vert
  • Funder: EC Project Code: 694307
    Overall Budget: 2,383,620 EURFunder Contribution: 2,383,620 EUR

    The endo-lysosomal system is critical to diverse processes, including protein homeostasis, signaling and antigen presentation. The vesicular compartment is organized as a collective unit wherein the bulk of endosomes derived from disparate origins resides in a cloud in the perinuclear region and extends outwards to include quickly moving vesicles in the periphery. At this busy intersection between the endocytic and biosynthetic pathways, lies the late endosomal compartment, responsible for protein degradation and antigen processing. In dendritic and other immune cells, this major constituent of the perinuclear cloud serves as a hub for MHC class II antigen loading. Previous work by us and others has elucidated key elements of MHC class II biology through the study of late endosomal transport to and from the cell periphery. It is clear that cell biology of endosomes is modulated by their proximity to other membrane compartments during transport, maturation, cargo selection and delivery and even during cytokinesis in cell division. However, how endosomal positioning in the perinuclear cloud and how their release for further transport is controlled remains largely unknown. The aim of this proposal is to define the molecular basis for endosomal positioning and then to interrogate the relationship between spatial regulation of the endocytic compartment and its functions with respect to i) MHC class II antigen presentation, ii) bacterial infection and iii) mitotic resolution. From a genome-wide siRNA screen for factors influencing MHC class II biology, we have identified a unique and previously uncharacterized ubiquitin ligase that resides in the ER membrane, from where it controls endosomal positioning and times their arrivals and departures as a function of its catalytic activity. On this basis, the work proposed herein is poised to resolve an entirely new molecular network in control of endosomal biology with implications for diverse biological processes.

    visibility14
    visibilityviews14
    downloaddownloads15
    Powered by Usage counts
    more_vert
  • Funder: EC Project Code: 677289
    Overall Budget: 1,493,780 EURFunder Contribution: 1,493,780 EUR

    Cancers are the leading cause of death in the developed world, with populations facing a 30% chance of developing the disease by the age of 75. As part of a concerted effort to open up new treatments and improve patients’ experiences with existing ones, the concept of drug delivery – using non-toxic carriers to transport medicines directly to the location of disease – has emerged. Metal-organic frameworks (MOFs), porous materials comprised of organic linkers and metal joints, show considerable promise as drug delivery vectors due to their high storage capacities, amenability to functionalization and the ability to prepare entirely non-toxic nanoparticulate derivatives. This proposal will use the PI’s expertise in advanced MOF synthetic methods to facilitate dramatic technological breakthroughs through unprecedented control of MOF self-assembly and surface chemistry. Management of MOF surface chemistry will allow installation of stimuli responsive release mechanisms and offer control over the trapping and release of cargo within MOFs, ensuring drugs are released only at the site of disease in the body. Surface incorporation of sophisticated biotargeting units such as peptides and aptamers will facilitate selective uptake of the MOFs by diseased tissues only. Rapid clean microwave syntheses will allow metal radionuclides to be incorporated for PET imaging, offering a novel alternative to traditional chelates. Comprehensive in vitro and in vivo testing will ensure that this multidisciplinary streamlining of materials, supramolecular and medicinal chemistries with the biosciences will generate highly efficient theranostic devices, offering more efficient, targeted drug delivery to improve treatment efficiency, mitigate side effects and open up new therapeutic avenues such as siRNA delivery. The fundamental advances required to generate these novel materials will also impact across the many applications of MOFs, from molecular storage and separations to catalysis.

    visibility197
    visibilityviews197
    downloaddownloads1,318
    Powered by Usage counts
    more_vert
  • Funder: EC Project Code: 714693
    Overall Budget: 1,295,060 EURFunder Contribution: 1,295,060 EUR

    In the last several decades, it has been extensively studied how strategic behavior of economic agents could affect the outcomes of various institutions. Game theory and mechanism design theory play key roles in understanding economic agents' possible behavior in those institutions, its welfare consequences, and how we should design economic institutions to achieve desired social objectives even if the agents behave strategically for their own interests. However, existing studies mostly focus on somewhat narrow classes of economic environments by imposing restrictive assumptions. The proposed projects aim at providing novel theoretical frameworks which enable us to study agents' behavior and desirable institutions under much less assumptions. I believe that the projects have significant relevance in policy recommendation in practice and empirical studies, even though the proposed projects are primarily theoretical. In mechanism design, most papers in the literature focus on environments with independently distributed private information. We propose two novel (robustness-based) approaches to analyze mechanism design in correlated environments, motivated by their practical and empirical relevance. The robustness brought by my approach can be useful to mitigate certain types of misspecifications in mechanism design in practice. Moreover, the desirable robust mechanisms I obtain appear to be more sensible, and hence, can be useful for empirical studies of auction and other mechanism design problems. In game theory, it is often assumed that the game to be played is common knowledge, or even with uncertainty, uncertain variables are assumed to follow a common-knowledge prior .However, in many situations in reality, those do not seem to be satisfied. Our goal is to provide a novel theoretical framework to predict players' behavior in such incompletely specified games, and to identify conditions for (monotone) comparative statics. Both could be useful in empirical studies.

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