Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet Dietary biomarkers (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Justification of relationships between foods and health is significantly limited by lack of versatile and accurate analytical tools. Metabolomics has in a few years revealed many novel food intake biomarkers but only few of these markers have been validated and applied in clinical settings. The primary aim of the proposed work at Department of Nutrition, Exercise and Sports (NEXS) is to identify, validate and methodologically combine a large number of biomarkers, covering broadly common foods, beverages, and supplements to provide a robust and objective tool to assess recent dietary intakes. The dietary assessment tool will be thoroughly validated through application to fully dietary controlled studies and to studies where the current subjective instruments have been applied. My new objective tool will help compliance assessment in clinical trials, observational studies and in the care of patients with food-related disorders. This is timely because all current instruments are subjective and have major flaws when applied to e.g. causes of overweight and failing dietary interventions. The host institution has a strong background in metabolomics, biomarker development, human trials and studies of weight loss and is internationally highly recognized within the nutrition area. My proposal includes several innovative features for dietary assessment and analytics and through advanced training provides me ample skills acquisition such as advanced analytical method development, data analysis, statistics, networking, project management, etc. of major importance for my research career plans.

Mots clés : dietary biomarkers, compliance

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet KaIROS (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

KaIROS proposal focuses on earthquake disasters; its main purpose is to provide beyond-state-of-the-art approaches to reduce seismic risk worldwide. That is, keeping and increasing the opportunities for resilience and the sustainability of communities against earthquakes. The key to reducing seismic risk is decreasing the vulnerability of existing structures and providing new insights to improve the design of new structures. Thus, main specific goals and modules are inventory, assessment, strengthening and regulations. Each module embodies state-of-the-art knowledge and new advances to form a robust and efficient tool for risk assessment. Concerning inventory, a new comprehensive BTM will include the most relevant building types around the world. The assessment tool will be based on fully probabilistic Incremental dynamic analysis of realistic structural models subjected to realistic seismic actions, so that the simulation results approach real outcomes. Thus, an innovative outcome of KaIROS is that it will provide probabilistic damage curves for the enhanced BTM. Specific measures related to reinforcement and/or to protection devices will be analyzed within the Strengthening module. Concerning Regulations, the main contributions will be associated with specific recommendations for strengthening, retrofitting and designing buildings. In addition, simplified coefficients allowing considering the directionality and weakening effects in the expected physical damage will be developed. KaIROS is sensitive to the gender dimension of natural disasters and a special module will investigate this issue. An open access soft-ware that can be used to assess the expected damage at urban level by considering several structural typologies and to perform cost-benefit analyses of strengthening measures, amongst many other possibilities, will be created and promoted. Special attention will be devoted to dissemination so that policy-makers and stakeholders can benefit from KaIROS.

Mots clés : seismic damage assessment, strengthening, increasing resilience, increasing sustainability, gender dimension

Participants :
- Universitat Politècnica de Catalunya (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 170121.6 €
Projet MOTKA (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Karst covers approximately 20% of land on Earth, and most caves are in these regions. Temperature records of most caves in the vadose zone (above the phreatic level) have a limited variability through the year and its value is close to the mean annual temperature of the atmosphere above the cave. This thermal coupling is the result of the atmospheric thermal signal being transferred underground by conduction and its anomalies being attenuated and delayed with depth. However, during persistent climate changes, cave and external atmosphere temperatures are temporarily decoupled. The change in cave temperatures (and in the full vadose zone) has major implications for numerous disciplines: ecology of underground environments, conservation of cave art, endurance/formation of ice in alpine caves or in permafrost regions, geochemistry of groundwater and paleoclimate records of speleothems, and also climate change because of the radiation of ground heat to the atmosphere. Experimental studies in karst regions already confirmed that thermal conduction models reproduce the cave temperature of past decades. So, the MOTKA proposal aims to simulate the temperature of caves during long-term climate changes using thermal conduction models, as well as to study the consequences of those changes in one particular discipline: paleoclimate d18O records from speleothems. Our integrated view of ocean paleoclimate records and cave environments is pioneer and enables to simulate past cave temperature records. The MOTKA proposal will apply for the first time thermal models to long-term climate changes, including glacial cycles, millennial oscillations, the ongoing global warming and its projection into the future. The simulations of this research will add a temporal dimension to the complex dynamics in underground environments. As an applied example, MOTKA proposal will explore the impact of thermal decoupling in the paleoclimate interpretation of speleothem d18O records.

Mots clés : modelling, thermal conduction, caves, glacial cycle, global warming, speleothem records

Participants :
- Universidad de Salamanca (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160932.48 €
Projet CORLINK (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Keratoconus is an eye disorder in which the normally curved cornea, the clear window of the eye, progressively thins and begins to bulge into a cone-like shape, leading to significant visual impairment. Corneal cross-linking is the gold standard treatment for halting disease progression by using riboflavin activated by ultraviolet light (UVA) to introduce covalent chemical bonds (cross-links) into the cornea. To enhance permeability of riboflavin into the corneal stroma, epithelium removal is required and thus, patients with thin corneas are not eligible for this approach, as several complications have been reported, some temporary and some irreversible. There is, therefore, an urgent need to develop new innovative therapeutic approaches that ideally avoid deepithelialization and the use of radiation. Genipin, is a naturally occurring cross-linking agent that has been proposed to have a biomechanical effect comparable to that of the contemporary cross-linking approach, without the need for deepithelization, and importantly to exhibit anti-inflammatory properties. This research will investigate the potential application of Genipin for the treatment of keratoconus corneas and corneal inflammatory diseases. With the overarching aim to elucidate the efficacy and mechanism of action of Genipin in the cornea and to ascertain its anti-inflammatory activity on resident corneal cells called keratocytes, a combination of biomedical techniques and advanced 3D structural imaging modalities will be integrated, in a drive towards the establishment of a new therapeutic strategy for keratoconus and inflammatory diseases. The results of this study will elucidate the effect of Genipin on corneal keratocytes in vitro and in vivo and will provide the first ever direct measurement of the effect of Genipin on the corneal architecture in 3D, which will importantly serve to propose a new therapeutic approach for keratoconus, particularly advanced cases, and corneal inflammatory diseases.

Mots clés : cornea, corneal crosslinking, inflammation, genipin, keratocytes

Participants :
- Universidad Nacional de Colombia (Colombie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Cardiff University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 226413.0 €
Projet RCC_Evo (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Kidney cancer is among the 10 most frequently diagnosed cancers and its incidence is rising. Clear cell Renal Cell Cancer (ccRCC) is the most common subtype and is characterized by early 3p loss. The deleted region on chromosome 3p harbours a number of tumour suppressor genes namely VHL, PBRM1, SETD2 and BAP1, which are frequently mutated subsequent to 3p loss. TRACERx Renal is a multi-center, longitudinal cohort study, which studies tumour evolution and intratumoural heterogeneity through multi-region profiling of primary tumours. Interim findings have defined 7 evolutionary subtypes. I will model the predictability and repeatability of these evolutionary trajectories in patient-derived tumour organoids (PDO), in patient-derived xenografts (PDX), and in gene-edited human proximal tubule cells (HPTC). Preliminary evidence suggests that ccRCC genotypes are associated with specific TME conditions. I will develop PDO models in which I will co-culture tumour cells with tumour infiltrating leucocytes and cancer associated fibroblasts. I will refine the mutational ordering and clonal resolution in selected cases of the TRACERx Renal Study by micro-biopsy profiling. Predictability of evolutionary trajectories will then be addressed through repeated passaging of tumour PDOs followed by targeted panel sequencing. The function of metastatic driver events will be characterised in PDX. The repeatability of the evolutionary trajectories will be studied through experimental manipulation of the genotype sequence in HPTCs. Co-culture PDOs will be used to define response to immune checkpoint inhibition. The results will allow a personalized prediction of the clinical course of ccRCC and the response to immune checkpoint inhibition. I will identify mechanisms of tumour progression and the involvement of the TME. This will result in the identification of previously unknown targetable weaknesses in ccRCC.

Mots clés : tumour evolution, clear cell renal cell cancer, patient derived organoids, patient derived xenografts, crispr, cas9 mediated gene editing

Participants :
- The Francis Crick Institute (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 224933.76 €
Projet CARDIOTOX (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Kinase inhibitors (KIs) are a major class of highly effective anti-cancer drugs. Unfortunately, therapeutic use of KIs is often associated with cardiotoxicity (CT), a serious adverse condition which limits their use. This fellowship aims to develop mathematical systems pharmacology models for KI-induced CT. These models will be used to identify predictive CT signatures that will allow to decrease CT risk of new KIs. This innovative multi-disciplinary approach consists of integrating mathematical systems pharmacology modelling, with state-of-the-art experimental data generation. To this aim, KIs with different magnitudes of CT will be selected based on clinical adverse event databases. Human cardiomyocytes derived from pluripotent stem cells will then be treated with the selected KIs and in combination with CT modifying drugs. The effect of these treatments on changes on untargeted mRNA and protein expression will be measured and then analyzed using network modelling. This approach allows identification of key regulatory proteins. The selected proteins will then be quantified over time along with cardiomyocyte health markers. With this data, dynamical models will be developed to capture the relationship between exposure to KIs and the effects on protein expression and cardiomyocyte health over time. Ultimately these models will allow generation of predictive network-based dynamically-weighted signatures for CT. The fellow aims to establish himself as independent researcher in systems pharmacology. Training in state-of-the-art computational and experimental technologies at the leading systems pharmacology group at Mount Sinai in New York will fundamentally strengthen and broaden the experience of the fellow. This project will significantly contribute consolidate the career track of the fellow, foster future collaboration between Mount Sinai and Leiden University, and disseminate training in Europe.

Mots clés : cardiotoxicity, systems pharmacology, kinase inhibitors, systems biology, signatures, toxicity

Participants :
- Leiden University (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 242929.8 €
- Mount Sinai Health System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet CREATION (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Knee cartilage defects and consequent degeneration contribute to the development of osteoarthritis (OA). OA affects the mechanical integrity of the tissue, whose main function is to absorb shock and minimize peak loads in the underlying subchondral bone. Tissue engineering methods propose solutions to OA by implanting chondrocyte cell-enriched hydrogel/scaffold constructs within degenerative cartilage defects. By applying mechanical loads to stimulate the cells within the constructs, they initiate cartilage extracellular matrix (ECM) synthesis. The mechanical environment of the cell-seeded construct has a crucial role in defining the quality and quantity of the regenerated ECM. This will determine the mechanical performance of the cartilage tissue. Indeed, any repair method has to aim at restoring the unique cartilage mechanics, in particular, the energy absorption capacity. This project aims at restoring energy absorption of degenerative cartilage by optimizing regeneration in cell-enriched construct implants. The goal will be pursued by developing an in-silico framework for mechanobiological modelling of the regeneration and degeneration in the cartilage-implant compound during loading. Unique in the in-silico framework is the simultaneous modelling of regenerative and degenerative processes through adaptive modelling of the ECM. An innovative regeneration algorithm will be developed and integrated with a previously developed degeneration model. The adaptive model will then be used in an optimization scheme to minimize differences between energy absorption of construct implant and native human cartilage. An iterative performance evaluation is foreseen in comparison with biological experiments. In collaboration with the participating research groups and using my background, I will have a unique chance to take a step forward in furthering insights on OA disease process. The anticipated collaborations and training will contribute to making me a mature researcher.

Mots clés : articular cartilage, mechanobiological modelling, degeneration, regeneration, finite element analysis, adaptive modelling, construct implants, osteoarthritis joint, energy absorption, cartilage repair

Participants :
- KU Leuven (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178320.0 €
Projet LOSFARE (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

LOSFARE focuses on the practice of States in imposing navigational restrictions on foreign ships and aircraft in densely navigated maritime regions in the context of hybrid warfare and hybrid conflict. Foreign ships that were navigating through important chokepoints of maritime commerce have recently been repeatedly subjected to the use of force or coercion by the coastal State of the relevant strait, incl. the Kerch Strait incident in November 2018 and the Strait of Hormuz incidents in the summer of 2019. These incidents have been characterised as examples of hybrid warfare. Hybrid warfare/conflict poses new challenges for the rights of navigation in important maritime routes. LOSFARE seeks to determine how the law of the sea can contribute to ensuring the rule of law in major commercial shipping routes that are impacted by hybrid warfare/conflict. The objective of LOSFARE is to analyse the legitimacy of naval hybrid warfare/conflict by identifying the limitations under the law of the sea to the jurisdiction of States in imposing their political influence on other States. To reach this aim, LOSFARE scrutinises State practice and examines whether it has affected the state of the law. This project seeks to verify if State practice demonstrates the emergence of a new concept of hybrid naval warfare/conflict which should be distinguished from the traditional phenomena of naval warfare and law enforcement. LOSFARE also examines if the concept of hybrid warfare/conflict is useful for assessing the (il)legality of an aggressor’s actions in the maritime domain. As a result, LOSFARE will provide States and decision-makers the knowledge necessary to respond to the challenges posed by hybrid warfare/conflict. LOSFARE will address this need not only by publishing research articles and organising topical workshops, but also via the conclusion of a roadmap-brochure for the policy-makers on how to determine the applicable legal framework in naval hybrid conflict.

Mots clés : law of the sea, navigation, hybrid warfare, international humanitarian law, law enforcement, international security law, eu maritime security strategy, russian federation, united states, iran, nato

Participants :
- UiT The Arctic University of Norway (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214158.72 €
Projet LandFlux (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Landslides are a primary erosion process in steep landscapes and are among our most deadly and damaging geohazards. However, it is extremely difficult to constrain long-term or past rates of landslide activity, which prevents accurate predictions of their activity in the face of climate change. This project aims to develop and apply a new methodology to quantify long-term landslide activity and contribution to sediment fluxes. To achieve this goal, I will integrate two growing research lines that have identified signatures of landslide activity: grain-size distributions and cosmogenic radionuclide (CRN) concentrations, which I will integrate in a numerical model. We will exploit, for the first time to our knowledge, the differences in depth production profiles between CRNs (14C and 10Be), using the 14C/10Be ratio to infer erosional depth-provenance and track erosional processes. We will sample grain-size distributions, and 14C and 10Be concentrations across different grain sizes, in landslide deposits and river sediments within catchments with excellent published constraints on landslide activity in Italy and New Zealand. We will develop a new Matlab numerical model, which will be calibrated using our new data, to determine landslide rates and fluxes using CRN and grain-size data, hence creating a tool that can be used to predict long-term or past landslide activity in other areas where good constraints are not available. This project has the potential to expand the uses of CRNs to include erosional depth-provenance. Furthermore, being able to infer long-term and past landslide rates would be a major step forward in how we tackle landscape evolution and landslide hazards. This project will be developed at the GFZ Potsdam (host) and ETH Zurich (secondment), bringing together outstanding infrastructures and researchers, and offering the best possible environment for my training and networking, which will in turn enhance my future career opportunities.

Mots clés : landslides, cosmogenic radionuclides, grain size distributions, sediment flux, numerical modeling, erosion processes, landscape evolution

Participants :
- Helmholtz Centre Potsdam - GFZ German Research Centre for Geosciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €
Projet Modeling ERPs (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Language and meaning processing have been investigated with event-related brain potentials (ERPs), providing direct time-resolved measures of electrical brain activity, and with connectionist network models, providing mechanistic implementations of the assumed processes. However, there has been very little contact between these fields, even though a combination of both methods could be highly beneficial. Based on initial evidence from the applicant, the present project therefore aims to integrate ERPs and computational models in research on language and meaning. Specifically, the N400 ERP component is widely used in research on language and meaning. As the computational mechanisms underlying this component are still unclear, we recently related the N400 to a model of word meaning and observed a close correspondence between N400 amplitudes and semantic network error. As network error is often conceptualized as implicit prediction error, we took these results to indicate that N400 amplitudes may reflect implicit prediction error in the semantic system. However, because the most typical N400 effects are observed during sentence processing, I propose to extend connectionist N400 simulations to sentence processing (Objective 1). Furthermore, the development of syntactic and semantic knowledge in the model should be related to the development of syntactic and semantic ERP components, both in developmental time and when processing words in sentences over time (Objective 2). Next, we aim to test behavioral predictions derived from this model-based account of N400 amplitudes, namely that larger N400 amplitudes should enhance implicit memory formation (Objective 3). Finally, the model-based account of N400 amplitudes as reflecting implicit prediction error should be tested in a conceptually similar theoretical framework, namely the Bayesian brain hypothesis. Thus, we will model N400 amplitudes as Bayesian surprise in the semantic system (Objective 4).

Mots clés : semantic cognition, language, erps, connectionist modeling, bayesian surprise, n400, fmri

Participants :
- Freie Universität Berlin (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 159795.6 €
- Stanford University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €