AMERISKA: Analysis of Multivariate Extremes and RISKs Assessment. An international research network on food and environmental risks assessment. The project AMERISKA aims at encouraging interactions of people of different backgrounds and from different countries to assess risks of different kinds. In particular, the project focuses on the assessment of risks in the contexts of food, hydrology and climatology which are major issues of concern for society. • Food risks assessments: The use of chemical products and the degradation of the natural environment are responsible for the presence of contaminants in food usually accumulated by human body. The degree of toxicity of the products and the consequences for human health require better stochastic modeling of the accumulation process. • Environmental risks assessments: modeling accurately the spatio-temporal structures of some atmospheric extreme variables like heavy rainfall, storms, still remains a statistical challenge. This is due to the complex multivariate structure within and between rare events. Inferring in space and time will be at the core of this environmental applications. To assess the aforementioned risks, a careful use of statistics is required. One major difficulty is that extremal events are often not well modeled due to the lack of observations. It is a major challenge for applied mathematicians to understand heavy tail phenomena observed. In particular, it appears that the importance of the events requires a global point of view, involving many researchers form different disciplines. It seems possible to use more information on extremal events because of the emergence of bigger mass of data. A major problem is to deal with the interaction (dependence) of extremes which necessarily leads to a multivariate context. Suitable mathematical tools have been developed only recently: multivariate regular variation processes are suitable new concepts for dealing with extremes and dependence in space and time. The literature on stochastic models for spatio-temporal extremal phenomena is still rather sparse. Statistical inference on these phenomena has just started and convincing applications are still missing. It is necessary to bundle the working forces of various researchers to face the challenges. AMERISKA will be a project where applied mathematicians concerns on issues of extremal risks will met; they will discuss the problems mentioned and and collaborate on their solution. One of the goals is the organization of a semester on risks that could be partly funded by Labex MME-DII. The research will be coordinated and led by 4 principal investigators: Olivier Wintenberger, Patrice Bertail, Philippe Naveau and Thomas Mikosch. They will manage a team of 8 experts from different countries, 12 french professors with strong experiments, 9 young french researchers and 2 PhD students, all working in the domain of quantitative risk analysis.

Intensive agricultural practices in Europe and Canada have led to high levels of non-point source nutrient pollution, threatening drinking water quality and contributing to the destruction of aquatic ecosystems. Despite widespread implementation of a range of conservation measures to mitigate the impacts of fertilizer-intensive agriculture, nitrogen (N) and phosphorous (P) concentrations of inland waters are in many cases remaining steady or continuing to increase. This lack of response to conservation measures is increasingly attributed to the presence of legacy nutrient stores, which cause the long-term release of N and P, hence delaying the expected water quality benefits in receiving water bodies. However, our current knowledge regarding the magnitudes and spatial distributions of legacy nutrients across the landscape, as well as the time scales over which these legacies may contribute to elevated nutrient concentrations in surface and groundwater, remains woefully inadequate. The proposed LEAP project will move beyond a simple focus on nutrient concentrations and fluxes, and instead work towards the explicit quantification of the spatio-temporal dynamics of non-point source nutrient legacies within watersheds and the ongoing and future impacts on water quality. The quantitative understanding of nutrient legacies and the associated legacy-related time lags to achieving improvements in water quality at the project's study sites will allow us to develop an integrated analysis framework and innovative modelling tools to predict agricultural N and P loadings. Due to the strong impacts of nutrient legacies on the time scales for recovery in at-risk landscapes, integration of legacy dynamics into a hydro-economic modelling framework will enable a more accurate assessment of the outcomes of alternative management approaches in terms of both short- and long-term costs and benefits, and the evaluation of temporal uncertainties associated with different intervention strategies. In addition, our mapping of legacy nutrient stores and attention to spatial variations in legacy accumulation will inform the development of targeted, and thus more cost-effective, nutrient mitigation strategies. At a larger scale, our analysis of similarities and differences in agricultural trajectories, and thus differences in legacy nutrient dynamics, across Europe and North America will facilitate the exchange of ideas and perspectives and create new synergies with ongoing EU and Canadian water research and policy development.

Hepatitis C virus (HCV) is an important human pathogen that infects the liver and establishes chronic infection in the majority of cases, leading to cirrhosis and hepatocellular carcinoma over the course of many years. Despite recent progress, details of the HCV life cycle are still missing, with the HCV assembly process being particularly poorly understood. Lipid droplets (LDs) appear to play a central role in HCV assembly since all the viral proteins involved in morphogenesis as well as the viral genome replication accumulate in close proximity of this organelle. Moreover, the viral nonstructural (NS) proteins NS2, p7 and NS5A have emerged as central players in HCV assembly. However, the contribution of host cell factors to HCV morphogenesis remains poorly understood. The objective of this project is to characterize the contribution of the cell factory to HCV assembly and to determine the pathophysiological consequences of these virus-host interactions. To achieve this goal, we will use a dedicated phenotypic assay relying on the monitoring of NS5A-mediated recruitment to LDs by high content confocal imaging and apply it to the screening of a genome wide small synthetic interfering RNA (siRNA) library and a small lipidic compounds library. We will also use a proteomic strategy using NS2, p7 and NS5A as baits in pull-down experiments followed by interactors identification. The integration of the data from the genetic, chemical and proteomic screens will allow for the identification of key cellular pathways involved in HCV morphogenesis. Subsequently, in depth elucidation of the interactions of some of the host gene products from these pathways with HCV will be conducted, and we will determine whether these interactions are conserved across HCV genotypes and Flaviviridae. Finally, we will determine the potential in vivo relevance of these virus-host interactions on the progression of chronic hepatitis C by exploring the expression of host factors in infected patients. In conclusion, this project will shed light on a poorly understood step of the HCV life cycle and it will help to understand how this virus exploits cellular pathways for its propagation. Importantly, the variety of advanced techniques and the different approaches encourage us to anticipate the identification of cellular factors involved in lipid metabolism. Furthermore, the participation of clinical partners will also help us to determine the consequences of these virus-host interactions on the progression of the disease and the potential identification of biomarker molecules. Finally, another major outcome will be the validation of new host factors as drug targets for HCV and thus will lead to the establishment of novel target-based cellular assays immediately applicable to the screen of large compounds libraries that will be a benefit to the pharmaceutical efforts for the continuous search of first class novel candidate drugs.

The overall aim of the RETHINK project is to translate the concept of a knowledge-based society into a framework for agricultural and rural development. 15 major case studies will improve our understanding of the multiple mechanisms underlying rural prosperity and resilience. Each case is an expression of innovative development trajectories, highlighting potential synergies between farm modernization and sustainable rural development. The core theme of RETHINK has emerged from the combination of six of the research topics listed in the 1st ERA-NET RURAGRI call. RETHINK connects the 'development' of agriculture and the wider societal and policy goal of vibrant rural areas. It explicitly recognizes the complexity of challenges, the diversity in situations, and the multidimensionality of strategies forward. The project's aim was translated into core research questions, and these were used to select the 15 cases. The cases are diverse and have different boundaries. A joint analytical framework ensures the comparability of analyses and allows recommendations at European level. RETHINK combines an explorative perspective with an action-oriented policy and governance orientation: right from the start, decision-makers from the public and private sectors will be involved, shaping the implementation of the project. The comparative analysis and synthesis will focus on issues that are particularly relevant for decision-makers. Factors that enable and encourage the creation of synergies will be identified; the influence of contextual factors, the role of agency and of institutional structures will be explored. RETHINK is highly structured through a tight working schedule and well-defined deliverables. At the same time, it will be organised as an open research process connecting and integrating other work. RETHINK wants to facilitate an informed and productive interaction among industry, government, academic institutions, civil society organisations and farmers.