Differences in how patients experience disease can be explained in great part by their genomic differences. Enabling precision medicine, that is to say, being able to tailor treatment to the personal characteristics of patients, hence requires identifying genomic features associated with disease risk, prognosis or response to treatment. This is often achieved using genome-wide association studies (GWAS), which look for associations between single nucleotide polymorphisms (SNPs) and a phenotype. However, for many complex traits, the SNPs these studies uncover account for little of the known heritable variation. One key explanation for this missing heritability is that few of the established approaches for GWAS account for the joint epistatic effect of multiple SNPs, although several SNPs might act together towards a phenotype, for example by regulating multiple redundant parts of a same pathway. Moreover, GWAS are statistically underpowered, as the number of SNPs investigated is orders of magnitude larger than the sample sizes: only SNPs with a large effect size can be detected. This additionally results in a robustness issue, particularly when using complex models: which SNPs are deemed associated with the phenotype can vary a lot across related datasets. This suggests that current approaches often capture spurious associations rather than truly relevant SNPs. SCAPHE is built on the hypothesis that part of the missing heritability can be discovered by combining GWAS data with established biological knowledge. We surmise that this calls for novel machine learning procedures, which successfully model non-linear interactions between genetic loci and compensate for the lack of statistical power due to relatively small sample sizes by incorporating multiple sources of evidence. More specifically, these include molecular networks and data collected for multiple related phenotypes. SCAPHE propose to develop novel machine learning algorithms for GWAS, cast as a feature selection problem, through three orthogonal research directions: (1) the development of methods for non-additive, multi-locus, network-guided GWAS; (2) the development of biomarker discovery algorithms explicitly designed for robustness, that is to say, to reliably return the same SNPs on overlapping subsets of the same data; and (3) the joint analysis of multiple related phenotypes. These three research directions will be complemented by three transversal tasks, ensuring a focus throughout the project on the control of false discovery rate, high-performance computing, and applicative aspects. To achieve its objectives, SCAPHE will build on a machine learning framework called regularized relevance. This framework formalizes the idea of encouraging the selected loci to be connected on a pre-defined biological network, supposing that SNPs along pathways or in a set of co-expressed genes are more likely to act together towards the phenotype of interest. It also allows for the combination of evidence from multiple data sets pertaining to related phenotypes, and the inclusion of nonlinear interactions between SNPs. SCAPHE will propose new tools that will benefit human geneticists and clinicians by providing novel precision medicine insights, potentially resulting in new diagnostic tools or therapeutic targets. Moreover, the application of feature selection methods for high-dimensional data, far from being restricted to genomic studies, is of broad interest in a variety of domains ranging from medical imaging to quantitative finance and climate science. To facilitate the dissemination of our work, the results of SCAPHE will be published in Open Access peer-reviewed publications, and we will put a strong emphasis both on Open Source code development and on facilitating usability via tutorials and user-friendly interfaces.

This project will contribute to the development of international and comparative forms of media research. It is located at the intersection of two domains: first the history and sociology of representations of the television audience, second cultural globalization. The aim of the project is to explain the construction and the current changes of quantitative audience indices, among other forms of representations of the audience used by television organizations in four countries. It focuses on this form of representation of the audience as it seems to have become the dominant one in all broadcasting systems, private as well as public. It circulates way beyond the world of television, it is published by all other major media and it permeates the public debate. The proposed research will analyze its arrival in different national contexts, in relation with the previous forms of audience representation, but also its confrontation with the need to measure more volatile forms of media consumptions due to audience fragmentation and new technologies. To appreciate the global dimension of this phenomenon, the project will use a common theoretical background to study countries with significant differences and historical variations. It will start from Europe, in three countries: France, whose system was once dominated by a major public service organization, but which was early affected by commercial characteristics (advertising, internal competition); the UK, long the model of highly regulated (albeit competitive), quality television, where deregulation has been most gradual, Italy, to the contrary, where monopolistic RAI has been taken into the storm of competitive deregulation by the emergence of pirate stations and the building of Berlusconi's empire. It will also exploit work done in the USA, where the use of ratings has been most developed. It will also look in Latin America, where commercial television and ratings have developed early but in a very different cultural context: first at Brazil, the giant of Latin-American television, where audience measurements have developed sophisticated methods, second at Argentina, where commercial television is more fragile and its evaluation done according to Brazilian techniques. It will add more countries for shorts comparisons, starting with the recently deregulated and very Americanized (but much smaller) Israel.. An international team of researchers will conduct the project, including the fieldwork. Two senior researchers at the CSI willl coordinate the project and deal with the French case. Four research fellows in Great-Britain, Italy and Argentine, will be integrated to the team and do the fieldwork. The comparative investigation will deal with three points: 1. The emergence of quantitative, audimeters-based, audience measurement in the 1980s and the 1990s. 2. The moments of crises when the measurement system is questioned and reelaborated by the actors who initially agreed on it, professional of public and private channels, advertisers and agencies, but also by actors of the public world, political or economical and even to a wider audience. 3. The present situation when the (relatively) stable audimeters system is being questioned from the outside, because of the need to measure the consumption of new technologies and the new ways of distribution programs. The project is original in two ways. In the first place, it takes audience measurement seriously. Overall, this kind of data is neglected if not scorned by research. Some pieces of research take it for granted as scientific data, others treat it as a form of political domination of the public – in different ways, both attitudes disregard the social character of audience measurement. In the second place, the project propose a compared view of television, which makes it a part of a more general trend of globalizing if not de-westernizing media studies. However, it keeps a strong national dimension – that is, it considers globalization as a way of articulating the global and the national. From this point of view, audience measurement produces effect in the representation of each national public, homogenizing it in ways which make comparable categories of public, performances of channels and programs. It is also a symptom of a change in television, from a medium predominantly used as a tool by a State with specific public objectives, to a commercial medium dominated by commercial entrepreneurs negotiating with the State, but still operating programming within the nation considered as a Nation-Market. The project will make clear in which ways audience measurement is a truly global way of considering media audiences, in which ways it is still domesticated and adapted to national contexts. Beyond communication studies, this will be of interest to historians of culture, to political scientists, and to all disciplines who take an interest in the changing forms of representation of publics and audiences

The 3D-AER-HYAL project targets a new class of wound dressings based on aerogels, which are dry, highly porous and ultra-light polymer networks. The unique properties of aerogels potentially allow them to absorb a large amount of wound exudate, to facilitate O2 and CO2 exchange, to cover the wound and to act as a depot for the sustained release of therapeutic agents. Aerogels will be prepared from the natural and renewable polysaccharide hyaluronic acid (HA), which is known for its excellent biocompatibility and bioactivity in terms of dermal regeneration. The aerogel precursors will be printed in 3D to fabricate dressings that are adapted to the shape of the wound. HA will be crosslinked with an on-demand cleavable molecule, allowing for proper, painless removal of the dressings. The HA aerogels will be loaded with active agents that prevent wound infection and improve wound healing. It is expected that the unprecedented combination of HA aerogels, 3D printing, on-demand removability and controlled drug release yields wound dressings with significant advantages over currently available dressings in terms of clinical efficacy and patient comfort. The multidisciplinary approach of the 3D-AER-HYAL project is facilitated by the complementary expertise of the scientific coordinator, the host institute (CEMEF, Center for Materials Forming in Sophia Antipolis) and the collaborating laboratory (PHBM, Department of Polymers for Health and Biomaterials in Montpellier) regarding biomedical applications, materials science, polysaccharides, aerogel preparation methods and characterization techniques. The project is divided into 3 work packages (WPs) related to experimental work and 1 WP dedicated to management, reporting and strategies to maximize the exploitation and impact of the results by using a variety of both traditional and modern dissemination tools. In summary, the 3D-AER-HYAL project contains a number of clear objectives to address unmet clinical needs regarding wound healing, but it also offers various scientific challenges and possibilities for fundamental, ground-breaking research. Importantly, the 3D-AER-HYAL project fully meets the objectives of the ANR JCJC grant scheme as the project enables Dr. Buwalda to acquire scientific autonomy, to further develop his own research theme focusing on bio-based aerogels for biomedical applications and to constitute his own team within CEMEF. With its innovative and original approach to tackle scientific and technological obstacles in wound care, the 3D-AER-HYAL project will greatly help Dr. Buwalda in realizing his aim to attain a world-wide leading position in the emerging field of bio-based aerogels for biomedical applications.

Quenching processes of metals are widely adopted procedures in the industry, in particular automotive, nuclear and aerospace industries since they have direct impacts on changing mechanical properties, controlling microstructure and releasing residual stresses. Today there is a strong demand from many industrial companies to control this cooling process taking into account realistic quenching environments with their complexity in order to obtain the desired metallurgical properties such as hardness and yield strength. This demand is accented by the severe requirements in shorter deadlines to design new materials and high quality product. Indeed, the mastering of the cooling rates respecting the metallurgical route with a good homogeneity and reliability is essential to achieve the required microstructure and the mechanical performance. The numerical simulation is a quite standard tool in the framework of metallurgical industry for forming processes but at this time no software is enough predictable ensuring precise heat transfer between the quenching environments and the treated part. A precise numerical multiscale modeling that offers detailed understanding of the complex behavior of multiphase fluid flow and its impact on the part cooling is then a subject of major importance. Indeed, it allows first to reduce the time and cost of developing new materials and therefore to continually develop safe and reliable products that meet the customer specifications and second, to improve the design of existing or new quenching devices, limiting production costs and decreasing energy consumption. Despite the evident industrial interest for modeling precisely quenching process during alloy heat treatment, there is no global study neither global answer addressing this problem in an industrial context. Therefore, the INFINITY partners: ARCELORMITTAL, AREVA NP, AUBERT & DUVAL, CEFIVAL, CMI, FAURECIA, INDUSTEEL, LISI AEROSPACE, MONTUPET, SAFRAN, SCC and TSV, have decided to structure their needs by supporting the following chair proposal. Indeed, in order to predict precisely the liquid-to-vapor phase transition during boiling as well as to study the optimal combinations of quench parameters to reduce residual stresses in solid ingots, an innovative coupled numerical framework needs to be designed and implemented. We believe that achieving this breakthrough requires first the development of a unified ground-breaking adaptive finite element numerical strategy attended by experimental validations under well-defined and controlled conditions and, second, the development of an immersed multiphase strategy in order to leverage the simplicity and flexibility of fluid-solid-heat coupling. Through the INFINITY chair, the candidate and the involved researchers propose, thanks to a very promising immersed volume method, to consolidate a unified multiscale framework around this purpose and to integrate this work and capitalize it in the finite element software THOST® . Modeling the liquid-to-vapor phase change, predicting different boiling modes with the transition between them and modeling the fluid-solid-heat coupling with solid phase transformation are mainly aimed. Two main representative quenching environments will be considered: immersed quenching and jet quenching. Moreover a large part of the proposed work will be also dedicated to experimental investigations and validations. The INFINITY chair contributes then to a long-term vision of high fidelity numerical tool as a basis for reliable simulations of quenching processes allowing the partners to remove several major technical barriers, to faster aid to decision for delivering high quality parts while minimizing residual stresses, preventing cracking and thus optimizing heat processes.