Heart failure with preserved ejection fraction (HFpEF) is the most rapidly increasing form of heart failure in the Western world. Despite high public-health importance, no treatment strategy has yet been established to reduce morbidity and mortality. MINOTAUR is a multidisciplinary consortium of cardiologists, cardiac surgeons, systems biologists, biophysicists, biochemists and physiologists aimed at expanding our original observations that a natural caloric restriction mimetic (CRM) improves diastolic function in two different animal models with independent HFpEF risk factors, namely age and hypertension. To investigate the broader applicability of CRM treatment and its translational potential, we will extend our investigations to an animal model of HFpEF induced by metabolic syndrome, the most prevalent cause and comorbidity of HFpEF. We will concentrate our efforts on the mechanistic details by which CRMs counteract the development of HFpEF with metabolic dysfunction. Using a wide range of state-of-the-art techniques, we will provide a comprehensive in-depth characterisation of the CRM-treated HFpEF cardiac phenotype at the molecular, cellular and whole organism level, and considering the gender aspect. Gender-based correlation analysis of key biochemical parameters (polyamine levels and post-translational modification of titin) and diastolic dysfunction in humans will reveal new diagnostic and prognostic tools in HFpEF. This novel information will feed future clinical trials to evaluate the potential of CRM-rich diets as an effective therapy for managing HFpEF.

In the context of a European initiative already launched and currently under building (Call NMBP 22-2017) the ‘PSS-EURO-Network’ MRSEI has the ambition to create and establish a European scientific network on the management of the transformation of industrial Business Models, through servitization innovation strategies. Within the scientific and industrial community which is currently actively working on Product-Service-Systems, a strong originality of the PSS-EURO-Network is to put the focus of the research on the methods and tools to transform the industrial organizations themselves and their Business Models, as a way to go beyond current European researches focusing mainly on the engineering of the PSS solution. With the ambition to create, then deploy concretely via European projects, a consistent set of methods and tools aiming at strongly increasing the success rate of industrial Business Models transformations towards PSS solutions, the PSS-EURO-Network can bring important societal impacts via the transformation of consumptions behaviors thanks to the product-service approach. The first European project answer taken in charge by this PSS-EURO-Network is already quite mature, and the definition of the scientific aims, research program and full consortium is already well advanced for the first phase of the submission: a summary is given in the following sections. The project coordinated by ARMINES-Mines Saint Etienne has a large European representation, first based on 5 key scientific laboratories gathering strong complementary competencies on PSS and Business Models (France, Denmark, Germany, Italy, and United Kingdom). But, additionally, the consortium includes a rather large network of industrial and transfer actors (still under building), aiming at a large European impact of these research works. The activity program defined in the MRSEI project has the ambition not only to build a first submission to a European call (covering the finalization of phase 1 and all the phase 2) , but also to build a longer term active Network, with a clear Strategy of European project building. This PSS-EURO-Network would also use Digital Technology through a living internet virtual community, which would be created and implemented operationally thanks to the MRSEI project

This project focuses on three iron-base alloys that have growing potential for high-temperature, high-strength and strong- magnet applications: Fe-Cr, Fe-Mn and Fe-Co. Because of the key role of magnetism, an innovative materials design based on advanced modeling approaches is necessary to control key properties of these materials. Such a design strategy requires the combination of (i) highly accurate methods to determine atomic features with (ii) efficient coarse-graining techniques to access target physical properties and to perform the screening of materials compositions. For the former, density functional theory (DFT) has for many materials classes already proven to be a highly successful tool. For Fe-based alloys, however, a critical bottleneck is the role that magnetic ordering, excitations and transitions have on thermodynamic, defect and kinetic properties. Therefore, a complete and accurate modeling of magnetism is urgently needed to address the materials-design challenges: the resistance to radiation damage related to the chemical decomposition in Fe-Cr, the grain-boundary embrittlement in ferritic Fe-Mn and the high-strength of austenitic Fe-Mn, and the phase ordering and the relative stability of a and ? phases in Fe-Co cannot be fully understood without properly accounting for the magnetic effects. The novelty of the current approach is twofold: First, on the DFT-side, we will make use of the recent important progress in treating magnetism in pure idealized Fe lattices, in order to go towards an accurate modeling of magnetic multi-component systems with point/extended defects, and beyond the standard collinear approximation. Second, we will develop new methods that allow us to bridge the gap between (i) highly accurate electronic calculations and (ii) large-scale atomistic thermodynamic and kinetic simulations for iron based alloys by – and this is decisive – fully taking into account the impact of magnetism on defect properties, diffusion and microstructural evolution. For the latter, lattice-based effective interaction models (EIMs) and tight-binding (TB) models will be developed based on data from DFT, including magnetic configurations, excitations and transitions. This will allow us to provide a coherent description of the role of magnetism on various properties of Fe-based alloys at different length scales and at finite temperature. It will further give us the ability to perform the optimization of key parameters controlling the relevant properties like phase decomposition in Fe-Cr, phase ordering in Fe-Co or decohesion of grain boundaries in Fe-Mn. Dedicated experiments in bulk alloys and along intergranular / interphase boundaries grown on demand will be performed in the project, which are essential for verifying the robustness of the theoretical predictions. The three chosen alloys exhibit a large variety of magnetic behavior. The methods developed and applied in this proposal are therefore expected to be transferrable to the modeling of other magnetic materials. The results of our simulations will lead to the improvement of thermo¬dynamic and diffusion databases and tools (such as DICTRA) that are nowadays routinely used in industrial R&D but that at present have difficulties in accounting for magnetism. In this way a better and more systematic understanding of the role of magnetism in Fe-based alloys will help to improve significantly the predictive power of the simulations and thus contribute to a more efficient and accurate development of new steel grades. Once fully implemented, the availability of such computational tools is expected to boost the efficiency, change the strategy in designing new steel grades and to form an important contribution for the future competitiveness of steelmakers.