Epilepsy is among the most common neurological diseases, affecting between 0.5% and 1% of the general population. Therefore, new diagnosis and treatment methods have a high impact on society. Epilepsy is also among the most frequently diagnosed neurological paediatric disorders, with long-term implications for the quality of life of those affected. Only in two-thirds of cases, seizures can be adequately controlled with anticonvulsant drug treatment. For the remaining drug-refractory patients with focal epilepsy (up to about 2 Mill. in Europe), epilepsy surgery is currently the most effective treatment. However, only 15-20% of those patients are eligible for epilepsy surgery. That is either because the epileptogenic zone in the brain cannot be localized with sufficient accuracy with standard diagnostic means, or because the epileptogenic zone overlaps with eloquent cortical areas, so that it cannot be surgically removed without considerable neurological deficit. PerEpi aims to bring together a group of experts at the European level to improve this situation in two ways, both of which use concepts of non-invasive personalised medicine: The first one focuses on a new individualised multimodal approach to set a new milestone in localization accuracy of the epileptogenic zone in order to offer the most appropriate personalised therapy. The second one focuses on a new individually optimized transcranial electric brain stimulation technique as a new treatment option to reduce seizure frequency and severity. This is particularly attractive for those focal refractory patients where surgery is not an option because of an overlap with eloquent cortical areas. A dedicated ethics work package will ensure that the research in the consortium is designed and conducted following the highest ethical standards. In addition, this work package will study the translational pathways of the new approaches to foster clinical integration that is ethically and socially responsible.

The negative capacitance (NC) effect has been presented as a possible solution to the necessary reduction of the switching voltage in field effect transistors and could thus contribute to the future development of low power switching devices. The work that we plan to carry out is mainly positioned in the development of mature static NC structures. This maturity will be reached if we can control and stabilize the physical phenomenon at the origin of this NC. To succeed, it will be necessary to develop heterostructures alternating layers of a few nanometers thick made of ferroelectric (FE) materials on the one hand and paraelectric (PA) materials on the other hand, and to control the quality of the interfaces essential to the stabilization of the NC effect. The choice of materials, the control of epitaxial stresses and electrostatic effects will be crucial to bring the NC phenomenon back to near-ambient temperature ranges. The consortium set up for this project intends to take up this challenge and for that it gathers competences and strengths in the elaboration of heterostructures, the fine characterization at the elementary scale of the materials, of their interfaces, of the structure in ferroelectric domains, the electrical characterization of these structures at the local and macroscopic scale in wide frequency and temperature ranges, clean room technologies for the realization of specific test vehicles. In this context, the objectives of the NEGCAP project are: (i) to fabricate model FE/PA structures in superlattice (for direct measurement of negative capacitance) and multilayer (for indirect measurement of NC), (ii) to determine and model the dielectric response of these structures in a wide frequency range, (iii) to probe the properties at the FE/PA interfaces in order to understand the physical phenomena involved, (iv) to identify the fields of application of these structures and to propose "negative capacitance effect at room temperature" structures.

Endophagous hymenopteran parasitoids have evolved a variety of strategies to circumvent the immune defences of their insect hosts. An increased number of data on these factors is now available showing that they belong to different types: proteins from wasp venom gland or ovaries, particles of viral origin (polydnaviruses PDVs) and Virus-like particles (VLPs). Some main virulence factors used by parasitoids of dipteran and lepidopteran insects have now been characterized in more or less details (thanks to a previous ANR project an to several collaborations with the Genoscope) as a venom RhoGAP protein from the figitid Leptopilina boulardi, which alters the morphology of immune cells and whose targets in the Drosophila host have been identified. To determine if these factors are common to a majority of species or rather specific and understand the reasons explaining their occurrence in a given parasitoid species, we are using the larger set of data obtained on venom glands (EST from 10 species) and on ovaries (sequences of polydnaviruses genomes produced in the calyx of the ovaries and sequences of EST of ovaries). Preliminary results confirm that the use of one or the other virulence factor can not be deduced from the phylogeny of the wasp or its host taxon and they allow defining less than ten families of factors that can be chosen to perform advanced mechanistic and evolutionary studies. New questions have arised regarding the origin of these eukaryotic virulence factors including the molecular changes leading to transformation of an endogeneous protein into a functional toxin and the way these toxins are delivered into the host (viral symbiosis, secretory system as exosomes ). We then propose here a multidisciplinary approach to examine the diversification of venom toxins across the full range of the 160 million-year-old clade of parasitoid Hymenoptera. Molecules produced in the venom or encoded by PDV all belong to 'classical' eukaryotic protein families. If PDV-encoded factors are directly delivered inside host cells, venom-produced molecules have to be expressed in cells of the venom gland and then secreted into the lumen to be injected along the egg. Most often, cDNAs encoding proteins are also specifically overexpressed in the venom gland compared to the rest of the body (for instance, LbGAP, the Lb serpin LbSPNy, SODs, AGAs, neprilysins are overexpressed in the venom gland). Data are now available on virulence factors introduced in insect hosts by parasitoids but, surprisingly, little is known on the factors produced by hymenoptera gall inducers, except that they might combine maternal secretions initiating gall-formation and egg/larval products ensuring the next steps. Therefore, exploration of the diversity of parasitoid virulence molecules transferred into the insect host, will be extended to a comparison with molecules secreted by gall-forming parasitoids to modulate plant physiology, in an attempt to understand the fundamental bases for evolution of parasite-produced modulating factors for plant and animal.

There is growing consensus that mineral crystallization from ionic solutions involves a liquid-liquid phase separation (LLPS), where a reactant-rich liquid separates from water, just as in organic crystallization. However, mineral LLPS remains elusive because of the short lifetime of the liquid phases prior to solid precipitation. TITANS will provide fundamental knowledge on mineral LLPS by addressing the most debated questions in order to: 1) assess how liquid are the reactant-rich structures, 2) determine if they are a metastable thermodynamic phase or a kinetic pattern, and 3) rationalize the intricate evolutions of the liquid, the amorphous solid and the crystal. We will combine advanced fast microfluidic mixers, in situ characterization of structure, chemistry and dynamics at the synchrotron and in the laboratory, and in and out-of-equilibrium modeling. TITANS will thus provide a reliable depiction of the ubiquitous soft matter processes preceding the crystallization of carbonates, oxalates and sulfates.

The propositional satisfiability problem (SAT) is a fundamental formalism in constraint programming that is used to model and solve a wide variety of academic and industrial problems. While modern complete SAT solvers have achieved the ability to address instances featuring millions of variables and clauses within reasonable time frames, they still can fail drastically on certain instances. Indeed, the efficiency of SAT solvers is highly influenced by the decisions made during the search process. As such, branching heuristics play a pivotal role in enhancing the performance of SAT solvers, thereby elevating the development and optimization of such heuristics to a crucial research domain within the realm of SAT solving. In addition, there has been a recent surge of interest in integrating machine learning mechanisms in combinatorial problem solving and, more marginally, SAT. The BforSAT project is unequivocally committed to the enhancement and refinement of branching heuristics for SAT and beyond. Our intention is to delve into the exploration of innovative heuristics, incorporating machine learning mechanisms and thus taking advantage of its potential in enhancing the decision-making capabilities of modern SAT solvers. These novel heuristics will be rigorously evaluated thus contributing to the broader understanding of the SAT community regarding the development of highly efficient branching strategies. Our research endeavors will aim to bridge the gap between traditional combinatorial problem-solving techniques and cutting-edge machine learning methodologies. By harnessing the power of machine learning, we anticipate a paradigm shift in the way SAT and related problems are approached and resolved as the synergy between machine learning and traditional SAT solving holds the potential to not only improve solver efficiency but also to unearth novel strategies for addressing more complex real-world challenges, with far-reaching implications for both academia and indust