PLM software editors propose to the manufacturing industries (automotive, aerospace…) a set of tools to simulate the product and the manufacturing processes thanks to numerical models. One of these tools is the simulation of the part assembly or disassembly to validate the final assembly process or the maintainability of a complex product like an automobile or an aircraft. The commercial product, KineoWorks, developed by Kineo C.A.M. is able to automatically generate a collision free motion of a rigid part simulating its assembly (or disassembly) inside the digital mockup. This product is integrated in widely used CAD software like CATIA, DELMIA from Dassault Systèmes and NX, Vizmockup or Process Simulate from Siemens PLM Software. However, the algorithm cannot simulate the flexibility of the components in the digital mockup such as cables. They need to be removed from the study or considered as rigid. Thus, the simulation is not complete due to this lack of realism. Such a flexible component simulation nevertheless begins to be available on the market. In particular, CEA-LIST develops the XDE physics engine that is able to simulate cable deformation in a digital mockup with real time interaction. The project Flecto proposes to bring these two technologies together: path planning and flexible simulation. The goal is to develop an easy-to-use software component that automatically computes collision free extraction path of flexible components in a flexible assembly. We will focus our objectives on the end-user requirements so that the customer-installed base will provide real case scenarios. Moreover, we will integrate the results into an addon of CATIA to facilitate the testing and the validation by the industrial end-users. The project objectives perfectly fit with several thematic axes of the “Modèles Numériques” ANR program. The primary axis is axis 2, Design and Optimization because the result will be integrated in CAD/CAM tools to help the industries to check the assembly process and to optimize the product maintainability. The axis 1, Complex Systems Simulation and Modeling is the secondary axis because of the flexible models complexity. The project also matches with the axes 4 and 5. The consortium is made of the Kineo C.A.M. Company and the laboratories CEA-LIST and LAAS-CNRS. Kineo C.A.M. is an Independent Software Vendor (ISV) SME recognized as the international leader in industrial software solution for path planning and collision detection with more than 150 customers in 20 countries. The company will coordinate the project; it will gather the end-user requirements and it will exploit the final product. CEA-LIST is one of the best laboratories in interactive simulation and virtual reality. It will bring to the project its knowledge in flexible simulation with its XDE physics engine. Finally, the project will benefit from decades of LAAS-CNRS experience in motion planning algorithms. We will gather the end-user requirements and real usecase dataset. From this input, we will adapt the physics engine to match the path planning needs in term of performance and available data. In parallel, we will enhance the path planning algorithm to take into account additional degrees of freedom due to the flexibility of the component. Finally, we will integrate the algorithms into CAD software like CATIA V5 and we will propose to the end-user to test and to validate the solution. Kineo C.A.M. will exploit the result of the project thanks to a planned consortium agreement with integration in its product portfolio. The commercial solution will be proposed to its existing and future customers. The project has thus five main tasks: project management, flexible models, collision detection, path planning and solution deployment. The project is 36 months long. It represents 122 person.months for a total budget of 1310.4 K€ and we apply for a ANR grant of 609.6 K€.

Accelerators provide the majority of performance in modern High Performance Computing (HPC) systems and are the fundamental building blocks for Exascale systems. The European PILOT (Pilot using Independent Local & Open Technology) will be the first demonstration of two ALL European HPC and High Performance Data Analytics (HPDA) (AI, ML, DL) accelerators, designed, implemented, manufactured, and owned by Europe. The European PILOT combines open source software (SW) and open and proprietary hardware (HW) to deliver the first completely European full stack software, accelerator, and integrated ecosystem based on RISC-V accelerators coupled to any general purpose processor (CPU) via PCIe Gen 6.0 or CXL 3.0. This pilot will demonstrate key HPC and HPDA workloads and software stacks. The European PILOT is also the first to demonstrate an ALL European HPC ecosystem. The accelerators will be manufactured in the new European GlobalFoundries 12 nm advanced silicon technology, a major demonstration of European technology independence. The European PILOT combines cutting edge research utilizing SW/HW co-design to demonstrate HPC and HPDA accelerators running key applications and libraries in a full software stack including middleware, runtimes, compilers, and tools for the emerging RISC-V ecosystem. The European PILOT is able to produce a full stack (SW and HW) research prototype by leveraging and extending the work done in multiple European projects like: EPI, MEEP, POP2 CoE, EuroEXA, and ExaNeSt. This pre-production system can only be realized with a combination of existing IP, HW emulation using FPGAs, and real ASIC prototypes that demonstrate the full stack feasibility of the hardware and software. Finally, while the applications we use span AI to HPC, the aggressive ASIC implementation (chiplet size and small geometry) will be the smallest technology node manufactured in Europe and can easily be adapted for a near-future HPC implementation.

DEMOCRITE is a software platform which integrates tools for the analysis and coverage of risks on a territory. They could be used in cold planning mode or in crisis management, and will be used to optimize the rescue response (nature, number, location) given a risk coverage level agreed by the Authority. Some tools will be tested on a limited territory (2,5 km²) but the extension at larger scale will be studied. These tools are meant to map risk probabilities and potential consequences as well as intrinsic vulnerabilities. Techniques for the optimization of resources will be studied. Models for the development of complex risks: These low probability risks imply a level 3 operational answer [BSPP 2011]. They are likely to cause large scale consequences and may require engaging numerous vehicles / crews. DEMOCRITE tackles for the moment two such risks: urban fire and explosion. Others (flood, epidemic...) will be studied in a future version. Fire propagation will be based on an urban representation given by a GIS. The propagation will be handled by a cellular automaton whose transition rules will be based on numerical simulations. A local model will be able to replicate the different phases of an indoor fire for different kinds of buildings. Explosion effects (accident, bombing ...) will be first computed will be computed by an hydrocode (reference results). The geometry will be imported from the GIS. Simplified approaches will be tested against the reference results in order to select the best one for DEMOCRITE. The explosion will be allowed to be either the cause or the consequence of a fire. Risk propensity maps: High probability risks (such as first aid to persons, representing more than 80% of the BSPP actions) may require a level 1/2 operational setup. The analysis of past events shows that risk propensities are far from being isotropic. Optimizing risk coverage thus requires a precise mapping of risks. The aggregation of unitary risks will be studied. Experience feedback will be coupled to statistical approaches in order to predict land use planning impact on territory risks. For instance, car-crash intervention statistics are not sufficient to predict risk evolution due to the creation of new roads: they must first be correlated to other data (traffic density, average velocity, meteorological conditions, etc.). Intrinsic vulnerability maps: Intrinsic vulnerabilities are characteristics of territory stakes having a direct link with consequences should an unwanted event happen. they may also vary with space and time. For instance, public access buildings with a high density of people (stadium during a sport meeting) will increase the local human vulnerability during a few hours. Another aspect, functional vulnerability, describes the functions (government, education ...) performed by a society and how they could be threatened. These functions rely on mappable items. Sometimes the localization of a vulnerable item (a transformer substation) may differ from the affected zone in case of failure (a whole district). Human and functional vulnerabilities will be mapped, and the vulnerability of networks will be tackled. Theses maps will aid in making operational decisions (priority evacuation zones, safety perimeters ...).

The aim of our project is to develop up to regulatory preclinical level a drug candidate with broad-spectrum inhibitory activities against intracellular toxins and pathogens (viruses, intracellular bacteria and parasites). A realistic approach imposes pharmaceutic development of the drug candidate for a single medical indication. This indication will be the prevention of the Hemolytic Uremic Syndrome (HUS), the complication of infections by Shigatoxin-producing entero-hemorrhagic Escherichia coli (health crisis Hamburg 2011). However, a series of smaller work-packages will enable to strengthen the in vivo efficacy proof of concept of our treatment against other bacterial and viral life threatening infectious diseases responsible in the past and potentially in the future for major bio-threat health crisis. We have discovered and optimized the molecule Retro-2.1, an inhibitor of the transport of toxins and intracellular pathogens from early endosomes to the trans-Golgi network. This molecule is active in the nanomolar range, a concentration suitable for drug development. It is remarkably non-toxic in mice. In collaboration with the members of our network, demonstration of efficacy of the hit molecule Retro-2 (precursor of Retro-2.1) was done in mice models of ricin intoxication, Shiga toxin-producing E. coli O104:H4, Leishmania parasite, poxviruses and enterovirus 71. In vitro data showing a strong level of protection of cells by Retro-2.1 was observed for Ebola and Marburg viruses, Chlamydia trachomatis responsible for eye and sexually transmitted infections, Francisella tularensis a rare but extremely deadly bacteria, and other viruses. Recent work enabled to formulate Retro-2.1 for intravenous administration, the preferred route of treatment for many of the targeted diseases listed above during which the health condition restricts oral administration (nausea, vomiting, diarrhea…). Pharmacokinetics measures were performed. The next steps, aim of the proposal, are to assess for the formulated Retro-2.1: - Structure of interaction with its molecular target - Full pharmacokinetics and biodistribution in mouse and a large animal (dog or monkey) - Full absorption, metabolism and excretion in mouse and a large animal - Non-regulatory and regulatory toxicology in mouse and a large animal - In vivo dose efficacy in mouse against our primary targeted disease, Shigatoxin-producing E. coli strains O157:H7 and O104:H4. - In vivo efficacy in mouse against our secondary targeted diseases: Ebola virus, poxviruses, enterovirus 71, Chlamydia trachomatis, Francisella tularensis. European society is extremely vulnerable to internal, imported or global infectious health crisis. Emerging infectious diseases raise exponentially from year to year. Currently, more than 100 outbreaks occur each year, some with devastating human and economic impacts. Thus there is a need for broad-spectrum therapies that could be efficient on endemic, rare or even unknown pathogens because development of new agent-specific drugs is too long (>10 years) and costly (25 M€<<300 M€). Such drugs must reduce the risks of resistanceacquisition by the pathogens. Although not fully demonstrated, many experts consider that drugs targeting the host rather than the pathogen may reduce the risk of resistance. This is precisely how our drug candidate is designed. It targets a component of the intracellular trafficking machinery that is exploited by intracellular pathogens and thus protects the host rather than kills the pathogens.