The project ” Regulators and explicit formulae ” aims at drawing together a group of mathematicians working on various aspects of regulator maps : analytic issues, motivic and K- theoretic problems, explicit formulae and reciprocity laws, links with L-functions, geometric interpretations via Arakelov theory. The main themes of the project are: - Motivic cohomology - Arakelov theory and explicit formulae - L-functions of number fields and elliptic curves. Polylogarithms

Enhancement of lung tissue regeneration and functional recovery following an acute pulmonary insult by regenerative therapy based on the use of heparan sulfate mimetics (HSM) is a promising approach for the treatment of diffuse alveolar damage (DAD), observed in acute respiratory distress syndrome (ARDS), acute exacerbations of fibrotic interstitial lung diseases or severe COVID-19 pneumonitis. The beneficial effects of HSM would be mainly related to the regeneration of the injured tissue by restructuring the destroyed matrix, protecting the cellular communicating peptides (growth factors, cytokines, chemokines), and by limiting the fibrosis usually observed during the repair process. Using of innovative approaches and models developed by 4 partners including a private one, the MAT-PL project will explore the ability of a heparan sulphate mimetic agent (OTR4132) to reduce inflammation, dysregulated angiogenesis and fibrosis, and improves the outcome of acute pulmonary injuries characteristic of DAD, thus opening a new approach for the prevention and the treatment of lung fibrosis.

The current biopsy procedure is to introduce a needle inside the patient towards a given target using echography imaging for control of the position. Reaching the target at the right position is a real issue for diagnosis, therapy and also prognosis, for example concerning tumors or abscess. The NOCT project aims at developing two apparatus, one for imaging and one for navigation, integrated in a complete clinical application of real-time echography navigated biopsy, which would be the first of its kind in the world. We will build an optical imaging system with a needle-like probe that could perform virtual “optical biopsy” prior to the excision of the sample by revealing in vivo the fine microstructures of the tissue. Full-Field OCT is the best-suited technique for this purpose. This technology is now commercialized in a microscope for ex vivo imaging, and we plan on adapting it in a system with a thin rigid probe, with emphasize on ergonomic constraints such as the diameter and length of the needle. We will create a precise surgical navigation system that will be adapted to the clinical ambulatory context, so that it would become in the next decade a reference system for computer assisted medical interventions. This project is a translational research between physics, informatics and medicine, where a key point is to adapt novel technologic apparatus to specific clinical needs. With the aim of the future clinical application we will characterize the preclinical and clinical performance and pay attention on risk management and authorization from the CPP, ANSM and HAS. We will meet these challenges as a consortium of five partners: two laboratories specialized in optics and in computer assisted medical interventions, Institut Langevin-ESPCI and TIMC-IMAG, one clinical investigation center specialized in interventional radiology and computer assisted medical interventions, CIC-IT, and two private companies that will industrialize the final resulting systems, LLTech and Surgiqual Institute.

The ultimate challenge of molecular sensing is the detection of ultralow concentrations of a specific analyte in a complex mixture using fast, simple and easy to handle analytical tools. The main objective of the present project is to develop a new generic analytical technology able to reach ultra-low detection limits of organic, inorganic or biological analytes in environmental or biological samples, with an improved simplicity and cost-efficiency. Our strategy relies on the unprecedented combination of molecular and enzymatic switches coupled with electrochemical methods for highly sensitive detection of small analytes and will be validated with targets as H2O2, fluoride, or H2S. Such detection is of great importance because those molecules plays important roles in various disease or biological functions: excess amount of fluoride causes fluorosis, urolithiasis, or even cancer; elevated levels of hydrogen peroxide have been found in a number of respiratory disorders as well as in renal dysfunction; unregulated, abnormal levels of H2S may contribute to various diseases since its implication is now well established in the cardiovascular domain, in the control of inflammation, in the central nervous system as a neuromodulator or neuroprotectant, and in cellular bioenergetics, with relevance to hypoxia sensing or tumor proliferation. The key idea is to design molecular switches which combine a target-triggered autocatalytic reaction and the release of a cofactor for the activation of a surface confined apoenzyme. This strategy would provide unprecedented sensitivity since it adds up two amplifications. The first is the autocatalytic amplification of the small analytes coupled with the exponential release of the cofactor from a suitably designed molecular pro-cofactor. The second amplification is based on the electrochemically-monitored activation of a surface confined inactive apo-enzyme thanks to the release of the cofactor in the previous reaction. The biocatalyst activation allowed so far detection of picomolar concentrations of the cofactor in solution and femtomolar concentrations of analytes should be detectable from the combination of the two amplifications. This strategy will be then advantageously adapted to design ultrasensitive immunoassays with the upstream addition of a fluoride or H2O2 producing enzyme. These small molecules will be considered as intermediate products generated by an enzyme label in an affinity binding immunoassay of ELISA type. An ideal gain of sensitivity close to 1 million over classical ELISA is projected. Developing more sensitive technologies will provide a great step forward in clinical diagnosis. For instance, lowering the detection limit of biomarkers would provide a great tool for several applications as the early detection of cancer and cancer recurrence, the early detection of infectious disease or neurologic disorder, or the identification of new biomarkers. Our project thus aims at reaching similar low detection limits of protein biomarkers as those achieved with the scarce number of commercialized ultrahighly sensitive immunoassays, but with a much lower cost, simplicity, and a greater adaptability to existing technology and laboratory practices. Important efforts will be made to design and synthesize the pro-cofactor in a highly pure form. Evaluation of their ability to release the cofactor together with autocatalytic amplification of the initial low amount of the target will be crucial for the later development of this innovative technology. Presented in the challenge “Renouveau du tissu industriel” (Challenge 3, White biotechnology and bio-inspired chemistry; orientation 15: Sensors and Instrumentation), the overall objective of ECOSENS is the deployment in the market of modular sensing platform for the accurate detection of multiple compounds of interest (from small molecules to proteins) in various samples, with time to market realistically within five to ten years.

MUSICOVID is an interdisciplinary research project that places at its centre the analysis of the modes of adaptation, resistance and innovation of musicians and their audiences in times of Covid, when the question of a brighter tomorrow is so acute. It aims to question the new place of live music in a society in crisis, both from the point of view of restrictions and prohibitions ("non-essential" or potentially dangerous practices), and from the point of view of the factors that seem to express an irrepressible need to live and to ensure that music lives on (adaptation, resistance, innovation), thereby endowing the musical experience – declared to be "non-essential" – with essential virtues (for physical and emotional well-being, for sociability). This study, which sheds light on the link between pandemics and music, between biopolitics and musical life, and the analysis of the stakes attached to prohibitions and practice, goes beyond a simple academic framework to open up concrete results, available to social, political and economic actors and citizens. The team, with its strong experiential capital in terms of surveys on musical practices and cultural situations of great crisis, will mobilise partners representing the richness of the worlds of music. By articulating five areas (memory, resilience, constraint, pedagogy, representations), MUSICOVID seeks to meet a fourfold challenge: (1) To document a crisis, to collect material (musical experiences) and to conserve/preserve the memory of the health crisis in order to analyse it in the light of several theoretical approaches; to constitute this memory as a resource; (2) To understand which individual or collective strategies social actors adopt to get through the ordeal of a pandemic, from the threefold lens of adaptation (adjusting practices to the constraints of the situation), resistance ( to resist the repressive models of an accepted imaginary, imposed actions and political decisions) and innovation (choosing or being forced to introduce something new into something that is well established); to characterise a society's relationship to music in terms of a benefit/risk cursor; to understand how a society faced with a crisis organises and ensures the survival of its members and the maintenance of social cohesion; (3) To supervise and organise, on the basis of these scientific results, a common reflection between researchers, the different actors of the music worlds, policy-makers and public authorities, favouring the dynamisms of collective intelligence; to provide concrete solutions and tools in the cultural and socio-economic fields aimed at solving the challenge of arbitration between bare life and social life; to strengthen the place of humanities and social sciences in the expertise serving society; 4) To equip citizens with the knowledge and tools required to imagine alternative ways to fight the pandemic and to realise that music is a cultural asset essential to life (Freiburg Declaration on Cultural Rights, 1993 and 2007) and more broadly a springboard capable of "recreating the participatory experience of democracy" (Honneth 2020); By preserving the memory of musical experiences in times of Covid, by analysing the strategies of the actors (adaptation, resistance, innovation), by making collective intelligence a source of shared profit to prepare for the aftermath, by proposing a global model likely to be duplicated in other fields of culture, MUSICOVID aims to respond to a social need in a strong ontological reading: can we build ourselves without music?