Fluorescence has become an essential observable in Biology and Medicine. The discrimination of a fluorescent label usually relies on optimizing its brightness and its spectral properties. Despite its widespread use, this approach still suffers from important limitations. First, extraction of a fluorescent signal is challenging in light-scattering and autofluorescent samples. Second, spectral deconvolution of overlapping absorption and emission bands can only discriminate a few labels, which strongly limits the discriminative power of emerging genetic engineering strategies, and falls short from the several tens needed for advanced bioimaging and highly multiplexed diagnostic assays. Our consortium of chemists, physicists, and biologists introduces the HIGHLIGHT concept (PHase-sensItive imaGing of reversibly pHotoswitchable Labels after modulatIon of activatinG ligHT) to achieve chromatic aberration-free highly multiplexed fluorescence imaging with only single and dual wavelength channels in emission and excitation. HIGHLIGHT aims at expanding the discriminative dimensions of fluorophore sets much beyond spectral and concentration information such as classically implemented in multicolor labeling approaches. In HIGHLIGHT, label discrimination will not necessitate anymore singular spectroscopic signatures, sophisticated reading-out instruments, or delicate data processing for signal unmixing. In contrast, it shifts towards designing reactive schemes and observables to selectively promote and retrieve the response of a targeted label. HIGHLIGHT exploits reversibly photoswitchable fluorescent proteins (RSFPs) as labels. Increasingly exploited in super-resolution microscopy and dynamic contrast, they are not only fluorescent but as well engaged in rich photocycles. The HIGHLIGHT protocols exploit their specific fluorescence responses to light modulation under well-designed conditions, which provides several dimensions of dynamic contrast to overcome the limitations encountered with spectral discrimination; These responses will serve as readouts either alone or combined using statistical machine learning strategies, which will enable us to perform real time multiplexed imaging of more than ten spectrally similar fluorescent labels and discriminate more than one hundred hues created by mixing these labels in variable amounts and cell territories. As a proof of principle, we propose to challenge HIGHLIGHT in two types of contexts where the paucity of spectrally distinct fluorescent markers has until now been a major hindrance: the analysis of the lineage of retinal cell subtypes and that of their connectivity. In this project, we will namely (i) design and implement a suite of transgenic tools enabling to express varied combinations of 6-12 RSFPs within a population of cells; (ii) design HIGHLIGHT protocols for wide-field and scanning microscopies as well as relevant barcoding strategies to discriminate different cells; (iii) evaluate the photoswitching properties of several tens of RSFPs with one- and two-photon excitation under various environments; (iv) validate HIGHLIGHT for its implementation in a commercial confocal microscope and in state-of-the art Single Plane Illumination scanning Microscopes to push forward acquisition depth and speed; and eventually (v) perform multiplexed clonal analysis in the vertebrate retina, and single-neuron tracing and analysis of axonal convergence. Eventually, the tools and protocols introduced in this project will have near-universal applicability in Biology for multiplexed fluorescence-based observations within biological samples.

TRUST focuses on personal data protection measures to meet the objectives of the RGPD but also the texts in preparation such as the "Data Act" or the "Data Governance Act". We propose to study and develop new security solutions, based on advanced cryptography, for use cases involving the reuse of personal data. These use cases will present various configurations in terms of actors, type of data and processing, opening the way to different technical and legal issues. We thus seek to anticipate legal evolutions and prepare technical architectures to allow the reuse of personal data in compliance with the various legal frameworks.

EDMs, i.e. electric dipole moments of electrons, neutrons or nuclei are sensitive probes for new physics beyond the Standard Model of particle physics. In the present project, we propose to measure the EDM of those systems embedded in a cryogenic solid matrix of inert gas or hydrogen. Matrices offer unprecedented sample sizes while maintaining characteristics of an atomic physics experiment, such as the possibility of manipulation by lasers. An EDM experiment on molecules in inert gas matrices has the potential to reach a statistical sensitivity of the order of 1e–36 e cm; a value beyond that of any other proposed technique. With this project, in a strong collaboration between experimental (LAC, ISMO,LPL) and theoretical (CIMAP) groups, we first aim at performing a detailed investigation of all limiting effects (mainly the ones limiting the optical pumping performance and coherence time) using Cs atoms. This should provide a first proof of principle EDM measurement and set the ground for precise study of systematic effects which will allow EDMMA to reach unprecedented precision

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

The goal of the LACIS's project is to demonstrate the validity of a new approach for color and spectral imaging sensor and camera systems. The demonstration will be given by building one or two prototypes showing the functionality of the novel approach and measuring the improvement compared to the state of the art. The novel approach is based on two principles inspired from the human visual system. First, human retina consist of a mosaic of cone photoreceptors (LMS) but the mosaic arrangement of cones is changing from individual to individual without impinging on color vision capability of the individual. A generalization of this principle would say that we can build a color sensor with any arrangement of color samples in the color filter array that cover the camera. This flexibility of sensor colorization allows optimizing the sensor for many type of application, particularly those that need multispectral encoding. Our prototypes would be therefore equipped with different color filter array and the performance of these different sensors will be tested. Second, instead of being perfectly linear with light intensity, the human retina response is non-linear and adaptive. Adaptation to light allows the human visual system to be sensitive to a large range of light value despite the noisy nature of the retina cells. We will implement this property on the prototypes in analog, before the analog to digital converter to prevent from noise amplification due to digitalization. A previous prototype have already been build and tested favorably by two members of the project. A new implementation has been proposed for a patent and will be implemented in the project. The general goal of the project is to build a demonstrator composed by (1) new filters, either pseudo-random 6x6 RGB, or multispectral based on COLOR SHADE technology, (2) a locally adaptive color CMOS sensor and (3) a motherboard including embedded processing for color or spectral image reconstruction optimized for spatio-spectral information. The demonstrator will be given by a functioning prototype that will deliver images of size 256x256 and showing the properties of the new approach for color or spectral sensor. The consortium is composed on three entities, two laboratories (LPNC, TIMA) and a company (SILIOS Technologies). The two laboratories have already worked together on a first prototype of light adaptive sensor. TIMA is well recognized in microelectronic and have a long achievement in sensor building. LPNC has developed several models for spatio-spectral representation and demosaicing method as well as high dynamic range and tone mapping inspired from human vision. SILIOS is a SME that develops technology and know-how on micro-optics and more specifically on multispectral filters for spectrometry and multispectral imaging. The project will open new products and skill for the company and new intellectual property for the consortium.