The past three years have witnessed the striking discovery of twisted multilayer graphene as a versatile plateform to realize quantum phases of matter in a controlled setting. Recent experiments have demonstrated tunable superconductivity, correlated insulators and topological phases. These phases emerge from flat bands in Moire twisted profiles and can be explored at low electrical doping. As our understanding of these graphene systems is improving with an intense theoretical and experimental activity, there are still many open questions on the nature of the exotic phases and on how they can be probed experimentally. The aim of our project is to combine progresses in analyzing the rich physics of twisted graphene materials with a more precise understanding of the various experimental probes to distinguish competing phases, detect superconducting order, insulating mechanisms, topological properties or transport regimes.

Foams, emulsions, pastes, porous media, biological suspensions or living tissues, are involved in many industrial processes and are largely studied since several decades. However, mainly two questions are still a challenge for the physicists: the stability and the dynamic of these systems. These questions have been classically addressed in the frame of classical low Reynolds hydrodynamics. However, they have been entirely renewed thanks to experimental improvements these last years: the considerable developments of nanoscale fluid dynamics, allowing to probe fluid transport down to nanoscales, as well as the fine control of the physico-chemical properties of interfaces, has provided refreshed views on these questions. The physical phenomena involved in these nano-films call upon studies often addressed separately: local shear rates that can overcome the imposed shear rate by orders of magnitude, intermolecular forces (DLVO theory), surface rheology, or electro-/diffusio-/thermo-osmosis, to cite a few. These topics have been largely addressed by the four groups of the consortium leading to important contributions using innovative experimental tools: M.-C. Jullien and O. Theodoly showed the importance of intermolecular forces effects on droplet dynamics and more recently the non homogeneous surfactant surface concentration along a traveling droplet using RICM; while A. Colin and L. Bocquet provided a clear view of discontinuous shear-thickening transition as the breakdown of lubricated contact between particles, at a critical normal force using a tuning fork apparatus, these observations are clearly correlated to macroscopic measurements At this stage of the state the art, a major issue is the coupling of these mechanisms taking place at nano-scales on larger scale transport dynamics (droplet, cell, suspension). We therefore feel that, in view of the recent experimental and theoretical progress, it is timely to address these questions, which are shared by various systems; and therefore to address these questions from a unified and intertwinned point of view and methodology. This is the objective of the ILIAAD project. Interestingly, the observables that are analyzed to study these systems are very similar, if not identical, for these different systems, such as interface velocity, object velocity, normal stress as function of film thickness to cite a few. As a whole, this fully justifies studying these systems, more precisely their stability and dynamics, in a concerted and concomitant manner. There is no doubt that the expertise of each partner will significantly enrich the understanding of all experimental configurations. As such, the consortium is able to fully address the stability and dynamics of two-phase systems in a general framework. We will especially focus on the coupling between the interface, the transport within the thin films, and the flow: role and transport of the surfactant for fluid interfaces; coupling of the flow in the thin liquid film with the elastic deformations for solid boundaries; coupling of the flow in the thin liquid film with the visco-elastic deformation and external membrane treadmilling motion with living cells; role of the intermolecular forces and; at the most nanoscopic limit, role and specificities of the thermal fluctuations in both phases. The different partners will closely interact all along the project in order to share their results and address the global objective: deriving a comprehensive framework describing/predicting the dynamics and stability of confined films with interfaces (whether deformable or not) to improve our understanding of multi-phase systems. This project will identify generic flow properties associated to confinement at the smallest scales, which are shared by these systems despite the variety of geometrical, mechanical and physico-chemical properties of their confining interfaces.

Rapidly Progressive Glomerulonephritis (RPGN) is a class of acquired renal disease that remains one of few human autoimmune diseases representing an acute threat to survival. Focal necrotizing crescentic GN is the renal lesion typically associated with the clinical syndrome of RPGN and is a medical emergency that requires side-effect prone immunosuppressive therapies. Untreated RPGN progresses rapidly to renal insufficiency. During crescent formation in experimental RPGN in mice, podocytes assume a migratory phenotype and proliferate. Immune-mediated glomerulonephritis can also develop chronically. IgA nephropathy (IgAN) is the most common primary GN. The realization that around 30% of patients with this apparently benign condition progress to end-stage renal disease revealed IgAN to be a major health problem. It thus appears that a sub-group of IgAN patients undergo a phenotypic switch to accelerated disease progression and poor outcome. The basis for this switch is poorly understood, yet common pathological features between RPGN and severe IgAN may suggest that a second insult could convert IgAN to an RPGN-like phenotype, begging the question of what such an insult would be, and whether there is mechanistic convergence in the pathogenesis of the two diseases. This project relies on two recent findings in our laboratories: 1/ We demonstrated de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in podocytes from both mice and humans with RPGN. Such induction correlated with increased phosphorylation of EGFR in podocytes from mice with anti-GBM disease. Glomerular EGFR activation was absent and the course of RPGN markedly improved in HB-EGF-deficient mice. Moreover, conditional deletion of the Egfr gene from podocytes or administration of a clinically available EGFR inhibitor both markedly alleviate RPGN in mice. 2/ With the aim of identifying the pathogenic molecular pathways involved in mesangial cell transformation in IgAN, we performed a gene expression screen to identify genes induced by IgA1-complexes in human mesangial cells (HMC). HMC were stimulated by IgA1 complexes purified from IgAN patients or by serum IgA1 purified from normal subjects. HB-EGF was one of the most prominent genes up-regulated in HMC stimulated with patient-derived IgA1 complexes. These observations suggest that engagement of EGFR by HB-EGF constitutes a pathogenic switch in RPNG that may also be common to IgAN. We will first address whether the EGFR is a pathogenic mediator common to inflammatory GN. We then aim to identify pathological conversions and signaling pathways upstream of EGFR and determine to what extent they are shared in RPGN and IgAN. We are interested in defining points of mechanistic convergence between the two disease forms in attempt do identify a pathogenic switch that can convert relatively benign chronic GN such as IgAN to a rapidly progressing form of the disease. We postulate that engagement of EGFR signaling might constitute such a switch. To test this hypothesis, will first use transgenic models to address whether expression of EGFR and its ligands is sufficient to either trigger RPGN or convert IgAN to RPGN. As we anticipate that an additional insult will be required, we will then seek to identify upstream pathways and events that may elicit EGFR signaling, potentially by release of ligands such as HB-EGF. Transactivation of EGFR by G-protein-coupled receptors (GPCRs), also implicated in GN, has been documented. This interaction allows GPCRs to take advantage of pathways downstream of EGFR to influence cell function. Seeking to identify GPCRs that may engage the EGFR pathway, we focus on GPCR families likely to be engaged in both RPGN and IgAN due to dysfunction of the capillary barrier, including protease-activated receptors (PARs) and endothelin receptors (ETA and ETB). We hope to identify dominant signaling pathways of EGFR and additional targets.

Measurement of atmospheric HO2 radicals is important to investigate the tropospheric chemistry during field campaigns or in atmospheric simulation chambers. The current HO2 measurement techniques are all indirect and rely on chemical conversion of HO2 into OH or a species measurable by conventional chemical analytical instruments (LIF or CIMS), which may result in serious interference and artefacts. In addition, these instruments are, for the most part, very expensive and bulky, which limits their deployment on a large scale. In this proposal, we propose to develop a compact and innovative optical instrument for interference-free, in-situ, real time and direct measurement of atmospheric HO2 concentration with high sensitivity and accuracy. This spectrometer relies on an unique combination of Frequency-Stabilized Cavity Ring-Down Spectroscopy (FS-CRDS) with Balanced-Detection Faraday Rotation Spectroscopy (BD-FRS). The expected detection limit would be of ˜10^6 molecules/cm^3 (0.1 pptv @ STP), suitable for HO2 detection in atmospheric simulation chamber and field campaigns. In fact the typical atmospheric concentration of HO2 is of 10^7-10^8 molecule/cm^3. Our team is composed of experts in the development of FRS (LPCA), FS-CRDS (GSMA) and HO2 detection by cw-CRDS and FAGE (PC2A). We propose to develop such hybrid instrument which will be tested and characterized at each step of development, in terms of sensitivity and accuracy, in lab by means of a calibration cell used for calibration of the PC2A's FAGE instrument. The first step (WP2) consists in developing and calibrating the BD-FRS by the LPCA team. The experience of the LPCA team on the development of FRS to detect OH radicals (at 3568.5 cm-1 with LoD above atmospheric OH concentration) is valuable for the development of the present FRS for HO2 detection at 6638.20 cm-1 (the line used by the PC2A using cw-CRDS). The balanced detection scheme (BD) added to the FRS could allow us to eliminate common mode noises like laser intensity fluctuation and interference fringes. The BD-FRS will coupled with a well-designed inlet sampling system to minimize HO2 wall losses, which will significantly improve the measurement sensitivity and accuracy. In parallel, the GSMA team will develop a prototype of FS-CRDS (WP3). Frequency stabilization of the CRDS will allow for minimization of the frequency drifts of the absolute position of the cavity modes (as well as the mode spacing) due to ambient temperature variations, therefore permitting a fast ON-line measurement mode (measurement on the maximum absorption of the line with an expected integration time of 1-3 seconds). The expected LoD would be of 6×10^7 molecules/cm^3 in 3 s integration time. In the WP4, the CRDS cavity will be integrated into the magnetic coil of the BD-FRS, leading to a hybridization of BD-FRS-FS-CRDS. The obtained instrument will be insensitive to laser intensity fluctuations, free of interference with diamagnetic molecules (H2O, CO2, CH4, etc...) and differential (therefore, calibration-free for CRDS measurement). Such original combination of two highly sensitive spectroscopic instruments will result in a LoD of about 10^6 molecule/cm^3 in 3 s. Finally in the WP5 coordinated by the PC2A team, the resulting instrument will be firstly tested and characterized in the CHARME chamber of the LPCA in comparison with the FAGE of the PC2A. After that, the developed instrument will be finally investigated and validated in the EU-SAPHIR chamber (Jülich) under realistic, near-atmosphere conditions.

Most living cells exhibit a difference in electrical potential across their plasma membrane resulting from differences in ion concentration maintained by ion channels and pumps. The membrane of a neuron can be suddenly (≈1 ms) depolarised (its intracellular potential rising from -70 mV to +30 mV) by the synchronised opening of these channels, stimulated by other neurons, thus generating an 'action potential' that spreads to other cells to which that neuron is connected by synapses. Monitoring this depolarisation thus provides information on synaptic transmission, which is essential for cognitive and neuromotor processes. The classical approach consists of measuring electrophysiological activity using micropipettes on a few cells at a time ("patch-clamp"), or with a microelectrode array able to record the extracellular potentials of a group of neurons. In recent decades, optical measurement methods have been introduced to obtain the electrical activity of a large number of cells simultaneously with high resolution. Apart from a few works exploiting the modulation of electroplasmonic effects of gold nanoparticles or semiconductor nanocrystal charges, these methods present a certain number of drawbacks (photobleaching, toxicity...) or limitations regarding the measurement of an extracellular electrophysiological signal. The objective of our project is to develop and biologically validate a new photoluminescent probe of the extracellular potential based on a transduction mechanism never explored for this application and which should lead to a very high spatiotemporal resolution. These probes are ferroelectric nanocrystals (FENC) doped with rare-earth ions (RE3+) whose spectral modulation of photon up-conversion (UC) will be detected as a function of the surrounding electrical potential. The variations of this potential, under the effect of the opening of the ion channels, modify the surface density of the polarization charges P of the FENC, making P vary which in turn leads to a deformation of the FENC by inverse piezoelectric effect, inducing finally a change of intensity of certain emission lines of UC. This process is supported by our recent observation of such a UC modulation in an FNCE exposed to an electric field. First, we will synthesize BaTiO3 NCFEs of size≈200 nm doped with Er3+ and Yb3+ ions and also test other matrices with stronger piezoelectric response, and other dopants. Ab initio calculations will help us determine the most favourable crystallographic sites for ion incorporation. We will characterise the intensity of the CU and its lifetime. Next, we will image the ferro/piezoelectric domains of individual NCFEs by piezoelectric force microscopy (PFM) where an oscillating potential is applied to the tip. We will aim to produce bright single-domain FENCs. We will quantify the variation of the UC spectrum during PFM measurements, as well as under ion flux from a discharge tip. Finally, we will test the ability of FENCs to detect changes in charge density in solution, before using them, after biofunctionalization, as optical sensors of near-membrane potential changes during electroporation, and then to monitor nerve regeneration. This highly interdisciplinary project requires the complementary skills of five teams, in the synthesis and characterisation of FENCs, optical spectroscopy and near-field probe microscopy, bio-conjugation of nanoparticles and bioelectrochemistry. This project exploiting the polarisation charges of ferroelectric nanosystems will open up a new field of applications beyond the biomedical one.