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Synchronous Miocene radiations and geographic-dependent diversification of pantropical Xylopia (Annonaceae).
No full textInternational audienc
Magneto-: Heavy neutral lepton search using Pu decays
No full textInternational audienceWe present experimental beta spectra of Pu as part of the Magneto- experiment aimed at searching for keV heavy neutral leptons (HNLs). Total 200 million beta decays are measured by metallic magnetic calorimeters (MMCs), representing the highest statistical precision achieved for Pu to date. The end-point energy of Pu beta decay is measured via in-situ alpha calibration, yielding a value of 21.52(2) keV. The differential decay rate of the first forbidden non-unique transition of Pu is described with a quadratic shape correction factor . Using these high-statistics spectra, we set an upper limit on the admixture of a 10.5 keV sterile neutrino to the electron neutrino at for HNL mass of 10.5 keV
LIM kinase/inhibitor binding study in cell lysates using microscale thermophoresis in the red spectrum
No full textInternational audienceBackground: Cellular function depends on complex molecular interactions that activate signaling pathways - central to drug discovery projects. LIM kinases (LIMKs) are attractive therapeutic targets implicated in various diseases, yet no clinically approved LIMK inhibitors exist, likely due to limited understanding of their molecular behavior under near-physiological conditions. This breach stems in part from the difficulty in purifying these proteins. To address this, there is a crucial need for a simple and rapid method to determine LIMK-inhibitor binding affinities (Kd values) directly in cell lysates, bypassing challenging purification and immobilization steps.Results: The monomeric near-infrared fluorescent protein miRFP670 (excitation/emission: 640/680 nm) is an advantageous fluorescent tag for microscale thermophoresis (MST) assays in cell lysates. The miRFP670-tagged LIMKs were successfully overexpressed in HEK293 cells, characterized, and validated by western blotting. MST assay conditions - including MST buffer composition and target storage - were carefully optimized and negative controls were consistently used to ensure data reproducibility as well as assay specificity. The MST conditions were as follows: miRFP670-kinases at a fixed concentration of a few tens of nM in cell lysate supplemented with 30 % (v/v) glycerol for convenient storage; 0.005 % (v/v) DMSO in the MST buffer; 37 ◦C; 20 % LED power; medium MST power; and standard capillaries. The presence of 0.1 % Triton X-100 in the MST buffer was essential to prevent protein aggregation, as evidenced by smooth MST time traces. The reproducibility and stability of signals across all capillaries attest to the optimality of the incubation conditions and the attainment of a stable binding equilibrium. This consistency also validates the robustness of the assay. MST analysis of cell lysates yielded Kd values for full-length and kinase domains and show strong agreement with literature where available. Notably, sub-micromolar Kd values were confirmed for the reference inhibitors LX7101, BMS-5, and TH-257, with slight differences observed between full-length LIMKs and their kinase domains - differences often overlooked in the literature.Significance and novelty: This work establishes the first detailed production, characterization, and use of miRFP670 in MST-based evaluation of biomolecular interactions under near-native conditions. miRFP670 operates in a spectral region (red) with minimal cellular autofluorescence, enhancing signal specificity and sensitivity. This approach offers a straightforward and broadly applicable, purification-free platform for early-stage drug discovery
Premature aging and neuropathic behaviours induced by an acute low-dose exposure to a sarin surrogate
No full textInternational audienceAcute poisoning from organophosphorus (OP) compounds induced a cholinergic toxidrome. Neurological complications may manifest weeks after the initial exposure, including muscle weakness and progressive loss of sensitivity. These symptoms may be analogous to those observed in elderly individuals. However, the delayed neurological impact of OP exposure has received limited attention and remains an under-explored area of research. The present study investigated the long-term effects of OP exposure on the sensorimotor system using a mouse model exposed to a sublethal dose of a sarin surrogate. The mice received a 0.5 LD50 dose of 4-nitrophenyl isopropylmethylphosphonate (NIMP), and were observed for a period of six months. Our results demonstrate that NIMP exposure induced a mild intoxication severity in mice, without affecting weight evolution. Behavioral evaluation, using locomotor and sensory tests, revealed that mice exhibited persistent muscle weakness and an increase in mechanical sensitivity. Six months after NIMP exposure, acetylcholinesterase activity remained inhibited in specific regions of the cerebral cortex, while the spinal cord exhibited a return to normal values. Positron emission tomography scans and microcomputed tomography imaging revealed alterations in cerebral glucose metabolism and bone density. Luminex multiplex immunoassay analyses revealed an increase in specific biomarkers of aging. The present study demonstrates that a sublethal dose of NIMP triggered premature aging phenotype, resulting in long-term sensorimotor impairments, neurometabolic and cellular disturbances. These findings underscore the importance of identifying intoxication hallmarks, even in cases of asymptomatic OP exposure
Damping RF waves with low reflection in simulations of slab or curved magnetized plasma: parametrization, verification and implementation of Bermudez Perfectly Matched Layers.
No full textInternational audienceMost Radio-Frequency antenna simulations in magnetic fusion require emulating radiation at infinity at some boundaries of the simulation domain. To this end, the Perfectly Matched Layer (PML) technique amounts to stretching artificially the (real) spatial coordinates into the complex plane. Following reference [1], this contribution parametrizes, tests numerically and implements unbounded stretching functions, whose only numerical limitations arise from the PML discretization: refining the mesh can reduce the spurious reflections from the PML arbitrarily low, at the expense of a larger numerical cost. We tune the PML to ensure low wave reflection in a prescribed spectral range [kn,min, kn,max] in a direction n, with a minimal discretization (i.e. at a minimal computational cost). We extensively quantify the reflection coefficients using 1D Finite Element simulations. The minimal discretization for a regular mesh scales as kn,max/kn,min. We extend the PML formulation to a cylindrical geometry, where the wave eigenmodes involve Bessel functions. We implement slab radial and parallel Bermudez PMLs in realistic multi-2D RF simulations [2], to attenuate the propagative Slow Waves parasitically emitted by the ITER ICRF antenna into a tenuous scrape-off layer
Prosumers: Grid vs. individual storage
No full textInternational audienceWe present a stylized microeconomic model to analyze solar panels and storage investment decisions of a representative consumer under either grid (credit regulation) or individual (price regulation) storage. We identify the conditions under which prosumers become storers. We show that solar technology must be more competitive under credit than price regulation for consumers to invest in storage. We calibrate our model using French data from 2023 and 2030 and consider batteries and fuel-cells as potential individual storage technologies. France’s current price regulation incentivizes investment in solar capacity, but not in storage. Conversely, credit regulation would immediately encourage energy storage. Looking ahead to 2030, both regulatory frameworks would incentivize energy storage. The distribution system operator prefers credit regulation, provided the regulator allows full energy recovery. Overall, energy storage enhances welfare under both regulatory frameworks
Plug-and-play learned proximal trajectory for 3D sparse-view X-ray computed tomography
No full textPlug-and-Play algorithms (PnP) have recently emerged as a powerful framework for solving inverse problems in imaging. They leverage the power of Gaussian denoising algorithms to solve complex optimization problems. This work focuses on the challenging task of 3D sparse-view X-ray computed tomography (CT). We propose to replace the Gaussian denoising network in Plug-and-Play with a restoration network, i.e. a network trained to remove arbitrary artifacts. We show that using a restoration prior tailored to the specific inverse problem improves the performances of Plug-and-Play algorithms. Besides, we show that plugging a basic restoration network into a PnP scheme is not sufficient to obtain good results. Thus, we propose a procedure to train the restoration network to be a robust approximation of a proximal operator along a pre-defined optimization trajectory. We demonstrate the effectiveness and scalability of our approach on two 3D Cone-Beam CT datasets and outperform state-of-the-art methods in terms of PSNR. Code is available at https://github.com/romainvo/ pnp-learned-proximal-trajectory</p
MIRI Deep Imaging Survey (MIDIS) of the Hubble Ultra Deep Field
No full textInternational audienceThe recently launched James Webb Space Telescope (JWST) is opening new observing windows on the distant universe. Among JWST's instruments, the Mid Infrared Instrument (MIRI) offers the unique capability of imaging observations at wavelengths \lambda > 5\mum. This enables unique access to the rest frame near infra-red (NIR, \mum) emission from galaxies at redshifts z>4 and the visual (Å) rest frame for z>9. We here report on the guaranteed time observations (GTO) from the MIRI European Consortium, of the Hubble Ultra Deep Field (HUDF), forming the MIRI Deep Imaging Survey (MIDIS), consisting of an on source integration time of hours in the MIRI/F560W (5.6 m) filter. To our knowledge, this constitutes the longest single filter exposure obtained with JWST of an extragalactic field as yet
Development of a numerical thermal-hydraulic model of the ELIPSE process
No full textInternational audienceWe developed a numerical solver to study the gas-liquid multiphase flow in the ELIPSE process developed at CEA Marcoule. The numerical strategy used to simulate its dynamics is particularly challenging because of the multi-scale nature of the flow, which involves both large gas pockets, formed during the injection of a submersed turbulent gas jet in a liquid flow, and small dispersed bubbles resulting from the breakup of these large-scale interfaces. To this purpose, the Volume Of Fluid method is coupled to a Lagrangian tracking of the emerging bubbles, by using an Adaptative Mesh Refinement strategy with a criterion of size to convert the smaller bubbles into Lagrangian objects. An LES model is used to describe the turbulent flow. By this way, we constructed the flow regime map as a function of the operating conditions of the reactor. Moreover, the heat balance is solved, and the numerical method is adapted to account for gas-liquid phase change occurring in the process. The whole simulation model allows investigating the influence of heat transfer on the flow features and gas distribution in the liquid bath
Experimental evaluation of multiaxial test-tailored specifications based on Fatigue Damage multi-Spectra
No full textInternational audienceIn the industrial sector, laboratory tests are frequently performed to evaluate the durability of structures under mechanical loads. These tests typically involve sequentially applied uniaxial loads, even though operational conditions are often multiaxial. To address this inconsistency, a new frequency-domain approach has been developed to generate test-tailored specifications for multiaxial vibration based on the Fatigue Damage multi- Spectrum (FDmS). This paper analyzes this procedure through experimental trials, showing the accuracy of the generated multiaxial test-tailored specifications, as well as its ability to synthesize and generate cross-correlations