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NanoPULSE: The First Micromixing Method Delivering Consistent Lipid Nanoparticle Formulations Seamlessly Across All Scales
No full textInternational audienceThe ongoing development of RNA-based vaccines and therapies employing lipid nanoparticle (LNP) formulations is currently hindered by the absence of a unified formulation technology spanning seamlessly the entire development pipeline – from microliter-scale screening to tens-of-liters manufacturing. This gap forces drug developers to transition between different formulation techniques during scale-up. This poses significant challenges as the manufacturing process critically affects all key LNP quality parameters such as particle size, polydispersity index (PDI), drug loading efficiency, or morphology, leading to prolonged, expensive, and sometimes unsuccessful drug development. Currently, state-of-the-art methods predominantly rely on microfluidic-based mixing, which excels at the microliter scale by providing precise mixing under laminar flow conditions. However, these systems face substantial limitations in scalability and throughput. In contrast, T-mixers and impingement jet mixers (IJM) are better suited for large-scale production, but struggle to accommodate the low-volume formulations essential for early-stage development. Here, we introduce NanoPULSE, a novel, patented active micromixing technology that ensures consistent LNP characteristics across all production volumes, from µL-scale screening to continuous, high-volume, aggregation-free manufacturing. The device employs high-frequency valves with rapid response times to sequentially inject aqueous and organic phases into a T-junction, creating fringes that enhance the diffusion within the mixing channel according to the Taylor-Aris Dispersion principle. Lagrangian numerical simulations, performed using a Python-based code, have been used to predict the impact of different input parameters on particle characteristics and optimize the mixing channel’s dimensions. These simulations have led to the introduction of a novel index to quantify the mixing efficiency of NanoPULSE. Dynamic light scattering (DLS) measurements confirm that both empty and RNA-loaded LNPs maintain constant sizes over a production volume range from 500 µL to 4 L, with polydispersity indexes (PDI) remaining consistent and below 0.2, validating the seamless scalability of the technology. The encapsulation efficiencies/yield and structural morphology of RNA-loaded LNPs produced with NanoPULSE are characterized at different scales and compared to those synthesized using standard microfluidic approaches. Finally, by modulating the injection periods of the solvents, NanoPULSE can produce LNPs of variable sizes using the same formulation. The nanoparticle sizes and PDIs measured at different input parameters are correlated with the simulation results, linking the mixing performance to the nanoparticle characteristics, paving the way for a predictive model of LNP synthesis. These findings underscore the promising repeatability, scalability, and efficiency of LNP synthesis via NanoPULSE
« Informer et s’informer », Dossier E1 [extraits de W. Shakespeare et G. Orwell, dessin de J. Keppler, Jr] (réédition)
No full textNational audiencePréparation à l'épreuve écrite de composition du CAPES externe d'anglais 2026 : mise en relation de deux documents littéraires ou civilisationnels, joints à un troisième document, de nature iconographique. Concours : Niveau Master 2
Icy Moons as Probes of Carbon-Rich Conditions During Giant Planet Formation
No full textInternational audienceThe densities and moments of inertia of Jovian and Saturnian icy moons, dwarf planets, and other trans-Neptunian objects (TNOs) suggest the presence of a significant low-density carbonaceous component in their rocky cores. In a homogeneous accretion scenario, where these components are mixed in solar proportions, ices differentiate from the carbon-rich refractory core, while silicate hydration may occur. Thermal models that account for the presence of carbonaceous matter indicate that originally hydrated silicates are now largely dehydrated in the refractory cores of large moons and dwarf planets, due to interactions with volatiles released by the metamorphism of carbonaceous matter.Progressive gas release from the slowly warming, carbonaceous matter-rich cores may sustain, up to the present day, the replenishment of ice-ocean layers with organics and volatiles, as well as outgassing to the surface. This process accounts for the observation of nitrogen, light hydrocarbons, and complex organic molecules at the surface, in the atmospheres, or in the plumes emanating from moons and dwarf planets. The formation of large carbon-rich icy bodies in the outer solar system suggests that a carbon-rich environment prevailed during ice giant planet formation—a scenario that could also lead to the formation of carbon-rich planets at the outskirts of extrasolar systems.In the Neptunian system, Triton—presumed to be a captured TNO—shares density and surface composition characteristics with other large TNOs, including Pluto, Eris, Makemake, Gonggong, Quaoar, and others. Notably, the carbon-bearing molecules at the icy surfaces of TNOs shift from CO₂-dominated compositions in smaller objects (Pinilla-Alonso et al., 2024) to CH₄-rich compositions in the largest TNOs, including Triton (Brown, 2012; Emery et al., 2024; Grundy et al., 2024).In the Uranian system, the latest estimates of regular satellite masses (Jacobson, 2014) reveal a power-law relationship between size and density, reflecting varying rock/ice ratios caused by fractionation processes (Reynard and Sotin, 2025). This relationship is explained by mild enrichment of rock relative to ice in the solids that aggregated to form the moons, following Rayleigh's law of distillation (Rayleigh, 1896). In the outer solar nebula, Rayleigh fractionation may account for the separation of a rock-dominated reservoir and an ice-carbon-dominated reservoir, now represented by CI carbonaceous chondrites/type-C asteroids and comets, respectively. Potential consequences for the composition of Uranus’s moons and targets for future exploration are discussed. Acknowledgement. This work was supported by Institut National des Sciences de l’Univers through Programme National de Planétologie, by the Agence Nationale de la Recherche (ANR, project OSSO BUCO, ANR-23-CE49-0003) and by the European Union (ERC, PROMISES, project #101054470). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them
From photographic record to virtual worlds: the case of Apollo and rover missions
No full textEPSC-DPS Joint Meeting 2025, Helsinkin (Finland), 7-12 Septembre 2025International audienceThanks to the computational power of current graphic cards, photographic archives can be turned into three dimensions virtual worlds. The Structure from Motion photogrammetry technique simply requires a set of overlapping images, acquired from different viewing points, to reconstruct in 3D the observed landscape elements. This technique can also be applied on rock samples characterized in the laboratory. We have applied this technique to scanned photographs of the Moon acquired during the Apollo 17 mission [1, 2, 3]. In the case of the “Station 6” geological waypoint investigated by the astronauts at Taurus Littrow during their third EVA, we found that 154 images can be automatically aligned into a single photogrammetric project [4]. This allows to generate a textured polygonal mesh of the nearly complete Station 6 area and to retrieve the respective size and orientation of the large main boulders that bounced down the North Massif, coming to rest at a change in slope. We have also shown in [4] that 3D reconstruction process also works for lunar rock samples that have been photographed during the 70s before being sawed for analysis. This allows for example to setup a Virtual Reality (VR) immersive simulation where the user can replace the samples at their exact location and orientation directly on their parent boulder. Satellite images such as Kaguya/TC or LRO/LROC can be used to provide the general context in the VR simulation. They can eventually be completed by other cartographic products, as would be done in a GIS system, to include for example false color composites from Clementine to give some compositional context to the in situ sites. Following the work on Station 6, we have undergone new 3D reconstructions on the next geological waypoint, the Station 7. In this case, we were able to reconstruct three rock samples in 3D using 96 LPI laboratory archived photographs. Their parent boulder and the local lunar ground was reconstructed using 85 Apollo images. These new 3D elements have been added in the previous VR simulation (Figure 1). The 3D analysis can be used for outreach, education or scientific investigation. For outreach, the use of an application designed for a standalone VR headset provides the most versatile and cost effective solution. More ambitious projects (with a wider high-resolution cartographic coverage and several highly detailed digital outcrop models) would benefit from a VR headset connected by a cable to a gaming computer. In addition to students, this kind of 3D reconstructions could also be used in astronaut training simulations to provide realistic cases. On the science side, it allows to investigate problematics linked for example to the effect of space weathering on lunar surface rocks. We could also envisage deriving the absolute position and orientation of specific lunar rock samples, which could give new insight and constrains to paleo-magnetic studies [5, 6]. Forthcoming robotic (and possibly manned) missions could take advantage of these new photogrammetric capabilities to optimize the image acquisition strategy during the in situ exploration phase.Figure 1: Perspective view of a Virtual Reality scene of Station 7 reconstructed using photogrammetry on a set of Apollo photographs. The ground is mainly retrieved from the 360° panorama taken by G. Cernan. An LRO image provides the context. Astronaut’s footprints and rover tracks appear readily in the textured photogrammetric ground. The LRV is a 3D model added to give a better sense of scales. Sample 77115 has been also reconstructed in 3D from archived photographs and replaced at its original location on the parent boulder. Station 6, located at 475m and also included in the VR simulation, is seen in the upper lef
Immunomodulatory function of chitosan is dependent on complement receptor 3
No full textInternational audienc
Singular walks in the quarter plane and Bernoulli numbers
No full textWe consider singular (aka genus 0) walks in the quarter plane and their associated generating functions , which enumerate the walks starting from the origin, of fixed endpoint (encoded by the spatial variables and ) and of fixed length (encoded by the time variable ). We first prove that the previous series can be extended up to a universal value of (in the sense that this holds for all singular models), namely , and we provide a probabilistic interpretation of . As a second step, we refine earlier results in the literature and show that is indeed differentially transcendental for any . Moreover, we prove that is strongly differentially transcendental. As a last step, we show that for certain models the series expansion of is directly related to Bernoulli numbers. This provides a second proof of its strong differential transcendence
How to Assess Fungal Contamination of Indoor Air in Dwellings of Patients with Cystic Fibrosis?
No full textInternational audienceAbstract The copper ionophore disulfiram (DSF) is commonly used to treat chronic alcoholism and has potential anti-cancer activity. Using a yeast-based screening assay of FDA-approved compounds, DSF was herein identified for its ability to improve oxidative phosphorylation-dependent growth of various yeast models of mitochondrial diseases caused by a wide range of defects in ATP synthase, complexes III and IV, cardiolipin remodeling, maintenance and translation of the mitochondrial genome. This compound also showed beneficial effects in cells derived from patients suffering from Barth or MELAS syndromes, two mitochondrial diseases associated respectively with a lack in cardiolipin remodeling and protein synthesis inside the organelle. We provide evidence that the rescuing activity of DSF results from its ability to transport copper ions across biological membranes. Indeed, other copper ionophores (pyrithione and elesclomol) and supplementation of the growth media with copper ions had also beneficial effects in yeast and human cells with dysfunctional mitochondria. Our data suggest that the copper-dependent rescuing activity in these cells results from a better capacity to assemble cytochrome c oxidase. Altogether, our findings hold promise for the development of new therapeutic strategies for mitochondrial disorders
Veille
No full textInternational audienceVeille normative et juridique mai/juin 2025: assurance des collectivités territoriales, rapport 2024 ACP
Synovial Biomarkers C-Reactive Protein and Calprotectin for Diagnosing Chronic Periprosthetic Joint Infection: A Prospective Multicenter Evaluation
No full textInternational audienceBackground: The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice, and synovial fluid (SF) analysis is a valuable diagnostic tool. Recently, two synovial biomarkers (leukocyte esterase strip test and alpha-defensin [AD]) have been incorporated within the MSIS (Musculoskeletal Infection Society) algorithm for PJI diagnosis. Although AD is promising, with high sensitivity and specificity, it remains expensive. Calprotectin, another protein released upon activation of articular neutrophils, offers a low-cost alternative. Calprotectin and CRP (serum C-reactive protein) joint determination is now feasible in routine laboratory practice. This study aimed to evaluate the diagnostic performance of two synovial biomarkers, calprotectin and CRP, for PJI diagnosis.Methods: From April 2022 to June 2024, all adult patients undergoing preoperative or intraoperative aspiration of hip or knee prosthetic joints were included in this prospective, multicenter, noninterventional study. Patients who had prosthetic implantation less than three months prior or those who had systemic inflammatory diseases were excluded. For each SF sample, calprotectin and CRP synovial measurements were performed. Patients were classified as infected (PJI group) or noninfected (non-PJI group) based on decisions made during multidisciplinary meetings. During the study period, 157 patients were enrolled. There were 59 patients excluded due to insufficient synovial fluid volume or failure to meet inclusion criteria. There were 52 patients classified into the PJI group and 46 into the non-PJI group.Results: The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of synovial calprotectin were 94.23%, 78.26%, 4.24, and 0.07, respectively, while those of synovial CRP were 80.77%, 86.96%, 6.19, and 0.22, respectively.Conclusions: The present study demonstrates that synovial calprotectin and synovial CRP assays have excellent accuracy for the diagnosis of PJI. These findings suggest that these two synovial biomarkers should be incorporated into a new decision-making algorithm for PJI diagnosis