150 research outputs found

    CARIOQA: Definition of a Quantum Pathfinder Mission

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    A strong potential gain for space applications is expected from the anticipated performances of inertial sensors based on cold atom interferometry (CAI) that measure the acceleration of freely falling independent atoms by manipulating them with laser light. In this context, CNES and its partners initiated a phase 0 study, called CARIOQA, in order to develop a Quantum Pathfinder Mission unlocking key features of atom interferometry for space and paving the way for future ambitious space missions utilizing this technology. As a cornerstone for the implementation of quantum sensors in space, the CARIOQA phase 0 aimed at defining the Quantum Pathfinder Mission's scenario and associated performance objectives. To comply with these objectives, the payload architecture has been designed to achieve long interrogation time and active rotation compensation on a BEC-based atom interferometer. A study of the satellite architecture, including all the subsystems, has been conducted. Several technical solutions for propulsion and attitude control have been investigated in order to guarantee optimal operating conditions (limitation of micro-vibrations, maximization of measurement time). A preliminary design of the satellite platform was performed.Comment: Proceedings of International Conference on Space Optics (ICSO) 2022; 3-7 October 2022; Dubrovnik; Croati

    Structural analysis and corrosion studies on an ISO 5832-9 biomedical alloy with TiO2 sol–gel layers

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    The aim of this study was to demonstrate the relationship between the structural and corrosion properties of an ISO 5832-9 biomedical alloy modified with titanium dioxide (TiO2) layers. These layers were obtained via the sol–gel method by acid-catalyzed hydrolysis of titanium isopropoxide in isopropanol solution. To obtain TiO2 layers with different structural properties, the coated samples were annealed at temperatures of 200, 300, 400, 450, 500, 600 and 800 C for 2 h. For all the prepared samples, accelerated corrosion measurements were performed in Tyrode’s physiological solution using electrochemical methods. The most important corrosion parameters were determined: corrosion potential, polarization resistance, corrosion rate, breakdown and repassivation potentials. Corrosion damage was analyzed using scanning electron microscopy. Structural analysis was carried out for selected TiO2 coatings annealed at 200, 400, 600 and 800 C. In addition, the morphology, chemical composition, crystallinity, thickness and density of the deposited TiO2 layers were determined using suitable electron and X-ray measurement methods. It was shown that the structure and character of interactions between substrate and deposited TiO2 layers depended on annealing temperature. All the obtained TiO2 coatings exhibit anticorrosion properties, but these properties are related to the crystalline structure and character of substrate–layer interaction. From the point of view of corrosion, the best TiO2 sol–gel coatings for stainless steel intended for biomedical applications seem to be those obtained at 400 C.This study was supported by Grant No. N N507 501339 of the National Science Centre. The authors wish to express their thanks to J. Borowski (MEDGAL, Poland) for the Rex 734 alloy

    COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

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    Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available

    Neodymium isotope constraints on provenance, dispersal, and climate-driven supply of Zambezi sediments along the Mozambique Margin during the past ∌45,000 years

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    Marine sediments deposited off the Zambezi River that drains a considerable part of the southeast African continent provide continuous records of the continental climatic and environmental conditions. Here we present time series of neodymium (Nd) isotope signatures of the detrital sediment fraction during the past ~45,000 years, to reconstruct climate-driven changes in the provenance of clays deposited along the Mozambique Margin. Coherent with the surface current regime, the Nd isotope distribution in surface sediments reveals mixing of the alongshore flowing Zambezi suspension load with sediments supplied by smaller rivers located further north. To reconstruct past changes in sediment provenances, Nd isotope signatures of clays that are not significantly fractionated during weathering processes have been obtained from core 64PE304-80, which was recovered just north of the Zambezi mouth at 1329 m water depth. Distinctly unradiogenic clay signatures (ENd values <214.2) are found during the Last Glacial Maximum, Heinrich Stadial 1, and Younger Dryas. In contrast, the Nd isotope record shows higher, more radiogenic isotope signatures during Marine Isotope Stage 3 and between ~15 and ~5 ka BP, the latter coinciding with the timing of the northern hemisphere African Humid Period. The clay-sized sediment fraction with the least radiogenic Nd isotope signatures was deposited during the Holocene, when the adjacent Mozambique Shelf became completely flooded. In general, the contribution of the distinctly unradiogenic Zambezi suspension load has followed the intensity of precession-forced monsoonal precipitation and enhanced during periods of increased southern hemisphere insolation and high-latitude northern hemispheric climate variability

    Comparative Therapeutic Effects of Velaglucerase Alfa and Imiglucerase in a Gaucher Disease Mouse Model

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    Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid ÎČ-glucosidase (GCase). Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bony manifestations. Here, similar in vitro enzymatic properties, and in vivo pharmacokinetics and pharmacodynamics (PK/PD) and therapeutic efficacy of GCase were found with two human GCases, recombinant GCase (CHO cell, imiglucerase, Imig) and gene-activated GCase (human fibrosarcoma cells, velaglucerase alfa, Vela), in a Gaucher mouse, D409V/null. About 80+% of either enzyme localized to the liver interstitial cells and <5% was recovered in spleens and lungs after bolus i.v. injections. Glucosylceramide (GC) levels and storage cell numbers were reduced in a dose (5, 15 or 60 U/kg/wk) dependent manner in livers (60–95%) and in spleens (∌10–30%). Compared to Vela, Imig (60 U/kg/wk) had lesser effects at reducing hepatic GC (p = 0.0199) by 4 wks; this difference disappeared by 8 wks when nearly WT levels were achieved by Imig. Anti-GCase IgG was detected in GCase treated mice at 60 U/kg/wk, and IgE mediated acute hypersensitivity and death occurred after several injections of 60 U/kg/wk (21% with Vela and 34% with Imig). The responses of GC levels and storage cell numbers in Vela- and Imig-treated Gaucher mice at various doses provide a backdrop for clinical applications and decisions

    Barcoding T Cell Calcium Response Diversity with Methods for Automated and Accurate Analysis of Cell Signals (MAAACS)

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    International audienceWe introduce a series of experimental procedures enabling sensitive calcium monitoring in T cell populations by confocal video-microscopy. Tracking and post-acquisition analysis was performed using Methods for Automated and Accurate Analysis of Cell Signals (MAAACS), a fully customized program that associates a high throughput tracking algorithm, an intuitive reconnection routine and a statistical platform to provide, at a glance, the calcium barcode of a population of individual T-cells. Combined with a sensitive calcium probe, this method allowed us to unravel the heterogeneity in shape and intensity of the calcium response in T cell populations and especially in naive T cells, which display intracellular calcium oscillations upon stimulation by antigen presenting cells

    Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly

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    Type I lissencephaly or agyria-pachygyria is a rare developmental disorder which results from a defect of neuronal migration. It is characterized by the absence of gyri and a thickening of the cerebral cortex and can be associated with other brain and visceral anomalies. Since the discovery of the first genetic cause (deletion of chromosome 17p13.3), six additional genes have been found to be responsible for agyria–pachygyria. In this review, we summarize the current knowledge concerning these genetic disorders including clinical, neuropathological and molecular results. Genetic alterations of LIS1, DCX, ARX, TUBA1A, VLDLR, RELN and more recently WDR62 genes cause migrational abnormalities along with more complex and subtle anomalies affecting cell proliferation and differentiation, i.e., neurite outgrowth, axonal pathfinding, axonal transport, connectivity and even myelination. The number and heterogeneity of clinical, neuropathological and radiological defects suggest that type I lissencephaly now includes several forms of cerebral malformations. In vitro experiments and mutant animal studies, along with neuropathological abnormalities in humans are of invaluable interest for the understanding of pathophysiological mechanisms, highlighting the central role of cytoskeletal dynamics required for a proper achievement of cell proliferation, neuronal migration and differentiation

    Computational Homogenization of Architectured Materials

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    Architectured materials involve geometrically engineered distributions of microstructural phases at a scale comparable to the scale of the component, thus calling for new models in order to determine the effective properties of materials. The present chapter aims at providing such models, in the case of mechanical properties. As a matter of fact, one engineering challenge is to predict the effective properties of such materials; computational homogenization using finite element analysis is a powerful tool to do so. Homogenized behavior of architectured materials can thus be used in large structural computations, hence enabling the dissemination of architectured materials in the industry. Furthermore, computational homogenization is the basis for computational topology optimization which will give rise to the next generation of architectured materials. This chapter covers the computational homogenization of periodic architectured materials in elasticity and plasticity, as well as the homogenization and representativity of random architectured materials
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