The Comparative Exploration of the Ice Giant Planets with Twin Spacecraft: Unveiling the History of our Solar System

In the course of the selection of the scientific themes for the second and third L-class missions of the Cosmic Vision 2015-2025 program of the European Space Agency, the exploration of the ice giant planets Uranus and Neptune was defined "a timely milestone, fully appropriate for an L class mission". Among the proposed scientific themes, we presented the scientific case of exploring both planets and their satellites in the framework of a single L-class mission and proposed a mission scenario that could allow to achieve this result. In this work we present an updated and more complete discussion of the scientific rationale and of the mission concept for a comparative exploration of the ice giant planets Uranus and Neptune and of their satellite systems with twin spacecraft. The first goal of comparatively studying these two similar yet extremely different systems is to shed new light on the ancient past of the Solar System and on the processes that shaped its formation and evolution. This, in turn, would reveal whether the Solar System and the very diverse extrasolar systems discovered so far all share a common origin or if different environments and mechanisms were responsible for their formation. A space mission to the ice giants would also open up the possibility to use Uranus and Neptune as templates in the study of one of the most abundant type of extrasolar planets in the galaxy. Finally, such a mission would allow a detailed study of the interplanetary and gravitational environments at a range of distances from the Sun poorly covered by direct exploration, improving the constraints on the fundamental theories of gravitation and on the behaviour of the solar wind and the interplanetary magnetic field.Comment: 29 pages, 4 figures; accepted for publication on the special issue "The outer Solar System X" of the journal Planetary and Space Science. This article presents an updated and expanded discussion of the white paper "The ODINUS Mission Concept" (arXiv:1402.2472) submitted in response to the ESA call for ideas for the scientific themes of the future L2 and L3 space mission

Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo

The proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. In vitro, Ascl1 induces efficient reprogramming of proliferative astroglia from the early postnatal cerebral cortex into interneuron-like cells. Here, we examined whether Ascl1 can similarly induce neuronal reprogramming of glia undergoing proliferation in the postnatal mouse cerebral cortex in vivo. Toward this goal, we targeted cortical glia during the peak of proliferative expansion (i.e., postnatal day 5) by injecting a retrovirus encoding for Ascl1 into the mouse cerebral cortex. In contrast to the efficient reprogramming observed in vitro, in vivo Ascl1-transduced glial cells were converted into doublecortin-immunoreactive neurons only with very low efficiency. However, we noted a drastic shift in the relative number of retrovirus-transduced Sox10-positive oligodendrocyte progenitor cells (OPCs) as compared to glial fibrillary acidic protein (GFAP)-positive astrocytes. Genetic fate mapping demonstrated that this increase in OPCs was not due to Ascl1-mediated astrocyte-to-OPC fate conversion. Rather, EdU incorporation experiments revealed that Ascl1 caused a selective increase in proliferative activity of OPCs, but not astrocytes. Our data indicate that rather than inducing neuronal reprogramming of glia in the early postnatal cortex, Ascl1 is a selective enhancer of OPC proliferation.</p

MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders

Intoxication à la metformine en réanimation : étude clinique, pronostique et pharmacocinétique

Rationale: metformin is the most prescribed anti-diabetic drug in the world. Its main complication called metformin associated lactic acidosis (MALA) is rare, but potentially fatal. The most common cause is the incidental metformin overdose, often triggered by acute renal failure or sepsis. Self-poisoning seems to have a better prognosis. We aimed to compare the self-poisonings and incidental overdoses and assess the prognostic factors of mortality. We also wished to investigate the relationships between plasma metformin and blood lactate levels as well as describe thepharmacokinetics of metformin when possible. Methods: we conducted a single-center retrospective observational study including all successive patients admitted in the Department of Medical and Toxicological Critical Care in Lariboisière Hospital between 2007 and 2016 for metformin poisoning defined by plasma metformin concentration > 2 mg/L and analyzed all the registry of data from the Phamaco-toxicology Laboratory in Cochin Hospital. Results: eighty-seven patients were included. Chronically metformin-overdosed patients differed from self-metformin-poisoned patients mainly by their co-morbidities and their presentation severity like the SOFA score on admission (p10 mmoL/L (OR=8.80), blood metforminc >10mg/L (OR=10.40) and prothrombin ratio 2 mg/L et analysé le registre des données du laboratoire de pharmaco-toxicologie de l’Hôpital Cochin. Résultats : quatre-vingt-sept patients ont été inclus. Les patients intoxiqués par surdosage accidentel différaient de ceux intoxiqués par ingestion volontaire, par leurs comorbidités et la sévérité du tableau clinique représentée notamment par le score SOFA à l’admission (p10 mmol/L (OR=8,8), une metforminémie à l’admission >10 mg/L (OR=10,4) et un taux de prothrombine <50% (OR=12,9). Un modèle pharmacocinétique a été obtenu à partir des données de deux patients admis pour surdosage accidentel. La relation lactatémie/metforminémie était prédite par un modèle sigmoïdal Emax. Conclusion : l’intoxication à la metformine est grave, même après ingestion volontaire à but suicidaire. Notre étude confirme les probables différences de mécanisme de toxicité entre ingestion volontaire et surdosage. La mesure de la metforminémie intra-érythrocytaire pourrait permettre de mieux en comprendre les mécanismes de toxicité et de prédire l’évolution en réanimation

Lewis acid mediated cyclisation of methylenecyclopropane derivatives

This thesis is concerned with the synthesis, and cyclisation of compounds containing a methylenecyclopropane moiety. Special interest is given to the Lewis acid mediated cyclisation of methylenecyclopropyl ketones and ketals, which proceed with high yields of highly functionalised carbocycles.Chapter 1 discussed the synthesis and the cyclisation of methylenecyclopropyl ketones and aldehydes 122, which gave cyclised compounds 125 and 126. (Fig. 8562A).In addition, a rapid method for the preparation of precursors for the Lewis acid mediated cyclisation of methylenecyclopropane derivatives was developed with addition of methylenecyclopropyl cuprate to conjugated ketones.Chapter 2 focused on the cascade process of 1,2-disubstituted methylenecyclopropanes with first cyclisation induced by Lewis acid to give an allyl cation intermediate which can be trapped in a cycloaddition reaction.Chapter 3 also discussed the cyclisation of 1,1-disubsittuted methylenecyclopropane derivatives mediated by Lewis acid, especially the synthesis of spirocycle compounds.Chapter 4 discussed the effect of a silyl group on the cyclisation reaction. Ketone 300 gave, under treatment with Lewis acid, cyclised compounds 303 and 304 in very good yields, due presumably to the ability of silicon to stabilise β-carbocation intermediate 301. (Fig. 8562B).Chapter 5 is concerned with the development of a cascade process as the silicon atom can be used to transfer allyl and phenyl groups. (Fig. 8562C).Finally Chapter 6 is concerned with an attempt, which failed, to synthesise the natural product Norketoagarofuran.</p

Antibiothérapie des pneumopathies hospitalisées après passage aux urgences (analyse rétrospective sur 11 ans)

Objectif : Déterminer l'évolution entre 2002 et 2012 des céphalosporines de 3ème génération dans les pneumopathies hospitalisées en services de médecine après passage aux urgences et analyser les autres classes d'antibiotiques dans cette pathologie de l'ambulatoire aux urgences. Matériels et méthodes : Série rétrospective monocentrique de patients hospitalisés pour pneumopathie après administration d'antibiotiques aux urgences adultes sur onze années consécutives. L'analyse de l'évolution a été faite en fonction du pourcentage de patients traités par céphalosporines de 3ème génération puis une régression logistique a été réalisée pour rendre indépendantes les années en fonction de facteurs de risques identifiés. L'analyse des autres antibiotiques a été réalisée en fonction du pourcentage de patients traités pour chacune des classes. Résultats : Sept cents trente-deux patients ont été inclus. L'âge médian est de 78 ans. Les scores de FINE et REAICU médians sont de 4 et 4. La mortalité est de 9,7%. 124 patients (16,8%) avaient reçu une antibiothérapie ambulatoire préalable à l'admission aux urgences dont 31,5% était représentée par l'association amoxicilline-acide clavulanique. La prescription de C3G augmente entre le début (13,9%) et la fin de l'étude (29,5%), indépendamment (p < 0,05) des facteurs de risque de prescription (Score REAICU élevé, Remplissage vasculaire, Immunodépression ou antibiothérapie dans les 3 mois précédents). Dans le même temps les prescriptions d'amoxicilline-acide clavulanique sont passées de 70,8% en début d'étude à 57,4% en fin d'étude. Conclusion : Notre étude met en évidence une forte augmentation de la prescription de C3G, classe à fort potentiel d'émergence de bactéries résistantes, dans les PAC sur 11 années. De l'ambulatoire à l'hôpital, l'utilisation raisonnée des antibiotiques est un devoir au niveau individuel et collectif si nous ne voulons pas qu'ils deviennent des médicaments inefficaces et obsolètesNANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

ETUDE DE COUCHES D'ADSORPTION DE MACROMOLECULES A L'INTERFACE CHAMPAGNE/AIR (APPLICATION DE LA METHODE DE LA GOUTTE PENDANTE A LA PREVISION DES PROPRIETES MOUSSANTES)

PARIS-BIUSJ-Physique recherche (751052113) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Targeted temperature management for non-shockable cardiac arrests: the debate must go on

International audienc

Thermomechanical Effects in PVTα Measurements

Knowledge of the different properties of thermoset composite materials is of great importance for the manufacturing of high quality composite parts. The resin bulk modulus is one of them and is essential to define the composite parts compressive behaviour under uniform compression. The evolution of this property with temperature and conversion degree of reaction is a challenging task and has been tentatively measured with a home-made apparatus, named PVTα, on which temperature, volume change and degree of cure are simultaneously recorded. But as the sample is contained in a non-reactive and deformable capsule, which mechanical behaviour may interfere with the measurement, a validation is required. The aim of this work is to develop a finite element model of the problem in order to simulate the thermal mechanical behaviour of the sample and the capsule, and so to validate the measurement process. The multiphysical numerical model accounts for phase change kinetics and non-linear thermal properties as well as thermo-dependent elastic properties, all problems being solved through a strong iterative coupling scheme. Mechanical contact problems between the capsule and the resin sample are handled through a penalization method contact algorithm which enables to capture the effects of chemical and thermal shrinkage in the sample and the capsule. The heterogeneous stress state generated by the material transformation is assumed to induce heterogeneous strain states which may lead to misinterpretations of macroscopic measurements. This model is a first approach and will be improved using a more sophisticated rheological model. Nevertheless, results show that the usual experimental analysis method can be used as long as the gel point is not reached. After a certain conversion degree, the measured bulk modulus is different from the effective one so corrections have to be brought.</jats:p