199 research outputs found
Multilayer multifunctional advanced coatings for receivers of concentrated solar power plants
International audienceThe extending market of concentrated solar power plants requires high-temperature materials for solar surface receivers that would ideally heat an air coolant beyond 1300 K. This work presents investigation on high-temperature alloys with ceramic coatings (AlN or SiC/AlN stacking) to combine the properties of the substrate (creep resistance, machinability) and of the coating (slow oxidation kinetics, high solar absorptivity). The first results showed that high temperature oxidation resistance and optical properties of metallic alloys were improved by the different coatings. However, the fast thermal shocks led to high stress levels not compatible due to the differences in thermal expansion coefficients
Anchoring Secreted Proteins in Endoplasmic Reticulum by Plant Oleosin: The Example of Vitamin B12 Cellular Sequestration by Transcobalamin
BACKGROUND: Oleosin is a plant protein localized to lipid droplets and endoplasmic reticulum of plant cells. Our idea was to use it to target functional secretory proteins of interest to the cytosolic side of the endoplasmic reticulum of mammalian cells, through expressing oleosin-containing chimeras. We have designed this approach to create cellular models deficient in vitamin B12 (cobalamin) because of the known problematics associated to the obtainment of effective vitamin B12 deficient cell models. This was achieved by the overexpression of transcobalamin inside cells through anchoring to oleosin. METHODOLOGY: chimera gene constructs including transcobalamin-oleosin (TC-O), green fluorescent protein-transcobalamin-oleosin (GFP-TC-O) and oleosin-transcobalamin (O-TC) were inserted into pAcSG2 and pCDNA3 vectors for expression in sf9 insect cells, Caco2 (colon carcinoma), NIE-115 (mouse neuroblastoma), HEK (human embryonic kidney), COS-7 (Green Monkey SV40-transfected kidney fibroblasts) and CHO (Chinese hamster ovary cells). The subcellular localization, the changes in vitamin B12 binding activity and the metabolic consequences were investigated in both Caco2 and NIE-115 cells. PRINCIPAL FINDINGS: vitamin B12 binding was dramatically higher in TC-O than that in O-TC and wild type (WT). The expression of GFP-TC-O was observed in all cell lines and found to be co-localized with an ER-targeted red fluorescent protein and calreticulin of the endoplasmic reticulum in Caco2 and COS-7 cells. The overexpression of TC-O led to B12 deficiency, evidenced by impaired conversion of cyano-cobalamin to ado-cobalamin and methyl-cobalamin, decreased methionine synthase activity and reduced S-adenosyl methionine to S-adenosyl homocysteine ratio, as well as increases in homocysteine and methylmalonic acid concentration. CONCLUSIONS/SIGNIFICANCE: the heterologous expression of TC-O in mammalian cells can be used as an effective strategy for investigating the cellular consequences of vitamin B12 deficiency. More generally, expression of oleosin-anchored proteins could be an interesting tool in cell engineering for studying proteins of pharmacological interest
Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization
Background and Objectives Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half of all patients. We aimed to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD while identifying novel phenotypes and candidate genes. Methods A case series of patients of all ages with undiagnosed GWMD despite extensive standard-of-care paraclinical studies were recruited between April 2017 and December 2019 in a collaborative study at the Bellvitge Biomedical Research Institute (IDIBELL) and neurology units of tertiary Spanish hospitals. We ran sWES and WGS and applied our interactome-prioritization algorithm based on the network expansion of a seed group of GWMD-related genes derived from the Human Phenotype Ontology terms of each patient. Results We evaluated 126 patients (101 children and 25 adults) with ages ranging from 1 month to 74 years. We obtained a first molecular diagnosis by singleton WES in 59% of cases, which increased to 68% after annual reanalysis, and reached 72% after WGS was performed in 16 of the remaining negative cases. We identified variants in 57 different genes among 91 diagnosed cases, with the most frequent being RNASEH2B, EIF2B5, POLR3A, and PLP1, and a dual diagnosis underlying complex phenotypes in 6 families, underscoring the importance of genomic analysis to solve these cases. We discovered 9 candidate genes causing novel diseases and propose additional putative novel candidate genes for yet-to-be discovered GWMD. Discussion Our strategy enables a high diagnostic yield and is a good alternative to trio WES/WGS for GWMD. It shortens the time to diagnosis compared to the classical targeted approach, thus optimizing appropriate management. Furthermore, the interactome-driven prioritization pipeline enables the discovery of novel disease-causing genes and phenotypes, and predicts novel putative candidate genes, shedding light on etiopathogenic mechanisms that are pivotal for myelin generation and maintenance
Optimising monitoring in the management of Crohn's disease: a physician's perspective.
Management of Crohn's disease has traditionally placed high value on subjective symptom assessment; however, it is increasingly appreciated that patient symptoms and objective parameters of inflammation can be disconnected. Therefore, strategies that objectively monitor inflammatory activity should be utilised throughout the disease course to optimise patient management. Initially, a thorough assessment of the severity, location and extent of disease is needed to ensure a correct diagnosis, identify any complications, help assess prognosis and select appropriate therapy. During follow-up, clinical decision-making should be driven by disease activity monitoring, with the aim of optimising treatment for tight disease control. However, few data exist to guide the choice of monitoring tools and the frequency of their use. Furthermore, adaption of monitoring strategies for symptomatic, asymptomatic and post-operative patients has not been well defined. The Annual excHangE on the ADvances in Inflammatory Bowel Disease (IBD Ahead) 2011 educational programme, which included approximately 600 gastroenterologists from 36 countries, has developed practice recommendations for the optimal monitoring of Crohn's disease based on evidence and/or expert opinion. These recommendations address the need to incorporate different modalities of disease assessment (symptom and endoscopic assessment, measurement of biomarkers of inflammatory activity and cross-sectional imaging) into robust monitoring. Furthermore, the importance of measuring and recording parameters in a standardised fashion to enable longitudinal evaluation of disease activity is highlighted.Peer reviewe
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
Meeting abstrac
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
Highly compact micro-machined coplanar bandpass filter
Highly compact micro-machined coplanar bandpass filters based on end-coupled half-wavelength and quarter-wavelength resonators topologies have been investigated. Simple gap and interdigitated capacitive discontinuities have been modeled through an appropriate technique and have been implemented in order to achieve low loss and narrow bandpass membrane micromachined filters.Excellent performances,similar to the state of the art, together with an important improvement in term of compactness have been achieved
Couverture vaccinale à 6 mois et 2 ans chez le grand prématuré (étude de cohorte)
La grande prématurité, définie par une naissance avant 33 semaines d'aménorrhée est en augmentation en France depuis 1995. Elle représente environ 10000 naissances par an. Chez le prématuré, tout comme chez l'enfant né à terme, la maturité du système immunitaire dépend de l'exposition de l'enfant aux stimulations antigéniques après la naissance. La vaccination doit débuter chez le grand prématuré dès le deuxième mois en ne tenant compte que de l'âge chronologique réel de l'enfant. Il n'y a pas de programme vaccinal spécifique pour l'enfant né avant terme. Les recommandations vaccinales sont celles qui s'appliquent à la population générale, actualisées régulièrement par le CSHPF. Cette étude réalisée dans une population d'enfants prématurés issus d'une cohorte régionale a permis d'observer : - un décalage de l'initiation de la vaccination pour les valences de la coqueluche et de l'Huemophilus influenzae b augmentant la vulnérabilité des enfants de moins de 6 mois vis à-vis de ces agents bactériens. - un taux de couverture vaccinale à 2 ans, valence par valence, proche de celui des enfants non prématurés. - une bonne couverture vaccinale à 2 ans pour l'hépatite B. - l'observance partielle des recommandations pour les vaccins contre la grippe, le pneumocoque et la tuberculose. - l'absence d'impact de l'initiation de la vaccination à l'hôpital. - des modalités d'initiation du programme vaccinal différentes en ville et à l'hôpital. - le glissement vers l'utilisation du vaccin coquelucheux acellulaire, précédant l'arrêt de commercialisation du vaccin à germes entiers. - la faible utilisation du vaccin hexavalent. - un nombre insuffisant d'enfants satisfaisant aux recommandations pour leur classe d'âge à 2 ans (52% des enfants de la cohorte ont reçu le nombre d'injections vaccinales recommandées chez le nourrisson en France).ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF
Etude de facteurs de risque de sous-dosage du voriconazole à l'hôpital Saint Louis
PARIS-BIUP (751062107) / SudocSudocFranceF
Evaluation de l'efficacité du verrou antibiotique par la teicoplanine lors d'infections sur cathéters veineux centraux à staphylocoques coagulase négative dans l'unité d'assistance nutritive
ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF
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