51 research outputs found
Vortex-forced-oscillations of thin flexible plates
Fluid-structure interaction of a slender flexible cantilevered-element and
vortices in an otherwise steady flow is considered here by investigating the
dynamics of thin low-density polyethylene sheets subject to periodic forcing
due to B\'enard-K\`arm\`an vortices in a -meter long narrow water channel.
The vortex shedding frequency is varied via the mean flow speed and
the cylinder diameter , and mm, while the structures'
bending resistance is properly controlled via its Young's modulus ,
thickness and length . Thereby, it is first shown that the
non-dimensional time-averaged sheet deflection, namely, the sheet
\textit{reconfiguration} and also, the
time-averaged \textit{drag force} ,
where is the well-known Vogel number for flexible
structures in a steady flow and is the Cauchy number
comparing the relative magnitude of the profile drag force over a typical
elastic restoring force, if the sheet were rigid. Measurements and a simple
model based on torsional-spring-mounted flat plate illustrate that the tip
amplitude is not only directly proportional to the characteristic
size of the eddies, say , but also to the sheet mechanical properties and
the vortex flow characteristics such that . Furthermore, a rich phenomenology
of structural dynamics including vortex-forced-vibration, lock-in with the
sheet natural frequency, flow-induced vibration due to the sheet wake,
multiple-frequency and modal response is reported
Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management
International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended
A phase II study of cisplatin with intravenous and oral vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy with oral vinorelbine and cisplatin for locally advanced non-small cell lung cancer
Comparison of microbial populations in anaerobic digesters treating wastewater sludge : molecular analysis of the diversity and activity
La digestion anaérobie est un processus naturel de dégradation de la matière organique réalisé par l'action concertée de plusieurs populations microbiennes. Grâce au développement des techniques moléculaires, la connaissance de la diversité de ce monde microbien longtemps ignoré a connue une avancée significative ces dernières années. Dans cette étude, nous avons procédé à une étude moléculaire de la diversité procaryote à 30 autres digesteurs ayant des caractéristiques de fonctionnement variées. Cette première phase nous a permis d'identifier les phyla les plus couramment rencontrés. Nous avons pu mesurer l'étendue de la diversité de cet écosystème complexe et distinguer les phyla les plus diversifiés. Différents types de structures ont été observés : certains phyla sont constitués de phylotypes très fréquemment rencontrés alors que d'autres sont constitués essentiellement de phylotypes endémiques. Suite à cette première phase, nous avons sélectionné 7 digesteurs pour procéder à une exploration plus poussée de la diversité en séquençant un nombre important de clones pour les domaines Archaea et Bacteria. Nous avons ensuite utilisé une palette d'outils statistiques afin de comparer les populations rencontrées et de déterminer quel était leur degré de ressemblance/différence. Pour le domaine Archaea, 7 OTUs majeures ont été identifiées et sont en équilibre. Selon la disponibilité des substrats, certaines peuvent prendre le dessus. Les OTUs dominantes sont affiliées aux Methanosarcinales, Arc I et Methanomicrobiales. La lignée Arc I est particulièrement abondante dans certains digesteurs et est probablement en compétition avec le genre Methanosaeta. Cela implique que Arc I pourrait être un consommateur d'acétate et un acteur majeur de la méthanogenèse acétoclaste. Des expériences de mises en culture permettront d'approfondir nos connaissances sur le métabolisme de cette lignée qui sont limitées à l'heure actuelle. Par ailleurs, l'analyse statistique a révélé que les communautés bactériennes peuvent être décrites comme des modèles à 3 composantes : un tiers de phylotypes appartenant à un groupe noyau, un tiers de phylotypes partagés entre quelques digesteurs et un tiers de phylotypes endémiques. Le groupe noyau est composé de 6 OTUs affiliées aux Chloroflexi, Betaproteobacteria, Bacteroidetes et Synergistes. Parmi ces OTUs, 2 sont couramment retrouvées dans d'autres environnements alors que les 4 autres semblent être typiques d'environnements anaérobies. Ces populations couramment rencontrées dans les digesteurs anaérobies pourraient constitués des acteurs majeurs du procédé de dégradation de la matière organique. Grâce à la large base de données de séquences du gène de l'ARNr 16S, des sondes spécifiques ont été mises au point afin de cibler les groupes majoritaires et de quantifier leur activité au sein des réacteurs. Cette analyse quantitative a mis en évidence les groupes les plus actifs et notamment l'importance de la division candidate WWE1. Ces expériences d'hybridation ont également permis de mettre en évidence une diversité encore non ciblée par les différentes sondes existantes ainsi que les limites de l'utilisation des amorces 0008F et 1390R pour la réalisation des banques de clones. La comparaison des approches qualitative et quantitative a montré que certains groupes semblent être sur-représentés dans les banques de clones par rapport à leur réelle activité. Nous avons donc suivi une approche complète basée sur l'étude de l'ARNr 16S en partant d'un inventaire moléculaire jusqu'à la quantification à l'aide de sondes spécifiques. Cette comparaison des populations rencontrées dans les digesteurs anaérobies est un premier pas vers une meilleure compréhension du procédé. A terme, la clarification des relations existant entre biodiversité, conditions d'exploitation et performances devrait permettre d'atteindre une meilleure maîtrise du procédé de digestion anaérobie.Anaerobic digestion is a natural process of degradation of organic matter realised by a microbial consortium. With the development of molecular techniques, our knowledge of the diversity of this microbial ecosystem has been extended in the last years. In this study, the molecular study of prokaryotic diversity was performed on 30 digesters with various operating conditions. In this first phase, the most common phyla were identified. We were able to measure the extend of the diversity of this complex ecosystem and distinguish the most diversified phyla. Different types of structures were observed: some phyla are constituted of frequently observed phylotypes while others are mainly composed of endemic phylotypes. In a second phase, 7 digesters were selected to pursue the exploration of the diversity at a deeper level with a large number of clones sequenced for Archaea and Bacteria domain. A selection of statistic tools was used to compare the populations encountered and determine their level of similarity/difference. For Archaea domain, seven OTUs were found to be dominant and are in equilibrium. Depending on the availability and the concentration of the substrates, some OTUs of the seven may become more abundant. These dominant OTUs are affiliated with Methanosarcinales, Methanomicrobiales and Arc I phylogenetic groups. We highlighted the abundance of the lineage Arc I which is probably in competition with Methanosaeta species. This implies that Arc I could be an acetate consumer and therefore a major actor in acetoclastic methanogenesis. New cultivation experiments are being conducted to explore the metabolic ability of Arc I that are still unclear. Moreover, statistical analysis revealed that the Bacteria community can be described as a three component model: one third making up a core group of phylotypes defined as OTUs commonly found in most of the digesters, one third are phylotypes shared between a few digesters, and another third are endemic phylotypes. The core group is composed of 6 OTUs affiliated with the less diversified phyla: Chloroflexi, Betaproteobacteria, Bacteroidetes and Synergistetes. Other phyla such as Firmicutes, Alpha and Deltaproteobacteria are composed of a majority of endemic sequences. Among these OTUs 2 are commonly found in other environments while the other four seem to be specific of anaerobic environments. These populations commonly found in anaerobic digesters could be major actors of the degradation of the organic matter. Based on the large database of 16S rDNA sequences specific probes were designed to target the dominant groups and quantify their activity inside the reactors. This quantitative analysis underlined the most active groups and especially the importance of the candidate division WWE1. These hybridization experiments also revealed a diversity that is not yet targeted by the existent probes and the limits in the use of primers 0008F and 1390R for the clones libraries construction. The comparison of qualitative and quantitative approach showed that some groups seem to be over-represented in clones libraries compared to their real activity. We followed a full-cycle RNA approach from a molecular inventory to quantification with specific probes. This comparison of anaerobic digester populations is a first step toward a future understanding on microbial resource management in order to manage complex microbial system. Ultimately, the relationship between biodiversity, operating conditions and digester efficiency could be established for a better process engineering in anaerobic digestion
1-year mortality in lung cancer in France according to key timepoints of care pathways
Background
It is unclear whether delays in care affect prognosis of patients with lung cancer. The primary objective of this study was to describe the care pathway of patients diagnosed with lung cancer in a French region. Secondary objectives were to identify markers associated with 1) time from imaging to treatment and 2) with 1-year survival.
Methods
In a retrospective cohort study, clinical data from multidisciplinary team meetings for all incident lung cancer cases discussed in 2018 in one French region were matched with medico-administrative data from the National Health Insurance Database. Care pathway time intervals were estimated for small cell lung cancer (SCLC), resected nonsmall cell lung cancer (NSCLC) and unresected NSCLC. Factors associated with delay in the care pathway were identified using linear regression; 1-year survival was analysed using Cox modelling.
Results
A total of 685 patients were included. Median time between imaging and treatment was 49 days (interquartile range: 33–73), and was lower in cases of metastatic disease, SCLC and private care. At 1 year, 48% had died (resected NSCLC 12%). In unresected NSCLC, time from diagnostic imaging to first treatment <49 days was associated with a higher risk of death. Time intervals were similar in patients with squamous cell carcinoma versus adenocarcinoma or undifferentiated carcinoma.
Discussion
Time intervals in the care pathways of lung cancer were similar to previous reports, confirming the robustness of retrospective databases. In unresectable NSCLC, rapid care was not associated with better survival
A new high-throughput approach to characterize Presence/Absence Variant in Maize based on Affymetrix technology
National audienc
Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
International audienc
Development of a new high throughput 105K Presence/Absence Variation genotyping array for quantitative genetic studies
National audienc
Lack of an Immune Response against the Tetracycline-Dependent Transactivator Correlates with Long-Term Doxycycline-Regulated Transgene Expression in Nonhuman Primates after Intramuscular Injection of Recombinant Adeno-Associated Virus
We previously documented persistent regulation of erythropoietin (Epo) secretion in mice after a single intramuscular (i.m.) injection of a recombinant adeno-associated virus (rAAV) vector harboring both the tetracycline-dependent transactivator (rtTA) and the Epo cDNA (D. Bohl, A. Salvetti, P. Moullier, and J. M. Heard, Blood 92:1512-1517, 1998). Using the same vector harboring the cynomolgus macaque Epo cDNA instead, the present study evaluated the ability of the tetracycline-regulatable (tetR) system to establish long-term transgene regulation in nonhuman primates. The vector was administered i.m., after which 5-day induction pulses were performed monthly for up to 13 months by using doxycycline (DOX), a tetracycline analog. We show that initial inductions were successful in all individuals and that there was a tight regulation and a rapid deinduction pattern upon DOX withdrawal. For one macaque, regulation of Epo secretion was maintained during the entire experimental period; for the five remaining macaques, secreted Epo became indistinguishable from endogenous Epo upon repeated DOX inductions. We investigated the mechanism involved and showed that, except in the animal in which secretion persisted, delayed humoral and cellular immune responses were directed against the rtTA transactivator protein associated with the reduction of vector DNA in transduced muscles. This study provides some evidence that, when the immune system is not mobilized against the rtTA transactivator, the tetR-regulatable system is able to support long-term transgene regulation in the context of an rAAV in nonhuman primates. In addition, our results suggest potential improvements for vector design
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