Lois de paroi pour les écoulements turbulents présentant des gradients de pression adverses

RÉSUMÉ Ce mémoire s’attarde sur l’utilisation de lois de paroi améliorées dans le cadre de la simulation d’écoulements turbulents. L’utilisation de ces lois de paroi est motivée par la réduction du coût de calcul des simulations grâce à l’utilisation de modèles simplifiés permettant de décrire le comportement du fluide dans les zones de proches parois. Dans le cadre de simulations RANS, on développe ici des lois de paroi couplables à des modèles bas Reynolds et sensibilisées aux gradients de pression. Cette nouvelle forme de lois de paroi est appelée consistante. En effet, la loi de paroi est créée à partir des solutions unidimensionnelles pour un écoulement de Couette par un certain modèle de turbulence. On assure de cette manière la consistance entre la loi et le modèle de turbulence. Tout d’abord, il s’agit de s’occuper de l’implémentation d’un algorithme éléments finis adaptatif permettant de résoudre les écoulements unidimensionnels. Cette procédure adaptative permet de s’assurer de la qualité des résultats et des maillages utilisés. De plus, la technique des solutions manufacturées est utilisée dans le but de vérifier les solutions obtenues. Dans un second temps, on procède à la construction de la tabulation des lois de paroi grâce à l’utilisation de l’algorithme précédemment développé. Cette tabulation se présente sous la forme d’une matrice à trois entrées : la position, le gradient de pression et les différentes variables physiques. Lors de son utilisation, les conditions limites du problème à l’étude y sont directement interpolées linéairement. La maîtrise se termine sur l’essai concluant de la tabulation créée pour le modèle k − w SST dans le cadre d’un écoulement turbulent unidimensionnel avec différentes distances de raccordement.----------ABSTRACT In this master’s thesis, we focus on the utilisation of improved wall function for the simulation of turbulent flow. The use of these wall functions offers a reduced cost for the calculations of the simulations. Indeed, the simplified models allow to describe the behavior of the flow in the areas of near walls. In the RANS simulation framework, we develop wall functions that can be coupled to low Reynolds models of turbulence and sensitized to pressure gradients. This new form of wall functions is called "consistent". It is created from one-dimensional solutions for a Couette flow by a certain model of turbulence. In this way, we ensure the consistency between the law and the turbulence model. First, we take care of the implementation of an adaptive finite element algorithm able to solve the one-dimensional flow problems. This adaptive procedure allows us to claim the quality of the results and the meshes used. The method of manufactured solutions is also used to verify that the equations are rightly solved. Secondly, we create the tabulations of the wall functions thanks to the algorithm previously developed. This tabulation is a three index matrix : the position, the pressure gradient and the different physical variables. The boundary conditions of the problem under study can directly be interpolated linearly from the tabulations. The dissertation ends with the conclusive test of the tabulation created for the k − w SST model in the context of a one-dimensional turbulent flow with different connection distance

CD11b/CD18 mediates production of reactive oxygen species by mouse and human macrophages adherent to matrixes containing oxidized LDL

Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages adherent to matrix proteins that contain or have been modified by oxidized LDL (oxLDL) may play an important role in atherogenesis. In vitro, human macrophages adhere to matrixes containing oxLDL via scavenger receptors and are signaled to produce ROS partly by interactions of the class B scavenger receptor (SR-B) CD36 with ligands on the matrix. In this report, we show that macrophages from mice genetically deficient in SR-A or CD36 adhered equally as well and produced equal amounts of ROS on interaction with matrix-associated oxLDL. In contrast, macrophages from mice genetically deficient in the CD18 chain of β2-integrins produced insignificant amounts of ROS on interaction with oxLDL-containing matrixes, even though they adhered to these matrixes as efficiently as did macrophages from wild-type mice. Antibodies against CD18, CD11b, or EDTA, the last of which chelates divalent cations required for integrin function, had no effect on adhesion of normal mouse or human macrophages to matrixes containing oxLDL but almost completely inhibited ROS production by macrophages adherent to this matrix. Thus, CD11b/CD18 plays an important role in regulating production of ROS by mouse and human macrophages adherent to matrixes containing oxLDL. It may play a hitherto-unsuspected role in regulating macrophage signaling pathways involved in inflammation and atherogenesis

Microwave-assisted synthesis and characterization of novel chitosan-based biomaterials for pelvic organ prolapse treatment

Pelvic organ disorders affect up to one in four women in the United States. The prevalence of pelvic organ prolapse (POP) is increasing with each year, particularly in the setting of prolonged life expectancy and an aging population. Current treatment approaches, including polypropylene monofilaments are associated with numerous painful and worrisome side-effects. Therefore, scientists are looking for new solutions. A promising alternative to the current treatment is tissue engineering, which can be utilized to re-create support to the vagina and pelvic organs. Tissue engineering requires the use of three-dimensional scaffolds, derived from biocompatible materials. Chitosan is a natural polymer, obtained from shellfish exoskeletons. It is known for its biodegradability, lack of cytotoxicity and non-pyrogenicity. Due to the presence of free hydroxyl and amino groups, it may undergo various modifications. In this paper, we describe a new type of chitosan-based biomaterials, which can be used as a new alternative scaffold that may provide support to prolapse organs. The chitosan scaffold was obtained under microwave radiation using multifunctional amino and organic acids. We discuss the scaffold's characteristics, with an emphasis on its chemical structure and morphology. Fourier transform infrared spectroscopy (FT-IR) analysis confirmed cross-linking processes with preservation of free amino groups. Moreover, mechanical durability, the stability and swelling ability of the scaffolds in a simulated body fluid were investigated. All of the prepared scaffolds demonstrated very good antioxidant activity and biodegradability. Importantly, the biocompatibility of chitosan scaffolds was examined on human vaginal VK2/E6E7 cell line. No evidence of toxicity was documented, and the cells maintained their presence on the studied materials. These results allude to the lack of toxicity of the scaffolds, and indicate that chitosan-based scaffold should be further investigated in in vivo studies as they may be a promising alternative treatment to pelvic organ prolapse.Web of Science70349147

Autoimmune Epilepsy: Some Epilepsy Patients Harbor Autoantibodies to Glutamate Receptors and dsDNA on both Sides of the Blood-brain Barrier, which may Kill Neurons and Decrease in Brain Fluids after Hemispherotomy

Purpose: Elucidating the potential contribution of specific autoantibodies (Ab's) to the etiology and/or pathology of some human epilepsies. Methods: Six epilepsy patients with Rasmussen's encephalitis (RE) and 71 patients with other epilepsies were tested for Ab's to the –B— peptide (amino acids 372-395) of the glutamate/AMPA subtype 3 receptor (GluR3B peptide), double-stranded DNA (dsDNA), and additional autoimmune disease-associated autoantigens, and for the ability of their serum and cerebrospinal-fluid (CSF) to kill neurons. Results: Elevated anti-GluR3B Ab's were found in serum and CSF of most RE patients, and in serum of 17/71 (24%) patients with other epilepsies. In two RE patients, anti-GluR3B Ab's decreased drastically in CSF following functional-hemispherotomy, in association with seizure cessation and neurological improvement. Serum and CSF of two RE patients, and serum of 12/71 (17%) patients with other epilepsies, contained elevated anti-dsDNA Ab's, the hallmark of systemic-lupus-erythematosus. The sera (but not the CSF) of some RE patients contained also clinically elevated levels of –classical— autoimmune Ab's to glutamic-acid-decarboxylase, cardiolipin, β2-glycoprotein-I and nuclear-antigens SS-A and RNP-70. Sera and CSF of some RE patients caused substantial death of hippocampal neurons. Conclusions: Some epilepsy patients harbor Ab's to GluR3 and dsDNA on both sides of the blood-brain barrier, and additional autoimmune Ab's only in serum. Since all these Ab's may be detrimental to the nervous system and/or peripheral organs, we recommend testing for their presence in epilepsy, and silencing their activity in Ab-positive patients

The potential of novel chitosan-based scaffolds in pelvic organ prolapse (POP) treatment through tissue engineering

The growing number of female reproductive system disorders creates a need for novel treatment methods. Tissue engineering brings hope for patients, which enables damaged tissue reconstruction. For this purpose, epithelial cells are cultured on three-dimensional scaffolds. One of the most promising materials is chitosan, which is known for its biocompatibility and biodegradability. The aim of the following study was to verify the potential of chitosan-based biomaterials for pelvic organ prolapse regeneration. The scaffolds were obtained under microwave-assisted conditions in crosslinking reactions, using dicarboxylic acids and aminoacid as crosslinkers, includingl-glutamic acid, adipic acid, malonic acid, and levulinic acid. The products were characterized over their physicochemical and biological properties. FT-IR analysis confirmed formation of amide bonds. The scaffolds had a highly porous structure, which was confirmed by SEM analysis. Their porosity was above 90%. The biomaterials had excellent swelling abilities and very good antioxidant properties. The cytotoxicity study was performed on vaginal epithelial VK2/E6E7 and human colon cancer HCT116 cell lines. The results showed that after certain modifications, the proposed scaffolds could be used in pelvic organ prolapse (POP) treatment.Web of Science2518art. no. 428

International consensus recommendations on the diagnostic work-up for malformations of cortical development

Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management. In this article, the international MCD network Neuro-MIG provides consensus recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs with the aim of improving patient management worldwide. We reviewed the literature on clinical presentation, aetiology and diagnostic approaches for the main MCD subtypes and collected data on current practices and recommendations from clinicians and diagnostic laboratories within Neuro-MIG. We reached consensus by 42 professionals from 20 countries, using expert discussions and a Delphi consensus process. We present a diagnostic workflow that can be applied to any individual with MCD and a comprehensive list of MCD-related genes with their associated phenotypes. The workflow is designed to maximize the diagnostic yield and increase the number of patients receiving personalized care and counselling on prognosis and recurrence risk

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox–Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient–parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population

Association of ultra-rare coding variants with genetic generalized epilepsy: A case\u2013control whole exome sequencing study

Objective: We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods: We performed a case\u2013control whole exome sequencing study in unrelated individuals of European descent diagnosed with GGE (previously recruited and sequenced through multiple international collaborations) and ancestry-matched controls. The association of ultra-rare variants (URVs; in 18 834 protein-coding genes) with epilepsy was examined in 1928 individuals with GGE (vs. 8578 controls), then separately in 945 individuals with familial GGE (vs. 8626 controls), and finally in 1005 individuals with sporadic GGE (vs. 8621 controls). We additionally examined the association of URVs with familial and sporadic GGE in two gene sets important for inhibitory signaling (19 genes encoding \u3b3-aminobutyric acid type A [GABAA] receptors, 113 genes representing the GABAergic pathway). Results: GABRG2 was associated with GGE (p = 1.8  7 10 125), approaching study-wide significance in familial GGE (p = 3.0  7 10 126), whereas no gene approached a significant association with sporadic GGE. Deleterious URVs in the most intolerant subgenic regions in genes encoding GABAA receptors were associated with familial GGE (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 1.9\u20137.8, false discovery rate [FDR]-adjusted p =.0024), whereas their association with sporadic GGE had marginally lower odds (OR = 3.1, 95% CI = 1.3\u20136.7, FDR-adjusted p =.022). URVs in GABAergic pathway genes were associated with familial GGE (OR = 1.8, 95% CI = 1.3\u20132.5, FDR-adjusted p =.0024) but not with sporadic GGE (OR = 1.3, 95% CI =.9\u20131.9, FDR-adjusted p =.19). Significance: URVs in GABRG2 are likely an important risk factor for familial GGE. The association of gene sets of GABAergic signaling with familial GGE is more prominent than with sporadic GGE

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

Does Exposure to Interviewer Feedback Bias Observer Perceptions of The Suspect? A Test of Two Pathways to a Feedback Effect

Confronting suspects with feedback, such as “We know you are lying, you need to tell us the truth,” during an interrogation is a common tactic used by police. Can this feedback influence the perceptions of factfinders who later observe video recordings of these sessions? Amrom et al. (2020) proposed two pathways through which feedback might affect observers: a direct feedback pathway by which observers infer the suspect’s credibility from the interviewer’s feedback, and an indirect misattribution pathway by which observers infer credibility from the suspect’s feedback-induced change in demeanor. Given the increasing frequency with which interrogations are video recorded for presentation in court, it is important to understand how information transmitted in these videos can influence factfinders’ perceptions of suspects. This dissertation is an extension of research conducted by Amrom et al. (2020). The aims were twofold: (1) To strengthen the ecological validity by enhancing the feedback and the stakes for the participant suspects during an accusatory interview and (2) to explore how contextual information about the interviewer’s competence and the suspect’s incentives moderated this feedback effect. To address these aims, three experiments were conducted. Although the results demonstrated that all suspects claimed to be innocent and extremely truthful during the interview (Study 1), observers’ perceptions of guilt and truthfulness were influenced by the interviewer’s feedback. Specifically, evidence for the indirect misattribution hypothesis was found with regard to perceptions of guilt in Study 2. Additionally, support for the direct feedback hypothesis with regard to perceptions of truthfulness was found in Study 3. The findings are discussed in relation to the impact of presenting interrogation videos in court to jurors