120 research outputs found

    Étude expĂ©rimentale du comportement structural des panneaux Ă  revĂȘtement mĂ©tallique Murox

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    Le principal objectif est l'Ă©tude qualitative et quantitative du comportement structural de panneaux non-contreventĂ©s soumis Ă  un chargement horizontal reprĂ©sentant les efforts de vent et de sĂ©isme. Les objectifs spĂ©cifiques du projet sont: (i) de dĂ©terminer la capacitĂ© structurale des panneaux Murox non-contreventĂ©s afin d'Ă©valuer les charges de dimensionnement (Ă©tat limite ultime); (ii) de dĂ©terminer la rigiditĂ© latĂ©rale des panneaux Murox non-contreventĂ©s afin d'en Ă©valuer le comportement en service (Ă©tat limite de service); (iii) de dĂ©terminer le comportement et la capacitĂ© maximale des connexions vissĂ©es utilisĂ©es comme Ă©lĂ©ments connecteurs entre le revĂȘtement et l'ossature mĂ©tallique des panneaux Murox; (iv) de calculer la pĂ©riode fondamentale et l'amortissement d'une charpente composĂ©e de panneaux Murox dans le but d'en Ă©valuer le comportement dynamique de base; et (v) de rĂ©aliser un modĂšle par Ă©lĂ©ments finis d'un panneau standard non-contreventĂ© afin de pouvoir dĂ©montrer analytiquement la pertinence des hypothĂšses formulĂ©es en laboratoire par la reproduction du comportement expĂ©rimental et d'Ă©tablir les bases d'un dimensionnement."--RĂ©sumĂ© abrĂ©gĂ© par UM

    Formation professionnelle en gestion de conflits : une Ă©tude de cas

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    Mémoire numérisé par la Direction des bibliothÚques de l'Université de Montréal

    Metabolic Activity and mRNA Levels of Human Cardiac CYP450s Involved in Drug Metabolism

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    Tissue-specific expression of CYP450s can regulate the intracellular concentration of drugs and explain inter-subject variability in drug action. The overall objective of our study was to determine in a large cohort of samples, mRNA levels and CYP450 activity expressed in the human heart.CYP450 mRNA levels were determined by RTPCR in left ventricular samples (n = 68) of explanted hearts from patients with end-stage heart failure. Samples were obtained from ischemic and non-ischemic hearts. In some instances (n = 7), samples were available from both the left and right ventricles. A technique for the preparation of microsomes from human heart tissue was developed and CYP450-dependent activity was determined using verapamil enantiomers as probe-drug substrates.Our results show that CYP2J2 mRNA was the most abundant isoform in all human heart left ventricular samples tested. Other CYP450 mRNAs of importance were CYP4A11, CYP2E1, CYP1A1 and CYP2C8 mRNAs while CYP2B6 and CYP2C9 mRNAs were present at low levels in only some of the hearts analyzed. CYP450 mRNAs did not differ between ischemic and non-ischemic hearts and appeared to be present at similar levels in the left and right ventricles. Incubation of verapamil with heart microsomes led to the formation of nine CYP450-dependent metabolites: a major finding was the observation that stereoselectivity was reversed compared to human liver microsomes, in which the R-enantiomer is metabolized to a greater extent.This study determined cardiac mRNA levels of various CYP450 isozymes involved in drug metabolism and demonstrated the prevalent expression of CYP2J2 mRNA. It revealed that cardiomyocytes can efficiently metabolize drugs and that cardiac CYP450s are highly relevant with regard to clearance of drugs in the heart. Our results support the claim that drug metabolism in the vicinity of a drug effector site can modulate drug effects

    Development of monitoring systems for anomaly detection using ASTD specifications

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    Anomaly-based intrusion detection systems are essential defenses against cybersecurity threats because they can identify anomalies in current activities. However, these systems have difficulties providing entity processing independence through a programming language. In addition, a degradation of the detection process is caused by the complexity of scheduling the training and detection processes, which are required to keep the anomaly detection system continuously updated. This paper shows how to use the algebraic state-transition diagram (ASTD) language to develop flexible anomaly detection systems. This paper provides a model for detecting point anomalies using the unsupervised non-parametric technique Kernel Density Estimation to estimate the probability density of event occurrence. The proposed model caters for both the training and the detection phase continuously. The ASTD language streamlines the modeling of detection systems thanks to its process algebraic operators that provide a solution to overcome these challenges. By delegating the combination of anomaly-based detection processes to the ASTD language, the effort and complexity are reduced during detection models development. Finally, using a qualitative evaluation, this study demonstrates that the algebraic operators in the ASTD specification language overcome these challenges

    Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.

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    While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clones with EBV, but surprisingly not transduction with individual BL-associated latent viral genes, restored protection from apoptosis. Expression profiling and functional analysis of apoptosis-related proteins and transcripts in BL cells revealed that EBV inhibits the upregulation of the proapoptotic BH3-only proteins, BIM and PUMA. We conclude that latent EBV genes cooperatively enhance the survival of BL cells by suppression of the intrinsic apoptosis pathway signalling via inhibition of the potent apoptosis initiators, BIM and PUMA.Cell Death and Differentiation advance online publication, 29 September 2017; doi:10.1038/cdd.2017.150

    Evaluating model outputs using integrated global speleothem records of climate change since the last glacial

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    Although quantitative isotopic data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to use the speleothem data for data-model comparisons. Here, we illustrate this using 456 globally-distributed speleothem ή18O records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates procuring large numbers of records if data-model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotopic values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model’s ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotopic data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on 18O values, the optimum period for the modern observational baseline, and the selection of an appropriate time-window for creating means of the isotope data for palaeo time slices
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