91 research outputs found
Ăvaluation de l'influence de la variabilitĂ© naturelle du climat et des changements climatiques anthropiques sur les extrĂȘmes hydromĂ©tĂ©orologiques
La capacitĂ© maximale des infrastructures dâeaux est conçue Ă partir des sĂ©ries historiques dâextrĂȘmes hydromĂ©tĂ©orologiques et sur lâhypothĂšse que le climat est stationnaire. Toutefois, le consensus scientifique pointe vers un rĂ©chauffement planĂ©taire causĂ© par lâinfluence humaine, ayant des rĂ©percussions Ă long terme sur les prĂ©cipitations et les crues extrĂȘmes. De plus, plusieurs travaux rĂ©cents indiquent que la variabilitĂ© naturelle du climat a le potentiel de masquer les effets de ces changements climatiques anthropiques, donnant une illusion de stationnaritĂ© du climat. Ainsi, lâobjectif de cette thĂšse a pour but dâamĂ©liorer la comprĂ©hension des impacts de cette variabilitĂ© naturelle et des changements climatiques sur les extrĂȘmes hydromĂ©tĂ©orologiques.
Dans un premier lieu, la variabilitĂ© naturelle a Ă©tĂ© explorĂ©e Ă travers six indices climatiques importants (p. ex. : El Niño) influençant le climat en AmĂ©rique du Nord. Bien que ceux-ci aient dĂ©montrĂ© un certain potentiel de prĂ©diction au niveau de la variabilitĂ© saisonniĂšre des moyennes de tempĂ©ratures et de prĂ©cipitations, ils se sont trouvĂ©s beaucoup moins prometteurs au niveau de la variabilitĂ© des extrĂȘmes hydromĂ©tĂ©orologiques. La combinaison de ces indices climatiques nâa rĂ©sultĂ© quâen une faible valeur prĂ©dictive de la variabilitĂ© des crues et prĂ©cipitations extrĂȘmes.
Dans un second lieu, la variabilitĂ© naturelle des prĂ©cipitations moyennes et extrĂȘmes a Ă©tĂ© examinĂ©e Ă lâaide de grands ensembles de simulations climatiques. Ces travaux ont permis de dresser un portait plus clair de son influence sur la dĂ©tection du signal des changements climatiques. Ă lâĂ©chelle locale (p. ex. : une station mĂ©tĂ©orologique), la variabilitĂ© naturelle dominera vraisemblablement le signal des changements climatiques des precipitations extrĂȘmes jusquâĂ la fin du 21e siĂšcle. Toutefois, Ă lâĂ©chelle rĂ©gionale (p. ex. : plusieurs stations mĂ©tĂ©orologiques), la dĂ©tection du signal des changements climatiques serait plus rapide et robuste. Globalement, la variabilitĂ© naturelle a la capacitĂ© dâentraver la detection des changements climatiques sur les prĂ©cipitations moyennes et extrĂȘmes jusquâĂ la moitiĂ©, voire mĂȘme la fin du siĂšcle, pour plusieurs rĂ©gions de la planĂšte.
Les grands ensembles de simulations climatiques ont aussi Ă©tĂ© utilisĂ©s pour Ă©valuer lâimpact des changements climatiques sur la probabilitĂ© de rĂ©currence des Ă©vĂ©nements hydromĂ©tĂ©orologiques extrĂȘmes. Dâabord, les changements projetĂ©s pour la pluie 100 ans dâune durĂ©e dâune heure jusquâĂ cinq jours entre les pĂ©riodes de 1980-1999 et 2080-2099 ont Ă©tĂ© Ă©tudiĂ©s Ă lâaide de deux ensembles Ă lâĂ©chelle globale et un ensemble Ă lâĂ©chelle rĂ©gionale couvrant le nord-est de lâAmĂ©rique du Nord et lâEurope. Les rĂ©sultats des trois ensembles suggĂšrent que les Ă©vĂ©nements de prĂ©cipitation extrĂȘmes, correspondant Ă la pĂ©riode de retour 100 ans de la pĂ©riode de rĂ©fĂ©rence, deviendront environ de quatre Ă cinq (deux Ă quatre) fois plus frĂ©quents en moyenne pour le nord-est de lâAmĂ©rique du Nord (lâEurope). De plus, les rĂ©sultats suggĂšrent quâen gĂ©nĂ©ral, une pĂ©riode de retour plus Ă©levĂ©e et/ou une durĂ©e plus courte entraineront des augmentations relatives plus importantes.
Ensuite, les changements projetĂ©s dans les crues extrĂȘmes ont Ă©tĂ© investiguĂ©s plus spĂ©cifiquement pour 3 567 bassins versants de grande taille (> 500 km2) en AmĂ©rique du Nord. Les rĂ©sultats suggĂšrent des patrons spatiaux trĂšs distincts en termes dâaugmentation et de diminution de la crue 100 ans. Les changements les plus importants se rĂ©sument en une diminution des crues gĂ©nĂ©rĂ©es par la fonte de la neige dans les bassins versants situĂ©s en haute latitude et/ou haute altitude et une augmentation pour les bassins versants situĂ©s dans le sud-est des Ătats-Unis et sur la cĂŽte ouest, oĂč les prĂ©cipitations sont la principale cause des crues.
Finalement, des pistes de stratĂ©gies dâadaptation face aux changements climatiques ont Ă©tĂ© discutĂ©es Ă la suite de ces travaux. Ces derniĂšres, de concert avec les conclusions de cette thĂšse, pourraient aider davantage les ingĂ©nieurs et les preneurs de dĂ©cision Ă justifier lâimplĂ©mentation de mesures dâadaptation permettant de mieux protĂ©ger le milieu bĂąti et les populations vulnĂ©rables
MAT-701: PREDICTING THE COMPRESSIVE STRENGTH OF ULTRA-LIGHTWEIGHT CONCRETE BY AN ARTIFICIAL NEURAL NETWORK
Ultra-lightweight concrete (ULWC) has potential applications for floating structures and architectural elements because of its dry density coming in at under 1000 kg/m3. The objective was to develop an artificial neural network (ANN) to aid the ULWC designer according to his needs. Boundary conditions were set for each material and 13 constraints based on the water binder ratio, density, air content, binder and aggregate content. The ANN predicted the compressive strength with a comfortable margin of error, with the gap encountered being attributed to variability in workability. Precise constraints and boundary conditions are needed to ensure a lower variability in workability. The ANN, coupled with a genetic algorithm, can generate millions of mixes for a given compressive strength in a short amount of time. The designer is able to choose mixes according to additional needs, such as the carbon footprint, absolute density, polymer content, cost, etc
Drug-protein binding: a critical review of analytical tools
The extent of drug binding to plasma proteins, determined by measuring the free active fraction, has a significant effect on the pharmacokinetics and pharmacodynamics of a drug. It is therefore highly important to estimate drug-binding ability to these macromolecules in the early stages of drug discovery and in clinical practice. Traditionally, equilibrium dialysis is used, and is presented as the reference method, but it suffers from many drawbacks. In an attempt to circumvent these, a vast array of different methods has been developed. This review focuses on the most important approaches used to characterize drug-protein binding. A description of the principle of each method with its inherent strengths and weaknesses is outlined. The binding affinity ranges, information accessibility, material consumption, and throughput are compared for each method. Finally, a discussion is included to help users choose the most suitable approach from among the wealth of methods presented. Figure Range of binding constants (log Ka) assessable by the main separative and non-separative analytical tools used to characterize drug-protein interactions. ED: equilibrium dialysis, UF: ultrafiltration, PAMPA: parallel artificial membrane permeability assay, HPAC/ZE: high-performance affinity chromatography/zonal elution approach, HPAC/FA: high-performance affinity chromatography/frontal analysis approach, ACE: affinity capillary electrophoresis (mobility shift assay), CE/FA: capillary electrophoresis/frontal analysis, Spectro.: spectroscopic assays, ITC: isothermal titration calorimetry, comp.: competition studies, titration: titration studies, DSC: differential scanning calorimetry, SPR: surface plasmon resonance-based assay
Large scale composting model
One way to treat the organic wastes accordingly to the environmental policies is to develop biological treatment like composting. Nevertheless, this development largely relies on the quality of the final product and as a consequence on the quality of the biological activity during the treatment. Favourable conditions (oxygen concentration, temperature and moisture content) in the waste bed largely contribute to the establishment of a good aerobic biological activity and guarantee the organic matter stabilisation with limitation and control of odorous and greenhouse effect gaseous emissions. Several approaches (0D biochemical reducing, see Pommier et al. 2007, effective 1D modelling coupling transport and biochemical) have been made to understand the behaviour of such systems. In this paper we will present a 2D numerical model using Darcy scale equations for heat and mass transport coupled with a biochemical reactive scheme. Then, we will solve that system (using experimental measurements on reactivity and transport coefficients) with a commercial code (COMSOL TM). The model described here is based on the biological model presented in TrĂ©mier et al 2005 coupled with an upscale transport model detailed in HĂ©non 2008 which takes into account the major components of the gas phase: Nâ, Oâ, COâ and also HâO. This is a crucial point because of: - The reaction rate, depending on the moisture content (humidity comes from the initial condition of the sludge but also from the reactive scheme because reactions produce water), - heat content, very sensitive to the evaporation rate in the sludge. It has been shown in Pujol et al 2011 that the impact of drying could be important on the reactivity but also that the pseudo component air could not be sufficient to represent the drying in the sludge. The process studied was a closed reactor composting process (180 mÂł rectangular box) with positive forced aeration. The air was blown from the bottom of the reactor, via two ventilation pipes. In the upper part of the reactor, air was sucked and led to a biofilter treatment system. The treated waste was a mixture of sewage sludge and bulking agent that was composted during four weeks without turning. Several informations were recorded during the treatment like temperature evolutions at different locations (see Henon et al. 2009 for more details about the temperature recording). We have validated this code by comparing the temperatures obtained through the simulations with those recorded during the experiments. After this step of validation and a discussion on final composition of the organic matter in the experiments compared to the ones estimated by simulations, we have used this numerical model as an optimization tool. Modifying the initial, boundary and operating conditions we have been able to determine the best conditions to this particular composting process. A whole set of conditions is discussed in the paper
Fast log P determination by ultra-high-pressure liquid chromatography coupled with UV and mass spectrometry detections
Ultra-high-pressure liquid chromatography (UHPLC) systems able to work with columns packed with sub-2ÎŒm particles offer very fast methods to determine the lipophilicity of new chemical entities. The careful development of the most suitable experimental conditions presented here will help medicinal chemists for high-throughput screening (HTS) log P oct measurements. The approach was optimized using a well-balanced set of 38 model compounds and a series of 28 basic compounds such as ÎČ-blockers, local anesthetics, piperazines, clonidine, and derivatives. Different organic modifiers and hybrid stationary phases packed with 1.7-ÎŒm particles were evaluated in isocratic as well as gradient modes, and the advantages and limitations of tested conditions pointed out. The UHPLC approach offered a significant enhancement over the classical HPLC methods, by a factor 50 in the lipophilicity determination throughput. The hyphenation of UHPLC with MS detection allowed a further increase in the throughput. Data and results reported herein prove that the UHPLC-MS method can represent a progress in the HTS-measurement of lipophilicity due to its speed (at least a factor of 500 with respect to HPLC approaches) and to an extended field of application. Figure The UHPLC approach described here greatly enhanced the time required for log P determination (5' min by compound using UV detection) and, at least, 8 compounds measured in a 5' run when Mass Spectrometry detection in used. These developments offer to medicinal chemists a high-throughput method to estimate the lipophilicity of NCE
Analytical tools for the physicochemical profiling of drug candidates to predict absorption/distribution
The measurement of physicochemical properties at an early phase of drug discovery and development is crucial to reduce attrition rates due to poor biopharmaceutical properties. Among these properties, ionization, lipophilicity, solubility and permeability are mandatory to predict the pharmacokinetic behavior of NCEs (new chemical entities). Due to the high number of NCEs, the analytical tools used to measure these properties are automated and progressively adapted to high-throughput technologies. The present review is dedicated to experimental methods applied in the early drug discovery process for the determination of solubility, ionization constants, lipophilicity and permeability of small molecules. The principles and experimental conditions of the different methods are described, and important enhancements in terms of throughput are highlighted. Figure Scheme of the Drug Research Proces
Guide de lutilisation pédagogique des médias sociaux
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A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine.
Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels.
In this multi-institutional study, we first examined the histological features displayed by each collected tumour (nâ=â74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed.
Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa.
Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits
Human papillomavirus genotypes among women with or without HIV infection: an epidemiological study of Moroccan women from the Souss area
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