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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
821

Interpersoonlike verrykingsprogram vir multikulturele groepe / An interpersonal enrichment programme for multicultural groups

Vlok, Engela Susanna 01 1900 (has links)
Summaries in Afrikaans and English / Ons bevind ons in 'n nuwe Suid-Afrika waar die klem baie sterk op die uitwissing van die spore van die apartheidsera gele word. Die oopstelling van skole het nie daartoe bygedra dat kinders hulle vooroordele oorboord gooi en mekaar spontaan aanvaar nie. Die verandering in wetgewing wat 'n eksterne verandering is, het nie noodwendig tot verandering van gesindhede gelei nie. Daar kan derhalwe tereg gevra word hoe versoening tussen mense van verskillende kulture tot stand kan kom. In hierdie studie is gepoog om vas te stel of 'n verrykingsprogram in groepverband interpersoonlike vaardighede en verhoudinge van persone van uiteenlopende kulturele agtergronde kan bevorder. Die program is onder gekontroleerde omstandighede aangebied en die idiografiese navorsingsmetode is gebruik. Daar is bepaal watter faktore die aard en die kwaliteit van verhoudinge tussen persone van verskillende kulturele herkoms be'invloed. Riglyne is gestruktrueer en kriteria is ge'identifiseer waarvolgens die program saamgestel is. Die ouderdomme van die leertinge het tussen 15 en 21 jaar gewissel. Tydens die multikulturele groepsbelewing het die leertinge die geleentheid gehad om persoonlike en interpersoonlike vaardighede te ontwikkel sodat daar 'n openheid en 'n beg rip vir mekaar ontstaan het. Die interaksie met persone afkomstig van 'n verskeidenheid oriemtasies het daartoe gelei dat raakpunte in die diversiteit ontdek is en hulle het mekaar as individue begin erken en verstaan. Nuutgestigte verhoudings was gekenmerk deur vertroue, warmte en empatie. Deur middel van verbeterde selfbegrip en interpersoonlike vaardighede het die verhoudings tussen groeplede in verskeie dimensies beduidend verbeter. Hierdie navorsing het aangetoon dat mense van uiteenlopende kulturele orientasies soos in Suid-Afrika die geval is, deur middel van ervaringsleer in groepverband, tot grater eenheid en verdraagsaamheid saamgesnoer kan word. / Psychology of Education / D.Ed. (Psychology of Education)
822

Towards relevance in language teaching : an outcomes-based approach

Lombard, Ilse 06 1900 (has links)
Chapter one of this study outlines some of the problems encountered in education today, with particular reference to the 'relevance gap'. This is taken to mean that the education which learners receive does not adequately prepare them for life, i.e. academic life, social life and their later career. The South African scenario is described briefly, with the focus on English language teaching and learning. The importance of English language skills is underlined. This chapter also includes a discussion on the writer's awareness of the problem, the research proposal, aims and method of the study plus a definition of terms. The next chapter argues that the curriculum is at the centre of the education endeavour and indicates that a relevant curriculum is one that (a) is dynamic, (b) focuses on the learner, (c) considers the context within which and for which the learning takes place and (d) includes all the relevant role-players and stakeholders in its design and development. A set of guidelines for developing and implementing a relevant curriculum, are then suggested based on this assumption. This is followed by a description of the traditional curriculum model, as proposed by Robert Zais (1976), and the outcomes-based approach to curriculum design, development and implementation proposed by William Spady (1993). The latter formed the basis for the development of Curriculum 2005 currently being implemented in South Africa. This section serves to illustrate the differences between these two approaches with regard to the principles underlying the approaches and the elements which determine the structure of the curriculum. In chapter four the researcher attempts to evaluate the traditional curriculum and the outcomesbased approach descn"bed in Chapter 3 on the basis of the guidelines for a relevant curriculum outlined previously, i.e. to what degree do these two models satisfy the need for: * a dynamic curriculum which is true to life and responsive to changes within society; * a focus on learner needs and aptitudes; * a careful consideration of the context within which and for which the learning is taking place; and * the inclusion of the relevant stakeholders and role-players in its design, development and implementation. / Curriculum and Instructional Studies / M. Ed. (Didactics).
823

Eco-valorisation de la plante Kniphofia uvaria : de la plante à la galénique / Eco-valuation of the Kniphofia uvaria plant : from the plant to the galenic form

Duval, Johanna 14 November 2016 (has links)
À l’heure où l’intégration des enjeux environnementaux dans le développement de procédés éco-efficients joue un rôle essentiel dans le moteur de l’innovation responsable, la chimie verte est devenue l’un des sujets de préoccupation majeure. Ainsi, le développement de nouveaux procédés éco-respectueux pour la production d’ingrédients naturels issus de matières premières végétales renouvelables est devenu une démarche incontournable dans le modèle de recherche. L’objectif de cette thèse a consisté au développement d’une stratégie d’éco-valorisation innovante employant les fluides sub/supercritiques pour l’extraction, la caractérisation, la production et l’imprégnation sur support cosmétique de produits naturels d’origine végétale. Pour cela, nous avons utilisé comme modèle végétal : les graines oléagineuses de la plante Kniphofia uvaria, sélectionnée pour des applications cosmétiques grâce à ses propriétés bioactives antioxydantes et anti-âge. Dans un premier temps, le développement de méthodes complémentaires en SFC ainsi que le développement du couplage SFC-MS a été réalisé à l’aide de la source APCI afin d’identifier les molécules responsables des activités bioactives des graines de Kniphofia uvaria. Ainsi, le développement d’un système hybride (U)HPLC/SFC-HRMS a été réalisé afin de mettre en place ce couplage. Des optimisations en termes de proportion et nature de solvant make-up ainsi qu’un travail au niveau des paramètres SFC et MS ont été faits afin de d’améliorer la sensibilité et la spécificité des analyses lipidiques. Dans un second temps, nous nous sommes attachés au développement d’une stratégie d’enrichissement en composés bioactifs à l’aide des méthodes : SFE et CPC. Ainsi, en SFE, des optimisations en termes de température, pression, nature/proportions de co-solvant dans le fluide ont été réalisées alors qu’en CPC, des optimisations au niveau de l’injection ont été faites. Des conditions optimales pour le fractionnement sélectif des anthraquinones et des triglycérides ont été déterminées en SFE et CPC. Dans un dernier temps, ce travail a consisté à développer un couplage en-ligne pour extraire et imprégner sélectivement sur silice cosmétique : les anthraquinones. Le développement et l’optimisation de ce procédé en-ligne ont été réalisés à l’échelle du laboratoire et ont démontré la faisabilité de ce couplage ainsi qu’un intérêt certain pour l’obtention de produits naturels sous une première forme galénique, destinée à une future incorporation dans la formulation de cosmétiques. / Nowadays, green chemistry is a great challenge. It seeks innovation in the development of eco-efficient processes. The production of natural products from renewable materials by these new environmentally friendly processes is more and more used. The aim of this Ph.D thesis is to develop an eco-valuation strategy to extract, characterize, produce and impregnate natural products onto a cosmetic support using sub/supercritical fluids. Consequently, we used oleaginous plant seeds from Kniphofia uvaria as a plant model, which was selected for its interesting cosmetic properties such as antioxidant or anti-ageing. Firstly, the SFC-MS hyphenation with the APCI as an ionization source was developed to screen bioactive molecules; responsible of cosmetic properties. This coupling was performed by the hybrid combination of (U)HPLC/SFC-HRMS. Various optimizations in terms of the solvent make-up (nature and proportion), modulation with SFC and MS parameters were carried out in order to improve sensitivity and selectivity of lipid analysis. Secondly, an enrichment strategy to concentrate bioactive compounds in the final extract was developed by SFE and CPC. Thus, in SFE, experimental parameters (temperature, pressure, nature/proportion of the modifier in the CO2 fluid) were optimized while in CPC, the injection optimization was realized. Methods for the selective fractionation of anthraquinones and triglycerides were obtained in CPC and SFE. Finally, an on-line sub/supercritical extraction-impregnation process was developed to extract and for simultaneously impregnating anthraquinones onto a cosmetic silica. Development and optimization of this process was realized on a laboratory scale. Consequently, this study demonstrated the feasibility of this concept and it presents a great interest to provide natural products as a galenic form, which could be used in the cosmetic formulation.
824

Les rapports patrimoniaux entre concubins et leur liquidation. Etude comparative des droits français et polonais / Property relations between cohabitants and their settlement. A comparative study of French and Polish law

Pfeifer-Chomiczewska, Katarzyna 12 June 2015 (has links)
Après avoir quitté le monde de la réprobation, le concubinage a intégré l'ordre social et par suite, l'ordre juridique. Le concubinage est devenu l'une des conjugalités. Contrairement au législateur français, le législateur polonais n'a pas donné de définition du concubinage. Nonobstant cette différence, les éléments constitutifs du concubinage dans les deux systèmes légaux se ressemblent. Le concubinage se caractérise tant en France qu'en Pologne par: l'absence de lien juridique entre les concubins, la monogamie, la stabilité et la continuité et la communauté de vie. Dans les deux pays, le concubinage n'est pas juridiquement inorganisé. Le concubinage ne fait naître aucun droit ni obligation entre concubins, que ce soit sur le plan personnel ou patrimonial. / After leaving the world of disapproval, concubinage has integrated the social order and consequently the legal order. In French law, cohabitation is legally defined. In Poland, a legal definition of cohabitation does not exist. Notwithstanding this difference, the elements of cohabitation in the two legal systems are similar. Cohabitation is characterized in France and in Poland by the absence of a legal relationship between partners, monogamy, stability and continuity, and community of life. In both countries, concubinage is not legally organized. Cohabitation does not create any rights or obligations between the cohabitants, whether in a personal, property or financial sphere. Property relationships of cohabitants and their liquidation pose many difficulties. In order to legally qualify the economic acts of the cohabitants, it is necessary to retrospectively analyse the facts.
825

Quantitative measurements of temperature using laser-induced thermal grating spectroscopy in reacting and non-reacting flows

Lowe, Steven January 2018 (has links)
This thesis is concerned with the development and application of laser induced thermal grating spectroscopy (LITGS) as a tool for thermometry in reacting and non-reacting flows. LITGS signals, which require resonant excitation of an absorbing species in the measurement region to produce a thermal grating, are acquired for systematic measurements of temperature in high pressure flames using OH and NO as target absorbing species in the burned gas. The signal obtained in LITGS measurements appears in the form of a time-based signal with a characteristic frequency proportional to the value or the sound speed of the local medium. With knowledge of the gas composition, the temperature can be derived from the speed of sound measurement. LITGS thermometry using resonant excitation of OH in the burned gas region of in oxygen enriched CH4/O2/N2 and CH4/air laminar flames was performed at elevated pressure (0.5 MPa) for a range of conditions. Measurements were acquired in oxygen enriched flames to provide an environment in which to demonstrate LITGS thermometry under high temperature conditions (up to 2900 K). The primary parameters that influence the quality of LITGS signal were also investigated. The signal contrast, which acts as a marker for the strength of the frequency oscillations, is shown to increase with an increase in the burnt gas density at the measurement point. LITGS employing resonant excitation of NO is also demonstrated for quantitative measurements of temperature in three environments – a static pressure cell at ambient temperature, a non-reacting heated jet at ambient pressure and a laminar premixed CH4/NH3/air flame operating at 0.5 MPa. Flame temperature measurements were acquired at various locations in the burned gas close to a water-cooled stagnation plate, demonstrating the capability of NO-LITGS thermometry for measuring the spatial distribution of temperature in combustion environments. In addition, the parameters that in influence the local temperature rise due to LITGS were also investigated in continuous vapour flows of acetone/air and toluene/air mixtures at atmospheric conditions. Acetone and toluene are commonly targeted species in previous LITGS measurements due to their favourable absorption characteristics. Results indicate that LITGS has the potential to produce accurate and precise measurements of temperature in non-reacting flows, but that the product of the pump intensity at the probe volume and the absorber concentration must remain relatively low to avoid significant localised heating of the measurement region.
826

Hydrologie et géochimie des transports fluviaux dissous et particulaires dans le bassin versant du Milo (République de Guinée) / Hydrology and geochemistry of dissolved and particulate fluvial transport in the Milo watershed (Republic of Guinea)

Sow, Mamadou Alpha 14 May 2018 (has links)
En Guinée, la disponibilité des ressources en eau est soumise à de graves problèmes de gestion avec des conséquences importantes pour les populations, notamment à Kankan où la plupart des puits tarissent pendant la saison sèche, et où la fourniture régulière de l’eau à partir de la rivière Milo n'est pas assurée dans tous les quartiers de la ville. Le Milo et son bassin versant représente donc un enjeu important pour les habitants de cette ville. Le Milo (480 km de long) qui draine un bassin versant 13 810 km2 est le plus important des affluents rive droite du Niger. Pour évaluer l’impact du bassin versant du Milo et de la ville de Kankan sur la qualité des eaux et des sédiments de ce cours d’eau, 30 échantillons de sédiments de fond ont été prélevés au cours d’une première campagne (juin-juillet 2013) sur l’ensemble des cours d’eau du bassin versant, tandis que durant une deuxième campagne (avril 2014-mai 2015), un suivi régulier a été mis en place sur le Milo en amont et en aval de Kankan. Au cours de cette dernière, 232 échantillons d’eau du Milo (dont 116 utilisés pour l’isotopie), et 26 échantillons de sédiments de fond ont été prélevés sur les stations de Bordo (amont de Kankan) et de Karifamoriah (aval de Kankan). Les concentrations en éléments majeurs et traces, terres rares, COP, COD, pH, alcalinité, l’azote organique, les isotopes de l’oxygène et de l’hydrogène, ainsi que la micro-granulométrie des sédiments ont été mesurés. Les résultats obtenus durant le cycle hydrologique 2014-2015 ont permis d’estimer le flux de matières exportées en solution par le Milo à Kankan à 47 863 t.an-1 et le flux de matières particulaires à 76 759 t.an-1. 92% de ce tonnage est exporté durant la période des hautes eaux. Ces flux permettent d’estimer des vitesses moyennes d’érosion physique (8 t.km-2.an-1) et d’altération chimique (5 t.km-2.an-1) du bassin relativement faibles. Le flux spécifique de CO2 consommé par l’altération chimique est lui aussi relativement faible (76.103 mole.km-2.an-1), mais il reste dans la moyenne des flux de CO2 mesurés sur les bassins couverts de sols latéritiques. Le degré de contamination des sédiments et sa variation spatio-temporelle ont été évalués grâce au calcul du facteur d’enrichissement (FE), en normalisant les concentrations en éléments traces par rapport à Al, Sc et Ti et en prenant le PAAS et l’UCC comme matériaux de référence. La quasi-totalité des éléments traces proviennent essentiellement des processus d’altération et sont d’origine naturelle. Toutefois, un enrichissement modéré à significatif (5 < FE < 20) a été mis en évidence pour Zr et Hf (enrichissements naturels) et As et Sb (impacts anthropiques). Finalement, l’apport anthropique en éléments traces, quand il existe, reste modéré. Les profils de concentrations en terres rares ont permis de montrer que la signature géochimique des sédiments de fond du Milo est homogène sur l’ensemble du bassin et caractéristique des sols latéritiques, non perturbée par la ville de Kankan et elle est proche des signatures du PAAS et de l’UCC. Pour l’ensemble des éléments traces et des terres rares la contribution anthropique reste faible et les fractions disponibles (phases labiles) sur les sédiments (extraction à l’EDTA) sont également faibles, confirmant ainsi que l’essentiel de ces éléments rentrent principalement dans la composition des phases résiduelles. / In Guinea, the availability of water resources is subjected to serious problems of management with important consequences for the populations, particularly in Kankan city where most of the wells dry up during the dry season and where the water supply from the Milo river is not assured for all the districts. Then the Milo river and its watershed represent an important issue for the inhabitants of Kankan. The Milo river (480 km in length) which drains an area of 13 810 km2 is the most important right-bank tributary of the Niger river. To evaluate the impact of the Milo watershed and of the Kankan city on the water and sediments of this river, 30 samples of bottom sediments have been collected during a first campaign (June-July 2013) on the main course from upstream to downstream and on the main tributaries, whereas during a second campaign (April 2014-May 2015) a regular monitoring was set up on the Milo river, upstream and downstream Kankan city. During this campaign, 232 river water samples (of which 116 for isotopic analyses) and 26 bottom sediment samples have been collected at Bordo (upstream) and Karifamoriah (downstream) stations. The concentrations of major and trace elements, rare earth elements, POC and PON, DOC, pH, alkalinity, the isotopic composition of O, H and the micro-granulometry of sediments have been measured. The results obtained during the hydrological cycle 2014-2015 allowed to estimate the fluxes of dissolved (47 863 t.y-1) and particulate (76 759 t.y-1) matters exported by the Milo river at Kankan. 92% of these fluxes are exported during the high flow period. These fluxes allowed us to estimate very low average rates of physical erosion (8 t.km-2.y-1) and chemical weathering (5 t.km-2.y-1) of the Milo catchment. The specific flux of CO2 consumed by chemical weathering (76.103 mole.km-2.y-1) is relatively low but within the range of CO2 fluxes measured in catchments draining lateritic soils. The degree of sediment contamination and its spatio-temporal variation have been assessed using the enrichment factor (EF), by normalizing the trace element concentrations with Al, Sc and Ti and by taking PAAS and UCC as the reference materials. Almost all the trace elements mainly originate from weathering processes and are of natural origin. Nevertheless, moderate to significant enrichments (5 < EF < 20) have been calculated for Zr and Hf (natural enrichments) and As and Sb (anthropogenic impacts). Finally, the anthropogenic contribution of trace elements, when it exists, remains moderate. The rare earth concentration patterns allowed to show the geochemical signature of river bottom sediments is homogeneous within the Milo catchment and characteristic of lateritic soils, non- perturbed by the city of Kankan and close to the PAAS and UCC patterns. For most of the trace and rare earth elements, the anthropogenic contribution remains low and the available fractions (labile phases) in the sediment (EDTA extraction) are also low, confirming that the main part of these elements are mainly in the residual phases.
827

Cell-free fetal DNA (cffDNA) enrichment for non-invasive prenatal testing (NIPT) : a comparison of molecular techniques

Sillence, Kelly January 2016 (has links)
Prenatal assessment of fetal health is routinely offered throughout pregnancy to ensure that the most effective management can be provided to maintain fetal and maternal well-being. Currently, invasive testing is used for definitive diagnosis of fetal aneuploidy, which is associated with a 1% risk of iatrogenic fetal loss. Developing non-invasive prenatal testing (NIPT) is a key area of research and methods to increase the level of cell-free fetal DNA (cffDNA) within the maternal circulation have been discussed to improve accuracy of such tests. In this study, three strategies; co-amplification at lower denaturation temperature polymerase chain reaction (COLD-PCR), inverse-PCR and Pippin Prep™ gel electrophoresis, were analysed to identify a novel approach to selectively enrich shorter cffDNA fragments from larger maternal cell-free DNA (cfDNA). The sensitivity of droplet digital PCR (ddPCR) against real-time PCR (qPCR) was compared for fetal sex and RHD genotyping. In addition RHD zygosity testing was carried out for non-maternal samples. Consequently, Pippin Prep™ gel electrophoresis was combined with ddPCR analysis for the NIPD of Down Syndrome (DS) in pseudo-maternal samples. The results revealed that the Pippin Prep™ gel electrophoresis enrichment approach successfully demonstrated 2-fold to 5-fold increases in the cffDNA fraction. However, further optimisation assays of COLD-PCR and inverse-PCR using actual maternal samples were required. The spike experiments for DS detection revealed that with the present assay IV overrepresentation of the chromosome 21 target could be significantly detected for samples with ≥15% ‘cffDNA fraction’. In conjunction with the Pippin Prep™ enrichment method, this would have enabled assessment of all 10 maternal samples. Alternatively, fetal sex and RHD genotyping results determined that ddPCR provides a more sensitive platform compared to qPCR approaches, particularly for samples that express low cffDNA fractions (<2%). The ddPCR platform also proved to be a rapid and accurate system for the determination of RHD zygosity. This study highlights that ddPCR could be used as opposed to qPCR for accurate determination of fetal sex and RHD status. While sequencing approaches currently provide the most sensitive platforms for NIPT of fetal aneuploidy, high costs (>£400) prevent universal application. The combination of cffDNA enrichment with ddPCR analysis could provide a cheaper and more widely available platform for NIPD. However, further large scale validation studies using actual maternal samples are required.
828

Functional association networks for disease gene prediction

Guala, Dimitri January 2017 (has links)
Mapping of the human genome has been instrumental in understanding diseasescaused by changes in single genes. However, disease mechanisms involvingmultiple genes have proven to be much more elusive. Their complexityemerges from interactions of intracellular molecules and makes them immuneto the traditional reductionist approach. Only by modelling this complexinteraction pattern using networks is it possible to understand the emergentproperties that give rise to diseases.The overarching term used to describe both physical and indirect interactionsinvolved in the same functions is functional association. FunCoup is oneof the most comprehensive networks of functional association. It uses a naïveBayesian approach to integrate high-throughput experimental evidence of intracellularinteractions in humans and multiple model organisms. In the firstupdate, both the coverage and the quality of the interactions, were increasedand a feature for comparing interactions across species was added. The latestupdate involved a complete overhaul of all data sources, including a refinementof the training data and addition of new class and sources of interactionsas well as six new species.Disease-specific changes in genes can be identified using high-throughputgenome-wide studies of patients and healthy individuals. To understand theunderlying mechanisms that produce these changes, they can be mapped tocollections of genes with known functions, such as pathways. BinoX wasdeveloped to map altered genes to pathways using the topology of FunCoup.This approach combined with a new random model for comparison enables BinoXto outperform traditional gene-overlap-based methods and other networkbasedtechniques.Results from high-throughput experiments are challenged by noise and biases,resulting in many false positives. Statistical attempts to correct for thesechallenges have led to a reduction in coverage. Both limitations can be remediedusing prioritisation tools such as MaxLink, which ranks genes using guiltby association in the context of a functional association network. MaxLink’salgorithm was generalised to work with any disease phenotype and its statisticalfoundation was strengthened. MaxLink’s predictions were validatedexperimentally using FRET.The availability of prioritisation tools without an appropriate way to comparethem makes it difficult to select the correct tool for a problem domain.A benchmark to assess performance of prioritisation tools in terms of theirability to generalise to new data was developed. FunCoup was used for prioritisationwhile testing was done using cross-validation of terms derived fromGene Ontology. This resulted in a robust and unbiased benchmark for evaluationof current and future prioritisation tools. Surprisingly, previously superiortools based on global network structure were shown to be inferior to a localnetwork-based tool when performance was analysed on the most relevant partof the output, i.e. the top ranked genes.This thesis demonstrates how a network that models the intricate biologyof the cell can contribute with valuable insights for researchers that study diseaseswith complex genetic origins. The developed tools will help the researchcommunity to understand the underlying causes of such diseases and discovernew treatment targets. The robust way to benchmark such tools will help researchersto select the proper tool for their problem domain. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: Manuscript. Paper 6: Manuscript.</p>
829

Sélection et caractérisation d’aptamères oligonucléotidiques régulateurs de la protéine STAT5B, impliquée dans les leucémies / Selection and characterization of DNA aptamers regulating STAT5B, a protein involved in leukemias

Loussouarn, Claire 20 March 2014 (has links)
Les cancers, qu’il s’agisse de leucémies ou de tumeurs solides, sont le résultat de proliférations cellulaires anormales et non contrôlées au sein des tissus. Ces proliférations anarchiques sont le reflet d’une surexpression et/ou sur-activation de protéines intracellulaires engendrées par un événement oncogénique. Aujourd’hui encore il est donc nécessaire de trouver de nouvelles molécules à usage thérapeutique ciblant spécifiquement ces protéines. C’est dans ce contexte que les facteurs de transcription STAT5 constituent de véritables cibles de choix puisque ces protéines participent activement à la leucogénèse. L’implication directe des protéines STAT5 dans la génèse des leucémies a été démontrée par l’utilisation de formes mutées constitutivement active de STAT5. Les facteurs de transcription STAT5 jouent un rôle essentiel dans la voie de signalisation JAK/STAT. Cette voie aboutit à la régulation de grandes fonctions biologiques telles que la prolifération cellulaire, la différenciation cellulaire ou encore l’apoptose. L’objectif de ce projet consiste donc à cibler spécifiquement les protéines STAT5 dans le but de rétablir le processus de mort cellulaire et empêcher la prolifération des cellules cancéreuses. Les inhibiteurs spécifiques des protéines STAT5 sont sélectionnés selon la méthode SELEX qui permet d’isoler des ligands structurés de forte affinité pour la protéine. L’affinité et la spécificité de ces inhibiteurs, appelés aptamères, sont caractérisées à partir de modèles cellulaires de leucémies dépendant de l’activité des facteurs de transcription STAT5. Les aptamères sont aujourd’hui de véritables outils thérapeutiques en pleine évolution. / Leukemias are due to abnormal cell proliferation, which is the result of intracellular over-expression or excessive activation of protein due to oncogenic event. Still today, it is necessary to find new therapeutic molecules, which specifically target these proteins. STAT5, via the JAK/STAT signaling pathway, controls fundamental cellular processes, including .cell survival, proliferation and differentiation. To struggle against tumorigenesis, JAK/STAT signaling pathway has to be inhibited. The aim of this project is to target specifically STAT5 factors to restore healthy signal transduction. We generated aptamers by an iterative in vitro selection. Aptamers are short-structured single strand DNAs or RNAs that bind with high affinity and specificity to their target. Once STAT5B recombinant proteins are produced, they are subjected to SELEX process. The number of rounds depends on various parameters. After seven rounds, two sequences are retrieved. The specificity and affinity of these aptamers are assessed by fluorescent immunoassays. Binding affinity and kinetics of interaction are characterized by SPR. Aptamer anti proliferative effects are determined by evaluation of the growth of cells depending on STAT5. Finally, we developed several .assays aiming at understanding the mechanism of an aptamer action on STAT5B such as phosphorylation measurement and EMSA. Aptamers are now emerging therapeutic tools; they exhibit significant advantages relative to protein therapeutics.
830

Étude des mécanismes du débordement de bien-être psychologique entre le travail et la famille

Provost Savard, Yanick 04 1900 (has links)
Le travail et la famille sont souvent vus comme deux domaines en compétition pour le temps, l’énergie et l’attention des travailleurs. Pourtant, des synergies positives existeraient à l’interface entre ces deux domaines de vie. Plus particulièrement, le bien-être psychologique pourrait déborder positivement d’un domaine à l’autre. Des articulations théoriques réfèrent au débordement de bien-être psychologique (p. ex., Edwards et Rothbard, 2000 ; Greenhaus et Powell, 2006), mais très peu d’études se sont attardées à évaluer les mécanismes par lesquels les bien-être psychologiques au travail et dans la famille s’influencent mutuellement. Les études antérieures ne permettent pas de capter adéquatement le processus à l’intérieur duquel les mécanismes de débordement opèrent, et ce, pour deux raisons. D’une part, elles recourent à des concepts-valises qui englobent l’ensemble du débordement et éludent ainsi les mécanismes internes à celui-ci. D’autre part, elles utilisent des devis majoritairement transversaux qui ne permettent pas de capter le déploiement temporel des mécanismes à l’étude. L’objectif de la présente thèse est donc d’évaluer un ensemble de mécanismes pouvant expliquer le débordement de bien-être psychologique entre le travail et la famille. Le premier article évalue le rôle médiateur de la performance au travail dans la relation du bien-être psychologique dans la vie hors travail vers le bien-être psychologique au travail, mécanisme le plus universellement soutenu par les théorisations de l’interface travail-famille. Ainsi, l’article explore plus en profondeur ce mécanisme en l’évaluant selon deux conceptualisations du bien-être psychologique, ainsi que deux types de performance. Deux études ont été réalisées : l’une à deux temps de mesure séparés de 7,5 mois et l’autre mesurant des expériences journalières concomitantes. Les résultats confirment le rôle médiateur de la performance dans les deux cas et mettent en lumière les distinctions entre le débordement de bien-être cognitif et celui de bien-être affectif. Le deuxième article explore trois autres mécanismes de débordement : la satisfaction dans la vie (médiateur), la centralité du domaine d’origine dans l’identité et la force des frontières travail-famille (modérateurs). Des théorisations périphériques au thème du débordement travail-famille enrichissent la compréhension du processus de débordement du travail vers la famille et inversement. Six-mille-soixante-dix-sept jeunes travailleurs ont répondu à trois questionnaires séparés de 11 semaines chacun. Des analyses acheminatoires soutiennent le rôle médiateur de la satisfaction dans la vie. Par ailleurs, nous avons trouvé que plus un individu accorde d’importance à sa famille, plus sa satisfaction dans la famille influencerait positivement sa satisfaction dans la vie. Finalement, la force des frontières entourant la famille limiterait le débordement de bien-être psychologique du travail vers la famille. Cette thèse a pour principale contribution l’articulation de plusieurs propositions théoriques en un modèle cohérent de débordement de bien-être psychologique entre le travail et la famille, ainsi que son évaluation empirique. Nos études étayent la documentation précédente en recourant à des échantillons diversifiés et à des méthodologies rigoureuses. Les résultats de cette thèse présentent des implications pratiques pour les travailleurs, les organisations et la société. / Work and family are often considered as two domains competing for the time, energy and attention of workers. Positive synergies could nonetheless exist at the interface between these two life domains. Notably, psychological well-being could spillover from one domain to the other. Theoretical frameworks about the spillover of psychological well-being exist (e.g., Edwards & Rothbard, 2000; Greenhaus & Powell, 2006), but very few studies have evaluated the mechanisms through which work and family psychological well-being influence each other. Previous studies do not adequately capture the process within which spillover mechanisms operate for two reasons. On the one hand, they use global concepts encompassing the whole spillover process, thereby disregarding internal mechanisms. On the other hand, they mainly use cross-sectional designs which cannot capture the processual nature of the proposed mechanisms. The objective of this thesis is therefore to evaluate mechanisms that could explain work-family psychological well-being spillover. The first article evaluates the mediating role of work performance in the influence of psychological well-being outside of work on psychological well-being at work, the mechanism most supported by work-family interface theories. Hence, the article explores this mechanism in depth by evaluating it according to two psychological well-being conceptualizations, as well as two types of performance. Two studies were conducted: one using a two-wave design with a 7.5-month delay and the other measuring experiences on a given workday. Results support the mediating role of performance in both studies and shed light on the distinction between cognitive well-being spillover and affective well-being spillover. The second article explores three other spillover mechanisms: life satisfaction (mediator), originating domain identity centrality, and work-family boundary strength (moderators). Theoretical articulations peripheral to work-family spillover enhance the understanding of the spillover process from work to family and inversely. Six thousand seventy-seven young workers answered three questionnaires with a delay of 11 weeks between each measurement time. Path analyses support the mediating role of life satisfaction. Furthermore, we discovered that the more an individual considers family as an important life domain, the more its family satisfaction will positively influence its life satisfaction. Finally, home boundary strength appears to limit the psychological well-being spillover from work to family. The main contribution of this thesis is its articulation of different theoretical propositions in one consistent work-family psychological well-being spillover model, as well as its empirical evaluation. Our studies build on previous literature by tapping on diverse samples and rigorous methods. The results of this thesis show practical implications for workers, organizations, and society.

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