L'évaluation de l'implication des récepteurs B [indice] 1 dans plusieurs pathologies est difficile car le temps de demi-vie des antagonistes est de très courte durée. Afin d'obtenir des antagonistes puissants et résistants au métabolisme enzymatique, plusieurs méthodes ont été utilisées: la cyclisation, introduction d'un lien pseudopeptidique, d'un espaceur ou d'acides aminés de configuration D, non-naturels avec ou sans méthylation. Ces différentes méthodes ont toutes été utilisées dans cette étude en modifiant la structure du R-715 (Ac-Lys[D[bêta]Nal[exposant]7 ,Ile[exposant]8 ]desArg[exposant]9 BK) ou de la desArg[exposant]9 BK. Dix analogues ont été obtenus: [Tableau omis.] L'affinité des composés pour le récepteur B [indice] 1 a été évaluée par essais fonctionnels in vitro sur la veine ombilicale humaine et leur résistance enzymatique à l'enzyme de conversion de l'angiotensine I (ECA) par des essais biochimiques in vitro. Les différentes stratégies utilisées ont permis de développer plusieurs composés résistants au métabolisme par l'ECA: R715c, R905, R955, R954, R909, R982 et R981. De plus, parmi les composés synthétisés, plusieurs ont gardé plus de 10% de l'activité antagoniste du R715: R905, R955, R954, R891 et R909. Quatre composés se distinguent pour avoir acquis une résistance enzymatique en plus de conserver une bonne activité antagoniste sur le récepteur B [indice] 1 : R905, R955, R954 et R909. Parmi les stratégies utilisées, l'utilisation du lien pseudopeptidique Phe [exposant] 5 -Ser [exposant] 6 dans le R905, du résidue Chg [exposant] 5 dans le R909, ainsi que la méthylation de la Phe [exposant] 5 dans le R955 et R954 se sont démarqués par leur efficacité. Parmi les autres objectifs du projet se trouve l'étude des interactions entre le ligand antagoniste et le récepteur B [indice] 1 . Avec les multiples modifications utilisées, il a été possible d'augmenter notre connaissance de ces interactions et de proposer des groupements nécessaires à ces interactions.

ITC/USA 2007 Conference Proceedings / The Forty-Third Annual International Telemetering Conference and Technical Exhibition / October 22-25, 2007 / Riviera Hotel & Convention Center, Las Vegas, Nevada / As the frequency spectrum becomes more crowded each day, preparation for placement of tracking ground station in tracking environment gains more importance. Existence of high power weather ground radars, airport approach equipment, and various other RF sources in the environment necessitates the test teams to be more cautious. This paper discusses, implemented design changes to an S-band antenna system to reduce the in-band interfering power, calculation of the effects from nearby interferers, analysis of the environment during placement of the mobile ground system by Honeywell telemetry teams.

Mouse polyomavirus (MPyV) is a small non-enveloped virus. Its capsid consists of 72 pentamers of the major capsid protein VP1. The central cavity of each VP1 pentamer contains one minor capsid protein, either VP2, or VP3. The minor capsid proteins are dispensable for capsid formation, but their presence is required for infection of the host cell, presumably because of their anticipated functions during virus entry. After internalization, MPyV virions traffic to endoplasmic reticulum (ER). VP2 and VP3 have been proposed to function as factors responsible for penetration of ER membranes, which is required for subsequent delivery of the viral DNA into the nucleus, a key step of the early phase of MPyV infection. Three hydrophobic domains were predicted in the sequence of VP2 and VP3. First in the unique Nterminal part of VP2, second and third in the common part of VP2 and VP3. The third domain corresponds to C-terminal VP1binding alpha-helix. It has been previously found in our laboratory, that VP2 and VP3 fused to N-terminus of EGFP, when expressed in mammalian cells, display properties similiar to the wild-type VP2 and VP3, namely affinity to intracellular membranes and high cytotoxicity. Expression plasmids carrying mutated VP2 and VP3 fused to Nterminus of EGFP were prepared to determine the hydrophobic...

Inclusive education policies in South Africa aim to reduce the barriers to learning of learners with learning disabilities (LDs).(1) Occupational therapists play an important role in identifying these barriers and collaborating with the educators to implement environmental modifications (EMs) in the classroom to enhance the academic performance of learners. This study aims to explore the use of as well as the effectiveness of EMs in grade two classrooms of learners with special education needs (LSEN) schools in the greater Johannesburg area. Eight semi structured interviews were conducted. The qualitative data was analysed using priori categories based on a framework provided by Mulligan(2). A wide variety of EMs were identified by the participants, indicating the effectiveness of the modifications used. In conclusion the EMs were more concisely divided into three categories, namely behavioural modifications, physical modifications and modifications to the delivery of the curriculum, demonstrating a diverse interrelationships between the categories. Keywords: Occupational therapy, learning disabilities, environmental modifications, classroom environment, LSEN schools.

Barley (Hordeum vulgare) is an economically important crop species with a large diploid genome. Around a half of the barley genome and a fifth of the genes are constrained within a low-recombining pericentromeric (LR-PC) region. I explored the LR-PC gene component with a genomic investigation of gene expression, diversity and evolution. Chromatin environments were also explored in the LR and high recombining (HR) regions by surveying the genic and genomic distributions of nine histone modifications. Firstly, regions of HR and LR were identified and compared for gene evolution, expression and diversity. LR regions of the barley genome were found to be restrictive for gene evolution and diversity, but not gene expression. I employed a bioinformatics approach to identify ancient gene pairs in barley to determine the long-term effects of residency in those regions upon gene evolution. Gene pair loss in LR regions was found to be elevated relative to the HR regions. Applying the same method to rice and Brachypodium distachyon revealed the same situation, suggesting a universal process in the grasses for loss of gene pairs in LR regions. The chromosomal distributions of transposable elements (TEs) were also explored and examined for correlations with recombination rate. Secondly, I developed a chromatin immunoprecipitation followed by Next Generation Sequencing (ChIP-seq) protocol for the investigation of histone modifications in barley seedlings. A protocol was optimised for the fixation, extraction and sonication of barley chromatin. The protocol was applied using antibodies against 13 different histone modifications. Following DNA library construction and Illumina sequencing, a bioinformatics pipeline was devised to analyse the sequence data. NGS reads were mapped to a custom assembly of the barley cultivar Morex reference genome sequence before peak calling. Genomic and genic locations were determined for the covalently modified histones. Four modifications were discarded from further study on the basis of low peak numbers or unexpected chromosomal locations. The remaining nine modifications were classified into four groups based on chromosomal distributions. Groupings were closely mirrored by peak sharing relationships between the modifications except histone H3 lysine-27 tri-methylation (H3K27me3). In addition, chromatin states representing local chromatin environments were defined in the barley genome using the peak sharing data. Mapping the states onto the genome revealed a striking chromatin structure of the gene-rich chromosome arms. A telomere-proximal region bearing high levels of H3K27me3-containing states was found adjacent to an interior gene-rich region characterised by active chromatin states lacking H3K27me3. The LTR retroelement-rich interior was found to be associated with repressive chromatin states. The histone modification status of TE classes were also probed revealing unexpected differences relating to the genomic and genic distributions of these elements. Finally, a genome browser was created to host the information publicly.

O estudo aborda as modificações corporais por meio de diversas técnicas, as possibilidades de vestuário que dão-se com as novas tecnologias e diferenciais nas modelagens básicas. As análises mostram como corpo e moda são simultâneos e ocorrem de acordo com a época em que estão inseridos. Tal estudo torna-se relevante por analisar corpo e moda no contemporâneo e como ambos estão em constante modificações. Para as análises, foram pesquisadas imagens diversas em que podemos verificar as transformações corporais e o motivo das mesmas, podendo ser por crenças religiosas, ou a fim de diferenciar-se ou enquadrar-se em determinados grupos, e imagens de moda em que podemos observar como as novas tecnologias são aplicadas a fim de obter um produto com aspectos inovadores, estes com propriedades desde as que podem auxiliar a medicina, como também aquelas com caráter apenas estético. Mostraremos como a moda pode obter determinados elementos a fim de termos um corpo híbrido nas passarelas e como, no contemporâneo, faz-se diferente até as apresentações de desfiles. / This essay deals with body modifications through many techniques, the possibilities of clothing which are obtained with new technologies and differentials in basic modelings. The analyses show how body and fashion are simultaneous and happen accordingly to the time in which they are inserted in. Such study becomes relevant by analysing body and fashion on contemporary days and how both of them are in constant changes. Several images were researched to enable the analyses, so that we can verify body transformations and the reasons why they happen ( be it for religious beliefs, for standing out from others or for taking part of a given group). We can observe in fashion images how new techniques are applied to get a product with innovative aspects which have properties that either may have only aesthetic character or can help medicine. We are going to show how fashion can get certain elements for us to have a hybrid body on stages and how even fashion shows are done differently nowadays.

Le cancer de la prostate est une pathologie impliquant des facteurs divers comme l'hérédité, l'appartenance ethnique mais aussi des facteurs environnementaux. En effet, il a été démontré que certains micronutriments dont les phyto-oestrogènes contenus dans l'alimentation pouvaient avoir un rôle protecteur vis-à-vis de cette pathologie. Ces molécules seraient capables de moduler les mécanismes épigénétiques observés dans le cancer de la prostate. L'objectif de ce travail a été de déterminer si les phyto-oestrogènes du soja pouvaient induire la réversion de la méthylation d'oncosuppresseurs impliqués dans la cancérogenèse prostatique et par quelles voies moléculaires. Nos études, in vitro, réalisées sur des lignées continues de cancer de la prostate (DU-145, PC-3 et LNCaP) ont montré dans un premier temps, une diminution de la méthylation des gènes GSTP1, RASSF1A, EPHB2 et BRCA1 et une augmentation des protéines correspondantes, suite au traitement par la génistéine (40μM) et la daidzéine (110μM) pendant 48H. Dans un deuxième temps, une étude comparative entre l'effet des phyto-oestrogènes et l'oestradiol sur la méthylation de l'ADN d'un panel de 24 gènes a permis de mettre en évidence une régulation des mécanismes épigénétiques par les phyto-oestrogènes via la voie des Récepteurs aux oestrogènes. En conclusion, les phyto-oestrogènes agissent sur les mécanismes épigénétiques dans la cancérogenèse prostatique laissant supposer que ces molécules pourraient jouer un rôle préventif dans cette pathologie. / Prostate cancer is a disease caused by a multiple interacting factors such as family history of prostate cancer, age and ethnic origin. Environnemental factors play also a role in prostatic carcinogenesis events. Indeed, several studies have reported the efficiency of nutrients such as phytoestrogens to possess anticancer properties. It has been reported that these compounds may have the ability to induce the reversion of epigenetic modifications observed in prostate cancer cells. The aim of this work was to determine if soy isoflavone could reverse the DNA methylation of oncosuppressor which are hypermethylated in prostate cancer and through which metabolic pathways. Our in vitro studies were carried out on tree prostate cancer cell lines: DU-145, PC-3 and LNCaP. The qualitative and quantitative studies performed demonstrated a decrease of methylation percentage of GSTP1, RASSF1A, EPHB2 and BRCA1 after soy isoflavone treatment. In a second step, a comparative study between the effect of phytoestrogens and estradiol on the DNA methylation of a panel of 24 genes was performed. Our results has highlighted that the regulation of epigenetic mechanisms by phytoestrogens may be mediated via the estrogen receptor pathway. In conclusion, phytoestrogen act on epigenetics mechanisms on prostate carcinogenesis suggesting that these molecules may play a role in the prevention of this pathology.

Epigenetic modifications, transcription factor (TF) availability and chromatin conformation influence how a genome is interpreted by the transcriptional machinery responsible for gene expression. Enhancers buried in non-coding regions are associated with significant differences in histone marks between different cell types. In contrast, gene promoters show more uniform modifications across cell types. In this report, enhancer identification is first carried out using an enhancer associated feature in mouse erythroid cells. Taking advantage of public domain ChIP-Seq data sets in mouse embryonic stem cells, an integrative model is then used to assess features in enhancer prediction, and subsequently locate enhancers. Significant associations with multiple TF bound loci, higher expression in the closest genes, and active enhancer marks support functionality and tissue-specificity of these enhancers. Motif enrichment analysis further determines known and novel TFs regulating the target cell type. Furthermore, the features identified can facilitate more accurate enhancer prediction in other cell types.

Epigenetic modifications, transcription factor (TF) availability and chromatin conformation influence how a genome is interpreted by the transcriptional machinery responsible for gene expression. Enhancers buried in non-coding regions are associated with significant differences in histone marks between different cell types. In contrast, gene promoters show more uniform modifications across cell types. In this report, enhancer identification is first carried out using an enhancer associated feature in mouse erythroid cells. Taking advantage of public domain ChIP-Seq data sets in mouse embryonic stem cells, an integrative model is then used to assess features in enhancer prediction, and subsequently locate enhancers. Significant associations with multiple TF bound loci, higher expression in the closest genes, and active enhancer marks support functionality and tissue-specificity of these enhancers. Motif enrichment analysis further determines known and novel TFs regulating the target cell type. Furthermore, the features identified can facilitate more accurate enhancer prediction in other cell types.

There is a genome in a cell, as everyone knows, but there is also an epigenome. The epigenome regulates the transcription of the underlying genome. In the last decade, it was discovered that the epigenome state and its regulation are important for differentiation and development. Correlation studies with aging samples had led to the hypothesis that misregulation of the epigenome causes aging and cancer. Furthermore, diseases were identified which are caused by errors in the epigenome state and its regulation. Identification of erroneous epigenome states and misregulation requires the prior knowledge of the common state. Several studies aim at measuring epigenome states in different organisms and cell types and thus, provide a huge amount of data. In this dissertation, a pipeline is developed to analyze and characterize histone modifications with respect to different cell types. Application of this pipeline is shown for a published data set of mouse consisting of data for H3K4me3, H3K27me3, and H3K9me3 measured in embryonic stem cells, embryonic fibroblasts and neuronal progenitors. Furthermore, methods for the detection of the epigenetic patterns are presented in this dissertation. Therefore, a segmentation method is developed to segment the genome guided by the data sets. Based on this segmentation, the epigenome states as well as epigenetic variation can be studied. Different visualization methods are developed to highlight the epigenetic patterns in the segmentation data. Application of the segmentation AND visualization methods to the mouse data set had resulted in not only colorful squares but also in biological conclusions! It demonstrate the power of the developed methods. Although the studied data set in this dissertation contains only ordinary tissue cells, the methods are not restricted to study the reference epigenome state. Comparison of normal and disease cells as well as comparison with aged cells are possible with all of the methods. Finally, the methods are compared based on the obtained results. It shows that all methods highlight different aspects of the data. Thus, applying all methods to the same data sets, deep insights into the epigenome in murine embryonic stem cells, embryonic fibroblasts and neuronal progenitor cells are gained. For example, it had been found that several mechanisms exist setting H3K4me3 marks. Furthermore, not all mechanisms are found in all cell types. Strong evidence had been found that catalysis of H3K4me3 and H3K27me3 is coupled.