Els governs de coalició poden, per una banda, dividir-se les tasques i funcionar de forma compartimentalitzada, on cada soci decideixi sol les polítiques sota les seves jurisdiccions ministerials. Per contra, també poden optar pel compromís entre els partits i decidir col•lectivament en cada àrea sectorial, amb independència del repartiment de carteres. En el seu primer paper, aquesta tesis ofereix un marc teòric per entendre aquesta variació, amb la intenció d’identificar les condicions sota les quals és més probable un tipus de governança coalicional o altra. El segon paper testa empíricament les implicacions d’aquests arguments sobre la manera com els membres d’una coalició es vigilen mútuament mitjançant l’ús de mecanismes de control. Finalment, en el tercer paper s’ofereix un exercici empíric on s’analitza fins a quin punt els votants jutgen de manera diferent cada un dels socis de govern en funció del tipus de coalició a què s’enfronten. / At an extreme, coalition partners can divide tasks and individually decide policy in their ministerial jurisdictions in a compartmentalized way. At the other extreme, parties sharing office can compromise and collectively set policy in each dimension regardless of portfolio allocation. In its first paper, this dissertation provides a theoretical account of this variation, trying to unravel the conditions under which one type of governance is more likely than the other. The second paper tests empirically the implications of these arguments on the way coalition partners keep tabs on each other through the establishment of control mechanisms. Finally, an empirical exercise is offered in the third paper to study the extent to which voters assess each coalition partner differently depending on the type of coalition they face. Variation in the types of coalition governance, we conclude, is an important factor to take into account in political science research in the field.

Submitted by Claudia Vanessa dos Santos Corrêa (claudiageobrax@yahoo.com.br) on 2018-06-06T02:32:25Z No. of bitstreams: 1 VERSAO FINAL COMPLETA.pdf: 29221186 bytes, checksum: e01b175cba96e8af54b4c7995ec5262a (MD5) / Approved for entry into archive by Ana Paula Santulo Custódio de Medeiros null (asantulo@rc.unesp.br) on 2018-06-06T12:02:22Z (GMT) No. of bitstreams: 1 correa_cvs_dr_rcla.pdf: 29196738 bytes, checksum: 8314696946ba060a96b1d3d2775068a3 (MD5) / Made available in DSpace on 2018-06-06T12:02:23Z (GMT). No. of bitstreams: 1 correa_cvs_dr_rcla.pdf: 29196738 bytes, checksum: 8314696946ba060a96b1d3d2775068a3 (MD5) Previous issue date: 2018-03-12 / Outra / As corridas de detritos são movimentos de massa que se desenvolvem ao longo de redes de drenagem e envolvem fluidos densos, compostos por materiais de diferentes granulometrias e composições, bem como quantidades variáveis de água, identificados como processos naturais constituintes da dinâmica e da modelagem da paisagem. Caracterizam-se pelo extenso raio de alcance, altas velocidades, altas vazões de pico e elevada capacidade de erosão e força de impacto. As áreas mais susceptíveis a ocorrência desses processos no Brasil estão situadas no sopé da Serra do Mar, da Serra da Mantiqueira e da Serra Geral, e no litoral norte do Estado de São Paulo foi registrado um grande evento de escorregamentos e corridas de detritos generalizados em 1967 que afetou a região de Caraguatatuba e São Sebastião, onde se encontra uma malha dutoviária associada a Unidades de Tratamento da Petrobras, outros empreendimentos, estruturas e uma grande área urbana em crescimento. O objetivo geral desta pesquisa é propor uma metodologia para avaliação da potencialidade de bacias hidrográficas à ocorrência de corridas de detritos, através do emprego da compartimentação fisiográfica, de estudos de retroanálise e da simulação numérica do terreno com o software RAMMS. A compartimentação fisiográfica revelou que as unidades que possuem contato direto com planícies são aquelas que possuem maior potencialidade a corridas de detritos. Na retro-análise, foi estabelecido o Fator de Desproporcionalidade, que possibilitou a análise de incoerências de incidência de cicatrizes de escorregamento em bacias hidrográficas, unidades geológicas e classes de declividade. As bacias Camburu, Pau D’Alho, Canivetal e Santo Antônio foram consideradas como as mais afetadas por escorregamentos e corridas de detritos, sendo que a classe de declividade de 350 a 500 é a mais atingida nesses locais e não houve uma unidade geológica preferencial durante a mobilização desses processos. A simulação numérica revelou que as corridas de detritos da Serra do Mar apresentam um fluxo com caráter reológico predominantemente granular e as zonas de deposição das corridas dão-se preferencialmente em regiões de baixa declividade. O emprego desta metodologia pode auxiliar na identificação de locais com potencialidade a corrida de detritos, especialmente na Serra do Mar, e contribuir com a gestão do meio físico. / The debris flows are mass movements that develop along drainage networks and involve generally dense fluids, compose of materials of different granulometries and compositions, as well as variable amounts of water, identified as natural processes that constitute the dynamics and the modeling the landscape. They are characterized by the long range, high speeds, high peak flows, high erosion capacity and impact force. The areas most susceptible to the occurrence of these processes in Brazil are in the foothills of the Serra do Mar, Serra da Mantiqueira and Serra Geral, and on the north coast of São Paulo State there was a great event of landslides and debris flows in 1967 which affected the region of Caraguatatuba and São Sebastião, where there is a pipeline network associated with Petrobras Treatment Units, other enterprises, structures and a large urban area in growth. The general aim of this research is to propose a methodology to evaluate the potential of watersheds to the occurrence of debris flows, using physiographic compartmentalization, retro-analysis studies and numerical simulation of the terrain with Ramms software. The physiographic compartmentalization revealed that the units that have direct contact with lowlands are those that have greater susceptibility to debris flows. In the retro-analysis, the Disproportionality Factor was established, which made it possible to analyze inconsistencies in the incidence of landslide scars in watersheds, geological units and declivity classes. The Camburu, Pau D’Alho, Canivetal and Santo Antônio watersheds were the most affected by landslides and debris flows, and the slope class of 350 to 500 is the most affected in these areas and there was no preferential geological unit during the mobilization of these processes. The numerical simulation revealed that the Serra do Mar debris flows have a predominantly granular rheological flow and the deposition zones of the flows are given in regions of low slope. Thus, the use of this methodology can help in the identification of areas with potential for the debris flows, especially in Serra do Mar, and contribute to the management of the physical environment.

Catharanthus roseus est une plante médicinale produisant divers types d’alcaloïdes indoliques monoterpéniques (AIM) d’intérêt en santé humaine. Ainsi, les AIM dimères comme la vinblastine et la vincristine sont utilisés en chimiothérapie anticancéreuse et les alcaloïdes monomères de type hétéroyohimbine présentent diverses activités pharmacologiques. La fabrication de ces molécules dans la plante est fort complexe. Elle requiert un haut niveau de compartimentation tissulaire et subcellulaire et met en jeu plus d’une trentaine d’étapes enzymatiques, dont certaines sont encore très mal connues. Dans ce contexte, l’objectif de la thèse a consisté à élucider plusieurs étapes enzymatiques de la voie de biosynthèse des AIM. Nos travaux ont permis de caractériser de nouvelles isoformes enzymatiques de la famille des cytochromes P450 ainsi que les réductases qui leur sont associées. Ils ont abouti à l’identification de nouvelles déshydrogénases et mis en évidence, in planta, leurs interactions avec la strictosidine synthase suggérant une biosynthèse orientée vers les divers alcaloïdes de type hétéroyohimbine. Enfin, en ayant recours à l’ingénierie métabolique, un segment de la voie de biosynthèse a été transféré dans la levure Saccharomyces cerevisiae, lui conférant la capacité de bio-transformer la tabersonine en vindoline, l’un des deux précurseurs finaux des alcaloïdes dimères. / Catharanthus roseus is a medicinal plant producing various types of monoterpene indole alkaloids (MIA) with a great interest in human health. Dimeric alkaloids such as vinblastine and vincristine are used in cancer chemotherapy and monomeric heteroyohimbine alkaloids exhibit various pharmacological activities. The production of these molecules in the plant is very complex. It requires a high level of tissular and subcellular compartmentalization and involves more than thirty enzymatic steps, some of which are largely unknown. In this context, the aim of this thesis was to elucidate several enzymatic steps of the MIA biosynthetic pathway. Our work allowed us to characterize new enzyme isoforms of cytochrome P450 and their associated reductases. They also resulted in the identification of new dehydrogenases and highlighted their interactions with the strictosidine synthase suggesting a directed biosynthesis towards various heteroyohimbine type of alkaloids. Finally, engineered yeast containing a segment of the MIA biosynthetic pathway was able to convert tabersonine into vindoline, one of the two final precursors of the dimeric alkaloids.

Phylloid-algal mounds form heterogeneous hydrocarbon reservoirs in the southeastern portion (Blanding sub-basin) of the Paradox Basin. Well-studied Lower Ismay mounds exposed along walls of the San Juan River gorge in the vicinity of Eight Foot Rapids, the west limb of the Raplee Anticline, and at the classic Honaker Trail locality (southwestern Paradox Basin) have often been cited as outcrop analogs of productive subsurface mounds. Until now, however, there has not been a complete description of the distribution, size, and spacing of outcropping algal mounds at the classic Eight Foot Rapids locality. The Lower Ismay sequence was analyzed in the context of a build-and-fill model of deposition. There are three facies associations within the sequence: 1) a basal lowstand to middle highstand pre-mound facies association, 2) a late highstand to middle falling stage phylloid algal-dominated relief-building facies association, and 3) a late falling stage, post-mound relief-filling facies association. Above the basal maximum flooding surface (Gothic Shale), the facies succession displays a distinct shallowing upward trend through the Lower Ismay sequence. Mound dimensions and facies stacking patterns permit evaluation of two depositional models. The first is a traditional, moderate- to low-energy model of vertical and radial mound accumulation of phylloid algal plates. The second is a high-energy, tidally influenced model of accumulation wherein mounds become hydrodynamically elongate. Outcrop data indicate that algal-dominated buildups are domal in shape with no preferred axis of elongation. These patterns do not support a hydrodynamic accumulation of loose algal plate fragments. The absence of in-situ algal thalli in all but the upper few tens of centimeters of the mounds, however, argues against a purely biological/ecological origin of mounds. A down-stepping ramp model is proposed wherein a muddy algal facies was deposited at the base of the mounds in the low energy of the outer ramp, followed by a grain-rich algal core in the mid-ramp environment. Mounds tops accumulated in an algal bafflestone facies in the inner ramp setting. Restriction of energy due to basinward algal buildup may have also contributed to deposition of algal bafflestone. Mounds accumulated radially at differential rates and were influenced by these variations in energy. This differential deposition of microfacies and subsequent diagenetic alteration have produced heterogeneities in algal reservoir rock, producing algal mound reservoirs that have a high potential for compartmentalization.

The mucosal system, which forms a barrier between internal organ systems and the external environment, is frequently exposed to pathogenic microorganisms. Immunoglobulin A (IgA) antibody secreting cells (ASCs) localize in the lamina propria, and produce IgA antibodies which help protect mucosal tissues. The concept of a common mucosal immune system in which IgA ASCs have the ability to populate any mucosal site has been proposed (1, 2). However, recent research has suggested that IgA ASCs primed in different mucosal sites might possess different sets of chemokine receptors, and therefore migrate specifically to particular mucosal locations (3). In this study, the specific compartmentalization of IgA ASCs in two mouse salivary glands: sublingual gland (SLG), and submandibular gland (SMG) was studied. It was observed that SLG had 12 times more IgA ASCs per gram of gland than that of SMG (p<0.01). This suggested that IgA ASCs migrated to the two salivary glands with different efficiencies. Since the migration of lymphocytes is mediated by interactions between tissue specific chemokines and chemokine receptors, I hypothesized that the specific compartmentalization of IgA ASCs in the SLG and SMG was mediated by the differential expression of IgA ASC attracting chemokines. Quantitative PCR was used and showed that SLG expressed high levels of CCL28 and its receptor CCR10, which correlated to the distribution of IgA ASCs in the two salivary glands. In agreement with QPCR data, reduced levels of IgA ASCs were found in the SLG of CCR10 deficient mice when compared to wild type (WT) mice. Adoptive transfer of CCR10 deficient mice with WT spleen cells reconstituted the WT phenotype. It was therefore concluded that the interaction between CCL28 and CCR10 play an important role in mediating the migration of IgA ASCs into SLG. These results suggested that the accumulation of IgA ASC to distinct salivary glands is a highly selective process. These data also suggested that homing within mucosal sites is not common but rather a highly regulated process with specific subsets of cells homing to different tissues within the mucosal immune system.

Orientador: Juércio Tavares de Mattos / Banca: Paulina Setti Riedel / Banca: Sérgio dos Anjos Ferreira Pinto / Banca: Ricardo Vedovello / Banca: Valter Casseti / Resumo: Apresenta-se a problemática do assunto Zoneamento Ecológico-Econômico (ZEE), a polêmica em torno dele e suas atribuições como instrumentos político e técnico para ordenamento territorial. A hipótese do trabalho foi definida com base na situaçãoproblema ZEE Tocantins, discutindo-se os procedimentos metodológicos e métodos usados. Assumiu-se que o mapeamento e o zoneamento geotécnico tenham uma importante aplicação no ZEE, sobretudo pela forma com que as unidades são caracterizadas, quer seja diretamente ou indiretamente. Demonstrou-se que o mapeamento geotécnico, embasado em unidades de compartimentação do meio físico classificadas por atributos inerentes ao ZEE, permite melhorar a percepção acerca dos usos potenciais da terra, pretendidos em um projeto de ZEE, principalmente pela possibilidade de elaboração de cartas específicas ou de síntese. Trabalhou-se criteriosamente na descrição dos processos de: (i) montagem e organização de uma base de dados geográficos para facilitar e permitir o desenvolvimento das atividades que se apóiam tecnologicamente em SIG e sistema de processamento digital de imagens de sensores remotos; (ii) aplicação do método Seplan-TO usado no ZEE Norte do Estado do Tocantins para a geração do plano de zoneamento ambiental, com ênfase na compartimentação ambiental (unidade territorial básica - UTB); (iii) aplicação do mapeamento geotécnico com base no Método Vedovello para a geração de um plano de zoneamento geoambiental, com ênfase na compartimentação ambiental (unidade básica de compartimentação - UBC) e inclusão de fatores bióticos; e (iv) comparação e avaliação dos resultados obtidos pela aplicação dos diferentes métodos com o intuito de indicar aquele que deve ser usado para estudos de ZEE no Tocantins. Os focos da avaliação foram a compartimentação do meio físico e a execução do ZEE em termos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The problematics of the subject Ecological-Economic Zoning (EEZ) is presented, as well as the controversy about it and its role as a political and technical instrument for a territorial ordenation. The hypothesis was defined based on the EEZ Tocantins problem-situation, discussing the methodological procedures and methods used. It was assumed that geotechnical mapping and zoning have an important application in the EEZ, particularly by the way the units are characterized, whether directly or indirectly. It was demonstrated that a geotechnical mapping based on compartmentalization units of the physical medium and classified by attributes inherent to the EEZ permits to improve the perception about the potential uses of land as intended in a EEZ project, particularly due to the possibility of preparing specific or synthetic charts. A judicious work was performed in the description of the processes of: (i) assembly and organization of a geographic data bank in order to facilitate and permit the development of the activities technologically supported by SIG and a digital image-processing system with remote sensors; (ii) application of the Seplan-TO method used at EEZ Northern of the State of Tocantins for generating the environmental zoning plan, emphasizing the environmental compartmentalization (basic territorial unit - BTU); (iii) application of the geotechnical mapping based on Vedovello Method for generating a geoenvironmental zoning plan emphasizing the environmental compartmentalization (basic compartmentalization unit - BCU) and inclusion of biotic factors; and (iv) comparison and assessment of the results obtained by the application of the different methods, with the intent of indicating that one that should be used for EEZ studies at Tocantins. The assessment was focused on the compartmentalization of the physical medium and the execution of the EEZ in terms of repeatability ...(Complete abstract click electronic access below) / Doutor

This work presents a geological/geomorphological analysis in the scale of 1: 100,000 of Domain Vaza Barris, using geoprocessing techniques, with the purpose of delivering data to geo-environmental planning. The study area is represented by the Vaza Barris Domain which displays a gneissic complex surfacing in two emplacements, being surrounded by a metavolcano-sedimentary cover highly deformed. This work is the mapping and the application of satellite imagery fusion techniques Landsat 8 with SRTM methodology data for the geological and geomorphological analysis by homologous zones and the use of RapidEye images to the classification of the Land Use employing the Index Normalized Difference vegetation (NDVI). As a result there was the development of the geological/geomorphological partitioning of the Vaza Barris domain, were generated the Digital Terrain Model, Shaded Relief, Contour, Topographic profiles, Slope maps, Hypsometric map and Anaglyph. The integration between the interpretations of Landsat 8, SRTM and field data allowed the identification of seven types of geomorphological modeled in the study area: Modeled of grooming Shanty be buried, Modeled of dissection Homogeneous tops Keen, Modeled of dissection Homogeneous tops Convex, Patterned Accumulation in ramps Colluvium, Modeled Dissection of Structural tops convex, Modeled of pediments and Modeled of grooming Retouched be buried. From the NDVI was generated the Land Use map where the pixels were grouped into classes of values and classified as: Clouds, Solo Exposed, Pasture / built-up areas, water bodies, shrub and tree vegetation. This work achieved important results with the use of geotechnology in making the Geological/ Geomorphological Map and the Land Use Map to provide support in environmental planning Vaza Barris Domain. / Neste trabalho será apresentada uma análise geológica/geomorfológica na escala de 1:100.000 do Domínio Vaza Barris, utilizando técnicas de geoprocessamento, com o propósito de fornecer subsídios ao planejamento geoambiental. A área de estudo é representada pelo Domínio Vaza Barris o qual exibe um complexo gnáissico aflorando em dois embasamentos, sendo envolvido por uma cobertura metavulcano-sedimentar altamente deformada. Este trabalho tem como metodologia o mapeamento e a aplicação de técnicas de fusão de imagens de satélite Landsat 8 com dados da SRTM para a análise geológica e geomorfológica por zonas homólogas e a utilização de imagens RapidEye para a classificação do Uso da Terra empregando o Índice de Vegetação por Diferença Normalizada (NDVI). Como resultados houve a elaboração da compartimentação geológica/geomorfológica do Domínio Vaza Barris, foram gerados o Modelo Digital do Terreno, Relevo Sombreado, Curvas de Nível, Perfis Topográficos, Mapas de Declividade, Mapa Hipsométrico e Anáglifo. A integração entre as interpretações de imagens Landsat 8, SRTM e dados de campo permitiu a identificação de sete tipos de modelados geomorfológicos na área de estudo: Modelado de Aplanamento Degradado Inumado, Modelados de Dissecação Homogênea de Topos Aguçados, Modelados de Dissecação Homogênea de Topos Convexos, Modelado de Acumulação em Rampas de Colúvio, Modelado de Dissecação Estrutural de Topos Convexos, Modelado de Pedimentos e Modelados de Aplanamento Retocado Inumado. A partir do NDVI foi gerado o mapa de Usos da Terra onde os pixels foram agrupados em classes de valores e classificadas como: Nuvens, Solo Exposto, Pastagem/Áreas Edificadas, Corpos D´Água, Vegetação Arbustiva e Vegetação Arbórea. O presente trabalho alcançou importantes resultados com a utilização das geotecnologias na confecção do Mapa Geológico/Geomorfológico e o Mapa de Usos da Terra para servir de subsídio no planejamento ambiental do Domínio Vaza Barris.

Introduction: 23 million patients worldwide suffer from heart failure. These patients depend on cardiac research, because cardiac research enables the development of new therapeutic strategies and –targets. In cardiomyocytes, the compartmentalization of cAMP and cGMP depends on many factors. T-tubuli and PDEs are responsible for the division of cells in microdomains in which localized and specific cAMP and cGMP-signaling occurs. The aim of this thesis was to develop a method to answer the open questions that remain about the physiological and pathophysiological significance of cAMP/cGMP compartmentalization. Methods: I used the zebrafish as a model, because the transparency of zebrafish larvae enabled non-invasive fluorescent imaging in cardiomyocytes in the living animal. I cloned the Fluorescence Resonance Energy Transfer (FRET) sensors EPAC1-camps for cAMP and cGi500 for cGMP and injected them into zebrafish fertilized embryos. Then I used the F0 generation for Fluorescence Lifetime Imaging (FLIM) -FRET-measurements of cAMP and cGMP. Ca2+ is an important downstream mediator of cAMP and cGMP, because Ca2+ regulates cardiac contraction. Therefore, I also cloned the Ca2+ sensor GCaMP6 and used the dye Fluo-4 AM to include intracellular Ca2+ in the imaging. Results: The cloned sensors for cAMP, cGMP and Ca2+ were successfully injected into the zebrafish and showed expression in individual cardiomyocytes. I developed a protocol to mount the living zebrafish embryos and to measure intracellular cAMP and cGMP with FLIM-FRET in vivo with high spatial resolution. I characterized the sensors in their functionality by showing that the sensors react to changes in intracellular concentrations of cAMP and cGMP. The results of this study include evidence that zebrafish have mechanisms that lead to cAMP/cGMP compartmentalization in the absence of T-tubuli, and these mechanisms keep compartmentalization constant even under extreme cAMP or cGMP increasing drug treatment. Furthermore, I imaged intracellular Ca2+ by confocal microscopy and developed a protocol to use Fluo-4 AM for Ca2+ imaging. Conclusion: The method used in this thesis should allow the investigation of subcellular cAMP/cGMP compartmentalization and Ca2+ and to subsequently answer open questions in the field, for example whether a change of cAMP compartmentalization leads to the pathological phenotypes of cardiac disease or if a changed compartmentalization of cAMP in cardiac disease influences Ca2+ concentrations and therefore contraction. Additionally, this method can be used to learn more about cAMP, cGMP und Ca2+ during regeneration in the heart, because the zebrafish cardiomyocytes can regenerate. / Einleitung: Weltweit sind mehr als 23 Millionen unter Herzinsuffizienz leidende Patienten auf die kardiologische Grundlagenforschung angewiesen, da diese die Voraussetzung für eine bessere Versorgung durch adaptierte und neue Behandlungswege schafft. In Kardiomyozyten hängt die Kompartimentierung von cAMP und cGMP von vielen Faktoren ab. T-Tubuli und PDEs werden unter anderem für die Aufteilung der Zellen in Mikrodomänen, in denen lokalisierte und spezifische cAMP- und cGMP-Signalgebung stattfinden kann, verantwortlich gemacht. Das Ziel dieser Arbeit war die Etablierung einer Methode, mithilfe derer offene Fragen bezüglich der physiologischen und insbesondere der pathophysiologischen Relevanz der cAMP- und cGMP Kompartimentierung beantwortet werden können. Methode: Als Modell diente der Zebrafisch, da die Transparenz von Zebrafisch Embryonen eine nicht-invasive Bildgebung von Fluoreszenz in Kardiomyozyten im lebenden Tier ermöglicht. Dafür klonierte ich die Förster Resonance Energy Transfer (FRET) -Sensoren EPAC1-camps als cAMP-Sensor und cGi500 als cGMP-Sensor und injizierte diese in befruchtete Zebrafisch Embryonen. Anschließend benutzte ich die F0-Generation für Fluorescence Lifetime Imaging (FLIM) -FRET-Messungen von cAMP und cGMP. Da Ca2+ als wichtiger downstream Mediator von cAMP und cGMP die kardiale Kontraktion reguliert, klonierte ich außerdem den Ca2+-Sensor GCaMP6 und benutzte den Farbstoff Fluo-4 AM, um intrazelluläres Ca2+ darzustellen. Ergebnisse: Die klonierten Sensoren für cAMP, cGMP und Ca2+ konnten erfolgreich in den Zebrafisch injiziert werden und zeigten alle Expression in einzelnen Kardiomyozyten. Ich entwickelte ein Protokoll, dass die Fixierung von lebenden Zebrafisch Embryonen und nachfolgender Bildgebung von cAMP und cGMP mit hoher zellulärer Auflösung mit FLIM-FRET in vivo erlaubte. Ich konnte eine funktionelle Charakterisierung der Sensoren durchführen, indem ich zeigte, dass sie auf Konzentrationsänderungen von intrazellulärem cAMP und cGMP reagieren sowie zeigen, dass Zebrafische trotz fehlender T-Tubuli eine signifikante cAMP- und cGMP Kompartimentierung aufweisen, auch unter extremen Bedingungen nach Gabe von cAMP/cGMP stimulierenden Substanzen in hoher Dosierung. Ich konnte zudem subzelluläres Ca2+ durch konfokale Mikroskopie bildgebend darstellen und entwickelte ein Protokoll, um mit Fluo-4 AM eine schnelle Möglichkeit zu haben, Ca2+ mit in die Messungen einzubeziehen. Ausblick: Die in dieser Arbeit benutzte Methode bietet eine gute Möglichkeit, subzelluläre cAMP- und cGMP-Kompartimentierung und Ca2+ zu untersuchen und damit zum Beispiel die Fragen zu beantworten, ob eine veränderte cAMP/cGMP Kompartimentierung zu Herzkrankheiten wie Hypertrophie führt oder ob eine veränderte cAMP Kompartimentierung den zellulären Ca2+ Haushalt und damit die kardiale Kontraktion beeinflusst. Darüber hinaus kann das von mir etablierte Protokoll dazu genutzt werden, mehr über cAMP, cGMP und Ca2+ während der Regeneration im Herzen zu lernen, da der Zebrafisch über ausgeprägte Regenerationsfähigkeiten verfügt.

Le cytomégalovirus humain (CMV) appartient à la sous-famille des Betaherpès virus. L’homme est son seul réservoir et il infecte 40 à 90% de la population mondiale. Ce virus, rarement dangereux pour le sujet immunocompétent, représente une réelle menace chez le patient immunodéprimé comme le transplanté d’organe. Après la primo-infection, le CMV diffuse dans tout l’organisme et alterne des phases de latence et de réactivation. Il consacre 20% de son génome à diverses stratégies d’échappement immunitaire.Les objectifs de notre travail sont de décrire dans une première partie 1- la variabilité de six gènes, codant quatre protéines immunomodulatrices (UL18, UL40, UL111a et US3) et deux protéines immunodominantes (IE1 et pp65), dans des souches de CMV directement séquencées à partir de sang total ou du LBA de patients infectés et immunodéprimés, 2- le mécanisme conduisant à cette variabilité 3- la répartition des souches virales dans le sang total et le LBA (compartimentation).La deuxième partie est consacrée à l’expression de la protéine immunomodulatrice pUL40.Nos travaux ont permis de confirmer l’existence d’un polymorphisme notable, supérieur à ce qui est déjà décrit. Des conséquences fonctionnelles pourraient en découler dans les protéines correspondantes. L’étude in silico de la variabilité du CMV met en lumière le rôle clé de la recombinaison comme mécanisme évolutif majeur. Nous n’avons pas mis en évidence de compartimentation des souches virales dans les échantillons analysés.Nos résultats préliminaires indiquent la faisabilité de la sur-expression de la protéine pUL40, permettant ultérieurement de mieux comprendre ses fonctions. / Human Cytomegalovirus (CMV) belongs to the Betaherpesviruses sub-family. Human beings are its sole reservoir and it infects 40 to 90% of the world population. This virus is rarely dangerous for the immunocompetent host, but represents a problematic opportunistic agent in immunocompromised patients, such as transplant recipients. After primary infection, CMV spreads widely in the organism and alternates latency and reactivation phases. CMV dedicates 20% of its genome to various immune escape strategies.Our aims were to describe, in a first part, 1- the variability of six CMV genes, which encode 4 immunomodulatory proteins (UL18, UL40, UL111a and US3) and two immunodominant proteins (IE1 and pp65), after direct amplification and sequencing from whole blood and bronchoalveolar lavages (BAL) taken from infected immune compromised patients, 2- the mechanism responsible for this variability 3- the distribution of CMV strains in whole blood and BAL (compartmentalization).In a second part, we attempted pUL40 expression.Our results confirmed the existence of a noticeable polymorphism, superior to what was previously described. Functional consequences could arise for the corresponding proteins. Our in silico study of CMV variation indicated a key role for recombination as a major evolutionary mechanism. We have observed little CMV compartmentalization among the investigated samples. Our preliminary results indicated pUL40 may be over-expressed, which could allow a better understanding of its functions in a near future.

Hurricane is one of the most destructive and costly natural hazard to the built environment and its impact on low-rise buildings, particularity, is beyond acceptable. The major objective of this research was to perform a parametric evaluation of internal pressure (IP) for wind-resistant design of low-rise buildings and wind-driven natural ventilation applications. For this purpose, a multi-scale experimental, i.e. full-scale at Wall of Wind (WoW) and small-scale at Boundary Layer Wind Tunnel (BLWT), and a Computational Fluid Dynamics (CFD) approach was adopted. This provided new capability to assess wind pressures realistically on internal volumes ranging from small spaces formed between roof tiles and its deck to attic to room partitions. Effects of sudden breaching, existing dominant openings on building envelopes as well as compartmentalization of building interior on the IP were systematically investigated. Results of this research indicated: (i) for sudden breaching of dominant openings, the transient overshooting response was lower than the subsequent steady state peak IP and internal volume correction for low-wind-speed testing facilities was necessary. For example a building without volume correction experienced a response four times faster and exhibited 30-40% lower mean and peak IP; (ii) for existing openings, vent openings uniformly distributed along the roof alleviated, whereas one sided openings aggravated the IP; (iii) larger dominant openings exhibited a higher IP on the building envelope, and an off-center opening on the wall exhibited (30-40%) higher IP than center located openings; (iv) compartmentalization amplified the intensity of IP and; (v) significant underneath pressure was measured for field tiles, warranting its consideration during net pressure evaluations. The study aimed at wind driven natural ventilation indicated: (i) the IP due to cross ventilation was 1.5 to 2.5 times higher for Ainlet/Aoutlet>1 compared to cases where Ainlet/AoutletCFD based IP responses. Comparisons with ASCE 7-10 consistently demonstrated that the code underestimated peak positive and suction IP.