Tese de Mestrado Integrado. Engenharia Electrotécnica e de Computadores. Faculdade de Engenharia. Universidade do Porto. 2012

Tese de mestrado integrado. Engenharia Química. Faculdade de Engenharia. Universidade do Porto. 2010

Depot intramuscularly administered testosterone cypionate (TC) is indicated for treatment of hypogonadism in males. However, illegal use of TC and other anabolic steroids in athletic competition has been occurring for over 50 years. A randomized three-arm clinical trial was conducted to investigate side effects of long-term abuse of testosterone cypionate. The objective of the thesis is to apply modeling approach to characterize pharmacokinetics of long-term TC injections as well as identify its side effects on healthy male volunteers. A linear one-compartment model with first-order absorption best described the concentration-time profile of testosterone obtained from 31 healthy males. The population clearance estimates for total and free testosterone were 2.42*103 and 6.03*105 L/day, respectively. Weight and albumin were identified as significant covariates for total testosterone. Given the known inhibitory effect of testosterone on HPG axis, an indirect effect model was applied to describe the suppression of luteinizing hormone and spermatogenesis. The estimated potency of total testosterone with respect to LH suppression was 9.38ng/ml. Model simulation showed that suppression of luteinizing hormone and spermatogenesis after TC injection was more severe and of greater duration in the highest dose level. A polynomial change point mixed effects model was successfully built to describe the change in weight and lipid profiles after weekly injection of testosterone cypionate. Model simulation showed that both 250mg and 500mg would incur an average increase of body weight of 3.5kg at 8 weeks after dosing. A polynomial change point model also identifies that there is a tendency for lipid decrease after TC administration. However, no difference was found in the lipid change between three dose groups, which precludes any definite conclusion on the effect of long-term TC administration on lipid profiles.

Providing access to clean drinking water will continue to be a challenge for civil engineers for generations to come. Since many communities around the world rely on groundwater as a source of drinking water, remediation technologies must be implemented at sites where groundwater contamination exists due to years of mismanagement of hazardous waste. Using nanosized zero-valent metals such as iron and zinc embedded within and on the surface of functionalized (PAA) membrane filters has shown to be an effective dechlorination technique for contaminated groundwater. Introducing a noble metal such as Pd or Ni increases reaction rates by acting a catalyst for the dechlorination reaction. This study focuses on the treatment of contaminated groundwater at a hazardous waste site in Louisville, Kentucky. Once a chlorinated organic chemical manufacturing plant, the site now operates a treatment system for the contaminated groundwater to prevent migration into the nearby Ohio River. A portable membrane treatment system, built at the University of Kentucky, incorporates this functionalized bimetallic membrane technology for treatment of the groundwater found at the former manufacturing plant. Three bench scale tests were performed with membrane treatment system using DI water spiked with the chemical trichloroethylene (TCE). Results showed that using the functionalized Fe/Pd membranes significant decreased TCE concentrations over time. While further tests should be conducted to verify the results of the preliminary bench-scale tests, the membrane treatment system shows potential for use at the hazardous waste site in Kentucky.

京都大学 / 新制・課程博士 / 博士(人間・環境学) / 甲第23976号 / 人博第1028号 / 新制||人||242(附属図書館) / 2022||人博||1028(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 吉田 寿雄, 教授 田部 勢津久, 教授 中村 敏浩 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM

Ce manuscrit se concentre sur l'analyse du GISAXS d'îlots sur un substrat. Les données GISAXS doivent être analysées de façon quantitative afin d'obtenir des paramètres morphologiques précis (courbes de croissance, forme d'équilibre de l'îlot et énergie interfaciale) pour le processus d'élaboration. L'accent est mis sur le facteur de forme de l'îlot, c'est-à-dire la transformée de Fourier de la forme de l'îlot. On montre que la forme de l'îlot et la taille peuvent être obtenues à partir de la symétrie de l'îlot, la présence de facettes de l''îlot, le comportement asymptotique loin dans l'espace réciproque pour une grande polydispersité et les zéros ou les minima de l'intensité pour une faible polydispersité. Une comparaison approfondie entre l'approximation de Born et l'approximation plus précise de l'onde distordue (DWBA) met en évidence la spécificité apportée par la géométrie en incidence rasante. L'analyse quantitative est illustrée pour des images GISAXS acquises in situ pendant l'épitaxie par jet moléculaire de nano-îlots Ag ou Pd sur MgO(001) pour différentes épaisseurs et températures. Les paramètres morphologiques obtenus sont en très bon accord avec des résultats de microscopie électronique à transmission. Finalement, la diffusion incohérente a été mise en évidence en GISAXS et a pour origine des corrélations entre les îlots.

<p>This thesis was done at DaimlerChrysler AG in Stuttgart,Germany. The aim of the thesis is to develop an algorithm for controlling a motor used in a Shift-by-Wire System. The control algorithm is to be implemented in a prototype car for further testing. The Shift-by-Wire System can be described as follows: An electrical actuator is mounted in an automatic gearbox to select gears instead of the gear stick. The actuator is controlled by a microcontroller, which runs a control algorithm. The position of the actuator is measured with a linear position sensor and sent to the controller.</p>

Dynamic Mechanical Analyzer (DMA) was used to study the frequency dependence of storage and loss modulus of amorphous Pd₄₀Ni₁₀Cu₃₀P₂₀ alloy over a broad frequency range around its glass transition temperature. The amorphous samples were subjected to two testing conditions: constant frequency with continuous heating and isothermal with frequency sweep. The storage modulus E′ exhibited a sigmoidal change from about 90 GPa to a low value of about 0 GPa over the glass transition region. The loss modulus, E″, was characterized by an asymmetrical peak with a smaller slope at the low temperature side than at the high temperature side upon heating. These changes in moduli were associated with mechanical relaxation due to atomic motion. Similar results were also obtained under isothermal condition. The Kohrausch-Williams-Watts function was used to fit the data obtained under the isothermal condition. The peak frequencies obtained were then fitted to the VFT equation and the scaling law equation. / Singapore-MIT Alliance (SMA)

This dissertation focuses on bridging the pressure and complexity gap between heterogeneous catalysis and surface science by introducing new instrumental tools that can operate under catalytically relevant conditions (i.e. atmospheric pressures and temperatures higher than room temperature). Thus, some of the few detailed examples of the polarization modulation infrared reflection absorption spectroscopy (PM-IRAS) as an in situ vibrational spectroscopic tool for the elevated-pressure investigation of gas/solid interfaces on planar single crystal model catalyst systems were presented in this work. Furthermore, for the first time in the literature, PM-IRAS technique was applied to study complex multi-component model catalyst structures exhibiting three dimensional morphologies such as metal nanoparticles deposited on a metal-oxide thin film. In order to achieve a molecular understanding of the properties of CO+NO catalytic reaction at elevated temperatures and pressures on Pd based catalysts, adsorption trends of each of the reactant molecules were studied separately on Pd (111). The adsorption properties of CO/Pd (111) and NO/Pd (111) systems both under UHV conditions and at elevated pressures were discussed in a comparative manner to highlight the pressure dependent behavioral differences between these two probe molecules by emphasizing the risks of extrapolating UHV trends to elevated pressure regimes. CO+NO reaction mechanism and kinetics was also studied on Pd (111) by in situ PM-IRAS. Factors affecting the conversion and the selectivity of the Pd (111) model catalyst towards CO+NO reaction at elevated pressures were discussed. Formation of isocyanate containing species?? was also observed and the catalytic implications of this observation was elaborated. Finally, design and characterization of a complex model catalyst composed of supported Pd nano-particles was investigated using CO adsorption at elevated pressures. Catalytic activity of the defect sites on the supported Pd nano-particles towards CO dissociation was demonstrated and compared with Pd (111) to elucidate the significance of the surface morphology of the active sites in a catalytic reaction.

Aujourd’hui, il est clairement établi que les lymphocytes T (LT) du donneur stimulés chroniquement par les antigènes mineurs (mHAgs) du receveur sont responsables du développement de la maladie du greffon contre l’hôte (GVHD). Il devient dès lors primordial de mettre au point des mécanismes permettant de contrôler l’activité et la fonctionnalité des LT du donneur soumis à une stimulation antigénique persistante. Nous avons montré dans un modèle in vivo de GVHD chronique qu’il est possible de réguler par deux mécanismes différents l’activité des LT du donneur stimulés chroniquement par un mHAg du receveur. Premièrement, la stimulation chronique des LT CD4+ du donneur par l’mHAg modifie fortement leurs fonctions. Ceux-ci s’adaptent à la présence de l’mHAg et y deviennent insensibles. Les LT CD4+ adaptés se caractérisent par un nombre élevé d’ARNm ainsi qu’une importante augmentation à leur surface de l’expression du récepteur inhibiteur PD-1. Nous avons montré que le blocage de la voie de costimulation négative PD-1/PD-L1 inverse et supprime l’adaptation des LT CD4+, stimule fortement leur production d’IFN-γ, entraînant le développement d’une maladie sévère. Le blocage de la voie de costimulation négative PD-1/PD-L1 aggrave aussi le choc toxique causé par l’injection de Lipopolysaccharide (LPS) et active la réaction immunitaire responsable du rejet de peaux mâles greffées sur des souris contenant des LT CD4+ adaptés. Ces résultats suggèrent que les LT CD4+ s’adaptent à la persistance de l’antigène en élevant leur seuil d’activation via la voie de costimulation négative PD-1/PD-L1. D’un autre côté, nos résultats soulignent la capacité que possèdent les cellules NK du receveur à contrôler l’activité ainsi que la prolifération des LT CD4+ du donneur soumis à une stimulation antigénique persistante. Cette faculté de régulation que détiennent les cellules NK préserve le receveur du développement d’une GVHD chronique. La régulation de la prolifération et de l’activité des LT CD4+ par les cellules NK s’effectue via NKG2D, un récepteur activateur présent à la surface de ces cellules. En effet, l’expression de certains ligands de NKG2D est augmentée dans les LT CD4+ activés. L’injection d’anticorps bloquant NKG2D inhibe l’activité régulatrice des cellules NK. Celle-ci semble s’effectuer par un mécanisme indépendant de la perforine. Nos résultats montrent que la voie de costimulation négative PD-1/PD-L1 est le mécanisme moléculaire utilisé par les LT CD4+ adaptés à l’mHAg pour calibrer leurs activités et leurs fonctionnalités en réponse à une stimulation antigénique persistante. Ils soulignent aussi le rôle des cellules NK dans le contrôle de l’activité et de la prolifération des LT CD4+ responsables du développement de la GVHD chronique.