ClC-6 und ClC-7 sind Chlorid/Proton Austauscher des späten endozytischen Wegs und lokalisieren entsprechend auf späten Endosomen und Lysosomen. Während die Relevanz von ClC-6 in der humanen Physiologie lange unerkannt war, hat ClC-7 seit lange eine etablierte Rolle als Gen, das, wenn mutiert, zu Neurodegeneration und verschiedenen Arten von Osteopetrose in Menschen führt, eine Pathologie, die von dicken und fragilen Knochen gekennzeichnet wird. Hier berichten wir über eine neue ClC-6Y553C de novo Mutation, die vor Kurzem in 3 unabhängigen Patienten entdeckt wurde, die unter einer früh-entstehenden neurodegenerativen Pathologie litten, die mit generellen Entwicklungsverzögerung, MRI Gehirn-Anomalien, Hypotonie und mangelhaftem Atem verbunden war. Mit-ClC-6Y553C-transfizierten Zellen zeigten ungewӧhnlich erhöhten Strömungen und Unempfindlichkeit an pH, was eine dramatische “gain-of-function” in dem nativen säuren Umfeld von späten Endosomen, wo ClC-6 exprimiert wird, darstellt. Zusätzlich erforschten wir die Relevanz von ClC-7 in der lysosomalen Funktion, um die molekulare Mechanismen besser zu verstehen, die hinter des lysosomalen Speicher und Osteopetrose steht, die in Menschen beobachtet werden, die von ClC-7 Mutationen betroffen sind. Zusammenfassend liefern wir Einblicke in den Konsequenzen von ClC-6 und ClC-7 Mutationen für Zelluläre Homöostase und unterstützen eine wichtige Rolle von ClC-6 und ClC-7 in endolysosomaler Funktion und, wenn mutiert, in humaner neurodegenerativen Pathologie. / ClC-6 and ClC-7 are chloride/proton exchangers of the late endocytic pathway and reside on late endosomes and lysosomes, respectively. While relevance in human physiology for ClC-6 has been long unknown, ClC-7 has an established role as a gene, that, if mutated, causes neurodegeneration and different types of osteopetrosis in humans, a sickness characterized by thick and fragile bones. Here we report a new ClC-6Y553C de novo mutation, recently reported in 3 unrelated patients, affected by an early-onset neurodegenerative disease leading to general developmental delay, MRI brain abnormalities, hypotonia and respiratory insufficiency. Transfected cells revealed abnormally enlarged currents and insensitivity to pH in the Y553C ClC-6 mutant, representing a dramatic gain of function in the native acidic environment of late endosomes, where ClC-6 is expressed. Additionally, we investigated the importance of ClC-7 in lysosomal function to better understand the molecular mechanisms behind the lysosomal storage and osteopetrosis observed in human patients affected by ClC-7 mutations. Collectively, we provide insight into the consequences of ClC-6 and ClC-7 mutations for cellular homeostasis and support a crucial role for both ClC-6 and ClC-7 in endolysosomal function and, if mutated, in human neurodegenerative disease.

Mutations in the chloride-proton antiporter, ClC-5, cause Dent’s disease, a kidney disease defined by excessive loss of proteins in the urine. ClC-5 resides on early endosomal membranes in proximal tubule epithelial cells, where it facilitates protein receptor-mediated endocytosis. Loss-of-function mutations in ClC-5 produce proximal tubule defects in protein reabsorption. This study characterized an epithelial cell phenotype for nonsense ClC-5 mutations, R648X and R704X. Both ClC-5 mutants displayed defective biosynthesis, mistrafficking and ER localization. This study showed that ClC-5 mutations, R718X and C221R, which are also misprocessed and ER retained, are targeted for proteasomal degradation as a means to be efficiently eliminated from the ER. In addition, we have shown that a missense mutation in ClC- 5, C221R, causes a global conformational change in the antiporter, which likely reflects protein misfolding, as evident by enhanced susceptibility to trypsin proteolysis. We have characterized ClC-5 disease-causing mutations in an epithelial cell model of the proximal tubule.

Mutations in the chloride-proton antiporter, ClC-5, cause Dent’s disease, a kidney disease defined by excessive loss of proteins in the urine. ClC-5 resides on early endosomal membranes in proximal tubule epithelial cells, where it facilitates protein receptor-mediated endocytosis. Loss-of-function mutations in ClC-5 produce proximal tubule defects in protein reabsorption. This study characterized an epithelial cell phenotype for nonsense ClC-5 mutations, R648X and R704X. Both ClC-5 mutants displayed defective biosynthesis, mistrafficking and ER localization. This study showed that ClC-5 mutations, R718X and C221R, which are also misprocessed and ER retained, are targeted for proteasomal degradation as a means to be efficiently eliminated from the ER. In addition, we have shown that a missense mutation in ClC- 5, C221R, causes a global conformational change in the antiporter, which likely reflects protein misfolding, as evident by enhanced susceptibility to trypsin proteolysis. We have characterized ClC-5 disease-causing mutations in an epithelial cell model of the proximal tubule.

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This thesis studies the reliability issues of encapsulated cholesteric LCD, and analyzes the defective pixel. Adjusting fabrication process parameters, we change the thickness of the buffer layer and absorption layer to explore the influence of different boundaries to CLC. It is found that the buffer layer can provide a good protection. When the buffer layer is getting thicker, the less the defective pixels appear, and the absorption layer cannot induce defect. The reflection band of the ITRI¡¦s encapsulated CLCs blue shifts to UV band and then become defective pixel. When CLCs exposed to the atmosphere with large area, the reflected color will be shifted. The shift of reflection band is due to CLC¡¦s inherent properties. Different kind of CLC has different properties, and we found the reflection band of ITRI¡¦s CLC is blue shift and the nematic E48 with chiral dopant R811 is red. Mixing different features of CLCs with appropriate proportion can reduce the color shift. In conclusion, mixing different characteristics CLCs with appropriate proportion and providing good protection to encapsulated CLC, we can reduce CLC¡¦s color shift and restrain the defective pixel.

Made available in DSpace on 2014-12-17T15:41:57Z (GMT). No. of bitstreams: 1 VitorRMM_DISSERT.pdf: 2544703 bytes, checksum: 4453e8b3e10e994e669daf77efdaa72b (MD5) Previous issue date: 2012-08-04 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Perovskites oxides win importance by its properties and commercials applications, they have a high thermal stability, have conductive properties, electrical, catalytic, electro catalytic, optical and magnetic, and are thermally stable. Because of these properties, are being widely studied as carriers of oxygen in the process of power generation with CO2 capture. In this work, the base carrier system La1-xMexNiO3 (Me = Ca and Sr) were synthesized by the method via the combustion reaction assisted by microwave. were synthesized from the combustion reaction method by microwave process. This method control the synthesi`s conditions to obtain materials with specific characteristics. The carriers calcined at 800 ? C/2h were analyzed by thermal analysis (TG-DTA), to verify its thermal stability, X-ray diffraction (XRD) to verify the phase formation, with subsequent refinement by the Rietveld method, to quantify the percentage of phases formed, the surface area by BET method was determined, scanning electron microscopy (SEM) was obtained to evaluate the material morphology and temperature programmed reduction (TPR) was done to observe the metallic phase of the nickel. After all proposed characterization and analysis of their results can be inferred to these oxides, key features so that they can be applied as carriers for combustion reactions in chemical cycles. The final products showed perovskite-type structures K2NiF4 (main) and ABO3. / ?xidos com estrutura tipo perovsquita destacam-se por suas diversas propriedades e aplica??es comerciais, pois possuem alta estabilidade t?rmica, apresentam propriedades condutoras, el?tricas, catal?ticas, eletrocatal?ticas, ?pticas e magn?ticas, al?m de serem termicamente est?veis. Devido a estas propriedades, est?o sendo amplamente estudados como carreadores de oxig?nio em processos de gera??o de energia com captura de CO2. Neste trabalho, carreadores a base do sistema La1-xMexNiO3 ( Me = Ca e Sr) foram sintetizados a partir do m?todo via rea??o de combust?o assistida por microondas. Este m?todo controla as condi??es de s?ntese para obten??o de materiais com caracter?sticas espec?ficas. Os carreadores calcinados a 800?C/2h foram analisados atrav?s de an?lise t?rmica (TG-DTA), para verifica??o de sua estabilidade t?rmica; difra??o de raios-X (DRX), para verifica??o das fases formadas, com posterior refinamento atrav?s do m?todo de Rietveld, para quantificar o percentual das fases formadas; ?rea superficial pelo m?todo BET; microscopia eletr?nica de varredura (MEV) e redu??o ? temperatura programada (TPR). Ap?s toda caracteriza??o proposta e an?lise dos seus resultados pode-se inferir a esses ?xidos, caracter?sticas fundamentais para que os mesmos possam ser aplicados como carreadores em rea??es de combust?o por ciclos qu?micos. Os carreadores de oxig?nio obtidos possuem estruturas perovsquitas do tipo K2NiF4 (principal) e ABO3.

Les cytokines de la famille de l’IL-6 possèdent comme caractéristique commune la capacité à recruter une chaine réceptrice membranaire nommée gp130. Au début de notre étude, cette famille comptait 8 membres : IL-6 et son homologue viral (vIL-6), IL-11, LIF, OSM, CNTF, CT-1 et CLC. Depuis, cette famille s’est enrichie de trois nouveaux membres, NP, IL-27 et IL-31. Ces cytokines sont essentielles au développement (LIF et CT-1) ou sont impliquées dans l’hématopoïèse, les réponses immunitaires et l’inflammation (IL-6, IL-11, IL-27, IL-31 et OSM) alors que d’autres agissent plus particulièrement au niveau du système nerveux, comme NP, CLC et CNTF. Le premier axe de recherche de ma thèse a porté sur l’identification d’un nouveau membre de cette famille,la neuropoïétine (NP), et plus précisément sur la caractérisation de son profil d’expression tissulaire et l’identification de son récepteur, des principales voies de signalisation intracellulaire induites ainsi que ses fonctions biologiques. Le deuxième axe de recherche a consisté à étudier la capacité de CLC à se comporter comme un ligand alternatif du récepteur tripartite au CNTF, impliqué dans le développement neuronal. Pour cela, nous avons mis en évidence la présence de la cytokine CLC et de ses partenaires de sécrétion, dans l’environnement des motoneurones lors du développement embryonnaire chez la souris. Enfin, le dernier axe de recherche s’est focalisé sur le rôle des états de glycosylation de CLC sur la sécrétion des cytokines composites CLC/CLF et CLC/solCNTFRα. / Members of the interleukin 6 (IL-6) cytokine family share a common characteristic, the capacity to signal via thegp130 subunit receptor. This family contains 8 members : IL-6 and its viral counterpart (vIL-6), IL-11, LIF, OSM, CNTF, CT-1 and CLC. This family has been more recently enriched with three new members, neuropoietin (NP), IL-27 and IL-31. These proteins are involved in development (LIF and CT-1), in hematopoiesis, immune responses and inflammation, such as IL-6, IL -11, IL-27, IL-31 and OSMor act in the nervous system (NP, CLC and CNTF). My first research work was focused on the identification of a new member of this family, neuropoietin. More specifically, this study allowed determining its tissue expression profile, its complex receptor and the signaling pathways induced, and its biological functions. A second research project was focused on determining whether CLC may constitute an alternative ligand for the CNTF receptor, involved in the neuronal development. We have evidenced the presence of CLC and its secretory partners, in the environment of motoneurons during embryonic development in mice. Finally, I have evaluated the role of the glycosylationstates of CLC on the secretion of the composite cytokines CLC/CLF and CLC/solCNTFR.

This work aims to develop fundamental insights about the underlying surface and bulk chemical processes instrumental to the efficiency of chemical looping combustion (CLC). CLC, which uses a solid-state oxygen carrier (e.g., metal oxides) to drive hydrocarbon combustion, is a promising combustion alternative that minimizes byproduct formation and facilities capture of CO2. In this work, we compare the performance of different transition metal oxides, namely iron, copper, cobalt, manganese, and nickel oxides, as oxygen carriers in CLC using CH4 as the reducing agent. Experiments used a continuous flow reactor across temperatures ranging from 500 to 800 oC and feed flowrates from 12.5 to 250 h-1. In addition to monitoring size-, temperature- and flow rate-dependent performance trends for CH4 conversion to CO2, microscopic and spectroscopic techniques were used to investigate the solid-state mechanism of oxygen carrier reduction and the coupled surface chemical and bulk material processes influencing performance. Bulk (XRD) and surface (XPS) analysis reveal that oxygen carrier reduction can be generally represented by two models, the unreacted shrinking core model (USCM) and the nuclei growth model (NNGM). The reduction of some metal oxides can also proceed via a two-stage solid-state mechanism; for example, hematite reduction to magnetite follows USCM, while the subsequent reductions of magnetite to wustite and wustite to iron metal follow NNGM. Furthermore, our results reveal that minimizing the particle size promotes oxygen carrier performance, but only for metal oxides reduced according to the USCM, where metal oxide reduction initiates on the particle surface. In contrast, no benefit of decreasing particle size was observed for materials reduced according to the NNGM because the reaction initiates in the particle bulk, such that a more critical determinant of reactivity may be the available oxygen carrier volume rather than surface area. Beyond these fundamental insights, cycling experiments were also performed to provide more practical information about the effect of oxygen carrier particle size on their long-term performance in CLC applications.

This paper study the influence of surface properties of encapsulated CLC on response time and reflectance via polymerization induced phase separation. The cured polymer layer, which is composed of the mixture of EMA and TRI, adhere to the inside of the non-treated glass substrate and change the surface properties to vertical alignments. Different boundary conditions caused by various UV curing intensity and cell gap lead to different electro-optical properties for CLC display. With a proper boundary structure, the transition time from homeotropic to planar of CLC can be reduced obviously with slightly reduced reflectance.

Submitted master thesis is by its character focused on development of polyaniline which would possess attributes typical for monolithic stationary phase. Developed polyaniline aims to be used in capillary liquid chromatography. Accompanying target of submitted master thesis is to provide solutions for variety of complications which follow the preparation of polyaniline in its desired form such as consistency in a form of solutions, gels and pastes, extremely fast polymerization reaction, limited solubility of cross-linking agents, solubility of monolithic polyaniline in polar mobile phases and insufficient bond of polyaniline to the inner wall of fused silica capillary tubing. Solutions for this complications are selection of ideal oxidation agent (ammonium persulfate), cross-linking agent (tris(4-aminophenyl)amine) and porogenic agent (methanol). Also, setting ideal ratio between oxidation agent, cross-linking agent and porogenic agent, heat treatment, choice of suitable mobile phase (tetrahydrofuran), adjustment of capillary wall using silanization agent (3-[3-(trimethoxysilyl)propyl]-aniline) and construction of equipment needed for quick filling of capillaries. Described development concluded in the preparation of solid polyaniline monolith which had a steady bond to the inner wall of fused...