Dissertations / Theses: 'Modelo TNT'

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Espejo, Lipacho Rodrigo Erik. "Desalineamiento del tipo de cambio real: efectos en la determinación de los precios relativos dentro la economía boliviana." Universidad Mayor de San Andrés. Programa Cybertesis BOLIVIA, 2010. http://www.cybertesis.umsa.bo:8080/umsa/2010/espejo_lr/html/index-frames.html.

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El presente trabajo busca determinar y cuantificar el desalineamiento del Tipo de Cambio Real respecto a su trayectoria de largo plazo, y los efectos que tiene dicho desalineamiento sobre los distintos sectores de la Economía Boliviana a partir del shock positivo de precios internacionales vivido a partir del año 2003 en el contexto mundial. Para dicho fin se ha dividido el mismo en tres partes. En una primera parte se identifica la situación de dicha variable al interior de nuestra economía y se plantea el periodo de estudio (1991 – 2008). En la segunda parte se plantea todo el marco teórico a utilizarse: Se presenta el modelo de PPC, mismo que se descarta, el modelo TNT para determinación del Tipo de Cambio Real, el cual finalmente se utiliza y un modelo de Booming Sector para una economía pequeña y abierta, el cual se utiliza para el testeo de Enfermedad Holandesa. La tercera parte es la de desarrollo a partir de series estadísticas para los modelos planteados en la segunda parte. Se utiliza el Modelo TNT para la obtención del Tipo de Cambio Real, utilizando la metodología de dos pasos de Engel – Granger. El primer paso consiste en plantear y determinar un Tipo de Cambio Real de Equilibrio a partir de variables que lo determinan (Fundamentos del Tipo de Cambio Real). El segundo paso determina la velocidad de ajuste del TCR hacia su trayectoria de equilibrio de largo plazo, luego de un shock externo. Para determinar la trayectoria de equilibrio de largo plazo es necesaria la eliminación de la tendencia para ello se utilizo el filtro de Hodrick y Prescott. A partir de lo anteriormente mencionado, se obtuvo una apreciación del Tipo de Cambio Real de 16% respecto a su trayectoria de equilibrio. Una vez obtenido el resultado que arroja apreciación del Tipo de Cambio Real, se utiliza el modelo de Booming Sector dividiendo a la economía en tres sectores y se corrobora insipiente presencia de Enfermedad Holandesa en la Economía Boliviana, cuantificándose el efecto causado por el boom de precios sobre el nivel de producción sobre los tres sectores en que se divide a la economía.

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Walker, Diane Kathryn. "Impact of a model soil on the biotransformation of 2,4,6-trinitrotoluene and its amine metabolites." Thesis, Montana State University, 2004. http://etd.lib.montana.edu/etd/2004/walker/WalkerD04.pdf.

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Johnson, Mark Steven. "Development and Application of Non-Traditional Vertebrate Models to Investigate Terrestrial Ecological Risk to 2,46-Trinitrotoluene Exposure." Diss., Virginia Tech, 1998. http://hdl.handle.net/10919/25987.

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Assessing ecological risk to wildlife exposed to anthropogenic contamination in soil has traditionally been problematic. Attempts to standardize an approach to evaluate risk for various community types in North America have been challenging, given the variation in terrestrial communities and the values in which policy makers are bound to protect. This has resulted in vague, yet flexible guidance from the U.S. Environmental Protection Agency and other interested parties (e.g., the U.S. Army Corps of Engineers, and the Tri-Service Ecological Risk Assessment Working Group). Interpretation of these and other guidance has been variable, often resulting in conflicting opinions on how best to address the question of ecological risk to receptors that are exposed to xenobiotics in a soil matrix. This work reports the results of research designed to address the question of ecological risk to terrestrial vertebrates. Objective, ecologically-relevant criteria were used in the selection and development of models in this research. Several lines of logic were considered: 1) substance sensitivity, 2) ecological sensitivity (i.e., the species importance to the system; e.g., keystone species); and, 3) probability and extent of exposure. A primary soil contaminant at many U.S. Army installations is 2,4,6-trinitrotoluene (TNT). This was a result of the mass manufacturing, storing, and assembly of weapons from the early 1900's until the 1950s. The Army has reported soil concentrations of TNT ranging from 0.12 to 38,600 ug/g (Walsh and Jenkins 1992) and 0.08 to 64,000 ug/g (Hovatter et al. 1997). The chemical-physical properties of TNT result in a relatively unique compound, not easily amenable to current modeling techniques to estimate exposure to terrestrial wildlife. Moreover, there are few data describing the effects of exposure to TNT in other than mammals, fish, and specific invertebrates. In this research, the pathways of exposure and selected potential toxic effects from TNT exposure were investigated in a terrestrial salamander: Ambystoma tigrinum (tiger salamanders). A. tigrinum was chosen since they are exclusively carnivorous, relatively long-lived, have a thin integument, and are large enough to investigate individual effects. These investigations were designed to mimic natural conditions as closely as possible, though maintain a degree of homogeneity in a laboratory environment. All studies exposed salamanders to soil and food (earthworms) in identical preparations. As such, these exposures were considered complete, eliminating assumptions made regarding daily food consumption, systemic dermal dose, etc. The first study examined the relative contribution of dermal or oral exposures to the whole-body burdens of TNT and primary metabolites. A poly-chlorinated biphenyl (PCB) mixture (Aroclor7 1260) was used with TNT to simultaneously to assist in the evaluation of each pathway, since the fate and transport of PCBs are well characterized. Tiger salamanders were exposed 28 days in situ. The dermal route of exposure contributed the most to the final burdens of TNT in salamanders, with the primary reduction products, 2-amino-4,6-dinitrotoluene and 4-amino, 2,6-dinitrotoulene reaching higher concentrations than of parent compound. Other TNT metabolites were found in insignificant quantities. The concentrations of PCBs were higher in the oral treatment, as expected. These results were corroborated in a subsequent study using Ambystoma maculatum (spotted salamanders). The second series of investigations evaluated the potential toxic effects from TNT exposure. Two treatments consisting of TNT and a control were used to evaluate these effects to A. tigrinum. The salamanders were exposed in situ for 14 days to TNT in soil and food (earthworms of which were exposed to TNT in the soil in similar preparations). Non-specific immune effects were evaluated through the characterization of splenic phagocytes in their ability to: 1) phagocytize foreign particles, and 2) digest (through oxygen radicals) phagocytized material. This was conducted using fluorescent microspheres and a fluorescent chemical probe specific to hydrogen peroxide, measured per each cell using flow cytometry. Other data collected included histological examination (e.g., liver, kidney, and other miscellaneous organs), blood differentials, weight changes over time, organ/ body weight comparisons, and an analysis of organ-specific metabolism. No significant effects were noted in salamanders exposed to these conditions. Coordinated with the preceding study included a search for biomarkers of exposure and an investigation of the metabolites of TNT in situ. Biotransformation products of TNT were found including primary (e.g., 2-amino-4,6-dinitrotoluene) and secondary (e.g., 2,4-diamino-6-nitrotoluene) in relative concentrations in skin, liver, and kidney. Biomarkers of exposure included an analysis of cytochrome p450, b5, and the glutathione antioxidant enzymes in liver, kidney, skin, lung, and serum, respectively. Traces of parent compound were found in the skin and liver only. Levels of 2,4-diamino-6-nitrotoluene were found only in the liver and kidney, suggesting that TNT is reduced primarily in or on the skin. Levels of p450 were higher in TNT exposed salamanders than controls. Glutathione and related enzyme levels are reported. This work suggests that salamanders have levels of detoxification enzymes capable of the biotransformation of anthropogenic substances in soil rivaling that of mammals. Another investigation evaluated these same immunological parameters in white-footed mice (Peromyscus leucopus). This species was chosen based on the relative importance of small mammals to the community structure in many North American ecosystems. Mice were exposed to TNT in the feed at 0.264, 0.066, 0.033, and 0.017%, where actual daily dose estimates for males were 604, 275, 109, and 65; and for females was 544, 282, 143, and 70 mg/kg/d. An investigation to evaluate the specificity of commercially-available monoclonal antibodies specific to cell surface markers for thymocytes and splenocytes in inbred mice was unsuccessful. These results suggest the recognition epitopes of monoclonal antibodies prepared against Old-World mice are not conserved into Peromyscus, a New-World species. However, high dose males and females had larger spleens consistent with the hemolytic effects previously reported for mammals exposed to TNT. Further, males exposed at all levels had reduced phagocytic activity of splenocytes, and reduced hydrogen peroxide production associated with the two highest doses relative to controls. Females showed no response relative to treatment. This research has shown the feasibility for these types of investigations, and provides toxicity information valuable for modeling estimates of ecological risk. Further, the in situ exposures have provided media concentrations that are or are not toxic for species of concern. This type of information reduces the uncertainty associated with ingestion modeling estimates, dermal exposure estimates, and other factors not traditionally considered in toxicity studies.
Ph. D.

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Daniels, William Julius. "Van Sendingkerk tot Verenigde Gereformeerde Kerk in Suider Afrika: 1960-1997." Thesis, University of the Western Cape, 1998. http://etd.uwc.ac.za/index.php?module=etd&amp.

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Bergeron, Alison. "Characterization of the Tet-On Grb 7 and Tet-On 14-3-3 sigma mouse models." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97101.

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ErbB2 is overexpressed and amplified in about 30% of all breast tumors and is correlated with poor patient prognosis. ErbB2 knock in mouse models mimic the amplification in chromosome 11 (human chromosome 17q21-25) comprising of ErbB2 and Grb7 and a deletion in chromosome 4 (human chromosome 1p35-36) including 14-3-3σ seen in human breast cancers. Grb7 is an adaptor protein known to regulate cell migration and transcription by interacting with a cell migration protein FAK and a transcription factor protein FHL2. Grb7 overexpression has been linked to an increase in metastasis and poor patient outcome. 14-3-3σ is negative cell cycle protein that is upregulated by p53. Interestingly, 14-3-3σ has a role in down regulating ErbB2 expression by sequestering EGR2 from the nucleus to the cytoplasm. These results suggest that 14-3-3σ deletion and Grb7 overexpression in ErbB2 tumors represents an interesting target to study as its deletion may be a targeted event in the development of ErbB2 tumors.To elucidate the role of Grb7 and 14-3-3σ I generated a mouse model utilizing the Tet-On mouse model system whereby these two proteins are overexpressed in the mouse mammary epithelium. Through this study we confirmed successful localized overexpression of both Grb7 and 14-3-3σ in the mouse mammary gland epithelium. Further, we were able to confirm that individual expression of both Grb7 and 14-3-3σ lead to a ductal outgrowth defect during mammary gland development. These observations confirm that Grb7 and 14-3-3σ both play a role in mouse mammary gland development.
ErbB2 est au-dessus d'exprimer et d'amplifier dans environ 30% de toutes les tumeurs de sein et est corrélé avec le pronostic patient pauvre. Le coup en ErbB2 dans des modèles de souris imitent l'amplification en chromosome 11 (chromosome humain 17q21-25) comportant d'ErbB2 et de Grb7 et une suppression en chromosome 4 (chromosome humain 1p35-36) comprenant le  14-3-3σ vu dans les cancers du sein humains. Grb7 est une protéine d'adapteur connue pour régler la migration et la transcription de cellules par l'interaction avec une protéine FAK de migration de cellules et une protéine FHL2 de facteur de transcription. Grb7 au-dessus d'expression a été lié à une augmentation de métastase et de résultats patients pauvres. Le  14-3-3σ est une protéine négative de cycle de cellules qui upregulated par p53. Intéressant, 14-3-3σ a un rôle en réglant vers le bas l'expression ErbB2 en séquestrant EGR2 du noyau au cytoplasme. Ces résultats suggèrent que la suppression 14-3-3σ et le Grb7 au-dessus de l'expression dans les tumeurs ErbB2 représente une cible intéressante pour étudier pendant que sa suppression peut être un événement visé dans le développement des tumeurs ErbB2. Ces résultats suggèrent que la suppression 14-3-3σ et le Grb7 au-dessus de l'expression dans les tumeurs ErbB2 représente une cible intéressante pour étudier pendant que sa suppression peut être un événement visé dans le développement des tumeurs ErbB2. Pour élucider le rôle de Grb7 et de 14-3-3 j'ai produit d'une utilisation de modèle de souris Tet-Sur le système modèle de souris par lequel ces deux protéines soient plus de exprimées dans l'épithélium mammaire de souris. Par cette étude nous avons confirmé réussi localisé au-dessus de l'expression de Grb7 et de 14-3-3σ dans l'épithélium de glande mammaire de souris. De plus, nous pouvions confirmer que l'expression individuelle des deux Grb7 et le  14-3-3 mènent à un défaut ductal de conséquence pendant le développement de glande mammaire. Ces observations confirment que Grb7 et 14-3-3σ les deux jeu un rôle dans le développement de glande mammaire de souris.

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Semerano, Luca. "Active anti-TNF alpha immunization in a murine model of rheumatoid arthritis : Relevance to human disease." Paris 13, 2013. http://www.theses.fr/2013PA132018.

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Current anti-TNFα treatments (monoclonal antibodies or soluble receptors) radically changed the treatment of rheumatoid arthritis (RA) and other TNFα-related diseases, but even show several drawbacks as far as safety, efficacy and costs are concerned. Active immunization with human TNFα kinoid (TNF-K) is an alternative anti-TNFα strategy that exploits vaccination principle in order to induce the production of polyclonal anti-TNFα Abs by recipients. We show the feasibility of this approach in a disease model that mimics the main features of human RA and that depends on deregulated TNFα production: the human TNFα transgenic mouse. We show that the treatment of arthritic mice with TNF-K dramatically ameliorates the disease, that the production of anti-hTNFα Abs is time-limited and renewable by a boost dose of TNF-K. Conversely, native hTNFα does not induce anti-hTNFα Abs. Immunosuppressant treatments do not seem to impair TNF-K efficacy. We bring evidence that polyclonal and monoclonal anti-TNFα Abs share some key features in their mechanism of action. Both treatments induce the same modifications in regulatory T-cell populations. Moreover, serum level of both polyclonal and monoclonal anti-TNFα Abs is a major factor determining whether the treatment results in protection from articular inflammation and destruction. These results contributed to the development of active anti-TNF immunization in human disease; TNF-K recently entered phase II clinical trials in RA
Les traitements utilisés pour le blocage de la cytokine pro inflammatoire TNFα (anticorps monoclonaux ou récepteurs solubles) ont révolutionné la prise en charge de maladies telles que la polyarthrite rhumatoïde (PR), mais montrent des limites en termes d’efficacité, effets secondaires et coûts. L’immunisation active par le kinoïde du TNFα humain (TNF-K) est une stratégie alternative de ciblage du TNFα, qui exploite le principe de la vaccination pour induire l’hôte à produire des anticorps (Ac) polyclonaux anti-TNFα. Nous montrons la faisabilité de cette approche dans un modèle d’arthrite qui reproduit les caractéristiques essentielles de la PR et qui dépende de la production déréglée de TNFα : la souris transgénique pour le TNFα humain (hTNFα). Nous montrons que le traitement des souris arthritiques par TNF-K améliore nettement la maladie, que la production d’Ac anti-hTNFα est limitée dans le temps et renouvelable par une dose de rappel de TNF-K. Au contraire, le hTNFα natif n’induit pas d’Ac anti-TNFα. Les traitements immunosuppresseurs ne semblent pas limiter l’efficacité du TNF-K. Nous apportons des preuves en faveur d’une homogénéité de fonctionnement entre les Ac polyclonaux et monoclonaux anti-TNFα. En fait, les deux traitements induisent les mêmes modifications des populations cellulaires de cellules T régulatrices. En outre, les taux sériques d’Ac monoclonaux et polyclonaux anti-TNFα sont le principal facteur qui détermine si le traitement protège ou pas de l’inflammation et de la destruction articulaire. Ces résultats ont contribué à faire avancer le développement de cette stratégie jusqu’à la phase II d’expérimentation clinique dans la PR

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Alves, Caio Cesar de Souza. "Infecção intratorácica com Paracoccidioides brasiliensis em modelo experimental murino." Universidade Federal de Juiz de Fora (UFJF), 2007. https://repositorio.ufjf.br/jspui/handle/ufjf/3201.

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A Paracoccidioidomicose é uma micose sistêmica humana causada pelo fungo dimórfico, Paracoccidioides brasiliensis, que acomete, principalmente, indivíduos adultos do sexo masculino. O presente estudo propôs a padronização do modelo de infecção com P. brasiliensis pela via intratorácica em camundongos BALB/c. Este estudo foi monitorado pela detecção do P. brasiliensis através da contagem de unidades formadoras de colônia e pela presença de DNA do fungo nos pulmões dos animais infectados em diferentes pontos pósinfecção (2o, 7o, 15o, 30o, 45o, 60o e 90o dias) e a taxa de sobrevida dos camundongos. Além disto, foram avaliados alguns parâmetros imunológicos como a produção de óxido nítrico, TNF-alpha, IFN-gama, e IL-10 por células presentes no lavado intratorácico, contagem total e diferencial do número de células do lavado intratorácico, o estudo histopatológico dos pulmões e a detecção de anticorpos específicos anti-P. brasiliensis nos pulmões e no soro. Os resultados mostram um aumento gradual do número de colônias e de DNA de P. brasiliensis nos pulmões. Até o 15o dia após a infecção pode ser observado um aumento na produção de óxido nítrico e IFN-gama pelas células do lavado intratorácico, bem como um aumento do número total de células e da porcentagem de leucócitos mononucleares. A partir do 30o dia após a infecção observa-se um aumento de anticorpos específicos (IgG1) no soro e no pulmão, um aumento da produção de IL-10 e TNF-alpha pelas células do lavado intratorácico e conseqüente diminuição da produção de IFN-gama e óxido nítrico. Além disso, observa-se um aumento da porcentagem de células polimorfonucleares no lavado. No estudo histopatológico pode ser constatado um aumento gradual no tamanho e complexidade dos granulomas presentes nos cortes histológicos. Os camundongos utilizados no estudo de sobrevida começaram a morrer no 60o dia após a infecção. Os resultados mostram uma resposta inicial do hospedeiro com um perfil Th1 mudando durante a infecção para uma resposta Th2 que leva ao óbito dos camundongos BALB/c.
Paracoccidioidomycosis or South American blastomycosis, is a chronic granulomatous human male infection caused by the Paracoccidioides brasiliensis. The present study it considered the standardization of the model of infection with P. brasiliensis for the intrathoracic route in BALB/c mice. This study was monitored by the detection of the P. brasiliensis through the counting of colony forming units and by the presence of DNA of fungi in the lungs of the infected animals in different points (2, 7, 15, 30, 45, 60 and 90 days) and the survival rate of the mice. Moreover, some immune parameters had been evaluated as the nitric oxide production, TNF-alpha, IFN-gamma, and IL-10 for cells in the intrathoracic washed, total and distinguishing counting of cells of the intrathoracic washed, the lung histopathology and the detection of specific antibodies anti-P. brasiliensis in the lungs and serum. The results show a gradual increase of the number of colonies and P. brasiliensis DNA in the lungs. Until 15 day after the infection can be observed an increase in the nitric oxide production and IFN-gamma for the cells of the washed, as well as an increase of the total number of cells and the percentage of mononuclear. From 30 day after the infection observes an increase of specific antibodies (IgG1) in the serum and the lung, an increase of the production of IL-10 and TNF-alpha for the cells of the washed and consequent reduction of the IFN-gamma production and nitric oxide. Moreover, observed an increase of the percentage of cells polimorphonuclear in the washed. In the histopathology it can be evidenced a gradual increase in the size and complexity of granulomas in the cuts. The mice used in the survival study had started to die in 60 day after the infection. The results show an initial reply of the host with a Th1 profile moving during the infection for a Th2 reply that leads to the death of the BALB/c mice.

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Borges, Antônio Carlos. "Expressão de um fragmento da Miosina Va inibe o crescimento de tumores de melanoma induzidos em modelo animal." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/17/17136/tde-10022012-135441/.

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A miosina Va é uma proteína motora envolvida no transporte e posicionamento de vesículas, organelas e mRNA. Além disso, postulou-se que a miosina-Va atua no seqüestro do fator pró-apoptótico, Bmf, no citoesqueleto de actina. Pesquisas realizadas em nosso laboratório demonstraram que um fragmento da miosina Va (MVaf), que corresponde ao sítio ligante de DLC2-Bmf, é capaz de induzir intensa apoptose em células de melanoma e de carcinoma in vitro. O presente trabalho teve por objetivo principal avaliar o potencial do MVaf como agente antitumoral, através de abordagens de terapia gênica em modelo animal. Foram geradas linhagens estabilizadas e com expressão controlada pelo sistema Tet-ON onde a expressão de EGFP ou EGFP-MVaf é induzida com a adição de doxiciclina. Essas linhagens foram testadas quanto à porcentagem de morte por apoptose e ativação de caspases. Tumores foram induzidos em camundongos C57BL/6 por inoculação subcutânea de células tumorigênicas positivas ou não para a expressão de EGFP-MVaf. Também foram utilizadas linhagens de fibroblasto embrionário murino selvagem (MEFs WT) e nocautes para os fatores Bim/Bmf e Bax/Bak (MEFsBim-/-,Bmf-/-; MEFsBax-/-,Bak-/-) para estudos do mecanismo de ação do fragmento da miosina Va. Observou-se que a adição de butirato de sódio potencializa a expressão de EGFP-MVaf e, conseqüentemente, o efeito pró-apoptótico desse fragmento e que essas células são mais sensíveis aos quimioterápicos etoposídeo e taxol, apresentando maior susceptibilidade à apoptose. Verificou-se que a expressão de EGFP-MVaf em células de tumores de melanoma induzidos em camundongos C57BL/6J dificulta o crescimento desses tumores. Quanto ao estudo com MEFs, observou-se que células nocautes para os fatores pró-apoptóticos Bim/Bmf e Bax/Bak são menos susceptíveis à morte induzida pelo fragmento da miosina Va. Indução da expressão de MVaf desencadeia a liberação da proteína proapoptótica Smac (fusionada ao repórter fluorescente Cherry) do espaço intermembranas da mitocôndria para o citoplasma sugerindo que a morte apoptótica induzida por MVaf requer a permeabilização da membrana mitocondrial externa (MOMP). Concluindo, os dados apresentados aqui nos permitem propor o MVaf como uma molécula promissora para o desenvolvimento de novas abordagens terapêuticas contra o câncer.
Myosin Va is a motor protein involved in the transport and positioning of vesicles, organelles and mRNA. Additionally, myosin-Va has been implicated in the sequestering of a proapoptotic factor, Bmf, to the actin cytoskeleton. Research in our laboratory demonstrated that a fragment of myosin Va (MVaf), which corresponds to the binding site of DLC2-Bmf, is capable to induce intense apoptosis in melanoma and carcinoma cells in vitro. Here, our goal was to assess the potential of MVaf as antitumor agent, through gene therapy approaches in animal models. We generated Tet-ON controlled B16-F10 melanoma cells whose expression of EGFP or EGFP-MVaf is induced with the addition of doxycycline. These cells were tested for apoptotic death and activation of caspases, and were used to induce tumors in C57BL/6J mice by subcutaneous inoculation. We also used cell lines of murine embryonic fibroblasts, wild-type (MEFs WT) and knockouts for the proapoptotic proteins Bim/Bmf or Bax/Bak (MEFsBim-/-,Bmf-/-, MEFsBax-/-,Bak-/-), to study the mechanism by which MVaf induces apoptosis. We observed that addition of sodium butyrate to the cultures enhances the EGFP-MVaf expression and, consequently, the pro-apoptotic effect of this fragment. Treated cells were more sensitive to the chemotherapeutic drugs etoposide and taxol, showing a higher susceptibility to apoptosis. Moreover, in vivo induction of EGFP-MVaf expression retards growth of B16-F10 melanoma tumors in mouse model. As for the study with MEFs, we observed that cells knockout for the proapoptotic factors Bim/Bmf or Bax/Bak are less susceptible to death induced by MVaf than wild-type MEFs. Accordingly, we showed that MVaf expression triggers release of the proapoptotic protein Smac (tagged with the fluorescent protein Cherry) supporting the involvement of the mitochondrial outer membrane permeabilization (MOMP) in the MVaf-induced apoptotic death response. In conclusion, these data lead us to propose MVaf as a promising molecule for the development of new therapeutic approaches against cancer.

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Saxton, Nina Elizabeth. "Anti-TNF-#alpha# treatment in the rat heterotropic cardiac allograft model." Thesis, Open University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321566.

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Mishra, Shrikant. "Mechanism of TNF-[alpha] cytotoxicity in a leukemia virus transformation model /." This resource online, 1991. http://scholar.lib.vt.edu/theses/available/etd-08232007-112933/.

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Mishra, Shrikant. "Mechanism of TNF-α cytotoxicity in a leukemia virus transformation model." Diss., Virginia Tech, 1991. http://hdl.handle.net/10919/39214.

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Taugher, Rebecca Jane. "Exploring the role of ASIC1a in mouse models of anxiety." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/6508.

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Carbon dioxide (CO2) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO2 can trigger fear and panic even in the absence of amygdalae, suggesting and important role for extra-amygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear- and anxiety-related behaviors and expresses acid sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO2-evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO2-evoked freezing and CO2-conditioned place avoidance. In addition, we found that CO2 inhalation caused BNST acidosis, and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO2-evoked freezing whereas viral vector mediated expression of ASIC1A in the BNST of Asic1a-/- and Asic1a+/+ mice increased CO2-evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO2-evoked fear-related behavior. Genetic disruption of the acid-sensing ion channel-1A (ASIC1A) in mice results in deficits in several fear- and anxiety-related behaviors. These deficits have been largely attributed to the loss of ASIC1A in neurons. However, recent studies have identified ASIC1A in several types of non-neuronal cells, including glia. To test the hypothesis that it is the loss of ASIC1A in neurons that results in the behavioral deficits seen in Asic1a-/- mice, we generated SynCre+Asic1aloxP/loxP mice, in which ASIC1A is disrupted specifically in neurons. To validate these mice, we confirmed by PCR that the Asic1a floxed allele was disrupted in brain, but not tail DNA. We further detected a reduction in ASIC1A protein in the SynCre+Asic1aloxP/loxP mice by western blotting and ASIC1A immunohistochemsitry. Further characterization of cre expression with a Rosa26 cre reporter mouse revealed that cre expression did not occur in all neurons, but verified that cre expression was neuron-specific. This neuron-specific knockout of ASIC1A led to behavioral deficits in several models of fear and anxiety, including cued and context fear conditioning, predator odor-evoked freezing and CO2-evoked freezing. Together, these findings suggest that it is ASIC1A in neurons that mediates these fear- and anxiety-related behaviors. Trimethylthiazoline (TMT), a predator odor isolated from fox feces, elicits freezing and avoidance responses in rodents. This TMT-evoked freezing behavior depends on the bed nucleus of the stria terminalis (BNST), a brain region thought to contribute to anxiety in both humans and mice. Because the acid-sensing ion channel-1A (ASIC1A) is robustly expressed in the BNST and has been previously implicated in TMT-evoked freezing, we hypothesized that the BNST might be a site of ASIC1A action in the TMT-evoked freezing response. Consistent with previous studies, we found that TMT-evoked freezing depended both on the olfactory bulb and on ASIC1A. Viral-mediated disruption of ASIC1A in the BNST reduced TMT-evoked freezing, whereas, viral mediated expression of ASIC1A in the BNST of Asic1a-/- mice increased TMT-evoked freezing. We further observed that TMT exposure induces a modest acidosis, likely due to TMT-induced respiratory suppression. However, this respiratory suppression was not unique to odors that evoke freezing, suggesting that it does not drive the TMT-evoked freezing response. Together, these findings suggest that the BNST is a key site of ASIC1A action in TMT-evoked freezing. Regulation of cerebral blood flow (CBF) is critical to insure that the brain has adequate resources to maintain normal function. One of the strongest regulators of CBF is carbon dioxide (CO2). CO2 and acidosis are thought to induce vasodilation and increase CBF by initiating nitric oxide (NO) synthesis, though the mechanism by which this occurs is unknown. Recent unpublished studies have suggested that the acid-sensing ion channel-1A (ASIC1A) plays a role in hypercapnia-induced vasodilation. Therefore, we hypothesized that CO2-induced NO production would depend on ASIC1A. We found that CO2 induced robust NO production in Asic1a+/+ but not Asic1a-/- mice. To test the role of neuronal ASIC1A in CO2-induced NO production, we generated SynCre+Asic1aloxP/loxP mice, in which ASIC1A is disrupted specifically in neurons. We found that CO2 did not induce significant NO production in the SynCre+Asic1aloxP/loxP mice, suggesting that it is ASIC1A in neurons that mediates this response. Together, these studies suggest that ASIC1A may mediate neurovascular coupling and regulate CBF.

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Paiva, Almino Afonso de Oliveira. "Avalia??o de uma fra??o polissacaridica da alga Lobophora variegata (Lamouroux) em modelo de artrite induzida em ratos por Zymosan." Universidade Federal do Rio Grande do Norte, 2010. http://repositorio.ufrn.br:8080/jspui/handle/123456789/18532.

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Fucans seaweed Lobophora variegata estructures are known for their chemical and biological properties. In this study, we analyzed, the action of fucans L. variegata and the fractions purified with acetone in Zymosan-induced arthritis. After differential fractionation with acetone, six fractions were obtained and named F0.3, F0.5, F0.8, F1, F1.5 and F2. The results showed that the fraction F1 showed high yield (51.9%) and was chosen for studies of antioxidant activity and induced arthritis. Nuclear magnetic resonance (NMR) of 13C showed signals at 103.3 and 15.78 ppm that are assigned to links ?13 galactose and of the C6 methyl fucose, respectively. The infrared (IR) showed absorbance at 1238 and 850 cm-1 which are attributed to sulfate. The fraction F1 showed antioxidant activities in vitro. For analysis of inflammatory parameters chosen the polysaccharide was administered in different doses (25, 50 and 75 mg / kg ip, per body weight) and diclofenac sodium (5 mg / kg ip) and L-NAME (25 mg / kg ip) in groups of animals (n = 6). After 6 h, were analyzed for cellular influx and levels of nitrite. In experiment five days, were made analysis of swelling and serum TNF-?. Histopathological analysis were performed for confirmation of results. The fraction F1 (25, 50 and 75 mg / kg ip) reduced the cellular influx (52.1 to 96.7%) and nitric oxide levels (27.2 - 39%) compared to control group. The reduction of edema (63.4 - 100%) and serum TNF-? (p <0.001) were observed when the polysaccharide F1 administered at a dose (50 mg / kg) These results suggest that these heterofucanas of Lobophora variegata have besides the activity antioxidant and potential anti-inflammatory activity in arthritis induced by zymosan
Fucanas da alga Lobophora variegata s?o conhecidas por suas estruturas qu?micas e propriedades biol?gicas. Nesse estudo, analisou-se a a??o de fucanas de L. variegata e suas fra??es purificadas com acetona na artrite induzida por Zymosan. Ap?s fracionamento diferencial com acetona, 6 fra??es foram obtidas e nomeados F0.3, F0.5, F0.8, F1, F1.5 e F2. Os resultados mostraram que a fra??o F1 apresentou alto rendimento (51,9%) e foi escolhida para estudos da atividade antioxidante e artrite induzida. A resson?ncia magn?tica nuclear (RMN) de 13C mostrou sinais a 103,3 e 15,78 ppm que s?o atribu?dos ?s liga??es ?1 3 da galactose e metil do C6 da fucose, respectivamente. O infravermelho (IV) mostrou absorb?ncia a 1238 e 850 cm-1 que s?o atribu?das ao sulfato. A fra??o F1 apresentou atividades antioxidantes in vitro. Para an?lise de par?metros inflamat?rios a fra??o polissacar?dica escolhida foi administrada em diferentes doses (25, 50 e 75 mg/kg i.p, por peso corporal), assim como diclofenaco de s?dio (5 mg/kg i.p.) e L-NAME (25 mg/kg i.p.) em grupos de animais (n=6). Depois de 6 h, foram realizadas an?lises de influxo celular e n?veis de nitrito. Em experimento de cinco dias, foram efetuadas analises de edema e TNF-? s?rico. An?lises histopatol?gicas foram realizadas para confirma??o de resultados. A fra??o F1 (25, 50 e 75 mg/kg i.p.) reduziu o influxo celular (52,1 ? 96,7%) e os n?veis ?xido n?trico (27,2 ? 39%) em rela??o ao grupo controle. A redu??o do edema (63,4 - 100%) e TNF-? s?rico (p < 0,001) foram observadas quando administrado o polissacar?deo F1 na dosagem (50 mg/kg) Esses resultados sugerem que essas heterofucanas de Lobophora variegata possuem al?m da atividade antioxidante, potencial atividade anti-inflamat?ria na artrite induzida por zymosan

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Nguyen, Danny. "Validation and Improvement of the TNO Model for Trailing Edge Noise Prediction." Thesis, University of California, Davis, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10933376.

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The TNO model, a trailing edge noise prediction method, is validated, modified, and analyzed for various input formats. Two different methods are used to calculate the flow field for this model: Reynolds averaged Navier-Stokes (RANS) and a viscous panel method, XFOIL. It is found that the RANS-based TNO model show good agreement with the experiments but the XFOIL-based TNO was found to overpredict the turbulence kinetic energy and, consequently, the sound pressure level. A modification is made in the XFOIL-based TNO model by substituting Prandtl's mixing length hypothesis from the original model with a new blended model consisting of the mixing length hypothesis and the Cebeci-Smith eddy viscosity model. Twenty-six different test cases are tested with airfoils: NACA 0012, NACA 0015, NACA 64-618, NACA 64₃-418, and DU 96-w-180. RANS input to the TNO model is able to predict the sound pressure spectrum to within 3 dB for the frequency range of 800Hz to 2000Hz in 16 of the 26 cases. The new blended model is found to show clear improvements to the prediction for 14 out of the 26 cases when compared to the original XFOIL input. Moreover, the new XFOIL input was able to predict sound pressure level to within 3 dB for 14 of the 26 cases. Overall, the new proposed model improves the prediction for the XFOIL-based TNO model.

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15

Villette, François. "Endommagement de milieux hétérogènes : Le papier en tant que matériau modèle." Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALI062.

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La compréhension, la modélisation et la prévision de la rupture dans les matériaux hétérogènes sont des enjeux importants pour de nombreuses applications comme la résistance des structures de génie-civil ou les détachements de blocs rocheux par exemple. Actuellement, la modélisation de la fissuration dans les modèles d’endommagement fait intervenir une longueur interne qui n’est pas encore reliée explicitement aux longueurs caractéristiques du matériau. L’objectif de ce travail est d’étudier l’influence des hétérogénéités du matériau sur les processus de fissuration en utilisant le papier comme matériau d’étude. Ce matériau a en effet la propriété de révéler sa structure (fibres et agrégats de fibres) par transmission optique et permet ainsi de suivre l’évolution de l’endommagement au cours de la rupture à moindres coûts. Dans un premier temps, les propriétés structurales et mécaniques locales des agrégats de fibres ont été obtenues à partir d’images acquises par tomographie à rayons X et d’essais de tractions. Des essais de traction filmés ont ensuite permis de visualiser le développement de la zone d’endommagement et de relier ses dimensions au comportement post-pic de la courbe de traction. Sur la base de cette analyse, une méthode originale de calage de la longueur interne a été proposée sur un modèle d’endommagement continu non local. Le rôle des différentes longueurs caractéristiques du matériau a été mis en évidence par ces résultats qui ont été complétés par une étude de la statistique de propagation de fissure dans un matériau hétérogène en utilisant un Fiber Bundle Model (modèle à faisceaux de fibres), que nous avons dans le cadre de cette thèse étendu à des champs aléatoires de rupture corrélés dans l’espace
The understanding, modeling and prediction of failure in heterogeneous materials are important issues for many applications such as the resistance of civil engineering structures or rock detachments for example. Currently, damage models involve an internal length that is not yet explicitly related to the characteristic lengths of the material. The objective of this work is to study the influence of material heterogeneities on cracking processes using paper as a model material. Indeed, this material has the property to reveal its structure (fibers and fiber aggregates) by optical transmission and thus allows following the evolution of the damage during the rupture at lower costs. In a first step, the local structural and mechanical properties of the fiber aggregates were obtained from images acquired by X-ray tomography and tensile tests. Filmed tensile tests were then used to visualize the development of the fracture process zone and to relate its dimensions to the post-peak behaviour of the tensile curve. On the basis of this analysis, a novel method of calibration of the internal length was proposed on a non-local continuous damage model. The role of the different characteristic lengths of the material was highlighted by these results which were complemented by a study of the crack propagation statistics in a heterogeneous material using a Fiber Bundle Model that we have extended to spatially correlated random fields of rupture

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16

Lyall, Marcus James. "TET mediated 5’hydroxymethylation in the pathogenesis of non alcoholic fatty liver disease." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/29524.

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Non-alcoholic fatty liver disease (NAFLD) now affects around one in four adults in the human population and parallels the global increase in obesity. Within the spectrum of NAFLD, simple steatosis is associated with insulin resistance and type 2 diabetes while progression to steatohepatitis (NASH) is associated with an increased risk of liver cirrhosis and all-cause mortality. The molecular pathology of NAFLD is incompletely understood, however observational studies in human cohorts suggest the regulation of DNA methylation may play a role. 5-hydroxymethylcytosine (5hmC) is a cytosine modification generated from 5- methylcytosine (5mC) by the Ten eleven translocase isoenzymes (Tets) as part of a demethylation process. The aim of this project was to examine the role of Tet enzyme activity on the pathogenesis and progression of NAFLD. Detailed characterisation of two established murine dietary interventions allowed the selection of a NAFLD mouse model which broadly recapitulated the metabolic, histological and transcriptional features of human disease. Using DNA immunoprecipitation coupled with whole genome next generation sequencing and RNA micro expression arrays I examined the effect of high fat diet feeding (HFD) on hepatic DNA 5hmC levels within annotated gene regions. Whilst the global 5hmC profile was not altered by HFD, there was profound genic enrichment of 5hmC in upregulated mediators of cholesterol synthesis and transport (Lss, Sc4mol, Fdps, Hsd17b7, Cyp17a1, Mvd, Cyp1a2, Dhcr7 and Apoa4) with no enrichment in genes with other pathological functions (drug detoxification, inflammation, cell cycle regulation). Induced peaks of 5hmC enrichment were subsequently abolished following rescue of the NAFLD phenotype by conversion to control diet. Cross species validation was performed in vitro utilising embryonic stem cell derived hepatocytes challenged with a cocktail of high energy substrates. My in vivo findings were broadly replicated with specific 5hmC enrichment in genes synthesising lipotoxic molecules (PLIN2, CIDEC, APOA4, ACADVL, HMGCS2, APOA5, CYP2J2, IGFBP1, PPAP2C, ACSL1, APOC3, ANGPTL4, NRG1) with no enrichment in upregulated genes of alternative function. To determine whether or not the 5hmC enrichment seen is of functional relevance, I studied Tet1-/- C57BL/6J mice. Tet1-/- mice are grossly normal in appearance, however loss of Tet1 conferred a striking resistance to diet induced obesity with reduced body fat mass, improved insulin-sensitivity and near complete absence of NAFLD compared to wild type littermates. Furthermore, the HFD fed Tet1-/- liver transcriptome showed a ‘protective’ profile, with suppression of genes for lipid synthesis, inflammation and fibrosis. Thus, in multiple cross-species models of NAFLD, over nutrition induces genic hydroxymethylation specifically within activated genes driving the synthesis and transport of lipid molecules. Such changes are reversible with resolution of the NAFLD phenotype strengthening functional association. Tet1 deficiency conveys an obesity and NAFLD resistant phenotype. I therefore introduce Tet1 mediated hydroxymethylation as a novel mechanism for NAFLD pathogenesis.

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17

Manosso, Luana Meller. "Avaliação do efeito da vitamina e em modelo animal de comportamento depressivo induzido por TNF-a." reponame:Repositório Institucional da UFSC, 2013. http://repositorio.ufsc.br/handle/123456789/103514.

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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2013.
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A vitamina E tem varias funcoes fisiologicas nos humanos, incluindo acao antioxidante e anti-inflamatoria, alem de ser um nutriente importante para o sistema nervoso central (SNC). O papel dessa vitamina na prevencao e/ou tratamento de algumas doencas neurologicas tem sido sugerido em estudos pre-clinicos e clinicos. Alem disso, o envolvimento da vitamina E na modulacao da depressao, uma doenca neuropsiquiatrica prevalente no mundo ocidental, e um assunto que tem emergido nos trabalhos recentes. Muitos fatores tem sido implicados na fisiopatologia da depressao, incluindo a inflamacao e a apoptose neuronal. Desse modo, o objetivo desse trabalho foi investigar o efeito antidepressivo do a-tocoferol, uma das formas mais abundantes da vitamina E, em um modelo animal de comportamento depressivo induzido pela citocina pro-inflamatoria fator de necrose tumoral-a (TNF-a), avaliar o possivel efeito sinergico do a-tocoferol com antidepressivos (fluoxetina, imipramina e bupropiona), bem como o envolvimento dos receptores N-metil-D-aspartato (NMDA) e da oxido nitrico sintase neuronal (nNOS). Alem disso, foi investigada a influencia da administracao aguda de TNF-a e/ou a-tocoferol sob os niveis de proteinas envolvidas na apoptose (Bax, Bcl2) e a fosforilacao da glicogenio sintase cinase-3B (GSK-3B) no hipocampo de camundongos. Os resultados demonstraram que: a) o TNF-a administrado de forma aguda (0,001 fg/sitio, i.c.v.) aumentou o tempo de imobilidade no teste de suspensao pela cauda (TSC); b) administracao aguda de diferentes doses de a-tocoferol (10, 30 e 100 mg/kg; p.o.) impediu o aumento no tempo de imobilidade induzido pelo TNF-a; c) uma dose subativa de a-tocoferol (10 mg/kg) e/ou doses subativas de fluoxetina (5 mg/kg, p.o.; inibidor seletivo da recaptacao de serotonina), imipramina (0,1 mg/kg, p.o.; antidepressivo triciclico), bupropiona (1 e 10 mg/kg, p.o.; inibidor da recaptacao de dopamina e noradrenalina), MK-801 (0,001 mg/kg, p.o.; antagonista de receptores NMDA); ou 7-nitroindazol (25 mg/kg, i.p.; inibidor da nNOS) preveniu o comportamento tipo depressivo induzido por TNF-a; d) nenhum dos tratamentos alterou o numero de cruzamentos no teste do campo aberto (TCA), demonstrando que a atividade locomotora dos camundongos nao foi afetada; e) o tratamento agudo com TNF-a ou a-tocoferol nao alterou os niveis hipocampais de Bax e Bcl2 ou a fosforilacao de GSK-3B. Em conjunto, os resultados sugerem um efeito tipo antidepressivo sinergico do a-tocoferol com antidepressivos em um modelo de comportamento tipo depressivo induzido por um insulto inflamatorio, sugerindo que esta vitamina e uma canditada para otimizar a farmacoterapia convencional da depressao.

Abstract : Vitamin E has various functions in humans, including antioxidant and anti-inflammatory actions, besides being an important nutrient for the central nervous system (CNS). The role of this vitamin in the prevention and/or treatment of some neurological diseases has been suggested by several preclinical and clinical studies. Furthermore, the involvement of vitamin E in the modulation of depression, a prevalent neuropsychiatric disease in the occidental world, is an issue that has been emerging in recent studies. Many factors have been implicated in the pathophysiology of depression, including inflammation and neuronal apoptosis. Thus, the aim of this study was to investigate the antidepressant effect of á-tocopherol, one of the most abundant forms of vitamin E, in an animal model of depressive behavior induced by the inflammatory cytokine tumor necrosis factor-á (TNF-á), and to evaluate the possible synergistic effect of á-tocopherol with antidepressants (fluoxetine, bupropion and imipramine), and the involvement of N-methyl-D-aspartate (NMDA)-receptor and the neuronal nitric oxide synthase (nNOS). Furthermore, it was investigated whether TNF-á and/or á-tocopherol might influence the expression of proteins involved in apoptosis (Bax, Bcl2) and glycogen synthase kinase-3â (GSK-3â) phosphorylation, in the hippocampus of mice. The results showed that: a) TNF-á administered acutely (0.001 fg/site, i.c.v.) increases the immobility time in the tail suspension test (TST); b) Acute administration of different doses of á-tocopherol (10, 30 and 100 mg/kg; p.o.) prevented the behavioral effect induced by TNF-á; c) sub-effective dose of á-tocopherol (10 mg/kg, p.o.) and/or sub-effectives doses of fluoxetine (5 mg/kg, p.o.; selective serotonin reuptake inhibitor), imipramine (0.1 mg/kg, p.o.; tricyclic antidepressant), bupropion (1 mg/kg, p.o.; dopamine and norepinephrine reuptake inhibitor), MK-801 (0.001 mg/kg, p.o.; NMDA receptor antagonist) or 7-nitroindazole (25 mg/kg, i.p.; nNOS inhibitor) prevented the depressive-like effect induced by TNF-á; d) none of the treatments altered the number of crossings in the open field test, demonstrating that the locomotor activity of mice was not affected, e) acute treatment with TNF-á and/or á-tocopherol did not alter the levels of Bax and Bcl2 or the phosphorylation of GSK-3â. Together, our results show a synergistic antidepressant-like effect of á-tocopherol with antidepressants against the depressive-like behavior induced by an inflammatory insult, suggesting that this vitamin may be interesting to optimize conventional pharmacotherapy of depression.

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Manhal, Ali, and Ali Tammam M. "Solar Tent : A Photovoltaic Generator Model for a Flexible Fabric with Inbuilt Cells." Thesis, Högskolan Dalarna, Energiteknik, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:du-30552.

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Natural disasters and conflicts in many different parts of the world force thousands of people to get displaced from their homes and live in refugee camps temporarily or permanently. For refugee families, lack of energy access has great impact on their lives. Tarpon Solar Company has developed a solar tent which is a combination of laminated cloth and flexible solar cells. In addition to producing renewable electricity, it can create a comfortable outdoor shelter from sun, rain and wind. The aims of this study were to define and size the solar system of the tent in both AC and DC systems and optimize the tent to work in different locations around the world. Besides designing a monitoring system for the solar tent to evaluate the performance. In addition, defining the social aspect and the consumer behavior for a better solar tent future design. As a case study, Tarpon AC solar tent in Glava, Sweden has been installed to cover the basic needs of the tent users. To understand the solar tent performance in different weather zones, 4 different locations were suggested. A monitor system was designed to monitor the tent solar system performance. The simulation software PVsyst was used to size the PV system in the different locations with different solar data. The PVsyst simulation results showed that the current Tarpon solar tent with 32 photovoltaic modules is extremely oversized to cover the basic needs loads (Lighting, mobile charging and ventilation) in the emergency cases. The current Tarpon solar tent has a standard number of photovoltaic modules integrated in the tent fabric while the photovoltaic modules number should vary from one location to another according to the weather data and solar irradiation. In this case the current Tarpon solar system used in Glava, Sweden can be optimized by decreasing the number of photovoltaic modules to only 6 photovoltaic modules instead of 32 modules. The study also shows that the features of the off-grid system components (battery and charge controller) are different from one location to another according to the criteria of selection. This study concludes that for the temporary short-term emergency use of the tent where only basic needs loads are needed, DC system is better than AC system in terms of energy efficiency, system size and cost in the different proposed locations. While AC system is better when using the tent for prolonged time in terms of user flexibility and ability to extend the system. Understanding the consumer behavior and the goal of the tent whether to be used for an emergency short term shelter or a permanent shelter for a prolonged time are important factors for a better solar tent design.

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Vera, Ortega Walter. "Approaching a Tat-Rev independent HIV-1 clone towards a model for research." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30755/.

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Human immunodeficiency virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative and the huge genetic variability of HIV-1 challenges drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require CD8+ depletion or large portions of the genome to be replaced by sequences derived from simian immunodeficiency viruses to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative, but need to be 'humanized' and breeding is not possible and knockout experiments are difficult. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes function of the HIV-1 accessory proteins Tat and Rev, hampering HIV-1 replication. The Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized genes and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. My results have determined that murine NIH 3T3 cells are able to generate pseudotyped HIV-1 particles, but they are not infectious. Codon-optimized HIV-1 constructs are efficiently made in human HEK-293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW (an HIV-1 vector genome) efficiently generates infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 replication competent genomes lacking tat expression and encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Finally, we developed a replication competent HIV-1 clone lacking tat and rev genes and encoding 4CTEs that could be a future candidate for HIV research. My results shown that the development of an HIV-1 Tat-Rev independent clone could become a candidate for HIV research in a near future, but further investigations are necessary before proposing our model as an alternative yet.

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Lapierre, Jessica A. "HIV Tat and Morphine-induced Neurodegeneration in a Beclin 1 Hemizygous Mouse Model." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3888.

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Early in infection, HIV crosses the blood-brain barrier and induces neuropathology. Viral presence in the CNS coupled with secretion of neurotoxic proteins causes neuroinflammation, glial dysfunction, excitotoxicity, and neuronal death. Despite advances in combined antiretroviral therapy, HIV-infected patients present with a spectrum of cognitive and psychomotor deficits collectively referred to as HIV-associated neurological disorders (HAND). A subset of HAND patients abuses drugs such as opiates like heroin and morphine show an exacerbation and rapid progression of HIV neuropathology; however, the mechanisms of this synergy are not well understood. Autophagy is a lysosomal degradative process which eliminates and recycles cytosolic components and is implicated in facilitating HIV-1 replication in the CNS and periphery, and in Tat-induced neurodegeneration. When a key initiator of autophagy Beclin 1 was silenced using siRNAs, there was a marked reduction of HIV-1 replication in human microglia and astrocytes and the corresponding inflammatory response. As such, the goal of the current study is to determine if diminished Beclin 1 is neuroprotective against Tat and morphine-induced neurodegeneration using heterozygous Beclin 1 (Becn1+/-) mice. Examination of Tat and morphine-induced inflammatory molecule secretion revealed that Becn1+/- mixed astrocyte and microglia (glia) exhibited attenuated secretion of cytokine IL-6 and chemokines RANTES and MCP-1 compared to control (C57BL/6J) glia, an effect mediated through the μ-opioid receptor. Dysregulation of autophagy-related gene expression and excessive intracellular calcium accumulation were limited in Becn1+/- glia. When determining the effects of Tat-and morphine co-exposure on neuronal survival in vitro, we found Becn1+/- neurons were particularly sensitive to injury, excitotoxicity, and toxic exposures; however, when C57BL/6J neurons were exposed to conditioned media of C57BL/6J and Becn1+/- glia treated with Tat and morphine, neurons treated with Becn1+/- supernatant had better outcomes than those treated with C57BL/6J conditioned media. Furthermore, despite minimal difference between strains in locomotor assessment, we observed significantly greater striatal neuron losses in adult C57BL/6J mice exposed to intrastriatal Tat-and systemic morphine compared to Becn1+/- mice. Our studies demonstrate the potential of targeting Beclin 1 in glia for the prevention of Tat and opiate-induced CNS dysfunction.

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Keswick, Tobias. "Ecology and morphology of the Kalahari tent tortoise, Psammobates oculifer, in a semi-arid environment." Thesis, University of the Western Cape, 2012. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_6549_1355385737.

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Southern Africa harbours one-third of the world&rsquo
s Testudinid species, many of which inhabit arid or semi-arid areas, but ecological information on these species is scant. I studied the habitat, morphology and ecology of Kalahari tent tortoises over 13 months in semi-arid Savanna at Benfontein farm, Northern Cape Province, South Africa. In order to allow continuous monitoring of individuals, I attached radiotransmitters to males and females, split equally between two habitats, sites E (east) and W (west), with apparent differences in vegetation structure. Results of the study were based on data obtained from 27 telemetered tortoises and 161 individuals encountered opportunistically. Female Kalahari tent tortoises were larger than males and the sex ratio did not differ from 1:1. Based on person-hours to capture tortoises, the population appeared to have a low density, with more time required to capture a juvenile (35 hours) than an adult (10-11 hours). The frequency distribution of body size ranges was indicative of recruitment. Relative age, based on annuli counts, suggested that males were younger than females, perhaps because males as the smaller sex are more predation-prone than females. Linear relationships between annuli counts and shell volume indicated that, after reaching sexual maturity, female body size increased faster in volume than did male body size, possibly because a larger volume may enhance female reproductive success. Body condition differed between sites, sexes and among seasons. The hot and dry summer may account for low summer body condition, whereas vegetation differences and size effects, respectively, may account for the low body condition of tortoises in site W and in males. Site E was sandy with grasses, particularly Schmidtia pappophoroides, being the prevalent growth form. This habitat resembled a Savanna vegetation type Schmidtia pappophoroides &ndash
Acacia erioloba described for a neighbouring reserve. Site W was stonier, dominated by shrubs, and was reminiscent of Northern Upper Karoo vegetation (NKu3). Neither site resembled Kimberley Thornveld (SVk4), the designated vegetation type of the area. Differences in substrate and grazing intensity may have contributed to site vegetation differences. Rainfall had an important influence on seasonal vegetation. Short grass abundance correlated with rainfall and annual plants sprouted after spring rain. Refuge use changed according to season and sex. Males selected denser refuges than females did, perhaps because males were smaller and more vulnerable to predation and solar heat. Tortoises selected sparse, short grass as refuges in cool months, probably to maximise basking whilst remaining in protective cover. During hot periods, mammal burrows were preferred to vegetation as refugia. The smaller males spent more time in cover than females, which may be related to predator avoidance or thermoregulation.
Females spent more time basking than males, perhaps due to their larger size and to facilitate reproductive processes. Tortoises did not brumate, but through a combination of basking, and orientation relative to the sun in their refuges, managed to attain body temperatures that allowed small bouts of activity. Body temperature for active tortoises was similar among seasons, and was higher for more specialised active behaviours, such as feeding and socialising, than for walking. Increased activity by males in spring could relate to mating behaviour while females were more active in autumn, when they foraged more than males, perhaps due to the high cost of seasonal reproductive requirements. Males displaced further per day than did females, but home range estimates did not differ between sexes. Annual home range estimates varied substantially among individuals: 0.7&ndash
306 ha for minimum convex polygons and 0.7&ndash
181 ha for 95% fixed kernel estimates. The ability to
cover large areas would assist tortoises in finding resources, e.g., food, in an area where resource distribution may be patchy. Differences among seasonal home ranges and movements probably reflect seasonal climatic change
activity areas shrinking when temperatures were extreme. In order to assess the effects of a semi-arid environment on the morphology of P. oculifer, I compared its morphology to that of its &lsquo
cool-adapted&rsquo
sister taxon Psammobates geometricus, using live and museum specimens. Both P. oculifer and P. geometricus are sexually dimorphic and differences between the two species could indicate environmental or sexual selection effects, or a combination of the two. The shorter bridge length, which allowed more leg space, and wider front feet in P. oculifer cohorts probably represent traits for manoeuvring in a sandy habitat, while wider heads in P. oculifer possibly relate to interspecific differences in diet. The flatter shell in female P. oculifer, relative to P. geometricus, may represent a trade-off between space for reproductive structures, e.g., eggs, and the need to fit into small refuges, e.g., mammal burrows. Male P. oculifer had wider shells, more space around their hind legs, and wider hind feet than P. geometricus males had, all characteristics which may assist males to fight and mate in a sandy environment.

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22

Franco, Vargas Alejandro Javier. "Análisis de sensibilidad numérica de tests de respuesta térmica (TRT) en pilotes geotérmicos." Tesis, Universidad de Chile, 2015. http://repositorio.uchile.cl/handle/2250/133913.

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Magíster en Ciencias de la Ingeniería, Mención Recursos y Medio Ambiente Hídrico
Ingeniero Civil
El desarrollo de los intercambiadores de calor como sistemas de aprovechamiento de energía geotérmica de muy baja entalpía, ha contribuido de forma significativa a reducir el consumo de energía en la climatización de edificios. Para obtener un buen rendimiento de este tipo de sistemas es necesario realizar un diseño óptimo, lo cual requiere una buena estimación de los parámetros térmicos. El test de respuesta térmica (TRT) es el método actualmente empleado para la determinación de las propiedades térmicas del suelo para el diseño de sistemas geotérmicos de muy baja entalpía tradicionales. Los sistemas de pilotes geotérmicos utilizan los pilotes de fundación requeridos en la construcción de edificios, como intercambiadores de calor con el suelo, al incorporarle un circuito de tuberías en su interior por donde fluye el líquido transportador de calor. Estos sistemas son relativamente nuevos y presentan ciertas diferencias con respecto a sistemas tradicionales, lo que hace necesario estudiar la validez de aplicar pruebas TRT para su diseño. Lo anterior es la motivación del trabajo de esta tesis, en la cual se utilizó un modelo numérico desarrollado en COMSOL Multiphysics® para reproducir TRTs sintéticos en un pilote geotérmico bajo ciertas condiciones ideales. Basado en el análisis de los resultados de las simulaciones numéricas, se concluye que la interpretación de los resultados de TRTs en este tipo de sistemas es complejo, ya que dependen de la relación entre la conductividad térmica del suelo y del concreto, la tasa de la capacidad calorífica volumétrica entre el suelo y el material de relleno, el diámetro del pilote, y el espaciamiento entre tuberías, entre otros factores. Los errores asociados a cualquiera de esos parámetros en la interpretación de dichas pruebas mediante el uso del método tradicional de análisis, que considera una fuente lineal de calor (LHS), pueden ser hasta un 50% de sobrestimación para pruebas de relativa corta duración. Por ejemplo, el análisis de las simulaciones indica que, para un pilote de un metro de diámetro, es necesario realizar pruebas de más de 400 horas para obtener resultados confiables. Además, estos errores pueden ser acumulativos lo que puede aumentar la incertidumbre respecto a la estimación de los parámetros de diseño. Por lo anterior, se recomienda utilizar el conjunto de resultados generados en este estudio para estimar factores de corrección que deben aplicarse al interpretar los resultados de TRT en pilotes geotérmicos. Se espera que de esta forma los resultados presentados en este estudio permitan una correcta interpretación de los resultados de pruebas de terreno de corta duración, con el consiguiente beneficio en términos logísticos y económicos.

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23

Franco, Vargas Alejandro Javier. "Análisis de sensibilidad numérica de tests de respuestas térmica (TRT) en pilotes geotérmicos." Tesis, Universidad de Chile, 2015. http://repositorio.uchile.cl/handle/2250/133969.

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Abstract:

Magíster en Ciencias de la Ingeniería, Mención Recursos y Medio Ambiente Hídrico
Ingeniero Civil
El desarrollo de los intercambiadores de calor como sistemas de aprovechamiento de energía geotérmica de muy baja entalpía, ha contribuido de forma significativa a reducir el consumo de energía en la climatización de edificios. Para obtener un buen rendimiento de este tipo de sistemas es necesario realizar un diseño óptimo, lo cual requiere una buena estimación de los parámetros térmicos. El test de respuesta térmica (TRT) es el método actualmente empleado para la determinación de las propiedades térmicas del suelo para el diseño de sistemas geotérmicos de muy baja entalpía tradicionales. Los sistemas de pilotes geotérmicos utilizan los pilotes de fundación requeridos en la construcción de edificios, como intercambiadores de calor con el suelo, al incorporarle un circuito de tuberías en su interior por donde fluye el líquido transportador de calor. Estos sistemas son relativamente nuevos y presentan ciertas diferencias con respecto a sistemas tradicionales, lo que hace necesario estudiar la validez de aplicar pruebas TRT para su diseño. Lo anterior es la motivación del trabajo de esta tesis, en la cual se utilizó un modelo numérico desarrollado en COMSOL Multiphysics® para reproducir TRTs sintéticos en un pilote geotérmico bajo ciertas condiciones ideales. Basado en el análisis de los resultados de las simulaciones numéricas, se concluye que la interpretación de los resultados de TRTs en este tipo de sistemas es complejo, ya que dependen de la relación entre la conductividad térmica del suelo y del concreto, la tasa de la capacidad calorífica volumétrica entre el suelo y el material de relleno, el diámetro del pilote, y el espaciamiento entre tuberías, entre otros factores. Los errores asociados a cualquiera de esos parámetros en la interpretación de dichas pruebas mediante el uso del método tradicional de análisis, que considera una fuente lineal de calor (LHS), pueden ser hasta un 50% de sobrestimación para pruebas de relativa corta duración. Por ejemplo, el análisis de las simulaciones indica que, para un pilote de un metro de diámetro, es necesario realizar pruebas de más de 400 horas para obtener resultados confiables. Además, estos errores pueden ser acumulativos lo que puede aumentar la incertidumbre respecto a la estimación de los parámetros de diseño. Por lo anterior, se recomienda utilizar el conjunto de resultados generados en este estudio para estimar factores de corrección que deben aplicarse al interpretar los resultados de TRT en pilotes geotérmicos. Se espera que de esta forma los resultados presentados en este estudio permitan una correcta interpretación de los resultados de pruebas de terreno de corta duración, con el consiguiente beneficio en términos logísticos y económicos.

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24

Candel, Camacho Sergio. "Caracterización del papel de los receptores de TNF en inflamación usando el pez cebra como modelo= Modelling the impact of TNF receptors in inflammation using the zebrafish." Doctoral thesis, Universidad de Murcia, 2013. http://hdl.handle.net/10803/124105.

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La psoriasis es una enfermedad inflamatoria crónica de la piel que afecta a millones de personas. Aunque en ratón no existen modelos de psoriasis, la facilidad para obtener muestras de piel de pacientes ha facilitado el estudio de las vías de señalización implicadas en la enfermedad, mostrando la importancia del sistema inmune en su desarrollo. Algunas terapias que utilizan anticuerpos específicos contra varias citoquinas, incluyendo TNFα, IL-23 y IL-17, son prometedoras, pero son caras y presentan efectos secundarios. Numerosos estudios han mostrado la aparición de nuevos casos de psoriasis después del tratamiento con antagonistas del TNFα en pacientes con Inflammatory Bowel Disease. Aunque esos datos indican un papel ambiguo del TNFα en psoriasis, su papel, y especialmente la contribución de sus receptores, en la regulación de la inflamación en piel han sido escasamente estudiados. OBJECTIVES: (1) Caracterización del papel de Tnfa y sus receptores (Tnfr1 y Tnfr2) en la función y distribución de los neutrófilos en larvas de pez cebra; (2) Caracterización de las vías de señalización de Tnfr1 y Tnfr2 involucradas en la homeostasis de la piel en larvas de pez cebra; (3) Caracterización del papel de Tnfa y sus receptores en inflamación crónica en piel en larvas de pez cebra; (4) Evaluación de las larvas de pez cebra como posible modelo para estudiar enfermedades inflamatorias crónicas humanas. METHODOLOGY: Líneas transgénicas de pez cebra y las ventajas de trabajar con sus embriones en in vivo imaging y cell tracking han sido utilizadas para estudiar los patrones de distribución de los neutrófilos. Además, la inflamación en la piel causada por la depleción de Tnfa o Tnfr2, pero no Tnfr1, ha sido estudiada mediante la inhibición genética (morpholinos y formas dominantes negativas) y farmacológica (DPI) de Duox1. La expresión de moléculas pro-inflamatorias ha sido medida mediante RT-qPCR, Neutrófilos y queratinocitos han sido aislados de larvas control y deficientes en Tnfr2 usando FACS-sorting. Sondas específicas para H2O2 han sido usadas para detectar su producción. RESULTS AND CONCLUSIONS: La depleción de Tnfa o Tnfr2, pero no de Tnfr1, causa inflamación en la piel a través de la activación de un bucle inflamatorio de retroalimentación positiva que implica a H2O2/NF-κB/Duox1. Tanto la inhibición genética como farmacológica de Duox1 revierten completamente la inflamación en piel, situando al H2O2 derivado de Duox1 aguas arriba de la activación de NF-κB. Extraemos las siguientes conclusiones: (1) La inhibición genética de Tnfa o Tnfr2, pero no de Tnfr1, resulta en la movilización de los neutrófilos desde la CHT hasta la piel; (2) El silenciamiento de Tnfa o Tnfr2 provoca la inducción en la piel de la expresión de genes que codifican para moléculas pro-inflamatorias; (3) La ausencia de señalización de Tnfa a través del receptor Tnfr2 desencadena la producción local de H2O2 por la enzima Duox1 en la piel; (4) La inhibición genética de Tnfa o Tnfr2 resultada en la activación del regulador maestro de la inflamación NF-кB en la piel, aguas abajo de la producción de H2O2; (5) La señalización de Tnfa a través del receptor Tnfr2 es indispensable para el mantenimiento de la homeostasis de la piel; (6) La inducción de DUOX1 y/o la consiguiente producción de H2O2 en la piel de pacientes con psoriasis, podrían ser nuevas dianas para terapias farmacológicas y genéticas para el tratamiento de la psoriasis. Estas nuevas estrategias podrían ser también aplicables para otras enfermedades inflamatorias crónicas; (7) El pez cebra puede utilizarse como organismo modelo para estudiar la psoriasis y otras enfermedades inflamatorias crónicas.
Psoriasis is a chronic, debilitating skin disease that affects millions of people worldwide. Although there is no mouse model that accurately reproduces all facets of the psoriasis, the accessibility of skin tissue from patients has facilitated the elucidation of some pathways involved in the pathogenesis of psoriasis and highlighted the importance of the immune system in the disease. Recently developed antibodies that selectively target several cytokines, including TNFα, IL-23 and IL-17, have shown promising results in early-phase clinical trials. However, these treatments are extremely expensive and show important side effects. Importantly, numerous studies have reported new-onset psoriasis following TNFα antagonist therapy in adult inflammatory bowel disease patients. Despite these clinical data pointing to an ambiguous function of TNFα in psoriasis, the role of TNFα, and in particular the contribution of each TNFR, in the regulation of skin inflammation has scarcely been studied. OBJECTIVES: Taking that into consideration, the objectives of the present work are: (1) Characterization of the role played by Tnfa and its receptors (Tnfr1 and Tnfr2) in the neutrophil function and distribution patterns in zebrafish larvae; (2) Characterization of the Tnfr1 and Tnfr2 signaling pathways involved in skin homeostasis in zebrafish larvae; (3) Characterization of the role played by Tnfa and its receptors in chronic inflammation in the skin in zebrafish larvae; (4) Evaluation of the zebrafish larvae as a potential model for the study of human chronic inflammatory diseases. METHODOLOGY: Some zebrafish transgenic lines and the unique advantage of the zebrafish embryo for in vivo imaging and cell tracking have been used for the study of the neutrophil distribution patterns. Furthermore, the skin inflammation caused by the depletion of Tnfa or Tnfr2, but not of Tnfr1, has been studied using both genetic (morpholinos and dominant negative forms) and pharmacological (DPI) inhibition of Duox1. The expression of pro-inflammatory molecules has been measured by RT-qPCR, while neutrophils and keratinocytes have been FACS-sorted from controls and Tnfr2-deficient larvae. H2O2-specific probes have been used in order to detect the production of that compound. RESULTS AND CONCLUSIONS: We found that depletion of Tnfa or Tnfr2, but not of Tnfr1, caused skin inflammation through the activation of an H2O2/NF-κB/Duox1 positive feedback inflammatory loop. Moreover, both genetic and pharmacological inhibition of Duox1 completely abrogated skin inflammation, placing Duox1-derived H2O2 upstream of the positive feedback inflammatory loop. Thus, these results lead us to the next conclusions: (1) Genetic inhibition of Tnfa or Tnfr2, but not of Tnfr1, results in neutrophil mobilization from the CHT to the skin, where they get infiltrated; (2) Target gene silencing of Tnfa or Tnfr2 results in the induction of the expression of genes encoding pro-inflammatory mediators in the skin; (3) The absence of Tnfa signaling through Tnfr2 triggers the local production of H2O2 by Duox1; (4) Genetic inhibition of Tnfa or Tnfr2 results in the activation of the master regulator of inflammation NF-кB in the skin, downstream the production of H2O2; (5) Tnfa signaling through Tnfr2 is critically required for skin homeostasis; (6) DUOX1 induction and/or the subsequent production of H2O2 in the skin of psoriasis patients, may be new targets for pharmacologic and genetic therapies for the treatment of psoriasis. These new strategies could be applicable to other chronic inflammatory diseases as well; (7) Zebrafish can be used as a model organism for the study of psoriasis and other inflammatory chronic diseases.

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25

Helms, Nick. "Wechselwirkungen von Agonisten und kompetitiven Antagonisten mit der Ligandenbindungsstelle des schnell desensitisierenden P2X3-Rezeptors." Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-197364.

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Purinerge P2X3-Rezeptoren spielen eine bedeutende Rolle in der Vermittlung chronischer Schmerzen, welche ein führendes Problem des Gesundheitswesens mit vielen sozioökonomischen Konsequenzen darstellen. Die Tatsache, dass P2X3-Rezeptoren fast ausschließlich von nozizeptiven Neuronen exprimiert werden, macht sie trotz ihres besonderen Desensitisierungsverhaltens zu vielversprechenden Angriffspunkten zukünftiger Schmerztherapien, beispielsweise mithilfe kompetitiver Antagonisten an diesen Rezeptoren. Zur Analyse der Wechselwirkungen zwischen Agonist und kompetitivem Antagonist wird meist der Schild-Plot benutzt. Jedoch ist dieser im Falle der sehr schnell desensitisierenden P2X3-Rezeptoren ungeeignet, da die Vorbedingung eines stabilen Gleichgewichts zwischen Agonist und Antagonist aufgrund der Desensitisierung nicht erfüllt ist. Ziel der vorliegenden Arbeit war es, eine neue Methode zur Analyse der Interaktion kompetitiver Antagonisten mit ihrer Bindungsstelle am Beispiel des P2X3-Rezeptors zu entwickeln und so für die Antagonistenbindung bedeutende Aminosäuren der Bindungsstelle zu identifizieren. Mittels der Patch-Clamp-Technik wurden die Effekte der Antagonisten A-317491, TNP-ATP und PPADS auf die vom P2X1,3-Rezeptor-selektiven Agonisten α,β-MeATP induzierten Ströme am P2X3-Wildtyp-Rezeptor und an fünf Rezeptormutanten mit veränderter Ligandenbindungsstelle untersucht. Alle Rezeptoren wurden in HEK293-Zellen exprimiert. Anhand der gemessenen Daten wurde ein Hidden Markov Model (HMM) erstellt, welches die sequentiellen Übergänge des Rezeptors von geschlossen zu offen und desensitisiert in An- und Abwesenheit des Antagonisten miteinander kombiniert. Die am P2X3-Rezeptor induzierten Ströme konnten mithilfe dieses Modells korrekt gefittet und die für die Antagonistenbindung wichtigen Aminosäuren innerhalb der Bindungsstelle bestimmt werden. Als Resultat dieser Arbeit konnte außerdem gezeigt werden, dass das HMM eine geeignete Methode zur Analyse der Wirkung kompetitiver Antagonisten an schnell desensitisierenden Rezeptoren darstellt. Die untersuchten Antagonisten A-317491 und TNP-ATP haben einen kompetitiven Wirkmechanismus, während PPADS eine pseudoirreversible Blockade verursacht.

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26

Golovkova, Nataliya. "Návrh protiopatření k útokům na konektivitu vozů." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2021. http://www.nusl.cz/ntk/nusl-442359.

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The diploma thesis is focused on the issue of connective cars and the types of threats that can occur and how to protect against them. The general part described the general model of the car. In the next part of the work, templates were created in the Microsoft Threat Modeling Tool with threats and countermeasures to them.

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27

WILSON, JR GERALDO. "Etude du transport et de la dispersion des sediments en tant que processus aleatoires." Paris 6, 1987. http://www.theses.fr/1987PA066670.

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Etude de la dispersion longitudinale par charriage et en suspension des particules d'un ecoulement turbulent a surface libre a l'aide de la theorie des processus aleatoires. Les expressions generales des modeles aleatoires unidimensionnels sont remaniees de facon a englober le transport en suspension. On examine plusieurs modeles. On propose d'autres expressions analytiques plus adaptees a la nature non-constante des probabilites de deplacement du grain ou fonctions d'intensite de changement d'etat cinematique. Enfin, on presente la technique de tracage utilisee pour verifier experimentalement la theorie probabiliste du transport de sediments

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28

Steffen, Brian. "Efficacy of TNF inhibitor treatment in a model of heart failure and resulting cachexia." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/6001.

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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.
"December 2007" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.

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29

Wei, Guo-Feng. "An image quality model based on the influence of Mura defects in TFT-LCDs." Thesis, University of Leeds, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581866.

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Mura is a type of defect on LCD's that affects image quality. Due to its subtle nature - gradually and non-uniformly changes in lightness within a specific area, how Mura defects can be effectively inspected and objectively graded has been an issue in the LCD manufacturing industry for many years. Although many studies using different approaches to the Mura detection issue have been carried out, there is still a lack of reliable standard and methods that can be fully adopted in the industry and replace the human eye in the inspection work. Based on demand from the LCD industry, a uniform Mura detection model is needed to provide a stable and reliable inspection system for image quality judgment. For many years, researchers have studied this topic by using uniform colour patches. Few of them extended investigations to conditions where Mura defects are viewed against complex images in background. This might be the first time that study of Mura detection has been extended to patterned and complex image backgrounds. There are four experiments in this study. Influences of colour, Mura size and the masking effect caused by background patterns on Mura detection were investigated. Among them, masking effect is the dominant factor that significantly affects the detection thresholds. Our analyses show that the influence of Mura size was mild for noise backgrounds. Orientations of the Mura patterns had no effect for uniform and noisy backgrounds, though some other studies of visual acuity and contrast sensitivity in humans have shown an unequal sensitivity across orientation. Although colours showed little effect in this study, some seemed to produce more stable results. Particularly for uniform backgrounds, colour and size caused problems for some observers who were unable to maintain consistent thresholds for Mura detection. Mura detection against still and moving pictorial backgrounds were also studied. It seems that the human visual system uses different strategies with different mechanisms to detect Mura patterns on uniform, patterned and pictorial backgrounds respectively. On uniform backgrounds, the human visual system uses colour difference, lightness difference and boundary detection theorem to discern a Mura pattern whereas detecting Mura patterns on patterned backgrounds is highly affected by the masking effect. For static pictorial backgrounds, detecting Mura patterns even relies very much on cognition and thus causes huge problems for observers to recognize them. This situation only improves when the position correlation between a Mura pattern and its background changes from static to dynamic; and it is until then detecting Mura patterns seems to be a quantifiable task again. A Mura detection model was constructed based on knowledge of the human visual system, which is mainly concerned with how a static image pattern projected on the retina is converted into neural signals, and how these signals are interpreted by our brains. Our analyses show that the model delivers more reliable results than the S-CIELAB model when masking effect take places.

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30

Adkins, Caleb, and Michelle Chandley. "Neuroinflammation in the C1q/TNF-related over-expression mouse model of chronic ethanol exposure." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/35.

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Alcohol use can negatively impact financial, cognitive, and psychiatric aspects of human life. In the brain, alcohol can have many devastating effects. Alcohol is a well-known cytotoxic agent that can cause specific brain pathology in humans; however, the exact biological mechanisms are not well-elucidated. Animal models are invaluable tools to investigate potential novel treatments in a substance abuse model. Mice studies can be used to screen for negative outcomes prior to human trials. We hypothesize that the C1q tumor necrosis factor-related protein, CTRP3, overexpression in mice reduces neuroinflammation from ethanol consumption that has been coupled with a high fat diet when compared to control mice. The CTRP family of proteins are adipokines and CTRP3 specifically influences cell viability, metabolism, and peripheral inflammation levels. Antibody specific immunoblotting is used to probe protein expression changes in neuroinflammatory markers in mouse cerebellum brain tissue in an overexpression mouse model of CTRP3 when compared to high-fat ethanol exposed mice and baseline control mice. The two proteins examined are MAG and GFAP. Myelin associated glycoprotein, or MAG, is a protein expressed by oligodendrocytes that mediate axonal growth and myelin interactions with neurons in the brain. Oligodendrocytes are extremely sensitive to oxidative stress to which cognitive deficits in ethanol exposure is thought to be attributed. Glial fibrillary acidic protein, or GFAP, is a marker of astrocyte reactivity. Astrocytes are cells in the brain that are responsible for environmental stabilization and actively participate in neurotransmission. Currently, GFAP alterations in ethanol-exposed animals are dose and age dependent. We chose to use young adult mice where GFAP reactiveness is increased during chronic ethanol exposure. The proposed studies are essential in determining CTRP3’s relationship to detrimental neuroinflammatory effects of alcohol and high fat diet in mice. The data obtained from these studies will provide compelling evidence for future clinical trials to investigate CTRP3 as a therapeutic agent in people with a high fat diet that use alcohol chronically.

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31

Flynn, Kathryn Eve. "Tit for tot a life course model of breastfeeding behavior /." 2003. http://catalog.hathitrust.org/api/volumes/oclc/52366723.html.

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Thesis (M.S.)--University of Wisconsin--Madison, 2003.
Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 41-43).

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32

Marcos, Daniel Teixeira. "Optimização da lavagem alcalina do mononitrobenzeno." Master's thesis, 2015. http://hdl.handle.net/10316/40243.

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Dissertação de Mestrado Integrado em Engenharia Química apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra
O desenvolvimento de modelos estatísticos de previsão da extracção de nitrofenóis na lavagem alcalina do processo de produção de mononitrobenzeno (MNB) na fábrica da CUF-QI em Estarreja foi o objetivo deste trabalho. Na maioria das empresas o MNB é obtido por nitração adiabática do benzeno. Reações secundárias levam à formação dos subprodutos dinitrofenol (DNF) e trinitrofenol (TNF). Estes, bem como matérias-primas não convertidas, devem ser removidos para garantir que as especificações do MNB são cumpridas. Para tal, várias separações são utilizadas com extrações líquido-líquido que tomam o nome de lavagem. Esta dá-se em dois passos: uma extração ácida, que remove ácidos minerais, seguida de uma extração reativa alcalina, onde os NF são eliminados. Esta extração alcalina foi o foco deste trabalho. Um levantamento da tecnologia disponível atualmente para a purificação do MNB, bem como o equipamento e as técnicas de tratamento de efluentes com DNF e TNF é aqui apresentado. Os modelos estatísticos construídos para a lavagem alcalina do MNB foram baseados em dados experimentais recolhidos previamente por Cardoso (2013) e Fuentes (2014). Ambos estudaram a influência das variáveis de entrada e das condições operatórias na extração do dinitrofenol e do trinitrofenol do MNB nos lavadores alcalinos na fábrica da CUF-QI. Os dados disponíveis foram utilizados para construir modelos distintos, um para cada subproduto. O processo de extração foi traduzido por meio de modelos estatísticos para os coeficientes de partição entre duas fases líquidas. Ferramentas de análise exploratória de dados para processamento de dados permitiram, numa primeira etapa, retirar informações e evidenciar tendências e regressores de entre as condições de operação da lavagem alcalina. Posteriormente, diferentes modelos foram construídos recorrendo ao método dos mínimos quadrados com seleção de variáveis por stepwise e através do método dos mínimos quadrados parciais (PLS). O modelo para o coeficiente de partição do DNF mostrou que T * , NH3 * , (T·NH3 ) * e (TNFFA·NH3 ) * são os regressores mais influentes. Para o coeficiente de partição do TNF foram selecionados dois modelos designados B e C. No modelo B os regressores que mais influenciam a operação são DNFFO * , DNFFA * , (T·DNFFA) * e (DNFFA·TNFFA) * . Quanto ao modelo C, que prevê o inverso do coeficiente de partição do TNF, os regressores mais expressivos são NH3 * e o seu quadrado e (NH4)2CO3 * e a sua raiz quadrada. A validação externa dos modelos com dados recolhidos nos lavadores da fábrica confirmou a capacidade de previsão dos modelos. Sugere-se que esta validação seja complementada com um conjunto de amostras que também inclua a operação do primeiro lavador. Uma análise de sensibilidade aos modelos validou informação dos estudos anteriores. Verificouse que para a previsão do coeficiente de partição do DNF em determinadas regiões da gama de aplicabilidade da razão água/MNB e fração de agente alcalino (NH3 ) o modelo exibe um comportamento diferente da restante gama.

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33

Pucik, Lara Ellen. "The behavior of TNT in model chemical redox systems and the fate of TNT reduction products in aerobic microbial systems." Thesis, 1996. http://hdl.handle.net/1911/14075.

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When exposed to the Fenton oxidation process, approximately 25% of the initial TNT was mineralized and approximately 63% was converted to unknown soluble products. When exposed to Fe(0) under acidic conditions, TNT was completely reduced to unknown products, approximately 20% of which were not soluble. Reduction of TNT by Fe(0) did not occur above pH 3.0. When exposed to sulfide, TNT was reduced to a mixture of 4ADNT, 2ADNT, DA6NT and unknown soluble products. TNT and its reduction products from chemical (iron and sulfide), aquatic plant, and Clostridia systems were not mineralized by either an activated sludge culture or a mixed aerobic culture grown on anthranilic acid. Biological transformation of TNT and sulfide-reduced TNT products, however, did appear to occur in the aerobic microbial culture grown on anthranilic acid.

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34

Beukema, Sarah Jenelle. "Models for tent caterpillar-virus interactions." Thesis, 1992. http://hdl.handle.net/2429/3276.

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Many species of forest Lepidoptera show eight to twelve year population cycles which may involve viral disease. To examine possible interactions between viral disease and population cycles of forest Lepidoptera I explored some models for insect-virus dynamics. All of the models produced population oscillations in their original form. However, after they were modified to conform more closely to the tent caterpillar system, none of the models produced realistic cycles. I then developed a new model specifically for the tent caterpillar system that included important features such as: reduced fecundity of individuals that had been exposed to the disease, transmission of the disease from mother to progeny, a free-living infective stage of the virus, and a horizontal transmission rate that varied with the larval stage, the number of individuals, and amount of virus present. Cyclic dynamics resulted from some simulations. The parameters producing the cycles were similar to actual data. However, unlike natural populations of tent caterpillars, in the simulated population the average fecundity decreased before the population started to decline and survival decreased at approximately the same time as the population. Important further research in the field should include investigation of the distribution and survival of free-living virus and factors that would reduce caterpillar survival at peak populations but not affect fecundity.

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35

Huang, Shu-Mei, and 黃淑美. "DC model and small signal model for LTPS TFT." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/14659468524303026145.

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碩士
國立臺灣大學
電機工程學研究所
97
Low-temperature poly-silicon (LTPS) is becoming a standard technology for the fabrication of thin-film transistors (TFTs) used in active matrix liquid crystal displays and in active matrix organic light emissive displays. In order to be able to simulate large number of matrix pixels or integrated drivers, this model is simple enough to allow simulator convergence. A analytical model for the DC characteristics of both n- and p-channel LTPS TFT is described. Our approach results in a physically based model with some parameters, which are related to the device structure and fabrication process. The DC model describes all regimes of operation: linear, saturation, and Kink. The effects of temperature and channel length are also included in our model. This thesis also contains the small-signal modeling. This method consists in a direct determination of all the FET parasitic elements. The knowledge of these parasitic element values allows us to determine the intrinsic parameters after a few simple matrix manipulations. Then all the extrinsic and intrinsic components are determined.

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36

武冠宏. "TFT-LCD Array Mask Decision Model." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/48900006080208503170.

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碩士
國立交通大學
管理學院碩士在職專班工業工程與管理組
97
The production environment in a traditional 4.5” TFT-LCD factory has changed dramatically over the last five years. Due to new generation factories arising, the traditional 4.5” TFT-LCD factories are forced to accept orders to produce various small size display products instead of make-to-stock products. A large number of products are produced concurrently in a production line. In general, the photo machine is the bottle-neck machine in TFT-LCD array manufacturing process. There are variety types of photo machines existed in a production line. Mask is the main fixture of photo machine. The price of mask is very expensive. There are five photo operations in each product routing. Each operation for each product needs a mask as fixture of the photo machine. The type of mask must match with the type of photo machine. A large numbers of mask types and numbers must be decided. The performance of this decision is the outputs. In this study, we deal with the uncertain demand problem that the uncertain demand is represented by the probability distribution of product mixed. A linear programming model is formulated to decide the type and number of mask for each product to maximize the profit under the constraints of machine capacity. A real case is given to illustrate the decision model. And we also do sensitivity analysis.

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Lauritzen, John Robert III. "Catharanthus roseus as a model system for the study of the phytoremediation of TNT." Thesis, 1998. http://hdl.handle.net/1911/17191.

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C. roseus hairy roots cultures were employed to prove the ability of plants to take up and transform TNT in the absence of microbes. Mass balances performed with 14C-TNT showed that the TNT was being taken up and transformed and not mineralized. The transformation pathway was seen to be at least initially reductive. However, in cases where no TNT was detectable at experiment's end, standards could only account for 5% of the final products. Pseudo-first order reaction kinetics were observed for low initial concentrations of TNT in both stationary and exponential phase hairy root cultures. Kinetic constants ranged from 0.0103 to 0.0161 L/g-day for stationary phase experiments performed with 15 to 35 mg/L initial TNT concentrations. Kinetic constants of 0.0075 to 0.0156 L/g-day were observed for experiments performed on exponential growth phase hairy roots with an initial TNT concentration of 20 to 40 mg/L. Toxic effects were seen at all phases of growth and all concentrations measured.

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38

Modi, Nita. "Hepatic Steatosis and TNF-?? Signaling." Thesis, 2007. http://hdl.handle.net/10012/2768.

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The overall objective of this research was to investigate the status of tumor necrosis factor-?? (TNF-??), and molecules associated with its signaling, in the pathological state of hepatic steatosis. The effect of NSAID piroxicam, a cancer preventive agent also known to affect TNF-?? signaling on hepatic steatosis, was also investigated. The biological state of the tissue was assessed by examining the expression of TNF-?? signaling molecule in whole tissue, as well as in hepatic lipid raft. Lipid rafts are dynamic assemblies of cholesterol and sphingolipids, microdomains that form in the exoplasmic leaflet of the biological membranes shown to play a role in compartmentalization, modulation and integration of the cell signaling. In the present research, Zucker obese rats were used as a model of human obesity and insulin resistant state. These rats exhibit hepatic steatosis in adulthood similar to those noted in obese individuals. Female Zucker obese and lean rats (5 weeks old) were fed a semisynthetic diet with or without piroxicam (150 ppm). Zucker lean counterparts served as control. After 8 weeks of feeding, rats were euthanized and liver from each animal was collected. Liver tissue from each animal was processed for histology and biochemical analysis which included lipids and proteins (COX-1 and 2, TNF-??, TNF-RI and RII, IKK-??, I??B-?? and NF-??B). Liver histology and the level of total lipids confirmed that Zucker obese rats had hepatic steatosis, which was further augmented by piroxicam treatment. Whole tissue protein expression, using western blot, showed that the steatotic liver differed from non-steatotic livers by having lower levels of TNF-RII. TNF-RII showed a trend which was inversely proportional to the pathological state of the tissue. The obese-piroxicam liver had the lowest level of TNF-RII and lean livers had the highest (p<0.05). The total NF-??B level was higher in the obese and obese-piroxicam groups compared to the lean or lean-piroxicam groups (p<0.05). Piroxicam treatment lowered the level of NF-??B in obese and lean livers. I??B-?? was higher in obese livers than in lean livers. The nuclear level of NF-??B by western blot analysis showed the same pattern as noted in the whole tissue homogenate. However, the difference in the level between obese and lean was marked. The obese nuclei contained two to three fold higher levels of NF-??B protein than the lean liver nuclei. I??B-?? level was significantly higher in the obese liver tissues and nuclei than their lean counterparts. While transcriptionally active NF-??B was higher (p<0.05) in the obese livers than in the lean livers, the difference between obese and lean groups was not as significant as that noted for the level of NF-??B assessed by western blot. This suggests that the proportion of active NF-??B present in the nuclear fraction is much higher in the lean than in the obese nuclei. Lipid raft was extracted and identified successfully from obese and lean livers. The total caveolin and flotillin levels were significantly higher in the liver lipid rafts of the obese-piroxicam than that of the other groups. This is the group that also exhibited higher steatosis. Piroxicam treatment significantly decreased the level of caveolin in the lean liver and significantly increased the level of flotillin in the obese liver. While COX-1 was not detectable, however, the level of COX-2 and TNF-RII in lipid raft was opposite to the level noted in the whole tissue homogenate. TNFRII was highest in the obese-piroxicam lipid raft and lowest in the lean-piroxicam lipid raft. TNF-RII, COX-2, I??B-?? and NF-??B proteins were the molecules profoundly affected by the pathological state of the tissue and piroxicam treatment. This research is the first to report the presence of I??B-?? in the nuclear compartment with a higher level in the nuclei and whole tissue in the obese liver than in the lean liver. This research demonstrates that TNF-?? to NF-??B axis is altered in steatotic liver, and analysis of lipid rafts in steatotic and non-steatotic liver demonstrates that lipid rafts play a distinct role in modifying the biological availability of key proteins in the pathological state of liver steatosis.

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Wang, Sheng-Zhe, and 王聖哲. "The Multi-site Material Planning Model for TFT-LCD IndustryThe Multi-site Material Planning Model for TFT-LCD Industry." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/95836205693488854574.

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碩士
東海大學
工業工程與經營資訊學系
94
The issues of Supply Chain Management of global logistical environment, so many enterprises own multi-site production situation in order to promote itself with an advantageous position. To face the customer requirement is many models and less quantity will be bound to increase the item of manufacturing product and to make planning be more complex of the material inventory at each manufacturing plant, the lead time of purchasing material, product mix, the purchasing cost, the holding cost, and the transporting cost. How to use the resources of each manufacturing plant appropriate for the satisfying production planning, that is to say the production flow that is the existence of substitute situation. The research interests in the material planning of the multi-site to find a good coordination mechanism that is the number of purchasing material and the number of transporting material between different manufacturing factories in per period. The research main presents development of a material planning for liquid crystal module manufacturing in multi-site environment and plans the material issue of the multi-site that uses the stock to satisfy the demand. Consider enterprise's whole framework operation cost and quantity of supplies stock of different factory, under handing in one and purchasing limiting with supplies to delivery date promise to customers, make the profit total that should plan to accept the order in the block largest, and improve interval resources of factory and share the degree. Because enterprises could meet various production environments, it indicates that through the number of orders, the scale of enterprises and the different allocation tactic to test the material planning approaches. The results prove that the number of orders is very influential factor and enterprises adopt the universe allotting will bring more profit.

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Tseng, Yu-Hsiang, and 曾毓翔. "Compact Model Parameter Extractions for MOS and TFT Devices." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/49288409339086360723.

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碩士
國立交通大學
電信工程研究所
99
A set of semiconductor device model and parameters bridges the communities between circuit design and chip fabrication. With the aggressive down-scaling technologies, the surface-potential-based PSP model has been regarded as the advanced one and has been selected a standard compact model for 45-nm CMOS technology and beyond. On the other hand, a-Si:H and poly-Si thin-film transistors have become essential devices for active matrix liquid crystal displays (AMLCDs). RPI model is the most widely used model for TFTs. The parameters of both PSP MOSFET model and RPI TFT model are required to be carefully extracted so that the results of circuit simulation are reasonable and accurate. However, the commercial parameter extraction tools are very expensive and there is no free parameter extraction tool for academic research use. In this thesis, the developed extraction CAD tool for PSP MOSFET model and RPI TFT model parameter extraction is introduced. The tool possesses manual adjustment mode and automatic extraction mode. In manual adjustment mode, users can select model parameters desired to be optimized. By tuning the corresponding slider box in the window dialog, the effects of parameter variation on the I-V curves can be seen simultaneously. By using the manual adjustment mode, the effective parameter extraction procedures for PSP MOSFET model and RPI TFT model are proposed. For PSP model parameter extraction procedure, we first optimize some parameters with respect to Id-Vgs curves then we optimize the other part of parameters with respect to Id-Vds curves. Regarding the RPI model parameter extraction procedure, we sequentially optimized the parameters related to linear region, subthreshold region, saturation region, and leakage region. Besides, we investigate the threshold voltage shift caused by bias stressing in a-Si:H TFT and its modeling technique. Combined with threshold voltage shift model and RPI a-Si:H TFT model parameter extraction technique, the current-voltage characteristics variation over time can be simulated and predicted. Besides, we find the geometry dependence effect in RPI a-Si:H TFT model and propose a model for parameter MUBAND. The MUBAND model will help the simulation of TFTs with various dimensions. Furthermore, we present a new SPICE-compatible mobility function together with parameter extraction procedure which give more accurate results than conventional RPI mobilty model for excimer laser annealed LTPS TFTs. Concerning automatic parameter extraction, users can select a limited region of I-V curves and perform automatic extraction with numerical optimization Levenberg-Marquardt method when good enough approximate solution is obtained. We further investigate the application of evolutionary based algorithms on PSP model parameter extraction, including genetic algorithm (GA), differential evolution (DE), and particle swarm optimization (PSO). We propose a hybrid DE-PSO algorithm which combines the advantages of high diversity from DE and fast convergence from PSO. Individuals in the population are first sorted according to their fitness values. The better half of population proceeds as PSO and the worse half of population are replaced by new individuals generated by DE. This algorithm maintains the fast convergence of PSO and creates good potential solutions by the differential operation from DE. Good accuracy and efficiency are obtained by several sub-45 nm NMOSFET testing cases. In summary, the parameter extraction and modeling techniques for PSP MOSFET model and RPI TFT models will benefit nano-CMOS and TFT-LCD panel circuit design and fabrication.

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Chen, Chien-Wen, and 陳鑑文. "Design Chain Operations Reference Model of TFT-LCD Industry." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/2n5788.

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碩士
國立臺北科技大學
機電整合研究所
98
The ongoing conduct of research and development activities is the lifeblood of sustainable development for every business, and shortening product launch time and reducing cost are the only rules for business survival. In today’s industry, the continuous improvement and introduction of new products and the acceleration of product life cycle are common phenomena, therefore the design chain now becomes an important part in business activities. The pursuit of increasing manufacturing efficiency alone is not sufficient for the goal of business sustainability, hence the best management must be executed during the product development process in order to shorten the time of product launch and reduce costs. In the panel industry which is particularly promoted and fully supported by government in the" Two Trillion & Twin Star" plan, the process building and effective management of its design chains are the major tasks to enhance the future competitiveness in the TFT-LCD industry. This study attempts to explore the introduction of "Design Chain Operations Reference" (DCOR) model to the TFT-LCD industry. The template resulted from the study provides the basic definition and the indicators of performance evaluation to design chains in the TFT-LCD industry, is expected to assist in the process integration and to foster the communication among research and development team members, and contributes to the reduction in both the research and development schedule and the cost of new product design. In order to verify the effectiveness of D-DCOR, a certain company was selected to conduct a case study, and the proposed D-DCOR was simultaneously verified and compared with the traditional design process of the studied company. The final results show that the most obvious benefit of D-DCOR is to shorten the design process schedule by nearly one month compared to the original one of the C company. In summary, the reasons why the overall performance of the studied company will be raised by using D-DCOR to implement the new product development are as follows: 1.D-DCOR has rigorous definitions and a clear process. The design development process followed the correct steps all the time, and fewer design or manufacturing errors occurred in the verification of the case study; as a result, everything would follow the product manager’s schedule, and the delay situation was relatively minor. 2.In the traditional process, because manufacturing and design units do not have proper communication regarding the production limit in process at the early stage of product design, designers have no idea about the limit of current production equipment or parameters. In LEVEL1 of D-DCOR, the communication between design and production units are completely mentioned in the sub-processes under the main process of “Integration”, and the purpose of the communication is to confirm whether the existing equipment and techniques can meet the production demand of design products. 3.In D-DCOR, the input and output of documents have to be uploaded to the system so that the next step can be proceeded, and the measure avoids missing important and relevant information of new product designs during information transfer. Although the traditional design process has a similar work items, it is not mandatory. 4.In D-DCOR, the total cost of new product design development is lower due to fewer trials and no secondary development of new masks. 5.In D-DCOR, the asset utilization ratio of new product design development is higher due to fewer trials. Although the current design development process can sustain the new product development in the studied company, the D-DCOR model proposed in this study has more efficiency. The panel industry is in a plight today, and if the D -DCOR model can be effectively introduced in time, maybe the design and production costs can be reduced, the profits and shareholders’ interests can be increased, and the competitiveness of the studied company can be enhanced in the industry.

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42

"Eenvoudige ekonometriese vooruitskattingsmodelle vir geselekteerde invoergoedere deur Suid-Afrika se seehawens vir die periode 1982 tot 1994." Thesis, 2014. http://hdl.handle.net/10210/11446.

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43

Madan, Aditi. "Developmental and Functional Roles of Troponin-T Isoforms, and Exploring Genome-Wide Alterations in Drosophila Indirect Flight Muscle Mutants." Thesis, 2015. http://etd.iisc.ernet.in/2005/3601.

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Muscle contraction is a highly fine-tuned process that requires the precise and timely construction of large protein sub-assemblies to form sarcomeres, the individual contractile units. Mutations in many of the genes encoding constituent proteins of this macromolecular machine result in defective functioning of the muscle tissue, and in humans, often lead to myopathic conditions like cardiomyopathies and muscular dystrophies, which affect a considerable number of people the world over. As more information regarding causative mutations becomes available, it becomes imperative to explore mechanisms of muscle development, maintenance and pathology. In striated muscles, contraction is regulated by the thin filament-specific tropomyosin (Tm) – troponin (Tn) complex (Ca2+-binding troponin-C, inhibitory troponin-I and tropomyosin-binding troponin-T). These troponin subunits are present in 1:1:1 ratio on thin filaments, with 1 Tm-Tn complex present on every 7th actin molecule. This stoichiometry is tightly regulated, and disturbances have been associated with functional defects. Each of these proteins has multiple isoforms, whose expression is controlled both spatially and temporally. The expression of specific combination of isoforms confers specific contractile properties to each muscle subtype. Drosophila melanogaster has been a preferred model of choice to study various aspects of muscle development for decades. In this study, the Indirect Flight Muscles (IFMs) of Drosophila have been used to investigate developmental and functional roles of two temporally regulated isoforms of a vital structural and regulatory component of the sarcomere – Troponin T (TnT). On a larger scale, whole genome expression profiles of mutants that are null for major myofbrillar proteins have also been discussed. IFMs serve as an excellent model system to address these questions, owing to the extreme ease of genetic manipulability in this system, and high degree of homology between mammalian and Dipteran cytoskeletal proteins. Chapter 1 covers basics of muscle biology, and the role of TnT in muscle contraction. Phenomena responsible for generating diversity in genes encoding muscle proteins – alternative splicing and isoform switching – have also been discussed. These mechanisms are highly conserved, as are patterns of TnT splicing and isoform expression across phyla. Mutations leading to altered splicing patterns lead to myopathic conditions, and the importance of model systems to study muscle biology has been emphasized. The advantages of studying Drosophila IFMs and a comprehensive overview of IFM development has been covered. The resources and experimental tools used have been described in Chapter 2. Two isoforms of TnT are alternatively spliced in the Drosophila thorax – one containing alternative exon 10a (expressed in adult IFMs and jump muscle); and one containing alternative exon 10b (expressed in pupae and newly eclosed flies). These exons are spliced in a mutually exclusive manner, and defects in splicing have been reported to cause uncontrolled, auto-destructive contractions. In Chapter 3, a splice mutant of TnT, up1, has been discussed, with respect to its developmental profile. Transgenic rescue experiments with two separate isoforms demonstrate rescue at the structural as well as functional level. Transgenic over-expression, however, leads to functional abnormalities, highlighting the importance of stoichiometry in multi-protein complexes. In Chapter 4, molecular signals that bring about the developmentally regulated TnT isoform switch are discussed. A splicing factor, Muscleblind, has been transgenically knocked down in normal and mutant IFMs to study effects on muscle function. Chapter 5 looks at whole genome transcriptional alterations in muscles null for either actin or myosin. All significant expression changes have been classified into categories based on different biological processes, and an attempt to differentiate generic muscle responses from filament-specific responses has been made. In conclusion, the studies have highlighted the importance of TnT isoform switching, and that extended expression of a pupal stage-specific isoform can partially compensate for loss of the adult isoform. Also, in the absence of major myofibrillar proteins, stress response pathways like heat shock response and protein degradation pathways are activated, along with a subset of metabolic responses that are unique to the thin or thick filament systems.

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44

Bhudia, Shiv Jyotindra. "Static and dynamic modelling for IGZO-TFT devices with high-k multilayer dielectric." Master's thesis, 2017. http://hdl.handle.net/10362/31864.

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Indium-Gallium-Zinc-Oxide thin-film transistors (IGZO-TFT) are a strong alternative technology for the current trend of Si based field-effect transistor (FET) for flat-panel display backplane and internet of things internet of things (IoT). In these applications, comprehensive understanding and accurate modelling of thin-film transistor (TFT) is compulsory for systematic circuit design. In this study, IGZO-TFTs with high- multilayer dielectric, which were previously fabricated at CENIMAT/I3N Portugal are characterized in the University of Cambridge at the department of electrical engineering. Alongside this characterization, it is developed a compact static model that is capable of describing above-threshold linear behaviour. This model is based on physical parameters and also accounts the effects of contact resistance in source and drain terminals. Furthermore, it is developed a dynamic small signals model, based on conventional FET models and its validity is studied with the help of S-Parameters and capacitance-voltage characteristics (C-V) characteristics. The great advantage of the developed models, in both static and dynamic aspects, is the low number of parameters required to be extracted physically with good fitting results. This can empower new users that are not so familiar with the modelling aspect to design simple electrical circuits with IGZO-TFTs.

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Graulich, Michael [Verfasser]. "Spinale Effekte von TNF-α [TNF-alpha] am Modell des tumorinduzierten Knochenschmerzes der Maus / vorgelegt von Michael Graulich." 2010. http://d-nb.info/1010505998/34.

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Lin, Wen-Long, and 林文隆. "The Model Of Collaborative Product Development Process-TFT-LCD Industry." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/45626666446025276754.

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碩士
明新科技大學
工程管理研究所
92
To shorten the time of new product development has already become one competitive condition in the trend of globalization, therefore the collaboration between enterprises is very important. How to integrate the business process and information in collaborative product development to quickly respond customer and competitor? Currently there is not much study referred to product collaboration development model. In general there is only a concept of ideas but lack of specific detail steps of operating efficiency with best practice configuration, workplace, and management. So building a proper collaborative product development strategy will reduces man-made mistakes and avoids process delay to enhance new product competence. Therefore, this research focuses on ODM product development model of TFT-LCD industry in Taiwan. We investigate the new product development phase of the business models, including Product and Project Planning, Product Design, Product Pilot Run (Laboratory Pilot Run, Engineering Pilot Run, Production Pilot Run) and Mass Productions (First Mass Production and Technology Transfer). Also explore collaboration design process and simulations of the enterprise headquarter, customers and supplier. At the end, the research uses the ARIS modeling tool to establish ODM product development model of TFT-LCD industry, to bring a useful practical reference.

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Hsu, Chung-Tai, and 許崇泰. "A Distributed Negotiation Model for TFT-LCD Panel Manufacturing Firms." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/8pe3tt.

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碩士
國立臺灣科技大學
工業管理系
99
As rapid technology innovation, thin film transistor liquid crystal display (TFT-LCD) manufacturers commit to improve the production efficiency in order to enhance competitiveness. In practice, manufacturers frequently struggle not only to increase profit but also to reduce cost. A planning sector in such industry intends to promise all the orders and focuses on maximizing production profit of the available capacity. In contrast, a production sector taking charge for preparing costly materials pertains to minimize the wastage of material cost, e.g., glass substrate cost. Due to the phenomenon of TFT-LCD industry, these contradictory objectives raise the conflicts between the sectors when developing a comprehensive resources planning and capacity allocation plan. In order to solve the conflicts, we implement a system for the users to proceed the negotiation between the planning and the production sectors mutually. In the system, a sector thus can simply select the desired tactics and input the corresponding parameters in the interface. Regarding to the sectors’ decision making, we apply ILOG Concert Technology for each sector to define its decision model under their private considerations as well as to evaluate the received value of negotiation offer. Furthermore, we apply distributed computing technology to realize the negotiation environment so as to increase the convenience of the negotiation. The implemented system also can immediately present the results of the negotiation process and illustrate graphics from the data providing to the users, so that they can understand explicitly the negotiation situation visually. The experiment results demonstrate that the implemented negotiation system provides a platform for users to consult the conflicts between the sectors, consequently, the convenience of negotiation also be improved significantly.

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48

LIN, H. Y., and 林慧怡. "TFT-LCD AL (Aluminum) Etching Process Machine Purchase Selection Model." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/98206423247093402028.

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碩士
國立勤益科技大學
工業工程與管理系
101
Due to the fast information and the digital transition, many digital product applications in human life bring us conveniences and entertainments. The TFT-LCD industrial structure has been matured, high-tech level, and with abundant professionals and resources. In addition, high density market benefits market competitive advantage. TFT-LCD results in a better yield rate, better quality, and a variety of dimension choices, which makes TFT-LCD industry vigorous and competitive. The government considers the TFT-LCD industry as one of the “two trillion” key implement policy. Etching process is an important TFT-LCD process. The most important etching equipment purchase design consideration includes pressure, flow, stability in temperature control and cleaning ability. The condition of the machine and changes in the process parameters can affect the time of etching process. Therefore the etching rate needs to be checked often to make sure etching duplication. This study interviews experts, designs expert questionnaire which establishes the machine selection hierarchical structure, and applies Delphi Method to gather experts’ ideas. Then by applying Analytic Hierarchy Process on each selection factor regarding the importance considered by experts. Furthermore, this study compares the selection factors within Taiwan, Japan and South Korea. The second level in this study applies Quality Function Deployment to transfer the AHP key factor of customer machine purchase selection to key technique for designing machines by manufacturers. As a result to provide an objective and the best proposal to fit customer needs.

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49

Tzu, Ying Yang, and 楊子瑩. "Material Procurement Planning in TFT-LCD Industry: Deterministic and Stochastic Models." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/88596407985714669508.

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碩士
輔仁大學
國際創業與經營管理學程碩士在職專班
100
This thesis focuses on the material procurement planning in the thin-film transistor liquid crystal display (TFT-LCD) manufacturing industry. With the changing surroundings of manufacturing industry, the customized services, such as customized product and customized production line from suppliers become more widespread. Nowadays, the traditional material requirement planning (MRP) using fixed bill of material (BOM) in the TFT-LCD manufacturing industry couldn’t satisfy customers’ needs any more. The main contribution of this research is to utilize two-stage stochastic programming in the material procurement planning is rarely discussed in literatures. Moreover, this research further illustrates the optimal solutions of material procurement planning in both deterministic and stochastic models. Provide four unique characteristics occur in TFT-LCD which are alternative bill of material (ABOM), customer preference for ABOM, purchase quantity ratio, and demand uncertainty, explaining the power of BOM gradually becoming unrealistic. In addition, we compare the optimal solutions of both deterministic and stochastic models based on a realistic case of a TFT-LCD company in Taiwan. Two-stage stochastic programming is rarely discussed when handling demand uncertainty problem where two-stage programming takes scenarios and probability into consideration. We also show that the outcome of proposed stochastic programming model is the optimal solution, as, compared with deterministic programming model. We also found that the stochastic material procurement method is more robust than the deterministic programming.

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50

chiu, chui-shun, and 邱垂勳. "TFT LCD Source Driver IC Testing-Fault Models and Test Generation." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/05050839174836673607.

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Abstract:

碩士
國立交通大學
電資學院學程碩士班
90
The high density and compact TFT LCD Source Driver IC has been developed recently. The IC contains many non-linear DAC arrays with a characteristic of polarity inversion during operating. Because of these characteristics, there is no well-developed method of the testing the IC. In practice, the test patterns are developed by the test engineer according to design specifications and then modified according to the feedback of the end user of IC, i.e., the TFT_LCD panel manufacturer. The test patterns are inefficient and waste time. In the paper, we have, through the SPICE simulation, developed thirteen fault models to accommodate the tests. And then we create an expert system, in accordance to the real-site IC test statistics, to achieve a better and more efficient set of test patterns. Experimental results have shown that the developed patterns are effective in reducing test time while achieve a good test coverage

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