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Davila-Peralta, Christian, Justin Hyatt, Dan Alfred, Morgan Struble, Frank Sodari, and Roger Angel. "Dish-based CPV-T for rooftop generation." AMER INST PHYSICS, 2017. http://hdl.handle.net/10150/626483.
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Hybrid CPV-T with combined electrical and thermal output is well suited to solar generation from fixed limited areas, such as on the roof of an industrial or commercial facility with need for heat. This application will become especially attractive once overall electrical conversion efficiency of 40% is reached, as is projected for REhnu CPV systems using multijunction cells of 50% efficiency, anticipated in a few years. We outline here a configuration of dishbased CPV trackers optimized for close packing on a flat roof in a triangular grid, with a mirror area-to-ground area ratio of 50%. When the geometry of shadowing averaged over a year is taken into account, 80% of all the sunlight that would strike the rooftop is directed into the receivers. Such an array on a given area of flat roof will generate more electrical energy than would be possible with conventional PV panels, even if covering the entire rooftop, because of silicon's relative inefficiency. For example, in Tucson, the annual average global flux of 5.7 kWh/m2/day on a horizontal surface covered with 22% silicon modules will yield 1.25 kWh/m2/day. We show that a CPV system collecting 80% of all the direct sunlight of 7.0 kWh/m2 and converting it with 40% efficiency will yield 2.24 kWh/m2/day of rooftop area, nearly twice as much4. Thermal power will double again the total energy yield A dual axis CPV-T tracker designed specifically very close spacing has been built to carry a single dish mirror of the standard type used in REhnu's M-8 generator, described by Stalcup et al in these proceedings1,2. Sunlight is collected and focused by a single square paraboloidal mirror, 1.65 x 1.65 m with focal length of 1.5 m. For closest possible packing without mechanical interference, and for broad distribution of load on a rooftop, the mirror and receiver are mounted to a C-ring structure, configured such that the elevation and azimuth axes intersect at a virtual pivot, at the center of the sphere that just clears the receiver and the corners of the mirror. Initial tests of closed loop tracking show an accuracy of 0.03 degrees rms under calm conditions, and 0.04 degrees rms in 6 m/sec wind.
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Stalcup, Thomas, Roger Angel, Andrew Geary, Frank Sodari, Matt Rademacher, Andy Whiteside, John Will, Nick Didato, and Peter Strittmatter. "On-grid performance of REhnu’s 8-mirror CPV-T tracker." AMER INST PHYSICS, 2017. http://hdl.handle.net/10150/626484.
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REhnu has built and tested two 6 kW CPV-T trackers using dish-receiver architecture. In these trackers, only the light collection elements are large, namely mirrors on dual axis trackers. The inherently small parts, the multijunction cells, are packaged in a small, inexpensive receiver at each mirror focus. Optics in the receiver apportion the intensely focused sunlight equally to many cells, for high optical efficiency and simplified manufacture. Heat is removed by recirculated liquid. The tracker carries eight 2.7 m(2) mirrors and receivers. The CSTC DC efficiency of the individual mirror receiver units is measured at 32.5%. When used for electrical generation alone, the tracker system delivers an AC electrical output of 6.27 kW to the grid, referenced to a solar flux of 1 kW/m(2) DNI and 20 degrees C ambient temperature, corresponding to a total CSOC system efficiency of 29.1%, matching the best grid-connected system efficiency reported for any CPV system4. When used to generate also a thermal output of 9 kW at 64 degrees C, the electrical efficiency of the tracker was reduced by 0.8%, while the total efficiency, thermal plus electrical, rose to 77%.
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Hayakawa, M., and A. I. Sanda. "Searching for T, CP, CPT, and ΔS = ΔQ rule violations in the neutral K meson system: A guide." The American Physical Society, 1993. http://hdl.handle.net/2237/7157.
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Fernandes, Gilson. "Rede local de processadores de uma CPA-T." [s.n.], 1992. http://repositorio.unicamp.br/jspui/handle/REPOSIP/261556.
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Orientador: Michel Daoud YacoubDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
Made available in DSpace on 2018-07-15T20:24:07Z (GMT). No. of bitstreams: 1 Fernandes_Gilson_M.pdf: 16055731 bytes, checksum: dc376ba382f4dd9581ecf4ca2e91191f (MD5) Previous issue date: 1992
Resumo:Devido a redução nos custos dos processadores, causada pela evolução tecnológica, ocorreu uma revolução nos sistemas de controle e de processamento. Os sistemas de controle que tradicionalmente eram quase que exclusivamente centralizados, passaram a ser preteridos em função dos sistemas distribuídos. Os sistemas distribuídos propiciam uma capacidade de processamento ampliável, teoricamente infinita, pela agregação de novas unidades de processamento, além de prover um nível de confiabilidade superior ao dos sistemas centralizados convencionais. O propósito desta tese é descrever a arquitetura e a implementação de uma rede local de processadores particular que caracteriza um sistema distribuído. O objetivo imediato deste desenvolvimento foi servir como suporte ao controle de uma central CPA-T (central temporal com controle por programa armazenado) de grande porte (Sistema TRÓPICO RA). Como resultado obteve-se uma estrutura de controle que atendeu a todos os requisitos especificados. Além disso, a sua flexibilidade é tal que a mesma solução permite ser utilizada em outras aplicações onde seja necessário um sistema de comunicação entre processadores com características como alta performance, modularidade, confiabilidade, com a vantagem de utilizar-se um reduzido número de componentes de fácil aquisição no mercado
Abstract: Not informed.
Mestrado
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Kranzer, Katharina Theresa. "Direkte und indirekte Effekte von CpG-Oligodeoxynukleotiden auf humane T-Lymphozyten." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=964644800.
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Scherer, Barbara Marion. "Effekt von CpG-Oligonukleotiden auf die Funktion humaner T-Zellen und NK-Zellen." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972046356.
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Soares, Aurore. "Etude des symetries t et cpt dans les desintegrations semileptoniques des kaons neutres." Paris 6, 1996. http://www.theses.fr/1996PA066392.
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Cette these a ete realisee au sein de l'experience cplear situee aupres de l'anneau d'accumulation d'antiprotons, lear, du cern. Cette experience est destinee a l'etude des symetries cp, t et cpt. Grace a une methode interferometrique entre les k0 et les k0bar produits dans les annihilations au repos proton-antiproton, cplear mesure les parametres de violation de cp, t et cpt a partir des desintegrations des kaons neutres dans les modes deux pions, trois pions et semileptonique. Ce memoire traite de l'etude des desintegrations semileptoniques et de la mesure des parametres de violation de t et cpt. Il commence par une rapide presentation des symetries discretes c, t, p, cp et cpt. Le formalisme des kaons neutres est ensuite developpe. Puis l'ensemble du dispositif experimental, comprenant le detecteur et le systeme de selection en ligne, est presente. Pour finir, la selection et l'analyse des evenements semileptoniques sont developpees et suivies d'une presentation et discussion des resultats obtenus
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Fazano, Laura. "Um sistema baseado em conhecimento para dimensionamento e configuração de centrais telefonicas CPA-T." [s.n.], 1991. http://repositorio.unicamp.br/jspui/handle/REPOSIP/261396.
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Orientador: Fernando A. C. GomideDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
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Resumo: Um dos principais ramos da Inteligência Artificial é o de Sistemas Baseados em Conhecimento. Dentre esses, uma das principais áreas de atuação é a de configuração de equipamentos de grande porte, envolvendo grande quantidade de componentes e de diferentes combinações entre esses componentes. Este trabalho descreve o SSEA, Sistema de Suporte à Engenharia Aplicada, um sistema baseado em conhecimento para dimensionamento e configuração de centrais telefônicas CPA-T da família TRÓPICO RA. É descrito todo o processo de desenvolvimento do sistema, desde a Especificação de Requisitos até a implementação e testes do protótipo
Abstract: Not informed.
Mestrado
Mestre em Engenharia Elétrica
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Cioffi, Romulo. "Metodologia para a criação de produtos e serviços aplicada ao desenvolvimento de uma CPA-T." [s.n.], 1994. http://repositorio.unicamp.br/jspui/handle/REPOSIP/261557.
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Orientador: Michel Daoud YacoubDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
Made available in DSpace on 2018-07-19T12:33:22Z (GMT). No. of bitstreams: 1 Cioffi_Romulo_M.pdf: 7222784 bytes, checksum: dda153e3afb8d2d616433479911fac20 (MD5) Previous issue date: 1994
Resumo: A Rede de Telecomunicações passa por transformações que conduzem a expressivas mudanças em vários setores da vida humana. É toda uma evolução, e revolução, motivada pelo interesse por novos negócios e pela capacidade inventiva do ser humano, onde buscam-se oferecer serviços de comunicação em geral: voz, dados e imagens. O mercado de telecomunicações toma-se dia a dia mais exigente, seus valores são universais e a competição para atendê-Io é cada vez mais global. A finalidade desta tese é apresentar uma Metodologia para a Criação de Produtos e Serviços aplicável em qualquer nível de rede. Essa metodologia foi usada na prática do desenvolvimentodo SistemaTrópico-RA, que é um componente da Rede de Telecomunicações. Mas, neste trabalho de tese, ela será demonstrada na criação de produtos software. A sua generalidadeé tal que ela poderia contribuir também para o desenvolvimentode outras várias aplicações. Os fornecedores de produtos e serviços para a Rede de Telecomunicações, por exemplo, estão em busca de metodologias que cumpram com o requisito de economia, ou seja, qualidade a baixo custo. O conceito de Rede Inteligente foi criado para racionalizar a disponibilidade de novos serviços na Rede de Telecomunicações. A metodologia proposta neste trabalho poderia ser usada para essa aplicação. Neste caso ela proveria um suporte a todas as fases do desenvolvimento de um novo serviço, desde a sua criação até a operação e manutenção, acelerando-se a oferta de novos serviços para a Rede Inteligente
Abstract: Not informed.
Mestrado
Mestre em Engenharia Elétrica
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Moreno, Puerto Jose. "Performance Evaluation of the Solarus AB Asymmetric Concentrating Hybrid PV/T Collector." Thesis, Högskolan i Gävle, Avdelningen för bygg- energi- och miljöteknik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-17096.
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The energy sector is currently in a state of change as conventional energy sources are questioned by the need of new clean and sustainable energy sources to satisfy the global energy demand in the long term. Renewable energies respond to this increasing demand and solar energy is an advanced example of them. Photovoltaic modules are experiencing a steady reduction in their production costs. It is needed that this trend continues and, along with it, their propagation and expansion in the market continues. One way of reducing production costs is by using inexpensive light concentrators to increase the output of the costly photovoltaic cell. In this respect, the Solarus AB hybrid PV/T collector has been designed based on this principle. This collector is a CPC (Compound Parabolic Collector) and belongs to the MaReCo (Maximum Reflector Collector) family. The aim of this thesis is to deeply investigate this technology in two main areas. Firstly, the collector will be tested both electrically and thermally in order to evaluate its performance. To do so, a solar test rig has been built and connected at the building Hall 45 of Högskolan i Gävle, Gävle, Sweden. The second main area of investigation of this thesis is to determine the optimal price for the Solarus AB hybrid PV/T collector in order to be competitive in the solar energy market. This study will be based in the current market prices of photovoltaic and thermal collectors. Regarding the electrical performance of the collector, the results obtained show that the front side of the receiver produces more electricity throughout the day than the reflector side. This has guided Solarus AB to decide to change the design of its receiver to improve its performance. With the current design, it has been obtained a peak power at STC of 220W. In relation with the thermal part, the heat losses of the collector have been estimated obtaining a U value of 6,8W/(m2*K), a thermal optical beam efficiency of 63,5% and a total optical beam efficiency of 74,5%. The price market study of photovoltaic and thermal collector has shown that 2m2 of the Solarus AB hybrid PV/T collector produces approximately the same annual electricity and heat as 1,1m2 of a photovoltaic module with an efficiency of 15,5% and a flat plate collector of 0,85m2 of aperture area. According to the market study, its cost is equivalent to 190€ for the PV module and 220€ for the flat plate collector. This means that the price of the Solarus AB hybrid PV/T collector should be lower than 410€.
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Benelli, Angela. "A test of T and CPT symmetries in the neutral kaon system at the CPLEAR experiment." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243033.
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Touzart, Aurore. "Leucémies aigüs lymphoblastiques T (LAL-T) et dérégulation épigénétique Site- and allele-specific polycomb dysregulation in T-cell leukaemia Epigenetic silencing affects L-asparaginase sensitivity and predicts outcome in T-ALL Low level CpG island promoter methylation predicts a poor outcome in adult T-ALL." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB221.
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Les LAL-T sont des proliférations malignes de précurseurs lymphoïdes T bloqués à un stade précis de leur maturation. Si les anomalies génétiques impliquées dans la leucémogenèse T sont de mieux en mieux connues, les modifications de la régulation épigénétique sont beaucoup moins étudiées. Mon travail de thèse a consisté à étudier la dérégulation épigénétique intervenant dans les LAL-T au travers de 3 projets principaux. Dans le premier travail, nous avons identifié un mécanisme original de dérégulation de l’oncogène TAL1 consistant en la création d’un « neo-enhancer » oncogénique. TAL1 est l’un des oncogènes les plus fréquemment dérégulés dans les LAL-T. Cette dérégulation résulte principalement de translocations avec le locus du TCR ou des micro-délétions interstitielles SIL-TAL1, anomalies chromosomiques altérant des éléments de cis-régulation engendrant une expression ectopique monoallélique de TAL1. Mais dans une proportion importante de cas (environ 50%) de LAL-T TAL1+, une expression aberrante de TAL1 est observée sans que le mécanisme en cause ne soit identifié suggérant l’existence de mécanismes génétiques ou épigénétiques non connus. Nous avons découvert une nouvelle anomalie somatique consistant en une micro-insertion focale et récurrente 7 kpb en amont de TAL1, dans une région intergénique non-codante, responsable de la création d’un « neo-enhancer » oncogénique accompagné d’une modification des marques épigénétiques d’histones i.e. une substitution des marques répressives H3H27me3 par des marques activatrices H3K27ac. Ces micro-insertions sont un événement récurrent dans les LAL-T et ont été retrouvées dans 20% des LAL-T TAL1+ inexpliquées. Au travers du deuxième projet, j’ai tenté de mieux comprendre les bases biologiques à l’origine de différences de réponse au traitement. En effet, considérant deux groupes oncogéniques proches, le pronostic des patients TLX1+, déjà plutôt favorable dans le protocole LALA-94, n’a pas été significativement amélioré dans le protocole thérapeutique intensifié d’inspiration pédiatrique GRAALL 2003-2005 alors que les patients TLX3+ semblent avoir particulièrement bénéficié de ce dernier; les deux protocoles différant majoritairement par les doses de L-asparaginase. Nous avons montré que les patients TLX1+ exprimaient moins d’ASNS (Asparagine synthétase) que les patients TLX3+ et TLX- et que cette moindre expression résultait d’une inhibition épigénétique d’ASNS, à la fois par méthylation du promoteur et diminution des marques histones activatrices. Un niveau de méthylation d’ASNS bas est par ailleurs associé à une moindre sensibilité in vitro à la L-asparaginase. Enfin, la méthylation d’ASNS est un facteur pronostic indépendant pour les patients inclus dans le protocole GRAALL 2003-2005 suggérant que le statut de la méthylation d’ASNS au diagnostic pourrait intervenir dans l’adaptation des doses de L-asparaginase. Dans le troisième projet, je me suis intéressée à la méthylation globale de l’ADN. L’étude de la méthylation par MeDIP-array d’une série de 24 LAL-T nous a permis d’identifier des signatures de méthylation différentielle et de définir un panel minimum de 9 promoteurs de gènes dont l’étude de la méthylation par MS-MLPA a permis de déterminer un ratio de méthylation pour une large série de LAL-T adultes du GRAALL 2003-2005. Le statut de méthylation semble dicté par l’oncogène dérégulé avec en particulier les LAL-T TLX1+ ou TLX3+ associées à une signature d’hyperméthylation et les LAL-T SIL-TAL1+ à une signature d’hypométhylation. Ce statut de méthylation est par ailleurs un facteur pronostique indépendant. Ainsi, les patients hypométhylés ont un pronostic significativement plus défavorable que les patients hyperméthylés. Ensemble, ces résultats illustrent comment des perturbations de la régulation épigénétique peuvent intervenir à la fois dans l’oncogénèse des LAL-T mais aussi dans la réponse au traitementT-ALLs are rare lymphoid neoplasms characterized by the proliferation of immature T precursors arrested at specific stages of maturation. While the genetic abnormalities involved in T-ALL leukemogenesis are becoming better known, alterations in epigenetic regulation, a very important component of the cellular homeostasis, are much less studied. My work was to tsudy the epigenetic deregulation in T-ALL through 3 main projects. In the first project, we identified an original mechanism of TAL1 oncogene deregulation. TAL1 is one of the most frequently deregulated oncogenes in T-ALL. This deregulation results mainly from translocations with the TCRδ locus or micro-deletions SIL-TAL1, two chromosomal abnormalities altering cis-regulatory elements leading to monoallelic TAL1 expression. But in a significant proportion of cases (about 50%) of TAL1+ T-ALL, an aberrant expression of TAL1 is observed without recognized mechanism suggesting unknown genetic or epigenetic mechanisms. We discovered a new somatic alteration consisting of a focal and recurrent microinsertion 7 kbp upstream of TAL1, in a non-coding intergenic region, responsible for the creation of an oncogenic "neo-enhancer" accompanied by a modification of epigenetic histone marks i.e. a “switch” from H3H27me3 repressive marks to H3K27ac activating marks. These microinsertions are a recurrent event in T-ALL and have been found in 20% of “unresolved” TAL1+ T-ALL. Through the second project, I tried to better understand the biological bases for discrepancies in patients related response to treatment. Indeed, considering two close oncogenic groups, the prognosis of TLX1+ patients, already rather favourable in the LALA-94 protocol, has not been significantly improved in the paediatric-inspired GRAALL2003-2005 trial , whereas TLX3+ patients seem to have benefited particularly from the latter; the two protocols differing mainly by L-asparaginase doses. We showed that TLX1+ patients expressed less ASNS (Asparagine synthetase) than TLX3+ and TLX- patients and that this lower expression resulted from ASNS epigenetic silencing, both by methylation of the promoter and reduction of active histone marks. A low level of ASNS methylation is also associated with lower in vitro sensitivity to L-asparaginase. Finally, ASNS methylation is an independent prognostic factor for patients included in the 2003-2005 GRAALL trial suggesting that the ASNS methylation status may be relevant for the adaptation of L-asparaginase doses. In the third project, I was interested in the global DNA methylation. MeDIP-array methylation data of a series of 24 T-ALLs allowed us to identify differential methylation signatures. We then studied the methylation status in a large series of adult T-ALL by MS-MLPA using a predictor containing 9 gene promoters. We observed that main driver oncogenes dictated methylation status. TLX1+ and TLX3+ T-ALLs displayed a hypermethylated profile and conversely, SIL-TAL1+ cases were associated with a hypomethylated profile. This methylation status is also an independent prognostic factor and hypomethylated patients have a significantly unfavorable prognosis compared to hypomethylated patients. Together, these results illustrate how disruptions in epigenetic regulation can be involved both in the T-ALL oncogenesis and in the response to treatment
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Silva, Diego Wesllen da. "Diagnóstico de influência bayesiano em modelos de regressão da família t-assimétrica." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/45/45133/tde-10082017-005536/.
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O modelo de regressão linear com erros na família de distribuições t-assimétrica, que contempla as distribuições normal, t-Student e normal assimétrica como casos particulares, tem sido considerado uma alternativa robusta ao modelo normal. Para concluir qual modelo é, de fato, mais robusto, é importante ter um método tanto para identificar uma observação como discrepante quanto aferir a influência que esta observação terá em nossas estimativas. Nos modelos de regressão bayesianos, uma das medidas de identificação de observações discrepantes mais conhecidas é a conditional predictive ordinate (CPO). Analisamos a influência dessas observações nas estimativas tanto de forma global, isto é, no vetor completo de parâmetros do modelo quanto de forma marginal, apenas nos parâmetros regressores. Consideramos a norma L1 e a divergência Kullback-Leibler como medidas de influência das observações nas estimativas dos parâmetros. Além disso, encontramos as distribuições condicionais completas de todos os modelos para o uso do algoritmo de Gibbs obtendo, assim, amostras da distribuição a posteriori dos parâmetros. Tais amostras são utilizadas no calculo do CPO e das medidas de divergência estudadas. A principal contribuição deste trabalho é obter as medidas de influência global e marginal calculadas para os modelos t-Student, normal assimétrico e t-assimétrico. Na aplicação em dados reais originais e contaminados, observamos que, em geral, o modelo t-Student é uma alternativa robusta ao modelo normal. Por outro lado, o modelo t-assimétrico não é, em geral, uma alternativa robusta ao modelo normal. A capacidade de robustificação do modelo t-assimétrico está diretamente ligada à posição do resíduo do ponto discrepante em relação a distribuição dos resíduos.The linear regression model with errors in the skew-t family, which includes the normal, Student-t and skew normal distributions as particular cases, has been considered as a robust alternative to the normal model. To conclude which model is in fact more robust its important to have a method to identify an observation as outlier, as well as to assess the influence of this observation in the estimates. In bayesian regression models, one of the most known measures to identify an outlier is the conditional predictive ordinate (CPO). We analyze the influence of these observations on the estimates both in a global way, that is, in the complete parameter vector of the model and in a marginal way, only in the regressor parameters. We consider the L1 norm and the Kullback-Leibler divergence as influence measures of the observations on the parameter estimates. Using the bayesian approach, we find the complete conditional distributions of all the models for the usage of the Gibbs sampler thus obtaining samples of the posterior distribution of the parameters. These samples are used in the calculation of the CPO and the studied divergence measures. The major contribution of this work is to present the global and marginal influence measures calculated for the Student-t, skew normal and skew-t models. In the application on original and contaminated real data, we observed that in general the Student-t model is a robust alternative to the normal model. However, the skew-t model is not a robust alternative to the normal model. The robustification capability of the skew-t model is directly linked to the position of the residual of the outlier in relation to the distribution of the residuals.
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Pacagnella, Raquel de Carvalho. "Perfil epidemiológico de saúde bucal da população do parque indígena do Xingu, entre os anos de 2001 e 2006." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/17/17139/tde-03032008-145628/.
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A epidemiologia da saúde bucal dos povos indígenas no Brasil ainda é pouco conhecida. Os dados disponíveis, em geral, são pertinentes às zonas urbanas. As informações sobre a epidemiologia dessas doenças no Parque Indígena do Xingu (PIX) resultam de investigações nas quais foram utilizadas diferentes metodologias de coletas e análises de dados, dificultado assim um adequado panorama epidemiológico. A partir da implantação do Distrito Sanitário Especial Indígena do Xingu (DSEI-Xingu), em 1999, foram realizados três inquéritos epidemiológicos para doenças bucais, baseados na metodologia proposta pela OMS. O presente estudo teve como objetivo analisar a epidemiologia das referidas doenças no PIX, especificamente de quatro aldeias de diferentes etnias, considerando as necessidades assistenciais odontológicas. Para tal, foi realizado um estudo epidemiológico descritivo, utilizando dados secundários colhidos pela equipe do DSEI-Xingu, provenientes de inquéritos realizados em três momentos distintos: 2001, 2003 e 2006. Foram utilizados:o índice CPO-D, para avaliação da experiência de cárie e para aferir a doença periodontal, o índice periodontal comunitário (IPC). A análise dos resultados mostrou que nas aldeias estudadas, o principal problema de saúde bucal é a cárie, atingindo no ano de 2006, 81% da população. Em relação à cárie, nota-se uma queda nas médias do CPO-D para a maioria das faixas etárias no ano de 2006 em relação a 2001 e houve melhora também nos percentuais de pessoas livres de cárie para as idades entre 0 e 19 anos. As médias de ceo-d para o grupo etário de 0 a 3 anos apresentam elevação no período, exceto na aldeia Moigu, que mostrou diminuição de 8,0 em 2001 para 1,8, em 2006. Ao se analisar os componentes do CPO-D e ceo-d, quando comparados os dados obtidos em 2006 e 2001, foi possível verificar que o componente \"cariado\" apresentou redução para a maioria das faixas etárias em todas as aldeias, assim como o aumento dos componentes \"obturados e perdidos\". Observou-se que para a dentição decídua o componente cariado possui grande contribuição no ceo-d em todas as aldeias, variando entre 69% a 86% do índice. Isso traduz dificuldades no acesso dessa população aos serviços odontológicos. O índice IPC mostrou aumento do percentual de pessoas sem doença periodontal em todas as aldeias, queda no percentual de pessoas com algum tipo de bolsa periodontal e cálculo como o principal problema. Em relação às necessidades de tratamento verificou-se que restaurações foram as indicações mais freqüentes e houve um aumento no número de dentes sem nenhuma necessidade. Para a doença periodontal, observou-se que mais de 80% das pessoas acima de 15 anos precisam de tratamento e necessidade de profilaxia; as necessidades por cuidados mais complexos representam apenas 3% . Concluímos que no período de 2001 a 2006,houve uma melhoria nas condições de saúde bucal dessas populações. Uma hipótese explicativa seria a estruturação do programa de saúde bucal nestas áreas.There is a lack of information about the epidemiology of oral health conditions of the Indian population in Brazil. In general, available data are related to urban regions. Information about the epidemiology of oral health in the Xingu Indian Park (PIX) derive from surveys that employed different methodologies for collecting and analyzing the data, making it difficult to have an adequate picture of the problem. Since the creati of the indian Special Sanitary District of Xingu (DSEIXingu) in 1999, three epidemiologic surveys for oral health were carried out, based on the methodology proposed by the World Health Organization - WHO. The present study analyzed the oral health conditions in four villages of the PIX, considering treatment needs. A descriptive study was performed, using data already collected by surveys carried out by the health team of the DSEI-Xingu, employing the same methodology, in the years 2001, 2003 ead 2006. The DMF-T index was used to avaluate the caries experience, and for periodontal disease, the community periodontal index (CPI). The analisys of the results showed that the main oral health problem in the studied villages was tooth decay, reaching 81% of the population in 2006. In relation to caries, it was observed a decline in the mean of the DMF-T for majority of the age-groups in 2006 in relation to 2001 and an improvement in the proportion of people free of caries for the ages between 0-19 years. The mean of the dmf-t for the 0 to 3 year age-group was higher in 2006, except in the Moigu village, where a decline was observed (from 8.0 in 2001 to 1.8 in 2006). Comparing the DMF-T and dmf-t between 2006 and 2001, it was observed that the component \" decayed\" decreased in most of the age-groups in the four villages, as well as an increase in the component \"filled and missing\". For the deciduous teeth, the component \"decayed\" had greater contribution in the dmft in all the villages. The CPI index showed an increase in the proportionof persons without periodontal disease and a decrease in the proportion of persons with some kind of periodontal pockets in all the villages. Calculus was the main problem. In relation to treatments needs, indication of restoration was the most frequent and there was a increase in the number of teeth without any need. For periodontal disease, more than 80% of the persons aged 15 years or more need treatment and professional tooth cleaning; more complex treatment was required only by 3% of the individuals. We concluded that there was an improvement in the oral health conditions of this population, in the period 2001 to 2006. an explanatory hypothesis for this findings could be the implementation of the strutured oral health program in this region.
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Marabelle, Aurélien. "Targeting Tumor Specific Regulatory T-cells for Cancer Therapy." Thesis, Lyon, École normale supérieure, 2013. http://www.theses.fr/2013ENSL0832.
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L'activation de TLR9 par injection directe de nucléotides CpG non méthylés dans une tumeur peut induire une réponse immunitaire thérapeutique, mais les lymphocytes T régulateurs (Tregs) inhibent ensuite la réponse immunitaire antitumorale et limitent ainsi le pouvoir des stratégies d'immunothérapies contre le cancer.Chez des souris porteuses de tumeurs, nous avons constaté que les Tregs dans la tumeur expriment préférentiellement les marqueurs cellulaires de surface CTLA-4 et OX40. Nous montrons que la co-injection intratumorale d'anti-CTLA-4 et anti-OX40 avec du CpG en intra-tumoral aboutit à l’élimination des Tregs infiltrant la tumeur. Cette immunomodulation in situ, réalisée avec de faibles doses d'anticorps dans une tumeur unique, génère une réponse immunitaire antitumorale systémique capable d’éradiquer la maladie disséminée chez la souris. De plus, cette modalité de traitement est efficace contre des lésions de lymphome du SNC avec métastases leptoméningées, des sites qui sont généralement considérés comme des sanctuaires de cellules tumorales pour les traitements systémiques conventionnels.Ces résultats démontrent que les effecteurs immunitaires anti-tumoraux activés par immunomodulation locale peuventt éradiquer des cellules tumorales siègeant dans des sites éloignés. Nous proposons que, plutôt que d'utiliser des anticorps monoclonaux pour cibler les cellules cancéreuses par voie systémique, des anticorps monoclonaux pourraient être utilisés pour cibler les cellules immunitaires infiltrant la tumeur localement, provoquant ainsi une réponse immunitaire systémiqueActivation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, regulatory T-cells (Tregs) eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. We show that intratumoral coinjection of anti–CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. Further, this treatment modality was effective against established CNS lymphoma with leptomeningeal metastases, sites that are usually considered to be tumor cell sanctuaries in the context of conventional systemic therapy. These results demonstrate that antitumor immune effectors elicited by local immunomodulation can eradicate tumor cells at distant sites. We propose that, rather than using mAbs to target cancer cells systemically, mAbs could be used to target the tumor infiltrative immune cells locally, thereby eliciting a systemic immune response
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Tigno-Aranjuez, Justine Daphne Tiglao. "Adjuvant Guided T cell Responses." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1244035297.
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Kozeiha, Mohamad. "Search for T violation and CP violation in the Weak Semileptonic Λ0b and Λ+c Decays with the LHCb Detector." Thesis, Université Clermont Auvergne (2017-2020), 2017. http://www.theses.fr/2017CLFAC103/document.
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Kronschnabl, Manuela [Verfasser], T. [Akademischer Betreuer] Decker, C. [Akademischer Betreuer] Peschel, and H. [Akademischer Betreuer] Bernhard. "Einfluß der Stimulation mit CpG-Oligodesoxynukleotiden und Kostimulation mit CpG-Desoxynukleotiden und IL-2 auf Proliferation, Zytokinproduktion und Expression von Oberflächenmolekülen bei B-CLL-Zellen / Manuela Kronschnabl. Gutachter: C. Peschel ; H. Bernhard. Betreuer: T. Decker." München : Universitätsbibliothek der TU München, 2002. http://d-nb.info/1056975180/34.
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Maués, Bartira. "Uma introdução à Cp (X)." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/45/45131/tde-30082015-180119/.
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Neste trabalho estudamos algumas propriedades do espaço das funções contínuas munido da topologia da convergência pontual. Começamos estudando o espaço Cp(X) de forma geral, verificando que propriedades topológicas principais valem em Cp(X), usando teoremas de dualidade entre X e Cp(X). Em seguida estudamos a relação da estrutura topológica de X e a estrutura algébrica e topológica de Cp(X), onde o Teorema de Nagata é fundamental. Observamos algumas propriedades de X que são preservadas por l-equivalência ou t-equivalência, ou seja, que são determinadas pela estrutura linear topológica, ou pela estrutura topológica de Cp(X), respectivamente. Por último estudamos as condições para que Cp(X) seja um espaço de Lindelöf. Concluímos com a prova de Okunev de que o número de Lindelöf de Cp(X) é igual ao número de Lindelöf de Cp(X)xCp(X), para espaços fortemente zero-dimensionais X.In this work we study some properties of the space of continuous functions endowed with the topology of pointwise convergence. We begin by studying the space Cp(X) in general terms, verifying that the main topological properties are valid in Cp(X), using duality theorems between X and Cp(X). Next we study the relationship between the topological structure of X and the algebraic as well as topological structure of Cp(X), in which the Nagata theorem theorem is essential. We observe some properties of X, which are preserved by l-equivalence or t-equivalence, i.e., which are respectively determined either by the linear topological structure of Cp(X) or by its topological one. Finally we study in which conditions Cp(X) is a Lindelöf space. We conclude with the proof of Okunev that the Lindelöf number of Cp(X) is equal to the Lindelöf number of Cp(X)xCp(X), for strongly zero-dimensional spaces X.
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Teixeira, Guilherme Puchalski. "T?cnica processual voltada ao comprimento das obriga??es de fazer, n?o fazer e entregar coisa (artigos 461 e 461-A do CPC) : an?lise a partir da Constitui??o." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2009. http://tede2.pucrs.br/tede2/handle/tede/4071.
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Previous issue date: 2009-03-23A presente disserta??o de mestrado inicia destacando a influ?ncia dos ideais do Estado Liberal sobre a jurisdi??o e sobre o ordenamento jur?dico brasileiro. Dentre outros aspectos, confere especial destaque: a) ? elei??o da legalidade como principal fundamento do Estado; b) ao dogma da intangibilidade da vontade humana; c) ? consagra??o da tutela indenizat?ria como ?nica resposta poss?vel; d) ? impessoalidade da presta??o jurisdicional. Analisa a repercuss?o desses ideais sobre o processo civil da ?poca, ressaltando os sintomas da crise do processo civil cl?ssico diretamente relacionados ao pensamento liberal, dentre outros: a) a insufici?ncia da tutela gerada pelo bin?mio conhecimento-execu??o; b) a aus?ncia de mecanismos aptos ? preven??o do il?cito; c) a aus?ncia de tutela apta ?s situa??es de urg?ncia; d) a uniformidade de procedimentos. A segunda parte do trabalho destaca o surgimento do Estado Social e a sua influ?ncia, juntamente com a Constitui??o de 1988, sobre a jurisdi??o e sobre o ordenamento jur?dico brasileiro. Exp?em-se, resumidamente, aspectos gerais da teoria dos direitos fundamentais ? vista da Constitui??o de 1988, propondo-se o reconhecimento do direito fundamental de todo e qualquer cidad?o ? presta??o jurisdicional efetiva e adequada (dever do Estado). Defende-se um novo conceito de jurisdi??o, respons?vel, al?m da declara??o do direito, pela sua efetiva??o no mundo dos fatos. D?-se relev?ncia ? chegada da tutela espec?fica das obriga??es n?o pecuni?rias (obriga??es de fazer, n?o fazer e dar) no ordenamento jur?dico brasileiro e a sua import?ncia como meio de concretiza??o do direito fundamental ? efetividade e adequa??o da presta??o jurisdicional. A terceira e ?ltima parte aborda, em toda a sua extens?o, o procedimento estabelecido pelos artigos 461 e 461-A do C?digo de Processo Civil Brasileiro, com especial ?nfase aos mecanismos sancionat?rios de conduta (coercitivos e sub-rogat?rios), voltados ? obten??o do resultado espec?fico da obriga??o reconhecida em decis?o final ou interlocut?ria.
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Damen, Daniela [Verfasser], Rolf [Gutachter] Heumann, Jörg T. [Gutachter] Epplen, and Charlotte [Gutachter] Kilstrup-Nielsen. "The Rett-associated methyl-CpG-binding protein 2 interacts with the dual-specificity kinase Dyrk1A / Daniela Damen ; Gutachter: Rolf Heumann, Jörg T. Epplen, Charlotte Kilstrup-Nielsen ; International Graduate School of Neuroscience." Bochum : Ruhr-Universität Bochum, 2014. http://d-nb.info/1205971971/34.
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Gonschor, Bernhard [Verfasser], and Bernhard [Akademischer Betreuer] Zwißler. "Lässt sich flächendeckend eine Laienreanimation innerhalb des kritischen Zeitfensters von vier Minuten etablieren? : eine Untersuchung anhand der Auswertung der Echtdaten zum Klickalgorithmus T-CPR der Rettungsleitstellen Bayerns / Bernhard Gonschor ; Betreuer: Bernhard Zwißler." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1223849856/34.
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El, Rifai Ibrahim. "Mesure de la polarisation du baryon lourd Λb avec le détecteur LHCb. Recherche de la violation directe de la symétrie de renversement du temps T." Thesis, Clermont-Ferrand 2, 2015. http://www.theses.fr/2015CLF22560/document.
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Le sujet de cette thèse porte sur l’étude de la désintégration faible du baryon beau Λb → Λ J/Ψ avec le détecteur LHCb. Cette étude offre la possibilité de tester, d’une part, la validité de la symétrie CP dans le secteur baryonique et, d’autre part, celle de la symétrie de renversement du temps T dont les preuves expérimentales de sa violation sont limitées. L’accent est mis sur la mesure des composantes des vecteurs-polarisations du Λb et des résonances intermédiaires Λ et J/Ψ, dont certaines du type ”T-odd” (impaires par T) représentent un signe clair de violation directe de T. Le développement d’un modèle phénoménologique des désintégrations Λb → Λ J/Ψ dans le cadre du formalisme d’hélicité de Jacob-Wick et de Jackson conduit aux calculs de distributions angulaires qui permettent de déduire les valeurs des composantes des vecteurs-polarisations. Une étude approfondie de la reconstruction et de la sélection des données enregistrées par LHCb en 2011 et 2012 est exposée, ainsi qu’une simulation Monte-Carlo complète. La compatibilité entre les valeurs mesurées des vecteurs-polarisation du Λb et du Λ ̄b implique l’absence de violation de CP. La violation directe de la symétrie T n’a pas non plus été observée dans les désintégrations hadroniques du Λb (Λ ̄b). Sur un autre plan, les premières mesures des polarisations longitudinales du Λb et du Λ ̄b ainsi que de la polarisation longitudinale du méson-vecteur J/Ψ ont été réalisées dans le cadre de ce travailThis thesis subject focuses on the study of the weak decay of the beauty baryon Λb →Λ J/Ψ with the LHCb detector. Firstly, it offers the opportunity to test the validity of the CP symmetry in the baryon sector and, secondly, the one of time-reversal symmetry T whose experimental evidence is tiny. Emphasis is put on the measurement of the components of the polarization-vectors of the Λb and the ones of the intermediate resonances Λ and J/Ψ, whose some components exhibit a clear sign of direct T violation. The development of a phenomenological model of the Λb → Λ J/Ψ decay in the framework of the helicity formalism of Jacob-Wick and Jackson leads to the calculations of the angular distributions which allow to deduce the values of the polarization vector components. A thorough study of the reconstruction and the selection of the data recorded by LHCb in 2011 and 2012 is exposed, as well as a full Monte Carlo simulation. The compatibility between the measured values of the polarization-vector of Λb and Λ ̄b implies the absence of CP violation. The direct violation of the T symmetry has not been observed in the hadronic decays of Λb ( Λ ̄b). On another side, first measurements of the longitudinal polarization of Λb and of Λ ̄b well as the longitudinal polarization of the vector-meson J/Ψ have been performed in the context of this work
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Jugdé, Fabrice. "Caractéristiques fonctionnelles des lymphocytes T dans la muqueuse intestinale saine et pathologique : profil de production des chimiokines MDC et TARC, comparaison de l'activation et de la co-stimulation des cellules sanguines et intestinales par les oligodésoxyribonucléotides CpG." Rennes 1, 2003. http://www.theses.fr/2003REN10092.
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Les maladies inflammatoires chroniques de l'intestin (MICI) incluent la maladie de Crohn (MC) et la recto-colite hémorragique. Ce travail a participé à une meilleure compréhension de leurs mécanismes physiopathologiques. Les chimiokines étant impliquées dans le recrutement de lymphocytes T dans la muqueuse intestinale, nous avons d'abord montré une augmentation significative de l'expression des ARN messagers de MDC (Macrophage-Derived Chemokine) et TARC (Thymus and activation-regulated Chemokine) dans les tissus inflammatoires de sujets MC. Puis, les motifs cytosine-guanosine (CpG) de l'ADN bactérien jouant un rôle dans l'immunité, la stimulation de cellules mononucléées par des oligodésoxyribonucléotides (ODN) CpG induisait une prolifération, significativement augmentée des cellules de tissus inflammatoires de sujets MICI. Mais, aucune co-stimulation par les ODN des lymphocytes T activés par les voies CD2 ou CD3 n'a été observée, les ODN entraînant une inhibition de leur activation.
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Dahlin, Anna. "The CpG island methylator phenotype in colorectal cancer : studies on risk and prognosis." Doctoral thesis, Umeå universitet, Patologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-41270.
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Background Colorectal cancer (CRC) is the second most common malignancy in developed countries. The mortality is high, with nearly half of patients dying from the disease. The primary treatment of CRC is surgery, and decisions about additional treatment with chemotherapy are based mainly on tumor stage. Novel prognostic markers that identify patients at high risk of recurrence and cancer-related death are needed. The development of CRC has been described in terms of two different pathways; the microsatellite instability (MSI) and chromosomal instability (microsatellite stable, MSS) pathway. More recently, the CpG island methylator phenotype (CIMP), characterized by frequent DNA hypermethylation, has been described as an alternative pathway of tumorigenesis. The event of DNA methylation is dependent on one-carbon metabolism, in which folate and vitamin B12 have essential functions. The purpose of this thesis was to study CIMP in CRC. The specific aims were to investigate the potential role of components of one-carbon metabolism as risk factors for this subgroup of tumors, and the prognostic importance of CIMP status, taking into consideration important confounding factors, such as MSI and tumor-infiltrating T cells. Methods CRC cases and referents included in the Northern Sweden Health and Disease Study (NSHDS, 226 cases and 437 referents) and CRC cases in the Colorectal Cancer in Umeå Study (CRUMS, n=490) were studied. Prediagnostic plasma concentrations of folate and vitamin B12 were analyzed in NSHDS. In both study groups, CIMP status was determined in archival tumor tissue by real-time quantitative PCR using an eight-gene panel (CDKN2A, MLH1, CACNA1G, NEUROG1, RUNX3, SOCS1, IGF2 and CRABP1). MSI screening status and the density of tumor-infiltrating T cells were determined by immunohistochemistry. Results An inverse association was found between plasma concentrations of vitamin B12 and rectal, but not colon, cancer risk. We also found a reduced risk of CIMP-high and CIMP-low CRC in study subjects with the lowest levels of plasma folate. We found that patients with CIMP-low tumors in both NSHDS and CRUMS had a poorer prognosis compared with CIMP-negative, regardless of MSI screening status. We also found that MSS CIMP-high patients had a poorer prognosis compared with MSS CIMP-negative. The density of tumor-infiltrating T cells and CIMP status were both found to be independent predictors of CRC patient prognosis. A particularly poor prognosis was found in patients with CIMP-low tumors poorly infiltrated by T cells. In addition, the density of T cells appeared to be more important than MSI screening status for predicting CRC patient prognosis. Conclusion Rather than being one disease, CRC is a heterogeneous set of diseases with respect to clinico-pathological and molecular characteristics. We found that the association between risk and plasma concentration of vitamin B12 and folate depends on tumor site and CIMP status, respectively. Patient prognosis was found to be different depending on CIMP and MSI screening status, and the density of tumor-infiltrating T cells.
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Gianoto, Antonio Carlos. "O processo de migração de sistemas corporativos de comunicação TDM para plataformas convergentes IP com preservação de ativos." Universidade Presbiteriana Mackenzie, 2006. http://tede.mackenzie.br/jspui/handle/tede/2749.
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Previous issue date: 2006-06-29Fundo Mackenzie de Pesquisa
The aim of this elaboration is to present a study of the migration process involved transforming the digital PBX (Private Branch Exchange), TDM (Time Division Multiplex), SPC (Stored Program Control) based platforms of corporate communications on technology to converged IP (Internet Protocol) systems supported by the TCP/IP (Transmission Control Protocol/Internet Protocol) protocol. This proposal analyzes the necessary interventions in order to preserve the investments made in these platforms, integrating them to existent data networks. Beside other benefits presented in this work, one key advantage is the possibility to transport voice over an existing data infrastructure, optimizing usage of carrier connections.
O objetivo desta dissertação é o de apresentar um estudo do processo de migração de plataformas de voz PABX (Private Automatic Branch Exchange) TDM (Time Division Multiplex) de comunicações corporativas baseadas na tecnologia CPA-T (Controle por Programa Armazenado estágio de comutação temporal digital), para sistemas convergentes suportados pelo protocolo TCP/IP (Transmission Control Protocol/Internet Protocol). São analisadas as intervenções necessárias para esta migração, preservando ao máximo os investimentos efetuados nestas plataformas, integrando-as as redes de dados existentes. Dentre outras vantagens apresentadas no texto, destaca-se a otimização dos acessos fornecidos pelas operadoras de telecomunicações pelo compartilhamento da infra-estrutura da rede de dados para o tráfego de sinais de voz.
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Conte, E. "Recherche de la violation des symétries CP et T dans les réactions Lambda0_b –> Lambda0 + un méson vecteur. Validation de l'architecture de lecture des canaux du détecteur de pied de gerbe de l'expérience LHCb." Phd thesis, Université Blaise Pascal - Clermont-Ferrand II, 2007. http://tel.archives-ouvertes.fr/tel-00261494.
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Cette thèse explore la physique des baryons beaux dans le cadre de l'expérience LHCb. L'axe de recherche considéré porte sur les désintégrations Lambda0_b –> Lambda0 V avec V un méson vecteur tel que J/Psi(mu+mu-), phi(K+K-), omega(pi+pi-pi0) ou encore le mélange rho0-omega0(pi+pi-). Ces processus offrent la possibilité de tester la symétrie CP, dans un secteur (celui des baryons) où aucune violation n'a été observée, et la symétrie T, dont les preuves de sa violation sont limitées. Parmi les autres perspectives envisageables, une mesure précise du temps de vie du Lambda0_b pourrait contribuer à la résolution du puzzle théorico-expérimental aujourd'hui observé. Un modèle phénoménologique des désintégrations Lambda0_b –> Lambda0 V a été développé, à partir duquel les rapports d'embranchement et les distributions angulaires ont été estimés. Une étude approfondie de la reconstruction et de la sélection de ces réactions par le détecteur LHCb montre que le canal Lambda0_b –> Lambda0 J/Psi est le canal phare sur le plan statistique et pureté du signal. La mesure du temps de vie du Lambda0_b est le résultat le plus rapidement accessible ; les contraintes sur les asymétries dues à la violation de CP et la violation de T nécessitent plusieurs années de prise de données, avant d'obtenir un résultat significatif. En outre, un travail instrumental a été mené sur l'électronique de lecture, dite Front-End, des canaux du détecteur de pied de gerbe de l'expérience. Cette contribution comprend la validation des cartes électroniques prototypes et la mise en place des outils requis pour la qualification des 100 cartes de production.
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Conte, Eric. "Recherche de la violation des symétries CP et T dans les réactions Lambda0_b -> Lambda 0 + un méson vecteur. Validation de l'architecture de lecture des canaux du détecteur de pied de gerbe de l'expérience LHCb." Clermont-Ferrand 2, 2007. http://www.theses.fr/2007CLF21785.
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Cette thèse explore la physique des baryons beaux dans le cadre de l'expérience LHCb. L'axe de recherche considéré porte sur les désintégrations lambda0b en lambda0 V avec V un méson vecteur tel que J/psi (µ+ µ-), phi (K+K-), oméga (pi+pi-pi0) ou encore le mélange rhô0 _ oméga0 (pi+pi-). Ces processus offrent la possibilité de tester la symétrie CP, dans un secteur (celui des baryons) où aucune violation n'a été observée, et la symétrie T, dont les preuves de sa violation sont limitées. Parmi les autres perspectives envisageables, une mesure précise du temps de vie du lambda0b pourrait contribuer à la résolution du puzzle théorico-expérimental aujourd'hui observé. Un modèle phénoménologique des désintégrations lambda0b en lamda0 V a été développé, à partir duquel les rapports d'embrachement et les distributions angulaires ont été estimés. Une étude approfondie de la reconstruction et de la sélection de ces réactions par le détecteur LHCb montre que le canal lambda0b en lambda J/psi est le canal phare sur le plan statistique et pureté du signal. La mesure du temps de vie du lambda0b est le résultat le plus rapidement accessible ; les contraintes sur les asymétries dues à la violation de CP et la violation de T nécessitent plusieurs années de prise de données, avant d'obtenir un résultat significatif. En outre, un travail instrumental a été mené sur l'électronique de lecture, dite Front-End, des canaux du détecteur de pied de gerbe de l'expérience. Cette contribution comprend la validation des cartes électroniques prototypes et la mise en place des outils requis pour la qualification des 100 cartes de production
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Ogawa, Yoko Emily. "The Effects of Nicotine Conditioned Place Preference in D2 Primed Adolescent Rats: Age-Related and Gender Effects." Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etd/2129.
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This study investigated nicotine conditioned place preference (CPP) in two different ages of adolescence using a rodent model of schizophrenia. Both 2- and 3-chambered CPP apparatuses were used to test whether the CPP was due to an aversion to the white chamber. Animals were neontally treated with the dopamine D2/D3 agonist, quinpirole, or saline and raised to either early postweanling age (P 22) or adolescence (P 29). Rats were conditioned to prefer the white chamber using nicotine. Results showed that nicotine induced CPP and appeared to alleviate an increased stress response in D2 primed animals, which appeared to diminish over time. Additionally, adult D2 and non-D2 primed rats were tested on the elevated T-maze. Results revealed that D2 primed rats demonstrated a significant increase in unconditioned fear. This study showed that nicotine induced CPP in D2 and non-D2 primed rats regardless of age, and D2 primed rats appear to demonstrate an increase in stress levels that was alleviated by nicotine.
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Régnier, Paul. "Effet des interactions homéostatiques entre cellules dendritiques, lymphocytes effecteurs et régulateurs sur les réponses immunitaires anti-tumorales : étude du rôle de différentes cellules dendritiques in vivo chez la souris, et étude algorithmique des relations complexes entre transcriptome tumoral, populations immunitaires et survie in silico chez les patients A paradoxical role for Flt3 ligand in tumor immune response reveals homeostatic control of NK and treg cells by dentritic cells Tumor infiltration by immune cells favors patient survival in some cancers bur is highly detrimental in immune-privileged sites." Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2244&f=15657.
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Le cancer, l'une des principales causes de décès dans le monde, peut apparaître dans presque tout type de tissu, et est caractérisé par la prolifération anarchique de cellules et l'établissement d'une réponse immunitaire tolérogène favorisant la croissance tumorale, rendant souvent toute intervention médicamenteuse peu efficace. Les cellules dendritiques (DCs), véritables sentinelles de l'organisme, semblent jouer un rôle dans l'établissement à la fois d'une réponse anti-tumorale efficace et d'une tolérance face au cancer. Malgré tout, le rôle des différents sous-types de DCs dans le développement tumoral reste mal connu. Au cours de cette thèse, j'ai étudié différents acteurs cellulaires dendritiques et lymphocytaires, leurs relations et leur implication dans la réponse ou la tolérance immunitaire aux tumeurs. Durant la première partie de ma thèse, j'ai abordé l'effet de la modulation artificielle de l'homéostasie des DCs sur les autres cellules immunitaires ainsi que sur la réponse anti-tumorale in vivo chez la souris. J'ai montré qu'il existait un rôle paradoxal de la cytokine Flt3-L (FL) - un facteur de croissance essentiel à la différentiation et à l'homéostasie des DCs dites classiques/conventionnelles (cDCs) et des DCs plasmacytoïdes (pDCs) - sur la croissance du mélanome B16. En effet, sa surexpression ou son absence mènent à un meilleur contrôle du développement tumoral, accompagnées par une survie accrue des souris. L'absence de FL induit, en sus d'une disparition des cDCs et pDCs, une réduction drastique des lymphocytes T régulateurs (Tregs) protégeant la tumeur, ainsi qu'un renforcement général de la réponse immunitaire anti-tumorale adaptative via les lymphocytes T helpers. Sa surexpression induit une augmentation du nombre de cDCs et pDCs, et malgré une présence accrue de Tregs, un fort recrutement intra-tumoral de lymphocytes natural killer (NK) activés, un des acteurs majeurs de la réponse anti-tumorale innée. L'étude de souris déficientes en cDCs m'a également permis de démontrer l'existence d'un contrôle de l'homéostasie des NK par les DCs. De plus, la combinaison d'un traitement par FL et un anticorps déplétant les Tregs a un effet thérapeutique exacerbé chez la souris. Ensuite, par l'analyse bio-informatique de transcriptomes provenant de 35 types de cancers différents, j'ai montré que le paradoxe du FL existe également chez l'Homme, du moins pour certains cancers, et que les signatures géniques spécifiques de sous-populations de DCs peuvent être corrélées de manière paradoxale, bénéfique ou préjudiciable à la survie. En parallèle, j'ai évalué la présence de diverses cellules immunitaires dans l'infiltrat tumoral et leurs effets sur la survie des patients. Grâce aux algorithmes en langage R que j'ai développés, j'ai pu analyser pour tous les cancers étudiés les signatures géniques spécifiques de populations cellulaires immunitaires ainsi que les gènes et fonctions biologiques (pathways) les plus fortement dysrégulés ou impliqués dans le contrôle de la survie à 5 ans. Les résultats indiquent que les cellules immunitaires de l'infiltrat tumoral dans leur ensemble peuvent jouer, selon le cancer, un rôle bénéfique ou délétère. Cet infiltrat et les pathways immunitaires associés se sont révélés généralement de mauvais pronostic dans les cancers des organes dits immuno-privilégiés, mais en revanche bénéfiques dans les cancers du sein et de la peau. Pour chaque type de cancer, j'ai déterminé l'impact individuel sur la survie de différents types de cellules immunitaires et ai établi les corrélations entre les pathways impliqués et certaines de ces populations cellulaires. L'ensemble de ces résultats permet de mieux comprendre les relations complexes entre chaque cancer et son infiltrat cellulaire, et permettra à terme d'aider à développer des stratégies immuno-thérapeutiques plus adaptées à un environnement tumoral donné, en ciblant les populations immunitaires pouvant réellement impacter la survie des patientsThe cancer, one of the main causes of death in the world, can appear in almost any type of tissue, and is characterized by an anarchic proliferation of cells and the establishment of a tolerogenic immune response favouring the tumour growth, leading to low efficiency of drug interventions. Dendritic cells (DCs), real sentinels of the body, seem to play a role in the establishment of both efficient anti-tumoral immune response and tolerance against cancer. Nevertheless, the role of the different DCs subtypes in the tumoral development stays poorly known. During this thesis, I studied different dendritic and lymphocytic cellular actors, their relationships and their involvement in the immune response or tolerance to tumours. During the first part of my thesis, I studied the effect of the artificial modulation of DCs homeostasis on other immune cells and also on anti-tumoral response in vivo in mice. I proved the existence of a paradoxical role of the Flt3-L (FL) cytokine - a growth factor essential to the differentiation and the homeostasis of classical/conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) - on the B16 melanoma growth. In fact, its overexpression or absence both lead to a better control of the tumoral development, accompanied by an increased survival of mice. FL deficiency induces, together with the loss of both cDCs and pDCs, a drastic reduction of regulatory T lymphocytes (Tregs) protecting the tumour, and also a global reinforcement of the anti-tumoral adaptive immune response via helper T lymphocytes. Its overexpression induces an increase of the numbers of cDCs and pDCs, and despite a raised presence of Tregs, also a strong intra-tumoral recruitment of activated natural killer (NK) cells, one of the major actors of the anti-tumoral innate response. The study of cDCs-deficient mice allowed me to demonstrate the existence of a DCs-mediated control of the NK cells homeostasis. Furthermore, the combination of both FL treatment and antibody-mediated Tregs depletion has an exacerbated therapeutic effect in mice. Next, using bioinformatic analysis of transcriptomes of 35 different cancer types, I showed that the FL paradox also exists in humans, at least for some cancers, and that gene signatures specific of DCs subsets can be correlated in a paradoxical, beneficial or detrimental manner to survival. In parallel, I evaluated the presence of several immune cells in the tumour infiltrate and their effects on patients survival. Thanks to R language algorithms I developed, I was able to analyse for each studied cancer the immune cell populations-specific gene signatures and the most involved or dysregulated genes and biological functions (pathways) in the control of the 5 years survival of patients. My results indicate that the immune cells of the tumour infiltrate can play, according to the cancer, a beneficial or deleterious role. This immune infiltrate and the associated pathways were generally of bad prognosis in cancers of immune-privileged organs, but on the other hand were beneficial in skin and breast cancers. For each cancer type, I determined the individual impact on survival of several types of immune cells and established correlations between involved pathways and some of these cell populations. Altogether, the results allow to better understand the complex relationships between each cancer and the associated immune infiltrate, and will later lead to help the development of immunotherapeutic strategies more adapted to a given tumour environment, by targeting the immune populations that could really impact the survival of patients
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Forni, Fabio. "Investigating the axial response of pile foundations for offshore wind turbines." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2017.
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I crescenti problemi legati ai cambiamenti climatici rendono l'impiego delle energie rinnovabili sempre più interessante.
In questa ottica, in Germania si sta pianificando di aumentare la produzione di energia pulita attraverso lo sfruttamento dell’energia eolica. Nuovi impianti di turbine eoliche sono previsti nel Mare del Nord in acque medio profonde (25-45m) dove la parte immersa della struttura della turbina eolica (chiamata sottostruttura) è spesso costituita da una struttura jacket (traliccio) o tripod (a treppiedi). Questo tipo di sottostrutture trasmettono principalmente carichi assiali alle fondazioni (in genere fondazioni su palo), e il carico a trazione è la forza che maggiormente ne influenza il dimensionamento.
Molte compagnie energetiche tedesche sono interessate a migliorare l’efficienza e i costi dei loro impianti eolici e, per questo, incaricano università ed istituti di ricerca (come il Fraunhofer IWES) per indagarne gli aspetti, come ad esempio il comportamento delle fondazioni offshore.
All’autore di questa tesi è stata data l’opportunità di studiare e lavorare al Fraunhofer IWES e perciò questa tesi tratterà del compramento di pali caricati assialmente e staticamente pensati per sottostrutture jacket o tripod per turbine eoliche.
Nello studio effettuato per questa tesi, i dati seprimentali, ottenuti da una campagna sperimentale condotta (in larga scala 1:10 1:5) su pali infissi in terreno sabbioso, sono confrontati attraverso l’impiego delle load-transfer curves (funzioni che descrivono il comportamento d’interfaccia palosuolo) usando sia un’approccio classico (fornito dal metodo di calcolo API Main Text) sia approcci più recenti (dati dai metodi di calcolo CPT).
Uno script Matlab creato appositamente dall’autore di questa tesi riesce ad implementare 11 diversi tipi di load-transfer curves. Il lavoro di tesi si conclude con un esempio pratico in grado di fornire un’idea di come questo script può essere usato nella progettazione.
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Kulenda, Vít. "Univerzální mikropočítačová jednotka." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2011. http://www.nusl.cz/ntk/nusl-219068.
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Master’s thesis contains description parameters of microcontroller ATMEGA644P, also contains differences between older and newer version of microcontrollers ATMEGA644 and ATMEGA644PA. Inside structure of microcontroller, memories and peripherals are described here. The construction of the universal microcontroller unit is main target of this thesis. The unit contains supply, A/D converter, current loop, communication interfaces, temperature sensor, accelerometer and other. The unit collects and saves data, communicates by interfaces and manages other functions. Using devices and circuits are described in this thesis. Development of software for microcontroller(firmware) are positioned to last part of this thesis. This software control functions of all parts positioned on the unit.
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CHIANI, GABRIELE. "Messa a punto e caratterizzazione di un sistema termo-fotovoltaico lineare a concentrazione." Doctoral thesis, 2012. http://hdl.handle.net/2158/794614.
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"Towards the measurement of CP, T, CPT and the ⊿S=⊿Q rule violations in the neutral K meson system." Thesis, 1994. http://hdl.handle.net/2237/11204.
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早川, 雅司, and Masashi Hayakawa. "Towards the measurement of CP, T, CPT and the ⊿S=⊿Q rule violations in the neutral K meson system." Thesis, 1994. http://hdl.handle.net/2237/11204.
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Lu, Wan-Chi, and 呂婉綺. "A simulation study on the process incapability index Cpp''(s',t)." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/16405452541728713609.
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碩士輔仁大學
數學系碩士班
101
This thesis focuses on the C''pp(s',t) index, which not only takes into account the degree of process targeting but also takes into account the location of process mean related to the target value. First of all, the comparison between the natural estimator of C''_pp(s',t) with the generalized pivotal estimator Cpp''GPQ(s',t) was made. Secondly, applying the concept of generalized pivot quantity to find an upper confidence bound for C''pp(s',t). Thirdly, a confidence bound of C''pp(s',t) index based on bootstrapping method was discussed. Finally, inconsistency between (modified)proportion of conformance and process (in)capability indices are studied.
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Kranzer, Katharina Theresa [Verfasser]. "Direkte und indirekte Effekte von CpG-Oligodeoxynukleotiden auf humane T-Lymphozyten / Katharina Theresa Kranzer." 2001. http://d-nb.info/964644800/34.
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Scherer, Barbara Marion [Verfasser]. "Effekt von CpG-Oligonukleotiden auf die Funktion humaner T-Zellen und NK-Zellen / Barbara Marion Scherer." 2004. http://d-nb.info/972046356/34.
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Cheng, Han-Yin, and 鄭涵尹. "A Novel Emulsion-Type Adjuvant Contains CpG Oligodeoxynucleotides Enhances CD8+ T Cell Immunity against Cervical Cancer." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/91044665150701002070.
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碩士中國醫藥大學
免疫學研究所碩士班
99
A rational approach towards the development of strong CTL-inducing adjuvant formulation is to combine vaccine delivery system and immune-stimulating reagents. PELC is an emulsion-type vaccine delivery system which contains a bioresorbable polymer PEG-b-PLACL, Span®85 and squalene. Our previous report has been shown that PELC formulated with TLR9 ligand (CpG) (PELC/CpG) in H5N1 vaccine could enhance humoral immunity to against H5N1 virus. In order to determine whether PELC/CpG can also enhance cellular immunity to treat cervical cancer, both protein and CTL epitope-based immunotherapies were used in this study. Peptide RAHYNIVTF (RAH) is an H-2Db-restricted CTL epitope that derived from HPV16 E7 (amino acid 49-57). We formulated this peptide with PELC/CpG to induce CTL for developing therapeutic cervical cancer vaccine. The RAH formulated with PELC/CpG, immunization with C57BL/6 mice could induce higher number of IFN-γ-secreting cells and CD107a+CD8+ cytotoxic T cells than RAH formulated with PELC or CpG only. RAH formulated with PELC/CpG could also induce higher number of RAH-specific CD8+ T cells that determined using PE conjugated RAH/H-2Kb tetramer. Furthermore, RAH formulated with PELC/CpG to immunize TC-1 tumor-bearing mice once could induce strong inhibition of tumor growth compare to formulate with PELC or CpG only. In order to test whether this formulation could be used for protein antigen, recombinant mutant E7 protein (rE7m) was formulated with PELC/CpG. We found that rE7m formulated with PELC/CpG could induce a Th1-bias immunity against tumor. Our results demonstrate that antigen formulated with both delivery system and immune-stimulating reagent (TLR9 ligand) could induce strong CTL responses against cancer.
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Gulvady, Apeksha Ashok. "The influence of obesity and lipid metabolism on thymic function." Thesis, 2011. http://hdl.handle.net/2152/ETD-UT-2011-05-3276.
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Approximately two-thirds of US adults are overweight or obese, and obesity is also becoming more prevalent in children and adolescents. Similar to adults, obese children are at a higher risk of developing health problems due in part to dysfunctional immune surveillance. Obesity has been shown reduce the generation of new T-cells by accelerating thymic aging in an adult mouse. This study therefore aimed at determining whether similar diet induced obesity (DIO) changes can be induced in a young mouse. Comparisons made between lean and DIO C57Bl/6 mice showed a significant increase in thymic weight, decrease in thymic cellularity and thymic output, and impaired T-cell development at the double negative stage. We associate these alterations with changes in thymic architecture and accumulation of lipid droplets within the thymic cortex and medulla of the obese mice. The above observations indicate that DIO can induce fat accumulation and reduce thymic function at a young age. Resveratrol, a natural polyphenolic compound, was then used to regulate fat metabolism in an attempt to reduce these DIO changes we observed. Resveratrol induces fat oxidation via 5' adenosine monophosphate-activated protein kinase (AMPK), and its reciprocal regulation of glycerol-3-phosphate acyltransferase-1 (GPAT-1) and carnitine palmitoyltransferase-1 (CPT-1), the rate-limiting enzymes required for glycerophospholipid biosynthesis and oxidation, respectively. Through resveratrol feeding, we were able to prevent the effects of DIO on thymic architecture and thymic T-cell proliferation. This was achieved by manipulating AMPK into inhibiting GPAT-1 and enhancing CPT-1 activity. Since the expression of GPAT-1 was upregulated in the obese mice, we investigated whether deleting GPAT-1 altogether might prevent the thymic involution, by inhibiting synthesis of glycerophospholipids and triacylglycerol. Instead, we found that GPAT-1 deletion slowed thymic growth and reduced cellularity in young mice, which we associated with impaired thymic T-cell function and development, suggesting that the deleterious effects of GPAT-1 deficiency may be due to perturbations in thymic T-cell activation and signaling. These data provide a novel link between lipid metabolism and T-cell development, and identify the use of the naturally-occurring resveratrol to reduce lipid accumulation within the involution-prone thymus, thus providing a useful approach to preventing a decline in thymic function in childhood.text
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Marschner, Anja [Verfasser]. "Immunstimulatorische Aktivität von CpG-Oligonukleotiden im Menschen und im Rhesusaffen : Aktivierung humaner natürlicher Killer-T-Zellen durch CpG-Oligonukleotide und α-Galaktosylceramid und Etablierung eines nicht-humanen Primatenmodells für präklinische Studien mit CpG-Oligonukleotiden / vorgelegt von Anja Marschner." 2004. http://d-nb.info/973138076/34.
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Zheng, Wangzhi. "Experiments of Search for Neutron Electric Dipole Moment and Spin-Dependent Short-Range Force." Diss., 2012. http://hdl.handle.net/10161/5493.
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It is of great importance to identify new sources of discrete symmetry violations because it can explain the baryon number asymmetry of our universe and also test the validity of various models beyond the standard model. Neutron Electric Dipole Moment (nEDM) and short-range force are such candidates for the new sources of P&T violations. A new generation nEDM experiment was proposed in USA in 2002, aiming at improving the current nEDM upperlimit by two orders of magnitude. Polarized
A Monte-Carlo simulation is used to simulate the entire
We also built an apparatus to demonstrate that the
During this SQUID test, two interesting phenomena were discovered. One is the pressure dependence of the T1 of the polarized
In addition to the nEDM experiment, polarized
Dissertation
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Chiodetti, Ana Laura. "Estudio de la capacidad adyuvante del CpG-ODN formulado en una nanoestructura en fase coagel para la inducción de inmunidad humoral y celular mediada por linfocitos T CD8." Doctoral thesis, 2017. http://hdl.handle.net/11086/15367.
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Tesis (Doctora en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2017Durante las últimas décadas se han comenzado a desarrollar las denominadas “vacunas de la nueva generación”. Su diseño difiere de las vacunas tradicionales y está basado en el uso de antígenos altamente purificados o recombinantes débilmente inmunogénicos combinados con poderosas estrategias adyuvantes capaces de compensar esta pérdida de inmunogenicidad. Adicionalmente el mayor problema de los adyuvantes licenciados para uso humano recae en su incapacidad de generar una respuesta del tipo celular Th1 y T CD8+ citotóxica adecuada para proteger contra patógenos intracelulares que perdure en el tiempo. El oligodeoxinucleótido con motivos citocina fosfato guanina no metilados (CpG-ODN), ligando sintético agonista del receptor de la respuesta inmune innata tipo toll 9 (TLR9), ha sido ampliamente considerado por sus efectos inmunoestimulantes como un candidato ideal como adyuvante. El CpG-ODN tiene la capacidad de generar una respuesta humoral y adicionalmente polarizar la respuesta inmune celular hacia un perfil Th1, induciendo también, bajo ciertas modalidades, células T CD8+ citotóxicas. Sin embargo, padece de una biodisponibilidad reducida, lo cual afecta su desempeño. Con el objetivo de optimizar su actividad adyuvante, proponemos una nueva estrategia de formulación para el CpG-ODN basado en un sistema nanoestructurado derivado de palmitato de ascorbilo (Coa-ASC16). En este trabajo, demostramos el potencial de una formulación constituida por ovoalbúmina (OVA), CpG-ODN y el Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) para generar una respuesta humoral superior en magnitud y calidad que la solución OVA/CpG-ODN. La magnitud de dicha respuesta humoral resultó ser independiente de la vía de señalización mediada por IL-6. Además, la inmunización con OVA/CpG-ODN fue capaz de inducir una robusta respuesta de células T CD8+ citotóxicas efectoras, dependiente de interferones tipo I e independiente de IL-6 y de la asistencia mediada por células T CD4+. Consistentemente con esos resultados, la estrategia adyuvante demostró promover la internalización simultánea de OVA y CpG-ODN por células dendríticas. En adición, también fue capaz de inducir una buena respuesta de células T CD8+ de memoria. Ambas respuestas celulares T CD8+, efectora y de memoria, probaron su eficiencia protegiendo contra un modelo de infección intracelular con Listeria monocytogenes. Por otra parte, esta plataforma permite la reducción del número de inmunizaciones y la dosis antigénica sin afectar significativamente la inmunidad humoral o celular generada. Estos resultados demuestran el potencial de esta innovadora estrategia adyuvante para el desarrollo de futuras vacunas.
Chiodetti, Ana Laura. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina.
Maletto, Belkys Angelica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.
Maccioni, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.
Irazoqui, Fernando José. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica. Consejo Nacional de Investigaciones Científicas y Técnicas.Centro de Investigaciones en Química Biológica de Córdoba; Argentina.
Allemandi, Daniel Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.
Rumbo, Martín. Universidad Nacional de La Plata. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina.
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Savid, Frontera Constanza. "Estudio y caracterización de células T CD8+ innatas como posibles mediadores terapéuticos en cáncer." Doctoral thesis, 2020. http://hdl.handle.net/11086/16503.
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Tesis (Doctora en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2020El sistema inmune adaptativo es un componente esencial del sistema inmunológico que permite la inducción de una respuesta específica y de memoria contra antígenos determinados. Entre los principales actores que median este tipo de respuesta se encuentran los linfocitos T CD4+ y CD8+, los cuales se desarrollan y diferencian en timo, y se activan en periferia al contactar a través de su receptor de células T (TCR) a su antígeno (Ag) específico en el contexto de una molécula del Complejo Mayor de Histocompatibilidad (MHC), adquiriendo marcadores de activación y memoria, y generando una respuesta efectora con la finalidad de eliminar el agente extraño. Sin embargo, hace algunos años se describió que en órganos linfáticos secundarios (OLS) de animales WT no expuestos a antígenos, existía entre un 10-15% de células T CD8+ que presentaban un fenotipo similar al de memoria (CD44hi CD122+) con capacidad de producir interferón gamma (IFN) de manera rápida frente a estímulos innatos, independientemente de la señalización del TCR. En base a estas características y a su similitud con células de memoria convencional dependientes de antígeno, estas células fueron designadas originalmente como: “células T CD8+ innatas”, “células con fenotipo de memoria”, “células de memoria innata” (IM, por Innate memory cells) a las presentes en timo o “células de memoria virtual” (VM, por virtual memory cells) a las presentes en periferia. Inicialmente, las células T CD8+ innatas fueron identificadas en timo de animales transgénicos que carecían de la expresión de distintas moléculas involucradas en la señalización a través del TCR. Desde entonces, muchos autores se han abocado a su estudio y a determinar diversas señales que pudieran ser importantes en la inducción de esta población, principalmente en timo (células IM, por innate memory cells). Hoy se sabe que estas células también pueden originarse en OLS, sin embargo, su origen y desarrollo en periferia (células VM) aún es controversial. En este trabajo de tesis aportamos evidencias de la distribución diferencial de las células VM en distintos OLS de animales WT portadores de tumor en condiciones normales y evaluamos además las alteraciones que esta población sufre en un contexto inflamatorio sistémico tipo T cooperador o “helper” (Th)-1 mediado por la expresión de interleuquina (IL-)12 e IL-18. Observamos en animales, que la inyección hidrodinámica (IH) de los plásmidos de expresión de IL-12 e IL-18, logra incrementar la población VM CD122+ en ambos OLS (bazo y ganglio drenante de tumor) y más aún, dentro del tumor, siendo la población CD8+ de memoria preponderante en este tejido, comparado a lo observado en animales libres de estímulo (controles no estimulados con IL-12 e IL-18). Este resultado, a su vez, estuvo correlacionado con un efectivo control del crecimiento del tejido neoplásico, sugiriendo un posible rol de las células T CD8+ innatas en la respuesta antitumoral. Utilizando modelos de animales transgénicos determinamos el aporte de citoquinas como IL-4 e IFNs tipo-I en la adquisición del fenotipo innato en periferia (expresión de Eomesodermina (Eomes) y CD122) y un posible rol de IFN en la expansión de las células VM en OLS y dentro del tumor, principalmente en el contexto de una respuesta pro-inflamatoria. Constanza Savid-Frontera Nuestros datos en animales enriquecidos en células T CD8+ Ag-independientes (animales con células T CD8+ portadoras de TCRs transgénicos para el Ag OVA), demuestran que en un contexto donde prima la respuesta de células T CD8+ no específica del TCR, un proceso pro-inflamatorio es capaz de inducir una respuesta antitumoral eficaz al igual que en un sistema policlonal (animales WT). Más aun, el estímulo con IL-12 e IL-18 en estos animales favorecería el establecimiento de una interacción entre estas células y las células tumorales e incrementaría la respuesta funcional de las células innatas, la cual podría estar siendo mediada por receptores de muerte, como NKG2D, de manera independiente al reconocimiento de un antígeno vía TCR. Los resultados obtenidos en esta tesis doctoral aportan evidencias en la inducción y distribución de las células T CD8+ innatas en periferia, de las alteraciones que estos parámetros sufren durante respuestas inflamatorias sistémicas de tipo Th1 y del posible rol de las células de memoria virtual en la respuesta antitumoral.
2022-08-31
Fil: Savid Frontera, Constanza. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina
Fil: Rodríguez Galán, María Cecilia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina.
Fil: Rodríguez Galán, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.
Fil: Stempin, Cinthia Carolina. Universidad Nacional de Córdoba. Faculta de Ciencias Químicas; Argentina.
Fil: Stempin, Cinthia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.
Fil: Maldonado, Cristina Alicia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.
Fil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.
Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental; Argentina.
Fil: Gil, Germán Alejandro. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina.
Fil: Gil, Germán Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina.
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Villanueva, Alexander Ian. "The influence of Toll-like receptors on murine invariant natural killer T cell activation." Thesis, 2013. http://hdl.handle.net/10214/7252.
Full textAbstract:
Invariant natural killer T (iNKT) cells are a versatile subclass of T lymphocytes which recognize glycolipid antigens. iNKT cells are capable of rapidly producing a broad array of cytokines in response to stimulation; thus, they play an important role in the early regulation of a variety of immune responses. It was hypothesized that iNKT cells express functional Toll-like receptors (TLRs) and that stimulation of TLRs by their ligands modulates iNKT cells responses. In the first objective, it was revealed that upon stimulation with anti-CD3 monoclonal antibody and interferon (IFN)-α, expression of TLRs was enhanced in iNKT cells. Furthermore, stimulation of iNKT cells with TLR ligands led to a significant increase in the expression of several cytokines. In the second objective, the mechanisms behind the modulatory effects of the TLR9 ligand (CpG-ODN) on iNKT cells were determined. Altogether, these findings suggest a direct role for TLRs in iNKT cell activation.Ontario Graduate Scholarship
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Mathieu, Mélissa. "Étude de la différenciation des lymphocytes T CD8+ effecteurs et mémoires : rôle de la cellule présentatrice d’antigène et de la voie de signalisation Notch." Thèse, 2014. http://hdl.handle.net/1866/11791.
Full textAbstract:
Lors d’une infection par un pathogène, des lymphocytes T CD8+ naïfs (LTn) spécifiques de l’antigène sont activés, prolifèrent et se différencient en LT effecteurs (LTe). Les LTe produisent différentes cytokines et acquièrent une activité cytotoxique menant à l’élimination du pathogène. Seulement 5 à 10 % des LTe survivront et se différencieront en LT mémoires (LTm), qui sont capables de répondre plus rapidement lors d’une seconde infection par le même pathogène, contribuant au succès de la vaccination. Toutefois, la compréhension de l’ensemble des mécanismes régulant le développement des LTe et des LTm demeure incomplète. Afin de mieux comprendre les signaux requis pour la différenciation des LT CD8+ lors de la réponse immune, nous avons posé deux hypothèses.
Nous avons d’abord proposé que différentes cellules présentatrices d’antigène (CPA) fournissent différents signaux au moment de la reconnaissance antigénique influençant ainsi le devenir des LT CD8+. Vu leur potentiel d’utilisation en immunothérapie, nous avons comparé la capacité d’activation des LT CD8+ par les lymphocytes B activés via le CD40 (CD40-B) et les cellules dendritiques (CD). Nous avons montré que l’immunisation avec des CD40-B induit une réponse effectrice mais, contrairement à l’immunisation avec des CD, pratiquement aucun LTm n’est généré. Les LTe générés sont fonctionnels puisqu’ils sécrètent des cytokines, ont une activité cytotoxique et contrôlent une infection avec Listeria monocytogenes (Lm). Nous proposons qu’une sécrétion plus faible de cytokines par les CD40 B ainsi qu’une interaction plus courte et moins intime avec les LT CD8+ comparativement aux CD contribuent au défaut de différenciation des LTm observé lors de la vaccination avec les CD40-B.
Ensuite, nous posé l’hypothèse que, parmi les signaux fournis par les CPA au moment de la reconnaissance antigénique, la voie de signalisation Notch influence le développement des LTe, mais aussi des LTm CD8+ en instaurant un programme génétique particulier. D’abord, grâce à un système in vitro, le rôle de la signalisation Notch dans les moments précoces suivant l’activation du LT CD8+ a été étudié. Ce système nous a permis de démontrer que la voie de signalisation Notch régule directement l’expression de la molécule PD-1. Ensuite, grâce à des souris où il y a délétion des récepteurs Notch1 et Notch2 seulement chez les LT CD8+ matures, un rôle de la voie de signalisation Notch dans la réponse immune des LT CD8+ a été démontré. Nos résultats démontrent que suite à une infection avec Lm ou à une immunisation avec des CD, la signalisation Notch favorise le développement de LTe, exprimant fortement KLRG1 et faiblement CD127, destinés à mourir par apoptose. Toutefois, la signalisation Notch n’a pas influencé la génération de LTm. De façon très intéressante, l’expression des récepteurs Notch influence la production d’IFN- en fonction du contexte d’activation. En effet, suite à une infection avec Lm, l’absence des récepteurs Notch n’affecte pas la production d’IFN- par les LTe, alors qu’elle est diminuée suite à une immunisation avec des CD suggérant un rôle dépendant du contexte pour la voie de signalisation Notch.
Nos résultats permettent une meilleure compréhension des signaux fournis par les différentes CPA et de la voie de signalisation Notch, donc des mécanismes moléculaires régulant la différenciation des LT CD8+ lors de la réponse immunitaire, ce qui pourrait ultimement permettre d’améliorer les stratégies de vaccination.Following an infection with a pathogen, antigen-specific naive CD8+ T lymphocytes (Tn) will proliferate and differentiate into effector (Te) cells. Those Te cells will produce different cytokines and acquire a cytotoxic activity, leading to pathogen clearance. Only 5 to 10 % of Te cells will survive and differentiate into memory CD8+ T lymphocytes (Tm) able to respond rapidly following a second encounter with the same pathogen, contributing to the success of vaccination. However, the mechanisms regulating Te and Tm cells development remain incompletely understood. To better understand the signals required for CD8+ T lymphocytes during an immune response, we proposed two hypotheses. First, we propose that different antigen presenting cells (APCs) can deliver different signals to CD8+ T lymphocytes at the time of priming leading to different outcome. Given their potential for use in immunotherapy, we compared the ability of CD40 activated B lymphocytes (CD40-B) and dendritic cells (DCs) to activate CD8+ T lymphocytes. We have shown that CD40-B cell immunisation leads to an effector response but very few Tm cells are generated compared to DC immunisation. The Te cells generated following CD40-B cell immunisation are functional because they secrete cytokine, are cytotoxic and control a Listeria monocytogenes (Lm) infection. We propose that CD40-B cells secrete less cytokines and interact during shorter period of time with the CD8+ T lymphocytes, without engulfment, contributing to the decreased Tm generation observed following immunisation with CD40-B cells. Second, among the signals provided by APC at the time of CD8+ T lymphocyte priming, we have hypothesised that the Notch signalling pathway influences Te and Tm cell differentiation by inducing a particular genetic program. Using an in vitro system, we first studied the role of the Notch signalling pathway in the hours following CD8+ T lymphocyte priming. We demonstrated that Notch signalling directly regulates PD-1 expression. Then, studying mice where Notch1 and Notch2 receptor genes are deleted only in mature CD8+ T lymphocytes, we characterised the role of the Notch signalling pathway on Te and Tm differentiation during an immune response. Our results show that following Lm infection or a DC immunisation, the Notch signalling pathway promotes the differentiation of short lived effector cells Te cells (KLRG1highCD127low) meant to die by apoptosis. However, the Notch signalling pathway did not influence the generation of CD8+ Tm cells. Most interestingly, IFN- regulation by the Notch signalling pathway depends on the activation context. Indeed, following Lm infection, lack of Notch receptors does not impact IFN- secretion by Te cells while it is significantly decreased following a DC immunisation suggesting a context dependant role for the Notch signalling pathway. Our findings provide a better understanding of the key signals provided by APC as well as the Notch signalling pathway, and thus the molecular mechanisms leading to CD8+ lymphocyte effector and memory generation which is crucial as this knowledge may ultimately lead to improved vaccination.