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Stephan, Heike Isabell [Verfasser], Ellen [Akademischer Betreuer] Niederberger, and Bernhard [Akademischer Betreuer] Brüne. "Untersuchungen zur Rolle der TANK-Binding Kinase (TBK) 1 bei entzündlichen Schmerzreaktionen / Heike Isabell Stephan. Gutachter: Ellen Niederberger ; Bernhard Brüne." Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2015. http://d-nb.info/1070911038/34.
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Stephan, Heike [Verfasser], Ellen [Akademischer Betreuer] Niederberger, and Bernhard [Akademischer Betreuer] Brüne. "Untersuchungen zur Rolle der TANK-Binding Kinase (TBK) 1 bei entzündlichen Schmerzreaktionen / Heike Isabell Stephan. Gutachter: Ellen Niederberger ; Bernhard Brüne." Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2015. http://d-nb.info/1070911038/34.
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Harris, Jennifer. "Regulation of nuclear factor kappa B subunit c-Rel through phosphorylation by two IKK-related kinases, IKK epsilon and TBK-1." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82250.
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The nuclear factor kappaB (NF-kappaB) transcription factors are key regulators of immunomodulatory genes regulation. NF-kappaB activity is regulated through the phosphorylation of inhibitory proteins (IkappaBs) by the IkappaB kinase (IKK) complex (IKK alpha/beta/gamma), leading to IkappaB degradation and NF-kappaB translocation to the nucleus where they promote transcription of immunoregulatory genes. Moreover, cRel and p65 activities are also regulated by direct phosphorylation of their transactivation domain. Recently, two IKK non-canonical homologues, IKKepsilon and TBK-1 (TANK binding kinase-1) have been identified with functions distinct from the classical IKKalpha/IKKbeta. TBK-1/IKKepsilon trigger antiviral immunity through direct phosphorylation of the IRF3/IRF7 transcription factors, which are key regulators of the interferon response. Since IKKepsilon modulates the activity of IRF3/IRF7, it is of interest to assess whether IKKepsilon/TBK-1 also regulates the transactivation activity of NF-kappaB. Our hypothesis was that IKKepsilon/TBK-1 modulates the activity of cRel by direct phosphorylation of its transactivation domain (TD). In this study, we demonstrate that IKKepsilon and TBK-1 directly phosphorylate cRel in vitro and in vivo. Two of the three consensus sequences recognized by IKKepsilon/TBK-1 in the cRel TD are directly phosphorylated by IKKepsilon. cRel was translocated to the nucleus in cells expressing wild type versus kinase dead variant. The expression of IKKepsilon increases c-Rel transactivation in reporter gene assays. Serine to alanine mutation was further used to characterize the function of this phosphorylation at the level of nuclear translocation and transactivation potential using immunofluorescence and reporter gene assay. Furthermore, co-expression studies revealed that IKKepsilon and not the kinase dead variant is responsible for cRel degradation in a dose-dependent manner and this effect is partially revert
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Lack, Jeremy David. "The solution structure and surface properties of TB3 of LTBP-1." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249190.
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Elizondo, Juan Iraburu. "Medição de Densidade no Tokamak TBR-1 por Rotação de Faraday." Universidade de São Paulo, 1996. http://www.teses.usp.br/teses/disponiveis/43/43131/tde-02072013-115509/.
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Neste trabalho, são apresentados os resultados experimentais de medições de densidade eletrônica no tokamak TBR-l, obtidas por meio de rotação de Faraday num feixe de micro-ondas. O feixe (65 GHz, 500 m W) é gerado por uma klystron e atravessa o plasma no plano médio horizontal. Os valores obtidos para a densidade concordam bem com as medições feitas com um interferômetro de micro-onda o; convencional. A partir das simulações numéricas e das medições, conclui-se ser recomendável o uso de comprimentos de onda menores, para minimizar a refração do feixe no plasma, Os resultados obtidos demonstram a viabilidade do método de medição de densidade por rotação de Faraday. em experiência feita pela primeira vez em tokamak, para a geometria considerada.In this work, the experimental results of electronic density measurements in the TBR-l tokamak, obtained by Faraday rotation of a microwave beam, are presented. The beam (65 GHz, 500 mW) is generated by a klystron and crosses the plasma in the horizontal plane. The density values obtained are in agreement with the measurements of a conventional microwave interferometer. As a result of numerical simulations and measurements, it can be concluded that it would be advisable the use of lower wavelengths, to minimize the beam refraction when it crosses the plasma. The results show the feasability of the Faraday rotation method for density measurement, in the first experiment performed in a tokamak for the geometry considered.
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Littlejohn, Erica Latrice. "INSULIN-LIKE GROWTH FACTOR-1 OVEREXPRESSION MEDIATES HIPPOCAMPAL REMODELING AND PLASTICITY FOLLOWING TBI." UKnowledge, 2018. https://uknowledge.uky.edu/physiology_etds/39.
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Every year over 2.5 million traumatic brain injuries (TBI) occur and are the leading cause of death and disability among adolescents. There are no approved treatments for TBI. Survivors suffer from persistent cognitive impairment due to posttraumatic tissue damage and disruption of neural networks which significantly detract from their quality of life. Posttraumatic cognitive impairment depends in part on the brain's limited ability to repair or replace damaged cells. Immature neurons in the hippocampus dentate gyrus, a brain region required for learning and memory, are particularly vulnerable to TBI. Insulin-like growth factor-1 (IGF1) is a potential therapeutic for TBI because it is a potent neurotrophic factor capable of mediating neuroprotection, neuro-repair, and neurogenesis. We hypothesized that conditional IGF1 overexpression in the mouse hippocampus following experimental controlled cortical impact injury (CCI) would enhance posttraumatic neurogenesis chronically. To this end, conditional astrocyte-specific IGF1 overexpressing mice (IGFtg) and wild-type (WT) mice received CCI or sham injury. The proliferation marker BrdU was used to label neurons born the first week after injury. Six weeks after injury, when surviving posttrauma-born neurons would be fully developed, we counted proliferated cells (BrdU+) and the subset expressing a mature neuronal marker (NeuN+/BrdU+) in the hippocampus. We also assessed cognitive performance during radial arm water-maze reversal (RAWM-R) testing, a neurogenesis-sensitive assay. IGF1 promoted end-stage maturity and decreased mis-migration of neurons born after trauma. These effects coincide with IGF1 induced improvements in performance on neurogenesis sensitive cognition following TBI.
Mammalian target of rapamycin (mTOR), an early signaling molecule downstream of IGF1, has been identified as a potential target for TBI interventions because of its regulatory role in neuronal plasticity and neurogenesis. However, recent studies have also reported maladaptive plasticity and recovery associated with posttraumatic mTOR activation. It is imperative to elucidate the mechanism of action of IGF1 during pre-clinical evaluations. We hypothesized that IGF1 mediates posttraumatic neurogenic effects through IGF1 induction of mTOR activation. We injured cohorts of IGFtg and WT mice and harvested their brains for immunohistochemistry to assess IGF1 overexpression effects on posttraumatic mTOR activation at 1, 3, and 10 days post-injury (dpi). We found that IGF1 upregulated mTOR activation following TBI in a region-specific manner at 1 and 3dpi. To determine if IGF1 regulated differentiation and arborization through the mTOR pathway, injured WT and IGFtg mice received daily i.p. injections of rapamycin (10mg/kg), the inhibitor of mTOR, or its vehicle for 7 days. Vehicle and rapamycin administration began 3dpi, after the cells dividing at the peak of posttraumatic proliferation were labeled with BrdU. IGF1 enhancement of posttraumatic neurogenesis was not dependent on mTOR activation.
In summary, IGF1 directs newborn neuron localization, promotes end-stage maturation, and chronically improves cognition. IGF1 can stimulate posttraumatic neurogenesis and plasticity independent of mTOR activation. These data suggest that IGF1 can stimulate neuron replacement following trauma-induced hippocampal neuron loss and cognitive improvement. Further studies should investigate IGF1 and mTOR inhibition as a combination therapy for neurorehabilitation.
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Russell, Nicholas H. "Heme Oxygenase 1 expression after traumatic brain injury and effect of pharmacological manipulation on functional recovery." VCU Scholars Compass, 2017. https://scholarscompass.vcu.edu/etd/5525.
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Traumatic Brain Injury (TBI) is an increasingly diagnosed constellation of injuries derived from acute mechanical trauma to the brain. With the rise of advanced neuroimaging techniques recent focus has oriented primarily towards the mild-moderate range of TBI which previously was missed diagnostically. Characteristically, these advances have shown increasing areas of micro-hemorrhage in susceptible areas of the brain and to date there are no treatment modalities targeting micro-hemorrhages or their sequelae. This dissertation explores the effects of the resulting heme processing response in the days following injury with a particular focus on inducing early heme clearance from the parenchyma using a rat central fluid percussion injury model in the mild-moderate injury range. Since heme is released ~24-48 hours post-injury and is known to be cytotoxic we observed there may be a critical window for treatment to clear heme before it is spontaneously released and to increase the buffering capacity of the tissue. We targeted heme clearance by using drugs known to increased expression of Nrf2, an upstream transcriptional regulator of the canonical heme processing protein heme oxygenase 1 (HO-1), and tracking expression of HO-1, the iron sequestration/storage proteins Lipocalin 2 (LCN2) and Ferritin (FTL), as well as the activity of matrix metalloproteinases 2 and 9 (MMP2, MMP9). We examined both tissue known to be frankly hemorrhagic (the neocortex) as well as tissue lacking any identifiable bleed (the hippocampus). We demonstrated that using the HO-1 inducers Hemin and Sulforaphane in a single dose paradigm given 1 hour post-injury heme clearance was accelerated in the neocortex with the majority of heme pigment processed by 24 hours post-injury. Further there was significant attenuation of protein expression in HO-1 and ferritin as well as the enzyme activity of MMP2 and MMP9 in both the neocortex and the hippocampus. Behavioral attenuation was also seen in both rotarod and Morris water maze tests. While we intended to target hemorrhagic processing after injury, and indeed demonstrated improved clearance of heme from post-injury hemorrhagic regions of the brain, in both tissues studied we observed remarkably similar responses to the drugs utilized in protein expression, enzyme activity, and behavioral improvement which may suggest a globally improved pathologic state or that there are unidentified pathologic micro-hemorrhages or leaky vessels which extend further into the brain parenchyma than currently identified.
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Yuan, Xuemei. "NMR studies of a TB module from human fibrillin-1." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298231.
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Silva, Ruy Pepe da. "Transporte de partículas e energia no plasma do tokamak TBR-1: diagnósticos e estudo experimental." Universidade de São Paulo, 1989. http://www.teses.usp.br/teses/disponiveis/43/43131/tde-16122013-153129/.
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Os estudos sobre o plasma na região da borda de máquinas tokamak têm se intensificado nos últimos anos em decorrência da constatação de que o comportamento do plasma na região central da máquina é bastante influenciado por processos que ocorrem na borda da coluna. Neste trabalho feito um estudo experimental das propriedades de transporte do plasma na região da sombra do limitador do TBR-l, um tokamak de pequeno porte em operação no Instituto de Física da Universidade de São Paulo. São também determinados os tempos de confinamento globais de partículas e energia. Três foram os diagnósticos usados neste trabalho. Inicialmente, é abordada a utilização de sondas de Langmuir para a obtenção de perfis radiais e temporais da temperatura de elétrons, densidade e potencial de plasma; descreve-se também o arranjo experimental usado para este diagnóstico. A seguir, discute-se o projeto e a construção de uma sonda sensível a íons associada a um sistema eletrônico que permitiu a determinação simultânea das temperaturas locais de íons e elétrons. Finalmente, é discutido o dimensionamento e a implantação de um interferômetro de microondas para medidas de densidade de elétrons na região central da coluna de plasma do TBR-1; o sistema opera em 65 GHz e toda a eletrônica associada foi projetada e construída em nosso Laboratório. Os resultados obtidos com as sondas foram analisados com o ajuda de um modelo não colisional de transporte de partículas e energia para a região da sombra do limitador de máquinas tokamak. A partir dos decaimentos radiais da termperatura de elétrons (\'lâmbda IND. e\' \'APROXIMADAMENTE IGUAL A\' 2,6cm) e da densidade (\'lâmbda IND. n\' \'APROXIMADAMENTE IGUAL A\' 1,4cm), bem como do fator de transmissão de energia para os elétrons (\'delta IND. e\' \'APROXIMADAMENTE IGUAL A\' 4), determinou-se o coeficiente de difusão perpendicular ao campo magnético (\'D IND. 1\' \'APROXIMADAMENTE IGUAL A\' 6 \'m POT. 2\'\'s POT. -1\') e a difusividade térmica dos elétrons (\'qui POT. e IND. 1\' \'APROXIMADAMENTE IGUAL A\' 8 \'m POT. 2\'\'s POT. -1\'), resultados que indicam valores próximos aos previstos pelo modelo de Bohm. As medidas das temperaturas de íons e elétrons mostram um claro desacoplamento térmico entre íons e elétrons (\'T IND. i\'/\'T IND. e\' \'APROXIMADAMENTE IGUAL A\' 2). As medidas de densidade obtidas no centro da coluna, em conjunto com as obtidas na borda, permitiram a determinação dos tempos de confinamento globais de partículas (\'tau IND. p\'\'APROXIMADAMENTE IGUAL A\' 1,8 x \'10 POT. -3\'s) e de energia (\'tau IND. E\'\'APROXIMADAMENTE IGUAL A\' 1,2 x \'10 POT. -4\'s). Os resultados foram comparados com os previstos por várias leis de escala.The study of the plasma edge in Tokamak machines has increased in recent last years, since the recognition that the behavior of the plasma core is influenced by the Physical processes that occur in the edge region. This work develops an experimental stud) of plasma transport properties in the shadow region of TBR-l limiter. TBR-l is a small Tokamak in operation in the Physics Institute of São Paulo University. We have also determined the global confinement time of particles and energy. We have used three diagnostics: a Langmuir probe, an ion sensitive probe, and a microwave interferometer. Initially we discuss the use of Langmuir probes in Tokamak machines to obtain temporal and radial profiles of electron temperature, plasma density and potential; we show also the experimental arrangement used in the TBR-l for this diagnostic. Then, we discuss the design and construction of an ion sensitive probe associated with an electronic system, that was used to obtain, simultaneously, local ion and electron temperature. Finally we discuss a microwave interferometry system that has been built for the TBR-1. The microwave generator is a reflex Klystron (f = 65 GHz), and with the interferometer we obtained electron density time profiles of the center of TBR-l plasma column. All the electronics associated with the interferometer were designed and built in our laboratory. The results obtained with the probes are discussed with the help of a collisionless model for Tokamak scrape-off plasma. With the radial e-foldings of electron temperature (e 2.6 cm) and density (n 1.4 cm), and the sheath electron transmission coefficient (e 4) we have determined the cross-field diffusion coefficient (D1 6 m2s-1) and the electron cross-field thermal diffusivity (e1 8 m2s-1). These results indicate values near those predicted by the Bohm model. The measurements of electron and ion temperature shows a clear thermal decoupling between ions and electrons (T1/Te 2). The measurements of plasma parameters in the center of the plasma column, with that obtained with the probes permitted the determination of the particle (p 1.8 x 10-3s) and energy (e 1.2 x10-4s) global confinement times. These results were compared with those predicted by scaling laws.
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Neto, Ibrahim El Chamaa. "Estudo do Funcionamento do Tokamak TBR-1 sob a Influência de Perturbações Elétricas e Magnéticas." Universidade de São Paulo, 1998. http://www.teses.usp.br/teses/disponiveis/43/43131/tde-27022014-144055/.
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Neste trabalho foram realizados estudos experimentais de operação do tokamak TBR-I sob condições extremas de densidade e de campo magnético toroidal e, também, sob a influência de perturbações elétricas radiais e magnéticas helicoidais aplicadas na região periférica da coluna de plasma. Realizou-se, também, uma análise preliminar das características das descargas na região da corrente de plasma com predominância de elétrons fugitivos. Para isso foi utilizada a maioria dos diagnósticos já construídos no Laboratório de Física de Plasmas da USP, que são: diagnóstico por sondas eletrostáticas, bobinas de Mirnov, espectroscopia óptica, interferômetro de micro ondas, detector de raios-X duros, detector de H, bobinas de Rogowski, bobinas de posição, espiras das tensões de enlace e medição da pressão com \"ion-gauges\" e analisador de gás residual. Os resultados permitiram obter uma lei de escala para as descargas do TBR-1 associando a densidade média de partículas com a densidade média de corrente de plasma. Foram observados efeitos muito interessantes nas oscilações magnéticas do plasma sob ação dos campos perturbativos. Em particular, para os campos elétricos radiais com polarização negativa, observou-se uma diminuição considerável das frequências dessas oscilações e uma atenuação nas amplitudes das mesmas, segundo uma análise de Fourier. Ao contrário, para polarizações positivas, foi observado um plasma mais turbulento. Este resultado repetiu-se (porém não tão acentuado como descrito no caso anterior) quando foi aplicada uma perturbação magnética helicoidal simultaneamente com o campo elétrico radial. Finalmente, as descargas do TBR-1 são caracterizadas pela baixa densidade de elétrons n IND.e 10 POT.12 cm POT.-3 e alta corrente de elétrons fugitivos (I I IND.P). O parâmetro de Shafranov foi calculado a partir das medidas do campo magnético vertical e do deslocamento do centro da coluna de plasma. A diferença de A nos cálculos é explicada pelo deslocamento da órbita do feixe de elétrons fugitivos.In this work, experimental studies of operation limits of the TBR-l tokamak were accomplished under extreme conditions of density and toroidal magnetic field, a1so, under the influences of helical magnetic field and radial electric field perturbations, applied in the border zone of the plasma column. Also, a preliminary analysis of the charactetistics of the runaway discharges was performed. For measurements of the plasma charactetistics most of the diagnostics built in the USP Laboratório de Física de Plasmas, were used: electrostatic probes, Mirnov coils, optical spectroscopy, micro wave interferometer, hard X-rays detector, H detector, Rogowski coils, position sensors, loop voltage, pressure measurements with ion-gauges and a residual gas analyzer. From the result, the scaling law for the discharges of the TBR-l were obtained, associating the average densities of particles with average plasma current densities. Very interesting effects were observed in the magnetic oscillations of the plasma under the action of the perturbation fields. In particular, for the radial electric fields with negative polarization a considerable decrease in the frequency and an attenuation in the amplitude of the MHD oscillations were observed, according to a Fourier analysis. On the contrary, for positive polarization a more turbulent plasma was observed. Similar results, but not so strong, were obtained when a helical magnetic perturbation was applied simultaneously with the radial electric field. Finally, runaway discharges in the TBR-l were investigated and the current was found to be predominantly dominated by e1ectron beams. The Shafranov parameter A was calculated from the vertical field as well as from the plasma center displacement and found to be different, which can he explained by the orbit shifted runaway beams.
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Owraghi, Melissa. "Functions of TBX-35, CEH-51, and TCF/POP-1 in mesoderm specification in Caenorhabditis elegans." Diss., [Riverside, Calif.] : University of California, Riverside, 2010. http://proquest.umi.com/pqdweb?index=0&did=2019822751&SrchMode=2&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1274113144&clientId=48051.
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Thesis (Ph. D.)--University of California, Riverside, 2010.Includes abstract. Available via ProQuest Digital Dissertations. Title from first page of PDF file (viewed May 17, 2010). Includes bibliographical references. Also issued in print.
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Neto, Ibrahim El Chamaa. "IMPLANTACAO DE UM SISTEMA DE DIAGNOSTICOS POR ESPECTROSCOPIA E MEDIDA DE TEMPERATURA IONICA NO TBR-1." Universidade de São Paulo, 1992. http://www.teses.usp.br/teses/disponiveis/43/43131/tde-11052015-152545/.
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Um sistema de diagnóstico por espectroscopia no visível foi implantado no tokamak TBR-I. O diagnóstico consiste de um espectrógrafo (do tipo Czerny-Turner), um sistema de acoplamento óptico e um detetor multicanal (MCP). O diagnóstico foi usado para observar e identificar impurezas presentes no plasma do TBR-I. As principais impurezas observadas foram oxigênio (O-II) e nitrogênio (N-II). Foi feito um estudo no alargamento das linhas do hidrogênio e dos íons para se obter a temperatura a partir do efeito Doppler. As intensidades das linhas espectrais foram observadas de descarga em descarga.A visible spectroscopic diagnostic was implemented on TBR-I tokamak. The diagnostic system consist of a 1,5 m spectrograph (Czerny-Turner type), an optical coupling system and a microchannel plate (MCP) detector. The diagnostic system was used to examine and document the impurity content of the plasma in TBR-I. The main impurities discovered were oxygen (O-II) and nitrogen (N-II). Line broadening experiments were performed on hydrogen and ions to obtain the temperatures using Doppler broadening effects. The intensities of the spectral lines were measured on a shot to shot basis.
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Cortez, Escalante Juan José. "Modelo prognóstico de desenvolvimento de TB ativa nos pacientes com HIV/Aids." reponame:Repositório Institucional da UnB, 2008. http://repositorio.unb.br/handle/10482/1301.
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Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 2008.Submitted by Jaqueline Oliveira (jaqueoliveiram@gmail.com) on 2008-12-11T18:15:49Z No. of bitstreams: 1 TESE_2008_JuanJCEscalante.pdf: 4789546 bytes, checksum: 592c90d5f7b6e9da19c34782bde221bf (MD5)
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Antecedentes: a tuberculose (TB) tem causado importante morbidade e mortalidade durante séculos. Embora a incidência e letalidade diminuíram marcadamente no decurso do século XX, o surgimento da infecção pelo vírus da imunodeficiência humana (HIV) no final desse século mudou significativamente estas tendências. Objetivo: identificar características associadas à TB ativa nos pacientes com HIV/Aids, atendidos nos estabelecimentos de saúde especializados do Distrito Federal e desenhar um escore clínico‐epidemiológico para fins de predição. Método: Foi realizado um estudo de caso – controle em pacientes com 18 anos ou mais com diagnóstico de HIV/Aids, comparando os que desenvolveram TB ativa com os que não desenvolveram a doença entre os anos 2000 a 2004. Os pacientes foram identificados nas bases de dados da Secretaria de Saúde do Distrito Federal (DF), isto é no Sistema de Informação de Agravos de Notificação (SINAN) de TB e Aids, de HIV e do Sistema de Informações sobre Mortalidade (SIM), complementada com os dados dos laboratórios de TB e HIV do LACEN – DF. A identificação dos fatores de risco foi realizada utilizando regressão logística para análises uni e multivariada. Com esses fatores se desenvolveu um modelo de predição de TB ativa nos pacientes com HIV/Aids. O modelo foi avaliado no mesmo grupo de pacientes que o gerou, mediante análise de sensibilidade, especificidade, valores preditivos positivos e negativos, razões de verossimilhança, acurácia, curva ROC e a área sob esta curva, assim como o cálculo de probabilidade pós‐teste. Resultados: foram identificados 222 pacientes co‐infectados, dos quais, 206 apresentaram critérios de seleção adequados. Desses, 64 foram identificados como óbitos e 51 não foram encontrados. Foram incluídos na investigação 91 casos e 91 controles. A prevalência estimada de TB nos pacientes com HIV/Aids em 2000 e 2004 foi 0,55 e 0,43%, respectivamente. Na população geral, a prevalência da co‐infecção foi 2,62 casos por 100.000 habitantes. Dentre as características associadas à TB, sete permaneceram significativas após a análise multivariada: ter menos de 8 anos de estudos completos (OR ‐ ajustado = 4,6; IC 95% = 1,5 a 13,8), renda mensal menor que R$ 600,00 (US$ 300,00) (OR ‐ ajustado = 4,8; IC 95% = 1,5 a 14,8), mais de uma família morando no domicílio (OR ‐ ajustado = 48,7; IC 95% = 3,5 a 672,3), existência de doente com TB na família (OR ‐ ajustado = 13,6; IC 95% = 2,4 a 78,3), ter apresentado toxoplasmose cerebral nos últimos dois anos (OR ‐ ajustado = 7,2; IC 95% = 1,5 a 33,8), linfócitos T CD4+ inferior a 200 células/ μl no mesmo período (OR ‐ ajustado = 6,5; IC 95% = 2,1 a 20,1) e o não uso de um mesmo esquema HAART nos últimos 6 meses (OR ‐ ajustado = 27,2; IC 95% = 7,8 a 95,1). Estas sete características constituíram o modelo de predição recebendo escores de 1, 1, 3, 2, 1, 1 e 2, respectivamente. Na avaliação do modelo encontrou‐se 100% de sensibilidade quando o ponto de corte foi zero, 100% de especificidade quando foi igual ou maior que seis pontos, a maior razão de verossimilhança positiva (69) com seis pontos e a maior acurácia (90,1%) com quatro pontos. Com a prevalência de TB nos pacientes com HIV/Aids de 0,43% a maior probabilidade pós‐teste (23%) foi obtida com o ponto de corte 6. Conclusão: foi possível identificar características associadas à TB nos pacientes com HIV/Aids, que definem a co‐infecção no Distrito Federal e com estas características foi desenvolvido um modelo de predição clínica. _______________________________________________________________________________________ ABSTRACT
Antecedents: Tuberculosis (TB) has been causing important morbidity and mortality for centuries. Although, incidence and case fatality rates decreased remarkably in 20th century, the emergence of human immunodeficiency virus infection (HIV) at the end of that century changed these tendencies, significantly. Objectives: to identify active TB prognostic factors in HIV/AIDS patients looked after by specialized health‐care services in Brazilian Federal District (DF) and to develop a clinicalepidemiologic score. Method: a case‐control study were conducted in HIV/AIDS adult patients (> 18 years‐old) with active TB co‐infection, developed among 2000 to 2004, and the ones without active TB. The patients' identification took place in the databases of Federal District Health Department; they were: TB and AIDS Information System on Notification Diseases (SINAN‐TB and SINANAIDS), HIV database and Mortality Information System (SIM); it was complemented with TB and AIDS laboratories data of LACEN ‐ DF. Univariate and multivariate logistic regression were performed to indentify risk factors and to develop a prediction model of active TB in HIV/AIDS patients. Training group was used as the validation group. Results of the validation procedure were described by sensitivity, specificity, the positive and negative predictive value, the likelihood ratio, accuracy, the area under the receiver operating characteristic (ROC) curve and pos‐test probability. Results: Two hundred six co‐infected patients were identified with all the selection approaches. From this group of patients, 64 were died and 51 were not found. Therefore, 91 cases were included in this study, together with 91 controls. The estimated prevalence of TB in HIV/AIDS patients in 2000 and 2004 was 0.55% and 0.43%, respectively. In the general population, the prevalence of co‐infection was 2.62 cases for 100000 inhabitants. Seven characteristics were associated to active TB: a) less than 8 years of schooling (adjusted OR = 4.6; 95% CI = 1.5 to 13.8), monthly income less than R$ 600.00 (US$ 300.00) (adjusted OR = 4.8; 95% CI = 1.5 to 14.8), household with more than one family (adjusted OR = 48.7; 95% CI = 3.5 to 672.3), any relative with TB (adjusted OR = 13.6; 95% CI = 2.4 to 78.3), cerebral toxoplasmosis in the last two years (adjusted OR = 7.2; 95% CI = 1.5 to 33.8), lymphocytes T CD4+ count lower than 200 cells/μl in the last two years (adjusted OR = 6.5; 95% CI = 2.1 to 20.1) and non‐use the same HAART regimen in the last 6 months (adjusted OR = 27.2; 95% CI = 7.8 to 95.1). The prediction model was developed with these features with the following scores: 1, 1, 3, 2, 1, 1 and 2, respectively. In the evaluation model, sensibility was 100% (cutoff point = 0), specificity 100% (cut‐off point > 6), the higher positive likelihood ratio of 69 (cut‐off point = 6) and the higher accuracy of 90.1% (cut‐off point = 4). The higher pos‐test probability was 23% (cut‐off point = 6), it was estimated from 0.43% of TB prevalence in HIV/AIDS. Conclusion: It was possible to identify prognostic factors of TB in HIV/AIDS patients in the Federal District and to develop a clinical prediction model.
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Conceição, Elisabete Lopes. "Avaliação de fatores genéticos e imunológicos relacionados à imunopatogênese da tuberculose e co-infecção tb-hiv." INSTITUTO DE CIÊNCIAS DA SAÚDE, 2016. http://repositorio.ufba.br/ri/handle/ri/23264.
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Capes
O Mycobacterium tuberculosis e o vírus da imunodeficiência humana (HIV) agem em sinergia prejudicando a resposta imune para eliminação de ambos os patógenos. Fatores genéticos dos hospedeiros podem ser determinantes para o risco de progressão da tuberculose (TB) e infecção pelo HIV. Algumas variações genéticas têm sido associadas a diferenças no potencial para indução de apoptose e a alterações na produção de citocinas, tais como os polimorfismos de base única (SNPs) TNF-308G>A, DDX39B -22 G>C e -348C>T. Outra característica que acompanha a evolução da infecção é o estresse oxidativo sistêmico e o aumento da peroxidação. A Heme oxigenase-1 (HO-1) é o principal agente anti-oxidante expresso no tecido pulmonar, uma enzima de resposta ao estresse que degrada moléculas heme para a liberação de íons ferro, monóxido de carbono (CO) e biliverdina (BV). O presente trabalho propôs investigar fatores genéticos e imunológicos relacionados à imunopatogênese da TB e co-infecção TB-HIV. Para a realização do trabalho foram realizados: 1) uma revisão sistemática da literatura sobre os polimorfismos genéticos envolvidos nas vias e morte e associados com TB, 2) um estudo observacional de corte transversal para determinar a frequência de polimorfismos em voluntários monoinfectados com TB latente ou ativa e coinfectados com TB-HIV. Para este último foram recrutados 109 pacientes com tuberculose pulmonar (PTB), 60 pacientes coinfectados com HIV (TB-HIV) e 74 indivíduos com infecção tuberculosa latente (LTBI), e 3) Uma coorte avaliando os níveis de HO-1 e MMP-1 em pacientes com TB. Na revisão sistemática os polimorfismos dos genes do TNF, TNFR, IL-1 e P2RX7 estavam associados com tuberculose. No estudo de corte transversal a frequência do genótipo TNF-308G foi maior para o grupo LTBI comparado com TB e TB-HIV. A produção de TNF foi maior 8 entre os pacientes com PTB portadores do genótipo TNF -308GG. Os níveis de IL- 1α e IL-1β também foram mais elevados entre os pacientes com PTB portadores dos genótipos DDX39B -22CC e DDX39B -348CC. Não houve relação entre a produção de citocinas e a extensão da doença. Na coorte, os pacientes com TB apresentaram uma dicotomia na resposta de HO-1 MMP-1 com dois fenótipos, HO-1hiMMP-1lo e MMP-1 HO-1loMMP-1hi. Nosso estudo sugere que polimorfismos envolvidos na via de morte podem estar associados com susceptibilidade para o desenvolvimento da tuberculose, contudo, a frequência dos alelos e genótipos para os polimorfismos estudados não diferiram na co-infecção pelo HIV. O mecanismo entre o estresse oxidativo e remodelamento do tecido pode ter aplicabilidade clínica nos estágios da progressão da TB.
Mycobacterium tuberculosis and human immunodeficiency virus (HIV) act synergistically damaging immune response to eliminate both pathogens. Genetic factors of the host can be decisive for the risk of progression of tuberculosis (TB) and HIV infection. Some genetic changes have been associated with differences in potential for induction of apoptosis and changes in cytokine production such as single nucleotide polymorphisms (SNPs) TNF-308G> A, DDX39B -22 G> C and -348C> T. Another feature that monitors the infection is systemic oxidative stress and increased peroxidation. The heme oxygenase-1 (HO-1) is the primary anti-oxidant expressed in lung tissue, a response of the enzyme to stress that degrades heme molecules to the release of iron ions, carbon monoxide (CO), and biliverdin (BV) . This study proposed to investigate genetic and immunological factors related to TB immunopathogenesis and co-infection TB-HIV. To carry out the work were performed: 1) a systematic review of the literature on genetic polymorphisms involved in the pathways and death associated with TB, 2) an observational cross-sectional study to determine the frequency of polymorphisms in volunteers monoinfected with latent TB or active and co-infected with TB-HIV. For the latter were recruited 109 patients with pulmonary TB (PTB), 60 patients co-infected with HIV (HIV-TB) and 74 individuals with latent tuberculosis infection (LTBI), and 3) a cohort evaluating the levels of HO-1 and MMP- 1 in patients with TB. In the systematic review of TNF polymorphisms of genes, TNFR, IL-1 and P2RX7 were associated with tuberculosis. In the cross-sectional study the frequency of TNF-308G genotype was higher for LTBI group compared with TB and TB-HIV. The production of TNF was higher among patients with PTB patients TNF -308GG genotype. IL-1α and IL-1β were also higher among patients 10 with genotypes of PTB patients DDX39B -22CC and DDX39B -348CC. No relation between the production of cytokines and the extent of disease. In cohort, patients with TB presented a dichotomy in HO-1 MMP-1 response with two phenotypes, HO- 1hiMMP-1lo HO-1 and MMP-1loMMP-1hi. Our study suggests that polymorphisms involved in the death pathway may be associated with susceptibility to the development of tuberculosis, however, the frequency of alleles and genotypes for the studied polymorphisms did not differ in co-infection with HIV. The mechanism of oxidative stress and remodeling of the tissue may have clinical applicability in the progression of TB staging.
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Herman, Melina. "Uncovering novel genetic etiologies of childhood herpes simplex encephalitis : hypothesis-based candidate gene approach." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00831293.
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L'encéphalite herpétique (EH), causée par l'herpès simplex virus-1 (HSV-1), peut résulter de défauts monogéniques de l'immunité médiée par TLR3. L'induction d'interférons (IFNs)-α/β ou -λ via TLR3 est cruciale à la protection après infection primaire avec HSV-1 dans le système nerveux central (SNC). Nous décrivons deux enfants avec l'EH portant différentes mutations hétérozygotes (D50A et G159A) dans TBK1, encodant TANK-Binding Kinase 1, une kinase aux carrefours de multiples voies de signalisation induisant des IFNs. Les deux allèles mutants de TBK1 sont perte-de-fonction par des mécanismes différents: instabilité de la protéine (D50A) ou perte d'activité kinase (G159A). Ces allèles sont associés à un trait autosomal dominant (AD) par des mécanismes différents: haplotype-insuffisance (D50A) ou dominance négative (G159A). Un défaut de réponses à poly(I:C) par TLR3 est observable dans les fibroblastes hétérozygotes pour G159A, et non pour D50A TBK1. Néanmoins, la réplication virale et la mortalité cellulaire après infection par deux virus dépendants de TLR3 (HSV-1 et VSV) étaient élevées dans les fibroblastes des deux patients. Ces phénotypes peuvent être sauvés par IFN-α2b. De plus, la production d'IFNs en réponse à des agonistes et virus indépendants de TLR3 est maintenue dans les PBMCs et fibroblastes des patients. Le phénotype cellulaire restreint, partiel représente ainsi le phénotype clinique de ces patients, limité à l'EH. Ces données identifient la déficience partielle AD de TBK1 comme une nouvelle étiologie génétique de l'EH de l'enfance, et indiquent que TBK1 est essentiel pour le contrôle de HSV-1 dans le SNC, médié par TLR3 et dépendant des IFNs
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Carling, Carl. "Sjukgymnastikbehandling av patienter med nacksmärta efter klassificering i subgrupper enligt Treatment Based Classification, TBC. : Tre kvasi-experimentella fallstudier med AB-design och 1-månadsuppföljning." Thesis, Uppsala universitet, Fysioterapi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-314855.
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Objective: In three kvasi-experimental single-case studies regarding patients with neck-pain who after sub-grouping using Treatment Based Classification (TBC), were placed in the subgroups centralization or mobilization, describe how and why they were placed in that particular subgroup and then to evaluate the effects on function and pain of the specific treatment proposed for that subgroup. Method: The process of sub-grouping is described. Function and pain were measured with the Neck Disability Index (NDI) and Numeric Pain Rating Scale 0-10 (NPRS) before, during and after the treatment-period and 1 month after the treatment-period had ended. Results: The use of TBC showed positive results with increased levels of function and decreased patient-reported neck pain in all three single-cases. Conclusion: The TBC-system may be used for improving function and pain in patients with neck pain. More studies of the validity and reliability and randomized studies of the TBC-system are needed before it could be recommended generally for physiotherapists.
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Evans, Corey. "THE EFFECTS OF SDF-1α TREATMENT ON THE MIGRATION OF NEURAL STEM/PROGENITOR CELLS AFTER TRAUMATIC BRAIN INJURY." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2486.
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Traumatic Brain Injury (TBI) is one of the leading causes of death and disability among young adults and has been a significant field in medical research over the past decades. Intensive studies focusing on how to repair tissue damage resulting from head injuries have discovered that the central nervous system (CNS) retains a regenerative capacity throughout life due to the persistent presence of neural stem/progenitor cells (NS/NPCs) in the neurogenic regions. In the normal brain, cells generated in the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to the olfactory bulb and cells in the subgranular zone (SGZ) migrate laterally into the granule cell layer of the dentate gyrus. Directed movement of these NS/NPCs is controlled by a variety of factors, and among them the chemoattractant SDF-1 is of particular importance. Studies have identified that the chemokine SDF-1α and its receptor CXCR4 play an important role in guiding cell migration in many types of cells including NS/NPCs. The current study tested if SDF-1 could be delivered through alginate to attract and guide migration of NS/NPCs and its progeny both in vitro and in vivo. Using a Boyden chamber migration assay, we found SDF-1α either added directly in the medium or incorporated into alginate threads was capable of influencing migration of cultured NS/NPCs in a dose-dependent manner. In the in vivo study, when injected directly into the cerebral cortex, SDF-1 showed limited capability in inducing neuroblasts migration off the normal tract to the site of SDF-1 injection. When SDF-1 was delivered via alginate thread to the focal injury site at 2 days post TBI, significantly increased number of migrating neuroblasts derived from the SVZ was observed around the injury site. Increased expression of SDF-1 receptor CXCR4 was observed in the NS/NPCs in the SVZ and around the injury site following TBI. These data suggest that bioactive SDF-1α can be delivered via alginate thread and exogenous delivery of SDF-1α and its interaction with receptor CXCR4 mediates migration of newly generated neurons from the SVZ to the site of injury following TBI. Collectively, our study indicates that SDF-1α could be utilized as a guidance cue for tissue repair following brain injury.
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Ozbas, Bengi. "Gis Based Assessment Of Excavation Difficulty By Tbm-epb Along Mecidiye - Tandogan Segment Of The Tandogan - Kecioren Metro Tunnel." Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/12608915/index.pdf.
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Tunnel structures are important investments especially for urban areas. Keçiö
ren - Tandogan metro alignment is one of those investments executed by Ankara Metropolitan Municipality. The purpose of this research is to evaluate Tunnel Boring Machine (Earth Pressure Balance type) (TBM-EPB) performance within different lithological units encountered along Tandogan -Mecidiye segment of the Keç
iö
ren - Tandogan metro tunnel. The evaluation is based on the data obtained from traditional site investigation methods, statistical approaches and Geographic Information Systems (GIS). Complex geological and hydrogeological conditions are found to be effective in the advancement of a TBM implemented in tunnel boring works. A good understanding of the geology is essential in such cases. Available field (in-situ) and laboratory tests have been used in order to determine geological, hydrogeological and geotechnical properties of the metro tunnel alignment. Advancements in the tunnel boring process also proved that hydrogeological conditions are effective on the performance of TBM so related data are considered carefully while preparing cross-section layers and calculating weights in order to display the distribution of excavation difficulty classes through the tunnel alignment.
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Pourcelot, Marie. "Implication de l’appareil de Golgi et de l’ubiquitination dans l’activation de TBK1 après détection des ARNs viraux." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS230/document.
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L’immunité innée antivirale repose en grande partie sur la production des interférons de type I (IFN-α/β) par les cellules infectées et les cellules immunitaires. Cette synthèse résulte de la reconnaissance de motifs viraux caractéristiques par des récepteurs cellulaires, parmi lesquels les RIG-I-Like Récepteurs (RLR) et le Toll-Like Récepteur 3 (TLR3) détectent l’ARN viral respectivement au niveau du cytosol et des endosomes. La signalisation induite par les RLRs et TLR3 conduit à l’activation d’IRF3 et de NF-κB, deux facteurs de transcription impliqués respectivement dans la production d’IFN-α/β et de cytokines pro-inflammatoires. TBK1 (TANK-Binding Kinase 1) joue un rôle essentiel dans l’immunité innée antivirale, de par la phosphorylation du facteur de transcription IRF3, nécessaire à la production des IFNs de type I. Bien que de nombreuses études aient montré le rôle crucial de cette kinase dans la signalisation antivirale, le processus entrainant son activation est encore mal déterminé à ce jour. Lors de cette étude nous avons démontré que suite à la stimulation du TLR3 et des RLRs, la forme active, ubiquitinylée et phosphorylée, de TBK1 se relocalise au niveau de l’appareil de golgi, grâce à son ubiquitination sur les résidus K30 et K401. Ce mécanisme implique la reconnaissance des chaines d’ubiquitines associées à TBK1 par l’Optineurine (OPTN), permettant la formation d’un complexe autorisant le rapprochement des molécules de TBK1 puis la trans-autophosphorylation au niveau de l’appareil de Golgi. Au cours de ce travail nous avons également découvert qu’OPTN est la cible d’une protéine virale, la protéine NS3 du BTV (Bluetongue Virus), qui neutralise son activité et diminue ainsi l’activation de TBK1 et la signalisation responsable de la sécrétion de cytokines antiviralesType-I interferons (IFN-α/β) production and release is a major event in innate antiviral immunity. IFN production depends on the interaction between viral structures and their corresponding cellular sensors. RIG-I-Like Receptors (RLRs) and Toll-Like Receptor 3 (TLR3) sense dsRNAs in the cytosol and endosomes respectively. Stimulation of these receptors by their ligands promotes a signal transduction leading to the activation of the transcription factors NF-κB and IRF3, and consequently to the production of proinflammatory cytokines and Type I Interferons (IFN-I). TBK1 (TANK-Binding Kinase 1), plays a crucial role in antiviral innate immunity, by phosphorylating the transcription factor IRF3, required for the production of type I IFNs. Although many studies have shown the critical role of this kinase in antiviral signaling, the molecular mechanism of its activation are largely unknown. We report here the localization of the ubiquitinated and phosphorylated active form of TBK1 to the Golgi apparatus after the stimulation of RLRs or TLR3, due to TBK1 ubiquitination on lysine residues 30 and 401. The ubiquitin-binding protein optineurin (OPTN) recruits ubiquitinated TBK1 to the Golgi apparatus, leading to the formation of complexes in which TBK1 is activated by trans-autophosphorylation. We also found that a viral protein binds OPTN at the Golgi apparatus, neutralizing its activity and thereby decreasing TBK1 activation and downstream signaling
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SANTOS, Lorena Cristina. "Análise de resistência a antimicrobianos de cepas de Mycobacterium tuberculosis isoladas no Estado de Goiás." Universidade Federal de Goiás, 2010. http://repositorio.bc.ufg.br/tede/handle/tde/1567.
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Previous issue date: 2010-12-07Tuberculosis (TB) is a serious global public health. In Brazil for the confirmed TB cases is recommended a multi-drug therapy regimen which combines different drugs during at least 6 month. However, because of treatment inconsistency, the emergency and spread of drug resistant M. tuberculosis become a serious threat. Actually, strains resistant to at least one drug used in the TB treatment have been one of the main factor that avoid the effective TB control. According to WHO M. tuberculosis strains that are resistant to at least INH and RMP, the key drugs used in the TB treatment, are considered multidrug resistant (MDRTB). The main mutations responsible for INH and RMP resistance occur at some specific regions in the katG, inhA and rpoB genes. We analyzed by phenotypic and genotypic methods the susceptibility profile of M. tuberculosis isolated from 132 patients treated at a reference hospital in Goiânia-Goiás, between January of 2006 and July of 2007 and then performed the resistant strains genotypic identifications by RFLP-IS6110. Additionally, clinical and epidemiological informations from the patients was collected. A high frequency of drug resistance was observed in previously untreated patients (13.6% to at least one antibiotic and 6.1% MDR-TB), and a high DNA polymorphism was observed among these strains. Our results suggest that the prevalence of resistant TB in Goiás is underestimated and that resistance in new TB cases was not associated with an outbreak in this region.
A tuberculose (TB) é um problema de saúde pública em todo o mundo. Nos casos confirmados de tuberculose (TB) no Brasil, preconiza-se o esquema multidroga terapêutico que combina diferentes drogas por um período mínimo de 6 meses de tratamento. Devido, principalmente, ao tratamento inadequado, a emergência e disseminação de linhagens de M. tuberculosis multi resistentes a drogas se tornou uma séria ameaça. Atualmente, linhagens resistentes a pelo menos uma droga utilizada no tratamento da TB têm sido um dos principais fatores que impedem o controle efetivo da doença. De acordo com a OMS, linhagens multi-droga resistentes (MDR-TB) são aquelas resistentes a no mínimo isoniazida (H) e rifampicina (R), as principais drogas utilizadas no tratamento da TB. As principais mutações responsáveis por desenvolvimento de resistência à H e R acontecem principalmente em algumas regiões dos genes katG, inhA e rpoB, respectivamente. No presente estudo foi analisado o perfil de suscetibilidade de M. tuberculosis isolados de 132 pacientes atendidos em um hospital de referência em doenças infecciosas em Goiânia-Goiás, no período de janeiro de 2006 a julho de 2007. Foram coletados dados clínicos, epidemiológicos e utilizados testes de susceptibilidade à drogas, sequenciamento parcial dos genes katG e rpoB, análise de mutação por PCR do gene inhA e genotipagem por RFLP-IS6110. Foi observada uma alta frequência de resistência à drogas em pacientes virgens de tratamento (13,6% de resistência a no mínimo uma das droga testada e 6,1% de MDR-TB), e um alto grau de polimorfismo de DNA entre as linhagens resistentes. Estes resultados sugerem que a prevalência de linhagens resistentes na região está subestimada e que resistência aos antimicrobianos não está associada a um surto específico na região.
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Veschambre, Philippe. "Mécanisme d'action du transactivateur viral Tat sur l'initiation de la transcription du promoteur HIV-1 : rôle de l'interaction de Tat avec les facteurs généraux de transcription TBP et TFIIB." Lyon 1, 1995. http://www.theses.fr/1995LYO1T290.
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Juraszek, Jean. "Dommages induits par irradiation aux ions lourds dans des matériaux magnétiques : multicouches metalliques Fe/Tb et grenat isolant Y 3Fe 5O 1 2." Rouen, 2000. http://www.theses.fr/2000ROUES016.
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Ce travail concerne l'étude de l'endommagement induit par excitation électronique dans des multicouches Tb/Fe et dans le grenat de fer-yttrium. Les multicouches ont été préparées par évaporation sous ultra-vide et irradiées par des ions de différents pouvoirs d'arrêt électronique au GANIL. Les transformations structurales et magnétiques ont été caractérisées par réflectométrie et diffraction des rayons X, microscopie électronique à transmission haute résolution, mesures d'aimantation et spectrométrie Mössbauer par électrons de conversion. Dans le cas des ions Pb ou U, une forte interdiffusion entraine une perte de la structure en couche et de l'anisotropie magnétique perpendiculaire. L'efficacité de mélange est d'autant plus grande que l'épaisseur des couches de fer et que la vitesse des ions est faible. Une modélisation des cinétiques d'endommagement des couches de fer, ainsi que des variations avec la fluence de la direction des moments magnétiques, a été utilisée pour estimer le diamètre des zones de mélange ainsi que la longueur de diffusion induite. Des plans sondes de 5 7Fe déposés à différents endroits dans la couche de fer naturelle ont permis d'étudier sélectivement les interfaces abruptes Tb-sur-Fe, les interfaces diffuses Fe-sur-Tb et le Cur cristallin des couches de fer pour différents pouvoirs d'arrêt électronique. A partir d'un pouvoir d'arrêt électronique seuil, une démixtion du fer et du terbium est observée à basse fluence à l'interface Fe-sur-Tb. On observe uniquement un mélange interatomique à l'interface Tb-sur-Fe. Ce mélange est indépendant du sens de parcours des ions à travers l'interface. Dans les grenats Y 3Fe 5O 1 2 irradiés aux ions Pb de haute énergie, la détermination des fractions volumiques des différentes phases introduites par irradiation nous a permis de proposer un modèle phénoménologique permettant de déterminer les sections efficaces des différents domaines.
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Jerjini, Mehdi. "Etude des propriétés magnétiques des composés TGa6 avec T : Ce, Pr, Nd, Tb, Ho, Dy et des solutions solides Ce (Ga(1-x) Al(x))2." Grenoble 1, 1987. http://www.theses.fr/1987GRE10132.
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Etude des structures magnetiques de tga::(6) et ce(ga::(1-x)al::(x))::(2). Comportement de l'ion cerium dans cega::(6). Determination par des experiences de diffusion inelastique de neutrons du schema des niveaux d'energie de champ cristallin de l'ion cerium. Effet d'une insertion d'aluminium dans les sites du gallium de cega::(2) sur le caractere de kondo du compose et sur l'hybridation
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Rivalin, Romain. "Intégration de la régulation post-transcriptionnelle et des interactions mitochondries/cytosquelette dans les voies de contrôle du métabolisme mitochondrial." Phd thesis, Université d'Angers, 2013. http://tel.archives-ouvertes.fr/tel-01022923.
Full textAbstract:
La mitochondrie fournit l'énergie nécessaire au fonctionnement cellulaire, grâce au mécanisme de phosphorylation oxydative. Cette fonction nécessite une expression coordonnée des génomes nucléaires et mitochondriaux assurée par la famille de coactivateurs transcriptionnels PGC-1 (Peroxisome proliferator-activated receptor γ Coactivator-1), sensibles aux signaux endogènes et/ou environnementaux. Une régulation plus fine de la phosphorylation oxydative par des miRNAs est maintenant soupçonnée. Afin de préciser ces différents modes de régulation dans des modèles cellulaires de carcinomes thyroïdiens, nous avons exploré la voie PRC-dépendante (PGC-related coactivator) et les miRNAs spécifiquement exprimés dans ces modèles présentant une richesse en mitochondries et des niveaux de PRC et de PGC-1α différents. Ce travail a permis de mettre en évidence miR-218 comme marqueur clé de régulation de la fonction mitochondriale. Au-delà de la régulation de l'expression génique, une fourniture énergétique adéquate nécessite également une répartition optimale des mitochondries au sein de la cellule, grâce à d'étroites connexions entre le cytosquelette et la mitochondrie. Des peptides issus de la sous-unité légère des neurofilaments, dont le NFL-TBS.40-63, sont capables d'entrer spécifiquement dans les cellules de glioblastomes humains et d'y déstabiliser le réseau microtubulaire, conduisant à la mort cellulaire par apoptose. Pour étudier l'impact de ce peptide sur le réseau de mitochondries et leurs fonctions, nous avons traité le modèle cellulaire de glioblastomes humains T98G, par différentes concentrations de NFL-TBS.40-63. Ce travail révèle une perturbation du réseau de mitochondries et une diminution de la respiration mitochondriale dans les cellules exposées. L'ensemble de ces travaux doit permettre le développement de traitements ciblés de la fonction mitochondriale.
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Junker, Michel. "Etude et optimisation des propriétés optiques et morphologiques d'un luminophore du type La1-x-yCexTbyPO4." Phd thesis, Ecole Nationale Supérieure des Mines de Saint-Etienne, 1995. http://tel.archives-ouvertes.fr/tel-00843196.
Full textAbstract:
L'un des luminophores utilisés dans les lampes trichromatiques est un phosphate mixte de lanthane-cérium-terbium La1-x-yCexTbyPO4. Ses propriétés optiques et morphologiques doivent être adaptées à son utilisation. Ce travail concerne l'étude et l'optimisation de ces propriétés. Comme le luminophore est obtenu par calcination d'un précurseur, il apparaît que cette étape a une influence sur son rendement quantique, c'est à dire sur son efficacité. C'est la nature de l'atmosphère de calcination qui est déterminante. La morphologie finale du luminophore peut être contrôlée par l'ajout, avant l'étape de calcination, d'un composé au précurseur. La nature de ce composé dépend des impuretés présentes dans le précurseur et provenant de la synthèse de celui-ci.
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Peralta, Aguilar Luis Manuel. "Síntesis y caraterización de los ligandos tiosemicarbazona,Ph-CH=N-NH-C(=S)-NR1R2 y sus respectivos complejos de platino (II) y paladio (II)ón a la matriz en forma selectiva de pozos inyectores reentubados con TBG 3 1/2” ERFV." Universidad Nacional de Ingeniería. Programa Cybertesis PERÚ, 2007. http://cybertesis.uni.edu.pe/uni/2007/peralta_al/html/index-frames.html.
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OUAHMANE, HASSAN. "Elaboration et etude des proprietes magnetiques des couches minces amorphes de type a(cozr)#1#0#0#-#xtr#x (tr=dy,tb,pr,nd,sm et gd) a faible teneur en terre rare (ox4)." Paris, CNAM, 1993. http://www.theses.fr/1993CNAM0172.
Full textAbstract:
Nous avons etudie les proprietes des couches minces amorphes de (cozr)#1#0#0#-#xtr#x ou tr est une terre rare et ox4. Les echantillons ont ete prepares par pulverisation radiofrequence en presence d'un champ magnetique applique (hd) parallelement au plan de la couche ; d'ou la formation d'une anisotropie induite : - pour les films substitues en tr = dy,tb,nd et pr, on obtient systematiquement une anisotropie dans le plan du film (k#u). Le champ coercitif et l'aimantation (a 300k) varient faiblement et presque independamment de la nature de la terre rare. Des mesures de la susceptibilite transverse montrent que la dispersion de k#u est negligeable et que les ripples d'aimantation sont liees a l'anisotropie locale. - dans les couches contenant tr=gd ou sm ; on observe, en plus d'une anisotropie planaire (k#u), le developpement d'une anisotropie perpendiculaire au plan du film (kp). Nous avons egalement etudie les proprietes dynamiques, par resonance ferromagnetique (r. F. M. ). Le mecanisme d'aimantation a ete caracterise par l'etude de l'absorption observee sur le spectre de resonance ferromagnetique a des champs tres voisins du champ d'anisotropie planaire induit h#k(h#k = 2k#u/m#s). L'etude du spectre de permeabilite complexe en fonction de la frequence a montre que l'on peut obtenir des echantillons presentant une permeabilite rationnelle et des pertes assez elevees dans une large gamme de frequence. Le spectre a pu etre fite par un modele theorique base sur l'hypothese que le processus d'aimantation s'effectue par rotation et que les pertes peuvent etre decrites par l'equation de landau-lifshitz
28
Rivalin, Romain. "Intégration de la régulation post-transcriptionnelle et des interactions avec le cytosquelette clans les voies de contrôle du métabolisme mitochondrial." Angers, 2013. https://tel.archives-ouvertes.fr/tel-01022923/document.
Full textAbstract:
La mitochondrie fournit l'énergie nécessaire au fonctionnement cellulaire, grâce au mécanisme de phosphorylation oxydative. Cette fonction nécessite une expression coordonnée des génomes nucléaires et mitochondriaux assurée par la famille de coactivateurs transcriptionnels PGC-I (Peroxisome proliferatoractivated receptor V Coactivator-l), sensibles aux signaux endogènes et/ou environnementaux. Une régulatioh plus fine de la phosphorylation oxydative par des miRNAs est maintenant soupçonnée. Afin de préciser ces différents modes de régulation dans des modèles cellulaires de carcinomes thyroïdiens, nous avons exploré la voie PRC-dépendante (PGC-related coactivator) et les miRNAs spécifiquement exprimés dans ces modèles présentant une richesse en mitochondries et des niveaux de PRC et de PGC-Ia différents. Ce travail a permis de mettre en évidence miR-218 comme marqueur clé de régulation de la fonction mitochondriale. Au-delà de la régulation de l'expression génique, une fourniture énergétique adéquate nécessite également une répartition optimale des mitochondries au sein de la cellule, grâce à d'étroites connexions entre le cytosquelette et la mitochondrie. Des peptides issus de la sous-unité légère des neurofilaments, dont le NFL-TBS. 40-63, sont capables d'entrer spécifiquement dans les cellules de glioblastomes humains et d'y déstabiliser le réseau microtubulaire, conduisant à la mort cellulaire par apoptose. Pour étudier I'impact de ce peptide sur le réseau de mitochondries et leurs fonctions, nous avons traité le modèle cellulaire de glioblastomes humains T98G, par différentes concentrations de NFL-TBS. 40-63. Ce travail révèle une perturbation du réseau de mitochondries et une diminution de la respiration mitochondriale dans les cellules exposées. L'ensemble de ces travaux doit permettre le développement de traitements ciblés de la fonction mitochondrialeMitochondrion provides energy for cell metabolism through the mechanism of oxidative phosphorylation. This function requires a coordinated expression of nuclear and mitochondrial genomes provided by the family of transcriptional coactivators PGC -1 (peroxisome proliferator-activated receptor V Coactivator -1), responding to endogenous and/or environmental signals. A fine regulation of the oxidative phosphorylation by miRNAs is now suspected. To specify these regulatory pathways in cellular models of human follicular thyroid carcinomas, we have explored the PRC-related (PGC- related coactivator) pathway and specific microRNAs, in models presenting various mitochondrial abundance and differences in PRC and PGC- la expression levels. We have highlighted the role of miR-218 as a key regulatory factor of mitochondrial functions. An adequate energy supply also requires close connections between cytoskeleton and mitochondria to ensure an optimal distribution of mitochondria within the cell. Peptides derived from the light neurofilament subunit, as NFL - TBS. 40 -63, are able to specifically enter into human glioblastoma cells and destabilize the microtubule network, leading to cell death by apoptosis. To study the impact of this peptide on mitochondrial network and oxidative phosphorylation, we have treated the T98G human glioblastoma cells by different concentrations of NFL- TBS. 40 -63. Our work showed disturbance in mitochondrial network and reduction in mitochondrial respiration rate in the treated cells. All these results should allow the development of therapy targeting the mitochondrial function
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Pillay, Santhoshan Thiagaraj. "Phenotypic and functional characterization of cytotoxic T lymphocytes in HIV-1 infected South African adults." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/5182.
Full textAbstract:
BibliographyThesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2010.
ENGLISH ABSTRACT: In just 25 years since the first reported cases in 1981, the number of Human Immunodeficiency virus (HIV) infected people has risen to 65 million, and over 25 million have died of acquired immunodeficiency syndrome (AIDS). Sub-Saharan Africa accounts for 67% of all people living with HIV and 72% of deaths in this region were AIDS related. Tuberculosis (TB) is one of the most common opportunistic infections in AIDS patients, particularly in developing countries, where 60 - 70% of TB cases occur in HIV-1-infected persons. HIV-1 is a high risk factor for the development of TB, the reactivation of a latent Mycobacterium tuberculosis infection and also progressive TB. CD8+ Cytotoxic T Lymphocytes (CTL) are pivotal in the host immune response to HIV infection. CTL are associated with resolution of acute infection and with reduction in viral load. Studies in macaques and humans indicate the importance of CTL in the control of HIV infection, where reduction in CD8+ T cell number has been correlated with progression to AIDS. The current study was a cross-sectional descriptive study of CD8+ T cells of HIV+ adult South Africans with and without TB co-infection (TB disease). The cohort consisted of anti-retroviral therapy (ART) naive patients and all CTL analyses were carried out on peripheral blood mononuclear cells (PBMCs). A total of 60 South African adults from the Western Cape were utilized in this study, including 15 healthy controls; 30 HIV+TB-individuals and 15 HIV+TB+ individuals. Expression of phenotypic, activation and functional markers were investigated by flow cytometry with the use of fluorochomeconjugated antibodies. The markers examined included the novel activation marker CD137, the CTL associated markers Perforin, Granzyme A, CD107a/b, Fas (CD95), and FasL (CD95L), intracellular cytokines IFN-y and TNF-a and the chronic HIV CTL dysfunction marker PD-1. HIV infection alone was associated with increased baseline expression of TNF-a, Perforin, Granzyme A, PD-1, Fas (CD95), and FasL (CD95L), but not CD137(4-1BB) or IFN-y as compared to uninfected controls. TB co-infection resulted in further increased baseline expression of TNF-a, perforin, PD-1, FasL (CD95L), as well as increased IFN-y. HIV-1 antigen (gag)-specific stimulation in vitro indicated that in HIV infection was associated with antigen-specific upregulation of activation and cytotoxicity markers CD137, IFN-y, TNF-a, Fas, FasL and CD107a/b. In TB co-infection a reduction in antigen-specific degranulation (CD107a/b up-regulation) and also Fas and FasL expression was observed. TB co-infection (in the form of active pulmonary TB) reduced antigen-specific CTL functional activity, but simultaneously there was an association with increased baseline PD-1 expression and also cytolytic marker expression (Fas, FasL, TNF-a). These cytolytic markers could be involved in non-antigen-specific bystander target cell death. The expression of the co-stimulatory molecule CD137 appeared to correlate with interferon-y production and levels of degranulation, confirming its usefulness as a putative surrogate marker of functional responsiveness. These data indicate that in addition to impacting on CD4 T cell function, TB co-infection leads to higher baseline expression of CTL-associated markers, but to dysfunctional antigen-specific CTL responses.
AFRIKAANSE OPSOMMING: Slegs vyf en twintig jaar na die eerste berigte van die menslike immuniteitsgebrekvirus (MIV) in 1981, het die getal MIV-geinfekteerde individue gestyg tot 65 miljoen en het meer as 25 miljoen mense alreeds gesterf aan die verworwe immuniteitsgebrek sindroom (VIGS). Sub Sahara Afrika maak 67% uit van alle HIV gevalle en het `n MIVverwante doodsyfer van 72%. Een van die algemeenste opportunistiese infeksies in VIGS pasiente is Tuberkulose (TB). In ontwikkelende lande, veral, kom 60-70% van TB gevalle voor in MIV-1 geinfekteerde individue. MIV-1 is `n hoe risiko faktor vir die ontwikkeling van TB, die heraktivering van latente Mycobacterium tuberculosis infeksie en progressiewe TB. Die CD8+ sitotoksiese T Limfosiete (STL) se immuun reaksie teen `n MIV infeksie is noodsaaklik en word geassosieer met `n resolusie van die akute infeksie en `n afname in viruslading. Studies in die mens en macaque het getoon dat sitotoksiese T limfosiete belangrik is vir die beheer van MIV infeksies aangesien die afname in CD8+ sel getalle korreleer met die verloop tot VIGS. Hierdie deursnit-beskrywende studie het die CD8+ T selle van MIV+ volwasse Suid-Afrikaners, met of sonder`n TB mede-infeksie, ondersoek. STL analise is gedoen op die perifere bloed mono-nuklere selle (PBMS) van pasiente wat geen teen-retrovirale terapie (TRT) ontvang het nie. `n Totaal van sestig Suid-Afrikaanse volwassenes van die Wes-Kaap het deelgeneem aan die studie wat 15 gesonde kontroles; 30 MIV+TBen 15 MIV+TB+ individue ingesluit het. Die uitdrukking van fenotipiese, aktiverings en funksionele merkers is ondersoek deur middel van vloeisitometrie en fluorochroomgekonjugeerde teenliggaampies. Laasgenoemde het ingesluit die nuwe aktiversingsmerker CD 137, die STL geassosieerde merkers Perforien en Gransiem A, CD 107a/b, Fas (CD95) en FasL (CD95L), intrasellulere sitokiene IFN-y en TNF-a en PD-1, die merker vir chroniese MIV CTL disfunksie. Daar is gevind dat `n TB mede-infeksie (in die vorm van aktiewe pulmonere TB) die antigeen-spesifieke STL funksie verlaag en terselftertyd `n verhoging in die uitdrukking van PD-1 en sitolitiese merkers (Fas, FasL, TNF-a) bewerkstellig. Hierdie sitolitiese basislyn merkers is moontlik betrokke by die dood van nie-antigeen-spesifieke omstander teiken selle. Die uitdrukking van die mede-stimulatoriese molekule CD 137 blyk om te korreleer met die produksie van STL IFN-y en die vlakke van degranulasie. Dit bevestig die merker se bruikbaarheid as `n gewaande surrogaat merker vir funksionele reaksies. Die data toon verder dat `n TB mede-infeksie nie net `n effek het op die CD4 T sel funksie nie, dit lei ook tot `n verhoogde basislyn uitdrukking van STLgeassosieerde merkers, maar met disfunksionele antigeen-spesifieke STL reaksies. Hierdie studie het bepaal dat `n MIV infeksie verbind word met `n toename in die basislyn uitdrukking van TNF-a, Perforien, Gransiem A, PD-1, Fas (CD95) en FasL (CD95L). Dit is egter nie die geval wanneer die uitdrukking van CD 137 (4-1BB) of IFN-y vergelyk word met nie-geinfekteerde kontroles. `n TB mede-infeksie het `n verdere toename in die uitdrukking van TNF-a, Perforien, PD-1, FasL (CD95L) getoon, asook `n verhoging in IFN-y vanaf die basislyn. In vitro MIV-1 antigeen (gag)-spesifieke stimulasies het aangedui dat `n MIV infeksie met die antigeen-spesifieke op-regulasie van aktiverings en sitotoksiese merkers CD137, IFN-y, TNF-a, Fas, FasL en CD107a/b geassosieer word. In `n TB mede-infeksie, is `n verlaging van antigeen-spesifieke degranulasie (CD 107a/b op-regulasie) asook die uitdrukking van Fas en FasL waargeneem.
The Poliomyelitis Research Foundation
The National Health Laboratory Service
30
Ding, Chia-Nung, and 丁嘉農. "Screening and Confirmation of Tbr-1 target genes." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/47031781276136629454.
Full textAbstract:
碩士國立陽明大學
遺傳學研究所
93
Tbr-1, a T-box transcription factor, expresses highly in embryonic cerebral cortex. Tbr-1 can bind to T element (5'-AATTTCACACCTAGGTGTGAAATT-3') and induce gene expression. Tbr-1 KO mice lose the normal cortical lamination and correct axonal projection, suggesting that Tbr-1 is important for cerebral cortex development. Dr. Ting-Fang Wang identified Tbr-1 target genes by computational search using the core sequence of T-element (5'-ACTGGTGTGAGAAGGG-3'). 25 genes including NR2B and NR1 were identified to contain T-element in the promotor regions. The results of EMSA assay and Luciferase assay demonstrated that Tbr-1 could bind to these promotor regions and enhance promotor activity. In Tbr-1 KO mice, NR2B and NR1 expression level were lower than those of wild type littermate. These evidences suggest that expression of NR2B and NR1 is regulated by Tbr-1 gene in developing cerebral cortex. In order to fully explore the function of Tbr-1 during development, we also used another method to identify downstream target gene of Tbr-1, which is DNA microarray. The gene expression patterns were compared between Tbr-1 KO and wild type mice in ICR and B6 strain. We cross the last two DNA array results (in B6 background). From the gene list, we further found out the gene function, gene structure, and spatial and temporal expression pattern in on-line database. We also perform Western Blot with commercial antibodies against SSTr2 to confirm the results from DAN array. SSTr2 was indeed down regulated in the Tbr-1 KO, suggesting that SSTr2 is one of Tbr-1 target genes and might be involved in the Tbr-1 KO phenotype.
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Lin, Shu-Ju, and 林書如. "Study the Relationships of Halobacterium sp. NRC-1 TBP-TFB Combinatorial Partnerships and Transcription Initiations." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/25750621917296376713.
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碩士國立陽明大學
醫學生物技術研究所
95
Halobacterium sp. NRC-1 is an extremophiles that grow under condition of high salinity. The complete genome sequence was available in year 2000, contained six copies of TBP (TATA-box binding proteins) and seven copies of TFB (transcription factor II B) that are homologous to the eukaryotic TFIID ((transcription factor II D) and TFB, respectively. It is possible various kinds of promoters are regulated by up to 42 combinations of TBP and TFB. Here 13 NRC-1 clones that expressed TBP/TFB-protein A fusion proteins were estabilished. The fusion proteins complexes were captured by IgG sepharose beads under different experimental conditions. The protein complexes were analysed by tendem mass spectrometry.The results suggested TbpF-TbpD, TfbE-TbpE, TbpF-TbpB, TbpD-TbpB and TbpC-TbpB pairs might be identified under high salt condition. TbpE existed in many protein complex, including TbpA, TbpB, TbpD, TbpF, TfbB, TfbD, TfbE, TfbF and TfbG, implied that TbpE might be the major transcription factor in NRC-1 gene regulation. We even found that TBP-TBP and TFB-TFB pair together in our experiential conditions. On the other hand, to find out whether each promoter is recognized by a specific or multiple pairs of TBP/TFB, streptavidin beads were used to capture the biotin-labeled promoter region of gvpA1 and bop respectively, and incubated with Halobacterium cell lysates.We found that transcription regulators sirR and trh5 presest in the elution by mass spectrometry. These results showed that not only basal transcription factors TBP and TFB were needed, other factors might also participate in regulating the complicated mechanism of transcription in NRC-1.
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Hsu, Hsiao-Ju, and 徐筱茹. "1. Intramolecular Diels-Alder Reactions of Azadienynes: Synthesis of Hexahydrobenzo[cd]indoles 2. BF3-Assisted Synthesis of Fluorinated Carbospirocycles from TBS-Protected 3-(5-Arylpent-4-yn-1-yl)cyclohex-2-en-1-ols." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/73344075993909987522.
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碩士國立臺灣師範大學
化學系
101
This study covers three separated topics. The first work is the synthesis of hexahydrobenzo[cd]indoles via intramolecular Diels-Alder reaction from 1-tosylpropargylamino-3-vinylcyclohex-2-enes. The reaction proceeded via [4+2] cycloaddition followed by oxidation to generate hexahydrobenzo[cd]- indoles. The second part of the thesis is the synthesis of fluorinated spiro[4.5]- decenes from tert-butyldimethyl-silyl-protected 3-(5-arylpent-4-yn-1-yl)cyclo- hex-2-en-1-ols using BF3•OEt2. In this reaction, BF3 reacted as both the Lewis acid and the fluoride source for cyclization/fluorination. The method provided an easy access to spirocyclic skeletons with concomitant formation of a C(sp2)−F bond. Finally, the gold(I)-catalyzed intramolecular cycloisomeri- zation of the 3-(N,3-diphenylpropiolamido)cyclohex-2-en-1-one proceeded through a cationic gold intermediate to afford a dihydroquinolinone. The reaction underwent an endo-dig cyclization to generate an iminium intermedi- ate followed by deprotonation/protodeauration to give a dihydroquinolinone and regenerate the Au(I) catalyst into the catalytic cycle.
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Traulsen, Iris. "X-ray Diagnostics of Accretion Plasmas in Selected Soft Polars." Doctoral thesis, 2009. http://hdl.handle.net/11858/00-1735-0000-0006-B498-1.
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Gravel, Simon-Pierre. "Rôles des kinases IKK et IKK-related dans les maladies inflammatoires chroniques : implications dans l’athérosclérose et la réponse hypoxique." Thèse, 2010. http://hdl.handle.net/1866/5299.
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L’inflammation est un procédé complexe qui vise l’élimination de l’agent causal de dommages tissulaires en vue de faciliter la réparation du tissu affecté. La persistance de l’agent causal ou l’incapacité à résoudre l’inflammation mène à un dérèglement homéostatique chronique qui peut avoir une incidence sur la morbidité et la mortalité. L’athérosclérose est une condition inflammatoire chronique des vaisseaux sanguins dont l’origine est multifactorielle. L’hypertension et l’état infectieux représentent respectivement des facteurs de risque classiques et émergents du développement de cette maladie. Les fondements initiaux de l’inflammation font intervenir l’immunité innée, la première ligne de défense dont disposent les cellules pour répondre à un signal de danger. Le but de cette thèse est d’examiner le rôle pro-inflammatoire d’une famille de kinases essentielles à l’immunité innée, soit celle des kinases de IkappaB (IKK) et des kinases IKK-related. Les kinases IKKalpha et IKKbeta forment le complexe IKK avec la molécule adaptatrice NEMO/IKKgamma. Ce complexe est chargé d’effectuer la phosphorylation de l’inhibiteur de NF-kappaB, IkappaBalpha, ce qui mène à sa dégradation et à la libération du facteur de transcription NF-kappaB. Nous montrons que le peptide vasoactif angiotensine II (AngII) induit l’activité phosphotransférase d’IKKbeta dans les VSMC par immunoprécipitation de NEMO puis essai kinase in vitro. Grâce à une approche ARN interférence (ARNi) dirigée contre IKK, nous montrons que cette kinase est responsable de la phosphorylation de p65/RelA. Nous montrons que le mécanisme d’induction de NF-kappaB par l’AngII est atypique, puisqu’il ne module pas IkappaBalpha, et montrons à l’aide d’inhibiteurs pharmacologiques que l’activation de p65 est indépendante des voies MEK-ERK-RSK, PI3K et de la transactivation du récepteur de l’EGF. Les kinases IKK-related Tank-binding kinase 1 (TBK1) et IKK-i sont quant à elles principalement activées suite à une infection bactérienne ou virale. Ces kinases phosphorylent directement le facteur de transcription interferon regulatory factor (IRF)-3. Nous montrons que le cytomégalovirus humain, un pathogène associé à l’athérosclérose, a la capacité d’induire l’activation de TBK1 dans les VSMC. L’usage d’ARNi dirigé contre TBK1 et IKKi montre que les 2 kinases sont impliquées dans l’activation d’IRF-3. De plus, nous montrons à l’aide d’une lignée de VSMC exprimant une version dominante négative d’IRF-3 que ce dernier est essentiel à la synthèse des chimiokines RANTES et IP-10, tel qu’analysé par RT-PCR. Par ailleurs, il a récemment été montré que les kinases IKK-related étaient étroitement liées à la transformation oncogénique, et que TBK1 était pro-angiogénique. Or, l’angiogenèse est le plus souvent modulée par la réponse hypoxique qui est d’ailleurs commune à la majorité des processus inflammatoires. Le facteur de transcription hypoxia inducible factor (HIF)-1 module l’angiogenèse, l’inflammation et la survie cellulaire. Nous montrons à l’aide de cellules Tbk1 et Ikbke -/- et d’une approche lentivirale que TBK1 est spécifiquement impliquée dans l’induction traductionnelle de HIF-1alpha en condition de stress hypoxique. L’expression de TBK1 est induite sous ces conditions, et cette kinase module la phosphorylation de ERK, RSK, Akt et TSC1. Les résultats originaux présentés dans cette thèse montrent donc que les kinases IKK et IKK-related exercent leurs actions pro-inflammatoires par des mécanismes distincts.Inflammation is a complex process that allows elimination of tissular damaging agents and thus facilitates wound repair. Persistance of a damaging agent or the incapacity to resolve the inflammatory state leads to chronic homeostatic deregulation with putative incidence on morbidity and mortality. Atherosclerosis is an inflammatory state of blood vessels which origins are multifactorial. Hypertension and the infectious state represent classical and emerging factors of atherosclerosis development, respectively. The innate immune response takes place in the initial steps of inflammation, and represents the first cellular line of defense against danger signals. The goal of this thesis is to examine the pro-inflammatory roles of the IkB kinases (IKK) and the IKK-related kinases, which are essential innate immune response protein kinases. IKKalpha and IKKbeta form, together with NEMO/IKKgamma, the IKK complex. This complex is responsible of the phosphorylation of the inhibitor of NF-kappaB, IkappaBalpha, a process that leads to its degradation and NF-kappaB release. By immunoprecipitation of NEMO and assessment of the IKK complex activity in vitro, we show that the vasoactive peptide angiotensin II (AngII) induces IKKbeta phosphotransferase activity in vascular smooth muscle cells (VSMC). The use of RNA interference (RNAi) against IKKbeta reveals that this kinase is responsible for p65/RelA phosphorylation. AngII modulation of NF-kappaB is atypical since it does not modulate IkappaB. Moreover, the use of pharmacological inhibitors shows that p65 induction is independent of both MEK-ERK-RSK and PI3K pathways, and that it does not involve EGF receptor transactivation. IKK-related kinases Tank-binding kinase 1 (TBK1) and IKK-i are known to be induced by bacterial and viral infections. These kinases are able to phosphorylate directly interferon regulatory factor (IRF)-3 transcription factor. Human cytomegalovirus (HCMV) seropositivity was shown to be linked to atherosclerosis development. We show that TBK1 activity is induced in HCMV-infected VSMC. RNAi directed against TBK1 and IKK-i reveals that both kinases are required for IRF-3 activation. The use of a VSMC line that express a dominant negative version if IRF-3 shows that this transcription factor is involved in the induction of RANTES and IP-10 chemokines, as assessed by RT-PCR. In addition, IKK-related kinases were recently shown to be implicated in oncogenic transformation. TBK1 was also shown to be pro-angiogenic. Angiogenesis is known to be regulated by the hypoxic response, a common condition of inflammatory processes. Hypoxia-inducible factor (HIF)-1 is a transcription factor that modulates angiogenesis, inflammation and cell survival. We show with the use of Tbk1 and Ikbke -/- cells combined with the use of a lentiviral approach that TBK1 is specifically involved in HIF-1alpha translational induction under hypoxic stress. We also show that TBK1 expression is enhanced under theses conditions, and that this kinase modulates the phosphorylation of ERK, RSK, Akt and TSC1. In conclusion, the results presented in this thesis show that the IKK and IKK-related kinases are both pro-inflammatory, and exert their actions by distinct mechanisms.