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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Impactos econômicos da implantação de um trem de alta velocidade – uma análise comparativa

Samôr, Juliano de Barros 15 December 2013 (has links)
Dissertação (mestrado)—Universidade de Brasília, Departamento de Economia, Centro de Estudos e Regulação de Mercados, 2013. / Submitted by Ana Cristina Barbosa da Silva (annabds@hotmail.com) on 2014-10-29T17:42:08Z No. of bitstreams: 1 2013_JulianodeBarrosSamor.pdf: 868957 bytes, checksum: c546f6ad79ab59c56292963c7d671ebb (MD5) / Approved for entry into archive by Tania Milca Carvalho Malheiros(tania@bce.unb.br) on 2014-10-30T14:36:35Z (GMT) No. of bitstreams: 1 2013_JulianodeBarrosSamor.pdf: 868957 bytes, checksum: c546f6ad79ab59c56292963c7d671ebb (MD5) / Made available in DSpace on 2014-10-30T14:36:35Z (GMT). No. of bitstreams: 1 2013_JulianodeBarrosSamor.pdf: 868957 bytes, checksum: c546f6ad79ab59c56292963c7d671ebb (MD5) / Uma discussão atual no Brasil envolve o projeto de construção de um trem de alta velocidade, planejado para o trecho entre as cidades do Rio de Janeiro (RJ) e Campinas (SP), passando pela cidade de São Paulo (SP), o TAV Brasil. O projeto do TAV Brasil apresenta como estimativa inicial um investimento de cerca de R$ 35 bilhões, com prazo de concessão de 30 anos. Investimentos dessa natureza são caracterizados por intensivos de capital e comumente financiados via project finance. O project finance pode ser definido como uma forma de financiamento para projetos de investimentos de capital economicamente separável, em que os fluxos de caixa do projeto constituem as fontes primária de recursos para o serviço da dívida e o retorno sobre o capital investido. O project finance exige o estabelecimento de uma sociedade de propósito específico, cujos ativos e fluxo de caixa são dissociados daqueles de seus patrocinadores. Além disso, os patrocinadores envolvidos na execução do projeto assumem, cada qual, riscos específicos conforme sua capacidade de gestão e expertise. No projeto TAV Brasil se prevê a participação do governo como um patrocinador e financiador do projeto. Isso se justifica pelo grande potencial de benefícios difusos, as externalidades, que o projeto potencializa. Nesse contexto, este trabalho visa apresentar o projeto do TAV Brasil, argumentar sobre sua adequação à forma de financiamento por project finance, bem como discutir os potenciais benefícios difusos que justifiquem a participação do governo no empreendimento, a partir das informações apresentadas no projeto básico e da comparação com experiências internacionais em investimentos em trens de alta velocidade. ______________________________________________________________________________ ABSTRACT / A current discussion in Brazil involves the project of a high-speed train, the so called Brazilian TAV, between the cities of Rio de Janeiro (RJ) and Campinas (SP). The design features of the Brazilian TAV considers an investment of about US$ 15 billion and a concession period of 30 years. Such investments are capital intensive and commonly financed via project finance. A project finance can be defined as a form of financing for capital investment projects economically separable, in which the cash flows of the project are the primary sources of funds for the debt service and the return on invested capital. A project finance requires the establishment of a special purpose entity whose assets and cash flows are decoupled from those of their sponsors. Furthermore, each sponsor involved in the project undertakes specific risks according to their management capacity and expertise. Moreover, the Brazilian TAV is expected to have the government as a financial sponsor. This is justified by the great potential for externalities. In this context, this paper presents the design of the Brazilian TAV, argues its suitability to a project finance funding, as well as discusses the potential externalities that justify government involvement in the project based on its project and on international experiences.
2

Influência do uso de trens de caixa móvel na implantação e operação de novas ferrovias. / Influence of the use of tilting trains on the implementation and operation of new railways.

Lucas, Felipe Rabay 16 March 2015 (has links)
O presente trabalho tem por objetivo primário abordar os atuais conhecimentos sobre o transporte ferroviário interurbano e regional de passageiros, com foco na tecnologia dos trens de caixa móvel, também conhecidos como trens pendulares. Como objetivo secundário busca-se analisar a influência dos trens de caixa móvel ou pendulares na implantação e operação de novas ferrovias, com ênfase na adequação em fase de projeto, mostrando-se o potencial dessa tecnologia para o aumento da velocidade média e a redução dos tempos de viagem. São tratados os tópicos relevantes para o transporte ferroviário de passageiros, como o conforto do usuário, as especificações técnicas do material rodante e referências dos custos de implantação e operação envolvidos, mostrando-se também dentro de cada aspecto as diferenças dos trens pendulares em relação aos trens convencionais. Três estudos de caso elaborados terão como objetivo explicitar as interveniências da operação dos trens pendulares com o projeto ferroviário, em especial com o projeto geométrico, e através de simulações de marcha e comparações, mostrar de maneira prática o potencial do uso dos trens pendulares. Através do embasamento teórico e dos estudos de caso, é feita uma análise crítica de modo a possibilitar tanto um entendimento do transporte ferroviário de passageiros, quanto do material rodante de caixa móvel e suas possibilidades. Os resultados dos estudos de caso e a análise crítica mostram uma redução significativa dos tempos de viagem, entre 8,1 e 20,0%, mediante a operação de trens pendulares em substituição ao material rodante convencional. / As a primary objective, the present work aims to summarize the current knowledge on intercity and regional passenger railway transportation, focusing on tilting train technology, also known as car body tilt. As a secondary objective, the present work seeks to analyze the influence of tilting train technology on the design, implementation and operation of new railway corridors, with emphasis on design phase, showing the potential of this technology to increase speeds and reduce travel times. Railway passenger transportation issues, such as passenger comfort, rolling stock technical specifications and implementation and operational costs are addressed. Additionally, different aspects between conventional and tilting trains are also discussed. Three case studies help clarify the correlation between tilting train operation and railway design, especially the geometric design; further, with the help of speed simulations and comparisons, the potential use of tilting train operations are demonstrated. With the theoretical basis and the case studies, a critical analysis is made, allowing as a better understanding of railway passenger transportation with regards to the use of tilting rolling stock and its possibilities. The results of the case studies and the critical analysis present a considerable reduction in travel times, between 8,1 and 20,0%, with the operation of tilting trains in the place of the conventional rolling stock.
3

Trens de alta velocidade e arranjos produtivos locais : uma investigação sobre suas inter-relações e impactos para o desenvolvimento / High speed rail and industrial clusters : a study about its interrelationships and impacts on development

Batista, Dino Antunes Dias 30 March 2011 (has links)
Dissertação (mestrado)—Universidade de Brasilia, Faculdade de Tecnologia, Departamento de Engeharia Civil e Ambiental, 2011. / Submitted by Max Lee da Silva (bruce1415@hotmail.com) on 2011-06-28T01:15:11Z No. of bitstreams: 1 2011_DinoAntunesDiasBatista.pdf: 3884882 bytes, checksum: 6753d05f2aed526e9e8897c5d0dbbb6a (MD5) / Approved for entry into archive by Guilherme Lourenço Machado(gui.admin@gmail.com) on 2011-06-28T12:48:02Z (GMT) No. of bitstreams: 1 2011_DinoAntunesDiasBatista.pdf: 3884882 bytes, checksum: 6753d05f2aed526e9e8897c5d0dbbb6a (MD5) / Made available in DSpace on 2011-06-28T12:48:02Z (GMT). No. of bitstreams: 1 2011_DinoAntunesDiasBatista.pdf: 3884882 bytes, checksum: 6753d05f2aed526e9e8897c5d0dbbb6a (MD5) / Desde 1981 o Governo Federal brasileiro estuda a possibilidade de construção de um TAV no eixo Rio – São Paulo. A demora na concretização do projeto é resultado da sua grande complexidade, que dificulta a avaliação da sua viabilidade: se por um lado o investimento previsto é da ordem de algumas dezenas de bilhões de Reais, por outro o TAV traz potencial de mudança das estruturas econômicas do território onde será implantado (além da eliminação de gargalos já existentes no sistema de transporte atual). O TAV é uma tecnologia de transporte que altera significativamente a relação tempo-espaço, mudando as características de acessibilidade e proximidade dos atores sociais presentes nas regiões influenciadas. As sinergias existentes entre a infraestrutura de transportes e as atividades econômicas devem ser aproveitadas para a construção de um ambiente mais propício ao desenvolvimento, o que justifica a associação do TAV com outros projetos produtivos. O presente trabalho investiga as possíveis interações existentes na associação da implantação do TAV Brasil com o fortalecimento do APL do setor aeronáutico de São José dos Campos. Tal investigação é feita com o uso de um método de pesquisa qualitativa, que visa sistematizar a busca por interações entre TAVs e APLs na literatura. A análise demonstrou que, para o caso concreto, a maior parte das possíveis interações não é robusta. Foram consideradas válidas apenas duas interações decorrentes da implantação do TAV Brasil: um impacto positivo para a imagem do APL e um impacto negativo para o desempenho das empresas presentes no APL decorrente da pressão de alta dos preços no mercado imobiliário. Assim, conclui-se que não há evidências suficientes que demonstrem que o TAV Brasil pode contribuir para o desempenho produtivo do APL de SJC. Tal resultado pode advir da diferença na lógica espacial dos projetos: o APL é concentrado espacialmente, e o TAV é adequado ao transporte de média distância. Portanto, os resultados não invalidam a sugestão de que o TAV Brasil pode ter efeitos no desenvolvimento econômico da região, mas enfraquecem a proposta de que tal desenvolvimento esteja atrelado ao desempenho do APL do setor aeronáutico de São José dos Campos. _________________________________________________________________________________ ABSTRACT / Since 1981 Brazilian Federal Government is considering building a HSR in the Rio de Janeiro – São Paulo corridor (TAV Brazil). The project kickoff is delayed due to its complexity, what makes it difficult to assess its sustainability: on the one hand the planned investment is up to several tens of billions dollars, on the other HSR has a potential for changing the economic structure of the territory where it will operate (which is a wider benefit, beyond the elimination of existing bottlenecks in the current transportation system). The HSR is a transport technology that significantly changes time-space convergence, changing the characteristics of proximity and accessibility of people and firms located in the area of influence. Synergies between transport infrastructure and economic activities should be used to build a more development friendly environment, which justifies the association of HSR with other productive projects. This study investigates the possible interactions existing in the association of TAV Brazil with the strengthening of the aeronautics industry cluster located in São José dos Campos. Such investigation is done using a qualitative research method, which aims to systematize the search for interactions between HSR’s and clusters in the literature. The analysis showed that, for the case, most of the possible interactions are not robust. Only two interactions were considered valid following TAV Brazil construction: a positive impact to the image of the cluster and a negative impact to the performance of the clustered companies due to real estate prices upward. Thus, it is concluded that there is no sufficient evidence to demonstrate that TAV Brazil may contribute to the economic performance of the cluster located in Sao José dos Campos. This result may arise from differences in the spatial logic of projects: clusters are spatially concentrated, and HSR’s are suitable for medium-distance moves. Therefore, the results do not invalidate the suggestion that TAV Brazil may bring economic development effects to the region, but weaken the proposition that such development could be tied to a better performance of the São José dos Campos aeronautics industry cluster.
4

Influência do uso de trens de caixa móvel na implantação e operação de novas ferrovias. / Influence of the use of tilting trains on the implementation and operation of new railways.

Felipe Rabay Lucas 16 March 2015 (has links)
O presente trabalho tem por objetivo primário abordar os atuais conhecimentos sobre o transporte ferroviário interurbano e regional de passageiros, com foco na tecnologia dos trens de caixa móvel, também conhecidos como trens pendulares. Como objetivo secundário busca-se analisar a influência dos trens de caixa móvel ou pendulares na implantação e operação de novas ferrovias, com ênfase na adequação em fase de projeto, mostrando-se o potencial dessa tecnologia para o aumento da velocidade média e a redução dos tempos de viagem. São tratados os tópicos relevantes para o transporte ferroviário de passageiros, como o conforto do usuário, as especificações técnicas do material rodante e referências dos custos de implantação e operação envolvidos, mostrando-se também dentro de cada aspecto as diferenças dos trens pendulares em relação aos trens convencionais. Três estudos de caso elaborados terão como objetivo explicitar as interveniências da operação dos trens pendulares com o projeto ferroviário, em especial com o projeto geométrico, e através de simulações de marcha e comparações, mostrar de maneira prática o potencial do uso dos trens pendulares. Através do embasamento teórico e dos estudos de caso, é feita uma análise crítica de modo a possibilitar tanto um entendimento do transporte ferroviário de passageiros, quanto do material rodante de caixa móvel e suas possibilidades. Os resultados dos estudos de caso e a análise crítica mostram uma redução significativa dos tempos de viagem, entre 8,1 e 20,0%, mediante a operação de trens pendulares em substituição ao material rodante convencional. / As a primary objective, the present work aims to summarize the current knowledge on intercity and regional passenger railway transportation, focusing on tilting train technology, also known as car body tilt. As a secondary objective, the present work seeks to analyze the influence of tilting train technology on the design, implementation and operation of new railway corridors, with emphasis on design phase, showing the potential of this technology to increase speeds and reduce travel times. Railway passenger transportation issues, such as passenger comfort, rolling stock technical specifications and implementation and operational costs are addressed. Additionally, different aspects between conventional and tilting trains are also discussed. Three case studies help clarify the correlation between tilting train operation and railway design, especially the geometric design; further, with the help of speed simulations and comparisons, the potential use of tilting train operations are demonstrated. With the theoretical basis and the case studies, a critical analysis is made, allowing as a better understanding of railway passenger transportation with regards to the use of tilting rolling stock and its possibilities. The results of the case studies and the critical analysis present a considerable reduction in travel times, between 8,1 and 20,0%, with the operation of tilting trains in the place of the conventional rolling stock.
5

Recife no tempo da maxambomba (1867-1889): o primeiro trem urbano do Brasil

Duarte, José Lins January 2005 (has links)
Made available in DSpace on 2014-06-12T18:36:27Z (GMT). No. of bitstreams: 2 arquivo7823_1.pdf: 6919328 bytes, checksum: a82fcea6fe21e856ac7f5bd450296adc (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2005 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Este trabalho apresenta a introdução de um sistema de transporte urbano sobre trilhos na capital pernambucana em 1867. Entendemos tal fato como um acontecimento histórico relevante, não só em termos de incremento tecnológico, mas como um fator de transformação sob diferentes aspectos de integração urbana. Na segunda metade do século XIX, a cidade portuária se consolidava como centro financeiro e social da região, assim, disseminando um ambiente de prosperidade e progresso; mesmo envolta nesse clima de entusiasmo, demonstrava descontentamento com a situação dos serviços públicos vigentes, dentre eles o de transporte coletivo. Numa conjuntura mais ampla, o Brasil enfrentava uma nova fase na rota do comércio internacional em decorrência da abertura dos portos na primeira década desse período, daí, permitindo a afluência de produtos e idéias vindas do exterior, com forte tendência da concepção de modernidade, direcionada pela modernização. Tais influxos foram marcantes no âmbito da cidade, pois efetivamente um número acentuado de habitantes da localidade passou a dedicar mais atenção aos espaços públicos. A implantação do trem urbano, denominado pelos citadinos de maxambomba, foi resultado do empenho de grupos sociais preocupados em obter um meio de condução compatível com a necessidade e o prestígio do Recife. Esse desígnio contou com a participação de empreendedores britânicos, os quais se dispuseram a empregar elevada monta financeira no setor ferroviário, pois acreditaram nas condições favoráveis apresentadas pela urbe. Associada ao interesse pernambucano, a procura de novos mercados fazia parte do projeto expansionista europeu. Para tanto, podemos nos remeter ao transporte urbano de passageiro, com o qual se buscava expressar o sentimento de abertura de um caminho sem retorno, em que o antigo não recuperaria seu espaço, além de proporcionar consideráveis alterações no cotidiano da cidade
6

TLT-1 régule l’activation leucocytaire et contrôle la réponse inflammatoire systémique au cours du sepsis / TLT-1 regulates leukocyte activation and controls inflammatory response during polymicrobial sepsis

Derive, Marc 23 November 2011 (has links)
Le récepteur TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) joue un rôle crucial dans la mise en place du sepsis en amplifiant la réponse immunitaire de l'hôte. TLT-1 (TREM-Like Transcript-1) appartient à la famille des récepteurs TREMs, est exprimé exclusivement sur les plaquettes activées et est connu pour faciliter l'agrégation plaquettaire en liant le fibrinogène. Ces travaux montrent qu'une forme soluble de TLT-1 est impliquée dans la régulation de l'inflammation au cours du sepsis en modulant l'activation leucocytaire et le dialogue plaquette-neutrophile. Un peptide de 17 acides aminés issu de sa portion extracellulaire est porteur de cette activité par compétition avec le ligand de TREM-1. Alors que l'administration tant précoce que tardive de LR17 au cours du sepsis expérimental murin augmentait la survie, les animaux KO TLT-1 étaient hautement susceptibles à l'infection. Nous avons identifié ici un récepteur soluble libéré au cours de l'activation plaquettaire comme un potentiel régulateur de la réaction inflammatoire au cours du sepsis, ouvrant ainsi de nouvelles perspectives thérapeutiques / The Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) plays a crucial role during the onset of sepsis by amplifying the host immune response. The TREM-Like Transcript-1 (TLT-1) belongs to the TREM family, is selectively expressed on activated platelets, and is known to facilitate platelet aggregation through binding to fibrinogen. Here we show that a soluble form of TLT-1 is implicated in the regulation of inflammation during sepsis by dampening leukocytes activation and modulating platelet-neutrophil crosstalk. A 17-aa sequence of the TLT-1 extracellular domain (LR17) is responsible for this activity through competition with the TREM-1 ligand. While early or late LR17 treatment of septic mice improves survival, treml-1-/- animals are highly susceptible to polymicrobial infection. The present findings identify platelet derived sTLT-1 as a potent endogenous regulator of sepsis associated inflammation and open new therapeutic perspectives
7

La multimérisation de TREM-1 est essentielle pour son activation sur les monocytes et les neutrophiles / TREM-1 multimerization is essential for its activation on monocytes and neutrophils

Carrasco, Kevin 25 January 2018 (has links)
TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) est un récepteur exprimé par les cellules de l’immunité innée qui amplifie l’inflammation initiée par les TLRs (Toll-like Receptors) et est impliquée dans plusieurs pathologies inflammatoires aigües et chroniques. À ce jour, peu de choses sont connues quant aux mécanismes moléculaires d’activation de TREM-1. Ainsi, nous avons développé des outils pour pouvoir stimuler TREM-1 de façon monovalente et multivalente. Ces travaux montrent que TREM-1 est activé par multimérisation et qu’il est régulé différemment sur les neutrophiles et monocytes. En effet, sur les monocytes activés au LPS, l’activation de TREM-1 s’effectue en deux étapes tandis qu’une seule est nécessaire dans les neutrophiles. Grâce à des approches de protéomiques, nous avons confirmé la dimérisation de l’ectodomaine de TREM-1 en solution. De plus, la multimérisation semble aussi être médiée par le ligand naturel de TREM-1, qui est, entre autres, libéré par les neutrophiles activés au LPS. Le travail présenté ici est une première étape vers la compréhension des mécanismes moléculaires conduisant à l'interaction de TREM-1 et son ligand, ouvrant ainsi de nouvelles perspectives thérapeutiques / Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a receptor expressed on innate immune cells which amplifies inflammatory signals initially triggered by TLRs (Toll-like receptors) and TREM-1 has been characterized as a major player in the pathophysiology of acute and chronic inflammatory diseases. Currently, the molecular mechanisms leading to the activation of TREM-1 remain unknown. We have developed specific tools to stimulate TREM-1 in a monovalent and divalent way. Here we show that TREM-1 is activated by multimerization and is differentially regulated on neutrophils and monocytes. Indeed, TREM-1 activation on primary human monocytes by LPS required a two-step process while one is required on neutrophils. Using proteomic approaches, we have confirmed that TREM-1 ectodomain dimerizes in solution. Furthermore, the multimerization seems to be mediated by the natural ligand of TREM-1, which is released by LPS activated neutrophils. Collectively, our findings uncover molecular mechanisms leading to TREM-1 and its ligand interaction, painting the way of new therapeutics
8

Exploration du rôle de TREM-1 dans l'athérosclérose / TREM-1 inhibition reduces atherosclerosis

Joffre, Jérémie 25 November 2016 (has links)
Les cellules myéloïdes jouent un rôle majeur dans le développement et les complications de l’athérosclérose. TREM (Triggering Receptor Expressed on Myeloid cells)-1 est un récepteur, exprimé par les cellules myéloïdes, impliqué dans l’amplification de la réponse inflammatoire en réponse à une stimulation de la voie des TLRs. Notre objectif était d’étudier les conséquences de l’inhibition de TREM-1 sur le développement de l’athérosclérose expérimentale.Matériel et résultats : Dans un modèle de souris chimères Ldlr-/- retransplantées avec une moelle de souris Trem-1+/+ ou Trem-1-/-, nous avons montré que la déficience hématopoïétique en Trem-1 induisait une réduction de 42% de la taille des plaques d’athérosclérose au niveau du sinus aortique après 6 semaines de régime gras et une réduction de 60% après 14 semaines. De plus, la déficience hématopoïétique en Trem-1 induisait un phénotype lésionnel plus stable avec une moindre accumulation macrophagique, un centre nécrotique moins volumineux. Ces résultats ont été confirmés dans un modèle de souris ApoE-/-/Trem1-/-. Parallèlement, l’inhibition pharmacologique de TREM-1 par des injections répétées de peptide LR12 induisait une réduction significative de la taille des plaques au niveau du sinus et de l’aorte thoracique chez la souris ApoE-/- sous un régime riche en matières grasses. En utilisant différentes approches in vitro et in vivo, nous avons montré que l’invalidation génique de Trem-1 ou son inhibition pharmacologique induisait une déviation de la réponse immune vers un profil moins inflammatoire, réduisait le recrutement des monocytes non classiques dans la plaque d’athérosclérose et enfin limitait l’endocytose des lipides oxydés en régulant l’expression du CD36. Ces données de modulation de la réponse immune et de l’endocytose des lipides ont été confirmées sur des macrophages humains. Nous avons enfin montré que TREM-1 est exprimé dans des plaques d’athérosclérose humaines essentiellement par les macrophages spumeux. L’expression de TREM-1 est significativement plus importante dans les plaques athéromateuses par rapport aux plaques fibreuses. Conclusion : Nous avons montré que TREM-1 est impliqué dans le développement de l’athérosclérose à différents stades de la maladie, en modulant la réponse immune systémique et l’endocytose des lipides oxydés. L’inhibition de TREM-1 pourrait constituer une nouvelle cible thérapeutique des maladies cardiovasculaires. / Innate immune responses activated through myeloid cells contribute to the initiation, progression and complications of atherosclerosis in experimental models. However, the critical upstream pathways that link innate immune activation to foam cell formation are still poorly identified.Objectives: We hypothesized that activation of TREM (Triggering Receptor Expressed on Myeloid cells)-1 plays a determinant role in macrophage atherogenic responses. Methods and Results: Ldlr-/- mice reconstituted with bone marrow deficient for Trem-1 (Trem-1-/-) showed a strong reduction of atherosclerotic plaque size in both the aortic sinus and the thoraco-abdominal aorta, and were less inflammatory compared to plaques of Trem-1+/+ chimeric mice. Genetic invalidation of Trem-1 led to alteration of monocyte recruitment into atherosclerotic lesions and inhibited Tlr4-initiated pro-inflammatory macrophage responses. Furthermore, we identified a critical role for Trem-1 in the upregulation of Cd36, thereby promoting the formation of inflammatory foam cells. Genetic invalidation of Trem-1 in Apoe-/-/Trem-1-/- mice or pharmacological blockade of Trem-1 in Apoe-/- mice using LR-12 peptide also significantly reduced the development of atherosclerosis throughout the vascular tree, and lessened plaque inflammation. TREM-1 was expressed in human atherosclerotic lesions mainly in lipid-rich areas, with significantly higher levels of expression in atheromatous compared to fibrous plaques. Conclusion: We identify TREM-1 as a major upstream pro-atherogenic receptor. We propose that TREM-1 activation orchestrates monocyte/macrophage pro-inflammatory responses and foam cell formation through coordinated and combined activation of CD36 and TLR4. Blockade of TREM-1 signaling may constitute an attractive novel and double-hit approach for the treatment of atherosclerosis.
9

TREM-1, nouvel acteur de la cellule endothéliale et de la plaquette / TREM-1, a new player in endothelial cells and platelets

Jolly, Lucie 01 March 2018 (has links)
TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) est un immunorécepteur connu pour être exprimé par les neutrophiles et les monocytes/macrophages. Il joue un rôle fondamental dans l’amplification de la réponse inflammatoire via les TLR (Toll-like receptor). A l’aide de plusieurs outils expérimentaux, nous montrons pour la première fois que TREM-1 est exprimé par deux nouveaux types cellulaires : la cellule endothéliale et les plaquettes. La délétion sélective de TREM-1 au niveau endothélial protège du choc septique en réduisant la dysfonction et l’inflammation vasculaire, en modulant le recrutement et l’activation des cellules inflammatoires, et en améliorant la survie. De plus, la modulation pharmacologique via l’utilisation du peptide LR12 ou l'invalidation génétique de TREM-1 altère l'activation plaquettaire et prévient la formation de thrombus. Ces résultats fournissent un nouvel aperçu de la biologie TREM-1 et peuvent expliquer l'action protectrice de la modulation TREM-1 au cours des maladies inflammatoires aiguës comme le choc septique, au-delà de leurs effets sur les cellules myéloïdes. De plus, les agents modulateurs de TREM-1 tels que LR12 pourraient potentiellement être des ajouts utiles dans les thérapies antiplaquettaires dans le cadre de troubles thrombotiques / TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an immunoreceptor known to be expressed by neutrophils and monocytes/macrophages. It plays a fundamental role in the amplification of the inflammatory response mediated by TLR (Toll-like receptor) engagement. Using several experimental tools, we show for the first time that TREM-1 is expressed by two other cell types: endothelial cells and platelets. The selective deletion of TREM-1 at the endothelial level protects against septic shock by reducing dysfunction and vascular inflammation, modulating the recruitment and the activation of inflammatory cells, and improves survival. In addition, pharmacological modulation via the use of the LR12 peptide or genetic invalidation of TREM-1 alters platelet activation and prevents the formation of thrombi. These results provide new insights on the TREM-1 biology and may explain the protective effect of the TREM-1 modulation during acute inflammatory diseases such as septic shock beyond its role on myeloid cells. In addition, TREM-1 modulating agents such as LR12 could potentially be useful additions in antiplatelet therapies for thrombotic disorders
10

An Investigation into the Most Effective Therapy for Female Victims of Sex Trafficking

Tomback, Alexandra 01 January 2017 (has links)
The current literature on victims of sex trafficking lacks adequate research on effective therapeutic treatments for this population. This study aims to find an effective therapy for female victims of sex trafficking to treat trauma-related symptoms including PTSD, depression, anxiety, self-blame, self-esteem, and overall well-being by testing the effectiveness of eye-movement desensitization reprocessing (EMDR), trauma recovery and empowerment model (TREM), and psychoeducation. In this study, approximately 180-200 female victims of sex trafficking ages 18 or older will be randomly assigned to either the EMDR, TREM, psychoeducation, or a control-wait-list group. Trauma-related symptoms will be assessed pre-treatment (Time 1), post-treatment (Time 2), and 6- months post-treatment (Time 3) to assess the effectiveness of each intervention over time. It is expected that participants in all therapy groups will display significantly improved trauma-related symptoms compared to participants in the control-wait list group at time 2. It is further expected that participants in the TREM group will display significantly reduced self-blame and increased self-esteem and overall well-being at time 2 compared to participants in the EMDR and psychoeducation groups. Lastly, it is expected that improvement in trauma-related symptoms will be maintained from time 2 to time 3. These expected findings suggest that TREM will be the most effective long-term therapy for female victims of trafficking.

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