by Paul Moroney, Alan S. Willsky, Paul K. Houpt. / Bibliography: leaves 32-34. / "October, 1979." / NASA Ames Grant NGL-22-009-124

Made available in DSpace on 2016-03-10T13:16:17Z (GMT). No. of bitstreams: 2 diana_viveiros_ioc_dout_2014.pdf: 2553058 bytes, checksum: cd6b615f6279917df0cb1eea71997b6f (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2015-04-14 / Doenças pulmonares crônicas, como a asma e a silicose, são caracterizadas por inflamação das vias aéreas e fibrose que levam à marcada deterioração da função pulmonar. O objetivo da presente tese é investigar o impacto das propriedades anti-inflamatórias e antifibróticas do composto LASSBio-897 na asma e silicose experimental. Utilizaram-se metodologias diversas, incluindo a quantificação da reatividade de vias aéreas por pletismografia barométrica, além da quantificação do teor tecidual de mediadores inflamatórios por ELISA e do infiltrado celular pulmonar com técnicas de histologia e imunohistoquímica. Foram ainda quantificados a produção de citocinas por fibroblastos e macrófagos \201Cin vitro\201D. O tratamento oral profilático com LASSBio-897 (2 e 5 mg/kg) preveniu a instalação do quadro de hiper-reatividade brônquica, o infiltrado celular e a geração de citocinas pró-inflamatórias em modelos de asma aguda em camundongos. Por outro lado, o tratamento mostrou-se inativo quando feito após a instalação da resposta asmática. Resultados mais promissores foram obtidos na condição da silicose experimental, onde o tratamento oral terapêutico com LASSBio-897 (2 e 5 mg/kg) claramente inibiu o comprometimento da função pulmonar, o processo inflamatório e a fibrose observados induzidos pela exposição à sílica. O composto não interferiu com a atividade de mastócitos e células epiteliais estimuladas com sílica \201Cin vitro\201D No entanto, a administração de LASSBio-897 reduziu a expressão de F4/80 e \03B1-SMA no tecido pulmonar de animais silicóticos, evidenciando assim sua atividade sobre macrófagos e miofibroblastos, respectivamente. Ensaios \201Cin vitro\201D confirmaram esse efeito, uma vez que o composto reduziu a liberação de TNF-\03B1 por macrófagos alveolares estimulados com sílica e inibiu a proliferação e produção de colágeno induzida por IL-13 em fibroblastos pulmonares oriundos de animais silicóticos. Por fim, a administração do composto resultou na redução da expressão tecidual de NF-\03BAB após o desafio com sílica. Conclui-se que o composto LASSBio-897 pode prevenir a instalação do quadro de asma aguda, sem contudo alterar a resposta asmática já instalada. A capacidade do LASSBio-897 de reverter a resposta inflamatória e fibrótica pulmonar induzida por partículas de sílica sugere que uma aplicação na silicose, mais do que na asma, seja uma perspectiva verdadeiramente promissora / Chronic lung diseases such as asthma and silicosis are characterized by airway inflammation and fibrosis leading to marked deterioration of lung function. The aim of this thesis is to investigate the effect of compound LASSBio - 897 on experimental asthma and silicosis. Various pathol ogical parameters were assessed, including airway hyper - reactivity by barometric plethysmography, lung tissue content of inflammatory mediators by ELISA and cellular infiltration using histology and immunohistochemistry techniques. Cytokine generation from fibroblasts and macrophages in vitro was also quantified. Oral prophylactic treatment with LASSBio - 897 (2 and 5 mg/kg) prevented airway bronchial hyper - reactivity, leukocyte recruitment and cytokine generation in a model of acute asthma in mice. However, this treatment was inactive when performed after installation of the asthmatic response. More promising results were obtained in the experimental silicosis condition, where the LASSBio - 897 therapeutic treatment (2 and 5 mg/kg, oral) clearly inhib ited airway hyper - reactivity, as well as inflammation and peribronchial fibrosis induced by silica particles. Furthermore, LASSBio - 897 did not interfere with mast cells and epithelial cells activity after silica stimulation in vitro . However, LASSBio - 897 c learly reduced F4/80 and α - SMA expression in the lung of silicotic mice, showing its inhibitory effect on macrophages and myofibroblasts, respectively. In vitro assays confirmed this effect, since the compound reduced TNF - α release by an alveolar macrophag e cell lineage after silica exposure, and inhibited proliferation and collagen production induced by IL - 13 in lung fibroblasts recovered from silicotic mice. Finally, LASSBio - 897 reduced sil ica - induced upregulation of NF - κ B expression in the lung tissue. I t is concluded that LASSBio - 897 can prophylactically prevent the development of acute asthma, without altering the already installed asthmatic response. The capacity of LASSBio - 897 to reverse silica but not allergen - induced lung inflammation and fibrosis s uggests the application in silicosis, rather than in asthma, as a truly promising perspective

Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-11-20T12:15:35Z No. of bitstreams: 2 Dissertação - Telma Matos Guimaraes - 2013.pdf: 3613198 bytes, checksum: 0db69968e4da150a386327dd2a7a8213 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2014-11-20T12:16:24Z (GMT) No. of bitstreams: 2 Dissertação - Telma Matos Guimaraes - 2013.pdf: 3613198 bytes, checksum: 0db69968e4da150a386327dd2a7a8213 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-11-20T12:16:25Z (GMT). No. of bitstreams: 2 Dissertação - Telma Matos Guimaraes - 2013.pdf: 3613198 bytes, checksum: 0db69968e4da150a386327dd2a7a8213 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-05-27 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The " Microbial Models of Mammalian Metabolism" using filamentous fungi be used to study the biotransformation as an alternative to identify and product mammalian metabolites, with the goal of evaluate the profile of biotransformation of LASSBio 897, this This model was appliedto 3-thyenilidine-3,4-methylenedioxybenzoylhydrazide (LASSBio-897), a potential antihypertensive agent. The fungi Aspergillus alliaceus NRRL315, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC9244, NRRL1757 and Mortierela isabelina NRRL 1757 e Muccor plumbeus ATCC4740 were selected for the biotransformation LASSBio-897. The biotransformation was carried outin culture medium PDSM and Corn Steep at two different concentration sof the substrate.The monitoring of there action kinetics was done by methods thin layer chromatography (TLC) and high performance liquid chromatography(HPLC), separation and purification of the formed products was performed by colun chromatography (CC). Nuclear magnetic resonance (RMN) methods, mass spectrometry and spectroscopyin the region of Infrared (IR) assisted in the elucidation of the structure of the biotransformation products of LASSBio 897. We identified four metabolites in the reaction mixture and, based on information obtained by MS and NMR was proposed structure of 3-tienilidena-3,4-dihydroxybenzoilidrazine (Met. I), 1,3-benzodioxol-5-carboxamide (Met. II), 1, 3-benzodioxol acid (Met. III) and sulfoxide (Met. IV); A simultaneous study of the pharmacokinetics of LASSBio 897 in healthy Beagle dog indicated the presence of MET.I and II in dog serum confirming the importance of applying this model.to obtain metabolites mamalia. / O ―Modelo Microbiano do Metabolismo Animal‖ utilizando fungos filamentosos, pode ser usado para estudos de biotransformação como forma alternativa para identificar e produzir metabólitos de mamíferos. Com o objetivo de avaliar o perfil de biotransformação do LASSBio 897, esse modelo foi aplicado a 3-tienilidina-3,4- metilenedioxibenzoilidrazida (LASSBio-897), um potencial agente anti-hipertensivo. Os fungos Aspergillus alliaceus NRRL 315, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC 9244, Mortierela isabelina NRRL 1757 e Muccor plumbeus ATCC4740 foram selecionados. A biotransformação foi realizada nos meios de cultura PDSM e Corn Steep em duas concentrações diferentes. O monitoramento das cinéticas reacionais foi feito por Cromatografia em Camada Delgada (CCD) e Cromatografia Líquida de Alta Eficiência (CLAE), a separação e purificação dos produtos formados foi realizada por Cromatografia em Coluna (CC). Métodos de ressonância nuclear magnética (RMN), Espectrometria de Massas (EM) e Espectroscopia na região do Infravermelho (IV) auxiliaram na elucidação da estrutura dos compostos obtidos pela biotransformação do LASSBio 897. Quatro metabólitos foram identificados na mistura reacional, com base em informações obtidas por MS e RMN foram propostas as estruturas 3,4-tielidina diidroxibenzoilidrazina (Met. I); 1,3-benzodioxol-5-carboxiamida (Met. II); ácido 1,3-benzodioxóico (Met. III) e sulfóxido (Met. IV). Um estudo simultâneo de farmacocinética do LASSBio 897 em cão saudável da raça Beagle indicou a presença do Met. I e do Met. II no soro do animal. Confirmando a importância da aplicação deste modelo para obtenção de metabólitos de maíferos.

This thesis analyzes the inherent significance of trade wars in a practical as well as in a theoretical sense. The preliminary intention of the present research is to provide three different understandings of the trade war concept. Firstly, a general understanding of trade wars is introduced, primarily focusing on the technical aspects of the issue and its political and economic dimensions. Secondly, trade wars are viewed in a specific case study context: the Japanese-American commercial relations and their bilateral trade disputes that escalated into trade wars are investigated, focusing on semiconductor and biotechnology industries. Thirdly, the trade wars concept is correlated to Raymond Vernon&amp / #8217 / s Product Cycle theory, introducing the theoretical understanding of trade wars. The combination of these research themes endeavors to establish whether trade wars are primarily fought between successful industrial states over leading strategic core industries, those that are knowledge-intensive, and produce high-value-added products.

Les épigones de la Négritude nous ont habitués, dans la confrontation de l’Afrique et l’Europe, à la mise en scène d’un personnage qui, après avoir rêvé d’Europe avec des stéréotypes de l’image de la France véhiculées par l’école coloniale, est confronté, lors de son séjour en Europe, aux conditions de l’exil avec l’éloignement de la terre maternelle à laquelle porte toutes ses aspirations. Mais avec les écrivains de la Migritude, l’émigration vers l’Europe prend un contour différent, elle n’est plus motivée par une volonté de découverte mais une fuite de la terre maternelle devenue répulsive alors que l’Europe est aux yeux du migrant un lieu attractif enjolivé par les récits des immigrés qui ont déjà fait le voyage. Ce présent travail de recherche s’efforce de rendre compte de l’évolution qui s’est opérée sur la représentation de l’immigration en Europe depuis les écrivains de la première génération jusqu’à ceux de la seconde. / The followers of the Negritude accustomed us to the confrontation between Africa and Europe through the staging of a character-dreaming of Europe with stereotyped images of France conveyed by the colonial school-who is confronted with the conditions of exile during his stay in Europe and the remoteness of motherland which bears all his aspirations. But for the writers of Migritude, emigration to Europe takes a different turn; it is no longer motivated by a desire for discovery but an escape from the native land which has become repulsive, while Europe is in the eyes of migrants, an attractive place embellished by the stories of immigrants who, have already made the journey. The present research seeks to reflect on the change that has taken place on the representation of immigration in Europe, from the writers of the first generation to those of the second generation.

Dans la littérature de la Corne de l’Afrique d’expression française, on assiste très souvent à l’image caricaturée des personnages féminins qui sont engagés dans un quotidien difficile à vivre. Aussi bien dans les textes de Waberi que dans ceux de Nuruddin Farah, les personnages féminins sont constamment en fuite pour échapper au destin tragique d’une existence douloureuse où la misère morale et matérielle constitue un obstacle majeur. Si l’un des facteurs qui tend les personnages féminins vers une marginalisation effective est en rapport avec un espace acariâtre, dominé « par la volonté assassine d’un soleil impérial » (Waberi : 2002.32), il y en a également d’autres qui contribuent à étouffer leur identité dans un environnement traditionnel où « tout ce qui sort du troupeau est l’ailleurs, le lointain inconnu, les limbes du néant » (Waberi : 2002.104), . Nous intégrons cette perception essentiellement misogyne dans une dimension critique où la marginalisation liée à l’exploration du corps féminin dans Les Nuits d’Addis-Abeba se précise au fil de la narration à travers les différents rites sexuels gravés dans la chair des personnages féminins comme « une surface sur laquelle la société inscrit les différentes modalités de transaction » (Rangira Gallimore : 1994. 56). La présente thèse s’interroge dans un premier temps sur les problématiques liées à la question du genre dans l’univers romanesque des écrivains de la Corne de l’Afrique tout en prenant en considération l’imaginaire populaire et les faits sociologiques relatifs aux représentations de la femme dans cette même zone géographique. / In the Horn of Africa French-speaking literature, there are very often the caricatured images of female characters who are engaged in a difficult daily life. In both texts Waberi and Nuruddin Farah, female characters are constantly on the run to escape the tragic fate of a painful existence where moral and material/financial poverty is a major obstacle. If one of the factors that tends the female characters towards effective marginalization is related to a cantankerous space, dominated “by the vicious will of an imperial Sun”, there are also others who are contributing to stifle their identity in a traditional environment where "anything out of the herd is the elsewhere, the unknown distance, the limbo of oblivion”. We integrate this essentially misogynist perception in a critical size where marginalization related to exploration of the female body in” the nights in Addis Ababa takes shape over the narrative through exploitation the sexual rites that is graved in the flesh of female characters as” a surface where society registers the various terms of transaction”. This present thesis questions initially on issues related to the gender issue in the novelistic universe of writers while taking into account the popular imagination on the representations of women in the Horn of Africa.

La Corne de l’Afrique comme le reste du continent noir possède une littérature orale traditionnelle riche et variée, qui va de la mythologie pastorale à la poésie en passant par la légende et le conte. Avec les bouleversements sociaux intervenus avec l’arrivée des colons européens et l’introduction de l’écriture, la chaîne de transmission de la tradition orale est menacée. De nombreux Européens ont cherché à décrire les us et coutumes de ces populations. D’autre part, les écrivains de la Corne de l’Afrique s’inspirent souvent de l’oralité en lui octroyant ainsi une nouvelle virginité. Le présent travail de recherche s’efforce de rendre compte des formes traditionnelles de l’oralité et de leur impact sur la littérature moderne. / The Horn of Africa has a traditional oral literature which is rich and varied as the rest of the continent, starting from pastoral mythology to poetry, legend and storytelling. But with the social upheaval which occurred with the arrival of European settlers and the introduction of writing, the chain of transmission of the oral tradition is threatened. Many Europeans have sought to describe the habits and customs of these people. Whereas on the other hand, the writers from the Horn of Africa are often inspired by giving it (orality) and a new way of doing it. The following research work strives to reflect traditional forms of orality and their impact on modern literature.

Una de las principales razones de la existencia de las organizaciones estatales son las necesidades que tienen los usuarios para ser atendidos ante cada requerimiento que se tenga, algunas instituciones ya han logrado modernizarse frente la exigencia de todos, aunque muchos también están en ese camino, el Centro de Gestión Tributaria de la ciudad de Chiclayo ha presentado ciertos niveles de insatisfacción por parte de sus usuarios, en muchos casos por lo extenso de los procesos y la actitud de los colaboradores. El objetivo general de esta investigación fue determinar si el modelo de satisfacción de usuarios es una herramienta de apoyo para la organización en estudio. El enfoque fue cuantitativo, descriptivo y correlacional, se tomó una encuesta a 344 usuarios para determinar la relación entre los aspectos de factor humano, calidad de servicios, espacios físicos, satisfacción, factor organizativo y la imagen. Se plantearon las respectivas hipótesis y objetivos específicos según cada uno de los elementos estudiados. Los resultados del análisis de correlación muestran que, todas las significancias de las variables se realizan, mientras que la Imagen se relaciona con una alta significancia con el Factor Organizativo (0.781), a su vez, el Factor Organizativo frente a la Calidad obtuvo una baja correlación (.0450). Se concluye que el modelo de satisfacción de usuarios es una herramienta indispensable de apoyo para el Centro de Gestión Tributaria, además, se plantean algunas recomendaciones, los más importantes es la mejora de la actitud de los colaboradores y la simplificación de procesos que están afectando el servicio.