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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.
11

Imunoexpressão das proteínas inibidoras da apoptose (xiap; survivina) e de seu antagonista SMAC/DIABLO no carcinoma mamário ductal invasivo, sem outra especificação (SOE): correlação com os marcadores imunoistoquímicos prognósticos usuais, índice apoptótico e prognóstico / Immunoexpression of apoptosis inhibitor proteins (xiap; survivine) and its antagonist SMAC/DIABLO on ductal invasive breast carcinoma, not otherwise specified (NOS) carcinoma: correlation with usual prognostic immunohistochemical markers,apoptotic index and prognosis

Carvalho Filho, Ivan Rodrigues de [UNESP] 20 December 2016 (has links)
Submitted by IVAN RODRIGUES DE CARVALHO FILHO null (ircf71@uol.com.br) on 2017-05-30T18:49:07Z No. of bitstreams: 1 TESE FINALIZADA EM PDF.pdf: 3632299 bytes, checksum: 7a61adaae038965031f187518ca0c4de (MD5) / Rejected by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: No campo “Versão a ser disponibilizada online imediatamente” foi informado que seria disponibilizado o texto completo porém no campo “Data para a disponibilização do texto completo” foi informado que o texto completo deverá ser disponibilizado apenas 6 meses após a defesa. Caso opte pela disponibilização do texto completo apenas 6 meses após a defesa selecione no campo “Versão a ser disponibilizada online imediatamente” a opção “Texto parcial”. Esta opção é utilizada caso você tenha planos de publicar seu trabalho em periódicos científicos ou em formato de livro, por exemplo e fará com que apenas as páginas pré-textuais, introdução, considerações e referências sejam disponibilizadas. Se optar por disponibilizar o texto completo de seu trabalho imediatamente selecione no campo “Data para a disponibilização do texto completo” a opção “Não se aplica (texto completo)”. Isso fará com que seu trabalho seja disponibilizado na íntegra no Repositório Institucional UNESP. Por favor, corrija esta informação realizando uma nova submissão. Agradecemos a compreensão. on 2017-05-30T20:42:08Z (GMT) / Submitted by IVAN RODRIGUES DE CARVALHO FILHO null (ircf71@uol.com.br) on 2017-05-31T02:30:55Z No. of bitstreams: 1 TESE FINALIZADA EM PDF.pdf: 3632299 bytes, checksum: 7a61adaae038965031f187518ca0c4de (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-05-31T14:32:58Z (GMT) No. of bitstreams: 1 carvalhofilho_ir_dr_bot.pdf: 3632299 bytes, checksum: 7a61adaae038965031f187518ca0c4de (MD5) / Made available in DSpace on 2017-05-31T14:32:58Z (GMT). No. of bitstreams: 1 carvalhofilho_ir_dr_bot.pdf: 3632299 bytes, checksum: 7a61adaae038965031f187518ca0c4de (MD5) Previous issue date: 2016-12-20 / A maioria dos tumores malignos da mama apresenta aspecto morfológico de carcinoma ductal invasivo que pode apresentar diferentes prognósticos. Diante disso, conclui-se que a identificação do padrão morfológico não é suficiente para o estabelecimento do prognóstico, e que existe a necessidade da identificação de novos biomarcadores imunoistoquímicos que indiquem moléculas sinalizadoras importantes para proliferação e sobrevivência das células neoplásicas, e que possam ser alvos de modalidades terapêuticas oncológicas. A ocorrência de alterações dos mecanismos regulatórios genéticos da apoptose pode resultar em uma hiperativação das proteínas antiapoptóticas, com a perda da sensibilidade aos sinais de morte fisiológica, evitando-se a ocorrência da apoptose e resultando, desse modo, na preservação de células geneticamente alteradas com consequente aumento no seu número. Esse é um evento crítico para o início do crescimento tumoral, com repercussões no prognóstico e na resistência ao tratamento oncológico. Dessa forma, o entendimento da maquinaria das vias do processo apoptótico é de crucial importância na avaliação prognóstica do processo neoplásico, pois suas moléculas são importantes biomarcadores da proliferação e sobrevivência celular. Objetivos: Avaliar a relação entre as proteínas inibidoras do processo apoptótico (IAPs) e seu inibidor Smac/DIABLO no carcinoma mamário ductal invasivo, sem outra especificação (SOE). Analisar, também, sua correlação com os marcadores imunoistoquímicos usuais, aplicados para a avaliação prognóstica, índice apoptótico e taxa de sobrevida dos pacientes. Material e Métodos: Foram confeccionados blocos de parafina de TMA com tecido de câncer mamário ductal invasivo sem outra especificação (SOE), extraído de pacientes operadas no Hospital das Clínicas da Faculdade de Medicina de Botucatu, entre 1980 e 2000. Estes foram submetidos à reação imunoistoquímica para Survivina, XIAP, Smac, Caspase 3 clivada (índice apoptótico) e Ki67 (índice de proliferação celular), RE, RP, HER2, P53. Dois patologistas realizaram a leitura das lâminas e obteve-se escores de intensidade de imunoexpressão e/ou percentuais de positividade celular. Esses escores foram correlacionados entre as proteínas apoptóticas, com outros marcadores imunoistoquímicos prognósticos usuais, com os dados de sobrevida dos pacientes, com o grau histológico e com o perfil molecular especifico do carcinoma ductal invasivo. Resultados: Ocorreu uma correlação positiva entre Smac, Survivina e XIAP, houve maior intensidade de imunoexpressão dos marcadores de apoptose nos tumores de maior grau e uma correlação de imunoexpressão inversa entre Smac e um status hormonal positivo. Um estímulo pró-apoptótico pareceu ser dominante no carcinoma mamário de subtipo molecular HER2, quando comparado a outros subtipos. XIAP foi a única proteína apoptótica estudada que guardou correlação com a taxa de mortalidade. Conclusão: A detecção de uma correlação estatística significante entre as proteínas apoptóticas, corrobora a integração múltipla que ocorre entre essas durante o processo apoptótico no carcinoma mamário invasivo, sem outra especificação (SOE). Estudos adicionais das proteínas apoptóticas com uma maior amostragem de pacientes serão necessários para o estabelecimento de valores prognósticos mais acurados de sobrevida. / Most of malignant breast tumors exhibit morphological aspect of invasive ductal carcinoma, not otherwise specified (NOS) carcinoma, that can present different prognosis. It concludes that the identification of the morphological type of the breast cancer is not enough to establish tumor prognosis. So there is the need to recognize new immunohistochemistry biomarkers that can identify important molecular signaling proteins of neoplastic cell proliferation and survival that can be used as target of oncological therapeutic. Changes in these regulatory mechanisms that favors the hiperactivation of antiapoptotic proteins can set the loss of the physiological signs of cell death avoiding the occurrence of apoptosis and preserving genetic modified cells. This is a critical event to the beginning of tumor growth which may further lead to repercussions in prognosis and cancer resistance to therapy. The knowledge about the different pathways to apoptosis is crucial to evaluate the prognosis of the neoplastic process. Objectives: To study the relation between the inhibitors of apoptosis proteins (IAPs) and their antagonist, the protein SMAC/DIABLO, in invasive ductal breast carcinoma and also evaluate their correlation with the usual prognostic immunohistochemical markers, Apoptotic Index and clinical prognostics factors. Design: TMA paraffin blocks were made with invasive ductal breast carcinoma tissue samples of patients operated at the Botucatu School of Medicine Hospital from 1980 to 2000. Those samples were submitted to immunohistochemical reactions to Survivin, XIAP, cleaved Caspase 3 (apoptotic index) and Ki67 (cell proliferation index), RE, RP, HER2, P53. Two experienced pathologists analyzed the microscope slides and retrieved intensity scores and/or the percentage of positive cells of immune-expression. Those scores were interrelated and with IA, anti-cleaved caspase 3, the other usual immunohistochemical biomarkers and survival patients records, as well as the specific type and grade of the invasive ductal carcinoma. Results: There was a positive correlation between SMAC, Survivina and XIAP, as well as a higher immunoexpression intensity of apoptosi’s markers with high grade tumor, and a inverse immunoexpression correlation between SMAC and positive progesterone hormonal status. The pro-apoptotic stimulus seemed be dominant in breast carcinoma HER2 molecular subtype when compared to other subtypes.A pro-apoptotic stimulus seemed be dominant in breast carcinoma HER2 molecular subtype when compared to other subtypes.XIAP was the only one apoptotic protein studied that played correlation with mortality rate. Conclusion: The detection of a statistically significant correlation between the apoptotic proteins corroborates the multiple integration that occurs between these during the apoptotic process in invasive mammary carcinoma with no other specification. Further studies of apoptotic proteins in a large survey will be necessary to establish more accurate values of prognostic survival.
12

Fysiklärares val och hinder vid laborationsbedömning

Magnusson, Björn January 2020 (has links)
Många lärare framhäver laborationen som viktig, medan forskning visar på svårigheter i att uppnå dess mål. Syftet med denna studie är att inom svensk gymnasiefysik undersöka lärares beskrivningar av sin examination av de laborativa kunskapskraven, deras val av bedömningsform, samt de ramfaktorer de upplever hindrar dem uppnå deras ideala examination. Fem lärare intervjuades kvalitativt med ett resultat som mestadels bekräftar tidigare forskning. Sammanfattningsvis var elevens förmåga att tolka resultat, det som till högst grad examinerades, med labbrapport som vanligaste examinationsformen. Lärarna hade även till stor del reflekterat över andra examinationssätt, men upplevde sig hindrade av främst ekonomiska resurser och tid.
13

A Comparison of Cultured Human Dermal Fibroblasts Derived from Terminal and Vellus Hair Bearing Skin. Differences in the expression of inhibitors of apoptosis proteins, oestrogen receptors, and responses to oestradiol under normal and wound induced conditions

Kamala, Ola January 2014 (has links)
Wounds heal better in skin with terminal hair follicles (large and pigmented) as opposed to those with vellus hair follicles (small and unpigmented), while dermal fibroblasts from different anatomical regions also exhibit phenotypical differences. Tissue repair requires a tight control of cell proliferation, migration and apoptosis, and recent studies have shown the importance of inhibitors of apoptosis proteins (IAPs), which are proteins that prevent the process of apoptosis via their interaction with caspase molecules in wound healing. Oestrogens improve the rate and quality of wound healing, but their relationship with IAPs in human skin has not been studied. Therefore, terminal (scalp) and vellus (facial) hair bearing skin from the same donor was compared in situ and matching primary cultures of dermal fibroblasts were established from terminal (DF(T)) and vellus (DF(V)) hair bearing skin. Using immunofluorescent staining, the expression of IAPs and their antagonists was compared at different stages of the hair cycle following depilation using a murine model and then in terminal and vellus hair bearing human skin. The size and granularity of matching DF(T) and DF(V) cultures was compared by FACS analysis and mRNA and protein expression of Apollon, cIAP2, NAIP and XIAP and their antagonists DIABLO and Xaf1 analysed by qRT-PCR and immunocytochemistry in unwounded and mechanically wounded fibroblast cultures. Differences in proliferation, migration, viability and caspase 3 activity in the presence of 17β-oestradiol and changes in mRNA expression of the oestrogen receptors (GPR30, ERα and ERβ) were compared between the two cell types. IAP protein expression was generally found higher during mid anagen of the hair cycle in murine skin and hair follicles. Overall, expression was slightly higher in human terminal hair bearing skin compared to corresponding vellus hair bearing skin. IAP protein expression was similar in unwounded DF(T) and DF(V) cells with the exception of Apollon which was higher in DF(V) cells. With the exception of XIAP and its direct antagonist Xaf1, mRNA expression was higher in DF(V) cells compared to corresponding DF(T) cells. FACS analysis demonstrated that DF(V) cells were more granular than matching DF(T) cells and proliferated faster. 17β-oestradiol accelerated migration of DF(T) cells only. Mechanical wounding decreased XIAP mRNA in DF(T) and increased it in DF(V) cells, while simultaneously decreasing Xaf1 expression. In unwounded cells, 17β-oestradiol stimulated the expression of XIAP mRNA in both DF(T) and DF(V) cells, but in scratched monolayers, while it also increased expression in DF(T) cells it decreased it in DF(V) cells. A XIAP inhibitor reduced cell viability in both DF(T) and DF(V) cells, which was rescued by 17β-oestradiol in unwounded and mechanically wounded DF(T) cells, but only in unwounded DF(V) cells. 17β-oestradiol decreased caspase 3 activity in the presence of a XIAP inhibitor only in DF(T) cells. These results demonstrate significant differences between dermal fibroblasts cultured from terminal and vellus hair bearing skin of the same individual. The correlation between an increase in XIAP in response to 17β-oestradiol and a higher number of viable cells, along with a reduction in caspase 3 activity suggests that the protective effect of 17β-oestradiol may be modulated via the regulation of XIAP. Further elucidation of these different signalling pathways in dermal fibroblasts from hair bearing skin may lead to improved therapies for chronic non-healing wounds, particularly in postmenopausal females.
14

Habitação social no nordeste: a atuação das CAPs e dos IAPs (1930-1964) / Social housing in the northeast: the role of CAPs and IAPs (1930-1964)

Almeida, Caliane Christie Oliveira de 03 August 2012 (has links)
Criados principalmente ao longo das três primeiras décadas do século XX, os institutos de previdência existentes possuíam como objetivo primordial conceder auxílios financeiros em caso de doença ou morte do chefe de família, voltados principalmente ao funcionalismo público do país. Paulatinamente, suas funções foram se ampliando para o campo do trabalho, passando a se conformarem como órgãos de assistência e de seguro para as demais categorias trabalhistas, culminando na criação e diversificação das Caixas e Institutos de Aposentadoria e Pensões subordinados ao MTIC. Foi nesse contexto que a construção e o financiamento de unidades habitacionais passaram a serem tidos como de responsabilidade estatal no Brasil. A identificação e análises da política pública habitacional empreendida pelos referidos órgãos no Nordeste do país, entre 1930 e 1964, bem como da produção de moradias resultante, sua arquitetura, urbanismo e profissionais envolvidos, se conformaram como os principais objetivos desta tese. Um estudo empírico analítico, baseado em distintas fontes, sobretudo primárias, que dialogam em diferentes níveis para a desconstrução de verdades historiográficas fossilizadas sobre o tema e para o conhecimento de uma atuação ainda ofuscada por análises centradas na produção do centro-sul do país. Livrando-se do atual otimismo historiográfico acerca da atuação dos IAPs, que pouco estudou sobre as CAPs, evidenciou-se no Nordeste uma política restritiva focada, sobretudo, no atendimento dos anseios imobiliários dos trabalhadores urbanos mais abastados, incluindo os empregadores, que chegou a representar 45,74% dos pleitos concedidos. A quantificação dessa produção habitacional se coloca em torno das 20.000 unidades, que corresponde a 62,46% do volume de pleitos apontados pela historiografia para as regiões Norte, Sul e Nordeste do país, confirmando a hipótese da necessidade de estudos mais aprofundados acerca da atuação dos supracitados institutos de previdência em todo o território nacional. Mais precisamente foram identificados 147 grupos residenciais, entre unidades unifamiliares e edifícios coletivos, na maior parte das vezes, destituídos de equipamentos de uso coletivo. Amplo também foi o quadro do corpo técnico, conformado principalmente por engenheiros e arquitetos, atuantes direta ou indiretamente por meio das CAPs/IAPs no campo da moradia naquela região: um montante de aproximadamente 200 profissionais. No que concerne à arquitetura e urbanismo, constatou-se um diversidade de modelos vinculados a diferentes referências arquitetônicas. Surpreendentemente, evidenciou-se que para além do financiamento dos primeiros conjuntos residenciais modernos, as CAPs e os IAPs foram os responsáveis pela execução de diversas obras urbanas, pela criação e/ou ampliação de diferentes indústrias de base, se configurando como importante ator no processo de industrialização no país, financiando inclusive a construção de alguns dos principais ícones da arquitetura moderna brasileira, a citar, os prédios do Ministério da Educação e da Previdência, além da construção de Brasília. No Nordeste, mais precisamente, foram os propulsores da verticalização da maior parte de suas capitais. / The existing security institutes were created mainly along the first three decades of the twentieth century, and they had as main objective to ensure financial assistance in case of illness or death of the breadwinner, mainly focused on the civil service of the country. Gradually, their roles were expanding to the field of work, going to conform to service agencies and insurance for other labor categories, culminating in the creation and diversification of boxes and the Retirement and Pension Institutes subordinated to MTIC. It was in this context that the construction and financing of housing units started to be regarded as a state responsibility in Brazil. The identification and analysis of public policy undertaken by the aforementioned housing agencies in the Northeast, between 1930 and 1964, and the resulting production of housing, architecture, urbanism and professionals involved, conformed as the main objectives of this thesis. An empirical analytical, based on different sources, especially primary, that dialogue at different levels for the deconstruction of historiographic fossilized truths on the subject and the knowledge of an action still overshadowed by analyzes focused on the production of the center-south. Getting rid of the current historiographical optimism about the role of IAPs, which are little studied on the CAPs, there was a restrictive policy in the Northeast focused mainly on meeting the housing aspirations of the wealthier urban workers, including employers, who came to representing 45.74% of the granted claims. The quantification of this housing production stands around 20,000 units, representing 62.46% of the volume of claims raised by the history for the North, South and Northeast, confirming the hypothesis of the need for further studies on the activities the above security institutes throughout the country. One hundred fifty more residential groups were precisely identified, including single-family units and collective buildings, in most cases devoid of equipment for collective use. Broad was also the part of staff, formed mainly by engineers and architects, acting directly or indirectly through the CAPs/IAPs in the field of housing in the region: an amount of approximately 200 professionals. In terms of architecture and urbanism, it was found a variety of models linked to different architectural references. Surprisingly, it was observed that in addition to the funding of the first modern residential complexes, the CAPs and the IAPs were responsible for the implementation of various urban development, the creation and/or expansion of different industries, shaping up as an important actor in the process industrialization in the country, including financing the construction of some of the major icons of modern Brazilian architecture, quote, the buildings of the Ministry of Education and Welfare, besides the construction of Brasilia. In the Northeast, more precisely, were the drivers of vertical integration of most of their capital.
15

Habitação social: origens e produção (Natal, 1889-1964) / Social habitation in Natal (1889-1964)

Almeida, Caliane Christie Oliveira de 26 September 2007 (has links)
A presente dissertação tem como tema \"políticas públicas habitacionais\", tomando a capital norte-riograndense - Natal - como estudo de caso. O objeto de estudo conforma-se na relação entre a questão da habitação social no Brasil, as soluções dadas ao problema da habitação por órgãos estatais, os agentes financiadores, propulsores e construtores envolvidos neste processo e a construção e idealização da cidade de Natal. Sendo assim, a pesquisa objetiva entender quais as lógicas e objetivos que impulsionaram as ações estatais no campo da habitação social em Natal, entre 1889 e 1964, como também, o contexto ideológico, econômico e social imbuído nesse processo. A partir dessa análise, buscou-se especificar as origens e delimitar o processo de evolução da produção de moradias pelas administrações públicas, além de registrar e periodizar essa produção, dando especial atenção à atuação dos Institutos de Aposentadorias e Pensões (IAPs) na cidade. Posteriormente procedeu-se a interpretação e a análise das justificativas e discursos que basearam as ações estatais, considerando os diferentes agentes envolvidos no processo, além do estudo da configuração arquitetônica e urbanística dos conjuntos de moradias erguidos na capital no referido período. Para tanto, realizou-se principalmente o levantamento de dados primários em arquivos públicos e privados da cidade. A pesquisa se justifica pela insuficiência de historiografia local no que dizia respeito à política pública de habitação no período que antecede a criação do BNH, em 1964, pelo volume significativo de moradias erguidas pelo Estado e por órgãos associados a ele e pelas especificidades da política de habitação em Natal, como as parcerias realizadas pelo governo, inclusive com órgãos internacionais, e a construção e financiamento de casas de taipa. Nesse sentido, foi identificado um número significativo de moradias construída em taipa e inseridas nas ações imobiliárias dos IAPs em Natal, fosse por via de construção, de aquisição e de repasse, ou por meio de financiamentos para a realização de reformas. Tais moradias chegaram a corresponder a 20% dos financiamentos concedidos pela Carteira Predial do Instituto, como foi o caso IAP dos industriários. Os IAPs em conjunto com a Fundação da Casa Popular e com a Fundação da Habitação Popular do RN conceberam moradias à aproximadamente 3.100 famílias, entre os anos de 1946 e 1963, o que correspondeu a 8,12% da população da cidade em meados da década de 1960. Pretende-se nessa pesquisa contribuir para o conhecimento da história da moradia social no Brasil, através da análise das ações realizadas em Natal. / The subject of this dissertation is \"the public politics for habitation\", and it has as case of study, the capital of Rio Grande do Norte - Natal. The object of the study consists in the relation between the issues of social habitation in Brazil, the solutions given to the problem by the means of the state, the financial supporters, propelling and constructors involved on this process and the construction and he idealization of the city of Natal. Being thus, the research intend to understand which are the logics and the objectives that stimulated the State actions in the field of social habitation in Natal, from 1889 to 1964, and also, the ideological, economical and social contexts in this process. From this analysis, one searched to specify the origins and to delimit the production\'s evolution process of the social habitations, and also register and divide in periods that production, standing out the Retirement and Pension\'s Institute\'s (IAPs) actuation in the city. Later, the justifications and the speeches based on the State actions were interpreted and analyzed, considering the different agents involved in the process, beyond the study of the housing estate\'s architectonic and urban configuration, built in this period. Doing so, one realized the primary data survey at the city\'s public and private archives. The research is justified by the deficiency of local historiography on habitation\'s public politics in the period before the creation of the BNH, in 1964, by the significant number of houses built by the State and by associated organs and by the habitation\'s politic particularities in Natal, such as the government partnerships, including those with international organs, and the mud houses\' financing and construction. Considering this, it was identified as significant number of mud houses and inserted on IAP\'s real estate actions in Natal, by meanings of construction, acquisition and repass or by reform\'s financings. Such housings had arrived to correspond to 20% of financings granted by the Carteira Predial do Instituto, as the IAP dos industriários\' case. The IAPs in set with the Popular House Foundation and with the Popular Habitation Foundation had conceived housings to, approximately 3.100 families, between the years 1946 and 1963, which corresponds to 8,12% of the city\'s population in the middle of the decade of 1960. This research intends to contribute for the social habitation knowledge of the history in Brazil, through the actions\' analysis in Natal.
16

Habitação social no nordeste: a atuação das CAPs e dos IAPs (1930-1964) / Social housing in the northeast: the role of CAPs and IAPs (1930-1964)

Caliane Christie Oliveira de Almeida 03 August 2012 (has links)
Criados principalmente ao longo das três primeiras décadas do século XX, os institutos de previdência existentes possuíam como objetivo primordial conceder auxílios financeiros em caso de doença ou morte do chefe de família, voltados principalmente ao funcionalismo público do país. Paulatinamente, suas funções foram se ampliando para o campo do trabalho, passando a se conformarem como órgãos de assistência e de seguro para as demais categorias trabalhistas, culminando na criação e diversificação das Caixas e Institutos de Aposentadoria e Pensões subordinados ao MTIC. Foi nesse contexto que a construção e o financiamento de unidades habitacionais passaram a serem tidos como de responsabilidade estatal no Brasil. A identificação e análises da política pública habitacional empreendida pelos referidos órgãos no Nordeste do país, entre 1930 e 1964, bem como da produção de moradias resultante, sua arquitetura, urbanismo e profissionais envolvidos, se conformaram como os principais objetivos desta tese. Um estudo empírico analítico, baseado em distintas fontes, sobretudo primárias, que dialogam em diferentes níveis para a desconstrução de verdades historiográficas fossilizadas sobre o tema e para o conhecimento de uma atuação ainda ofuscada por análises centradas na produção do centro-sul do país. Livrando-se do atual otimismo historiográfico acerca da atuação dos IAPs, que pouco estudou sobre as CAPs, evidenciou-se no Nordeste uma política restritiva focada, sobretudo, no atendimento dos anseios imobiliários dos trabalhadores urbanos mais abastados, incluindo os empregadores, que chegou a representar 45,74% dos pleitos concedidos. A quantificação dessa produção habitacional se coloca em torno das 20.000 unidades, que corresponde a 62,46% do volume de pleitos apontados pela historiografia para as regiões Norte, Sul e Nordeste do país, confirmando a hipótese da necessidade de estudos mais aprofundados acerca da atuação dos supracitados institutos de previdência em todo o território nacional. Mais precisamente foram identificados 147 grupos residenciais, entre unidades unifamiliares e edifícios coletivos, na maior parte das vezes, destituídos de equipamentos de uso coletivo. Amplo também foi o quadro do corpo técnico, conformado principalmente por engenheiros e arquitetos, atuantes direta ou indiretamente por meio das CAPs/IAPs no campo da moradia naquela região: um montante de aproximadamente 200 profissionais. No que concerne à arquitetura e urbanismo, constatou-se um diversidade de modelos vinculados a diferentes referências arquitetônicas. Surpreendentemente, evidenciou-se que para além do financiamento dos primeiros conjuntos residenciais modernos, as CAPs e os IAPs foram os responsáveis pela execução de diversas obras urbanas, pela criação e/ou ampliação de diferentes indústrias de base, se configurando como importante ator no processo de industrialização no país, financiando inclusive a construção de alguns dos principais ícones da arquitetura moderna brasileira, a citar, os prédios do Ministério da Educação e da Previdência, além da construção de Brasília. No Nordeste, mais precisamente, foram os propulsores da verticalização da maior parte de suas capitais. / The existing security institutes were created mainly along the first three decades of the twentieth century, and they had as main objective to ensure financial assistance in case of illness or death of the breadwinner, mainly focused on the civil service of the country. Gradually, their roles were expanding to the field of work, going to conform to service agencies and insurance for other labor categories, culminating in the creation and diversification of boxes and the Retirement and Pension Institutes subordinated to MTIC. It was in this context that the construction and financing of housing units started to be regarded as a state responsibility in Brazil. The identification and analysis of public policy undertaken by the aforementioned housing agencies in the Northeast, between 1930 and 1964, and the resulting production of housing, architecture, urbanism and professionals involved, conformed as the main objectives of this thesis. An empirical analytical, based on different sources, especially primary, that dialogue at different levels for the deconstruction of historiographic fossilized truths on the subject and the knowledge of an action still overshadowed by analyzes focused on the production of the center-south. Getting rid of the current historiographical optimism about the role of IAPs, which are little studied on the CAPs, there was a restrictive policy in the Northeast focused mainly on meeting the housing aspirations of the wealthier urban workers, including employers, who came to representing 45.74% of the granted claims. The quantification of this housing production stands around 20,000 units, representing 62.46% of the volume of claims raised by the history for the North, South and Northeast, confirming the hypothesis of the need for further studies on the activities the above security institutes throughout the country. One hundred fifty more residential groups were precisely identified, including single-family units and collective buildings, in most cases devoid of equipment for collective use. Broad was also the part of staff, formed mainly by engineers and architects, acting directly or indirectly through the CAPs/IAPs in the field of housing in the region: an amount of approximately 200 professionals. In terms of architecture and urbanism, it was found a variety of models linked to different architectural references. Surprisingly, it was observed that in addition to the funding of the first modern residential complexes, the CAPs and the IAPs were responsible for the implementation of various urban development, the creation and/or expansion of different industries, shaping up as an important actor in the process industrialization in the country, including financing the construction of some of the major icons of modern Brazilian architecture, quote, the buildings of the Ministry of Education and Welfare, besides the construction of Brasilia. In the Northeast, more precisely, were the drivers of vertical integration of most of their capital.
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Habitação social: origens e produção (Natal, 1889-1964) / Social habitation in Natal (1889-1964)

Caliane Christie Oliveira de Almeida 26 September 2007 (has links)
A presente dissertação tem como tema \"políticas públicas habitacionais\", tomando a capital norte-riograndense - Natal - como estudo de caso. O objeto de estudo conforma-se na relação entre a questão da habitação social no Brasil, as soluções dadas ao problema da habitação por órgãos estatais, os agentes financiadores, propulsores e construtores envolvidos neste processo e a construção e idealização da cidade de Natal. Sendo assim, a pesquisa objetiva entender quais as lógicas e objetivos que impulsionaram as ações estatais no campo da habitação social em Natal, entre 1889 e 1964, como também, o contexto ideológico, econômico e social imbuído nesse processo. A partir dessa análise, buscou-se especificar as origens e delimitar o processo de evolução da produção de moradias pelas administrações públicas, além de registrar e periodizar essa produção, dando especial atenção à atuação dos Institutos de Aposentadorias e Pensões (IAPs) na cidade. Posteriormente procedeu-se a interpretação e a análise das justificativas e discursos que basearam as ações estatais, considerando os diferentes agentes envolvidos no processo, além do estudo da configuração arquitetônica e urbanística dos conjuntos de moradias erguidos na capital no referido período. Para tanto, realizou-se principalmente o levantamento de dados primários em arquivos públicos e privados da cidade. A pesquisa se justifica pela insuficiência de historiografia local no que dizia respeito à política pública de habitação no período que antecede a criação do BNH, em 1964, pelo volume significativo de moradias erguidas pelo Estado e por órgãos associados a ele e pelas especificidades da política de habitação em Natal, como as parcerias realizadas pelo governo, inclusive com órgãos internacionais, e a construção e financiamento de casas de taipa. Nesse sentido, foi identificado um número significativo de moradias construída em taipa e inseridas nas ações imobiliárias dos IAPs em Natal, fosse por via de construção, de aquisição e de repasse, ou por meio de financiamentos para a realização de reformas. Tais moradias chegaram a corresponder a 20% dos financiamentos concedidos pela Carteira Predial do Instituto, como foi o caso IAP dos industriários. Os IAPs em conjunto com a Fundação da Casa Popular e com a Fundação da Habitação Popular do RN conceberam moradias à aproximadamente 3.100 famílias, entre os anos de 1946 e 1963, o que correspondeu a 8,12% da população da cidade em meados da década de 1960. Pretende-se nessa pesquisa contribuir para o conhecimento da história da moradia social no Brasil, através da análise das ações realizadas em Natal. / The subject of this dissertation is \"the public politics for habitation\", and it has as case of study, the capital of Rio Grande do Norte - Natal. The object of the study consists in the relation between the issues of social habitation in Brazil, the solutions given to the problem by the means of the state, the financial supporters, propelling and constructors involved on this process and the construction and he idealization of the city of Natal. Being thus, the research intend to understand which are the logics and the objectives that stimulated the State actions in the field of social habitation in Natal, from 1889 to 1964, and also, the ideological, economical and social contexts in this process. From this analysis, one searched to specify the origins and to delimit the production\'s evolution process of the social habitations, and also register and divide in periods that production, standing out the Retirement and Pension\'s Institute\'s (IAPs) actuation in the city. Later, the justifications and the speeches based on the State actions were interpreted and analyzed, considering the different agents involved in the process, beyond the study of the housing estate\'s architectonic and urban configuration, built in this period. Doing so, one realized the primary data survey at the city\'s public and private archives. The research is justified by the deficiency of local historiography on habitation\'s public politics in the period before the creation of the BNH, in 1964, by the significant number of houses built by the State and by associated organs and by the habitation\'s politic particularities in Natal, such as the government partnerships, including those with international organs, and the mud houses\' financing and construction. Considering this, it was identified as significant number of mud houses and inserted on IAP\'s real estate actions in Natal, by meanings of construction, acquisition and repass or by reform\'s financings. Such housings had arrived to correspond to 20% of financings granted by the Carteira Predial do Instituto, as the IAP dos industriários\' case. The IAPs in set with the Popular House Foundation and with the Popular Habitation Foundation had conceived housings to, approximately 3.100 families, between the years 1946 and 1963, which corresponds to 8,12% of the city\'s population in the middle of the decade of 1960. This research intends to contribute for the social habitation knowledge of the history in Brazil, through the actions\' analysis in Natal.
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The effects of invasive trees in riparian zones and implications for management and restoration : insights from Eucalyptus invasions in South Africa

Tererai, Farai 12 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Worldwide, invasive alien plants (IAPs) alter aspects of invaded ecosystems including geomorphology, above-ground vegetation, soil seed banks and soil nutrient regimes, thereby affecting the long-term stability of ecosystems. In many cases these invasions call for various management interventions, including restoration. Effects of alien plant invaders on native ecosystems are widely acknowledged, but compared to terrestrial ecosystems, riparian habitats are poorly studied. Riparian habitats are inherently rich in biodiversity, but are particularly prone to invasion by IAPs because of their dynamic nature and because these ecosystems are affected by many anthropogenic activities. This enhances the proliferation of IAPs, especially trees such as Tamarix spp. (e.g. in the southwestern United States), Salix spp. (e.g. in Australia), and Australian Acacia spp. and Eucalyptus camaldulensis (in South Africa). Initiatives such as the Working for Water (WfW) programme in South Africa that are focusing on clearing IAPs, particularly in riparian zones, have reported much success in the short term, but ecosystem recovery remains limited. There is a poor understanding of the nature of the impacts of invasive trees, and of the opportunities that exist for ecosystem restoration. The objective of my thesis was to investigate the effects of the widespread invasions of Eucalyptus camaldulensis in riparian zones. Methodological constraints have been identified as one reason for limited success of restoration projects. Many studies examining the effects of IAPs used a comparative approach of uninvaded (reference) and invaded sites. However, this approach often fails to separate cause from effect. An experimental removal approach has been suggested as an alternative, but it is often inappropriate for large invasive trees owing to time and cost constraints. I used a comparative gradient approach, involving sampling along a continuum from uninvaded sites, and varying E. camaldulensis invasion densities categorised as “lightly”, “moderately” and “heavily” invaded (hereafter the gradient of invasion), each with four replicates (n = 16). This approach enabled me to detect trends that could be reliably attributed to invasion. Furthermore, my study attempted to provide a comprehensive understanding of the effects of IAPs in invaded ecosystems by considering various components of the ecosystem and integrating their feedback relationships to establish the net effects on ecosystem processes. The riparian zone is a unique ecosystem which provides an opportunity for such a multifaceted study examining and integrating the effects of invasive trees on riparian geomorphology, above-ground vegetation, soil seed banks, and soil properties. I studied the effects of E. camaldulensis invasion in riparian zones along the Berg River in the Mediterranean-type climate zone of the Western Cape, South Africa. I asked the questions 1) Are environmental conditions (i.e. the riparian environment created by geomorphological processes) altered by Eucalyptus invasion and if so, are these conditions less suitable for recruitment of indigenous species? 2. Has Eucalyptus invasion altered the composition of indigenous species (potentially limiting post-clearing propagule supply)? 3: How does Eucalyptus invasion change the composition of the riparian soil seed bank; and its potential to re-initiate ecosystem recovery? 4: Do soil properties (physical and chemical) change with Eucalyptus invasion? Data for all four questions were collected in the same sites to enable cross comparisons. For the first question, I employed photogrammetry techniques in a GIS and remote sensing environment to analyse repeated aerial photographs (1938 -2010) to reconstruct the invasion history and riparian geomorphology evolutionary dynamics. For the second and third questions, I compared richness, diversity, evenness and composition of resident above-ground and seed bank vegetation between uninvaded sites and the gradient of invaded sites. For the fourth question, I compared a set of variables describing physico-chemical properties in uninvaded sites to the gradient of invaded sites seasonally. Results of the geomorphology study showed that the riparian zone has been very dynamic over the 70 years, with a 13.5% net decrease in area. There was evidence of channel narrowing, riverbank steepening and river bed incision in areas that were densely invaded. No significant trends were detected in hydrometeorological data. The above-ground vegetation study revealed that species richness, diversity and structural attributes (e.g. height, relative cover and mean basal diameter) of native species decreased consistently along the invasion gradient. Invasion also altered native and alien plant species composition, both of which showed a high preference for lightly invaded sites. The seed bank study revealed that E. camaldulensis invasion had no significant effect on total and native species richness, diversity and evenness, however the effects were bigger on native than alien species. Alien species density was significantly higher than native species density. Invasion also influenced the composition of the native seed bank. However, native seed banks were more diverse than above-ground plant assemblages with some native fynbos species occurring only in the seed bank. In the soil study, I found that soil pH levels were significantly lower in invaded sites than in uninvaded sites in all seasons. Litter cover and thickness increased significantly with invasion intensity. Soil moisture decreased consistently with invasion intensity while temperature increased in winter and spring. Total macro, micro and available nutrients did not vary significantly along the invasion gradient (p > 0.05), but exchangeable cation content was significantly higher in uninvaded than in invaded sites, especially in winter and spring. Narrowing of river channel and steepening of river banks reduces the suitability of the riparian zone to perform certain ecological functions such as soil seed storage and providing space for vegetation to grow. This reduces opportunities for seedling recruitment and consequently reduces species diversity. Conversely, the reduction of species diversity in above-ground vegetation reduces seed input into the soil leading to depauperate soil-stored seed banks. The abundance of seeds of Acacia mearnsii in the soil-stored seed bank poses a threat of secondary invasions post clearing of E. camaldulensis if this is adopted as a management action. The study was successful in addressing the stated objectives. The transition from a native-dominated riparian plant community to a monoculture of E. camaldulensis over c. 50 years has resulted in marked changes to riparian geomorphology and above-ground vegetation, but has yet to radically change the total soil seed bank and soil nutrient concentrations. The findings offer support to the WfW clearing initiatives and show that potential for recovery of native species after removal of the invasive eucalypts still exists. This knowledge not only enhances effectiveness of restoration and long term management of riparian ecosystems, but also advances the field of riparian ecology and restoration. Further experimental work is needed to establish the mechanisms responsible for the changes associated with Eucalyptus invasion. The contribution of agriculture in shaping channel morphology also needs to be investigated. / AFRIKAANSE OPSOMMING: Die langtermyn stabiliteit van ekosisteme wêreldwyd word bedreig deur uitheemse indringer plante (UIPs) wat, onder andere, die geomorfologie, bo-grondse plantegroei, onder-grondse saadbanke en voedingstofstatus van ekosisteme kan verander. In baie gevalle word bestuursoperasies vir indringer plante vereis, en sluit onder andere herstel (restorasie) in. Die invloed van UIPs op inheemse ekosisteme word wyd erken, maar kennis oor oewerbank-habitatte, in vergeleke met ander terrestriële ekosisteme, skiet steeds tekort. Oewerbank-habitatte is inherent ryk aan biodiversiteit maar uiters sensitief vir indringing deur UIPs. Dit is weens die dinamiese aard van hierdie ekosisteme asook vele menslike aktiwiteite in hierdie tipe habitat. Dit dra by tot die vermeerdering van UIPs, veral bome wat byvoorbeeld insluit Tamarix (tamariske) (bv. in die suid-wes van die Verenigde State van Amerika), Salix (wilger) (in bv. Australië) en die Australiese Acacia (wattel) en Eucalyptus spesies (bloekom) in Suid Afrika. Inisiatiewe soos die Werk vir Water (WvW) program in Suid Afrika fokus juis daarop om UIPs vanuit oewerbank areas te verwyder, en alhoewel groot sukses in die kort termyn behaal is, is die herstel van ekosisteme steeds beperk. Daar is dus min inligting beskikbaar oor die impak van indringer bome en gevolglik ook oor geleenthede vir die herstel van hierdie ekosisteme. My tesis ondersoek die impak van die wydverspreide voorkoms van die indringer, Eucalyptus camaldulensis, in oewerbank-omgewings. Beperkte metodes is tans beskikbaar om die impak van indringer plante te ondersoek, en dit is geïdentifiseer as een van die oorsake vir die beperkte sukses van herstelprojekte. Baie studies ondersoek die effekte van UIPs deur natuurlike areas sonder enige indringer plante te vergelyk met areas waar UIPs voorkom. Hierdie tipe benadering kan ongelukkig, in meeste gevalle, nie onderskei tussen die oorsaak en die impak nie. ʼn Alternatiewe voorstel is om UIPs eksperimenteel te verwyder, maar is ongelukkig nie van toepassing op groot bome nie weens die tyd en kostes verbonde hieraan. Ek het gebruik gemaak van ʼn vergelykende-gradiënt benadering wat steekproefnemings langs ʼn geleidelike kontinuum van natuurlike areas sonder enige indringer plante na areas wat effens gematig, en erg ingedring is (hiernaas bekend as die indringer-gradiënt) deur die indringer, E. camaldulensis. Die steekproefnemings van elke kategorie van indringing (geen, effens, gematig en erg) is vier keer herhaal (n = 16). Hierdie benadering het my toegelaat om neigings te identifiseer wat met sekerheid toegeskryf kan word aan die teenwoordigheid van indringers. My studie het ook verder gemik om ʼn omvattende beskrywing van die impak van UIPs in ekosisteme met indringers te verskaf deur verskeie komponente van die ekosisteem, sowel as hul terugvoer-verhoudinge, in ag te neem, en sodoende die totale effek op ekosisteem prosesse te bepaal. ʼn Oewerbank is ʼn unieke ekosisteem wat ʼn geleentheid bied vir ʼn veelsydige studie wat die impakte van indringer bome op oewerbank-geomorfologie, bo-grond plantegroei, grond saadbanke en grondeienskappe, kan bestudeer en integreer. Ek het die impak van die teenwoordigheid van die indringer, E. camaldulensis in oewerbank areas langs die Bergrivier, wat ʼn Meditereense-tipe klimaat het, in die Wes Kaap, Suid Afrika, bestudeer. My studie het die volgende vrae gevra: 1) Is omgewings-omstandighede (bv. die oewerbank-omgewing geskep deur geomorfologiese prosesse) verander deur die teenwoordigheid van die Eucalyptus indringing, en indien wel, is hierdie omstandighede minder geskik vir inheemse spesies?; 2) Het die indringing van Eucalyptus gelei tot ʼn verandering in die samestelling van inheemse spesie gemeenskappe (moontlik beperkte plant voorplantings materiaal nadat die indringer verwyder is)?; 3) Hoe verander die indringing van Eucalyptus die samestelling van saad teenwoordig in die grond (saad bank) van die oewerbank en het dit die potensiaal om ekosisteem-herstel weer aan die gang te sit?; 4) Verander indringer Eucalyptus grond eienskappe (fisies en chemies)? Data vir al vier vrae is by dieselfde plek versamel om vergelykings te kan tref. Vir die eerste vraag het ek fotogrammetrie-tegnieke in ʼn Geografiese Inligting Stelsel (GIS) en afstandwaarnemings-omgewing toegepas om herhaalde lugfotos (1938-2010) te analiseer om die indringings geskiedenis sowel as die oewerbank se geomorfologiese evolusionêre dinamika saam te stel. Vir die tweede en derde vraag, het ek die aantal, diversiteit, gelykheid en samestelling van die bo-grond en saad bank plantegroei tussen natuurlike (geen indringers) en die gradiënt met indringers vergelyk. Vir die vierde en laaste vraag, het ek ʼn stel veranderlikes wat die fisies-chemiese eienskappe van die natuurlike omgewing sonder indringers beskryf, vergelyk met die eienskappe van die indringers gradiënt op ʼn seisoenale basis. Die resultate van die geomorfologiese studie wys dat die oewerbank omgewing baie dinamies was oor die afgelope 70 jaar met ʼn totale afname van 13.5% in rivieroewer-area in die gebied wat bestudeer is. Daar is ook bewyse vir ʼn vernouing van die kanaal, toename in die steilte van die rivierbank sowel as insnyding in die rivierbedding in areas wat ernstige indringing ervaar. Daar was geen beduidende neigings in die hidro-meteorologiese data nie. Die studie van die bo-grondse plantegroei het gewys dat die aantal plantspesies, diversiteit en strukturele kenmerke (bv. hoogte, dekking en gemiddelde basale diameter) van inheemse spesies afneem soos wat die indringings gradiënt toeneem. Indringing verander ook die inheemse sowel as uitheemse plant spesies samestelling. Beide inheemse en uitheemse spesies het areas wat slegs effense indringing wys, verkies. ʼn Studie van die saad bank (aantal sade in die grond) het gewys dat die indringer, E. camaldulensis geen merkwaardige invloed op die aantal, diversiteit en gelykheid van die totale en inheemse spesies teenwoordig gehad het nie. Die aantal uitheemse spesies was merkwaardig meer as die aantal inheemse spesies. Alhoewel indringing ook die samestelling van die inheemse saadbank beïnvloed het, was die inheemse saad bank, waarvan sommige spesies slegs daar voorgekom het, meer divers as die bo-grond plant samestellings. ʼn Studie van die grond het gewys dat die pH vlakke, afgesien van die seisoen, aansienlik laer is in die areas met indringers in vergeleke met areas sonder die indringers. Die hoeveelheid en dikte van plantmateriaal op die grond neem ook toe met ʼn toename in indringers. Die waterinhoud van die grond het afgeneem met ʼn toename in indringers en temperatuur het verhoog in beide winter en lente. Die totale makro- en mikrovoedingstowwe het nie merkwaardig gewissel saam met die indringingsgradiënt nie (p > 0.05), maar die uitruilbare katioon inhoud was aansienlik hoër, veral in die winter en lente-maande, in die areas sonder indringers in vergelyking met die areas met indringers. Vernouing van rivierkanaal en versteiling van rivieroewers verminder die geskiktheid van die oewersone om sekere ekologiese funksies te verrig soos grond-saadstoring en die verskaffing van ruimte vir plante om te groei. Dit verminder geleenthede vir werwing van saailinge en verminder gevolglik spesiediversiteit. Aan die ander kant, die vermindering van die spesiediversiteit in die bogrondse plantegroei verminder saadinsette in die grond en dit lei tot verarming van grondgestoorde saadbanke. Die oorvloed van sade van Acacia mearnsii in die grondgestoorde saadbank hou die bedreiging van sekondêre indringing in na die skoonmaak van E. camaldulensis indien dit wel as 'n bestuursaksie aangeneem word. Hierdie studie het die uiteengesette doelwitte suksesvol aangespreek. Die oorgang van ʼn oewerbank-gemeenskap wat hoofsaaklik uit inheemse plante bestaan na ʼn gemeenskap wat slegs uit E. camaldulensis bestaan, oor ʼn periode van ongeveer 50 jaar, het duidelike veranderinge tot gevolg gehad. Hierdie veranderinge is veral opmerklik in die oewerbank-geomorfologie en bo-grondse plantegroei, maar tot op hede is dit nog nie so opmerklik in die saadbank en grond-voedingstowwe konsentrasies nie. Hierdie bevindinge bied ondersteuning aan die WvW verwyderings-ondernemings en wys dat daar wel moontlike herstel van inheemse spesies kan wees na die verwydering van die indringer Eucalyptus. Hierdie kennis dra nie net by tot verhoogde effektiwiteit van herstelwerk en langtermyn-bestuursplanne nie, maar ook tot die navorsingsveld van oewerbankekologie en-herstel. Verdere eksperimentele navorsing word benodig om die moontlike meganismes wat verantwoordelik is vir die waargeneemde veranderinge, geassosieerd met Eucalyptus indringing, te verduidelik. Die bydrae van landbou tot die vorming van kanaal morfologie moet ook verder bestudeer word.
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Importance of selecting research stimuli : a comparative study of the properties, structure and validity of both standard and novel emotion elicitation techniques

Constantinescu, Alexandra Caterina January 2018 (has links)
The principal aim of this doctoral research has been to investigate whether various popular methods of emotion elicitation perform differently in terms of self-reported participant affect - and if so, whether any of them is better able to mimic real-life emotional situations. A secondary goal has been to understand how continuous affect can be classified into discrete categories - whether by using clustering algorithms, or resorting to human participants for creating the classifications. A variety of research directions subserved these main goals: firstly, developing data-driven strategies for selecting 'appropriate' stimuli, and matching them across various stimulus modalities (i.e., words, sounds, images,films and virtual environments / VEs); secondly, comparing the chosen modalities on various self-report measures (with VEs assessed both with and without a head-mounted display / HMD); thirdly, comparing how humans classify emotional information vs. a clustering algorithm; and finally, comparing all five lab-based stimulus modalities to emotional data collected via an experience sampling phone app. Findings / outputs discussed will include a matched database of stimuli geared towards lab use, how the choice of stimulus modality may affect research results, the links (or discrepancies) between human and machine classification of emotional information, as well as range restriction affecting lab stimuli relative to `real-life' emotional phenomena.
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Antiapoptotic Proteins in Human Macrophage Survival, Differentiation, Innate Immunity and Protection from HIV-induced Apoptosis

Busca, Aurelia 02 April 2013 (has links)
Macrophages represent long lived immune cells that are remarkably resistant to apoptosis, which allows them to perform in highly stressful environments. Apoptosis resistance is a characteristic that develops during the differentiation process from monocytes to macrophages. However, the signaling pathways that mediate the development of macrophage antiapoptotic phenotype during differentiation remain mostly unknown. Because of their decreased susceptibility to cell death, macrophages are also key viral reservoirs during HIV infection. My research aims to understand the molecular mechanisms and signaling pathways that mediate cell survival during and after monocyte to macrophage differentiation and the involvement of the main families of antiapoptotic proteins, IAPs (inhibitors of apoptosis) and Bcl2 in this process. HIV accessory protein Vpr was used as an apoptotic stimulus, due to its death inducing abilities in other cell types. My results show that survival of macrophages is distinctively regulated during and after differentiation. I have identified a signaling pathway consisting of PI3K/Akt activation of NFκB that is important in survival of differentiating macrophages by specifically sustaining antiapoptotic Bcl-xL expression. However, once differentiated, Mcl-1, but not Bcl-xL is dependent on PI3K/Akt activation. Moreover, differentiated macrophages are resistant to the effect of HIV-Vpr, which is highly apoptotic for monocytes. In contrast, resistance to HIV-Vpr induced apoptosis of human macrophages is specifically mediated by antiapoptotic IAP proteins, with no involvement of the Bcl2 family, which maintains macrophage viability in the absence of any apoptotic stimuli. In addition to their antiapoptotic properties, IAPs are also important regulators of macrophage function. By using chemical compounds (SMAC mimetics) that target IAPs for degradation, I have shown that IAPs positively modulate LPS-induced IL10, IL-27 and MIG (monokine induced by IFNγ) production in human macrophages, by promoting TRAF2, JNK and p38 signaling and NFκB activation. In addition, IAPs also contribute to LPS-induction of CD80/CD86 costimulatory molecules. Overall, my results suggest that both IAPs and Bcl2 families contribute to survival of human macrophages and that IAPs are also involved in innate immune responses. Unraveling the mechanisms that control macrophage survival and function in various settings would provide therapeutic strategies aimed at eliminating cells when their survival is no longer beneficial for the host, as in the case of HIV infection or autoimmune diseases.

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