Os objetivos deste estudo foram descrever a composição taxonômica e distribuição horizontal das larvas de Serranidae na Plataforma Continental Sudeste Brasileira (PCSE), e verificar a interferência dos fatores ambientais e bióticos na distribuição larval. O material provém de 10 cruzeiros oceanográficos realizados nos meses de janeiro, maio, setembro e dezembro de 1975 a 1981, entre cabo Frio (RJ) e cabo de Santa Marta Grande (SC) e depositados na \"Coleção Biológica Prof. E. F. Nonato\". As larvas de Serranidae (933) foram identificadas em 14 táxons (Diplectrum formosum, Diplectrum spp., Serranus spp., Epinephelus itajara, Epinephelus morio, Epinephelus nigritus, Epinephelus tipo 1, Epinephelus spp., Mycteroperca spp., Pseudogramma gregoryi, Rypticus spp., Anthias menezesi, Hemanthias vivanus, Pronotogrammus martinicensis), distribuídos em nove gêneros e três subfamílias (Serraninae, Anthiinae, Epinephelinae). Com exceção de D. formosum, que apresentou ampla distribuição na plataforma interna da PCSE, e Epinephelus tipo 1 e Hemanthias vivanus, que se distribuíram preferencialmente na região sul da PCSE, os demais táxons se distribuíram na região norte da PCSE (cabo Frio-RJ a São Sebastião-SP), não ultrapassando a isóbata de 200 m. Os fatores salinidade, distância das ilhas e latitude foram significativos na distribuição de Diplectrum formosum, Diplectrum spp., Serranus spp., Epinephelus tipo 1, e Mycteroperca spp., táxons mais abundantes. Foi obtido um avanço na identificação de Epinephelus (E. morio, E. itajara e E. nigritus) e ratificada a morfologia dos espinhos alongados de E. nigritus. / This study describes the taxonomic composition and horizontal distribution of Serranidae larvae along Southeastern Brazilian Continental Shelf (SBSC), and investigates how environmental and biological factors influence the larval distribuction. The samplers, deposited in the Marine Biological Collection \"Prof. E. F. Nonato\", were collected on the 10 survey cruisers conducted on january, may, september and december from 1975 to 1981, between cape Frio (RJ) to cape Santa Marta Grande (SC). Larvae of Serranidae (933) were identified into 14 taxa (Diplectrum formosum, Diplectrum spp., Serranus spp., Epinephelus itajara, Epinephelus morio, Epinephelus nigritus, Epinephelus tipo 1, Epinephelus spp., Mycteroperca spp., Pseudogramma gregoryi, Rypticus spp., Anthias menezesi, Hemanthias vivanus, Pronotogrammus martinicensis), included in nine genera and three subfamilies (Serraninae, Anthiinae and Epinephelinae). Except for Diplectrum formosum, that was widely distributed throughout the southeastern continental shelf, and Epinephelus type 1 and Hemanthias vivanus, that were distributed into the south portion of the SBSC, other taxa distributed into the north portion of the SBSC (from cape Frio to São Sebastião), not exceeding the 200 m isobath. The salinity, latitude and distance of islands were significant factors in the horizontal distribution of Diplectrum formosum, Diplectrum spp., Serranus spp., Epinephelus type 1 and Mycteroperca spp., most abundant taxa. A significant progress was considered in identifying grouper larvae (Epinephelus morio, Epinephelus itajara and Epinephelus nigritus) and ratified the morphology of the elongated spines of E. nigritus.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-12-06T17:23:43Z No. of bitstreams: 1 NataliaMandarino.pdf: 1259793 bytes, checksum: 4c22457bb7148f23dd689ff0d6e19abc (MD5) / Made available in DSpace on 2017-12-06T17:23:43Z (GMT). No. of bitstreams: 1 NataliaMandarino.pdf: 1259793 bytes, checksum: 4c22457bb7148f23dd689ff0d6e19abc (MD5) Previous issue date: 2017-09-05 / FAPEMA / The role of vitamin D in the regulation of bone metabolism is already well established. However, in recent years, the role of vitamin D in extraskeletal health has been widely explored. In the cardiovascular area, vitamin D deficiency has been independently associated with the occurrence of myocardial infarction, stroke and cardiovascular death. The mechanisms to explain the association between hypovitaminosis D and cardiovascular disease are still not fully understood, and their association with atherosclerosis is postulated. However, studies attempting to correlate hypovitaminosis D with atherosclerosis markers have produced conflicting results, in the same way as small randomized trials of oral supplementation to evaluate intermediate outcomes, so there is currently considerable debate about whether hypovitaminosis D represents a new risk or would be just an inflammatory marker. In the first article, a comprehensive review was made of the role of vitamin D deficiency in the pathogenesis of cardiovascular disease, from basic aspects of its biosynthesis to the results of interventional studies, through its oral supplementation. The second article presents the results of a cross - sectional analysis of 382 individuals living in quilombola communities in Alcântara - MA, participants of the PREVRENAL cohort, presenting at least one cardiovascular risk factor, with a mean age of 57.79 (± 15.3) years and a slight predominance, in which the serum levels of 25-hydroxyvitamin D, the stable circulating form of the vitamin, were correlated with an established marker of subclinical atherosclerosis, carotid intima-media thickness, and other cardiovascular risk factors. Socio-demographic, lifestyle, anthropometric and clinical data were collected and biochemical tests were performed, including the dosage of 25-hydroxyvitamin D by means of the electrochemiluminescence assay. The urinary excretion of albumin was evaluated by means of the albumin / creatinine ratio in an isolated sample of urine. Hypovitaminosis D was defined as serum 25- hydroxyvitamin D levels <30 ng / mL. All participants underwent examination of the common carotid arteries by high-resolution ultrasonography to measure the intimamedia thickness, and the mean of the measurements on both sides was adopted. Serum levels of 25-hydroxyvitamin D were 50.4 (± 13.5) ng / mL, with a low prevalence of hypovitaminosis D (<5%). By simple linear correlation, there was a significant inverse association between 25-hydroxyvitamin D levels and carotid intima-media thickness (r = -0.174, p = 0.001). However, after multiple regression analysis, only the variables male gender, age, smoking, systolic blood pressure, fasting blood glucose and LDL-cholesterol remained significantly associated with carotid intima-media thickness. Levels of 25-hydroxyvitamin D were independently associated positively with HDL-cholesterol and inversely with urinary albumin excretion. In conclusion, in this Afrodescendant population, with a low prevalence of hypovitaminosis D, there was no independent association between serum 25- hydroxyvitamin D levels and carotid intima-media thickness, a finding that contradicts the hypothesis of its antiatherosclerotic role. On the other hand, its positive association with HDL-cholesterol and the inverse association with urinary albumin excretion, also considered as an independent predictor of cardiovascular events, does not allow the exclusion of cardiovascular protection actions of the vitamin in this population profile. / O papel da vitamina D na regulação do metabolismo ósseo já está bem estabelecido. Entretanto, nos últimos anos, o papel da vitamina D na saúde extraesquelética tem sido amplamente explorado. Na área cardiovascular, a deficiência de vitamina D tem sido associada de forma independente à ocorrência de infarto do miocárdio, acidente vascular cerebral e morte cardiovascular. Os mecanismos para explicar a associação entre hipovitaminose D e doença cardiovascular ainda não estão de todo esclarecidos, sendo postulada sua vinculação com a aterosclerose. No entanto, estudos procurando correlacionar hipovitaminose D com marcadores de aterosclerose têm produzido resultados conflitantes, da mesma forma que pequenos estudos randomizados de suplementação oral para avaliar desfechos intermediários, de modo que há atualmente considerável debate acerca de se a hipovitaminose D representa um novo fator de risco ou seria apenas um marcador inflamatório. No primeiro artigo, já publicado, procurou-se realizar uma revisão abrangente sobre o papel da deficiência de vitamina D na patogenia da doença cardiovascular, incluindo desde aspectos básicos de sua biossíntese até os resultados de estudos de intervenção, por meio de sua suplementação oral. O segundo artigo apresenta os resultados de uma análise transversal de 382 indivíduos habitantes de comunidades quilombolas em Alcântara - MA, participantes da coorte PREVRENAL, apresentando pelo menos um fator de risco cardiovascular, com média de idade de 57.79 (± 15.3) anos e discreto predomínio do sexo feminino, em que se procurou correlacionar os níveis séricos de 25-hidroxivitamina D, a forma circulante estável da vitamina, com um marcador estabelecido de aterosclerose subclinica, a espessura médio-intimal carotídea, e outros fatores de risco cardiovascular. Foram coletados dados sócio-demográficos, sobre estilo de vida, antropométricos e clínicos e realizados exames bioquímicos, incluindo a dosagem de 25-hidroxivitamina D, por meio do ensaio eletroquimioluminiscência. A excreção urinária de albumina foi avaliada por meio da razão albumina / creatinina em amostra isolada de urina. Hipovitaminose D foi definida como níveis séricos de 25-hidroxivitamina D <30 ng / mL. Todos os participantes foram submetidos a exame das artérias carótidas comuns por ultrassonografia de alta resolução para medida da espessura médio-intimal, sendo adotada a média das medidas de ambos os lados. A média dos níveis séricos de 25-hidroxivitamina D foi de 50.4 (± 13.5) ng / mL, observando-se uma baixa prevalência de hipovitaminose D (<5%). Por correlação linear simples, observou-se uma associação inversa significativa entre os níveis de 25-hidroxivitamina D e a espessura médio-intimal carotídea (r = -0.174, p = 0.001). Entretanto, após análise de regressão múltipla, apenas as variáveis sexo masculino, idade, tabagismo, pressão arterial sistólica, glicemia em jejum e LDL-colesterol permaneceram significativamente associadas com a espessura médio-intimal carotídea. Níveis de 25-hidroxivitamina D se associaram independentemente, de forma positiva com o HDL-colesterol, e inversa com a excreção urinária de albumina. Em conclusão, nesta população afrodescendente, com baixa prevalência de hipovitaminose D, não se observou uma associação independente entre os níveis séricos de 25- hidroxivitamina D e a espessura médio-intimal carotídea, achado que contraria a hipótese do seu papel antiaterosclerótico. Por outro lado, a sua associação positiva com o HDL-colesterol e inversa com a excreção urinária de albumina, também considerada um preditor independente de eventos cardiovasculares, não permite afastar ações de proteção cardiovascular da vitamina neste perfil populacional.

Com a finalidade de estudar as perturbações médias sobre a Plataforma Continental Sudeste (PCSE) causadas pela passagem de uma frente fria durante o verão, obteve-se um estado básico médio de correntes. Esse campo médio foi obtido com o POM (Princeton Ocean Model) através de simulação diagnóstica, seguida por curta rodada prognostica. As correntes modeladas para o verão na Plataforma Continental Sudeste assemelharam-se em alguns aspectos a correntes obtidas em fundeios de correntógrafos realizados pela Diretoria de Hidrografia e Navegação (DHN), e pelo Instituto Oceanográfico da Universidade de São Paulo, durante os projetos Ciculação Oceânica na Região Oeste do Atlântico Sul (COROAS) e Dinâmica do Ecossistema de Plataforma da Região Oeste do Atlântico Sul (DEPROAS), validando os resultados do modelo Durante a passagem da frente fria as correntes invertem em cerca de seis a nove horas após a passagem do sistema frontal por cada região da PCSE. As etapas da subsidência costeira foram modeladas, ocorrendo transporte de deriva do vento em direção à costa, na camada superficial (0-10m), e transporte de compensação ao longo da coluna d\'água, havendo empilhamento de água na região costeira. A força de gradiente de pressão barotrópica desenvolvida implicou na formação e intensificação do jato costeiro em direção a menores latitudes. Durante esse estado transiente associado à passagem do sistema frontal, a Água Tropical aproxima-se da costa em nível sub-superficial, misturando-se com as águas da plataforma continental A porção da Plataforma Continental Sudeste localizada ao sul da Ilha de São Sebastião é a que responde com maior intensidade à passagem do sistema meteorológico frontal. Na direção transversal à costa, predomina o balanço geostrófico, o qual é intensificado durante a passagem da frente fria, enquanto que ao longo da costa as águas são desviadas do referido balanço pela tensão de cisalhamento do vento e pela aceleração local. Em Cananéia, ocorre a maior amplitude de variação do nível do mar, que pode estar associada a um mecanismo de ressonância entre os ventos do sistema frontal e Ondas de Plataforma Continental geradas pelo vento, uma vez que possuem velocidades de propagação próximas. A plataforma continental adquire vorticidade relativa ciclônica durante a passagem da frente fria. / In order to study the pertubations caused on the South Brazil Bigth (SBB) caused by the passage of a cold front during Summer, a mean basic state for currents was obtained using the POM (Princeton Ocean Model) through diagnostic simulation, followed by a short round prognostic. The mean currents modeled are in certain instancies similar to the currents measured by meter moorings deployed by the Directorate of Hydrography and Navigation (DHN), and by Oceanographic Institute of the University São Paulo during the Projects Oceanic Circulation in the Western South Atlantic (COROAS) and Dynamic of the Ecosystem of the Shelf of the Western South Atlantic Region (DEPROAS), validating results model. During the cold front passage, the currents invert six to nine hours after the passage of the frontal system through each region of the SBB. The stages of coastal subsidence were modeled, with coastward wind drift transport at superficial layer and offshore compensation transport throughout the water column, with piling of water in the coastal region. The strength of the barotropic pressure gradient developed caused the formation and intensification of a coastal jet. During this transient stage associated with the passage of the frontal system, the Tropical Water approaches the coast within sub-surface layer, mixing with continental shelf waters. The portion of SBB located to the South of São Sebastião Island is the portion which is most influenced by the passage of the frontal system. In a normal direction to the coast, the geostrophic balance predominates, being intensified during the passage of the cold front, while along the coast, the waters is diverted from this balance by the wind stress and by the local acceleration, which tend to have opposite signs. Near Cananéia, there is the highest sea level elevation, which may be associated with a mechanism of resonance between the winds of the frontal system and the Continental Shelf Waves generated by the wind, since they have the same speed of propagation. The continental shelf acquires cyclonic relative vorticity during the passage of the cold front.

Introdução: Pacientes hipertensos resistentes (HR) são indivíduos com pressão arterial não controlada - apesar do tratamento com um diurético e dois anti-hipertensivos com mecanismos de ação diferentes em doses adequadas. Há duas áreas de interesse nesse contexto: a ancestralidade genética que, a princípio, poderia impactar em controles pressóricos, e a farmacometabolômica que, conceitualmente, é um conjunto de mudanças em concentrações de metabólitos - um novo campo que pode esclarecer mecanismos de variações de respostas farmacológicas. Assim, nossos principais objetivos foram: associar mensurações séricas de fármacos anti-hipertensivos e seus metabólitos às respostas farmacoterapêuticas em pacientes hipertensos e analisar a ancestralidade genética em pacientes hipertensos a fim de verificar uma possível associação com as respostas farmacoterapêuticas e a hipertensão resistente. Métodos: Foram utilizadas amostras de 1.597 pacientes, sendo 187 HR. A preparação e a análise da amostra foram realizadas usando uma coluna com nanotubos de carbono de acesso restrito (RACNTs) em um sistema de cromatografia líquida acoplada a espectrômetro de massa (UPLC-MS/MS), em modo column switching. A ancestralidade genética foi realizada usando um painel de 192 marcadores polimórficos; três referências foram usadas (europeia, ameríndia e africana). A raça foi determinada pela autodeclaração, segundo IBGE (branco, pardo, negro e outros). Resultados: O método foi totalmente validado de acordo com as diretrizes da Food and Drug Administration (FDA). O tempo de execução total para cada análise foi de 12,0 min - incluindo a preparação da amostra. Não foram encontradas diferenças significativas nas concentrações de cada analito de acordo com pacientes responsivos e não responsivos, possivelmente, por causa do número de amostra ainda baixo (n total de 171 amostras). As médias das mensurações no grupo dos respondedores foram: clonidina 1,308microg/L; amlodipina 44,044microg/L; enalapril 67,706microg/L; enalaprilato 44,144microg/L; losartana 202,622microg/L; ácido carboxílico de losartana 65,99microg/L, glicuronídeo N-2 de losartana 43,4microg/L e espironolactona 85,87microg/L. Para o grupo dos não respondedores, obtivemos: clonidina 1,4microg/L; amlodipina 78,89microg/L; enalapril 87,821microg/L; enalaprilato 78,878microg/L; losartana 148,026microg/L, ácido carboxílico de losartana 83,535microg/L, glicuronídeo N-2 de losartana 122,452microg/L e espironolactona 79,72microg/L. A raça autodeclarada foi associada aos componentes da ancestralidade genética desses pacientes (p<0,001). A ancestralidade genética, disponível para 1.503 pacientes, teve média geral de 0,53, para europeia; 0,11, para ameríndia; e 0,35, para africana. Não foram encontradas diferenças estatísticas nas médias de ancestralidade de acordo com os grupos respondedor ou HR. Conclusões: O método analítico foi validado e a ancestralidade genética foi realizada, ambos não associados à farmacoterapêutica e à hipertensão resistente / Background: Resistant hypertensive (RH) patients are individuals with uncontrolled blood pressure - despite treatment with one diuretic and two antihypertensives with different mechanisms of action in adequate doses. There are two areas of interest in this context: genetic ancestry that could initially impact on blood pressure controls, and pharmacometabolomics, which conceptually is a set of changes in metabolite concentrations - a new field that can clarify mechanisms of pharmacological response variation. Thus, our main objectives were: to associate serum measurements of antihypertensive drugs and their metabolites to the pharmacotherapeutic responses in hypertensive patients and to analyze genetic ancestry in hypertensive patients in order to verify a possible association with pharmacotherapeutic responses and resistant hypertension. Methods: Samples of 1,597 patients were used, being 187 RH. Sample preparation and analysis were performed using a column with restricted access carbon nanotubes (RACNTs) in a liquid chromatography coupled to mass spectrometer (UPLC-MS/MS) in column switching mode. Genetic ancestry was performed using a panel of 192 polymorphic markers; three references were used (European, Amerindian and African). The race was determined by self-declaration, according to IBGE (white, brown, black and others). Results: The method has been fully validated according to the guidelines of the Food and Drug Administration (FDA). The total run time for each analysis was 12.0 min including sample preparation. No significant differences were found in the concentrations of each analyte according to responsive and nonresponsive patients, possibly because of the still low number of samples (total n of 171 samples). The means of the measurements in the responders group were: clonidine 1.308microg/L; amlodipine 44.044microg/L; enalapril 67.706microg/L; enalaprilat 44.144microg/L; losartan 202.622microg/L; losartan carboxylic acid 65.99microg/L, N-2 glucuronide of losartan 43,4microg/L and spironolactone 85.87microg/L. For the group of non-responders, we obtained: clonidine 1.4 microg/L; amlodipine 78.89microg/L; enalapril 87.821microg/L; enalaprilat 78.878microg/L; losartana 148.026microg/L, losartan carboxylic acid 83.535microg/L, N-2 glucanide of losartan 122.452microg/L and spironolactone 79.72microg/L. Self-reported race was associated with the components of the genetic ancestry of these patients (p<0.001). Genetic ancestry, available for 1,503 patients, had an overall mean of 0.53 for European; 0.11 for Amerindian; and 0.35 for African. No statistical differences were found in the means of ancestry according to responder or RH groups. Conclusion: The analytical method was validated and genetic ancestry was performed, both unrelated to pharmacotherapeutic and resistant hypertension

This thesis seeks to systematically examine the contributions made by the dispute settlement bodies established under the United Nations Convention on the Law of the Sea (UNCLOS) to the development of the law of the sea. The two main research questions to be answered are: (i) what kind of contribution have UNCLOS dispute settlement bodies made to the development of the law of the sea? and (ii) what are the factors that impact the performance of UNCLOS dispute settlement bodies in developing the law of the sea? To that end, Chapter 1 provides a working definition for the concept of 'judicial development of international law' in order to establish a framework for an assessment of the contributions of UNCLOS tribunals. Based on this working definition, Chapters 2, 3 and 4 examine the significance of UNCLOS tribunals' decisions in the development of three main areas of the law of the sea, respectively the law on fisheries, the law on the outer continental shelf and the law on marine environmental protection. Based on the findings of these chapters, Chapter 5 analyses the factors that help explain the contributions of UNCLOS tribunals to the law of the sea as identified in the preceding chapters. These factors include: (i) the jurisdictional scope of UNCLOS tribunals, (ii) the institutional design of UNCLOS, (iii) the interpretative method employed by UNCLOS tribunals in deciding their cases and (iv) the perception that UNCLOS tribunals hold regarding their roles. Chapter 6 concludes by taking stock of the contribution of UNCLOS tribunal in these areas and offering some final observations on the role of UNCLOS tribunals in the development of the law of the sea.

Submitted by Cleide Dantas (cleidedantas@ufpa.br) on 2014-10-24T16:07:05Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_MovimentoXinguVivo.pdf: 4141761 bytes, checksum: 09e26f7605b7ab48755f082148b4036d (MD5) / Approved for entry into archive by Ana Rosa Silva (arosa@ufpa.br) on 2014-10-29T13:50:38Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_MovimentoXinguVivo.pdf: 4141761 bytes, checksum: 09e26f7605b7ab48755f082148b4036d (MD5) / Made available in DSpace on 2014-10-29T13:50:38Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_MovimentoXinguVivo.pdf: 4141761 bytes, checksum: 09e26f7605b7ab48755f082148b4036d (MD5) Previous issue date: 2014 / Esta dissertação desenvolve uma análise sobre um movimento social denominado Movimento Xingu Vivo Para Sempre, observado com base em suas ações e nas dos atores sociais que o integram. Como metodologia utilizamos o estudo de caso e como técnicas metodológicas para atingir nosso objetivo, optamos pelas entrevistas semi-estruturadas e observação-participante. A principal categoria analítica são os movimentos sociais, que analisamos sob a ótica dos Novos Movimentos Sociais, tendo por base autoras como Glória Gohn e Ilse Scherer-Warren. Além disso, utilizamos alguns conceitos, como: redes de movimentos sociais e estrutura de oportunidades, sendo o último desenvolvido por Tarrow. O objetivo principal foi produzir uma análise sobre o Movimento Xingu Vivo Para Sempre, a partir de suas ações, estratégias e reivindicações, atentando para a estrutura de oportunidades na qual esse processo ocorre. Como objetivos específicos tivemos: reflexão sobre a dinâmica do movimento social estudado a partir de sua história; análise da composição do movimento e sua forma de organização; e análise da relação entre o movimento e os vários segmentos sociais atingidos pela UHE Belo Monte; análise da relação entre o movimento e os distintos setores e instituições estatais. Ficou evidenciado em nossa pesquisa que o Movimento Xingu Vivo Para Sempre é uma rede de movimentos sociais que sofreu diversas transformações, com destaque para o rompimento e a saída da maior parte das entidades integrantes da rede em 2009. A histórica fragilidade institucional da região, que se reflete na carência de serviços públicos, contribui para a legitimação do movimento na condição de um canal de denúncias e contraposição. Todavia, mais do que apresentar um projeto de desenvolvimento alternativo, o movimento atua em uma conduta defensiva contra a construção de barragens na bacia do rio Xingu e Amazônia como um todo, através de outra rede denominada Aliança dos Rios Pan-amazônicos. Constatamos também que a relação com os distintos grupos sociais atingidos é prejudicada pela criminalização empreendida contra o movimento, bem como pelo pequeno número de militantes que o integram, desde as transformações ocorridas a partir de 2009. Por fim, analisamos que, não obstante a oposição frontal ao executivo, o movimento tem articulações em outras esferas estatais, especialmente no judiciário, com destaque para a Defensoria Pública do Pará e o Ministério Público Federal. / This dissertation carries out an analysis on a social movement known as Movimento Xingu Vivo Para Sempre, observed from its actions and social actors that composed it. The methodology used is the case study and as methodology techniques to achieve our goal, we chose the semi-structured interviews and participant observation. The main analytical category are the social movements, which reviewed about the optics of the New Social Movements, from authors such as Gloria Gohn and IIse Scherer - Warren. Furthermore, we use some concepts, such as: networks of social movements and opportunity structure, the latter being developed by Tarrow. The main objective was to provide an analysis of the Movimento Xingu Vivo Para Sempre, from their actions, strategies and claims, having regard to the opportunity structure in which this process occurs. The specific objectives we had: A reflection on the dynamics of the social movement studied from its history, analysis of the movement's composition and its form of organization, analysis of the relationship between the movement and the various social segments affected by Belo Monte HPP; analysis of the relationship between the movement and the different political and state institutions. It became clear in our research that the Movimento Xingu Vivo Para Sempre is a network of social movements that has undergone various transformations, especially the rupture and departure of most member entities of the network in 2009.The historical institutional frailty of the region, which is reflected in the lack of public services, contributes to the legitimacy of the movement as a channel for denunciation and opposition. However, rather than present an alternative development project, the movement operates in a defensive manner against the construction of dams on the basin of the Xingu river and the Amazon as a whole, through another network calIed Aliança dos Rios Pan-amazônicos. We also note that the relationship with the different social groups affected is impaired by the criminalization waged against the movement, as well as the small number of militants that integrate it, since the changes occurred from 2009. Lastly, we analyze that, despite the head-on opposition to the executive, the movement has articulations in other state sectors, especially in the judiciary, with emphasis on the Public Defender's Office of Pará and the Public Prosecution Service.

Submitted by Edisangela Bastos (edisangela@ufpa.br) on 2017-02-13T12:36:50Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_AspectosLitoestruturaisEvolucao.pdf: 73605865 bytes, checksum: c9ffc0c7102e40b8dc10e008710874ff (MD5) / Approved for entry into archive by Edisangela Bastos (edisangela@ufpa.br) on 2017-02-14T11:39:21Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_AspectosLitoestruturaisEvolucao.pdf: 73605865 bytes, checksum: c9ffc0c7102e40b8dc10e008710874ff (MD5) / Made available in DSpace on 2017-02-14T11:39:21Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_AspectosLitoestruturaisEvolucao.pdf: 73605865 bytes, checksum: c9ffc0c7102e40b8dc10e008710874ff (MD5) Previous issue date: 1985-11-13 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / Na região compreendida entre as cidades de Paraíso do Norte, Gurupi e Dianópolis, situada na parte centro norte do Estado de Goiás, reconhecem-se diversas unidades lito-estratigráficas e várias gerações de estruturas ligadas a eventos termo-tectônicos distintos. Considerando a distribuição e as características petrográficas e estruturais dos conjuntos rochosos antigos, foi possível individualizar quatro compartimentos ou domínios lito-estruturais atribuídos ao Arqueano. O domínio 1 inclui a região de Almas-Dianópolis, é interpretado como um terreno granito-greenstone, englobando um conjunto de gnaisses tonalíticos com supracrustais associadas (Complexo Goiano), e vários corpos de tonalitos (Suíte Serra do Boqueirão) embutidos nas unidades anteriores. A evolução geral do domínio compreende três eventos deformacionais principais. O primeiro se refere à formação dos anfibolitos e/ ou biotita gnaisse e granitóides, caracterizados estruturalmente por um bandamentos sub-vertical, orientado na direção N10° E. O desenvolvimento desse elemento planar foi acompanhado por transformações mineralógicas e fácies anfibolito. O segundo evento corresponde à deposição do Grupo Riachão do Ouro, seguida pela formação de estruturas sinclinais isoclinais empinadas, orientadas na direção N10° E, contemporânea a transformações em fácies xisto verde. A esse evento se relaciona a colocação dos diápiros tonalíticos da Suíte Serra do Boqueirão. O último é representado por uma foliação de transposição suavemente inclinada para sudeste, vinculada a um processo de cisalhamento simples dúctil-rúptil de baixo ângulo, que afetou a parte oeste do domínio e transformou as rochas do Complexo Goiano em gnaisses miloníticos em condições de fácies anfibolito. O domínio 2 envolve os municípios de Porto Nacional, Brejinho de Nazaré e Natividade, correspondendo à parte centro-leste da área. Caracterizado por gnaisses granulíticos (Complexo Porto Nacional), por gnaisses tonalíticos com supra crustais associadas (Complexo Manoel Alves), por conjuntos supracrustais, envolvendo metassedimentos e metavulcânicas (Formação Morro do Aquiles), e por granitos pegmatóides, a exemplo da Suíte Xobó. As diferentes unidades litológicas apresentam-se na forma de camadas e/ ou pacotes sub-horizontais, concordantes a sub-concordantes e orientadas na direção N30°. Exibem feições estruturais produzidas por um processo de cisalhamento simples dúctil-rúptil de baixo ângulo, em condições de fácies anfibolito. Várias zonas de cisalhamento dúctil de alto ângulo, com caráter direcional, com diferentes intensidades de deformação e desenvolvidas em condições de fácies xisto verde, superpõem-se às feições estruturais ligadas ao evento de cisalhamento de baixo ângulo. O domínio 3 acha-se totalmente incluído no município de Paraíso do Norte, na porção noroeste da área, e é interpretado como um terreno granito-greenstone, a exemplo do domínio 1. Fazem parte desse domínio o Complexo Colméia, o Grupo Rio do Côco e os gnaisses alcalinos de Monte Santo. Duas fases de deformação principais são responsáveis pela estruturação geral do domínio. A fase mais antiga corresponde ao dobramento do bandamento (s) dos granitoides gnaissificados do Complexo Colméia, em dobras recumbentes, orientadas na direção E-W. A xistosidade (S1) plano-axial se formou em condições de fácies anfibolito média a alta. A fase seguinte diz respeito à constituição do Grupo Rio do Côco em discordância com o Complexo Colméia. Nesse evento estabeleceram-se dobras empinadas orientadas na direção E-W e formou-se uma xistosidade em condições de fácies xisto verde. A segunda geração de dobras do Complexo Colméia está relacionada a esse evento deformacional. O domínio 4 é definido pela região que compreende parte dos municípios de Paraíso do Norte, Fátima, Gurupi e Porto Nacional, correspondendo à porção centro-oeste da área. Faz parte desse domínio o Complexo Rio dos Mangues, as suítes Matança e Serrote e os gnaisses alcalinos da Serra da Estrela, dispostos em corpos tabulares sub-concordantes orientados na direção N30°E. A exemplo do que se observa nas unidades do domínio 2, os diferentes conjuntos rochosos do domínio 4 exibem feições estruturais ligadas aos eventos de cisalhamento de baixo e alto ângulos. A passagem entre os domínios 1 e 2 e entre os domínios 3 e 4 é gradativa de modo que se delineiam dois blocos crustais antigos (domínios 1 + 2 e 3 + 4) separados pela faixa de rochas granulíticas (Complexo Porto Nacional). A zona de justaposição corresponde a um cinturão de cisalhamento dúctil de baixo ângulo, desenvolvido a partir do cavalgamento do bloco Brasília, a leste, sobre o bloco Araguacema, a oeste. Quadro geológico semelhante já foi muito bem caracterizado na África do Sul, no Oeste da Groelândia e no noroeste da Escócia, e começa a ser esboçado em várias regiões no Brasil, configurando-se uma nova maneira de entender as relações entre os terrenos arqueanos. Nesse segmento crustal, estabilizado no final do Arqueano, foram injetados corpos graníticos da Suíte Lajeado, no final do Proterozoico Inferior, e corpos básico-ultrabásicos na primeira metade do Proterozoico Médio. Nesta época, o Lineamento Transbrasiliano se individualizou como zona de cisalhamento rúptil. Na segunda metade do Proterozoico Médio instalaram-se as bacias, onde se depositaram as rochas que constituem o Supergrupo Baixo Araguaia e o Grupo Natividade, separadas por um bloco limitado hoje, pelas cidades de Paraíso do Norte, Gurupi ePorto Nacional. O lineamento Transbrasiliano voltou a ser ativo nesse período. No final do Proterozoico Médio, uma compressão regional, aproximadamente E-W, permitiu a edificação das faixas de dobramentos Araguaia e Uruaçu. A evolução da faixa de dobramentos Araguaia envolve quatro estágios de formação de estruturas. No primeiro estágio formaram-se dobras recumbentes submeridianas, com uma xistosidade plano axial (S1) desenvolvida em condições de fácies anfibolito média a xisto verde média. Os estágios intermediários referem-se a dobramentos e redobramentos de S1. O último estágio corresponde à formação dos corpos graníticos da Suíte Santa Luzia. Como resultado dessa evolução, verifica-se na faixa Araguaia uma assimetria importante, caracterizada pela atenuação de deformação e das transformações mineralógicas de leste para oeste. O quadro geral da faixa de dobramento Uruaçu é caracterizado por dobras desenhadas pelo acamamento, com planos axiais variáveis e por transformações mineralógicas em fácies xisto verde. Na região estudada não existem variações regulares na intensidade da deformação e do grau metamórfico. Os sedimentos imaturos da Formação Monte do Carmo são os produtos dos últimos processos litogenéticos de Proterozóico Médio na área. Durante a evolução das faixas de dobramentos Araguaia e Uruaçu, a parte norte do Maciço Goiano teve uma participação limitada, de tal modo que funcionou como um bloco rígido em relação aos dobramentos laterais. Os produtos finais ligados à evolução policíclica desse segmento crustalno Pré-Cambriano. São representados por sistemas de falhas direcionais orientadas principalmente nas direções N40°- 60° E e N40° - 50° W. O sistema de falhas NE reflete nova movimentação através do Lineamento Transbrasiliano no Proterozoico Superior. No Fanerozoico depositaram-se expressivas sequências sedimentares e novos movimentos foram registrados no Lineamento Transbrasiliano levando ao desenvolvimento de importantes desnivelamentos de blocos, refletidos, em parte, na morfologia atual da área. / The study area is bounded by the cities Paraíso do Norte, Gurupi, and Dianópolis in north-central Goiás State. The area contains diverse lithostratigraphic units and various generations of structures related to distinct thermo-tectonic events. Based on the distribution and the petrographic and structural characteristics of the ancient rock assemblage, four litho-structural domains were defined and attributed to the Archean. Domain "1" includes the region of Almas-Dianópolis and is interpreted as part of granite-greenstone terrane. It includes a group of tonalitic gneisses with associated supracrustal rocks (Goiano Complex), a sequence of metavolcanic rocks and metasediments (Riachão do Ouro Group), and various tonalite bodies (Serra do Boqueirão Suite) intruded into the earlier units. The evolution of the domain includes three principal deformational events: a) Formation of the amphibolites and/or biotite gneisses and granitoids characterized by sub-vertical banding oriented N10ºE and accompanied by mineralogical changes under conditions of amphibolite facies; b) deposition of the Riachão do Ouro Group, followed by isoclinal folding oriented N10°E and consequent transformation to greenschist facies. The emplacement of the tonalitic diapirs of the Serra do Boqueirão Suite is related to this event; c) a foliation gently inclined to the SE resulting from a simple low-angle ductile-brittle shearing process which affected the west part of this domain, transforming the rocks of the Goiano Complex into mylonitic gneisses under amphibolite facies conditions. Domain 2 includes the counties of Porto Nacional, Brejinho de Nazaré, and Natividade in the east-central part of the area. It is characterized by granulitic gneisses (Porto Nacional Complex), by tonalitic gneisses with associated supracrustal rocks (Manoel Alves Complex), including metasediments and metavolcanics (Morro do Aquiles Formation), and by pegmatitic granites such as the Xobó Suite. The different lithologic units take the form of lenses or sub-horizontal concordant to sub-concordant bodies with strike N30°E. They show structural features produced by a low-angle ductile-brittle shearing process under amphibolite facies conditions. Superposed on the low-angle features are various zones of high-angle directional shear having different intensities of deformation, but all in greenschist facies conditions. Domain 3 is within the NW part of Paraiso do Norte county and is interpreted as a granite-greenstone terrane similar to that of Domain 1. This Domain includes the Colméia Complex, the Rio do Coco Group, and the alkaline gneisses of Monte Santo. Two principal deformational phases are responsible for the structures in this domain: a) folding (S) of the gneissic granitoids of the Colméia Complex into recumbent folds oriented E-W. The axial plane schistosity (S1) formed in medium to amphibolite facies conditions; b) deposition of the Rio do Coco Group, discordant with the Colméia Complex, followed by sub-vertical folding oriented E-W. The second generation of folds in the Colméia Complex is related to this deformational event. Domain 4, in the west-central part of the area, includes parts of Paraíso do Norte, Fatima, Gurupi, and Porto Nacional counties. This domain is composed of the Rio dos Mangues Complex, the Matança and Serrote Suites, and the alcaline gneisses of the Serra da Estrela, distributed in sub-concordant sheets oriented N30°E. Similarly to that observed in Domain 2, these rock assemblages show structural features related to low-and high-angle shearing events. The transition between Domains 1 and 2 and between Domains 3 and 4 is gradational, such that two ancient blocks of crust are defined (Domains 1+2 and 3+4] separated by a belt of granulitic rocks (Porto Nacional Complex). The zone of juxtaposition corresponda to a belt of low-angle ductile shearing developed by the overthrusting of the Brazilian block, on the east, onto the Araguacema block to the west. Similar geologic conditions have been well characterized in South Africa, in western Greenland, and in NW Scotland and are beginning to be described in various regions in Brazil, constituting a new way to understand the relations between Archean terranes. Granite bodies of the Lajeado Suite at the end of the Lower Proterozoic and ultrabasic bodies in the first half of the Middle Proterozoic were injected into this crustal segment stabilized at the end of the Archean. During this epoch the Transbrazilian Lineament became defined as a brittle shear zone. Basins were developed in the second half of the Middle Proterozoic, with deposition of the Baixo Araguaia Supergroup and the Natividade Group. These two are separated today by a block limited by the cities of Paraíso do Norte, Gurupi, and Porto Nacional. The Transbrazilian Lineament was reactivated in this period.At the end of the Middle Proterozoic an E-W regional compression produced the Araguaia and Uruaçu fold belts. The evolution of the Araguaia fold belt involved four stages of structural deformation. In the first stage, N-S recumbent folds were formed having axial plane schistosity (S1) developed in intermediate amphibolite facies to intermediate greenschist facies conditions. The intermediary stages involved folding and refolding of the S1. The last stage is related to the formation of domai structures resulting from the intrusion of the granite bodies of the Santa Luzia Suite. As a result of this evolution, the Araguaia belt has an importent asymmetry characterized by intensification of deformation and mineralogical transformations from west to east. The Uruaçu fold belt is In general characterized by folds with variably-oriented axial planes and mineralogical changes tipical of greenschist facies. In the studied region, regular variations In deformational intensity and metamorphic degree were not found. The immature sediments of the Monte do Carmo Formation are the products of the last lithogenetic processes of the Middle Proterozoic in the area. During the evolution of the Araguaia and Uruaçu fold belts, the north part of the Goiano massif had a limited participation in such a way that it functioned as a rigid block with respect to the folding on either side. The final products related to the polycyclic evolution of this crustal segment during the Priecambrian are represented by directional fault systems oriented principally N40º -60ºE and N40º -50º W. The NE system of faults reflects a reactivation of the Transbrazilian Lineament in the Upper Proterozoic. Thick sedimentary sequences were deposited in the Phanerozoic and new movements on the Transbrazilian Lineament caused the development of important block faulting which is reflected in part by the present-day geomorphology of the area.

Although the clinical efficacy of statins has been well established, there is a wide inter-individual variation in the lipid responses to statins. Pharmacogenetic studies have identified some genetic differences that contribute to the variation, but overall the results have been disappointing. The studies described in this thesis were performed to examine whether certain genetic variants predicted the lipid responses to rosuvastatin in Chinese patients. Over 400 Chinese patients with increased risk of cardiovascular disease (CVD) who were treated with rosuvastatin 10 mg daily for at least 4 weeks (more than 97% of patients had at least 6 weeks treatment) were studied, including 166 having familial hypercholesterolaemia (FH) and 36 having rheumatoid arthritis (RA). They were genotyped for 135 polymorphisms in 62 candidate genes/loci potentially related to pharmacokinetics or pharmacodynamics of statins and lipid metabolism. Associations between genetic polymorphisms and the lipid responses to rosuvastatin were analyzed in 386 patients with good compliance. The associations between genetic polymorphisms and some risk factors for CVD including baseline lipid levels, high-sensitivity C-reactive protein (hsCRP), uric acid and bilirubin levels were also analyzed. / Some novel genetic determinants of the LDL-C response to rosuvastatin treatment have been identified in this study. The responses in HDL-C and triglycerides were related more closely to the baseline levels of these lipids than to any of the polymorphisms examined. Genetic associations with baseline lipid parameters, hsCRP, uric acid and bilirubin were identified and generally correspond with some of the previous reports of studies in Chinese and other ethnic groups. / The key findings of the study are as follows: 1. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 (ABCG2) gene (P=9.2x10 -7), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 (FMO3) gene (P=0.0002), 1421C>G in the lipoprotein lipase (LPL) gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II (APOE/C1/C4/C2) gene cluster (P=0.004). These genetic polymorphisms and having FH totally explained 13.6% of the variance in percentage change in LDL-C in response to rosuvastatin. The greater percentage reduction in LDL-C in patients with the ABCG2 421AA genotype compared to those with the ABCG2 421CC genotype was equivalent to at least doubling the dose of rosuvastatin. 2. Three SNPs (glucokinase regulator [ GCKR] rs1260326, apolipoprotein AS [APOA5] -1131T>C and the solute carrier organic anion transporter 1B1 [SLCO1B1] 521T>C) tended to be associated with percentage changes in high-density lipoprotein cholesterol (HDL-C) (P&lt;0.05), but none of these reached the overall significance level. In multivariate stepwise regression analysis, baseline HDL-C (P=1.6x10 -6), having diabetes (P=0.0004) or RA (P=0.002) and the SLCO1B1 521T>C polymorphism (P=0.03) were determinants of HDL-C responses, contributing 9.9% of the variance in percentage change in HDL-C, but the genetic factors only contributed to 0.8% of the variance. 3. The triglyceride response to rosuvastatin was highly variable and was strongly related to baseline levels. The diacylglycerol acyltransferase-2 (DGAT2) rs10899113 C>T polymorphism tended to be associated with reduced triglyceride response in a gene-dose dependent manner. However, in multivariate stepwise regression analysis, baseline triglyceride level was the only factor that strongly related to the triglyceride response, explaining 14.4% of the variance. 4. This study has also analyzed relationships between on-treatment plasma hsCRP concentrations and cardiovascular risk factors and 14 single nucleotide polymorphisms in CRP and other candidate genes, which showed that central obesity, low HDL-C and CRP polymorphisms are major determinants of higher hsCRP levels in Chinese patients on treatment with rosuvastatin. 5. The association between genetic polymorphisms and lipid traits were analyzed in FH and non-FH patients separately due to their different lipid profiles. The analysis has shown that there were different genetic predictors of lipid levels in patients with and without FH and that more genetic factors appeared to affect the baseline lipid levels in patients with FH compared to non-FH patients, suggesting complex interactions between genetic and environmental factors and plasma cholesterol levels in patients with and without FH. 6. The SLC2A9 (solute carrier family 2, member 9) rs1014290 T>C was significantly associated with plasma uric acid levels in a gene-dose dependent manner (P=1.0x10-5) and the relationship was more pronounced in women or in patients without hypertension than in men or patients with hypertension. The ABCG2 421 C>A did not show a significant effect on uric acid levels. 7. The UGT1A1 (uridine diphosphate glucuronosyltransferases family, polypeptide A1) variants *28 (P=1.5x10 -9) and *6 (P=2.2x10-7) were independently associated with increased baseline bilirubin levels. Polymorphisms in SLCO1B1 did not appear to affect bilirubin levels in this study. / Hu, Miao. / Adviser: Brian Tomlinson. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 230-264). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Jiang, Jieying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 170-186). / Abstract also in Chinese. / ACKNOWLEDGEMENT --- p.II / ABBREVIATIONS --- p.III / ABSTRACT OF THESIS ENTITLED: --- p.VI / 摘要 --- p.IX / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Individual variations of blood sex steroid levels and their determinants --- p.1 / Chapter 1.1.1 --- Introduction to Sex steroids --- p.1 / Chapter 1.1.2 --- Androgens --- p.1 / Chapter 1.1.2.1 --- Types of androgens --- p.1 / Chapter 1.1.2.2 --- Androgens plasma concentration and relative biological potencies --- p.2 / Chapter 1.1.2.3 --- Androgen biosynthesis and metabolism --- p.3 / Chapter 1.1.2.4 --- Testosterone transportation in plasma --- p.6 / Chapter 1.1.2.5 --- Measurement of free testosterone --- p.7 / Chapter 1.1.2.6 --- The hypothalamus-pituitary-testicular axis and testosterone secretion --- p.8 / Chapter 1.1.2.7 --- Androgen action --- p.10 / Chapter 1.1.2.8 --- Androgen biological function and diseases in men --- p.11 / Chapter 1.1.3 --- Estrogen biological function and diseases in men --- p.12 / Chapter 1.1.4 --- Factors influencing circulating sex steroid levels --- p.13 / Chapter 1.1.4.1 --- Genetic determinants affecting sex steroid levels --- p.15 / Chapter 1.2 --- Genetic variants in sex steroid metabolic pathway and hepatocellular carcinoma (HCC) --- p.18 / Chapter 1.2.1 --- Epidemiology of HCC --- p.18 / Chapter 1.2.2 --- Etiological factors of HCC --- p.22 / Chapter 1.2.3 --- The male predominance in HCC --- p.24 / Chapter 1.2.4 --- Genetic predisposition to HCC --- p.26 / Chapter CHAPTER 2 --- PART A STUDY: GENETIC VARIATIONS IN SEX STEROID METABOLIC PATHWAY AND ASSOCIATION WITH SEX STEROID LEVELS --- p.28 / Chapter 2.1 --- Introduction --- p.28 / Chapter 2.1.1 --- Candidate genes association with sex steroid levels --- p.28 / Chapter 2.1.2 --- Genes involved in androgen metabolism --- p.29 / Chapter 2.1.2.1 --- SRD5A --- p.29 / Chapter 2.1.2.2 --- HSD3B1 --- p.30 / Chapter 2.1.2.3 --- HSD17B2 --- p.31 / Chapter 2.1.2.4 --- AKR1C3 and AKRlC4 --- p.31 / Chapter 2.1.2.5 --- AKR1D1 --- p.32 / Chapter 2.1.3 --- Genes involved in estrogen metabolism --- p.32 / Chapter 2.1.3.1 --- CYP19A1 --- p.32 / Chapter 2.1.3.2 --- Other genes involved in estrogen metabolism --- p.33 / Chapter 2.1.4 --- Association of sex steroid related genes and blood concentrations of sex steroid levels --- p.33 / Chapter 2.1.4.1 --- Genes involved in androgen metabolic pathway and association with sex steroid levels --- p.33 / Chapter 2.1.4.2 --- Genes involved in estrogen metabolic pathway and association with sex steroid levels --- p.36 / Chapter 2.1.5 --- Aims of the study (Part A) --- p.37 / Chapter 2.2 --- Materials and methods --- p.38 / Chapter 2.2.1 --- Study subjects and biological samples --- p.38 / Chapter 2.2.2 --- TagSNP selection --- p.39 / Chapter 2.2.3 --- Genotyping of tagging SNPs --- p.41 / Chapter 2.2.4 --- Genotyping methods comparison --- p.52 / Chapter 2.2.5 --- Statistics --- p.53 / Chapter 2.3 --- Results --- p.54 / Chapter 2.3.1 --- Characteristics of study population --- p.54 / Chapter 2.3.2 --- Replication study for the association of CYP19A1 --- p.55 / Chapter 2.3.2.1 --- Association of the SNP rs2470152 and rs2899470 with serum estrogen and testosterone levels --- p.55 / Chapter 2.3.2.2 --- Halotype analysis and haplotype association in the tertile groups --- p.61 / Chapter 2.3.2.3 --- Haplotype construction of 3 SNPs --- p.63 / Chapter 2.3.3 --- SRD5A1 --- p.65 / Chapter 2.3.3.1 --- Association of SRD5A1 and sex steroid levels --- p.65 / Chapter 2.3.3.2 --- Haplotype analysis and haplotype association in the tertile groups --- p.71 / Chapter 2.3.4 --- SRD5A2 --- p.72 / Chapter 2.3.4.1 --- Association of SRD5A2 and sex steroid levels --- p.72 / Chapter 2.3.4.2 --- Haplotype association analysis of SRD5A2 in tertile groups --- p.76 / Chapter 2.3.5 --- HSD3B1 --- p.77 / Chapter 2.3.5.1 --- Association of HSD3B1 and sex steroid levels --- p.77 / Chapter 2.3.6 --- HSD17B2 --- p.80 / Chapter 2.3.6.1 --- Association of HSD17B2 and sex steroid levels --- p.80 / Chapter 2.3.6.2 --- Halotype association analysis of HSD17B2 in the tertile groups --- p.87 / Chapter 2.3.7 --- AKR1C4 --- p.89 / Chapter 2.3.7.1 --- Association of AKR1C4 and sex steroid levels --- p.89 / Chapter 2.3.7.2 --- Halotype association analysis of AKR1C4 in the tertile groups --- p.93 / Chapter 2.3.8 --- AKR1D1 --- p.94 / Chapter 2.3.8.1 --- Association of AKR1D1 and sex steroid levels --- p.94 / Chapter 2.3.8.2 --- Haplotype association analysis of AKR1D1 in the tertile groups --- p.99 / Chapter 2.3.9 --- AKR1C3 --- p.100 / Chapter 2.3.9.1 --- Association of AKR1C3 and sex steroid levels --- p.100 / Chapter 2.3.9.2 --- Haplotype association analysis of AKR1C3 in the tertile groups --- p.104 / Chapter 2.3.10 --- Overall association of polymorphisms in sex steroid metabolism genes and metabolites levels in blood --- p.105 / Chapter 2.4 --- Discussion --- p.106 / Chapter 2.4.1 --- SRD5A and sex steroid levels --- p.106 / Chapter 2.4.2 --- HSD17B2 and sex steroid levels --- p.110 / Chapter 2.4.3 --- "AKR1D1, AKR1C4, AKR1C3 and catabolic intermediates of sex steroids" --- p.112 / Chapter 2.4.4 --- HSD3B1 and sex steroid levels --- p.114 / Chapter 2.4.4 --- CYP19A1 and sex steroid levels --- p.114 / Chapter CHAPTER 3 --- PART B STUDY: GENETIC VARIATIONS IN SEX STEROID METABOLIC PATHWAY AND ASSOCIATION WITH HCC --- p.119 / Chapter 3.1 --- Introduction --- p.119 / Chapter 3.1.1 --- Previous genetic association studies of HCC on sex steroid metabolic pathways --- p.119 / Chapter 3.1.2 --- Previous genetic association studies of HCC in other pathways --- p.120 / Chapter 3.1.3 --- "Association of sex steroid related genes and other cancers, like prostate cancer" --- p.121 / Chapter 3.1.4 --- Aims of the study (Part B) --- p.123 / Chapter 3.2 --- Materials and method --- p.125 / Chapter 3.2.1 --- "Study subjects, Genomic DNA extraction" --- p.125 / Chapter 3.2.2 --- Tissue specimen and cell lines --- p.125 / Chapter 3.2.3 --- TagSNP selection --- p.126 / Chapter 3.2.4 --- Genotyping of tagging SNPs --- p.126 / Chapter 3.2.5 --- Statistics --- p.127 / Chapter 3.2.6 --- Extraction of RNA and Reverse-Transcription-PCR --- p.128 / Chapter 3.3 --- Results --- p.130 / Chapter 3.3.1 --- SRD5A1 --- p.130 / Chapter 3.3.1.1 --- SRD5A1 polymorphisms and risk of HCC --- p.130 / Chapter 3.3.2 --- SRD5A2 --- p.134 / Chapter 3.3.2.1 --- SRD5A2 polymorphisms and risk of HCC --- p.134 / Chapter 3.3.2.2 --- Haplotype analysis --- p.136 / Chapter 3.3.3 --- HSD3B1 --- p.137 / Chapter 3.3.3.1 --- HSD3B1 polymorphisms and risk of HCC --- p.137 / Chapter 3.3.3.2 --- Haplotype analysis --- p.139 / Chapter 3.3.4 --- HSD17B2 --- p.140 / Chapter 3.3.4.1 --- HSD17B2 polymorphisms and risk of HCC --- p.140 / Chapter 3.3.4.2 --- Haplotype analysis --- p.143 / Chapter 3.3.5 --- CYP19A1 --- p.144 / Chapter 3.3.5.1 --- CYP19A1 polymorphisms and risk of HCC --- p.144 / Chapter 3.3.5.2 --- Haplotype analysis --- p.146 / Chapter 3.3.6 --- AKR1C4 --- p.147 / Chapter 3.3.6.1 --- AKR1C4 polymorphisms and risk of HCC --- p.147 / Chapter 3.3.6.2 --- Haplotype analysis --- p.148 / Chapter 3.3.7 --- AKR1D1 --- p.149 / Chapter 3.3.7.1 --- AKR1D1 polymorphisms and risk of HCC --- p.149 / Chapter 3.3.7.2 --- Haplotype analysis --- p.150 / Chapter 3.3.8 --- AKR1C3 --- p.151 / Chapter 3.3.8.1 --- AKR1C3 polymorphisms and risk of HCC --- p.151 / Chapter 3.3.8.2 --- Haplotype analysis --- p.152 / Chapter 3.3.9 --- mRNA expression study of the 5 α -reductase isoforms --- p.153 / Chapter 3.3.9.1 --- Expression of SRD5A1 and SRD5A2 mRNAin HCC patients --- p.153 / Chapter 3.3.9.2 --- Expression of SRD5A1 and SRD5A2 mRNAin prostate and HCC cell lines --- p.154 / Chapter 3.3.10 --- Overall association of polymorphisms in sex steroid metabolism genes and risk of HCC --- p.154 / Chapter 3.3.11 --- GMDR analysis --- p.156 / Chapter 3.4 --- Discussion --- p.159 / Chapter 3.4.1 --- 5 α-reductase and risk of HCC --- p.159 / Chapter 3.4.1.1 --- SRD5A2 --- p.160 / Chapter 3.4.1.2 --- SRD5A1 --- p.161 / Chapter 3.4.2 --- Other genes and association with HCC --- p.162 / Chapter 3.4.2.1 --- HSD17B2 and risk of HCC --- p.162 / Chapter 3.4.2.2 --- "HSD3B1, AKR1C3, AKR1C4, AKR1D1 and risk of HCC" --- p.163 / Chapter 3.4.2.3 --- CYP19A1 and risk of HCC --- p.164 / Chapter 3.4.3 --- Gene-Gene interactions associated with HCC --- p.165 / Chapter CHAPTER 4 --- CONCLUSIONS AND PROSPECT FOR FUTURE WORK --- p.166 / Chapter 4.1 --- Conclusion --- p.166 / Chapter 4.2 --- Future works and prospect --- p.169 / REFERENCES --- p.170

The inspiration behind this philosophical endeavor is an ethical one: interested in what it means to flourish as a human being – how to live well and authentically. Similar to medicine and how the ability to prescribe the appropriate treatment depends on first making a diagnosis, the focus of this work will to be understand the human condition and the ways in which subjectivity, one’s sense of self, is constituted. Given the general dissatisfaction with the modern metaphysical picture of the world, which analyzes the world in terms of the mutually exclusive and completely separate categories of nature/objects and society/subjects, I proceed from an alternative conceptual perspective, that of non-modernity, offered by Bruno Latour. By focusing on the actual practice of the sciences Latour develops one of his central concepts: mediation. From this understanding of the practices of mediation the world is revealed as an ontological continuum of hybrids – mixtures of human and nonhuman elements – that ranges from quasi-object to quasi-subject. Rather than being separate, nature and society are intimately interwoven and co-constituted, forming a nature-culture collective that is connected and defined by the network of relations between existing hybrids. Given this philosophical landscape of mediation, hybrids and networks, the question that I seek to address is how does this effect what it means to be human? What does it mean to human living in a hybrid world? I answer this question by articulating and developing Latour’s concept of quasi-subject. This will ultimately amount to saying that as humans, our sense of self and agency is co-constituted through our networks of relations with both humans and nonhumans. I conclude the paper by exploring some of the ethical implications that naturally emerge from such an understanding.