Analisou-se neste trabalho a produção científica brasileira, no campo da Saúde, por meio da pesquisa de publicações, constantes da base de dados \"Web of Knowledge\", no período de 1990 a 2002. A pesquisa incluiu 3.066 revistas desse campo do conhecimento. Nesse período foram contabilizadas 38.349 publicações. Os métodos bibliométricos tradicionais e a \"co-word analysis\" foram utilizados como instrumento de análise para medir a atividade científica no campo da saúde. O pacote estatístico, Statistical Package for Social Science - SPSS, foi utilizado para a obtenção dos indicadores bibliométricos tradicionais. Demonstraram-se as etapas de trabalho e a potencialidade da \"co-word analysis\". Foram estudadas as palavras que representam os descritores e identificadores na base de dados e estas foram relacionadas com outras variáveis como autores, ano de publicação e filiação da publicação. Para tal, utilizou-se o \"Tétralogie\", um software que aplica tratamentos estatísticos para conseguir que o grau de co-ocorrência entre as palavras seja representado como distâncias no espaço. Desta forma, as palavras podem ser visualizadas como pontos no espaço, por meio dos mapas tecnológicos e a distância entre elas será representativa de sua co-ocorrência ou afinidade. Os mapas tecnológicos permitiram a identificação de redes de cooperação entre pesquisadores e instituições, bem como identificação de \"clusters\" entre autores e as palavras descritoras do campo de conhecimento estudado. Esta abordagem para a área de avaliação em Ciência e Tecnologia demonstrou ampliar as análises bibliométricas tradicionais, e pode incrementar as atividades de planejamento e definição de ações estratégicas indicando, para onde e como se poderiam dirigir esforços para desenvolvimento do campo estudado. / This work analyzed Brazilian scientific production in the health sciences field by analysis of publications present in the database \"Web of knowledge\" in the period from 1990 to 2002. The study covered 3,066 journals in this field of knowledge. During this period a total of 38,349 Brazilian publications were found. Bibliometric analysis and \"co-word analysis\" were used to measure the scientific activity in health sciences. A statistical software package (Statistical Package for Social Science – SPSS) was used to determine traditional bibliometric analysis. The words representing descriptors and identifiers in the database had been studied and the relationship to other variables such as authors, publication year, and affiliation within the publication was determined. For this analysis, the \"Tétralogie\" software that applies statistical methods to measure the co-occurrence among words and represents this measure as distances in space was used. In this way, words can be visualized as points in space on a map. The maps and distances between words will represent the co-occurrence or affinity between keywords. The technological maps have shown networks of cooperation among researchers and institutions, as well as identification of \"clusters\" of authors and a hierarchy of the descriptive keywords. This approach for evaluation of science and technology demonstrated an extension of the traditional bibliometric analysis and showed that it could improve planning activities by identification of strategic actions pointing to where and how efforts for improvement in the field of health sciences should be directed.

University of Macau / Institute of Chinese Medical Sciences

Text in English / The membership of the African Independent Churches is growing day by day. Research into the growth ohhis phenomenon is being conducted by various scholars. G.C. Oosthuizen studied the African Independent Churches in general, and the Shembe Church, in particular. This study examines Oosthuizen' s research of the African Independent Churches by analysing the three books that he devoted specifically to the Shembe Church. A set of five criteria is developed to evaluate Oosthuizen as a researcher. The study finds that his background and formation affected the research he conducted and contributed to the type of picture he portrayed of the Shembe Church. Oosthuizen, as a scholar of religion, sometimes allowed his theological interests to influence his research. As an empirical researcher Oosthuizen attempted to let the AICs "speak for themselves" but his theological interests caused him to make value judgements which influenced his research findings. / Christian Spirituality, Church History and Missiology / M. Th. (Missiology)

Analisou-se neste trabalho a produção científica brasileira, no campo da Saúde, por meio da pesquisa de publicações, constantes da base de dados \"Web of Knowledge\", no período de 1990 a 2002. A pesquisa incluiu 3.066 revistas desse campo do conhecimento. Nesse período foram contabilizadas 38.349 publicações. Os métodos bibliométricos tradicionais e a \"co-word analysis\" foram utilizados como instrumento de análise para medir a atividade científica no campo da saúde. O pacote estatístico, Statistical Package for Social Science - SPSS, foi utilizado para a obtenção dos indicadores bibliométricos tradicionais. Demonstraram-se as etapas de trabalho e a potencialidade da \"co-word analysis\". Foram estudadas as palavras que representam os descritores e identificadores na base de dados e estas foram relacionadas com outras variáveis como autores, ano de publicação e filiação da publicação. Para tal, utilizou-se o \"Tétralogie\", um software que aplica tratamentos estatísticos para conseguir que o grau de co-ocorrência entre as palavras seja representado como distâncias no espaço. Desta forma, as palavras podem ser visualizadas como pontos no espaço, por meio dos mapas tecnológicos e a distância entre elas será representativa de sua co-ocorrência ou afinidade. Os mapas tecnológicos permitiram a identificação de redes de cooperação entre pesquisadores e instituições, bem como identificação de \"clusters\" entre autores e as palavras descritoras do campo de conhecimento estudado. Esta abordagem para a área de avaliação em Ciência e Tecnologia demonstrou ampliar as análises bibliométricas tradicionais, e pode incrementar as atividades de planejamento e definição de ações estratégicas indicando, para onde e como se poderiam dirigir esforços para desenvolvimento do campo estudado. / This work analyzed Brazilian scientific production in the health sciences field by analysis of publications present in the database \"Web of knowledge\" in the period from 1990 to 2002. The study covered 3,066 journals in this field of knowledge. During this period a total of 38,349 Brazilian publications were found. Bibliometric analysis and \"co-word analysis\" were used to measure the scientific activity in health sciences. A statistical software package (Statistical Package for Social Science – SPSS) was used to determine traditional bibliometric analysis. The words representing descriptors and identifiers in the database had been studied and the relationship to other variables such as authors, publication year, and affiliation within the publication was determined. For this analysis, the \"Tétralogie\" software that applies statistical methods to measure the co-occurrence among words and represents this measure as distances in space was used. In this way, words can be visualized as points in space on a map. The maps and distances between words will represent the co-occurrence or affinity between keywords. The technological maps have shown networks of cooperation among researchers and institutions, as well as identification of \"clusters\" of authors and a hierarchy of the descriptive keywords. This approach for evaluation of science and technology demonstrated an extension of the traditional bibliometric analysis and showed that it could improve planning activities by identification of strategic actions pointing to where and how efforts for improvement in the field of health sciences should be directed.

This thesis was a research and analysis of the levels of different customer satisfaction standards in the family construction company. The analysis involved conducting internal and external environment assessments of the company. The data collected on customer satisfaction from clients was carried out by using a qualitative questionnaire method. This study provided the host family construction company with recommendations on how to develop the customer satisfaction standards, which in turn will improve their market position.

Research policy has become increasingly important for policymakers in Europe as it is considered to be a driving force behind the global knowledge-based economy. An array of new tools for the evaluation and funding of research have been implemented both by the European Union and its Member States; particularly distinctive are those that have been developed in the Czech Republic and Sweden. This dissertation, through four cases studies, investigates why these tools have appeared and what effects they have on the practice of research. Using a conceptual framework of public administration ideal-type narratives, the dissertation shows that these new tools can be considered as New Public Management type reforms. Further, the dissertation creates a theoretical model in which institutional theories are operationalized and used to reveal the politics behind the policy tools and the way that they affect individual behavior in the academic environment. The results demonstrate that strong influences are exerted by the rational choice logics embedded in New Public Management tools, which do distort the practice of research, yet these influences are also tempered by other historically and normatively-based logics within the complex system of research in higher education institutions. Powered by TCPDF (www.tcpdf.org)

Indiana University-Purdue University Indianapolis (IUPUI) / Disruptions of the endoplasmic reticulum (ER) cause perturbations in protein folding and result in a cellular condition known as ER stress. ER stress and the accumulation of unfolded protein activate the unfolded protein response (UPR) which is a cellular attempt to remedy the toxic accumulation of unfolded proteins. The UPR is implemented through three ER stress sensors PERK, ATF6, and IRE1. Phosphorylation of the α-subunit of eIF2 by PERK during ER stress represses protein synthesis and also induces preferential translation of ATF4, a transcriptional activator of stress response genes. Early UPR signaling involves translational and transcriptional changes in gene expression that is geared toward stress remedy. However, prolonged ER stress that is not alleviated can trigger apoptosis. This dual signaling nature of the UPR is proposed to mimic a 'binary switch' and the regulation of this switch is a key topic of this thesis. Adaptive gene expression aimed at balancing protein homeostasis encompasses the first phase of the UPR. In this study we show that the PERK/eIF2~P/ATF4 pathway facilitates both the synthesis of ATF6 and trafficking of ATF6 from the ER to the Golgi where ATF6 is activated. Liver-specific depletion of PERK significantly lowers expression of survival genes, leading to reduced expression of protein chaperones. As a consequence, loss of PERK in the liver sensitizes cells to stress which ultimately leads to apoptosis. Despite important roles in survival, PERK signaling is often extended to the vii activation of other downstream transcription factors such as CHOP, a direct target of ATF4-mediated transcription. Accumulation of CHOP is a hallmark of the second phase in the binary switch model where CHOP is shown to be required for full activation of apoptosis. Here the transcription factor ATF5 is found to be induced by CHOP and that loss of ATF5 improves the survival of cells following changes in protein homeostasis. Taken together this study highlights the importance of UPR signaling in determining the balance between cell survival and cell death. A topic that is important for understanding the more complex pathological conditions of diseases such as diabetes, cancer, and neurodegeneration.

Indiana University-Purdue University Indianapolis (IUPUI) / The antiretroviral drug efavirenz remains a cornerstone for treatment-naïve HIV patients. Subsequent to the demonstration that efavirenz is a substrate of cytochrome P450 (CYP) 2B6, a number of clinical studies found that the CYP2B6*6 allele is significantly associated with higher efavirenz exposure and/or adverse reactions. However, the mechanism of reduced efavirenz metabolism by this genetic variant is not fully understood and whether this variant exhibits differential susceptibility to metabolic inhibition is also unknown. Ths use of efavirenz is further complicated by the drug interactions associated with it. Therefore, I hypothezised that 1) the CYP2B6*6 allele reduces efavirenz metabolism by altering catalytic properties of CYP2B6; 2) efavirenz alters the pharmacokinetics of co-administered drugs by inhibiting drug metabolizing enzymes. A series of studies was carried out in hepatic microsomal preparations to determine the functional consequences of the CYP2B6*6 allele and to assess inhibition potency of efavirenz on 8 CYPs. The major findings for these studies include: 1) the CYP2B6*6 allele reduces efavirenz metabolism by decreasing substrate binding and catalytic efficiency; 2) functional consequences of the CYP2B6*6 allele appear to be substrate- and cytochrome b5-dependent; 3) the CYP2B6*6 allele confers increased susceptibility to metabolic inhibition; and 4) efavirenz inhibits the activities of CYP2B6, 2C8, 2C9 and 2C19 at therapeutically relevant concentrations. In addition, I explored the hypothesis that the incorporation of in vitro mechanism by which the CYP2B6*6 allele reduced efavirenz metabolism predicts the genetic effect of this allele on efavirenz clearance after a single oral dose by modeling approach. A pharmacogenetics-based in vitro-in vivo extrapolation (IVIVE) model was developed to predict human efavirenz clearance. Taken together, results from this dissertation provide new mechanistic information on how the CYP2B6*6 allale alters substrate metabolism and drug interactions; demonstrate new mechanisms of efavirenz-mediated inhibition interactions; and demonstrate the utility of a pharmacogenetics-based predictive model that can serve as a basis for future studies with efavirenz and other CYP2B6 substrates. Overall these data provide improved understanding of genetic and non-genetic determinant of efavirenz disposition and drug interactions associated with it.

Indiana University-Purdue University Indianapolis (IUPUI) / An investigation of the lipid metabolism pathway in the yeast Yarrowia lipolytica was conducted. Yarrowia is an oleaginous ascomycete that is capable of growing on many different substrates, which derives its name from its high efficiency of growth on lipids. Once the exogenous lipids are converted into free fatty acids and internalized by the yeast, the primary mode of degradation is through β-oxidation mediated by the peroxisomal oxidases, or POX genes. These enzymes catalyze the formation of a trans double bond, producing the trans-2-enoyl product. Our study looked at the comparison of the Y. lipolytica prototrophic strain against a knockout of the Pox2 gene on the uptake, incorporation, and degradation of relevant fatty acids. To construct this gene knockout, a novel gene deletion method using a combination of Cre recombinase and the AHAS* gene was synthesized, developed, and tested successfully. This knockout system allows for serial deletion of genes with the use of only one resistance marker, with excision of the marker after selection.

Indiana University-Purdue University Indianapolis (IUPUI) / The maternal liver shows marked growth during pregnancy to accommodate the development and metabolic needs of the placenta and fetus. Previous study has shown that the maternal liver grows proportionally to the increase in body weight during gestation by hyperplasia and hypertrophy of hepatocytes. As the maternal liver is enlarged, the transcript level of Ascl1, a transcription factor essential to progenitor cells of the central nervous system and peripheral nervous system, is highly upregulated. The aims of the study were to (1) identify hepatic Ascl1-expressing cells, and (2) study the functions of Ascl1 in maternal liver during pregnancy. In situ hybridization shows that most cell types (parenchymal, nonparenchymal, and mesothelial cells) express Ascl1 mRNA in maternal livers during gestation and in male regenerating livers. Notably, hepatic mesothelial cells abundantly express Ascl1 during pregnancy and liver regeneration. Inducible ablation of Ascl1 gene during pregnancy results in maternal liver enlargement, litter size reduction, and fetal growth retardation. In addition, maternal hepatocytes deficient in Ascl1 gene lack majority of their cytosols and exhibit β-catenin nuclear translocation, while maintaining their cellular boundary and identity. In summary, in both maternal liver during pregnancy and regenerating liver, the expression of Ascl1 is induced in most cell types. Mesothelial cells are potential origin of Ascl1-expressing cells. Ascl1 gene is essential for the progression of normal pregnancy