Ho Sin Ka Janice. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 105-119). / Abstracts in English and Chinese. / Chapter CHAPTER 1. --- Introduction / Chapter 1.1. --- Epidemiology of Type 2 Diabetes --- p.1 / Chapter 1.2. --- Risk factors contributing to Type 2 Diabetes --- p.3 / Chapter 1.2.1. --- Environmental and physiological factors --- p.3 / Chapter 1.2.2. --- Genetic factors --- p.3 / Chapter 1.3. --- Disruption of energy homeostasis in the pathogenesis of type 2 diabetes --- p.6 / Chapter 1.3.1. --- Clinical spectrum of diabetes --- p.6 / Chapter 1.3.2. --- Insulin as a key regulator of energy homeostasis --- p.7 / Chapter 1.3.3. --- Insulin secretion and glucose metabolism --- p.8 / Chapter 1.3.4. --- Insulin action and lipid metabolism --- p.9 / Chapter 1.3.5. --- Lipotoxicity and glucotoxicity --- p.12 / Chapter 1.3.6. --- Role of transcription factors as metabolic switch --- p.13 / Chapter 1.4. --- Candidate genes implicated in type 2 diabetes susceptibility --- p.15 / Chapter 1.4.1. --- Candidate genes involved in insulin secretion pathway --- p.15 / Chapter 1.4.1.1. --- HNF4A --- p.15 / Chapter 1.4.1.2. --- HNF1A --- p.16 / Chapter 1.4.1.3. --- PDX1/PBX1 --- p.17 / Chapter 1.4.1.4. --- NEUROD1 --- p.17 / Chapter 1.4.1.5. --- GCK --- p.17 / Chapter 1.4.1.6. --- KCNJ11/ABCC8 --- p.18 / Chapter 1.4.2 --- Candidate genes involved in insulin action pathway --- p.19 / Chapter 1.4.2.1. --- PPARG --- p.19 / Chapter 1.4.2.2. --- PPARA --- p.20 / Chapter 1.4.2.3. --- PPARGC1A --- p.20 / Chapter 1.4.2.4. --- ADIP0Q --- p.21 / Chapter 1.4.2.5. --- LPL --- p.21 / Chapter 1.4.2.6. --- UPC --- p.22 / Chapter 1.5. --- Hypothesis and objectives of the study --- p.23 / Chapter CHAPTER 2. --- Materials and methods / Chapter 2.1. --- Study design --- p.25 / Chapter 2.1.1. --- Two-stage candidate gene association design --- p.25 / Chapter 2.1.2. --- Power calculation --- p.27 / Chapter 2.2. --- Study cohort --- p.29 / Chapter 2.2.1. --- Subject recruitment --- p.29 / Chapter 2.2.2. --- Clinical and biochemical measurements --- p.30 / Chapter 2.2.3. --- Clinical definitions --- p.31 / Chapter 2.3. --- Genetic study --- p.32 / Chapter 2.3.1. --- Candidate gene selection --- p.32 / Chapter 2.3.2. --- SNP selection --- p.32 / Chapter 2.3.3. --- DNA sample preparation --- p.35 / Chapter 2.3.4. --- Genotyping methods --- p.36 / Chapter 2.3.4.1. --- Allele specific Tm shift assay --- p.36 / Chapter 2.3.4.2. --- Mass spectrometry assay --- p.40 / Chapter 2.4. --- Data quality control --- p.42 / Chapter 2.4.1. --- Stage 1 --- p.42 / Chapter 2.4.2. --- Stage 2 --- p.42 / Chapter 2.5. --- Statistical analysis --- p.45 / Chapter 2.5.1. --- Stage 1 analysis --- p.45 / Chapter 2.5.2. --- Stage 2 analysis --- p.45 / Chapter 2.5.3. --- Stage 1 and 2 combined analysis --- p.46 / Chapter CHAPTER 3. --- Results / Chapter 3.1. --- Clinical characteristics of subjects in stages 1 and 2 studies --- p.48 / Chapter 3.2. --- Case-control associations in stage 1 --- p.51 / Chapter 3.2.1. --- Association with T2D --- p.51 / Chapter 3.2.2. --- Association with T2D subset by metabolic syndrome --- p.54 / Chapter 3.3. --- Case-control associations in stage 2 --- p.60 / Chapter 3.3.1. --- SNP selection for genotyping --- p.60 / Chapter 3.3.2. --- Association with T2D --- p.63 / Chapter 3.3.3. --- Association with T2D subset by metabolic syndrome --- p.64 / Chapter 3.4. --- Case-control associations in combined stages 1 and 2 --- p.66 / Chapter 3.4.1. --- Association with T2D --- p.66 / Chapter 3.4.2. --- Association with T2D subset by metabolic syndrome --- p.70 / Chapter 3.4.3. --- Association with T2D subset by age at diagnosis --- p.74 / Chapter 3.4.4. --- Association with T2D subset by gender --- p.76 / Chapter 3.4.5. --- Genetic epistasis for T2D association --- p.79 / Chapter 3.5. --- Metabolic traits associations in control subjects in combined stages 1 and 2 studies --- p.83 / Chapter CHAPTER 4. --- Discussion --- p.86 / Chapter 4.1. --- Role of insulin secretion genes in type 2 diabetes --- p.87 / Chapter 4.2. --- Role of insulin action genes in type 2 diabetes --- p.92 / Chapter 4.3. --- Combined genetic effects on risk for type 2 diabetes --- p.97 / Chapter 4.4. --- Summary --- p.98 / Chapter 4.5. --- Limitation of this study and future direction --- p.101 / REFERENCES --- p.104 / APPENDICES --- p.119 / Chapter Appendix 1: --- Gene structure and linkage disequilibrium of genotyped SNPs of candidate genes --- p.119 / Chapter Appendix 2: --- Information of SNPs genotyped in stage 1 --- p.130 / Chapter Appendix 3: --- T2D association results (additive model) of 152 SNPs for stage 1 case- control samples --- p.137 / Chapter Appendix 4: --- T2D association results (additive model) of 152 SNPs for stage 1 case- control samples subset by metabolic syndrome status in cases --- p.144 / Chapter Appendix 5: --- T2D association results (additive model) of 22 SNPs for stage 2 case- control samples --- p.151 / Chapter Appendix 6: --- T2D association results (additive model) of 22 SNPs for stage 2 case- control samples subset by metabolic syndrome status in cases --- p.153

Wong, Ling Yee. / Thesis submitted in: August 2007. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 110-127). / Abstracts in English and Chinese. / Thesis Abstract --- p.i / 論文摘要 --- p.iv / Acknowledgements --- p.vi / Abbreviations --- p.vii / Thesis Content --- p.xii / List of Figures --- p.xv / List of Tables --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Literature Review --- p.3 / Chapter 2.1. --- Multiple Myeloma (MM) --- p.3 / Chapter 2.1.1 --- Epidemiology --- p.4 / Chapter 2.1.2 --- Cause and Risk Factors --- p.5 / Chapter 2.1.3 --- Pathophysiology --- p.5 / Chapter 2.1.4 --- Diagnosis and Clinical Presentation --- p.6 / Chapter 2.1.5 --- Classification of Plasma Cell Disorders --- p.6 / Chapter 2.1.5.1 --- Monoclonal Gammopathy of Undetermined Significance (MGUS) --- p.6 / Chapter 2.1.5.2 --- Asymptomatic (Smouldering) MM --- p.7 / Chapter 2.1.5.3 --- Indolent MM --- p.7 / Chapter 2.1.5.4 --- Symptomatic MM --- p.8 / Chapter 2.1.6 --- Staging --- p.9 / Chapter 2.1.7 --- Treatment --- p.11 / Chapter 2.1.8 --- Molecular Abnormality --- p.12 / Chapter 2.2 --- DNA Microarray Analysis in MM --- p.13 / Chapter 2.2.1 --- MM Pathogenesis --- p.15 / Chapter 2.2.2 --- Molecular Classification of MM --- p.18 / Chapter 2.2.3 --- Anti-MM Drug Studies --- p.22 / Chapter 2.3 --- Cancer Treatment Response Prediction --- p.24 / Chapter 2.3.1 --- MP Treatment --- p.24 / Chapter 2.3.1.1 --- Melphalan --- p.25 / Chapter 2.3.1.2 --- Prednisone --- p.27 / Chapter 2.3.1.3 --- MP Treatment Response Prediction in MM --- p.29 / Chapter 2.3.2 --- Cancer Prognosis using DNA Microarray --- p.31 / Chapter Chapter 3 --- Materials and Methods --- p.36 / Chapter 3.1. --- Patient Specimens for Gene Expression Profiling and Quantitative Real-time PCR --- p.36 / Chapter 3.2. --- Magnetic Cell Sorting of CD138-positive Plasma Cells --- p.37 / Chapter 3.2.1 --- Density Gradient Centrifugation --- p.37 / Chapter 3.2.2 --- Positive Selection of CD138-positive Cells --- p.37 / Chapter 3.3 --- Generation of Gene Expression Profiles --- p.39 / Chapter 3.3.1 --- RNA Extraction --- p.39 / Chapter 3.3.2 --- RNA Assessment --- p.40 / Chapter 3.3.3 --- Synthesis and Purification of Double-strand cDNA --- p.40 / Chapter 3.3.4 --- In vitro Transcription (IVT) and Recovery of Biotin-labeled cRNA --- p.41 / Chapter 3.3.5 --- cRNA Fragmentation and Hybridization Reaction Mixture Preparation --- p.41 / Chapter 3.3.6 --- Hybridization --- p.42 / Chapter 3.3.7 --- Post-hybridization Wash --- p.42 / Chapter 3.3.8 --- Detection with Streptavidin-dye Conjugate --- p.43 / Chapter 3.3.9 --- Bioarray Scanning and Spot Signal Quantitation --- p.43 / Chapter 3.4 --- Microarray Data Analysis --- p.45 / Chapter 3.4.1 --- Normalization and Filtering --- p.45 / Chapter 3.4.2 --- Unsupervised Clustering Analysis --- p.45 / Chapter 3.4.3 --- Supervised Class Comparison Analysis --- p.46 / Chapter 3.5 --- Microarray Verification and Candidate Gene Validation --- p.47 / Chapter 3.5.1 --- RNA Extraction --- p.47 / Chapter 3.5.2 --- Reverse Transcription PCR --- p.47 / Chapter 3.5.3 --- Quantitative Real-time PCR --- p.48 / Chapter 3.6 --- Predictive Value Calculation --- p.49 / Chapter 3.7 --- Experimental Flow --- p.49 / Chapter Chapter 4 --- Results --- p.53 / Chapter 4.1 --- Gene Expression Profiling of Chinese MM --- p.53 / Chapter 4.1.1 --- Unsupervised Clustering Analysis --- p.53 / Chapter 4.1.1.1 --- Hierarchical Clustering --- p.53 / Chapter 4.1.1.2 --- Principal Component Analysis (PCA) --- p.54 / Chapter 4.1.2 --- Identification of Statistically Differentially Expressed Genes --- p.58 / Chapter 4.1.2.1 --- Two-Sample t-statistics --- p.58 / Chapter 4.1.2.2 --- Significance Analysis of Microarrays (SAM) --- p.58 / Chapter 4.1.2.3 --- Microarray Verification --- p.66 / Chapter 4.2 --- Development of MP Treatment Response Biomarker in MM --- p.70 / Chapter 4.2.1 --- Unsupervised Clustering Analysis --- p.70 / Chapter 4.2.1.1 --- Hierarchical Clustering --- p.70 / Chapter 4.2.1.2 --- PCA --- p.70 / Chapter 4.2.2 --- Identification of Statistically Differentially Expressed Genes --- p.74 / Chapter 4.2.2.1 --- Two sample t-statistics --- p.74 / Chapter 4.2.2.2 --- SAM --- p.74 / Chapter 4.2.3 --- Verification of Candidate Gene CYB5D1 --- p.76 / Chapter Chapter 5 --- Discussion --- p.79 / Chapter 5.1 --- Global Gene Expression Profiling: DNA Microarray --- p.79 / Chapter 5.2 --- Microarray Data Normalization and Gene Filtering --- p.81 / Chapter 5.3 --- Microarray Data Analysis --- p.83 / Chapter 5.3.1 --- Unsupervised Clustering Analysis --- p.83 / Chapter 5.3.1.1 --- Hierarchical Clustering --- p.83 / Chapter 5.3.1.2 --- PCA --- p.85 / Chapter 5.3.2 --- Identification of Statistically Differentially Expressed Genes --- p.86 / Chapter 5.4 --- Verification of Candidate Genes by Quantitative Real-time PCR --- p.89 / Chapter 5.5 --- Gene Expression Profiling of Chinese MM --- p.90 / Chapter 5.5.1 --- Comparison of Gene Expression Patterns of MM and Normal Plasma Cells --- p.90 / Chapter 5.5.2 --- Differentially Expressed Genes between MM and Normal Plasma Cells..… --- p.91 / Chapter 5.5.2.1 --- Common Differentially Expressed Genes with Previous Studies --- p.94 / Chapter 5.5.2.2 --- Potential Tumor Suppressor Genes in Differentially Expressed Genes..… --- p.96 / Chapter 5.5.2.3 --- Verified Differentially Expressed Genes --- p.98 / Chapter 5.5.3 --- Future Studies --- p.101 / Chapter 5.6 --- Development of MP Treatment Response Biomarker in MM --- p.103 / Chapter 5.6.1 --- Comparison of Gene Expression Patterns of MP Good Responders (GR) and Poor Responders (PR) --- p.103 / Chapter 5.6.2 --- Differentially Expressed Gene between MP GR and PR: CYB5D1 --- p.104 / Chapter 5.6.3 --- Possible Role of CYB5D1 in MP Resistance in MM Cells --- p.104 / Chapter 5.6.4 --- Potential Clinical Application of CYB5D1 in MP Treatment Response Prediction in MM --- p.106 / Chapter 5.6.5 --- Future Studies --- p.106 / Chapter Chapter 6 --- Conclusion --- p.108 / Chapter 6.1 --- Gene Expression Profiling of Chinese MM --- p.108 / Chapter 6.2 --- Development of MP Treatment Response Biomarker in MM --- p.108 / References --- p.110 / Appendix --- p.128

Esta pesquisa visou identificar e compreender os lugares ocupados pelas crianças nas culturas identificadas com a ancestralidade afro-brasileira, predominantemente, o Candomblé. Trata-se de uma pesquisa na área da Educação que articula estudos advindos de distintas áreas para compor sua problematização, análises e possíveis caminhos. Como processo desta pesquisa, falar das crianças na herança ancestral afro-brasileira passou a significar a importância de afirmar os lugares por elas ocupados neste referencial, em suas facetas social, religiosa e espiritual e, ainda, em sua cosmovisão. Ao mesmo tempo, destaca a ancestralidade afro-brasileira como um importante referencial para se pensar as infâncias. Aponto um panorama teórico de como crianças e infâncias têm sido abordadas pelas áreas de estudos das infâncias, buscando identificar lacunas e avanços nos olhares e práticas sobre este ponto. Por outro lado, pesquiso como a área de estudos das culturas e ancestralidade afro-brasileira têm se dedicado às crianças. Apresento análises e relatos de trabalho de campo, realizado em diversos espaços e tempos, sempre em comunidades identificadas ao referencial afrobrasileiro, mais demarcado, com o povo-de-santo dos Candomblés Jeje e Ketu. Exponho, por fim, os caminhos em que o próprio referencial ancestral afro-brasileiro estrutura suas noções e práticas de infância, respaldadas, principalmente, nos Orixás Exu e Oxum. Ao passo que, internamente, a cosmovisão Exuística e a cosmovisão Oxumística estruturam uma noção de infância que afronta noções ocidentais de infância (como incompletude, apartação, ingenuidade e inferioridade), este referencial vem ao encontro das necessidades de valorização da identidade negra e infância, e também, de práticas espelhadas (negras) na educação da infância e no debate teórico na área. / The aim of this research was to identify and understand the place that the children occupy in cultures identified with the afro-brazilian ancestry, notably the Candomblé. This research is rooted in the Educational field and it articulates with other researches originally from different areas so as to compose its problematization, analysis and possible paths. As a process in this research, to talk about children in the ancestral afro-brazilian heritage has meant to signify the importance of affirming the places they occupy in this referential, being its social facets, social and spiritual, and also in their worldview. At the same time, this study highlights the afro-brazilian ancestry as an important referential to think and reflect upon the childhoods. In this study, I propose a theoretical panorama of how children and childhoods have been approached in the study areas of childhoods, trying to identify possible gaps and advances in the approaches and practices about this point specifically. On the other hand, I research how the area of Cultural Studies and Afro-brazilian ancestry have dedicated their effort to children. Reports and analysis of field work are presented, they were conducted in various spaces and time, Always within communities identified to the afro-brazilian referencial, especially with the devotees of Jeje and Ketu Candomblé. Finally, I expose the paths in which the referential of afro-brazilian ancestral constitute its notion and practices of childhood, principally based upon the Orishas Exu and Oxum. Simultaneously, internally the Exuistic and Oxumistic cosmovision fix up a notion of childhood that challenges western notions of childhood ( uch as incompleteness, secludness, ingenuity and inferiority), this referential comes along with the necessity of valorization of the black identity and childhood, also of black practices spread in children education and the theoretical debate within the area.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 19, 2010). Includes bibliographical references.

Thesis (Ph. D.)--University of Hawaii at Manoa, 2004. / Includes bibliographical references (leaves 157-169).

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed June 23, 2008). Includes bibliographical references (p. 51-59).

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed June 23, 2008). Includes bibliographical references.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from first page of PDF file (viewed on June 10, 2009). Includes bibliographical references (p. 93-103).

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from PDF title page (viewed on Sept. 17, 2009). Includes bibliographical references.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Sept. 10, 2009). Includes bibliographical references (p. 160-172).