Actualmente la Escoliosis Postural y el Síndrome Benigno de Hipermovilidad Articular ( SBHA ) tienen una significativa presentación en los niños, sin que existan hasta el momento estudios que establezcan alguna relación entre ellos. Por lo cual, el presente trabajo analítico-explicativo, de corte transversal, de casos y control, tiene como objetivo determinar la relación causal entre el SBHA y la Escoliosis Postural. Para ello se realizó una evaluación del SBHA y Escoliosis Postural en niños de 6 a 8 años de edad, de ambos sexos en la G.U.E. Mariano Melgar y en el Circuito de Playas de la Costa Verde, que conforman el grupo de casos y el grupo control respectivamente, sumando un total de 269 niños. Para proceder a la selección de casos se evaluaron 200 niños, de los cuales 169 niños presentaron Escoliosis Postural y para el grupo control se eligieron 100 niños sin Escoliosis Postural del Circuito de Playas. Ambos grupos fueron evaluados con la Ficha de Defectos Posturales (Anexo Nº1) para determinar la presencia de Escoliosis Postural y luego con la ficha de SBHA (Anexo Nº2) usando los criterios de Carter y Wilkinson con la modificación de Beighton empleando el sistema de puntuación de Bird. Resultó, que en el grupo de casos, 122 niños presentaron el SBHA lo que representa el 72,19%, conformado por mujeres en un 50,82%. El tipo de Escoliosis Postural más frecuente fue la curva en “C” con un 61,47% con respecto a la “S” de 38,53%. Al establecer la comparación del grupo de casos con el grupo control a través de la Tabla de Contingencia y usando el Análisis Estadístico de Chi Cuadrado (p=0,05) se concluye que existe relación causal entre el Síndrome Benigno de Hipermovilidad Articular y la Escoliosis Postural en los niños de 6 a 8 años.

Thesis advisor: Chia-Kuang (Frank) Tsung / Exchange reactions have enabled a new level of control in the rational, stepwise preparation of metal-organic framework (MOF) materials. However, their full potential is limited by a lack of understanding of the molecular mechanisms by which they occur. This dissertation describes our efforts to understand this important class of reactions in two parts. The first reports our use of a linker exchange process to encapsulate guest molecules larger than the limiting pore aperture of the MOF. The concept is demonstrated, along with evidence for guest encapsulation and its relation to a dissociative linker exchange process. The second part describes our development of the first quantitative kinetic method for studying MOF linker exchange reactions and our application of this method to understand the solvent dependence of the reaction of ZIF-8 with imidazole. This project involved the collection of the largest set of rate data available on any MOF linker exchange reaction. The combination of this dataset with small molecule encapsulation experiments allowed us to formulate a mechanistic model that could account for all the observed kinetic and structural data. By comparison with the kinetic behavior of complexes in solution, we were able to fit the kinetic behavior of ZIF-8 into the broader family of coordination compounds. Aside from the specific use that our kinetic data may have in predicting the reactivity of ZIF linker exchange, we hope that the conceptual bridges made between MOFs and related metal−organic compounds can help reveal underlying patterns in behavior and advance the field. / Thesis (PhD) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Ina V. S. Mullis / Because results from TIMSS 2007 showed a gap in mathematics and science achievement between students in the United States and those in the top-performing countries, TIMSS 2007 data were used to investigate how school effectiveness factors known to be strongly associated with higher STEM achievement operated in the United States compared to Chinese Taipei, the Czech Republic, Singapore, and Slovenia. In each of the five countries, multilevel modeling was used to examine STEM achievement in relation to 11 school effectiveness factors associated with school resources, fidelity of curriculum implementation, and school climate, controlling for student home resources. A secondary purpose of this dissertation research was to help the TIMSS & PIRLS International Study Center prepare for multilevel modeling planned for the TIMSS and PIRLS 2011 data. Findings from this research showed that across the five countries, there were differences in how important school effectiveness factors operated. Teacher preparation, teaching the curriculum, and using instructional strategies involving reasoning and inquiry all were important school characteristics related to STEM achievement in some countries. A school environment conducive to learning emerged as being strongly associated with high STEM achievement in three of the countries, including the United States. Both absence of discipline and attendance problems as well as a school climate supportive of academic success were important predictors of student STEM achievement. This dissertation research also showed the potential of using TIMSS data as a basis for conducting school effectiveness analyses across different country contexts. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Lynch School of Education. / Discipline: Educational Research, Measurement, and Evaluation.

En 8-bitarsdator är i dagens samhälle gammal teknik. De kan knappast konkurrera med dagens moderna datorer som arbetar snabbare och med större tal. Genom att del för del ändå konstruera en 8-bitarsdator ges dock än idag stor insikt i hur datorer i allmänhet är konstruerade. Med bakgrundskunskap inom grundläggande digital elektronik kan enskilda moduler förstås, vilket sedan leder till en förståelse för datorn i stort. Detta projekt kretsade alltså kring att konstruera en 8-bitarsdator. Denna dator ska efter projektets slut kunna finnas kvar i syftet att användas i undervisning av digital elektronik. 8-bitarsdatorn innefattar flera moduler som var för sig kan både simuleras i mjukvara och konstrueras för sig. Därefter kunde alla moduler sättas samman. Datorn kan enkelt programmeras för att köra olika program, och kan med hjälp av så kallade flaggor hoppa i programkoden för att upprepa kod. Den resulterade datorn har vissa förbättringspotentialer, men fungerar väl enligt förväntningarna. Med strategiska val av färger på kablage och ett stort antal lysdioder blev datorn lättare att förstå och undersöka.

Desde a descoberta do herpes vírus humano tipo 8 (HHV-8) como o agente etiológico do sarcoma de Kaposi (SK) nas suas diferentes formas clínico-epidemiológicas, vários estudos vêm sendo conduzidos com o intuito de determinar as vias de transmissão desse vírus em populações endêmicas e de risco epidemiológico. Em regiões endêmicas, a transmissão viral foi relacionada à transmissão horizontal de mães para filhos e entre irmãos e a sexual principalmente, nos casos de SK/aids. Com o objetivo de determinar segmentos do genoma viral em fluídos biológicos e consequentemente seu potencial infectante foi conduzido o presente trabalho. Foram avaliados quanto à presença de segmentos localizados em posições estratégicas do genoma do HHV-8 em sangue, saliva e urina de 76 pacientes com SK/aids, 19 pacientes com HIV/aids, 4 casos de SK clássico e 11 indivíduos sadios (HIV-soronegativos, sem SK). Foram utilizadas as técnicas de PCR "nested" para as ORF K1, ORF 25, ORF 26, ORF K8.1 e ORF 73 em DNA extraído de material de biópsia de lesão de SK (controle positivo), células do sangue periférico, saliva e urina. Os resultados de PCR positivo para o HHV-8 foram analisados quanto a variáveis epidemiológicas, clínicas e laboratoriais. Foram consideradas como variáveis: sexo, cor, origem étnica, tempo de infecção por HIV e de acompanhamento do SK, terapia ARV e para SK, contagem de células CD4+ e sorologia para o HHV-8 (IFI-LANA e IFI-Lítico). Os testes estatísticos de regressão logística e de razão de chances foram usados para detectar as associações estatisticamente significantes entre as PCRs positivas e as variáveis estudadas nos grupos SK/aids e HIV/aids. Os subtipos do HHV-8 foram também determinados pela técnica de PCR-RFLP da ORF K1 (VR1). Os resultados obtidos mostraram a detecção de DNA/HHV-8 em 80,2% do material de biópsia, 69,7% no sangue, 59,2% na saliva e 21,0% na urina de pacientes com SK/aids. No grupo HIV/aids, a PCR para o HHV-8 resultou positiva em 47,4% dos casos no sangue e em 26,3% na saliva e urina. Já no grupo SK clássico 100% das biópsias e salivas resultaram PCR positiva, 67% do sangue e 33% das urinas. A avaliação sorológica revelou 73,3% de reatividade para IFI-LANA e 85,3% para a IFI-Lítico no grupo SK/aids, enquanto o grupo HIV/aids mostrou reatividade de 15,8% para IFI-LANA e 47,4% para IFI-Lítico; todos os pacientes apresentaram resultados reagentes nas duas sorologias para o HHV-8 no grupo de SK clássico. No grupo controle sadio não houve reatividade na sorologia para o HHV-8, com exceção de um caso, que mostrou ser reagente na IFI-LANA. Foi possível realizar a subtipagem do HHV-8 em amostras de 69 pacientes, sendo detectadas 27 cepas do subtipo A, 13 do subtipo B, 28 do subtipo C e 1 do subtipo E. Após as análises estatísticas foi verificado que as PCRs que identificam as regiões ORF 26, ORF K8.1 e ORF 73 foram as que apresentaram melhor desempenho na identificação de DNA/HHV-8. Houve associação entre a reatividade de IFI-Lítico e a presença do vírus no sangue periférico, assim como a reatividade para IFI-LANA e a detecção de DNA/HHV-8 na saliva. Houve uma tendência dos subtipos B e C de HHV-8 serem detectados em pacientes com infecção profunda ou disseminada de SK. Estes resultados sugerem que a boca pode ser um sítio de latência da infecção por HHV-8 e confirmam a atuação de sangue, saliva e urina como fluídos potencialmente infectantes. / Since the discovery of the human herpesvirus 8 (HHV-8) as the etiological agent of Kaposi’s sarcoma (KS), several studies have been conducted in order to determine routes of virus transmission, mostly in endemic and at risk populations. The main of the present study was to determine target segments of the HHV-8 genoma and consequently infected bodily fluids. DNA sequences of ORF K1, ORF 25, ORF 26, ORF K8.1 and ORF 73 strategically localized in viral genoma were searched using nested PCR techniques in KS lesions (positive control), blood, saliva, and urine from 76 KS/aids patients, 19 HIV/aids patients, 4 classic KS patients, and among 11 healthy individuals (HIV-1 seronegative, without KS). HHV-8 subtypes were determined by PCR-RFLP of the ORF K1 (VR1), and HHV-8 antibodies by IFA-LANA and IFA-Lytic assays. The results obtained were analyzed according to epidemiological, clinical and laboratorial data, and the c2 test, logistic regression and odds ratio were applied to identify statistical association among variables in KS/aids and HIV/aids groups. The results obtained showed HHV-8 DNA in 80.2% of biopsies, 69.7% of blood, 59.2% of saliva, and 21% of urines from KS/aids group. Among HIV/aids patients, 47.4% resulted PCR positive in blood, 26.3% in saliva and urine. In classic KS cases, all biopsies and saliva resulted PCR positive, 67% in blood, and 33% in urine. The serology in KS/aids group showed 73.3% frequency of anti-latent antibodies, and 85.3% frequency of anti-lytic antibodies, while in HIV/aids group the frequencies were 15.8% and 47.4%, respectively. All classic KS cases resulted HHV-8 seroposite, while all individuals from control group resulted HHV-8 seronegative. Molecular characterization of 69 HHV-8 strains disclosed: 27 of subtype A, 13 of subtype B, 28 of subtype C, and 1 of subtype E. The ORF 26, ORF K8.1 and ORF 73 were the best segments for identifying HHV-8 DNA in bodily fluids. It was observed an association between antibodies to lytic antigens and the presence of HHV-8 in blood, and antibodies to latent antigens and the detection of HHV8 DNA in saliva of KS/aids patients. Indeed, HHV-8 subtypes B and C were detected mostly in disseminated KS cases. Taken together, the results obtained suggest that the mouth could be one site of HHV-8 latency, and confirm that blood, saliva and urine were potentially infectious bodily fluids.

The purpose of this study was to examine differences between school configuration and students' academic and behavioral outcomes. The participants were eighth grade students in K-8 schools who were matched with eighth grade students in 6-8 middle schools on factors including percentage of students receiving free or reduced lunch, percentage of students receiving services for special education and English language learners, average years of teacher experience, and percentage of boys and girls in each school. Eighth grade student's standardized math and reading achievement data were collected at the school level for a 3-year period. Additionally, school-level data on suspensions and expulsions over the same 3-year period were also collected. The data were analyzed using arc-sine transformation, means, standard deviation, and a repeated-measure analysis of variance. No statistical interactions were observed between time and school type for any of the research questions. However, main effects favoring K-8 schools were found for (a) Math Test, (b) Reading Test, (c) In-school Suspensions, (d) Out-of-school Suspensions, and (e) Expulsions. These findings are interpreted with a lens towards assisting school districts as to which school configuration they should consider as it relates to the district's values and long-range goals. / 10000-01-01

Les phéochromocytomes et les paragangliomes (PPGL) sont des tumeurs neuroendocrines rares qui se développent aux dépens des paraganglions et qui sont identiquement déterminées dans 40% des cas. Parmi les gènes de prédisposition, les mutations du gène SDHB qui code pour l’une des sous-unités catalytiques de la succinate déshydrogénase mitochondriale constituent un facteur de risque de phénotype métastatique associé à un mauvais pronostic. Mon travail de thèse avait pour objectif d’élucider le lien entre les mutations du gène SDHB et la malignité des PPGL par l’étude du rôle du microenvironnement tumoral et en particulier de la matrice extracellulaire (MEC) dans le processus métastatique. L’analyse transcriptomique de l’expression de 310 gènes associés a la MEC dans 188 PPGL humains de la cohorte COMETE, a mis en évidence une régulation spécifique de ces gènes dans les tumeurs présentant des mutations SDHx. J’ai utilisé un modèle murin de cellules chromaffines déficientes en succinate déshydrogénase, les cellules Sdhb-/-, en comparaison avec les cellules sauvages (wild-type, WT). Les cellules Sdhb-/‐ possèdent des capacités migratoires et adhésives accrues dues a l’accumulation de succinate inhibant les dioxygénases dépendantes du 2‐oxoglutarate (2‐OG). J’ai mis en évidence que la MEC secrétée par les cellules Sdhb‐/- est capable d’augmenter les capacités migratoires et d’adhésion des cellules WT. Inversement, la MEC secrétée par les cellules WT diminue la migration et l’adhésion des cellules Sdhb-/-. Ainsi, les cellules Sdhb‐/- semblent secréter une matrice qui favorise le replacement des cellules et donc leur potentiel métastatique. Afin d’identifier les acteurs responsables de ce phénotype particulier nous avons analyse le sécrétome de la MEC : le matrisome des cellules Sdhb-/- et des WT, nous permettant d’identifier la fibronectine, cible de l’hypoxie, comme l’une des protéines majeures de la MEC secrétée par les cellules Sdhb-/‐. J’ai montré que la fibronectine augmente de façon drastique la migration et l’adhésion des cellules WT et qu’elle participe a la migration des cellules Sdhb‐/-. L’analyse du transcriptome et du matrisome des cellules Sdhb-/- a également mis en évidence la surexpression de nombreux collagènes et en particulier le gène Col4a2 qui code pour l’un des composants majoritaires des membranes basales. J’ai montré que malgré l’accumulation de succinate dans les cellules Sdhb-/-, les collagènes hydroxylases 2-OG dépendantes, restent probablement actives ce qui permet la maturation des collagènes puis leur sécrétion dans le milieu extracellulaire. Cependant, le collagène IVα2 est fragmenté dans les cellules Sdhb-/- suggérant des modifications après sa sécrétion. J’ai ainsi montré que l’activation de la MMP9 dans les cellules Sdhb‐/-, participe à la dégradation du collagène IVα2. L’ensemble de ces résultats a ainsi révélé l’existence d’un remodelage de la MEC spécifique aux cellules Sdhb‐/- qui favorise le phénotype métastatique en promouvant notamment la migration et l’adhésion cellulaire. En parallèle de ce travail et dans le cadre d’un projet collaboratif, j’ai montré que seules les cellules Sdhb-/- sont capables d’induire le processus d’angiogenèse compare aux cellules WT et de le maintenir en faisant croître des vaisseaux pré-existants en 3-dimensions. Au sein de la même collaboration, j’ai également travaillé sur la mise au point d’une lignée humaine de cellules chromaffines tumorales en 3-dimensions à partir de culture primaire de PPGL humains. Ce travail se poursuit actuellement et pourrait donner lieu à la mise au point des premières conditions expérimentales permettant de cultiver ces cellules in vitro. / Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors, which arise from paraganglia and are genetically determined in 40% of cases. Among the predisposition genes, mutations in the SDHB gene, which encodes the catalytic core subunit of the mitochondrial enzyme, succinate dehydrogenase, are associated with malignancy and poor prognosis. The main objective of my thesis project was to elucidate the link between SDHB mutations and PPGL malignancy by studying the role of tumor microenvironment and in particular of the extracellular matrix (ECM) in the metastatic process. The transcriptomic analysis of 310 ECM‐associated genes in 188 human PPGL of the COMETE collection showed a specific regulation of ECM-encoding genes in SDHx-mutated tumors. I used a mouse model of Sdhb deficient chromaffin cells compared to their wild-type (WT) counterparts. Sdhb-/- cells display increased migratory and adhesive capacities cause by succinate accumulation that inhibit 2-oxoglutarate (2--‐OG) dependent dioxygenases. I showed that the ECM secreted by Sdhb‐/- cells is able to increase migration and cell adhesion of WT cells. Conversely, the ECM secreted by WT cells decreases migration and adhesion of Sdhb-/- cells. Hence, Sdhb-/- cells seem to secrete an ECM promoting cell motility and thus their metastatic potential. To identify specific ECM components responsible for this particular phenotype, we analyzed the ECM secretome, i.e. the matrisome, of both cells types. This study identified fibronectin as one of main ECM protein secreted by Sdhb-/- cells. I showed that fibronectin drastically increases migration and adhesion of WT cells and participates to Sdhb- /- cells migration. Sdhb-/- transcriptome and matrisome analyses also highlighted the overexpression of many collagens and in particular Col4a2 encoding one of main component of basement membranes. I demonstrated that despite succinate accumulation in Sdhb‐/- cells, 2-OG dependent collagen hydroxylases remain apparently active, allowing collagen maturation and their subsequent secretion in the extracellular space. Besides, collagen IVα2 is fragmented in Sdhb-/‐ cells suggesting post-excretion modifications. I showed that MMP9 activation in Sdhb‐/‐ cells, participates to collagen IVα2 degradation. Alltogether, these results revealed the existence of Sdhb‐/- specific remodelling of the ECM which may promote mestastatic phenotype by inducing migration cell and adhesion. In parallel, and as a part of a collaborative project, I showed that Sdhb‐/- chromaffin cells (but not WT cells) are able to induce the angiogenic process and to maintain the growth of pre-existing vessels in 3-dimensions. Within the same collaboration, I also worked on the development of a human tumoral chromaffin cells line using 3-dimensions spheroid cultures of human PPGL. This work is ongoing and could lead to the development of the first experimental conditions for growing human PPGL cells in vitro.

As reações iniciais dos materiais capeadores sobre o tecido pulpar não estão bem elucidadas. A metaloproteinase da matriz (MMP) atua no remodelamento da matriz extracelular e a mieloperoxidase (MPO) está associada com infiltração neutrofílica nos tecidos. O objetivo deste estudo foi avaliar polpas de molares de ratos após pulpotomia com agregado trióxido mineral (MTA), BiodentineTM (BDT) e Hidróxido de cálcio (HC) associado à solução salina estéril, nos períodos de 24, 72 horas, 7 e 15 dias correlacionando a atividade da MPO com neutrófilos ativos e atividade de MMP8 (EC3.4.24.34) com remodelação tecidual. Foram utilizados 36 ratos Wistar, distribuídos aleatoriamente nos grupos controle, MTA, BDT e HC e subdividos conforme o tempo de 24, 72 horas, 7 e 15 dias após pulpotomia e um foi utilizado para o controle.. A atividade da MMP8 foi avaliada utilizando a técnica de fluorescência e a atividade de MPO foi determinada utilizando o ensaio de MPO. Houve diminuição gradativa da atividade de MPO e MMP8 para o MTA ao longo dos períodos experimentais (p<0.05), ao contrário do BDT e HC que apresentaram aumento da atividade aos 7 e 15 dias (p<0.05). O MTA demonstrou decréscimo de valores de MPO e MMP8 indicando atividade potencialmente curativa no tecido pulpar. Já BDT e HC apresentaram aumento do potencial irritante dificultando o processo cicatricial. / The initial reactions of capping materials on pulp tissue are not well understood. The matrix metalloproteinases-8 (MMP8) acts on remodeling the extracellular matrix and myeloperoxidase (MPO) is associated to neutrophil infiltration in the tissues. This study aimed to evaluate the pulp tissue of rats’ molars after pulpotomies with mineral trioxide aggregate (MTA), BiodentineTM (BDT) and calcium hydroxide (CH) associated with sterile saline solution, at 24 and 72 hours, 7 and 15 days through correlating MPO activity with active neutrophils and MMP8 (EC3.4.24.34) activity with tissue remodelation. Thirty six Wistar rats were randomly distributed into groups: control, MTA, BDT and CH and subdivided according to the study period of de 24 and 72 hours, 7 and 15 days after pulpotomy and one was used for the control. MMP8 activity was evaluated through fluorescence technique and MPO activity was determined using the MPO assay. A gradual decrease of MPO and MM8 activity occurred in group MTA over the experimental periods (p<.05). Unlikely, groups BDT and CH exhibited an increase in the activity at 7 and 15 days (p<.05). MTA demonstrated a decrease in MPO and MMP8 values indicating a potentially curative activity in pulp tissue. Conversely, BDT and CH showed the increasing of the irritating potential which makes difficult the healing process. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES

This thesis explores the intersectional commodification of migrant labour from post-socialist EU Accession 8 (A8) countries and its effects on Polish and Slovenian migrant workers in the UK. Using historical and macro socio-economic contexts as its point of departure, the thesis aims to uncover how a postcolonial narrative surrounding A8 countries' transition to market economies and their accession to the EU has legitimised on-going colonial processes that construct A8 countries and their nationals as second class EU citizens and re-evaluate subjectivities in relation to the market. Further, it explores how this narrative has been appropriated by transnational employment agencies that colonise A8 countries and as such play an active role in commodifying A8 workers and supplying them to the UK. Moreover, the thesis sets out specifically to explore how this colonisation and its narrative affect workers' (self)value and emigration from Poland and Slovenia, as well as the value extraction possibilities and strategies of diverse actors involved in transnational labour relations between East and West. Through a transdisciplinary adoption of a Bourdieuian conceptual framework, this research offers an original theoretical and methodological toolkit for complex intersectional analyses that uncovers the multiple and misrecognised power relations associated with embodied categories, spatial and temporal dimensions and varying modalities of knowledge. As such, it uncovers on-going colonial processes that characterise a contemporary post-socialist world marked by changed transnationalised consumption and production processes and the marketization of cultural, diversity and identity politics. In this way, the research uncovers symbolic economy hidden under neoliberal (self)colonisation, which enables strategic utilisation of migrant labour and disciplines, segments and divides the global poor. By providing a broader comparative analysis of diverse actors and A8 groups, the thesis widens our understanding of A8 labour migration to the UK and also leads to insights into the remaking of class, race and gender politics on the local and global scales.

Leung Chin-lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 133-164). / Abstracts in English and Chinese. / Abstract --- p.iv / 摘要 --- p.vi / List of abbreviation --- p.viii / Chapter Chapter 1 --- Hepatocellular Carcinoma --- p.1 / Chapter 1.1 --- A Health Burden --- p.1 / Chapter 1.2 --- Pathology --- p.3 / Chapter 1.3 --- Epidemiology --- p.7 / Chapter 1.3.1 --- Global HCC distribution --- p.7 / Chapter 1.3.2 --- Age and Gender --- p.10 / Chapter 1.4 --- Risk Factors of HCC --- p.12 / Chapter 1.4.1 --- Hepatitis B virus (HBV) --- p.13 / Chapter 1.4.1.1 --- Chronic HBV infection --- p.13 / Chapter 1.4.1.2 --- Role of HBV in hepatocarcinogenesis --- p.16 / Chapter 1.4.1.2 a) --- Direct Oncogenesis --- p.16 / Chapter 1.4.1.2 b) --- Indirect Oncogenesis --- p.17 / Chapter 1.4.2 --- Hepatitis C virus (HCV) --- p.23 / Chapter 1.4.2.1 --- Chronic HCV infection --- p.23 / Chapter 1.4.2.2 --- Role of HCV in hepatocarcinogenesis --- p.23 / Chapter 1.4.3 --- Chemicals as liver carcinogens --- p.27 / Chapter 1.4.3.1 --- Aflatoxin Bi (AFB1) --- p.28 / Chapter 1.4.3.2 --- Vinyl chloride --- p.29 / Chapter 1.4.3.3 --- Alcoholic beverages --- p.29 / Chapter 1.4.4 --- Inborn Errors in Metabolisms --- p.30 / Chapter 1.4.4.1 --- Hereditary tyrosinemia --- p.30 / Chapter 1.4.4.2 --- Hereditary haemochromatosis --- p.30 / Chapter 1.4.4.3 --- α1-antitrypsin deficiency --- p.31 / Chapter 1.4.5 --- Liver lesions --- p.32 / Chapter 1.5 --- Genetic alterations in HCC --- p.33 / Chapter Chapter 2 --- Rationale of the study --- p.39 / Chapter Chapter 3 --- LOH study on 8p in HCC --- p.48 / Chapter 3.1 --- Introduction --- p.48 / Chapter 3.1.1 --- "Knudson's ""two-hit"" model and LOH" --- p.48 / Chapter 3.1.2 --- Microsatellite DNA and LOH study --- p.49 / Chapter 3.2 --- Materials and Methods --- p.51 / Chapter 3.2.1 --- Patients and Specimens --- p.51 / Chapter 3.2.1.1 --- Genomic DNA extraction from liver tissues --- p.53 / Chapter 3.2.1.2 --- Genomic DNA extraction from buffy coat --- p.55 / Chapter 3.3 --- LOH study on 8p in HCC --- p.57 / Chapter 3.3.1 --- Microsatellite markers --- p.57 / Chapter 3.3.2 --- 5-end labeling --- p.60 / Chapter 3.3.3 --- Amplification of microsatellite DNA --- p.60 / Chapter 3.3.4 --- Denaturing polyacrylamide gel electrophoresis --- p.61 / Chapter 3.3.5 --- Detection of LOH --- p.62 / Chapter 3.4 --- Results --- p.63 / Chapter 3.4.1 --- LOH status of 52 HCC cases --- p.63 / Chapter 3.4.2 --- Clinicopathological correlation --- p.67 / Chapter 3.4.3 --- Delineation of common deletion region (CDR) --- p.67 / Chapter 3.4.4 --- Common deletion region of interest --- p.77 / Chapter Chapter 4 --- Study on LZTS1 --- p.83 / Chapter 4.1 --- Introduction 一 LZTS1 --- p.83 / Chapter 4.2 --- Mutation analysis of LZTS1 in HCC --- p.87 / Chapter 4.2.1 --- Materials and Methods --- p.87 / Chapter 4.2.1.1 --- Patients and HCC cell lines --- p.87 / Chapter 4.2.1.2 --- Genomic DNA extraction from HCC cell lines --- p.87 / Chapter 4.2.1.3 --- Amplification of exons of LZTS1 --- p.89 / Chapter 4.2.1.3a) --- Primer pairs --- p.89 / Chapter 4.2.1.3b) --- PCR conditions --- p.90 / Chapter 4.2.1.4 --- Purification of PCR products --- p.93 / Chapter 4.2.1.5 --- Cycle sequencing reaction --- p.94 / Chapter 4.2.1.6 --- Purification of cycle sequencing reaction product --- p.94 / Chapter 4.2.1.7 --- Sequence analysis by automated sequencer --- p.95 / Chapter 4.2.1.8 --- Search for sequence variants of LZTS1 --- p.96 / Chapter 4.2.2 --- Results --- p.97 / Chapter 4.3 --- Expression analysis of LZTS1 in HCC with preliminary results --- p.103 / Chapter 4.3.1 --- Materials and Methods --- p.103 / Chapter 4.3.1.1 --- Patients and Specimens --- p.103 / Chapter 4.3.1.2 --- Total RNA extraction --- p.103 / Chapter 4.3.1.3 --- Reverse transcription --- p.104 / Chapter 4.3.1.4 --- Semi-quantitative PCR --- p.105 / Chapter 4.3.1.4a) --- Primer pairs --- p.105 / Chapter 4.3.1.4b) --- PCR conditions --- p.106 / Chapter 4.3.2 --- Results --- p.109 / Chapter Chapter 5 --- Discussion --- p.111 / Chapter 5.1 --- LOH study on 8p in HCC --- p.111 / Chapter 5.2 --- Study on LZTS1 in HCC --- p.125 / Chapter 5.2.1 --- Mutation analysis of LZTS1 --- p.125 / Chapter 5.2.2 --- Expression analysis of LZTS1 --- p.129 / Chapter 5.3 --- Future Study --- p.132 / References --- p.133