Chinese society has greatly emphasized filial piety and other related societal norms. This thesis explores how Mainland Chinese international students, especially those who are from one-child households, maintain their familial responsibilities while studying in Canada away from home. The research is framed by the family migration strategy literature and empirically adopts a qualitative approach. Semi-structured face-to-face interviews with Mainland Chinese international students are undertaken. The findings show that as with many other types of migration, student migration, in this case, is a familial decision. To a certain extent, obtaining a foreign degree is the foundation for fulfilling familial responsibilities in the future. In addition, a new concept, delay remittances, is introduced as a way of conceptualizing the concrete meaning of familial responsibility for Mainland Chinese international students. The findings also show that the most significant tension for Mainland Chinese international is related to the uncertainty of how and where they will be able to fulfill their familial obligations to their parents.

Glucocorticoids (Gc) are vital for development, maintenance of glucose homeostasis and the resolution of inflammation. As potent modulators of the immune response Gc are routinely prescribed in the management of a variety of inflammatory diseases including asthma and rheumatoid arthritis. However clinical use of Gc is limited by variation in patient sensitivity to Gc treatment and development of a wide range of side effects. In this thesis I present two studies that have advanced our understanding of Gc action in vivo. The first defines and characterises the cause of familial glucocorticoid resistance, and the second describes the action of two potent non-steroidal Gc in a cell line model. Familial Gc Resistance: Cases of primary generalised Gc resistance are very rare and typically present as mineralocorticoid and androgen excess leading to hypertension, hypokalemia and hirsutism. Gc resistance is attributed to loss of function mutations within the glucocorticoid receptor (GR). Here I identify a family with a novel mutation in GR exon 6 that gives rise to a very mild phenotype. Analysis of transformed patient peripheral blood lymphocytes revealed a 50% reduction in full length GR but no expression of a mutant form. As this did not rule out expression in vivo, the mutant receptor (Δ612GR) was characterised in a cell line. Investigation using reporter genes revealed that Δ612GR lacked any activity, but had dominant negative action when co expressed with full length GR. In response to Gc Δ612GR was not phosphorylated or targeted for degradation. Fluorophore tagged Δ612GR was unable to translocate to the nucleus in response to Gc, but delayed the translocation of full length GR when co-expressed. Together this indicates that Δ612GR is unable to bind ligand but has dominant negative action upon full length GR most likely due to heterodimerisation. Therefore I describe a novel GR mutation that results in Gc resistance but presents with a mild very phenotype. Novel Non-steroidal Gc: Non-steroidal Gc can be used as tools to determine how ligand structure directs GR function. Here I describe two highly potent non steroidal Gc ligands, GSK47867A and GSK47869A which alter the kinetics of receptor activity. Treatment with either ligand induces slow GR nuclear translocation, promotes GR nuclear retention and prolongs transcriptional activity following ligand withdrawal. Crystal structure analysis revealed that GSK47867A and GSK47869A specifically alter the surface charge of the GR at a site important for Hsp90 binding. GR bound to GSK47867A and GSK47869A shows prolonged activity in the presence of Hsp90 inhibitor geldanamycin. Therefore this work identifies a new chemical series that could prolong GR activity due to altered pharmacodynamics rather than altered pharmacokinetics.In summary this work uses a combination of genetic and chemical biology approaches to broaden our understanding of GR function. Characterisation of naturally occurring GR mutations gives insight into the complex function of the GR, and non-steroidal Gc act as useful tools that will aid in the design of improved therapeutics.

No description available.

LDL-receptor mutations and familial defective apolipoprotein B-100 (codon 3500) (FOB), the known causes of monogenic hypercholesterolemia (MH), have similar clinical features. The nature of the mutations responsible for MH in South Africans of Indian origin was previously unknown. Similarly, the mutations in the LDL-receptor gene of a South African Black FH homozygote had also not been characterised. The aim of this thesis was to identify and analyse the LDL-receptor mutations in the Indian homozygotes NS, D, AV and AA and in the Black homozygote JL. In addition, the possible importance of FOB as a cause of MH in South Africans was also assessed. The patient NS was characterized as having two "Null" LDL-receptor alleles. His skin fibroblasts expressed no detectable LDL-receptor protein and very low levels of LDL-receptor mRNA of approximately normal size. Since NS' s LDLreceptor promoter sequence was normal, his alleles are likely to harbour exonic point mutations or minor rearrangements that cause premature stop codons. The patient D was found to be a heteroallelic homozygote. Two new point mutations in the LDL receptor, Asp₆₉ -Tyr and Glu₁₁₉-Lys, were identified. D's fibroblasts expressed about 30% of the normal surf ace complement of receptors that bound LDL poorly. This low number could at least be partially explained by their decreased stability. These mutations were not identified in any other Indian FH or hypercholesterolemic patients. Patients AV and AA were both shown to be homoallelic homozygotes for the Pro₆₆₄ -Leu mutation. This mutation was identified in 4 unrelated Muslim families of Gujerati origin suggesting that the mutation arose from this area in India. Contrary to previous reports (Knight et al. 1990, Soutar et al. 1989), neither LOL nor β-VLDL binding were shown to be affected by this mutation. These mutant receptors were rapidly degraded. Thus the disease FH in these subjects is presumably due to the low steady-state level of mature receptors that are functionally normal but exhibit accelerated turnover. The Pedi FH homozygote, JL, expressed very few LOL receptors due to decreased receptor synthesis associated with low mRNA levels and not due to enhanced degradation. One of JL's LOL receptor alleles has a 3 b.p. deletion in repeat 1 of the promoter (G. Zuilani, H. Hobbs and L.F. de Waal, personal communication). The nature of the defect in his other allele is unknown. The importance of FOB as a cause of monogenic hypercholesterolemia in the South African Indian, "Coloured" and Afrikaner populations was determined by screening hypercholesterolemic subjects with or without xanthomata. The absence of FOB in such patients, in whom the relevant common or founder South African mutations were excluded, suggested that this disorder was rarer in these groups than in North America and Europe. FOB was identified in two different families of mixed British and Afrikaner ancestry. One family contained individuals who were heterozygous for the FOB mutation, as well as the FH Afrikaner-1 and the FH Afrikaner-2 LOL-receptor mutations. In addition, 4 compound heterozygotes, who had both FOB and the FH Afrikaner-1 mutation and one individual whu inherited all 3 defects, were identified. This family allowed us to characterise the compound heterozygotes with one mutant LOLreceptor allele and FOB as having a condition that was probably intermediate in severity between the FH heterozygote and homozygote states.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18142号 / 医博第3862号 / 新制||医||1002(附属図書館) / 31000 / 京都大学大学院医学研究科医学専攻 / (主査)教授 山田 亮, 教授 小杉 眞司, 教授 松田 文彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Punch-Drunk, a collection of 43 poems, deals with themes involving masculinity, violence, family, religion, and the apocalypse. As such, the collection shows an array of relationships the speaker has with various men, family members, religious figures, and forces of nature, thereby revealing the ways in which humans navigate loss and come to accept hard truths. Therefore, this collection shows the ways in which humans are not static creatures, but instead beings that are continually changing and achieving some kind of growth. By the end, the speakers have gone on personal journeys in which they learn the fact that love is not always constant, figuring out and coming to terms with your gay identity is a complicated ordeal, familial relationships are not always stable, and the world will sometimes crumble at your feet. / MFA

京都大学 / 新制・課程博士 / 博士(社会健康医学) / 甲第24806号 / 社医博第130号 / 新制||社医||12(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 松田 文彦, 教授 YOUSSEFIAN Shohab, 教授 永井 洋士 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

No description available.

No description available.

[pt] O presente estudo busca analisar significados atribuídos à família e cuidados cotidianos por famílias atendidas pelo núcleo de Desenvolvimento Humano do Centro Cultural A História Que Eu Conto, organização da sociedade civil localizada na Zona Oeste do município do Rio de Janeiro. Trata-se de uma pesquisa com abordagem qualitativa, a partir da elaboração de um roteiro aplicado em cinco famílias moradoras de um território vulnerabilizado, atravessado por intensa violência e invisibilidade do poder público, a fim de identificar suas concepções e práticas de cuidados familiares. O recurso metodológico para a análise de dados consistiu na análise de conteúdo em sua modalidade temática. Os resultados apontam para a necessidade de compreender as famílias em seu contexto histórico e sociocultural, considerando a pluralidade de formas de viver, onde se constroem diversas formas de cuidar. Também se constatou a existência de um cuidado pensado que por vezes diverge do cuidado vivido no cotidiano das relações, fortemente influenciado pelo contexto de um Estado Familista, pouco presente na garantia de políticas públicas de suporte às famílias em sua função cuidadora. / [en] The present study aims to analyze the meanings attributed to family and daily caretaking by families assisted at The Story I Tell Cultural Center, civil society organization located in the West Side of Rio de Janeiro capital. It is a research of qualitative approach, as from a script developed to be implemented within five families that inhabit a vulnerable territory, crossed by intense violence and invisible to public authorities, aiming to identify their conceptions and practices of family caretaking. The methodological resource for data analysis was the content analysis as from its theme modality. The results point to the need to understand families from a historical and sociocultural context, considering the ways of life plurality, in which are built various kinds of caretaking. The research certified the existence of a theoretical caretaking that occasionally dissent from the caretaking practice in daily relationships, strongly influenced by the State Familism context, a State little present in the assurance of family support public policies in its caretaker function.