published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Buddhist Studies / Master / Master of Buddhist Studies

Housing units in China are sometimes sold with fittings (including internal finishes, interior decorations, fixtures, electrical appliances, etc.) and sometimes as bare units (without fittings). This study formulates hypotheses that explain these phenomena and test these hypotheses with empirical data from a sample of 1,704 development projects in China that were sold in the primary market between 2003 and 2007. Based on developers’ risk-aversive behavior, we hypothesize that they are less likely to sell new units with fittings in areas with low land prices. The value of fittings is the highest if the developers can accurately predict the tastes of potential buyers. The risk facing the former is that the fittings may not suit the latter. The risks are higher when the cost of installing the fittings constitutes a relatively high proportion of the market value of a housing unit, which is the case when land prices are relatively low. Since housing construction costs are similar across the different regions in China, land price is a major determinate of housing prices. Due to the problem of information asymmetry between developers and buyers, the former’s reputable or goodwill is important. The market would give a higher valuation for fittings provided by more reputable developers. In addition, potential buyers may worry that the fittings had been used to cover up defective or sub-standard work. Therefore, we hypothesize that reputable developers are more likely to sell housing units with fittings, especially for developments with a high construction cost to market value ratio. Demand and supply conditions play a role in determining a developer’s decision to sell units with fittings. When supply is relatively abundant, competition amongst developers is keen. Developers will tend to compete by providing fittings as sweeteners to attract buyers. The provision of fittings may also be a non-price competition strategy used by developers to differentiate their products from that of their competitors. Therefore, we hypothesize that developers are more likely to sell housing units with fittings when demand is weak or when supply is abundant. Finally, we conjectured that as people’s incomes increase, their time becomes more valuable. Therefore higher income households are less likely to buy bare units, since the costs of shopping for interior decoration contractors, finishes and fittings, etc. are higher for higher income households. We conjecture that developers tend to provide units with fittings in areas with higher average household income. With the exception of the last hypothesis, our empirical results supported all hypotheses. The lack of empirical evidence to support the last hypothesis could be due to a possible opposing force. This force arises from the possibility that higher income households have more sophisticated tastes that are more difficult to predict. Developers, being risk-averse, would tend to supply bare housing units in high income areas. The results in this study contribute to our understanding of developers’ behaviors in the real estate market, particularly in China. The results are also of practical relevance to home buyers, developers, investors, and policymakers. / published_or_final_version / Real Estate and Construction / Doctoral / Doctor of Philosophy

Heat stress inhibits spermatogenesis partly by inducing apoptosis in the testicular germ cells. Using a cryptochid rat model, we identified a temperature-related ESTs 4 (TRS4) transcript from rat testis. Trs4 mRNA is specifically expressed in the mouse and rat testis from postnatal day 21 and 28 days onwards, respectively. Trs4 protein is located mainly in the elongating spermatids and mature spermatozoa at the acrosome and tail regions. Using a yeat-2-hybrid screening, Trs4 was found to bind Gstmu1, Rslh-2 and Ddc8 proteins. To further characterize the functional role of Trs4 in spermatogenesis, and study how Trs4 interacts its binding proteins for cellular functions, we aimed (1) to screen putative ES cells with Trs4 floxed allele for knockout mice generation, (2) to generate Trs4 deletion constructs and study the cellular localization of Trs4 and its putative binding partners in transfected spermatocyte GC-2spd(s) cell line, (3) to study how heat-treatment regulates the expression of Trs4 and apoptotic molecules. The Trs4 conditional targeting vector was constructed by flanking exons 4-6 with two LoxP sites and electroporated into ES cells. After screening of 480 clones, positive ES cell clones were identified by Southern blotting using 5’- and 3’- probes. Three putative positive clones were identified carrying the floxed allele. Trs4 protein contains putative ubiquitin-like motif (a.a. 119-224), IQ-calmodulin binding motif (a.a. 334-362) and a overlapping bipartite nuclear localization signal (BNL) (a.a. 346-362). Transfection of EGFP fused Trs4 truncated protein demonstrated that the IQ-calmodulin binding motif and BNL signal was important for localization of Trs4 protein in the cytoplasmic/Golgi regions; while the N-terminal contains ubiquitin-like motif and the C-terminal regions direct the expression of the EGFP-fusion protein mainly to the nucleus. The full-length sequence of Trs4 binding partners: Gstmu1, Rshl-2 and Ddc8 were cloned into the pDsRedmonomer-C1 vector, giving red fluorescence protein in the transfected cells. They were colocalized with EGFP-Trs4 in the cytoplasm of the cells, confirming that Trs4 and its interacting protein is likely interact with each other in vivo. As Trs4 colocalize with Gstmu1, a modulator of mitochondrial-dependent pathway in apoptosis, it is suggested that Trs4 is an upstream regulator of apoptosis under heat treatment in germ cells. The functional roles of Trs4 protein Trs4 and apoptotic molecules. The Trs4 conditional targeting vector was constructed by flanking exons 4-6 with two LoxP sites and electroporated into ES cells. After screening of 480 clones, positive ES cell clones were identified by Southern blotting using 5’- and 3’- probes. Three putative positive clones were identified carrying the floxed allele. Trs4 protein contains putative ubiquitin-like motif (a.a. 119-224), IQ-calmodulin binding motif (a.a. 334-362) and a overlapping bipartite nuclear localization signal (BNL) (a.a. 346-362). Transfection of EGFP fused Trs4 truncated protein demonstrated that the IQ-calmodulin binding motif and BNL signal was important for localization of Trs4 protein in the cytoplasmic/Golgi regions; while the N-terminal contains ubiquitin-like motif and the C-terminal regions direct the expression of the EGFP-fusion protein mainly to the nucleus. The full-length sequence of Trs4 binding partners: Gstmu1, Rshl-2 and Ddc8 were cloned into the pDsRedmonomer-C1 vector, giving red fluorescence protein in the transfected cells. They were colocalized with EGFP-Trs4 in the cytoplasm of the cells, confirming that Trs4 and its interacting protein is likely interact with each other in vivo. As Trs4 colocalize with Gstmu1, a modulator of mitochondrial-dependent pathway in apoptosis, it is suggested that Trs4 is an upstream regulator of apoptosis under heat treatment in germ cells. The functional roles of Trs4 protein / published_or_final_version / Obstetrics and Gynaecology / Master / Master of Philosophy

Multiple gut hormones are involved in the regulation of food intake. Secretin (SCT), a classical gut hormone, is released into the circulation from the duodenal S-cells when acidic chyme enters the duodenum and performs the major functions of delaying gastric emptying, stimulating fluid secretion from pancreas and liver to optimize the digestion process. In recent years, SCT and its receptor (SCTR) have been identified in discrete nuclei of the hypothalamus, including the paraventricular nucleus (PVN) and the arcuate nucleus (Arc). The occurrence of SCT and SCTR in the brain regions that are engaged in regulating body energy homeostasis and the release pattern of SCT after meals support a functional role of SCT in appetite control. In this study, the effect of SCT on feeding behavior was investigated using wild-type (wt), SCT?/?, and SCT receptor-deficient (SCTR?/?) mice. We found that both central and peripheral administration of SCT could reduce food intake in wt but not in SCTR?/?mice. SCT induce Fos expression in the PVN and Arc, suggesting the activation of hypothalamic feeding centers by this peptide. Consistent with this notion, SCT was found to increase proopiomelanocortin (POMC), but reduce agouti-related protein (AgRP) transcripts in the Arc, and augment thyrotropin-releasing hormone (TRH) and melanocortin-4 receptor (MC4R) mRNA expression in the PVN. In addition, pretreatment with SHU9119, an antagonist for MC4R, abolished the anorexia induced by SCT, suggesting that SCT may inhibit food intake via a melanocortin-dependent pathway. Gut hormones signals the brain to modulate the feeding behavior via the vagal afferent nerve, bloodstream or both. Here we showed that peripheral SCT-induced anorexia was attenuated in mice with subdiaphragmatic vagotomy, capsaicin treatment and bilateral midbrain transections. In summary, our data identify peripheral SCT as an anorectic peptide exerting its action via the melanocortin system and the vagal afferent contributes a major route in mediating the inhibitory effect of peripheral SCT on food intake. The present findings advance our understanding of the role of gut hormones in the regulation of appetite. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, with genetic factors playing critical roles in its pathogenesis. Mutations in APP, PSEN1 and PSEN2 genes are confirmed to be causative risk factors for early-onset Alzheimer’s disease (EOAD). For late-onset Alzheimer’s disease (LOAD), growing evidence suggests it is caused by multiple genetic risk factors in corporation with the environmental exposures. Although, so far, APOE is the most well recognized common genetic risk factor for LOAD, other susceptible candidate genes, such as CR1, CLU and PICALM, have recently been identified in Caucasians using genome-wide association approach. In order to have a better understanding on the genetic components of LOAD in Chinese as well as identify other potential genetic risk factors for Chinese ethnic population, we conducted a case-control study using candidate gene association approach. In view of increasing evidence on the neural protective effects of sex steroid hormones both in vivo and in vitro, we hypothesized variations on sex steroid metabolic pathway genes were associated with LOAD. Four candidate genes (ESR1, ESR2, CYP19A1, CYP11A1) were evaluated based on 462 cases and 350 non-demented controls. Apart from consistent result for APOE, polymorphisms in ESR2 and CYP11A1 were found to be significantly associated with the disease. When stratification according to gender, marginally significant associations were detected for ESR1 and ESR2 variants in men while CYP11A1 variants relevant to LOAD risk were detected exclusively in women. Additionally, genotypic and phenotypic correlation analysis revealed CYP19A1 was significantly relevant to serum 17-estradiol (E2) levels in 689 subgroup participants, especially in 400 LOAD patients of subgroup. Further gene-level analyses based on whole sample confirmed above disease association for ESR2 and CYP11A1 and pathway-level analyses highlighted the impact of sex steroid metabolic pathway on disease predisposition. The independent follow-up study for CR1, CLU and PICALM previously reported by genome-wide association study (GWAS) in Caucasians was conducted in the same Chinese cohort. Similar to the Caucasian cohort, polymorphisms in CR1 and CLU were found to be significantly different between cases and non-demented controls. However, significant disease association for PICAML was detected only in the APOE ε4 (-) subgroup of our Chinese cohort. In conclusions, genetic abnormalities were founded in Chinese LOAD patients. In addition to confirmation disease susceptibility for APOE, CR1, CLU and PICALM, we were first to report the associations between several sex steroid metabolic pathway genes and LOAD. This valuable genetic information obtained from Chinese patients may lead to the development of novel diagnostic strategies and therapeutic interventions in LOAD. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Hepatocellular carcinoma (HCC) is the major type of primary liver cancer which is well-known for its high heterogenicity and metastatic potential. Despite of the current advancement in surgical resection and the availability of targeted therapy, HCC remains a barely curable and fatal disease. We previously demonstrated that deregulation of epigenetic regulators is a common event in human HCC. Herein, we identified the frequent up-regulation of the prototype of H3K9 tri-methyltransferase SUV39H1 in clinical HCCs. SUV39H1 over-expression was also significantly associated with increased Ki67 expression and the presence of venous invasion. By using both SUV39H1 over-expression and knockdown model, we consistently demonstrated that SUV39H1 contributed to HCC tumor growth and migration. Most importantly, SUV39H1 knockdown drastically suppressed in vivo tumorigenicity and extra-hepatic metastasis of HCC cells in nude mice model. These findings evidently demonstrated the oncogenic role of SUV39H1 in HCC and implied potential therapeutic targeting of SUV39H1 for HCC treatment. Molecularly, SUV39H1 knockdown HCC cell underwent morphological changes and accompanied with increased lysosomal β-galactosidase activity and elevated p21 protein and γH2AX level. This data suggested senescence induction in SUV39H1 knockdown HCC cells. SUV39H1 has been implicated in telomere regulation and transcriptional control. However, neither telomere length nor expression of tumor suppressor genes was altered in SUV39H1 knockdown HCC cells. Interestingly, we demonstrated a novel observation that SUV39H1 may potentially methylate non-histone substrates that are yet to be identified, which may contribute to the pro-tumorigenic function of SUV39H1 in HCC. We also investigated the upstream regulation of SUV39H1 and identified miR-125b as the negative post-transcriptional regulator of SUV39H1. Ectopic expression of miR-125b abolished SUV39H1 3’UTR-coupled luciferase activity and suppressed endogenous SUV39H1 at both mRNA and protein level. Clinically, miR-125b level was found inversely correlated with SUV39H1 expression. We have previously reported the frequent under-expression of miR-125b in HCC. Collectively, our data suggested that SUV39H1 up-regulation in HCC may be the sequential outcome of miR-125b down-regulation. In conclusion, we demonstrated for the first time that SUV39H1 up-regulation contributed to HCC development and metastasis, potentially via senescence evasion. SUV39H1 elevation in HCC was attributed to the loss of its negative regulator, the tumor suppressive miR-125b. / published_or_final_version / Pathology / Doctoral / Doctor of Philosophy

Work-family conflict is a type of interrole conflict in which psychological stress arises when demands from work domain interfere with one’s capability to carry out responsibilities associated with family. Social support, on the other hand, is commonly regarded as a valuable coping resource that can alleviate job stress. In the past few decades, different models have been proposed to understand the role of work-family dynamics in the workplace. However, some of these models are mutually exclusive. While some studies found that either positive or negative experience from one domain will spill to the other domain, a different stream of research found that the negative experience from one domain can be compensated by the positive experience from another domain. In an attempt to understand the underlying mechanism of work-family conflict, a moderated-mediation model was proposed. The model encompasses the indicators, the consequences, and the moderators into the study of work-family conflict. More importantly, the model puts forward the importance of a situational fit between the source of stress and the type of social support being offered (Study 1). It also emphasizes the significance of relationship closeness in affecting the effectiveness of social support (Study 2). Adopting the Job Demand-Resources model, Study 1 attempted to test the contextual variability of social support. In particular, the buffering role of two types of domain-specific support, namely the coworker support and family support, were tested in the work context. The results showed that there is a domain difference of the effectiveness of social support. The moderating effect of within-domain social support was stronger than the cross-domain social support. Coworker support was found to buffer against the linkage between job demands and psychosomatic symptoms, whereas family support was found to strengthen the lethal impact of the same relationship. Based on a sample with two time points of 18- to 20-month interval, Study 2 further tested the impact of relationship closeness on social support. Work-family conflict was found to be a mediator between the linkage of job demands and psychological well-being. A main effect was shown for both coworker support and family support in which the both types of social support from Time 1 significantly predicted Time 2 work-family conflict reported by participants. Peer support was found to be a negative buffer in the moderated mediation model in which a higher level of peer support was shown to intensify the negative relationship of job demands on psychological well-being through work-family conflict. The findings from the current research challenge the perspectivethat views social support as favorable at all times. In particular, the proposed model showed that receiving social support in a right context, or social support from significant others will be beneficial to employees’ psychological well-being, whereas social support from non-significant others in a misfit context will be hazardous. / published_or_final_version / Psychology / Doctoral / Doctor of Philosophy

Wind energy is commonly considered to be a clean and environmentally friendly renewable energy resource, as they do not pollute our atmosphere with greenhouse gas, nor do they cause any radioactive problems compared to nuclear energy. However, there are still some environmental impacts due to the installation and operation of the wind turbines that cannot be ignored, such as noise, visual and climatic impact. Especially, the observed local climate change in some wind farm areas has attracted general concern in recent years. Experts suspected that long time operation of wind turbines in an area can cause changes to local precipitation, evaporation of the water on earth surface, and even affect the frequency of drought happening. Nevertheless, we still cannot figure out whether these changes would be caused by wind turbines or not. The target of this study is to investigate the potential local impact of an operating wind turbine by numerical simulation. Because of the big geometric size of commercial wind turbines, experimental method is very limited in this type of study. Numerical simulation using CFD is considered to be a suitable approach and commercial software “FLUENT” is utilized in this study. Firstly, an accurate 3-D numerical wind turbine model was established and the frozen blade method was used to realize the rotation of the wind blades. Before further simulation, a wind-tunnel test has been undertaken by using a scaled physical wind turbine model for validation purpose. The experimental results show good agreement with those predicted by the numerical simulation. This suggested that the computation results were validated and the computational model can be used for further study. In this research, three wind turbine cases, with different typical ambient temperature and surface temperature, were simulated. Characters like wake structure, turbulence intensity and local temperature change was collected and analyzed in each simulated case. The results show that the operating wind turbine can bring obvious velocity deficit in the wake and a strong turbulence intensity enhancement was observed at the top tip because of the rotation. Also, local temperature change was found in the near wake region. The investigation of the local impact of the operating wind turbine is very significant. This study provides a valuable insight into the potential impacts of wind farms on local meteorology, which is rarely studied before. Meanwhile, a more comprehensive study on the effect of a wind farm on the environment is highly recommended. / published_or_final_version / Mechanical Engineering / Master / Master of Philosophy

When compared with basic theory of mind (ToM), there is very limited research on advanced ToM. The two studies of the current research aimed to explore the underlying mentalistic processes leading to advanced ToM understanding in Strange Stories and possible factors that facilitate the development of advanced ToM from basic ToM. The participants were 25 adolescents with autism spectrum disorder (ASD) and 25 typically developing (TD) peers with matching age (12 to 15) and Verbal IQ. The first study explored the difference in level of difficulty with regard to two groups of stories in the Strange Stories test (Happe, 1994), non-literal and untrue literal. As predicted, stories with non-literal statements were found to be more difficult than untrue literal statements in both ASD and TD groups. With reference to Grice theory, the difference in level of difficulty was suspected to be related to the difference in level of complexity in the mentalistic processes involved. The underlying mentalistic processes of advanced ToM understanding were then explored by extending a hierarchy of 3 mentalistic processes developed from an irony study on TD population (Filippova and Astington, 2008) to other advanced ToM social situations. According to this hierarchy, to detect the speaker’s motivation/ attitude, i.e. advanced ToM understanding, in a statement, one has to first understand the speaker’s belief towards the statement. The speaker’s communication intention would then be identified with reference to this belief. Finally, with understanding at the belief and intention levels as basis, people could interpret the motivation or attitude of the statements. With reference to previous research findings, it was hypothesized that understanding at the motivation/attitude level of non-literal statements would follow the hierarchy of mentalistic processes which reflected more complex mentalistic processes. Understanding of untrue literal statements at motivation/attitude level would involve less complex mentalistic processes as it did not necessarily follow the hierarchy, since understanding of intention and (or) belief was not essential. The results partially supported the hypotheses with some exceptions. Re-categorization according to the adherence to the hierarchy reflected a greater difference between the two new story categories for both ASD and TD groups, which suggested salience in meaning is a better grouping factor to reflect the variation in levels of difficulty among Strange Stories. The factor of “intention and belief” derived from the delineation of mentalistic processes of advanced ToM understanding was found to have significant mediation effects in the link between basic ToM and advanced ToM in the ASD group, which suggested its facilitating role. Yet, the mediation effect was not found in the TD group. The second study investigated the possible facilitating role of knowledge of advanced ToM mental state concepts for the acquisition of advanced ToM. The ASD group was significantly weaker than their TD counterparts in both example and definition level of knowledge of advanced ToM mental state concepts. Similar to the results in Study One, knowledge of advanced ToM mental state concepts was found to be positively associated with advanced ToM understanding but such a relationship was not significant in the TD group. The lack of significant associations among basic ToM, advanced ToM and Intention-Belief as well as the absence of a significant relation between knowledge of advanced ToM mental state concepts and advanced ToM understanding in the TD group indicated the possibility that they are necessary but not sufficient factors for facilitating advanced ToM acquisition. The results shed light on the theoretical framework of advanced ToM acquisition and provided practical implications especially for intervention related to advanced ToM development. / published_or_final_version / Educational Psychology / Doctoral / Doctor of Psychology