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CUHK electronic theses & dissertations collection
No full textTang Wan-yee."July 2004."Thesis (Ph.D.)--Chinese University of Hong Kong, 2004.Includes bibliographical references (p. 192-212).Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Mode of access: World Wide Web
Epigenetic Effects of Polybrominated Diphenyl Ether Exposure on Airway Hyperresponsiveness in Offspring
Get PDFAsthma is a chronic lung disease with staggering disease burden in youth. Current literature suggests that maternal exposure to certain xenobiotic chemicals can affect developing offspring epigenetics, leading to a predisposition for asthma. Our previous study links polybrominated diphenyl ether congener 47 (PBDE-47), a chemical used as a flame-retardant within household products, with increased airway hyperresponsiveness (AHR). Of further concern is the potential influence of PBDE-47 in mice lung on the epigenetic alterations regulating asthma related genes that may play a role in pathogenesis, such as Tumor Necrosis Factor Alpha (TNFA) and Brain Derived Neurotrophic Factor (BDNF). This thesis tested the hypothesis that altered DNA methylation of key asthma related genes due to PBDE-47 exposure leads to modulation of gene transcription.
In Chapter 1, I begin by introducing PBDEs, and discuss the role of altered DNA methylation in disease pathogenesis. The major genes studied in the experiment, Bdnf and Tnfa, are also detailed, and I discuss the effects that dysregulation of these key genes has on health. In Chapter 2, I observed there is no difference in gene expression and DNA methylation of Bdnf and Tnfa in mouse exposed to a single postnatal PBDE-47. In Chapter 3, I investigated the epigenetic effect of maternal PBDE-47 exposure on offspring’s airway reactivity and asthma phenotypic genes. This multi-dose experiment found increased gene expression and promoter demethylation for Bdnf and Tnfa in the mouse model.
Overall, the completion of this research illuminates the epigenetic effects of exposure to PBDE-47 on asthma genes, and their connection with previously observed increased AHR. This study presents an innovative approach to observing the effect of PBDE-47 exposure on asthma risk through utilizing methylation profiling. While many previous studies look at direct adverse health effects, my approach demonstrates how PBDE-47 exposures have epigenetic effects in offspring of impacted mothers. Looking at in utero effects demonstrates that epigenetics underpins a mechanism of toxic action with PBDEs that would not be commonly seen in traditional animal experiments by establish a heritable epigenetic model of toxic action of PBDEs on key genes related to the development of asthma in mammals
Sex Differences in Ischemia-Reperfusion Injury and Cardioprotection-Revisited: The Role of S-nitrosoglutathione Reductase, S-nitrosylation, and Formaldehyde Regulation
Get PDFMyocardial infarction, which can be caused by coronary artery occlusions, and the subsequent treatment that restores blood flow (i.e. reperfusion) induces significant myocardial death; this damage is known as ischemia-reperfusion (I/R) injury. Many animal studies have postulated molecular strategies to protect the heart and reduce I/R injury, but these proposals have mostly failed to translate into the clinic. Interestingly, female hearts have an inherant cardioprotection against I/R injury and unlocking the cardioprotective mechanism that safeguards the female heart can provide new avenues for identifying novel therapies to combat I/R injury in patients. Previously, we demonstrated that male and female cardioprotection is mediated, in part, through an endogenous signaling molecule known as nitric oxide. This molecule can bind to free cysteines and serve as a post-translational modification, termed S-nitrosylation (SNO), thus participating in signaling cascades involved in cardioprotection against I/R injury. The goal of this dissertation was to characterize sex differences in the cardiac SNO proteome and investigate the role of S-nitrosoglutathione reductase (GSNO-R), a major regulator of SNO and formaldehyde metabolism.
Using traditional cardiac physiology techniques and novel molecular and biochemical procedures, we conducted a series of experiments to investigate sex-dependent cardioprotection against I/R injury. With these methods, we found that female hearts had more nitric oxide production, protein SNO, and GSNO-R activity compared to male hearts. Furthermore, we identified GSNO-R as a critical regulator of sex-dependent cardioprotection, as inhibition conferred protection to male hearts but ablated the endogenous, female protection. We demonstrated that this loss of female cardioprotection was mediated by dysregulated formaldehyde metabolism. Finally, we found that the mechanism for this loss of protection in female hearts was unlikely mediated by the inhibition of protein SNO or impaired glutathione dynamics.
Taken together, these studies enhance our understanding of protection against I/R injury by demonstrating that the GSNO-R-mediated regulation of formaldehyde is a new player in sex-dependent cardioprotection. Future studies can help to identify the molecular mechanisms responsible for the loss of protection in female hearts and new areas of research that can help to combat I/R injury in male and female hearts
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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