There is increasing evidence that biological factors (i.e., hormones) support the development of sex differences in behavior by organizing brain systems in prenatal life. However, the behavioral significance of the surge in reproductive steroids that results from the transient activation of the hypothalamic-pituitary-gonadal (HPG) axis around 3-months of age is largely unknown. The goal of the present study was to investigate the role of early postnatal activation of the HPG axis in the development of sex differences in human behavior. Participants included 54 children between 18 and 24 months (32 males and 22 females) and their parents. Infants and their caregivers participated in two, eight minute play sessions that were video-taped and later coded for children’s aggressive behavior and vocal ability. During each session, children wore an actigraph (Actiwatch, Philips Respironics) to provide a nonbiased assessment of activity levels. In addition, toddler’s temperament was measured using the Brief Infant Toddler Social-Emotional Assessment (BITSEA). Saliva samples from each infant were collected at 3-4 months of age and levels of testosterone were measured. Digit ratio levels were also measured at 3-4 months and used as a marker of prenatal androgen levels. The data indicated that boys were more aggressive, engaged in higher levels or activity, and showed less developed language ability. In addition, our results demonstrated that hormone markers associated with higher (i.e., more male-typical) testosterone were related to more aggressive behaviors, higher activity levels, expression of fewer total words, and a shorter duration of time spent vocalizing. A novel finding was that higher testosterone (i.e., more male-typical) levels in early postnatal life predicted less time spent vocalizing, for both sexes together and within males. The present research suggests that hormone levels in early postnatal life may contribute to the development of gender phenotypes, potentially making this a critical period for the development of language and other gender-linked behaviors.

Thesis (M. Med. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 33-36).

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 108-114).

Thesis (M.Med.Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 33-36). Also available in print.

The aim of this thesis is to identify key requirements for exploring Linked Data and design and implement a web application which serves as a Linked Data browser, including search and customization features. In comparison to existing approaches it will enable users to provide templates which define a visual style for presentation of particular types of Linked Data resources. Alternatively, the application can provide other means of altering the presentation of data or the appearance of the application. Powered by TCPDF (www.tcpdf.org)

Retinal degenerative disease, which includes age-related macular degeneration and retinitis pigmentosa, is the main cause of blindness in developed countries. Degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells through apoptosis is believed to be the main mechanism of cell death. X-linked inhibitor of apoptosis (XIAP) is an endogenous anti-apoptotic protein that mediates its effects through the inhibition of caspases - the proteins regulating the final stages of apoptosis. The neuroprotection of XIAP has been demonstrated in various neurodegenerative models. Retinal gene therapy based on adeno-associated virus (AAV) has recently been proven safe and effective in clinical trials of Leber's congenital amaurosis. However, studies are very limited so far about AAV-mediated XIAP effect on degeneration of the RPE and photoreceptor cells. In this thesis, a comprehensive study of AAV-mediated XIAP was performed in the RPE and photoreceptor degenerative models. First, an oxidative stress model was investigated using H2O2 in a human RPE cell line. Second, AAV2-mediated XIAP conferred marked protection on the RPE cells against H2O2 induced apoptosis. Third, an in vivo analysis using confocal scanning laser ophthalmoscope was applied to the NaIO3 induced retinopathy in two transgenic mice (NRL-GFP and B6TGOPN1LW-EGFP). However, subretinal injection of AAV2-XIAP did not rescue photoreceptor cells in the NaIO3-treated animals. Finally, AAV8-XIAP was tested in a rhodopsin mutant mouse line with retinal degeneration (the Rho-/- B6TGOPN1LW-EGFP mouse) but did not reveal any protection on cone photoreceptors. Overall the work in this thesis indicates a limited protection of AAV-mediated XIAP on the RPE and photoreceptor cells in the degenerative models used. XIAP based gene therapy may be helpful for RPE preservation in atrophic AMD, but it needs further research.

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The components involved in an immunoassay were investigated in order to improve the detection limits of the ELISA and to make the assay adaptable to a flow injection analysis (FIA) configuration. The goal being the total automation of the ELISA procedure which is long, tedious and has high standard deviation. The antibody purification and cleavage methods were studied with special emphasis on obtaining products with highest immunological activity. The antibody-enzyme coupling reactions using homobifunctional reagents and heterobifunctional reagents were studied in order to attempt the preparation of highly characterized reagents. The fragments of IgG were coupled to polymeric supports via the hinge thiol groups to retain the maximum immunological activity. This method was found to be superior to those methods involving coupling via amino group. These reagents were used in the development of a sandwich ELISA for bovine IgG. The range of assay was in the 20-1000 femtomole range with a linear dynamic range of 2 orders of magnitude and an accuracy of 2-5%. A competitive ELISA based on the use of immobilized anti-human IgG Fab' fragments was developed. The linear dynamic range for this assay was found to be less than one order of magnitude. The detection limit was in the low picomole range with an accuracy of 2-5%. Based on the principle used in the two assays an enzyme immobilization scheme was developed for the reversible immobilization of these enzymes. Which was subsequently utilized in the determination of substrate in the picomole range in a reagent less FIA technique. The goals of this research project were realized in that the FIA system utilized in this work was capable of carrying out totally automated ELISA assays with an accuracy far surpassing the conventional plate ELISA assays.

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No description available.