MSC (Med),Population-Based Epidemiology, Faculty of Health Sciences, University of the Witwatersrand, 2007 / Objective To compare risk factors between HIV-positive concordant and discordant couples. Study design This is a cross-sectional secondary data analysis study using data from Africa Centre Demographic Information System (ACDIS) database (June 2003 to December 2004) and data from the first round of population-based HIV surveillance conducted by the Africa Centre for Health and Population Studies. Methods Eighty-five HIV-positive concordant couples (both partners were HIV-positive) and 73 discordant couples (one partner was HIV-positive and other partner HIV-negative) were identified and selected from the first round of population-based HIV surveillance conducted from June 2003 to December 2004 in Hlabisa Demographic Surveillance System site. Partners health and sexual behaviour data were collected together with the blood sample for HIV test during the same round. Socio-economic and demographic data of partners were obtained from the ACDIS database and were collected within the same period (June 2003 to December 2004). The behavioural, biological, demographic and socio-economic risk factors for HIVpositive concordance and transmission within discordant couples were analysed. Circumcision and area of residence respectively were the biological and demographic factors considered. Number of household assets was used as a proxy for socioeconomic status. The behavioural factors considered were male condom-use, sexual debut (age at first sex), number of lifetime partners and premarital partners. The age and educational level of partners were considered as potential confounders. 5 RESULTS The uncircumcised men were more likely to be in HIV-positive concordant couples than to be in discordant couples (OR =10.8, 95% CI [1.93 – 60.30], p=0.007). Partners living in urban area were 4.7 times more at risk of being in a HIV-positive concordant relationship than to be in discordant relationship (OR=4.7, 95% CI [2.09 - 10.39], p<0.001). Male not using condom on regular basis with female partners, early sexual debut, greater number of premarital partners, household assets and lifetime partners were found not to be significantly associated with HIV-positive concordance. Conclusion There are several biologic, socio-economic, demographic and behavioural risk factors for HIV-positive concordance. However, identifying some of them might be used to address transmission of HIV among discordant couples through intervention programs. Although cross-sectional studies are not ideal for establishing temporality, this study corroborates the findings of other studies that living in urban areas and circumcision are associated with HIV transmission.

Based on an external school review, a large suburban high school outside a southeastern United States metropolitan area was not in compliance with state technology standards. The school leadership team concluded that because teachers were not effectively integrating technology for teaching, student achievement may have been negatively influenced. The purpose of this nonexperimental project study was to measure relationships among factors influencing degree of implementation of technology (ITC) in the classroom using Dewey's experiential theory with an emphasis upon constructivism as a theoretical framework. A modified survey, Technology and Professional Development Survey of Georgia High School Teachers, was distributed to all teachers in the local school (N = 109). The 8 research questions addressed the relationship between the dependent variable, Degree of ITC, and the independent variables: teacher disposition, instructional support, availability of technology, teacher collaboration, access and use of computers at home, teacher's level of education, number of years of teaching experience, and teacher participation in the Georgia Technology Initiatives. Using multiple regression and Chi-Square analysis, this quantitative investigation identified significant relationships between degree of ITC and both teacher disposition (B = .279, r = .473, p = .002) and instructional support (B = .249, r = .403, p = .012). These findings lead to professional development for increasing the use of technology for improving compliance with state technology standards, thus promoting positive social change through improved teaching and learning.

The relationship between breadth of perspective, defined as the range of alternative solutions that one is able to bring to mind whn presented with a problem, and selected aptitude and background factors was studied. Scholastic aptitude was the chosen aptitude factor. The background fac tors chosen were: (1) size of home town; (2) number of towns lived in; (3) number of children in the family of origin; (4) the subject ' s perception of his travel experience; (5) number of books read during the past year; and (6) number of friends of other nationalities. The sample consisted of 130 female students from five selected classes in the College of Family Life at Utah State University during the 1967 - 68 school year The instruments used were: (l) a background questionnaire; (2) scholastic aptitude, as measured by the students' ACT scores; and (3) Warshay's three unfamiliar problem situations . The statistical t es t used was the Independent x2 t es t of significance. No significant relationship was found between the number of alterna tives perceived and scholastic aptitude, size of home town, number of towns lived in, number of children in the family of origin, or number of books read during the past year. Perception of alternatives was related to the subject's perception of his travel experience at the .05 level and to number of friends of other nationalities at the .10 level .

"May 2003." Includes a list of publications by the author (journal articles related to thesis); and , copies of journal articles co-authored by the author. Includes bibliographical references (leaves 226-242) The solution structures of three peptides: Ala4Lys14-citopin 1.1 (amphipathic đ-helix); Gly15Gly19-caerin 1.1 (a less defined đ-helix); and, frenatin 3.1 (amphipathic đ-helix with a flexible c-terminal end) are presented in a discussion about structure/activity relationship

The ability of a cell to respond to extrinsic stimuli critically depends on its ability to regulate specific intracellular protein - protein interactions in a reversible manner and allow the temporal - spatial characteristics of the signal to be accurately transduced to downstream targets. Growth factor and cytokine receptors provide a link by which extracellular stimuli are propagated within the cell to accomplish specific cellular functions. Ligand - stimulation of these receptors activates cascades of intracellular events that transduce the signals that lead to a variety of cellular responses. The specificity of these signals and the fidelity with which they are communicated within the cell are critical for the fate of an organism as deregulation or misbalance of signalling networks is commonly associated with a wide range of pathologies and diseases. Cytokines are important regulatory proteins that regulate diverse cellular functions through their ability to bind to specific cell surface receptors. Most cytokines are pleiotropic effectors that regulate multiple cellular functions. For example, many cytokines can regulate diverse biological activities such as cell survival, proliferation and differentiation and in many cases these different biological activities can be independently regulated. The regulation of pleiotropic biological responses is mediated through the modulation of multiple intracellular signalling pathways. These pathways often present a high level of redundancy in terms of the biological functions that they control. However, pleiotropic cytokines have the ability to independently activate signalling pathways that lead to the regulation of specific biological functions such as survival, proliferation, differentiation or activation. The molecular mechanisms by which cytokines can regulate pleiotropic biological responses from the activation of a limited number, often redundant, of intracellular signalling pathways have not been fully resolved and remains one of the most important unanswered questions in cell biology. In particular, proteins and molecular mechanisms responsible for specifying different biological responses remain largely unidentified. In many cases, activation of multiple signalling pathways and integration of the signals they transduce is needed in order to modulate a biological function. One important mechanism by which signalling pathways are assembled within the cell is through the action of protein scaffolds that contain phosphotyrosine ( e.g. SH2, PTB ) or phosphoserine / threonine ( e.g. 14 - 3 - 3, WW, FHA, PBD, BCRT ) binding modules. Interestingly, although phosphotyrosine and phosphoserine / threonine - dependent signalling pathways are highly integrated within the cell, scaffold proteins containing both phosphotyrosine and phosphoserine or phosphothreonine - binding domains ( i.e. SH2 / PTB and WW / FHA / PBD / BCRT ) have not been identified. The broad aim of this thesis is to study the fundamental molecular mechanisms by which cytokines, through the binding of cell surface receptors, are able to activate and integrate signalling pathways that regulate and specify cellular responses. In particular, these studies examine the role of the 14 - 3 - 3 family of adaptor proteins in the assembly of signalling networks that couple the activated receptors of the haematopoietic cytokines IL - 3, IL - 5, and GM - CSF to downstream signalling targets and specific cellular functions such as survival and proliferation. The specific aims of this thesis are to examine the composition, molecular mechanisms of assembly and functional roles of signalling complexes that use the adaptor or scaffold protein 14 - 3 - 3 and are important for signal transduction in response to GM - CSF. This work shows that the phosphoserine / threonine - binding scaffold protein 14 - 3 - 3 ζ, previously reported to bind to Ser585 of the GM - CSF receptor, undergoes tyrosine phosphorylation. Using a panel of 14 - 3 - 3 ζ mutants a particular tyrosine residue, Tyr179, was found to be critical for the binding of the SH2 domain of Shc, the assembly of a PI3K signalling complex, the activation of the Akt / PKB signalling pathway and the control of cell survival in response to GM - CSF stimulation. Tyr179 of 14 - 3 - 3 ζ was also found to be important for specifying GM - CSF - mediated biological responses as it was found to play an important role in the control of cell survival versus cell proliferation. Furthermore, it was found that 14 - 3 - 3 ζ is able to simultaneously bind to Ser585 of the GM - CSF receptor and recruit Shc and PI3K through Tyr179, thus integrating phosphoserine / threonine and phosphotyrosine / dependent signalling pathways. The findings described in this thesis helped to identify a novel mechanism by which cytokine receptors achieve both integration in signalling and specificity in biological outcomes. The discovery that phosphoserine / threonine - binding proteins ( i.e. 14 - 3 - 3 ) are themselves tyrosine phosphorylated and able to recruit phosphotyrosine - binding molecules provides a new insight into how intracellular signal integration is achieved. Understanding how signal transduction is carried out within the cell is paramount to successful drug development in many therapeutic areas. The new insights in GM - CSF signalling provided by this work may help to successfully develop treatments to target diseases such as asthma, rheumatoid arthritis and leukaemia, where GM - CSF appears to play a pathogenic role. / Thesis (Ph.D.)--School of Medicine, 2006.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Meteorological aspects of geothermal energy development are first discussed in general terms. An instructive case study is then presented of a hypothetical 100 MW geothermal electrical generating plant at a site near Vale, Oregon. Long-term climate data from Ontario Airport near Ontario, Oregon, are used to describe meteorological characteristics of the Vale site and the effects of topography are discussed. Source data were taken from descriptions of similar plants. A simple Gaussian plume model is applied to the data to estimate typical visible plume lengths at different times of day and year, and fog inducement in terms of extra hours per year. A ballistic-type drift deposition model is used to analyze the impacts of cooling tower drift in terms of drift "rain" intensity and annual moisture deposition. Assumptions and approximations, made with the intention of presenting upper limits to predicted effects, are discussed. Comments and suggestions concerning the extension of the results to contaminant emissions and additional data that would be needed to perform a more detailed and conclusive study are included. / Graduation date: 1980

The overall goal of my work has been to gain a better understanding of Axenfeld-Rieger Syndrome (ARS), a human autosomal dominantly inherited mal-development of the anterior segment of the eye that is associated with glaucoma. By studying rare genetic causes of this complex disease we are gaining insight into the initial steps that ultimately lead to blindness. To achieve the goal of better understanding ARS, my research project had two parts. In the first part, I performed a retrospective clinical study in which I analyzed the glaucoma-related clinical presentation of ARS patients with FOXC1 and PITX2 defects. This study showed a good genotype-phenotype correlation which may be important for the physician in dealing with ARS patients. Patients with FOXC1 mutations had the mildest prognosis in glaucoma development, while patients with PITX2 defects and patients with FOXC1 duplication had a more severe prognosis in glaucoma development than patients with FOXC1 mutations. I tried to determine the best treatment for glaucoma in these patients. Unfortunately, in this study, current medical therapies did not successfully lower intraocular pressure or prevent progression of glaucoma in ARS patients with FOXC1 or PITX2 alterations. This clinical study also provided useful diagnostic criteria to identify the gene responsible for ARS. The second part of the project was to study the gene regulatory pathways of the PITX2 gene, mutations of which cause ARS. PITX2 is a transcription factor that regulates the expression of genes in the eye. The discovery of direct downstream targets of PITX2 is necessary for understanding the genetic mechanisms underlying complex, highly regulated processes such as development and underlying heritable human disorders. To find direct target genes of PITX2, I have used a recently developed method: the hormone receptor (HR)-inducible expression system for transcription factors coupled microarray analysis. The results obtained using this method have involved PITX2 in control of cellular stress. Recent investigations have suggested significant roles for cellular stress in glaucoma pathology. Understanding the control of these key aspects of cell function will have profound implications for understanding and treating the glaucoma that is the most clinically serious consequence of mutations of PITX2.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Also available online.

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