Thesis (Ph. D.)--University of Virginia, 2008. / Title from title page. Includes bibliographical references. Also available online through Digital Dissertations.

Magister Scientiae - MSc / This study investigates the most important reasons behind the rst-year students' decision to select University of the Western Cape (UWC) as higher education institution. These reasons were organized into a few factors for easy interpretation. The data to be analyzed for this project is a subsection of the data collected during the orientation period of 2008. During the orientation week of 2008, the questionnaires were completed on a voluntary basis by new rst-year students. All questionnaires were anonymously completed and therefore the data does not contain any information that could be linked to any individual. For the purpose of this study, only the black African and coloured students were considered. The other racial groups were not analyzed due to too small sample sizes. Questionnaires with missing information on the reasons for selecting UWC were not nalyzed. We ended up with a sample of size 600. The data were statistically analyzed, using descriptive statistics, bivariate analyses, factor analysis, coefficient of congruence and bootstrap factor analysis. The results indicated that the most important reasons a ecting students to choose UWC were identi ed as good academic reputation, family member's advice, UWC graduates are successful and UWC graduates get good jobs. The least important reasons were found to be not accepted anywhere, parents / family members graduated from UWC, recruited by UWC and wanted to study near to home. The results also indicated that there were significant differences among students according to population groups, parent's monthly income and grade 12 average. Factor analysis of 12 variables yielded three extracted factors upon which student decisions were based. Similarities of these three factors were tested, and a high similarity among demographic characteristics and grade 12 average were found. Additional analyses were conducted to measure the accuracy of factor analyses models constructed using Spearman and Polychoric correlation matrices. The results indicated that both correlation matrices were  nbiased, with higher variance and higher loadings when the Polychoric correlation matrix was used to construct a factor analysis model for categorical data. / South Africa

No description available.

Current multifactor valuation pricing models use size (measured by market capitalization) of a firm as one factor to determine the value of a security. The problem with current standard models was that none of them could explain the value of a security consistently and accurately based on current factors and in particular the size factor. The purpose of this quantitative study using existing time-series data over a 10-year period from 2006 to 2015 was to examine the impact of size factor on the realized rate of return of financial securities, while controlling for the impact of market rate of return. There are currently many valuation models but there is no 2-factor model or a model that uses a size factor that includes mid-cap sized securities. The research questions examined mid-cap sized securities for the size factor in a 2-factor model to determine the accuracy of predicting financial returns compared to the current standard Fama-French 3-factor model. The main theoretical framework that guided the study was the efficient market hypothesis that postulates that the price of a stock reflects all relevant available information. Data were collected for historical returns of 15 individual firms and portfolios of securities based on size. Multiple regression analysis methodology was used to examine the impact of size factor on the realized rate of return of financial securities, while controlling for the impact of market rate of return in the modified 2-factor model that included mid-caps. The results of the study indicate that size is a statistically significant factor in a 2-factor model that included mid-caps. The positive social impact of this study is that it could provide greater confidence in financial markets by providing a fair and equitable means of investment and flow of capital for a robust economy.

No description available.

Fibrosis is a disease where the normally transitory wound healing response enters a chronic state. Bleomycin and Adenovector models of pulmonary fibrosis have implicated TGF-β1 in this disease. Concern regarding a synergistic combination of TGF-β1 with an adaptive immune response within the Adenovector model prompted its use within mice devoid of T Lymphocytes, Balb/c SCIDs. The lack of an adaptive immune response within these mice did not affect the severity of fibrogenesis, as compared to Balb/c data in a hydroxyproline assay. TGF-β1 is a pluripotent cytokine with key roles in wound healing, immune regulation, and development, making it a dangerous molecule to therapeutically modulate directly. Future strategies will likely focus on downstream fibrotic molecules uninvolved in immune regulation, such as CTGF. While CTGF has been associated with fibrosis and is likely activated by TGF-β1, no conclusive evidence is available within an animal model. TGF-β1 stimulates cells by binding its receptor and signaling through the Smad signal transduction pathway. Smad3 knockout mice were used to examine the regulation of CTGF by TGF-β1, and study its role in pulmonary fibrosis. We show that these mice produce dramatically less CTGF in response to TGF-β1 than littermates expressing Smad3, and they show protection against TGF-β1 induced pulmonary fibrosis, using the Adenovector system. TGF-β1 can alter lung development, and is thought to be a causative agent in Bronchopulmonary Dysplasia, a disease affecting immature lungs. Utilizing the Adenovector system, we developed a neonatal rat model of BPD that closely resembles the human disease, providing researchers with a system to study the disease course. TGF-β1 is part of a family of growth factors, of which TGF-β3 is also a member. What role TGF-β3 plays in pulmonary fibrosis has not been evaluated. To allow future in vivo studies on the effect of TGF-β3 on lung morphology, we constructed a replication deficient Adenovector expressing constitutively active TGF-β3. / Thesis / Master of Science (MSc)

Results of experimental tests are presented for twelve 'Sleeved Column' specimens. All the specimens had an outer sleeve and an inner core, both of rectangular cross section. Outer sleeve was 23 in. long and the inner core was 23.5 in., with axial load applied only to the core. There was a gap between the sleeve and the core for all specimens except for one which had zero gap. The parameters considered for the study were core thickness and gap. It was concluded from the study that the sleeved column system carries substantially more load than the conventional Euler's column. The stiffness of the core and the gap between the sleeve and the core affects the load carrying capacity of sleeved column system significantly. For the same core size, specimens with least gap carried more load when compared to other specimens with larger gaps.

The objective of this study was to determine whether neutrophils play a significant role in anaphylaxis or in the response to the anaphylactic mediator platelet activating factor (PAF) in the rabbit. Vinblastine and anti-neutrophil antibodies were compared as neutrophil depleting agents, and 0.35 mg/kg vinblastine was selected as optimal for efficiency and specificity of depletion. Anaphylaxis was induced in sensitized rabbits by intravenous antigen challenge. Neutrophil depletion to 399 ± 101 cells/mm³ blood (14 ± 3%) did not significantly inhibit the physiologic and hematologic events associated with anaphylaxis except tachycardia. However, vinblastine pretreatment significantly reduced tachycardia and the right ventricular pressure increase and abolished the increase in pulmonary resistance caused by intravenous PAF. We conclude that although neutrophils do not play a significant role in IgE-anaphylaxis, they are important in the PAF-induced increases in right ventricular pressure and pulmonary resistance. PAF may not be a major mediator of these two physiologic alterations in IgE-anaphylaxis.

Interferon regulatory factor 1 (IRF-1), the founding member of IRF family, is a nuclear transcription factor first described as a transcription factor that binds to the upstream region of interferon induced genes following viral infection. In addition, IRF-1 has been reported to be involved in cell growth regulation, induction of apoptosis, immune responses, post-transcriptional modification, and cell transformation by oncogenes. Thus, IRF-1 shows accumulative evidence supporting the theory that IRF-1 functions as a tumour suppressor. However, we still lack the knowledge in the regulation and function behind IRF-1 and many other tumour suppressors due to the lack of synthetic tools that can aid in understanding the mechanism of cancer biology. Here we described the creation of synthetic tools that can be applied to study the role of a transcription factor(s) in cancer biology. Firstly, we described the creation, using recombineering technology, of universal bacterial artificial chromosome (BAC) targeting vector. This targeting vector, carry a cre-conditioned STOP cassette that can be targeted at a desired specific area. The resulted targeting vector can aid the generation of mice models with a conditioned knock-in subtle mutation(s). The resulted cre-conditioned mice models are an essential tool for any outstanding research project in cancer biology. Secondly, we described the development of Flp-In System™ from Invitrogen; the system can ease the generation of isogenic stable mammalian expression cell lines. Using this system, we created two isogenic stable cell lines expressing wild-type IRF-1 and a mutant that abolish IRF-1 DNA binding ability (W11R). Both cell lines were investigated using microarray analysis revealing new IRF-1 target genes. We reported the up-regulation of expected standard interferon regulatory genes such as, interleukin-24 (IL-24) and interferon regulatory factor-2 binding protein-2 (IRF2BP2) and the up-regulation of standard apoptotic genes such as, early growth response-1 (EGR-1) and prostate transmembrane protein, androgen induced-1 (PMEPA1) confirming the role of IRF-1 as a tumour suppressor. However, we also reported the up-regulation of secreted phosphoprotein-1 (SPP1) and SH3 and PX domains-2A (SH3PXD2A) which are matricellular protein produced by cancer cells playing a role in cellular adhesion, invasion, tumour growth progression and metastasis. Thus, we proposed a new biological role of IRF-1 in cellular movement. Thirdly, we described the development of a synthetic stable reporter cell line which can report IRF-1 transcriptional activity; such reporter cell line can be used once large scale screening is needed. The created stable reporter cell line was used to screen a kinase inhibitor library which has revealed C3 as an IRF-1 modifier. The newly identified IRF-1 modifier regulates IRF-1 transcriptional activity by inhibiting platelet-derived growth factor receptor (PDGFR) and/or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase. Finally, we validated the synthetic Flp-In System™ by testing the system using a novel oncoprotein model. We have developed a stable cell line that overexpresses an oncoprotein named Anterior Gradient 2 (AGR-2). We have found that AGR-2 can attenuate IRF-1 protein levels dependent of p53. In addition, AGR-2 has been identified as a cellular survivor factor during unfolding protein response. In conclusion, this study descried the creation and the validation of synthetic tools: synthetic cassette for cre-conditioned mice creation, the Flp-In System™ for isogenic stable cell line creation, and IRF-1 reporter cell line for high throughput screening. All synthetic tools were validated and used to investigate IRF-1, a transcription factor that plays a role in cancer and immune system.

Glycosaminoglycans (GAGs) such as heparin, heparan sulfate (HS), chondroitin sulfate (CS) and dermatan sulfate (DS) are sulfated polysaccharides that exist on animal cell surfaces and in the extracellular matrix. GAGs are important in providing structural and hydrating support and interaction points for proteins of varied functions, for example growth factors and homeostasis regulatory proteins. Hepatocyte Growth Factor (HGF) is a protein growth factor that regulates cell growth, survival, proliferation, chemotaxis, cell morphology, tissue regeneration and angiogenesis. It is involved in embryogenesis, wound healing and many cancers. In this project, the interactions between the GAG binding N and NK -domains of HGF (HGF-N and HGF-NK) and different types of GAGs are characterised with biophysical techniques. GAG oligosaccharides were produced by enzymatic digestion and purified by preparative gel filtration and ion exchange chromatography. Different constructs of HGF were cloned from human cDNA, expressed with the Pichia pastoris expression system, purified to homogeneity and characterised by mass spectrometry and nuclear magnetic resonance (NMR). The dissociation constants between the different HGF protein constructs, different heparin oligosaccharide lengths and the drug Fondaparinux were shown by isothermal calorimetry (ITC) to vary between 0.35 and 9.26 μM. It was found that the entropy contribution was favourable for short oligosaccharides and disfavourable for long oligosaccharides and that the enthalpy contribution was less important for shorter oligosaccharides than for longer oligosaccharides. NMR titrations of CS, DS, heparin, Fondaparinux and sulfated maltose into 15N labelled protein samples showed that all ligands bind to the same HGF-N binding site, but different binding modes exists. The binding site consists of three regions, with the α2-helix and L2 loops playing key roles (residues 70-84). All GAGs also utilise the N-terminal residues 32-42, whereas long heparin oligosaccharides can also utilise a binding region formed mainly by the β2-strand (residues 59-64, 66, 95, 96). The GAG binding mode changes if HGF-N has an N-terminal truncation and the β2- strand residues become more important, emphasising the role of the N-terminal residues in the HGF-GAG interaction. Spin-labelled fully sulfated heparin-derived hexasaccharide was used to determine its binding direction on the HGF-N surface. Affinity chromatography confirmed the importance of the N-terminal residues and that HGF binds to all investigated GAGs. The oligomeric states of HGF-N and HGF-NK were investigated by AUC, gel filtration and ITC. The results suggest that the proteins oligomerise like beads on a string for long oligosaccharides. An HGF-N self-associating dimer with a slow on/off rate was characterised by affinity chromatography, gel filtration and NMR.