γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter and is of great interest to the magnetic resonance spectroscopy (MRS) community due to its role in several neurological diseases and disorders. Since GABA acquisition without macromolecule contamination requires long scan times and strongly depends on magnetic field (B0) stability, it is highly susceptible to motion and B0 inhomogeneity. In this work, a pair of three-dimensional (3D) echo planar imaging (EPI) volumetric navigators (vNav) with different echo times, were inserted in MEGA-SPECIAL to perform prospective correction for changes in the subject's head position and orientation, as well as changes in B0. The navigators do not increase acquisition time and have negligible effect on the GABA signal. The motion estimates are obtained by registering the first of the pairs of successive vNav volume images to the first volume image. The 3D field maps are calculated through complex division of the pair of vNav contrasts and are used for estimating zero- and first-order shim changes in the volume of interest (VOI). The efficacy of the vNav MEGA-SPECIAL sequence was demonstrated in-vitro and in vivo. Without motion and shim correction, spectral distortions and increases in spectral fitting error, linewidth and GABA concentration relative to creatine were observed in the presence of motion. The navigated sequence yielded high spectral quality despite significant subject motion. Using the volumetric navigated MEGA-SPECIAL sequence, the reproducibility of GABA measurements over a 40 minute period was investigated in two regions, the anterior cingulate (ACC) and medial parietal (PAR) cortices, and compared for different analysis packages, namely LCModel, jMRUI and GANNET. LCModel analysis yielded the most reproducible results, followed by jMRUI and GANNET. GABA levels in ACC were unchanged over time, while GABA levels in PAR were significantly lower for the second measurement. In ACC, GABA levels did not differ between males and females. In contrast, males had higher GABA levels in PAR. This gender difference was, however, only present in the first acquisition. Only in males did GABA levels in PAR decrease over time. These results demonstrate that gender differences are regional, and that GABA levels may fluctuate differently in different regions and sexes.

Generalised osteoarthritis (OA) is a common disorder of the joints which can lead to pain and disability. Identification of the determinant gene(s) is limited in part by the lack of Mendelian inheritance in most forms of the disorder, the combination of genetic and environmental influences and the late development of the condition. An approach to the investigation of the aetiology of OA would be to take advantage of the monogenic basis of inherited skeletal dysplasias in which OA is a major component. For this reason, the molecular genetic basis of the epiphyseal dysplasias, which encompass a spectrum of phenotypes ranging from mild to severe skeletal involvement, is addressed in this thesis. Familial skeletal disorders in South Africa in which OA is a major feature were identified and investigated using intragenic and closely linked microsatellite markers in order to determine linkage to candidate genes. Mutational analysis was undertaken to identify the genetic defect.

Includes bibliographical references. / Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by a pathogenic expansion of a CAG repeat within the ataxin 7 gene, resulting in an expanded polyglutamine tract in the ATXN7 protein. SCA7 patients suffer from selective degeneration of cerebellar Purkinje neurons and retinal photoreceptors, which leads to the development of various neurological symptoms, and blindness. SCA7 is considered to be a relatively rare disease, but South Africa has an increased prevalence of the SCA7 due to a founder effect within the black African population. In this study, three distinct but complementary approaches were taken to investigate SCA7 in South Africa, with the aim of estimating the prevalence of the disease, developing improved approaches for molecular diagnostic testing, and establishing a model for in vitro studies of pathogenesis.

Includes abstract. / Includes bibliographical references (leaves 102-131). / T-box factors play crucial roles in embryogenesis and mutations in T-box factor genes have been implicated in multiple human disorders. In addition, an increasing body of evidence implicates the T-box family in cell cycle regulation and in cancer...The aim of this study was therefore to address this question by establishing TBX2 over-expression and knockdown cell culture models. The results show that TBX2 does indeed contribute directly to the oncogenic process and further reveals a novel mechanism by which it contributes to tumourigenesis.

Bibliography: leaves 200-204.

Includes abstract. / Includes bibliographical references. / The primary aim of the thesis was to investigate associations between TNFA (TNFA-308 G>A and -238 G>A) and IL-6 (-174 G>C, IVS3+281 G>T, IVS4+869 A>G) sequence variants and obesity and serum lipid concentrations in black and white SA women. This included identifying sequence variants in the IL-6 gene with a reported high heterozygosity in both the white and black SA populations (rs1554606 and sr2069845). Dietary intake data of adequate reporters was then included in the analysis to investigate whether dietary fatty acid intake modulated the interactions between the TNFA and IL-6 SNPs (TNFA -308 G>A and -238 G>A & IL-6 -174 G>C, IVS3+281 G>T, IVS4+869 A>G) and obesity, measures of adiposity and serum lipid concentrations, and whether interactions identified differed between black and white women.

Bibliography: leaves 240-285.

Includes abstract. / Includes bibliographical references (p. 291-303). / Various models of viscoelasticity exist based on continuum mechanics. In this work a statistical mechanical approach is taken to derive a new isotropic, hyperelastic, viscoelastic, incompressible constitutive equation for polymers. The result has been achieved by generating a novel physics for the microscopic behaviour of polymers. A vocabulary has been created to facilitate the physics. A new differential equation describing polymer behaviour is derived based on the mathematical description of the physics.

[T]he overall aim of this thesis was to investigate the ethnic-specific role of inflammation in obesity and related metabolic risk factors associated with T2DM and CVD in apparently healthy black and white premenopausal South African women.

Bibliography: leaves 176-189. / The description of biornechanical events measured during manual materials handling (MMH) activities has been a major focus for ergonomists attempting to understand the relationships between performance factors and injury mechanisms. Pulling exertions, while being frequently observed in occupational settings, requires more attention from researchers. The purpose of this work was to elucidate the influences of task-simulated factors upon subject performance while exerting pull forces within a stationary workstation.