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Sedimenting suspensions exist in a varity of natural phenomena and industrial applications. It is already observed in experiments that the dilute fibre suspensions experience a concentration instability under gravity at low Reynolds numbers. Initially well-mixed suspensions become inhomogeneous and anisotropic due to this instability. This project is focused on the development and validation of numerical models to understand the instability in a dilute fibre suspension by means of the mixture model and the point-particle model. For periodic boundary condition, we use a linear stability analysis to show that inertia and hydro dynamic translational diffusion damp perturbations at long wavelengths and short wavelengths, respectively, leading to a wavenumber selection. However, numerical simulations indicate a weak wavenumber selection even at zero Reynolds number. Numerical simulations also show that the induced flow may either die or saturate on a finite amplitude. The characterof this long time behaviour is dictated by the wavenumber, the presence or absence of the translational diusivity, rotational diffusivity, and the fluid inertia on particle motions. Moreover, the most unstable wavenumber decreases with time and the maximum amplitude increases. The smallest wavenumber obtains the largest amplitude at steady state. For a vessel bounded by sidewalls, the near-wall convection is an upward back flow in the very beginning, due to the combined effects of the steric-depleted layer and a hydrodynamiclly-depleted region near the wall. However, the evolution of the near-wall convection at later times depends on the aspect ratio of the bres, the translational diffusivity and the initial perturbations. The steric-depleted layer in the mixture model can be neglected for large widths. Multiple streamers are obtained due to the sidewalls, implying that the sidewalls can generate a wavelength which is smaller than the channel width. The suspension ends up with a single streamer on one side of the container, consistent with the results of the cases with periodic boundary condition but different from the experimental results. This might be due to the absence of the botton wall in the mixture model. Moreover, the global structure evolution of a suspension is dependent on the width of the vessel and the amplitude ofthe initial perturbations. / <p>QC 20140207</p>

Dissertation submitted in partial compliance with the requirements for the Masters Degree in Technology: Chiropractic, Durban University of Technology, 2010. / The aim of this study was to determine the inter-examiner reliability of motion palpation to detect joint dysfunction in hindfoot and midfoot joints of asymptomatic feet and feet with chronic ankle instability syndrome. The rationale for this study was that motion palpation is a commonly used assessment tool that is used by the chiropractic profession to detect the need for manipulation of the spine and extremities. Also until the reliability of motion palpation is known, other studies using motion palpation as an assessment tool to detect the need for manipulation in the hindfoot and midfoot are questionable. The study was conducted at Durban University of Technology (DUT). Patients that responded to the adverts were then screened via telephonic interview. The researcher performed a case history, physical examination and a foot and ankle regional examination on each patient. Three masters chiropractic students then independently assessed both the symptomatic and asymptomatic feet of each patient and recorded their results. The data was then statistically analysed using SPSS version 15. It was found that the inter-examiner reliability of motion palpation for detecting restrictions in feet with chronic ankle instability syndrome was fair and for detecting instability, there was moderate reliability. In the asymptomatic group the examiners showed to have poor reliability in detecting restrictions and moderate reliability in detecting instability. Inter-examiner reliability was better in the symptomatic group and in this group examiners had more agreement on detecting instability as opposed to restrictions. This study has showed that inter-examiner reliability ranged from poor to moderate in the symptomatic and asymptomatic group with the reliability ranging from poor to moderate. Therefore, one can conclude that motion palpation can be used as an assessment tool to detect joint dysfunction in hindfoot and midfoot joints. However, further studies are warranted to address other subjective and objective measurements such as tenderness and range of motion together with motion palpation.

Statement of Problem Telomere dynamics in the three-dimensional (3D) space of the mammalian nucleus plays an important role in the maintenance of genomic stability. However, the telomere distribution in 3D nuclear space of normal and tumor cells was unknown when the study was initiated. Methods Telomere fluorescence in situ hybridization (FISH) and 3D molecular imaging, deconvolution, and analysis were used to investigate telomere organization in normal, immortalized and tumor cells from mouse and human cell lines, and primary tissues. Results Telomeres are organized in a non-overlapping manner and in a cell-cycle dependant fashion in normal cells. In the late G2 phase of cell cycle, telomeres are assembled into a flattened sphere that is termed the telomeric disk In contrast, the telomeric disk is disrupted in the tumor cells. Moreover, telomeric aggregates (TAs) are found in tumor cells. Conditional c-Myc over-expression induces telomeric aggregation leading to the onset of breakage-bridge-fusion cycles and subsequent chromosomal abnormality. Conclusions Telomeres are distributed in a nonrandom and dynamic fashion in the 3D space of a normal cell. Telomeric aggregates are present in cells with genomic instability such as tumor cells and cells with deregulation of c-Myc. Consequently, TA can be a useful biomarker for research in cancer and other disease processes.

The gene that produces the precursor RNA transcript to the three largest ribosomal RNA molecules (rDNA) is present in multiple copies and organized into gene clusters. They represent 0.5% of the diploid human genome but are critical for cellular viability. The individual genes possess very high levels of sequence identity and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. Our laboratory has developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. In order to determine whether dysregulated recombination is a potential driving force of genomic instability in human cancer, adult patients with either lung or colorectal cancer, and pediatric patients with leukemia were prospectively recruited and assayed. Over half of the adult solid tumors show detectable rDNA rearrangements relative to either surrounding non-tumor tissue or normal peripheral blood. In contrast, there is a greatly reduced frequency of alteration in pediatric leukemia. This finding makes rDNA restructuring one of the most common chromosomal alterations in adult solid tumors, illustrates the dynamic plasticity of the human genome, and may have prognostic or predictive value in disease progression.

A numerical study is performed to model the 2-D axisymmetric turbulent flow of supercritical water flowing upward in vertical pipes with constant wall heat fluxes, using ANSYS CFX v14.5. This study was aimed to use CFD in analyzing supercritical flow instability and heat transfer. Two types of flow instabilities are analyzed and results are compared with 1-D non-linear code solutions. Also, conditions for approximating the thresholds of instabilities based on steady-state results are assessed. It is determined that the results of instability thresholds obtained using the k-ɛ and the SST models are similar. Also the results of CFD and 1-D codes are different mainly due to the difference in the pressure drop predictions. Moreover, approximating the flow instability threshold by the conditions proposed holds true for a CFD solution. Results also indicate that Prt does not have a noticeable effect on the instability threshold for the cases examined.

Statement of Problem Telomere dynamics in the three-dimensional (3D) space of the mammalian nucleus plays an important role in the maintenance of genomic stability. However, the telomere distribution in 3D nuclear space of normal and tumor cells was unknown when the study was initiated. Methods Telomere fluorescence in situ hybridization (FISH) and 3D molecular imaging, deconvolution, and analysis were used to investigate telomere organization in normal, immortalized and tumor cells from mouse and human cell lines, and primary tissues. Results Telomeres are organized in a non-overlapping manner and in a cell-cycle dependant fashion in normal cells. In the late G2 phase of cell cycle, telomeres are assembled into a flattened sphere that is termed the telomeric disk In contrast, the telomeric disk is disrupted in the tumor cells. Moreover, telomeric aggregates (TAs) are found in tumor cells. Conditional c-Myc over-expression induces telomeric aggregation leading to the onset of breakage-bridge-fusion cycles and subsequent chromosomal abnormality. Conclusions Telomeres are distributed in a nonrandom and dynamic fashion in the 3D space of a normal cell. Telomeric aggregates are present in cells with genomic instability such as tumor cells and cells with deregulation of c-Myc. Consequently, TA can be a useful biomarker for research in cancer and other disease processes.

Internal instability of a widely graded cohesionless soil refers to a phenomenon in which its finer particles migrate within the void network of its coarser particles, as a result of seepage flow. Onset of internal instability of a soil is governed by a combination of geometric and hydromechanical constraints. Much concern exists for embankment dams and levees built using soils with a potential for internal instability. Migration of finer particles to a boundary where they can exit, by washing out, may cause erosion or piping failure and, occasionally, induce collapse of these soil structures. There is a need, in professional practice, to better understand the phenomenon and to develop improved methods to evaluate the susceptibility of a soil. A series of permeameter tests was performed on six widely-graded cohesionless materials. The objectives are to assess the geometric indices proposed for evaluation of susceptibility, and examine hydromechanical factors influence the onset of internal instability. A modified slurry mixing technique, with discrete deposition, was found satisfactory for reconstitution of the homogeneous saturated test specimens. The onset of internal instability was founded to be triggered by a combination of effective stress and hydraulic gradient. The finding yields a hydromechanical envelope, unique for a particular gradation shape, at which internal instability initiated. Three commonly used geometric criteria were comprehensively evaluated with reference to these experimental data and also a database compiled from the literature. The relative conservatism of each criterion was examined and a modified semi-empirical geometric rule then proposed based on the capillary tube model. A theoretical framework for plotting the hydromechanical envelope was established based on an extension of the α concept of Skempton and Brogan, and subsequently verified by test data. Finally, a novel unified approach was proposed to assess the onset of internal instability, based on combining geometric and hydromechanical indices of a soil.

The integrity of the genome is critical to organisms and it is affected by many factors. Radiation, for example, poses a serious threat to genome stability of human beings. While physical monitors for radiation hazard are present, the biological consequences of long term exposure to radiation are not well understood. With the opportunity as part of the International Caenorhabditis elegans Experiment-1 flight project, several approaches using C. elegans were taken to measure mutational changes that occurred during the spaceflight. Among these methods, the eT1 balancer system was demonstrated to be well-suited as an integrating biological dosimeter for spaceflight. The dog-1 gene in C. elegans is required to prevent mutations at poly-G/poly-C tracts, and previous work has described that in the absence of DOG-1, small deletions initiate within these tracts, most likely as a consequence of improperly repaired replication blocks. The eT1 balancer system was adapted to investigate the broad mutational spectrum of dog-1 mutants. Using this system, I was able to determine a forward mutation rate of approximately 1 x 10-3, 10 fold higher than spontaneous. Both small deletions as reported previously and unreported large chromosome rearrangements were observed, and most of mutations analyzed are associated with G/C tracts. Thus, I propose that following dog-1-induced replication blocks, repair leads to a wide range of mutational events and chromosomal instabilities, similar to those seen in human cancers. The existence of the G/C tracts in C. elegans creates a fortuitous but perplexing problem. They are hotspots for genome instability and need enzymatic protection. In the genome of C. elegans, approximately 400 G/C tracts exist and are distributed along every chromosome in a non-random pattern. G/C tracts are also over-represented in another Caenorhabditis species, C. briggsae. However, the positions and distribution differ from those in C. elegans. Furthermore, in C. elegans, analysis of SAGE data showed that the position of the G/C tracts correlated with the level of gene expression. Although being a threat to genome stability, the genomic distribution of G/C tracts in C. elegans and their effect on regional transcription levels suggest a role for G/C tracts in chromatin structure.

Exposure of cells to hydrogen peroxide can cause oxidative damage to cellular constituents including lipids, protein, and DNA. At elevated concentrations, hydrogen peroxide can trigger cell death by apoptosis or necrosis. Apoptotic cell death can be prevented by overexpression of the oncoprotein Bcl-2. The exact mechanism by which Bcl-2 blocks cell death is controversial. Some researchers believe that Bcl-2 possesses antioxidant properties that protect cells from apoptosis. The purpose of this thesis was to assess oxidative stress and apoptosis following hydrogen peroxide exposure in Jurkat T cells overexpressing Bcl-2. One of the major objectives was to ascertain whether or not Bcl-2 overexpression elevated the antioxidant capacity of Jurkat T cells to provide protection from oxidant-induced cell death. Hydrogen peroxide treated Jurkat cells became apoptotic at moderate levels of oxidant (25-100 uM H2O2), and necrotic at higher doses (greater than 200 uM H2O2). Bcl-2 overexpression prevented caspase activation and cell death at the apoptotic doses of H2O2, but not the necrotic doses. Caspase inhibition studies demonstrated that Bcl-2 overexpression provided a greater level of resistance from H2O2-induced cell death than the broad-spectrum caspase inhibitor z-VAD.fmk. A systematic study was carried out examining the antioxidant status of Jurkat cells overexpressing Bcl-2. Several Bcl-2 transfectants were utilised for the study, so that any differences seen could be correlated to the level of Bcl-2 expression. Surprisingly, there were no statistically significant differences among the Bcl-2 transfectants for any of the antioxidant enzymes. Jurkat cells overexpressing Bcl-2 exhibited the same level of oxidative damage to lipids and protein in response to H2O2 exposure as the parental Jurkat cells. Interestingly, Jurkat cells overexpressing Bcl-2 continued to grow in culture after H2O2 exposure, despite harboring damage to cellular constituents. Consistent with these results, H2O2 treated Jurkat cells overexpressing Bcl-2, which failed to undergo apoptosis, were more prone to genomic instability. Together, these findings suggest that Bcl-2 overexpression protects Jurkat cells from H2O2-induced cell death by blocking apoptosis. Jurkat cells overexpressing Bcl-2 were no better at detoxifying oxidants and showed the same level of oxidative damage following H2O2 exposure. As a result, the overexpression of Bcl-2 considerably enhanced the mutagenicity of H2O2.