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  • Authors: Ainslie, Michelle
  • Date: 2020
  • Subjects: South African fiction (English) -- 21st century
  • Language: English
  • Type: text , Thesis , Masters , MA
  • Identifier: http://hdl.handle.net/10962/140597 , vital:37903
  • Description: This document consists of two (2) parts:Part A: Thesis (Creative Work)Part B: Portfolio.
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  • Date Issued: 2020

Application of machine learning, molecular modelling and structural data mining against antiretroviral drug resistance in HIV-1

  • Authors: Sheik Amamuddy, Olivier Serge André
  • Date: 2020
  • Subjects: Machine learning , Molecules -- Models , Data mining , Neural networks (Computer science) , Antiretroviral agents , Protease inhibitors , Drug resistance , Multidrug resistance , Molecular dynamics , Renin-angiotensin system , HIV (Viruses) -- South Africa , HIV (Viruses) -- Social aspects -- South Africa , South African Natural Compounds Database
  • Language: English
  • Type: text , Thesis , Doctoral , PhD
  • Identifier: http://hdl.handle.net/10962/115964 , vital:34282
  • Description: Millions are affected with the Human Immunodeficiency Virus (HIV) world wide, even though the death toll is on the decline. Antiretrovirals (ARVs), more specifically protease inhibitors have shown tremendous success since their introduction into therapy since the mid 1990’s by slowing down progression to the Acquired Immune Deficiency Syndrome (AIDS). However, Drug Resistance Mutations (DRMs) are constantly selected for due to viral adaptation, making drugs less effective over time. The current challenge is to manage the infection optimally with a limited set of drugs, with differing associated levels of toxicities in the face of a virus that (1) exists as a quasispecies, (2) may transmit acquired DRMs to drug-naive individuals and (3) that can manifest class-wide resistance due to similarities in design. The presence of latent reservoirs, unawareness of infection status, education and various socio-economic factors make the problem even more complex. Adequate timing and choice of drug prescription together with treatment adherence are very important as drug toxicities, drug failure and sub-optimal treatment regimens leave room for further development of drug resistance. While CD4 cell count and the determination of viral load from patients in resource-limited settings are very helpful to track how well a patient’s immune system is able to keep the virus in check, they can be lengthy in determining whether an ARV is effective. Phenosense assay kits answer this problem using viruses engineered to contain the patient sequences and evaluating their growth in the presence of different ARVs, but this can be expensive and too involved for routine checks. As a cheaper and faster alternative, genotypic assays provide similar information from HIV pol sequences obtained from blood samples, inferring ARV efficacy on the basis of drug resistance mutation patterns. However, these are inherently complex and the various methods of in silico prediction, such as Geno2pheno, REGA and Stanford HIVdb do not always agree in every case, even though this gap decreases as the list of resistance mutations is updated. A major gap in HIV treatment is that the information used for predicting drug resistance is mainly computed from data containing an overwhelming majority of B subtype HIV, when these only comprise about 12% of the worldwide HIV infections. In addition to growing evidence that drug resistance is subtype-related, it is intuitive to hypothesize that as subtyping is a phylogenetic classification, the more divergent a subtype is from the strains used in training prediction models, the less their resistance profiles would correlate. For the aforementioned reasons, we used a multi-faceted approach to attack the virus in multiple ways. This research aimed to (1) improve resistance prediction methods by focusing solely on the available subtype, (2) mine structural information pertaining to resistance in order to find any exploitable weak points and increase knowledge of the mechanistic processes of drug resistance in HIV protease. Finally, (3) we screen for protease inhibitors amongst a database of natural compounds [the South African natural compound database (SANCDB)] to find molecules or molecular properties usable to come up with improved inhibition against the drug target. In this work, structural information was mined using the Anisotropic Network Model, Dynamics Cross-Correlation, Perturbation Response Scanning, residue contact network analysis and the radius of gyration. These methods failed to give any resistance-associated patterns in terms of natural movement, internal correlated motions, residue perturbation response, relational behaviour and global compaction respectively. Applications of drug docking, homology-modelling and energy minimization for generating features suitable for machine-learning were not very promising, and rather suggest that the value of binding energies by themselves from Vina may not be very reliable quantitatively. All these failures lead to a refinement that resulted in a highly sensitive statistically-guided network construction and analysis, which leads to key findings in the early dynamics associated with resistance across all PI drugs. The latter experiment unravelled a conserved lateral expansion motion occurring at the flap elbows, and an associated contraction that drives the base of the dimerization domain towards the catalytic site’s floor in the case of drug resistance. Interestingly, we found that despite the conserved movement, bond angles were degenerate. Alongside, 16 Artificial Neural Network models were optimised for HIV proteases and reverse transcriptase inhibitors, with performances on par with Stanford HIVdb. Finally, we prioritised 9 compounds with potential protease inhibitory activity using virtual screening and molecular dynamics (MD) to additionally suggest a promising modification to one of the compounds. This yielded another molecule inhibiting equally well both opened and closed receptor target conformations, whereby each of the compounds had been selected against an array of multi-drug-resistant receptor variants. While a main hurdle was a lack of non-B subtype data, our findings, especially from the statistically-guided network analysis, may extrapolate to a certain extent to them as the level of conservation was very high within subtype B, despite all the present variations. This network construction method lays down a sensitive approach for analysing a pair of alternate phenotypes for which complex patterns prevail, given a sufficient number of experimental units. During the course of research a weighted contact mapping tool was developed to compare renin-angiotensinogen variants and packaged as part of the MD-TASK tool suite. Finally the functionality, compatibility and performance of the MODE-TASK tool were evaluated and confirmed for both Python2.7.x and Python3.x, for the analysis of normals modes from single protein structures and essential modes from MD trajectories. These techniques and tools collectively add onto the conventional means of MD analysis.
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  • Date Issued: 2020

The political ecological economics of coal mining and water resources: a participatory economic valuation approach in Carolina, Mpumalanga

Assessing linkages between local ecological knowledge, HIV/AIDS and the commercialisation of natural resources across Southern Africa

  • Authors: Weyer, Dylan James
  • Date: 2012
  • Subjects: AIDS (Disease) -- Africa, Southern , HIV infections -- Africa, Southern , Natural resources -- Management -- Africa, Southern , Traditional ecological knowledge -- Africa, Southern , Households -- Economic aspects -- Africa, Southern , Poverty -- Environmental aspects -- Africa, Southern , Ecology -- Economic aspects -- Africa, Southern
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:4769 , http://hdl.handle.net/10962/d1007180 , AIDS (Disease) -- Africa, Southern , HIV infections -- Africa, Southern , Natural resources -- Management -- Africa, Southern , Traditional ecological knowledge -- Africa, Southern , Households -- Economic aspects -- Africa, Southern , Poverty -- Environmental aspects -- Africa, Southern , Ecology -- Economic aspects -- Africa, Southern
  • Description: That natural resources (NRs) are important to those experiencing adversity, and, especially, vulnerability associated with HIV/AIDS, is well documented, particularly with respect to food and energy security. What is unclear is where HIV/AIDS ranks in terms of its significance in comparison to other household shocks, the role local ecological knowledge may (LEK) play in households' response to shock, a propos the types of coping strategies that are employed. Consequently, this research aims to bridge the knowledge gap between HIV/AIDS and the degree to which it is contributing to the expansion of NR commercialisation and to explore the unknowns surrounding the influence of LEK on people's choice of coping strategy. A two phase study was designed to provide quantitative rigour with qualitative depth. Phase one was an extensive, rapid survey of NR traders within urban and rural settings in five southern Africa countries. The principle objective was to profile the trade, the livelihoods of those involved and their reasons for entering the trade, to ultimately establish to what degree HIV/AIDS may have been a catalyst for this. Almost one third of the sample entered the trade in response to illness and/or death in their households, with 80% of deaths being of breadwinners. The findings illustrated considerable dependence on the sale of NRs; for almost 60% of the sample it was their household's only source of income. There was evidently increased blurring of the lines between rural and urban NR use with a greater diversity of products being traded in urban areas. Phase two involved in-depth interviews and work with a smaller sample at two sites selected based on the findings from the first phase. It incorporated three groups of households; non-trading, inexperienced trading and experienced trading households. Key areas of focus were household shocks, coping strategies employed in response to these and the role LEK may be playing in the choice of coping strategies. Within a two year period, 95% of households registered at least one shock, of which 80% recorded AIDS-related proxy shocks. Non-trading households were significantly worse-off in this regard, while in the case of non-AIDS proxy shocks, there was no such difference between groups. The most frequently employed coping strategy was the consumption and sale of NRs and was of particular importance when households were faced with AIDS proxy shocks. Trading households emerged as having superior levels of LEK in comparison to non-trading households, even for non-traded NRs, suggesting that prior LEK of NRs opened up opportunities to trade in NR as a coping strategy. Further inspection of the latter group however revealed that the portion of non-trading households who traded on a very ad hoc basis actually had comparable levels of LEK to the trading households. Despite the ad hoc trading households' vulnerable state and their disproportionately high level of AIDS proxy measures, they had at their disposal, sufficient LEK to unlock certain key coping strategies, namely the NR trade. In this sense there are apparent linkages between LEK, HIV/AIDS and the expansion of the commercialisation of NRs.
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  • Date Issued: 2012

Assessing the potential of submaximal extended duration exercise as an adjunct treatment for sub-acute schizophrenic in-patients: a pilot study

  • Authors: Munnik, James Barry
  • Date: 2006
  • Subjects: Aerobic exercises -- Therapeutic use , Schizophrenia , Schizophrenia -- Treatment , Exercise therapy
  • Language: English
  • Type: Thesis , Masters , MA
  • Identifier: vital:3029 , http://hdl.handle.net/10962/d1002538 , Aerobic exercises -- Therapeutic use , Schizophrenia , Schizophrenia -- Treatment , Exercise therapy
  • Description: Research into the therapeutic potential of aerobic exercise has proven fruitful over the past few years; however, no true experimental research undertakings have investigated the psychological benefits of aerobic exercise with schizophrenic semi-acute in-patients. The main objective of this thesis was to seek out evidence for the possibility that aerobic (submaximal long duration) exercise could be considered an adjunct treatment for hospitalised schizophrenic in-patients. In order to accomplish this objective the effects of a 45-minute walking programme, completed three days a week, for five weeks, was investigated. Various areas of mental health were explored in search of evidence of the therapeutic potential of aerobic exercise. These areas included, amongst other things: transfer and discharge rates, improvements in mood levels - Beck Depression Inventory-II (BDI-II; Beck, Steer, and Brown, 1996) Xhosa version; decreasing of anxiety levels (Beck Anxiety Inventory (BAI; Beck and Steer, 1993), Xhosa version); improved Global Assessment of Functioning (GAF; DSM-IV), Scale Scores; and decreases in the number of symptoms patients exhibited. 22 schizophrenic inpatients were randomly selected for this study and randomly assigned to either an aerobic (long duration submaximal) treatment group or (primarily anaerobic) control group. Results revealed that statistical significance could not be found in any of the treatment group's t-test results; despite the treatment group generally bordering on significance more so than the control group. Out of the five variables studied (Positive Symptoms, Negative Symptoms, BAI, BDI-II, and GAF Scale) three variables (Negative Symptoms, BDI-II, and GAF Scale) in the treatment group bordered more on significance than did the control group. Thus three (60 %) out of the five areas studied revealed that the treatment group had more significant results. This suggests an overall impression that the treatment group responded slightly better. The Researcher recommended that aerobic exercise therapy be considered a treatment protocol in psychiatric institutions and offered further suggestions pertaining to the effective implementation of these programmes. Included in these recommendations were motivational strategies and warnings about the possible negative effects of exercise therapy. A supplemental goal of this thesis was to explore all of the previously offered theoretical psychological mechanisms of positive mental change; and to seek out evidence, for or against these forces. Participants were given pre- and post- treatment quantitative interviews; as well as, qualitative posttreatment interviews where their phenomenological responses were analysed to seek out evidence of these mechanisms. Evidence of various causative factors was found and a new theoretical mechanism was proposed in this thesis.
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  • Date Issued: 2006

Investigating the viability of a framework for small scale, easily deployable and extensible hotspot management systems

  • Authors: Thinyane, Mamello P
  • Date: 2006
  • Subjects: Local area networks (Computer networks) , Computer networks -- Management , Computer network architectures , Computer network protocols , Wireless communication systems , XML (Document markup language)
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:4638 , http://hdl.handle.net/10962/d1006553
  • Description: The proliferation of PALs (Public Access Locations) is fuelling the development of new standards, protocols, services, and applications for WLANs (Wireless Local Area Networks). PALs are set up at public locations to meet continually changing, multiservice, multi-protocol user requirements. This research investigates the essential infrastructural requirements that will enable further proliferation of PALs, and consequently facilitate ubiquitous computing. Based on these requirements, an extensible architectural framework for PAL management systems that inherently facilitates the provisioning of multiple services and multiple protocols on PALs is derived. The ensuing framework, which is called Xobogel, is based on the microkernel architectural pattern, and the IPDR (Internet Protocol Data Record) specification. Xobogel takes into consideration and supports the implementation of diverse business models for PALs, in respect of distinct environmental factors. It also facilitates next-generation network service usage accounting through a simple, flexible, and extensible XML based usage record. The framework is subsequently validated for service element extensibility and simplicity through the design, implementation, and experimental deployment of SEHS (Small Extensible Hotspot System), a system based on the framework. The robustness and scalability of the framework is observed to be sufficient for SMME deployment, withstanding the stress testing experiments performed on SEHS. The range of service element and charging modules implemented confirm an acceptable level of flexibility and extensibility within the framework.
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  • Date Issued: 2006

The effect of work-hardening on the physical work capacity of manual labourers within South African industry

  • Authors: Jacka, Karen-Louise
  • Date: 1997
  • Subjects: Human engineering , Industrial accidents -- South Africa , Industrial safety -- South Africa , Musculoskeletal system -- Wounds and injuries
  • Language: English
  • Type: Thesis , Masters , MA
  • Identifier: vital:5165 , http://hdl.handle.net/10962/d1016237
  • Description: South Africa is a labour-intensive industrially developing country. As a result, in excess of 200 000 workers suffer from musculoskeletal injuries in a year. Research is thus essential to develop more effective strategies in the reduction and rehabilitation of occupational musculoskeletal disorders within industry. It was the hypothesis of this study that by improving the physical work capacity of manual labourers, through participation in an occupation specific work-hardening programme, that the ergonomic stress index and therefore the occurrence of musculoskeletal injuries within industry, may be reduced. Twenty-five male Black and Coloured manual labourers volunteered to participate in this study. In addition to in situ task analyses, the subjects participated in cardiovascular and strength assessments in the laboratory, both pre- and post-participation in the ten-week work-hardening programme. The data were statistically analyzed in order to identify any significant • improvements in the workers' physical work capacity, as measured by cardiovascular, strength and perceptual responses, following the period of work-hardening. Two significant reductions were noted in measures of working heart rate together with significant improvements in grip strength and trunk strength tested at a velocity of 60°.sec·1 at the post-conditioning assessments. In conclusion, the ten-week work-hardening programme resulted in nominal improvements in all the cardiovascular measures and significant improvements in the subjects' strength performance. However, industrialists must recognise that this study dealt with only one aspect of reducing the ergonomic stress index at the workplace and realise that, in addition to this focus, it remains essential to design the task to fit the human operator.
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  • Date Issued: 1997

The north gap dyke of the Transkei

  • Authors: Moore, Alan C
  • Date: 1964
  • Subjects: Petrology -- South Africa -- Transkei , Dikes (Geology) -- South Africa -- Transkei , Petrofabric analysis -- South Africa -- Transkei
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:5031 , http://hdl.handle.net/10962/d1007087
  • Description: Field work and mapping with the aid of aerial photographs have shown the north Gap Dyke to be a vertical intrusion 93½ miles long . It extends from a point about 4½ miles south of Cathcart to the coast where it enters the sea about 100 yards north of the Ngadla R lver mouth. It is composed of several rock types including dolerite pegmatite, granophyric dolerite, subophitic dolerite, and it has a more or less central core of mobilized sediment at the western end. The essential minerals of the dolerite types include zoned plagioclase, which is described in some detail, and augite. Less important are hornblende and micropegmatite. Accessories include apatite, ilmenite, magnetite, quartz, actinolite, prehnite, calcite and epidote. Iddingsite (?), saussurite and chlorite occur as alteration products. The mode of origin of the Gap Dyke magma remains an open question: it may have arisen as a result of normal crystal fractionation or as the result of hybridization in depth followed by differentiation.
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  • Date Issued: 1964
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