Faculty of Science (ETDs)
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Item Pricing Interest Rate Derivatives Using The Forward Market Model(University of the Witwatersrand, Johannesburg, 2024-10) Konaite, Tshana Tumelo; Mudavanhu, BlessingThe IBOR are due to be discontinued and their replacements have been chosen to be the overnight rates. This change in the risk-free rate comes with challenges of how the new rates will be modelled and how the products will be priced. In this dissertation, we look to explore the classical short-rates and the new generalized Forward Market Model proposed by Andrei Lyanschenko and Fabio Mercurio in 2019. We seek to utilize this model in pricing interest rate derivatives such as caps and swaptions.Item Metagenome sequencing of the lichen species Flavopunctelia flaventior and Parmotrema tinctorum from Gauteng, South Africa(University of the Witwatersrand, Johannesburg, 2024-06) Katane, Malebogo Dimpho; Botes, Angela; De Maayer, PieterLichens are defined as a mutualistic association between fungi (mycobiont) and an algal and/or cyanobacterial photobiont. Increasing evidence suggests that lichens comprise more diverse microorganisms than initially thought, where lichens represent an interaction between archaea, bacteria, filamentous fungi, green algae, yeasts, and viruses. Not many comprehensive studies have been done of South African lichen species. The present study employed metagenome sequencing to investigate the lichen microbiomes of Flavopunctelia flaventior and Parmotrema tinctorum sampled from Bryanston, Gauteng province, South Africa. Furthermore, the roles played by the members of the lichen microbiome within symbioses were also studied by functionally annotating the assembled metagenomes of the two lichen species. This study sets the groundwork for future studies on South African lichen species. In Chapter 1, an extensive literature review on lichens, their ecology, taxonomy and biology is discussed. Furthermore, it delves into the existence and shape of the microbiome beyond the mycobiont and the photobiont. Additionally, possible roles that the lichen microbiome may play in sustaining the lichen symbiosis is also discussed. In Chapter 2, the metagenomes of two lichen species were sequenced, the quality of the reads were assessed, and taxonomic classification was performed to elucidate the composition of microorganisms associated with each lichen species. Both microbiomes were dominated by bacteria, with limited fungi, viruses, and archaea. The majority of the identified phyla and genera were found to be common between the two lichen species. Similarities in the core microbiome was accounted for by the fact that F. flaventior and P. tinctorum were sampled from the same location and they are both members of the Parmeliaceae family. In Chapter 3, the metagenomic reads were assembled and functionally annotated using various bioinformatics tools. We demonstrate that the members of the lichen microbiome are involved in the cycling of nutrients such as carbon and nitrogen. We also found differences in carbon fixation pathways, which were attributed to the accessory microbiome. Finally, a summary highlights key results and recommendations on future work that could be undertaken to further provide insight into biological pathways essential to sustain the lichen symbiosis.Item Electrocatalytic detection of biomarkers of tuberculosis and cervical cancer(University of the Witwatersrand, Johannesburg, 2024-07) Peteni, Siwaphiwe; Ozoemena, Kenneth IkechukwuThe need for simpler, low cost and efficient diagnostic methods remains a matter of urgency. This has opened numerous streams of research. Electrochemistry is a simple, cost effective and efficient method that has been used for the detection of several diseases such as tuberculosis (TB) and human papilloma virus (HPV). TB has been ranked amongst the most problematic diseases in HIV/AIDS burdened communities, this alone calls for concern. Biomarkers of TB not only indicate mycobacterium infection but can also assist in the early detection of TB which is highly beneficial for the infected person and the health care system. HPV is the causative agent for cervical cancer. Cervical cancer is ranked as the fourth disease that causes mortality amongst women. With that in mind, HPV-16 L1 early detecting means possible early detection of cervical cancer. In this thesis, methyl nicotinate (MN), which is one of TB’s biomarkers was detected in phosphate buffer solution (PBS, pH 6.0) and commercial human serum using cobalt nanoparticles supported on carbon derived from trimesic acid (TMA) (abbreviated as Co-NPs@CTMA) and biphenyldicarboxylic acid (BPDC) abbreviated as Co-NPs@CBPDC) as electrocatalysts. These electrocatalysts were obtained using microwave-assisted metal-organic framework process with TMA and BPDC as ligands. XRD data showed that these electrocatalysts are cobalt nanoparticles with dominant {111} and {200} phase with traces of cobalt oxide (CoO). XPS and Raman data showed that Co-NPs@CBPDC is defect-rich compared to the Co-NPs@CTMA counterpart. BET showed that CoPs@CBPDC has higher surface area and pore size and volume than the Co-NPs@CTMA catalyst. Both electrocatalysts showed reversible cobalt nanoparticle oxidation and reduction reactions, in the absence and in the presence of the MN, thereby allowing for a facile indirect electrochemical detection of this biomarker. The calibration curves showed low limit of detection (LoD) of 0.47 and 0.147 µM for Co-NPs@CTMA and Co-NPs@CBPDC, respectively. The higher performance of the latter is attributed to its enhanced physico-chemical properties compared to the former. Next, HPV-16 L1, which is the conventional high-risk antigen that is present in cervical cancer, was detected using onion-like carbon (OLC) and polyacrylonitrile fibre integrated with OLC (OLC-PAN) as electrode platforms. Two electrode platforms were used; onion-like carbon (OLC) and its polyacrylonitrile (OLC-PAN) composites. Both platforms led to the detection in a wide linear concentration range (1.95 fg/ml to 50 µg/ml), excellent sensitivity (>5.2 µA/log([HPV-16 L1, fg/mL]) and ultra-low detection of ca. 1.0 and 1.4 fg/ml for OLC-PAN and OLC-based immunosensors, respectively. The high specificity of detection was proven by experimenting with an anti-Ovalbumin antibody (anti-Ova) and native Ovalbumin protein (Ova). An immobilized antigenic HPV-16-L1 peptide showed insignificant interaction with anti-OVA in contrast with the excellent interaction with anti-HPV-16 LI antibody. The immunosensors showed satisfactory stability of ~ 3 days of re-usability. The application of the immunosensor as a potential point-of-care diagnostic (PoC) device was investigated with the screen printed carbon electrode which showed the ability to detect ultra-low (~ 0.7 fg/ml) and high (~ 12 µg/ml) concentrations. This study opens the door of opportunity for further investigation with other electrode platforms and realization of PoC diagnostic devicesfor screening and testing of HPV biomarker for cervical cancer.Item Exploring the Structure, Function and Stability of Glutathione Transferases Engineered from Intra- and Inter-class Consensus Sequences: How Forgiving is Nature?(University of the Witwatersrand, Johannesburg, 2024-10) Mulenga, Thabelo; Achilonu, Ikechukwu; Sayed, YasienProtein folding is an enigmatic biochemical process that is foundational to the structural and functional requirements of a cell. The problem of protein folding, in a nutshell, concerns itself with the rate of protein folding as well as the conversion of amino acids from a linear sequence to a fully folded structure. This problem is partly answered by the existence of folding pathways. The folding funnel was conceptualised as a depiction of folding pathways, and it is a framework that illustrates that native proteins naturally favour the lowest energy state, encountering kinetic and thermodynamic barriers as they fold. Consensus protein design, based on this understanding, aims to: (1) enhance stability and (2) navigate the pitfalls of folding by modifying the folding funnel of a protein. This approach can also shed light on the significance of evolutionarily conserved residues. In this study, consensus protein mutants were generated for the Alpha and Mu glutathione transferases (GSTs) classes. The consensus proteins were then benchmarked against the parental proteins that were chosen (hGSTA1-1 and hGSTM1-1). The Alpha consensus mutant had 11 consensus mutations, including a notable M50L mutation, which affects the dynamic behaviour of helices α2 and α9, while the Mu consensus mutant had 13 unique mutations. Protein production and purification showed that the Mu consensus mutant had larger and purer yields. Data from far-UV circular dichroism studies and root-mean-squared-fluctuation (RMSF) from molecular dynamics (MD) simulations showed that the secondary structural components of the Alpha and Mu proteins remained largely the same, although the Alpha consensus mutant displayed a far lower molar residue ellipticity reading than its wildtype counterpart, indicating the disruption of secondary structural elements, likely caused by the M50L mutation. The ANS binding results showed that the M50L mutation in the Alpha consensus protein caused an increase in exposure of the surface area of the H-site, while the Mu consensus protein had a decrease in the solvent accessibility of its H-site. Thermal shift assay results indicated the consensus proteins had increased thermal stability. Enzyme kinetics results showed that the functionality of the proteins was severely diminished in the consensus mutants, particularly the Alpha consensus mutant. MD simulation results showed that there was an overall increase in the rigidity and compactness of the consensus mutant proteins, further affirming the improvement of thermal stability, while signalling the loss in functionality. The results produced herein have the potential to facilitate the proliferation of engineered GSTs for biotechnological applications that require proteins with an increased half-life and greater stability.Item Natural resource use and environmental perceptions in different types of rural villages in Bushbuckridge, South Africa(University of the Witwatersrand, Johannesburg, 2024-09) Mbedzi, Mary Emma; Twine, WayneHouseholds in rural communities in developing countries rely on natural resources that contribute to income generation, food, medicine, cooking energy, and act as livelihood safety nets. Levels of dependency vary between households within communities due to factors such as wealth status and household size. However, less is known about differences in household resource use between communities within an area. Environmental awareness, values, and preferences are shaped by various factors including, local context. Thus, perceptions of the environment and natural resources, and changes in these are likely to vary between communities. This study aimed to compare the levels of natural resource use and environmental perceptions across village types and determine if there is any relationship between the level of natural resource use and environmental perceptions across village types in the Bushbuckridge Local Municipality in the Mpumalanga province, South Africa. Village types were defined and categorised based on their size, socio-economic factors, access to basic services, connectedness, and remoteness. The level of natural resource use was analysed using existing data from a survey of 491 households across 12 villages located in the Agincourt Health and Demographic Surveillance System (AHDSS) site. This included data on the use, collection, buying, and selling of a range of natural resources used locally (e.g., wild foods, firewood, and medicinal plants), annual consumptions, ownership of resources made from natural resources, and livestock (cattle) ownership. The survey included questions on respondents’ perception of the change in the supply of natural resources over the past 5 years (2016-2021) before the survey. Focus group discussions were conducted in 10 of the study villages asking participants their perception of the changes in the environment and the causes thereof, the importance of the natural environment, natural resources used for their daily needs, income generation, their culture, as well as the changes in availability of natural resources and impacts on their livelihoods. The study villages were classified according to a village typology that had been developed for the AHDSS study site, based on factors such as connectedness, access to amenities and services, and the proportion of Mozambican refugee households. ANOVA and Kruskal Wallis tests were used for continual data, while the Chi-squared test was used for categorical data to test for significant differences across village types in the quantitative part of the study. For qualitative, responses of participants from each village were recorded and grouped into village types, and an overall picture of the perception of natural resources that participants used was developed using the focus group schedule. Similarities and differences in natural resources between villages were assessed by grouping widely and less used resources by villages and village types. There was no significant difference (p>0.05) in the mean prevalence of use, collection, buying, and selling of natural resources, or annual consumption of natural resources across villages and village types. Households in better-serviced villages owned more products from natural resources and were to greater extent, likely to own livestock than poorly-serviced villages. As to environmental perceptions, more respondents in the poorly serviced village types (refugee settlements (RS) and underdeveloped communities (UC)) perceived a decrease in the supply of natural resources than better-serviced village types (established communities (EC) and central communities (CC)). Participants in focus group discussions also noted a decrease in the supply of natural resources across all villages and village types. There was a relationship between village types, natural resource use, and perceptions of change in natural resource availability. Established communities correlated with a higher number of resources perceived as decreasing and central communities were associated with higher cattle ownership. Underdeveloped communities and refugee settlements were associated with a higher number of resources used/owned, a higher number of resources used often (more than 4 times a month), and a higher number of resources sold, and buying firewood. Natural resources were more highly used in, better-serviced village types (central communities, and established communities), than in poorly-serviced village types (underdeveloped communities, and refugee settlements), which was unexpected. However, there were quite a few proxies such as the collection and selling of resources, which were used that did not help back up these findings which could explain the unexpected results. Most respondents in remote and poorly-serviced village types perceived a change in the supply of natural resources, the greatest decrease being in the supply of natural resources. This is associated with awareness of the value of the environment and high reliance on natural resources for these poorly-serviced village types. This study suggests that differences exist in resource use patterns between villages, even in the same area. However, village characteristics were not a good predictor of all aspects of resource use. Changes in proxies of resource utilization and re-evaluating the existing village typology would be useful for further studies.Item Evaluating the impact of land use activities in and around Lake Kariba on the presence and levels of anions and cations in the water body(University of the Witwatersrand, Johannesburg, 2024-09) Monyai, Mokgaetji Andelina; Chimuka, Luke; Tutu, Hlanganani; Cukrowska, Ewa; Richards, Heidi L.Huge seas, lakes, and rivers come to mind when we think of surface water. Surface water is vulnerable to water pollution, with consequential repercussions for the well-being of both human and aquatic environments. Furthermore, the diminishing levels of oxygen have a profound effect on the natural ecological equilibrium within river and lake ecosystems. Lake Kariba, situated in the Southern African region, is a vital freshwater ecosystem supporting local communities, wildlife, and regional economies. However, it faces threats from human activities and erratic weather. This study investigated the influence of land use activities in and around Lake Kariba on water composition and the concentration of anions and cations. The research employed a combination of field surveys and laboratory experiments to identify potential sources of ions. Sixty-nine (69) water samples (53 downstream and 16 upstream) were collected during different seasons in October 2021, July 2022 and April 2023. The Ion Chromatography, Inductively Coupled Plasma equipped with Optical Emission and Mass Spectroscopy detectors were used to concentrations of various anions (Fˉ, Clˉ, NO3ˉ, SO4 2ˉ, and PO4 3ˉ) and cations (Ca, K, Mg, Na, Si, Al, Cr, Fe, Mn, As, Cu, Ni, Ti, and Zn) respectively. Acidic water was notably observed upstream in two sampling areas, namely the Malasha and Kanzinze rivers. The Malasha River exhibited pH levels ranging from 3.71 to 4.81, while the Kanzinze River showed a pH of 6.01. The electrical conductivity (EC) for Malasha ranged from 1035 to 1484 µS/cm, whereas for Kanzinze, it measured 878.0 µS/cm. These areas exhibited significantly elevated levels of both anions and cations. In the Kanzinze River, the detected concentrations showed the following descending order: SO4 2ˉ> Clˉ > NO3ˉ> Fˉ> PO4 3ˉ (anions); Ca > Mg > Na > K > Si > Fe > Al > Zn > Cu > Mn > Ni > Cr > Ti > As (cations). Conversely, the Malasha River, exhibited the following order for anions: SO4 2ˉ > Clˉ > NO3 ˉ > Fˉ > PO4 3ˉ, and for cations: Ca > Fe > Mg > Na > Si > K > Al > Mn > Zn > Cr > Cu> Ni > Ti > As. The significant presence of SO4 2- and NO3 - indicates that human activities and agricultural practices in certain areas of Lake Kariba's catchment can have a considerable impact on the lake's water quality. Despite this, the corresponding Water Quality Index (WQI) indicated that the water quality from Kanzinze and Malasha rivers was unsuitable for drinking purposes. The findings revealed variations in ions concentration at different sampling points, with discernible patterns corresponding to specific land use types, such as mining in the upstream that elevated the levels of SO4 2- and some heavy metals and also NO3 - levels in the downstream due to commercial cage fish farming. Statistical analysis showed significant downstream variations (p < 0.05) in water chemistry parameters related to land use, while upstream areas exhibited no significant differences (p > 0.05). Water quality index ranged from 13.1 to 230.0, categorizing water quality from "excellent" to "very poor." The study underscores the complex interplay between land use activities and water chemistry in Lake Kariba, emphasizing downstream impacts. These findings contribute valuable insights for sustainable management and conservation efforts in the region, considering the dynamic nature of the ecosystem and potential threats posed by anthropogenic activities. Continuous monitoring and mitigation strategies are crucial to reserving the ecological balance of Lake Kariba and safeguarding the well-being of its surrounding communities and wildlife.Item Surface water dependencies and activity patterns of mammalian herbivores in South Africa(University of the Witwatersrand, Johannesburg, 2024-10) Padayachy, Janiel; Hetem, Robyn; Strauss, Willem Maartin; Venter, JanAn increase in aridity in Africa may make water availability more variable, thus understanding how animals respond to these conditions is important for future wildlife management and conservation. However, mammalian herbivores with varying water requirements may respond differently to changes in water availability and predation. Using camera trap data, I analysed the spatial distribution relative to surface water sources and the 24-hour activity of 16 mammalian herbivores across 10 sites in South Africa. As expected, water dependent herbivores were generally closer to water, but only at sites where lions were absent. Herbivores with low water requirements were more nocturnal, potentially reducing water required to cool themselves evaporatively when active during the heat of the day. But that nocturnal activity was reduced when lions were present, likely reducing predation risk, increasing water requirements to dissipate heat and forcing herbivores to remain close to water. Nocturnal activity increased with body size in mixed-feeders and grazers, but decreased with body size in browsers, potentially reflecting more time spent foraging by large browsers. Using a novel approach of multistate diel occupancy models I showed that herbivores were generally active during both the day and night, and that the presence of lions impacted occupancy of preferred prey species (blue wildebeest, gemsbok and zebra). Diel occupancy of water-dependent prey (blue wildebeest) was influenced by an interaction between lion presence and distance to water sources. Thus environmental factors as well as physiological and morphological features affected the timing of activity and spatial distribution of several mammalian herbivore species in South African wildlife areas, which should be considered for future research and management of these species.Item Flood Susceptibility Modeling in the uMhlatuzana River Catchment using Computer Vision-Based Deep Learning Techniques(University of the Witwatersrand, Johannesburg, 2024-10) Chirindza, Jonas; Ajoodha, Ritesh; Knight, JasperIn this study, covolutional neural networks (CNN) models are employed for flood susceptibility modeling in the uMhalatuzana River catchment in KwaZulu-Natal, South Africa. The CNN models, including 1D-CNN, 2D-CNN, and 3D-CNN, pro-vide a detailed assessment of flood vulnerability in the region. The models use di- verse spatial information, such as topography, land use, and hydrological features, to estimate the likelihood of flooding in different areas of the catchment. The flood susceptibility maps within the uMhalatuzana River catchment, classified into five risk zones namely, ‘very low’, ‘low’, ‘moderate’, ‘high’ and ‘very high’ susceptibility zone, serve as proactive instruments for risk mitigation and disaster management. The 1D-CNN model displays strong overall performance in flood susceptibility modeling, evident in key metrics such as accuracy, precision, recall, area under curve (AUC) score, and F1-score. The results suggest that the model effectively captures patterns in the input data, emphasizing its potential for flood susceptibility modeling. Moreover, the 2D-CNN model outperforms the 1D-CNN, achieving higher values when evaluated using various performance metrics. Finally, the 3D-CNN model outperformed both the 1D-CNN and 2D-CNN, emphasizing its predictive abilities in flood susceptibility modelling. The flood susceptibility maps produced by the 1D-CNN model, shows that most of the study area exhibits very low flood susceptibility (96.4%), with localized areas of higher susceptibility, particularly in the very high-risk category (2.53%). The 2D CNN model demonstrates a more diverse risk distribution, with a substantial portion having very low susceptibility (74.19%) and significant areas of higher risk, notably in the very high-risk category (10.93%). The 3D-CNN model emphasizes a spatial pattern where a large portion has very low susceptibility (84.10%), but with a concentration of high and very high-risk areas, comprising 12.34% of the total area. Finally, the consistent identification of higher risk susceptibility areas enhances the robustness of the assessments. The models’ high accuracy and detailed risk assessments provide valuable tools for decision-makers, urban planners, and emergency response teams in the uMhalatuzana River catchment. The precision of the models facilitates informed strategies for flood risk management, including targeted interventions such as improved drainage systems and early warning systems.Item The effect of cholesterol depletion on TGF-ß-induced epithelial-mesenchymal transition in pancreatic cancer cells(University of the Witwatersrand, Johannesburg, 2024-06) Breytenbach, Andrea; Kaur, MandeepPancreatic ductal adenocarcinoma (PDAC) is a highly metastatic cancer that relies on the epithelial to mesenchymal transition (EMT) program for its spread. EMT is a cell plasticity program that involves the reorganization of cell structure as cells transition from an epithelial to a mesenchymal phenotype. The dysregulated cholesterol metabolism resulting from metabolic reprogramming in PDAC is thought to play a role in EMT by affecting EMT-related signalling pathways. However, no publication has yet investigated the impact of EMT on cholesterol content in PDAC. To shed light on these dynamics, EMT was induced in PANC-1 cells using TGF-β1, thereafter the effect of cholesterol-depleting agents (KS-01 and methyl-β-cyclodextrin) alone or in combination with chemotherapeutic agents (Gemcitabine (GEM) and 5-Fluorouracil (5-FU)) on cholesterol content, EMT state, drug resistance, and invasion were investigated. Our results showed that mesenchymal cells rely on reduced membrane cholesterol levels, synthesis, and uptake, while storing more cholesterol and promoting efflux. EMT also promoted drug resistance via upregulation of ABCB1 expression and reduced hENT1 expression. Targeting cholesterol using cyclodextrins promoted a cholesterol compensatory mechanism, leading to a hybrid EMT state, drug resistance, and metastatic potential. Treating mesenchymal PANC-1 cells with GEM or 5-FU monotherapies were seen to promote EMT-transcription factors, as well as promote cholesterol efflux, synthesis, and import, an unexpected result as these chemotherapeutic agents are not known to affect cholesterol. When GEM was combined with KS-01, drug resistance, invasion, EMT-transcription factors, vimentin, and E-cadherin was promoted indicating the promotion of a hybrid EMT state. Interestingly however, combining KS-01 with 5-FU resulted in an interplay that was seen to mitigate the EMT-promoting effects typically associated with cholesterol depletion alone. The exact mechanism linking the cholesterol compensatory mechanism to EMT remains complex and unknown. Based on work presented in this dissertation, it is proposed that targeting cellular cholesterol should be continued to be investigated, particularly in understanding the repercussions of the use of cholesterol depleting agents for the treatment of other disorders in patients with PDAC.Item Modelling and analysis of COVID-19 outspread at micro-levels using spatial autocorrelation: Case of eThekwini(University of the Witwatersrand, Johannesburg, 2024-09) Ngubane, Samukelisiwe; Chimhamhiwa, Dorman; Adam, ElhadiThe alarming effects of the COVID-19 pandemic on different socio-economic spheres have been felt across the globe. These destructive effects have prompted plenty of research to understand and control the coronavirus pandemic. Notably, one strategic method of mitigating the effects of the coronavirus epidemic has been the utilisation of spatial and geostatistical models to gain insights into the potential predictors of the prevalence of the coronavirus. Considering the above, it was the aim of this study to explore the use of advanced geospatial modelling and analysis techniques, including Moran’s I, spatial error models, spatial lag models, MGWR, and GWR for analysing and modelling the settlement level determining factors of COVID-19 incidence within the eThekwini Metro to inform effectual micro-level planning. Notably, the lack of micro-level modelling of COVID-19 prevalence predictors also motivated the undertaking of this study. To the above aim, the objectives of the research were to utilise spatial autocorrelation to map the granular level COVID-19 spatial distribution over the 3rd wave in the eThekwini Metro, compare the applicability of global and local models in analysing and modelling micro-level COVID-19 incidence, analyse the spatial dependence of the occurrence of COVID-19 on local level variables through Moran’s I and to spatially model the effects of significant local-level determinants on COVID-19. The incidence of COVID-19 cases for the 3rd wave, which was from the 2nd of May 2021 to the 11th of September 2021, was analysed and modelled. The Moran’s I result illustrated that COVID-19 incidence within the eThekwini settlement places had a positive spatial autocorrelation, with a Moran’s I value of 0.14 and a p-value of 0.00. Also, the MGWR model's local R2 value was greater (72.5%) as compared to the other models. Moreover, economic wellness score, the sum of TB cases and population density came out as the significant determining factors of settlement level incidence of COVID-19. This research report offers a great foundation for gaining insights into the applicability of advanced geospatial models in guiding targeted COVID-19 interventions at lower levels.