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 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.Item Envisioning the Future of Fashion: The Creation And Application Of Diverse Body Pose Datasets for Real-World Virtual Try-On(University of the Witwatersrand, Johannesburg, 2024-08) Molefe, Molefe Reabetsoe-Phenyo; Klein, RichardFashion presents an opportunity for research methods to unite machine learning concepts with e-commerce to meet the growing demands of consumers. A recent development in intelligent fashion research envisions how individuals might appear in different clothes based on their selection, a process known as “virtual try-on”. Our research introduces a novel dataset that ensures multi-view consistency, facilitating the effective warping and synthesis of clothing onto individuals from any given perspective or pose. This addresses a significant shortfall in existing datasets, which struggle to recognise various views, thus limiting the versatility of virtual try-on. By fine-tuning state-of-the-art architectures on our dataset, we expand the utility of virtual try-on, making them more adaptable and robust across a diverse range of scenarios. A noteworthy additional advantage of our dataset is its capacity to facilitate 3D scene reconstruction. This capability arises from utilising a sparse collection of images captured from multiple angles, which, while primarily aimed at enriching 2D virtual try-on, inadvertently supports the simulation of 3D environments. This enhancement not only broadens the practical applications of virtual try-on in the real-world but also advances the field by demonstrating a novel application of deep learning within the fashion industry, enabling more realistic and comprehensive virtual try-on experiences. Therefore, our work heralds a novel dataset and approach for virtually synthesising clothing in an accessible way for real-world scenarios.Item Investigating the DNA methylation status of the PXDN and PXDNL promoter regions in OSCC cell lines(University of the Witwatersrand, Johannesburg, 2024-06) Sebastian, Mistral; Mavri-Damelin, DemetraBackground: Oesophageal squamous cell carcinoma (OSCC) is the most prevalent form of oesophageal cancer in South Africa. Aberrant DNA methylation is a well-established epigenetic mechanism involved in various cancers, including OSCC. This study focuses on the DNA methylation status of the peroxidasin (PXDN) and perodixasin like (PXDNL) promoter regions and the expression of PXDN and PXDNL in OSCC cell lines. PXDN consolidates the basement membrane through collagen IV unit oligomerization, influences epithelial-mesenchymal transition and correlates with poor prognosis in various cancers. PXDNL modulates the extracellular matrix (ECM) by antagonising PXDN. Since PXDNL shares domains with PXDN, that allow PXDN to interact with the ECM, it is speculated that PXDNL may possess other ECM modulation roles that require further elucidation. Dysregulated PXDNL expression also correlates with poor cancer prognosis. To date, within the context of South African derived OSCC cell lines, no studies pertaining to the DNA methylation status of the PXDN and PXDNL promoter regions and the expression of PXDN and PXDNL have been carried out. Aim: The aim of this project was to investigate the DNA methylation status of the PXDN and PXDNL promoter regions and observe PXDN and PXDNL expression in the SNO and WHCO5 OSCC cell lines. Methods: PXDN and PXDNL localisation was observed using immunofluorescence microscopy; expression of PXDN and PXDNL was quantified using western blotting and the DNA methylation status of the PXDN and PXDNL promoters was assessed using methylation specific PCR and bisulfite sequencing, respectively. Results: Immunofluorescence microscopy results indicated that both cell lines show varying degrees of PXDN and PXDNL expression. In addition, these results also showed that PXDN and PXDNL localise in the ECM. The western blotting results established that these cell lines express the canonical version of PXDN and possibly a PXDNL isoform (146kDa). Methylation specific PCR has shown that the promoter region of PXDN is differentially methylated across both cell lines. The sequencing results of the bisulfite converted PXDNL promoter region were unsuccessful. Hence, bisulfite sequencing requires further optimisation before the DNA methylation status of the PXDNL promoter region can be determined. Conclusion: This study is the first to show the novel finding that PXDN and PXDNL are expressed in South African derived OSCC cell lines. Within the context of OSCC, further investigation is warranted in order to elucidate the underlying mechanisms that these proteins play a role in. In addition, further study may determine whether a correlation exists between PXDN and PXDNL promoter methylation, protein expression as well as prognosis and whether these aspects should serve as novel markers for diagnosis and therapy. This may subsequently lead to increased OSCC patient survival rates by contributing to early diagnosis of OSCC and efficacious targeted therapeutic intervention.Item Exploring the 95 GeV Excess with Extended Scalar Models(University of the Witwatersrand, Johannesburg, 2024-10) Mulaudzi, Anza-Tshilidzi; Mellado, Bruce; Kumar, MukeshThis thesis focuses on three interconnected studies investigating the presence of an additional scalar particle, S, of mass around mS ≈ 95 GeV. In the initial study, we explore the notion that an SU(2)L triplet scalar, characterised by a hypercharge Y = 0, could be the origin of the observed 95 GeV di-photon (γγ) excesses seen at ATLAS and CMS. By thoroughly examining its properties, particularly the neutral component, and considering a small mixing angle with the Standard Model Higgs boson, we uncover that this scalar naturally exhibits a substantial branching ratio to γγ. Additionally, we find that its Drell-Yan production via pp → W∗ → HH± adequately accounts for the observed excess. The second study examines how recent measurements of the W bosons’s mass by experiments such as ATLAS and CDF affect the theoretical predictions of the Two Higgs Doublet Model augmented with a Singlet Scalar (2HDM+S) model. It addresses how this model’s parameter space is further constrained by the inclusion of vector-like leptons, focusing on their impact on the muon g − 2 measurements. The third study involves exploring the potential discovery of the aforementioned scalar at future electron-positron colliders. Employing several methodologies, including the recoil mass method in e + e − collisions (e + e − → ZS, where Z → µ + µ − and S → b ¯ b), we leverage a Deep Neural Network to refine the differentiation between the Standard Model background and the targeted signal. The outcomes not only reinforce the potential for detecting the proposed scalar, but also enhance the scientific argument for the establishment of future electron-positron colliders like CEPC, FCC-ee or ILC. Together, these studies contribute valuable insights into the evolving landscape of particle physics.Item The Gene Catalogue and Functional Analysis of the Gut Microbiome of Lions in Etosha National Park(University of the Witwatersrand, Johannesburg, 2024-09) Belger, Carl Warner; Hetem, Robyn; Hazelhurst, ScottCharacterising the microbiomes of free-living mammals may aid conservation efforts, yet the gut microbiome of carnivores is underrepresented. This study represents the first description of the gut microbiome of free-living African lions (Panthera leo melanochaita). Faecal samples from 20 lions were collected in Etosha National Park, Namibia and microbial DNA was extracted. Samples were then whole genome sequenced, and classified using MetaPhlAn and Genome Taxonomy Database toolkit. The two most abundant bacterial genera in the lions’ gut microbiomes were Bacteroides (16.9%) and Phocaeicola (16.6%). Microbiome diversity was similar between the sexes and across seasons as assessed through Bray-Curtis dissimilarity and Shannon diversity index. The genus Clostridium_AH was more abundant in male lions (P = 0.007; d.f. = 22), while Aphodousia (P = 0.003; d.f. = 22) was more abundant in females. Lions captured in winter had a high abundance of Plesiomonas relative to those captured in summer (P = 0.008), whereas lions captured in summer a high abundance of Dysosmobacter (P = 0.038; d.f. = 22), Pelethomonas (P = 0.021; d.f. = 22), Metalachnospira (P = 0.033; d.f. = 22) and Clostridium Q (P = 0.012; d.f. = 22) compared to those captured in winter. Following various taxonomic classification approaches, a third of the reads (33.6%) present in the lion gut microbiome remained unclassified. We constructed 272 metagenome assembled genomes, from seven bacterial phyla, representing mostly new species which will contribute to understanding of the carnivore gut microbiome.Item The Taxonomy and Phylogeny of Varanopidae from the Middle Permian of outh Africa(University of the Witwatersrand, Johannesburg, 2024-08) Sibiya, Zoleka; Rubidge, Bruce; Benoit, JulienVaranopidae are the only pelycosaur-grade tetrapods from the Abrahamskraal Formation of the Beaufort Group. Although four varanopid species are described from the middle Permian of South Africa (SA), their validity has been questionable. Moreover, Ford and Benson recently proposed that varanopids belong to the Diapsida rather than Synapsida. Given this taxonomic and phylogenetic turmoil, this study i) describes two newly discovered and well-preserved varanopid specimens from the middle Permian of SA using CT scanning and ii) re-assesses the validity of the four species from the Karoo Basin in the light of new data from these specimens. The phylogeny of the group is addressed by updating two pre-existing cladistics matrices. The two new specimens exhibit a mosaic of features that overlap the diagnoses of several species of SA varanopids. In addition, some diagnostic traits of the four SA varanopid genera and species are found to be variable across ontogeny. For instance, dorsal osteoderms and the extent of ornamentation on the angular bone co-vary with size. It is therefore proposed that all varanopid specimens currently described from the middle Permian of South Africa belong to a single valid species, Heleosaurus scholtzi, with differences between specimens being accounted for by ontogenetic changes. The phylogenetic analysis supports Ford and Benson’s hypothesis but contra the prediction of this hypothesis, no differences in cranial fenestration during ontogeny are observed. Morphological characters preserved in the manus of the newly discovered specimen BP/1/8499 suggest that Heleosaurus was arboreal.Item A systematic study on the use of the sol-gel synthetic method for lithium manganese oxide-based cathode materials(University of the Witwatersrand, Johannesburg, 2024-09) Muntswu, Zwivhuya; Billing, Caren; Ferg, Ernst E.; Billing, David G.This dissertation investigated the synthesis of two lithium manganese oxide-based cathode materials (Li1.03Mn1.97O4 and LiAl0.4Mn1.6O4) using the sol-gel method and probing the phase transitions during the synthesis. The sol-gel synthetic method involved dissolving stoichiometric amounts of lithium nitrate, manganese nitrate hydrate, and citric acid in distilled water forming an aqueous solution. The starting precursor materials were dried at 140 °C which formed a crystalline phase of -Aqua-S-citrato (2-)-manganese(II) with an orthorhombic crystal system and P222 space group. The thermal behaviour of the precursor was explored to understand the effects of calcination/annealing temperatures. Thermal analysis of precursors prepared using nitrate salts with a 1:1 total metal ion to citric acid ratio displayed thermal stability to temperatures higher than 380 °C with the formation of a final metal oxide after 70% mass loss due to the decomposition of the organic and nitrate materials. However, when increasing the concentration of the complexing agent, an increase in material decomposition due to an increase in organic material is seen. The precursor materials prepared with a lower complexing agent concentration result in materials that have thermal instability when exposed to high temperatures. Thermal analysis of Li1.03Mn1.97O4 and LiAl0.4Mn1.6O4 prepared using acetate salts as starting materials shows material decomposition at high temperature of ~600 °C Calcining both undoped and Al-doped nitrate precursors at moderate temperatures (380 °C to 500 °C) resulted in the formation of Li1.03Mn1.97O4 and LiAl0.4Mn1.6O4 with a pure cubic spinel structure and an Fd-3m space group, however, increasing the calcining temperature to 800 °C for the undoped nitrate-based precursor revealed an impurity phase formation relating to dilithium manganese oxide with a monoclinic crystal system. On the other hand, calcining acetate-based precursors at moderate temperatures (380 °C to 500°C) results in metal oxides with low crystallinity compared to metal oxides prepared with nitrate-based precursors. Calcining acetate-based precursors at 800 °C was more favourable since they form the desired metal oxides without any impurities which might imply structural phase stability at high temperatures. The local and average crystallographic structures (via PDF and XRD respectively) of various nitrate-based metal oxides were investigated, where a good agreement between collected data and a calculated structural model revealed the formation of a cubic spinel structure of space group Fd-3m. Li1.03Mn1.97O4 and LiAl0.4Mn1.6O4 metal oxides were achieved from calcining precursors at moderate temperatures of 380 °C and 450 °C. The PDF high r-value signal displays a good fit which confirms to the average structure data information where the r-value signal which correspond to the local structure refinements have a minor discrepancy when fitted with a cubic spinel of space group Fd-3m.