3. Electronic Theses and Dissertations (ETDs)

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Prevalence and Molecular Epidemiology of Bordetella pertussis Infection in South Africa
(University of the Witwatersrand, Johannesburg, 2024) Moosa, Fahima; Wolter, Nicole; du Plessis, Mignon
Pertussis remains a public health concern in South Africa, with increases in cases and outbreaks in recent years. We determined the incidence, transmission dynamics, serological attack rates and molecular epidemiology of B. pertussis in South Africa. Data from a longitudinal study enrolling individuals each year in 2016–2018 from two communities were used. Nasopharyngeal swabs were collected from participants twice-weekly and tested by real-time PCR. Serum was collected at 8 time points and tested using the anti-pertussis toxin IgG ELISA kit. Whole genome sequencing was performed on all available cultures (n=32) sourced from three additional surveillance programs between 2015–2019. Data were described and analyzed using univariate and multivariable regression models. Among 1684 participants, the incidence of B. pertussis was 0.21 (95% confidence interval 0.17–0.25) per 100 person-weeks. The mean duration of infection was 12 days (±standard deviation 19.1). Transmission of infection was more likely to occur from male index cases [adjusted odd ratio 12.20 (95%CI 1.57–94.96)], and individuals with ≥7 day’s infection duration [aOR 24.80 (95%CI 2.74–224.30)]. B. pertussis seroprevalence ranged from 1.8% to 5.2% across eight blood draws. The serological attack rate was 5.8% (87/1509), which was similar to the PCR attack rate (6.2%, 94/1509) (p=0.64). PCR-positive individuals aged 5–18 years (vs 19-44, aOR 6.8, 95% CI 1.3-35.1) and with episode duration of ≥7 days (vs <7 days, aOR 13.3, 95% vi CI 3.4-51.1) were more likely to seroconvert. For all individuals that seroconverted, the ≥4-fold rise in anti-PT IgG titer was detected by the next blood draw (mean: 2.9 months (range 3 weeks – 5.9 months). Using genome data, all isolates were identified as the globally-disseminated sequence type 2 and harbored the pertussis toxin promoter ptxP3. The dominant genotype was ptxP3-ptxA1-ptxB2-prn2-fimH2 (31/32, 96.9%), with no pertactin-deficient or other mutations in vaccine antigen genes identified. Within the community, despite a high incidence of B. pertussis, there was an overall low seroprevalence. Our data highlighted that increases in cases in South Africa are not likely due to evolutionary changes in the genome but potentially waning immunity due to the use of acellular vaccines and/or population immunity gaps.
Mapping South African Teachers’ Recognition and Use of ICT Pedagogical Affordances: A Pilot Study of the E-Wits Model
(University of the Witwatersrand, Johannesburg, 2024-03) Mnqonywa, Ndileka; Ndlovu, Nokulunga Sithabile
Among the many challenges facing the effective integration of Information and Communication Technology (ICT) in the classroom, the lack of knowledge on what informs teachers’ pedagogical integration into their teaching practice is one of great concern. With the explosion of digital technology, teachers require explicit guidance in familiarising themselves with their ICT pedagogical approach to not compromise teaching and learning. South African ICT education policies and ICT teacher training initiatives have been implemented to ensure sustainable ICT pedagogical integration in the classroom. Nevertheless, these efforts have been proven ineffective, given the reported low uptake and unproductive use of the affordances brought about by digital tools. This study piloted the e-Wits model of the pedagogical affordances of ICTs to analyse 20 South African teachers’ recognition and use of ICT pedagogical affordances. This pilot study reports on how teachers perceive and use digital tools in their pedagogy. The e-Wits model locates teachers’ pedagogic practice and guides how teachers can integrate these technological affordances. The study used secondary data from secondary school teachers’ interviews collected by three Wits Scholars, Ndlovu (2016), Minty (2020) and Nhlapho (2022), who led research on Gauteng Secondary school teachers using ICT in their pedagogy. Teachers’ interviews were used as research instruments. Thematic analysis techniques were employed to re-analyse the data collected by the three scholars. This qualitative study is grounded on a critical realist paradigm. The findings will provide unambiguous guidelines for teachers to make informed pedagogical decisions to facilitate meaningful integration of ICT affordances. Secondly, the study's findings accentuate the need for teachers to encourage an upturn in knowledge construction, active learner participation and collaboration.
Design of an oral nanotherapeutic galantamine-loaded nanoemulsion composite system for the treatment of Alzheimer’s disease
(University of the Witwatersrand, Johannesburg, 2024) Sithole, Siphesihle Ntuthuko; Mndlovu, Hillary; Choonara, Yahya E.; Somandi, Khonzisizwe
Alzheimer’s disease (AD) is a progressive disorder that degenerates neural pathways in the brain. Alzheimer’s Disease continues to gain interest on new therapeutics with numerous pharmaceutical agents formulated to target the Central Nervous System (CNS) – namely the four acetylcholinesterase inhibitors which include galantamine, rivastigmine, donepezil and memantine. Nanotechnology focuses on the design and synthesis of nanomaterials which are functionally organised with at least one dimension of no more than 100 nm. The use of nanoparticles in medicine can be attributed to the fact that the human body contains numerous biochemical and biological mechanisms that occur at the nanoscale. Nanoparticles provide substantial support for the delivery of various macromolecules. Nanotechnologies are classified into different forms, which include nanotubes, nanofibers, polymeric nanoparticles, nanoemulsions, nanomicelles, and nanoliposomes. Alternative nanocomposites such as nanoemulsions are documented as highly selective delivery methods of dyes, lipophilic dyes and drugs of low molecular weight. Additionally, therapeutic agent-loaded nanoemulsions have revealed enhanced uptake of loaded therapeutic agents in degenerated cells significant to AD. The galantamine-loaded nanoemulsion in this study displayed desirable properties such as nanoparticulate size of 10.54 nm, 11.01 nm, 133.2 nm and 305.1 nm. Additionally, the galantamine-loaded nanoemulsion’s drug release profile, which included a burst release of 66.31% over 6 hours and total controlled release of 68.07% in 24 hours, was also observed in this study. These promising results, as well as those obtained from further evaluations such as thermal stability and chemical interactions during formulation development, support the design of galanatamine-loaded nanoemulsion composite systems that can facilitate the treatment of AD.
Design of a 5-Fluorouracil Copolymeric Nanogel Drug Delivery System for the Treatment of Breast Cancer
(University of the Witwatersrand, Johannesburg, 2024) Ramokgopa, Ofentse Grace; Mndlovu, Hillary; Choonara, Yahya E.; Somandi, Khonzisizwe
The present study investigates the development of a 5-fluorouracil (5-FU) loaded copolymeric nanogel for breast cancer treatment. Breast cancer remains the leading cause of cancer- related mortality among women globally, with current therapies often limited by adverse effects such as nausea, vomiting, fatigue, alopecia, and fertility issues. The standard administration method, intravenous (IV) injection or infusion of 5-FU, typically spans several hours or days, contributing to low patient compliance and potential drug resistance. This study aims to address these challenges by developing a nanogel formulation capable of sustained drug release over a two-week period, thereby reducing administration frequency and enhancing patient compliance. Nano emulsions offer promising potential as alternative cancer therapies due to their biocompatibility and high drug-loading capacity. This research focuses on formulating a nano emulsion into a nanogel with a small particle size to improve absorption in cancer cells and prolong circulation time. The mechanical and physical properties of the formulation were characterized using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and rheological analysis. The study successfully formulated a copolymeric nanogel loaded with 5-FU, achieving an average particle size of 75 nm and a polydispersity index (PDI) of 0.464, confirming an effective nanogel drug delivery system. The drug-loaded nanogel demonstrated a sustained release of 60% over 14 days. FTIR analysis identified key functional groups, confirming the chemical integrity of the formulation, while DSC indicated thermal stability. Rheological studies revealed the nanogel's elastic and flow behaviour, supporting its suitability as a drug delivery system. These findings suggest that the developed 5-FU-loaded copolymeric nanogel represents a promising step toward alternative drug delivery systems for cancer therapy
Business Case: Green-Certified Buildings in South Africa’s Residential Rental Market
(University of the Witwatersrand, Johannesburg, 2025) Roodt, Ilona
In this paper, the characteristics of the Excellence in Design for Greater Efficiencies (EDGE) green building certification system is explained, and the energy and water savings in a portfolio of residential units in the EDGE-certified residential building portfolio in South Africa was investigated. This research analysed the efficiency of energy and water usage, following certification, and the contribution to lowering building running costs and increasing property values was investigated. The research revealed that the portfolio design of EDGE-certified buildings results is, on average, a 42% energy saving and a 54% water saving across the portfolio. The research explores the overall reduction in building operating costs and the impact on property return by considering the payback period of the additional investment. The US Green Building Council indicate operating costs drop by 13%, with a drop of 10.5% in the first year and then an average of 16.9% over five years. The research revealed that overall cost savings are significant, the cost of greening is recouped on average over 6 years and this means that property returns increase. The US Green Building Council indicate that property values increase by between 4%-6% for a study relating to LEED-certified buildings. The research signifies the importance of bringing down energy and water costs to preserve and increase return and value, and this may be catalytic in increasing affordable housing investment and tenant standards of living. Where this activity is at scale within the right policy framework, an overall reduction in emissions may occur.
The Molecular Evolution of C14 Peptidases in Microbial Eukaryotes
(University of the Witwatersrand, Johannesburg, 2024-10) van Niekerk, Karen Elizabeth; Durand, Pierre M.
This thesis examines C14 peptidases within sets of eukaryotic predicted proteins, incorporating genomic and transcriptomic data from a wide range of microbial eukaryotes. It aims to elucidate aspects of this enzyme family that have been neglected in the literature, which focuses on animal caspases and plant and fungal metacaspases. The computational approach adopted here enables an exploration of proteomes across the eukaryote tree of life, presenting a novel perspective on the diversity within the C14 peptidase family. Chapter 1 introduces current knowledge about the eukaryote tree of life (eToL) and paracaspases, metacaspases and caspases (PMCs) of the C14 peptidase family, tracing the history of their discovery and classification. Chapter 1 further examines methods for identifying the taxonomic origins of proteins within a set, aiming to determine which protein nodes may represent ancestral forms. Chapter 2 presents two main conclusions from sequence similarity network (SSN) analyses. The first SSN confirms that C14 peptidases form part of the hub of the caspase-haemoglobinase fold superfamily. Structural analysis across the network reveals the presence of the p10 region of the protein in all examined sequences in the superfamily, in contrast with the view that it is absent in ancestral metacaspases. Analysis of a C14 peptidase SSN identifies bacterial generic PMCs as the likely ancestral versions, thereby challenging the existing paradigm of metacaspases as the most ancient members of the C14 family. In addition, the distribution of paracaspases in eukaryotes is far broader and more ancient than previously thought. Chapter 3 focuses on the region of the C14 peptidase network composed of eukaryote metacaspases. The evidence suggests that both type II and type III metacaspases likely appeared before the evolution of photosynthetic clades, rather than being confined to them. It is also apparent that there are many other metacaspase subtypes that have not been formally identified. Chapter 4 explores the presence of metacaspases in Nucleocytoviricota, a phylum of double-stranded large DNA viruses that infect protist hosts, further demonstrating the utility of SSNs in tracing the evolutionary history of these enzymes. In summary, this thesis contributes to the broader understanding of the C14 peptidase family. It offers insights that invite reconsideration of accepted theories and indicates an expanded diversity and evolutionary context for these enzymes. It underscores the value of integrating sequence similarity networks with structural and functional information for proteomic analysis.
The “Roots” of Early Homo’s Survival: The role of geophyte underground storage organs in the diet of Homo ergaster occupying the Cradle of Humankind during the middle Pleistocene
(University of the Witwatersrand, Johannesburg, 2024-09) Cordeiro, Jeanne; Stratford, Dominic
This research project explored the seasonal availability of geophyte USOs in the Cradle of Humankind throughout the year with the view of evaluating the energetic and nutritional contributions of USOs in the diet of early Homo. The study adopted an Optimal Foraging Theory and Niche Construction Theory approach to determine whether geophyte USOs in the Cradle could have offered feasible sources of energy and nutrition for Homo ergaster occupying the Cradle during the middle Pleistocene. The nutritional and calorific values were considered in context of the major cognitive and morphological adaptations that define the early Homo lineage, namely encephalisation and bipedalism. The average area required to be searched to achieve a portion of the assumed calorific requirement of H.ergaster, from USOs, was enumerated in this study. The findings support the hypothesis that geophyte USOs contributed to the year-round sustenance of H.ergaster, and may have been more important in the diet of early Homo than traditionally believed.
Characterisation of the Platinum Group Minerals in the Ombuku North intrusion peripheral to the Kunene Complex: Insights into its PGE potential
(University of the Witwatersrand, Johannesburg, 2024-03) Mothobekhi, Lorraine Masoko; Milani, Lorenzo; Hayes, Ben
The Kunene AMCG (Anorthosite-Mangerite-Charnockite-Granite) Complex, located in the southern part of Angola and northern part of Namibia, is known as one of the most extensive Proterozoic anorthosite complexes worldwide, with an extent of the area ≥ 18 000 km2, and positioned along the southwest margins of the Congo craton. The mafic-ultramafic intrusions within the vicinity of the Kunene Complex are mineralised with nickel, copper, and platinum group elements (PGEs). The area has not been extensively explored, and only minor exploration work has been conducted to search for magmatic sulphide deposits, particularly nickel deposits. The PGE potential of the mafic-ultramafic intrusions in the area and their potential mineral system has not previously been extensively studied. The available geochemical assay data of the Ombuku North intrusion in northern Namibia was sourced from African Nickel Limited (ANL) and was used in this study to assess its PGE potential and to better understand its potential mineral system. Petrographic work demonstrated Ombuku North intrusion was commonly associated with magmatic sulphides (pentlandite, pyrrhotite, chalcopyrite), formed from a Mono Sulphide Solution, and magnetite. Samples were selected for further detailed platinum group mineral (PGM) investigations on the basis of their PGE contents. Ombuku North is characterised by slightly anomalous PGE values and the available thin sections from Ombuku North with corresponding bulk rock PGE values of >80 parts per billion (ppb) were selected for the identification and characterisation of the PGMs, and for detailed petrographic analyses. In this study, PGM mineral analyses were done using a Tescan Integrated Mineral Analyser (TIMA) which is a fully automated instrument, whereas previous mineral analyses for PGMs in Ombuku North and some of the other mafic-ultramafic intrusions in this region were collected using Scanning Electron Microscopy Energy Dispersive Xray Spectroscopy (SEM-EDS) method, which is only partially automated. TIMA could identify the PGM in the selected samples from Ombuku North. The identified PGMs included sperrylite, michenerite, stibiopalladinite, and vincentite, all associated with serpentinised rocks. The platinum arsenides (sperrylite) are mainly hosted in magnetite and in pyrrhotite. The palladium bismuthotellurides (michenerite and vincentite) and a platinum antimonide (stibiopalladinite) are hosted in pentlandite. The origin of these PGMs can be associated with both magmatic and hydrothermal processes. Magmatic processes are primarily responsible for the initial formation and crystallisation of silicate minerals within the mafic-ultramafic intrusions, including primary magmatic sulphide assemblage. Late hydrothermal processes are related to the alteration of these rocks, where fluids circulated through the rock leading to the formation of secondary minerals such as serpentine, talc, and the redistribution of PGE. Although PGE data are also provided also for other intrusions, this study mainly focused on Ombuku North intrusion due to the limited availability of assay data. We infer that amongst all the mineralised mafic-ultramafic intrusions related to the Kunene Complex, the most prospective for PGE anomalies are the altered ultramafic lithologies at Ombuku North.
Parameter-Efficient Fine-Tuning of Pre-trained Large Language Models for Financial Text Analysis
(University of the Witwatersrand, Johannesburg, 2024-07) Langa, Kelly Kiba; Bau, Hairong; Okuboyejo, Olaperi
The recent advancements in natural language processing (NLP) have been largely fueled by the emergence of large language models (LLMs), which excel in capturing the complex semantic and syntactic structures of natural language. These models have revolutionized NLP tasks by leveraging transfer learning, where pre-trained LLMs are fine-tuned on domain-specific datasets. Financial sentiment analysis poses unique challenges due to the intricate nature of financial language, often necessitating more sophisticated approaches beyond what traditional sentiment analysis methods offer. Fine-tuning LLMs holds potential for improving modeling performance within the financial domain, but the computational expense of the standard full fine-tuning poses a challenge. This study investigates the efficacy of Parameter-Efficient Fine-Tuning (PEFT) methods for fine-tuning LLMs to specific tasks, with a focus on sentiment analysis in the financial domain. Through extensive analysis of PEFT methods, including Low-Rank Adaptation (LoRA), prompt tuning, prefix tuning, and adapters, several critical insights have emerged. The results demonstrate that by employing PEFT methods, performance levels that match or surpass those of full fine-tuning can be achieved. Particularly, adapting the Open Pre-trained Transformers (OPT) model with LoRA achieved the highest modeling performance, with an accuracy of 89%, while utilizing 0.19% of the model’s total parameters. This highlights the high modularity of PEFT methods, necessitating minimal storage sizes for trainable parameters, ranging from 0.1MB to 7MB for the OPT model. Despite slower convergence rates than full fine-tuning, PEFT methods resulted in substantial reductions in Graphics Processing Unit (GPU) memory consumption, with savings of up to 80%. Small-scale fine-tuned LLMs outperformed large-scale general-purpose LLMs such as ChatGPT, emphasizing the importance of domain-specific fine-tuning. Model head fine-tuning fell short compared to PEFT methods, suggesting additional benefits from training more layers. Compared to state-of-the-art non-LLM-based deep learning models, Long Short-Term Memory (LSTM), LLMs demonstrated superiority achieving a 17% increase in accuracy, thereby validating their higher implementation costs.
Development and Reliability Testing of a new Low-Voltage Power Supply for the ATLAS Hadronic Tile-Calorimeter Phase-II Upgrade
(University of the Witwatersrand, Johannesburg, 2024-06) Mckenzie, Ryan Peter; Solans, Carlos; Mellado, Bruce
The Large Hadron Collider (LHC), located at the Conseil Européan pour la Recherche Nucléaire (CERN) also known as the European Laboratory of Particle Physics, is a tworing-superconducting-hadron accelerator and collider located on the Franco-Swiss border. The LHC was successfully commissioned in 2010 for proton–proton collisions and is expected to deliver 500 f b−1 before Long Shutdown three (LS3) that is schedule to commence in 2026. Its successor, the HL-LHC, will provide a levelled instantaneous luminosity of L = 5x 1034 cm−2 s−1 and is projected to deliver an integrated luminosity of more than 4000 fb−1 to its two general purpose detectors, known as A Toroidal LHC Apparatus (ATLAS) and Compact Muon Solenoid (CMS), over a span of 10 years. The main motivation to upgrade the LHC is to fully exploit its physics potential. Through a series of machine and detector upgrades, it is possible to increase the instantaneous luminosity. This could unlock many of the physics processes that are today inaccessible to the LHC because of the lack of statistics. The primary impacts of the HL-LHC on the detector environment are a direct consequence of an increase in delivered instantaneous luminosity. The ATLAS experiment will undergo its Phase-II Upgrade during Long-Shutdown 3 to ensure peak performance during high-luminosity operations. ATLAS is composed of several specialized sub-detectors one of which is the hadronic Tile-Calorimeter (TileCal). The TileCal will undergo numerous upgrades on of which will be to the Low-Voltage (LV) power distribution system that services its on-detector electronics. The on-detector finger Low-Voltage Power supplies form the second stage of the LV system. Their primary functional device is a transformer-coupled buck converter, known as a Brick, which is responsible for converting bulk power to that required by the on-detector electronics. All legacy Bricks will be replaced with a new version that employs several design changes to enable their reliable operation within the HL-LHC detector environment. In this thesis, the development of the Phase-II Upgrade Brick is presented with an emphasis placed on its thermal performance and reliability. A thermal analysis of the proposed upgrade Brick versions is presented with design changes occurring as a result. Due to the design change incorporating a new active component an irradiation campaign is conducted to qualify it for use within the high-luminosity detector environment. A reliability analysis of the Phase-II upgrade Brick is conducted necessitated by the change of many critical components. The quality assurance procedure of the Bricks that is undertaken post-production is presented with particular attention placed on their Burn-in testing.

3. Electronic Theses and Dissertations (ETDs)

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