39624 research outputs found
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Evaluation and Application of Tools for mRNA Isoform Detection Using Nanopore Sequencing Data
No full textDissertation submitted in fulfilment of the requirements for the degree Master of Science to the Faculty of Science, School of in Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, 2025Alternative splicing contributes to RNA isoform diversity, enhancing functional complexity in biological systems. Recent advancements in long-read sequencing technologies, notably those by Oxford Nanopore Technologies (ONT), facilitate comprehensive analysis of RNA isoforms through the generation of longer reads capable of capturing full-length transcripts. However, such advancements introduce challenges associated with complex long-read data, particularly in terms of accurate basecalling and robust isoform identification. In this study, we benchmarked two basecalling algorithms, Guppy and Dorado, utilizing real ONT sequencing data, finding that Dorado greatly enhanced read length and quality, thus improving downstream isoform analysis accuracy. Subsequently, we evaluated five isoform identification and quantification tools (Bambu, IsoQuant, FLAIR, StringTie2, and lr-kallisto) using spike-in RNA datasets as a ground truth. To further dissect how sequencing parameters (read length, read accuracy, sequencing depth, and transcript length) impact tool performance, we generated 96 synthetic ONT RNA datasets. We identified distinct strengths and weaknesses for each tool in isoform discovery depending on varying sequencing qualities and provided guidance for selecting the most suitable tool based on specific research questions. Among the evaluated tools, Bambu exhibited superior performance under the specific conditions of our datasets. Applying the optimized workflow, we compared transcriptional profiles of lung and bladder epithelial cells following exposure to IFN-β, an antiviral cytokine. Notably, we discovered that a truncated form of RIG-I, a key receptor detecting dsRNA viruses such as influenza and coronaviruses, is specifically expressed in lung epithelial cells but not in bladder epithelial cells in response to IFN-β. These findings underscore the critical importance of selecting appropriate basecalling algorithms and isoform identification tools tailored to the characteristics of the sequencing data, ultimately enabling the identification of cell-type-specific isoform variations with potential therapeutic implications for viral infections.MMM202
Sustainability and Organisational Performance of South African Small and Medium Enterprises
No full textA research report submitted in fulfillment of the requirements for the Doctor of Philosophy, in the Faculty of Commerce Law and Management, Wits Business School, University of the Witwatersrand, Johannesburg, 2025This study adopted the method of a qualitative integrative literature review to investigate the sustainability and organisational performance (OP) of small and medium enterprises (SMEs) in South Africa (SA). The focus was on enablers to facilitate the attainment and the challenges impeding sustainability and organisational performance. Furthermore, the study examined the phases and steps to incorporate sustainability into organisational performance, as well as the approaches for achieving ecological, social, and economic sustainability within organisations. For the better understanding of the topic and to ensure that it has been consistently and sufficiently covered without missing any aspect of OP and sustainability phenomenon, the study integrated the four OP dimensions, namely financial, operational, market and growth performance, at the same time considering the environmental, social, economic, and cultural pillars of sustainability. The e-resources from the online library of the University of Witwatersrand were used for the selection of appropriate databases. The reading materials included academic articles, journals, conference papers, reports, dissertations, theses, handbooks, and books, and the collection of 5000 works of literature from the management field were transcribed and categorised in a comprehensive fashion to be assessed using content and thematic analysis. Of the 5000 reviewed literature publications, 2 947 (including SA literature) were excluded due to duplication, the size of the firms not mentioned, the incomplete (full version unavailable), outside the scope of interest of SMEs and SA SMEs, and not aligned with the research questions. The remaining 2 053 literature publications were selected for discussion and interpretation; of these 1 625 included SMEs in general and 428 SA SMEs. The comprehensive appendix of the collected literature provides validity and credibility to the findings. Ethical clearance was obtained from Wits Business School to conduct the study and all ethics were adhered to. The study implemented the theory of knowledge to conduct the literature review and contingency theory to build new theories. The findings revealed that the achievements of organisational performance and sustainability of SMEs in general, and particularly those located in South Africa, were enabled and challenged by organisational factors (OFs) or corporate factors (CFs), management factors (MFs), business factors (BFs), entrepreneurial factors (EFs), leadership factors (LFs), modernity factors (MOFs), and sustainable factors (SFs). Sustainable development (SD), sustainable development goals (SDGs), organisational changes (OC), the circular economy iv (CE), lean management (LM), sustainable corporate governance (SCG), corporate sustainable responsibility (CSR) and sustainable supply chain management (SCM), and other related sustainability practices (SPs) were implemented. Some sustainability pillars besides cultural sustainability were integrated and balanced in the OP of SMEs without mentioning the sequential sustainability implementation phases, integration steps and balance approaches. In addition, there is limited literature on sustainability and OP covering the SA context, leaving room for future research The findings of the reviewed literature were built by identifying the gaps in the literature, the construction of an integrated categorical-conceptual framework, the development of a contextual framework, developing novel theories, and business model designs including successful sustainable SMEs’ business performance. Furthermore, most of the reviewed literature was quantitative, therefore, future studies should consider using other research approaches. Further analysis revealed little to no mention of cultural sustainability. Although there is literature covering sustainability in SA SMEs, and OP of SA SMEs, it remains limited. Likewise, there is limited literature covering the implementation of sustainability in OP, as well as sustainability integration into OP, moreover, no published research could be found that covered the approaches to sustainability balance in SA SMEs. The analysis of all the literature reviewed for this study revealed steps to guide sustainability implementation and integration into OP as well as suggesting approaches for balancing sustainability in OPMM202
Regional variability of the impact of cardiometabolic diseases on incident dementia in United States Medicare beneficiaries
No full textThermophoretic particle deposition in a mixed convective bioconvection nanofluid with thermal radiation and chemical reaction over an exponential stretching sheet
No full textSynthesis and evaluation of flexible pyrimethamine analogues as antifolates against drug-resistant malaria
No full textThesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy, to the Faculty of Science, School of Chemistry, University of the Witwatersrand, Johannesburg, 2025In many parts of the world today, malaria still represents a major health crisis, with millions of cases and hundreds of thousands of deaths reported each year. The major malaria causing parasite is Plasmodium falciparum, which accounts for the majority of cases and deaths worldwide. This parasite has shown a remarkable ability to rapidly mutate and develop resistance against initially effective drug molecules. The continued threat of malaria today motivates the development of new molecules which can remain active despite point mutations that arise in the active site of the targeted enzymes. Previous work done by A. Rousseau and colleagues showed that modifying existing class II antifolates, which target the bifunctional parasite enzyme dihydrofolate reductase – thymidylate synthase (DHFR-TS), by adding a flexible four-atom linker allowed for high levels of antiplasmodial activity to be maintained against drug-resistant forms of the parasite. In the present work, molecular modelling techniques were used to optimize the structural elements of flexible pyrimethamine analogues for binding ability against mutant enzymes. The effects of various functional groups around a conserved structure were evaluated, and a library of compounds was selected for synthesis. Numerous flexible pyrimethamine analogues were successfully synthesized making use of partially established experimental procedures, and were submitted for various antiplasmodial assessments. The synthesized compounds showed excellent activity in single enzyme assays, inhibiting drug-resistant PfDHFR enzymes at low nanomolar concentrations. Whole cell assays were also conducted, where a significant decrease in activity was observed, with the most active compounds inhibiting the parasite cells at low micromolar concentrations. These results suggested that while the compounds were effective binders of the target enzyme, they had some pharmacokinetic limitations which prevented them from effectively exhibiting their mode of action inside the cell. A second-generation of analogues was then envisaged, taking inspiration from existing antifolate compounds which are known to have favourable pharmacokinetic properties. Methods for the synthesis of the devised second-generation analogues were developed as part of this work, and the binding ability of the compounds was validated with further molecular modelling studies. We are currently awaiting the results for the biological assessments of the second-generation analogues.MMM202
The Discursive Strategies in the Spoken Narratives of Multilingual Sepitori and Sesotho Speakers
No full textTwo new basal anomodont specimens from the Lower Abrahamskraal Formation (Beaufort Group: Karoo Supergroup) - implications for anomodont phylogeny and palaeoecology
No full textA dissertation submitted in fulfilment of the requirements of Master of Science, to the Faculty of Science, School of Geosciences, University of the Witwatersrand, Johannesburg, 2025Anomodontia is among the most prosperous therapsid clades in terms of abundance and diversity. Their largest subclade, the Dicynodontia, were present from the Middle Permian to the Late Triassic, reaching their maximum diversity during the Late Permian, before the end-Permian extinction event 252 million years ago. Basal anomodonts are known from South Africa, Russia, China, and Brazil. They are comparatively rare, and, as such, the earliest stages of anomodont evolutionary radiation remain obscure. Here, the cranial morphology of two new anomodont specimens from the Eodicynodon Assemblage Zone, lower Beaufort Group of South Africa are described: BP/1/8500 and BP/1/8740. The large size of BP/1/8500 makes it unique among early dicynodonts, and it combines features of both basal anomodonts and dicynodonts. Specimen BP/1/8500 is recovered as the second most basal dicynodont, stemwards to Nyaphulia oelofseni. In contrast, specimen BP/1/8740 is very small, and the large orbit and lack of canines are reminiscent of Patranomodon, Galechirus, and Galepus. A detailed description of this specimen indicates that it is a second specimen of Patranomodon and, most likely, a juvenile. This is supported by the phylogenetic analysis, which recovers it as a sister taxon to the holotype of Patranomodon. In addition, an analysis of body size suggests that anomodont body size has increased gradually over time while diversity decreased. Small-bodied anomodonts dominated before the end-Capitanian crisis, then large bodied anomodonts appeared during the Lopingian and went extinct at the end of the Permian. Anomodont size increased consistently during the Triassic, but the taxonomic diversity was extremely low. This supports that, as for many other tetrapod groups, large body size was a refugium niche for anomodonts as they approached extinction.DSI-NRF National Research Foundation of South AfricaGENUSCentre of Excellence in PalaeosciencesPASTMMM202
A Decision Support Framework for Solar PV System Selection in SMMEs Using a Multi-Objective Optimization by Ratio Analysis Technique
No full textPetrographic, whole-rock geochemical and δ34S isotope characterisation of the Middelvlei Reef in the Witwatersrand Basin
No full textThis dissertation submitted in fulfilment of the degree of Master of Science in Geology, to the Faculty of Science, School of Geosciences, University of the Witwatersrand, Johannesburg, 2025Gold is still one of the greatest sought-after metals in the world. The Witwatersrand Basin in South Africa has historically been a key gold metallogenic province. However, the extensive exploitation of the Mesoarchean Witwatersrand Basin has led to the exhaustion of many of its primary, regionally persistent orebodies known as “reefs”. Consequently, the exploration of secondary composite orebodies within the Witwatersrand Basin has become a necessity. Composite reefs, characterised by multiple auriferous conglomerate beds, present significant opportunities for continued gold recovery in the Witwatersrand Basin. However, their origin and gold content have often been overlooked due to their restricted or localised mineralisation extent and lower gold tenor compared to thin conglomerate beds and goldrich carbon seams. The Middelvlei Reef serves as an exemplary composite reef, that is found at the bottom of the Central Rand Group in the Witwatersrand Basin. The Middelvlei Reef, along with its counterparts such as the Elsburg Reefs, exhibits distinctive features where gold is frequently interlinked with multi-stacked auriferous and pyrite-rich conglomerates. The quartz-pebble conglomerates of the Middelvlei Reef are noted for their exceptional pyrite richness, relatively moderate gold grades (i.e., <5 g/t), and thin, alternating multicycle conglomerates, rendering them a complex subject for gold-bearing formation studies. This research focuses on the morphology and chemical composition of pyrite grains within the Middelvlei Reef to explain the depositional environment through comprehensive trace element chemistry and sulphur isotope (δ34S) analysis. The study identifies various pyrite morphologies based on textural distinctions, classifying them into detrital and authigenic types. Detrital pyrite can be classified as massive, inclusion-bearing (random, planarlaminated, concentrically laminated, and micro-spherical), and coarsely crystalline detrital pyrite. Authigenic pyrite is classified into euhedral/subhedral, overgrowth, infill, aggregates, and pseudo-morphic pyrite. Conventional and advanced analytical techniques such as reflected light optical microscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM-EDS), Tescan Integrated Mineral Analyser (TIMA), electron-probe microanalyses (EPMA), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and virtual secondary ions mass spectrometry (vSIMS) were employed to investigate the in-situ trace element and δ34S composition of pyrite grains. Proxies such as Au, Au/As ratios, Co/Ni ratios, Ni, and Mo/Ni ratios were used to infer the process of gold enrichment in the Middelvlei Reef. Detrital pyrite grains are characterised by low Co/Ni (1.51 ppm) and high Au contents (3.05 ppm). Contrarily, high Co/Ni (29.96 ppm) and low Au (0.15 ppm) concentrations imply authigenic pyrite grains. The elevated Mo/Ni ratios (0.005 ppm) in these pyrite grains indicate a source from felsic to mafic rocks within the granitoid-greenstone belts of the Kaapvaal Craton. Sulphur isotopic analyses from vSIMS reveal a broad range of δ34S values (-15.39 to +38.25 ‰.) in the pyrite grains of the Middelvlei Reef, suggesting multiple sources that include localised sulphurous pools and photochemical reactions. The broad range of high positive (+38.25 ‰) and negative (-15.39 ‰) δ!"S values are attributed to the high amounts of inclusions observed within the respective grains. Clusters of positive δ34S values (-6.32 to +25.27 ‰) observed in detrital pyrite grains imply erosion of sedimentary deposits, whereas low δ34S values (-2.18 to +3.87 ‰) in authigenic pyrite grains point towards metamorphic and hydrothermal fluid sources. These findings suggest that the composite Middelvlei Reef was formed in a combination of high to low-energy braided riverine environments that allowed the accumulation of large sulphide group minerals, which were reworked into auriferous conglomerate channels. Pyrite morphology, chemistry, and isotopic composition indicate that the detrital pyrite grains were generated by a combination of sedimentary and diagenetic processes, while the authigenic pyrite grains recorded fluid mobilisation evidence and multiple re-deposition processes. Detrital pyrite, which is a fingerprint of the composite Middelvlei Reef, was created by erosion and reworking of diagenetic pyrite. This complex process resulted in the accumulation of fine-grained gold within various pyrite grains, alongside other metals like As, Ag, Cu, Ni, Co, and Mo. This study provides insights into the complex depositional and post-depositional processes that have governed gold accumulation in the Middelvlei Reef, in that way laying the groundwork for future exploration and exploitation of similar composite reefs within the Witwatersrand Basin.National Research Foundation (NRF)Centre of Excellence for Integrated Mineral Energy Resource Analysis (CIMERA)MMM202
