WIReDSpace

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Communities in WIReDSpace

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Now showing 1 - 5 of 19

Recent Submissions

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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, Mandeep
Pancreatic 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.
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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, Elhadi
The 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.
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Envisioning Empowerment: Crafting a Realm of Learning for Visually Impaired Scholars in Mondeor
(University of the Witwatersrand, Johannesburg, 2024) Van Heerden , Stefan
To address the critical need for more inclusive schools in South Africa, this project focussed on designing a school for visually impaired learner in Mondeor, Johannesburg. Currently, only three of these schools exist in Gauteng, which limits the opportunity for children with visual impairment to access quality inclusive education. My proposal aimed to change this, by making education accessible to the visually impaired . According to the White Paper 6 model, children between the ages of 7 and 15 need to be in school. This project placed the building where it would likely have maximum impact in terms of assisting the communities in the chosen area. The location of the school should not dictate who can attend. Anyone who is able to enroll will be able to do so, with preference being given to the visually impaired. The research and the building design aimed to create an inclusive building and to question what an architectural design for the visually impaired would entail. The research delved into experimentation and architectural precedents. The experimentation involved a sensory analysis, during which I spent time blindfolded to get a better sense of what it is like to be blind. The outcomes of these experiments informed the design of the school. The project examined various design precedents for these types of buildings and used the human body as an important design concept. I envisioned the classrooms as the centre points or nodes of the design, similar to the core of a human body, branching out, like limbs, into the different services that the building will offer. The building design aims to engage with the community by having a percentage of its site allocated to public space. This will hopefully ensure that the public can be involved in the inner workings of the school, creating a sense of place and belonging. The building presents opportunities for prototyping a circular economy, thereby enriching the residential context. These combined concepts and ideas strengthen the connections between the research and design development for a building of this nature. I can briefly conclude that the integrated research methods did assist in creating a design proposal that places itself into the context.
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Crafting Communities: Empowering Bezuidenhout Valley Through Construction Workshops: A Blueprint for Self-Sufficiency and Collaboration
(University of the Witwatersrand, Johannesburg, 2024) Maxwell , Ryan
South Africa faces significant challenges in areas such as housing, job security, and skill development and addressing these issues requires a holistic approach. Providing training in construction skills enables the people to build necessary infrastructure like housing, training centers, and social spaces. In addition to this, many communities have spaces that are underutilized or neglected due to various factors such as limited accessibility, safety concerns (demolished buildings, dumping sites, etc), or distance from central areas. Despite these drawbacks, people often find ways to occupy these spaces. Why do they choose to use these areas? The utilization of such spaces typically stems from a lack of alternative options for housing, commerce, or social activities. In the blue-collar northeastern areas of Johannesburg such as Bezuidenhout valley, residents face a multitude of challenges that undermine the quality of life and urban fabric. The Jukskei River, a vital waterway, suffers from pollution, affecting both the environment and public health. Additionally, the community suffers from high unemployment rates and a significant skills shortage. Housing is insufficient, and many existing structures are in a state of disrepair, further compounding social and economic issues. The theories that have influenced my thinking and response are resilience, densification, sustainability, Renewable materials, the Garden city, and hands on teaching. These theories help to understand and view urban areas as dynamic systems and productive environments. “Productivity” in this context includes economic, social, cultural, and environmental dimensions. By addressing these factors, we create a foundation for identifying, planning, and designing appropriate interventions through research and design. The central research theme focuses on the connection between architecture and resilient urban spaces Architecture offers a unique opportunity to address these interconnected issues by empowering the community through construction skills training. By establishing a construction and learning center, residents can gain practical skills while contributing to the development of essential infrastructure, such as housing, training centers, craft spaces for entrepreneurs and social spaces. This approach not only addresses immediate needs but also fosters long-term socio-economic growth
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Examining the role of Braamfontein’s bike lanes: A potential infrastructural asset for waste reclaimers
(University of the Witwatersrand, Johannesburg, 2024) Makena, Pheladi Pearl; Charlton, Sarah
The research sought to address the mobility challenges that street reclaimers encountered and the misuse of bike lanes. Street reclaimers depend on their mobility to earn a sustainable income. Their mobility allows them to work from the early hours of the day, salvaging recyclables to sell to the buy-back centres in the late afternoons. The roads used by reclaimers are a territory for vehicles where street reclaimers are often stigmatised and not viewed as the rightful users of this infrastructure. On the other hand, to encourage cycling, the City of Johannesburg implemented bike lanes that have since been used by vehicles for parking and to bypass traffic, and by informal traders as a trading spots. Bike lanes are a potential infrastructural asset for street reclaimers as they can ease their mobility challenges and include them on the road space. With the concepts of Infrastructure Re-adaptation, Informal Economies and Non- Motorised Transport (NMT), the research discovered that street reclaimers had found ways to move around the roads and that transportation was at the bottom of their hierarchy of necessities. Furthermore, the city implemented bike lanes with reclaimers in mind; however, this form of the cycle lane infrastructure cannot be appropriated by physically modifying the material construction. Finally, the study concluded that with a bottom-up approach including reclaimers and other stakeholders, the city could consider converting bike lanes to NMT lanes, and the routes used by reclaimers can frame targeted interventions for future lanes.