Azadipyrromethenes for applications in photodynamic antimicrobial chemotherapy, photodynamic therapy and optical limiting
- Authors: Dubazana, Nadine
- Date: 2020
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Staphylococcus aureus , Nonlinear optics , Azadipyrromethenes , BODIPY
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166150 , vital:41333
- Description: Azadipyrromethenes, azaBODIPYs and zinc azadipyrromethene complexes were prepared and characterised to examine the effect on their photophysical properties of incorporating phenyl groups at the 1,3,5,7-positions with electron-donating and withdrawing groups at the para-positions. To enhance their ability to generate singlet oxygen, appropriate structural modifications were made through the addition of a Zn(II) ion or halogenation at the 2,6 positions. In vitro photodynamic therapy (PDT) studies targeting MCF-7 human breast cancer cells were carried out. To evaluate and understand the effectiveness of the dyes as photosensitisers, cellular uptake, phototoxicity and the half-maximal inhibitory concentration (IC50) values were analysed. Photodynamic antimicrobial chemotherapy (PACT) studies were also carried out to study the effectiveness of the dyes against Staphylococcus aureus (S. aureus). Dyes with donor-π-acceptor (D-π-A) properties were synthesised and tested against the second harmonic of the Nd:YAG laser in optical limiting (OL) studies. The second-order hyperpolarisability, third-order susceptibility and nonlinear absorption coefficient values were determined. The results suggest that 1,3,5,7-azaBODIPY dyes may be less suitable for use in this context than analogous D-π-A 3,5-distyrylBODIPY dyes. Molecular modelling was carried out to identify the structure-property relationships of the synthesised dyes by analysing trends in the energies of the frontier molecular orbitals (MOs) and spectroscopic properties.
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Barriers to, and enablers of urban tree planting in low-cost housing areas: lessons from participatory learning processes in South Africa
- Authors: Gwedla, Nanamhla
- Date: 2020
- Subjects: Urban ecology (Sociology) -- South Africa -- Eastern Cape , Tree planting -- South Africa -- Eastern Cape , Trees in cities -- South Africa -- Eastern Cape , Urban forestry -- Law and legislation -- South Africa -- Eastern Cape , Low-income housing -- South Africa -- Eastern Cape , Cultural Historical Activity Theory (CHAT)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/167065 , vital:41434
- Description: The recent pronouncement of low-cost housing areas as sustainable human settlements came with an expectation for their development in line with Sustainable Development Goal (SDG) 11. Unfortunately, the historical legacy and various socio-economic, socio-political, and socio-cultural dynamics characteristic of these areas have proven it challenging for them to conform to all requirements of urban sustainability, as evidenced in part by the virtual lack of greenspaces and urban trees. Through a three-tier inquiry of urban tree planting in low-cost housing areas using inductive and deductive mixed methods approaches, the aim of this research was to investigate the barriers to, and enablers of, tree planting in low-cost housing areas, and explore participatory learning opportunities to address the challenges and enhance the enablers. In the first segment, a participatory urban forest governance conceptual framing lens was used to situate the various actors in the development of the low-cost housing area urban forest and the dynamics of their involvement in that regard. Inquiry focused on an overview of tree planting across South Africa using key informant interviews, observations and document analysis. Secondly, distribution of trees, and barriers and enablers of tree planting in selected low-cost housing areas in the Eastern Cape province using household surveys, observations, key informant interviews and document analysis were investigated. Finally, drawing on interventionist methodology and adoption of Cultural-Historical Activity Theory (CHAT), the third segment tested scenarios of tree planting in three different small towns through focus group discussions and knowledge-sharing awareness events about trees and tree planting using an activity systems approach. Findings from the first segment ascertain the national Department of Environment, Forestry and Fisheries (DEFF) as the custodian of forestry, and by extension urban forestry in South Africa. Municipalities are tasked with implementing greening plans and strategies for public space planting, while private businesses collaborate with entities to contribute to tree-planting as part of their Corporate Social Responsibility (CSR). Civil society, including residents and Non-Governmental Organizations (NGOs) also contribute, especially for private space planting. However, there are currently very few initiatives implemented in low-cost housing areas. An assessment of ten tree planting initiatives revealed that the DEFF is the most common partner and stakeholder, and normally provides resources such as funding and trees. Most programs reported having undertaken community engagement before and during the tree planting. The general outcomes of these initiatives were centred on the survival rate of trees, job creation, and development of parks and gardens. Findings from the first part of the second segment, conducted in eight small-medium sized towns in the Eastern Cape, revealed a general lack of trees along streets of both the newly developed and old low-cost housing areas. In the private spaces, most households (52 %) reported having at least one tree in their yard, with households in the older suburbs (60 %) reporting more trees than the newer ones (44 %). Most of these trees (66 %) had been planted as opposed to natural regeneration. Previous participation in urban tree planting programs was low, but 75 % of residents expressed willingness to participate in the future. Municipal officials from these towns corroborated that they do not host tree planting events or initiatives, which was demonstrated by the limited incorporation of urban forestry and urban greening in municipal Integrated Development Plans (IDP). In the second part of the second segment, three groupings of barriers and enablers into biophysical, social, and resources revealed that the most mentioned barriers for the private space were resource barriers. The most prominent barriers were limited space in people’s yards, insufficient funds for tree purchases and associated resources, the lack of equipment, and damage to planted trees. Private space enablers of tree planting suggested include the availability of funds, allocation of space, and changes in attitudes towards trees. According to residents, the most prominent barriers to public space planting include the perceived incompetence of municipalities, limited space on the street, insufficient funds for tree planting programmes, damage to trees in public spaces, crime associated with street trees, and politics. Additionally, municipal officials reported that their efforts to plant trees were hindered by lack of communication and coordination between municipal departments. Residents suggested that enlisting the skills of residents for tree planting, engaging in education and awareness initiatives about trees and tree planting, and changing attitudes towards trees could enable tree planting. Municipal officials opined that education and awareness, revisions to and implementation of Environmental Management Plans, and inter-departmental collaborations and partnerships could improve the prospects for public space planting. Drawing on key findings from the second segment, an intervention to involve communities in tree planting using a case study approach in three towns ensued. Here an activity systems analysis of participatory tree planting initiatives was used. Findings revealed an array of multi-activity systems with multiple and partially overlapping objectives related to tree planting. Residents demonstrated that, with support, they can champion urban tree planting for their suburbs. However, contradictions and tensions within and between various activity systems emerged, creating opportunities for the expansive transformation of an activity that was previously not a priority. This study highlights the current distribution of power and resources in the governance system of the urban forest, ascertains the spatial heterogeneity of urban trees in areas of a similar socio-economic context, and provides lessons for best-practice in tree planting that involves multiple actors. It provides in-depth insights into what constrains tree planting, and highlights the importance of residents in the governance system of urban forests and how this can constrain or advance tree planting. Further research in participatory urban forest governance for a developing country, low-income context could utilize an expansive learning platform as this will provide first-hand experiences into learning what is not yet there, and provide communities with the opportunities to explore and devise localized solutions to the lack of trees in their residential areas.
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Bayesian accelerated life tests for the Weibull distribution under non-informative priors
- Authors: Mostert, Philip
- Date: 2020
- Subjects: Accelerated life testing -- Statistical methods , Accelerated life testing -- Mathematical models , Failure time data analysis , Bayesian statistical decision theory , Monte Carlo method , Weibull distribution
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/172181 , vital:42173
- Description: In a competitive world where products are designed to last for long periods of time, obtaining time-to-failure data is both difficult and costly. Hence for products with high reliability, accelerated life testing is required to obtain relevant life-data quickly. This is done by placing the products under higher-than-use stress levels, thereby causing the products to fail prematurely. Part of the analysis of accelerated life-data requires a life distribution that describes the lifetime of a product at a given stress level and a life-stress relationship – which is some function that describes the way in which the life distribution changes across different stress levels. In this thesis it is assumed that the underlying life distribution is the wellknown Weibull distribution, with shape parameter constant over all stress levels and scale parameter as a log-linear function of stress. The primary objective of this thesis is to obtain estimates from Bayesian analysis, and this thesis considers five types of non-informative prior distributions: Jeffreys’ prior, reference priors, maximal data information prior, uniform prior and probability matching priors. Since the associated posterior distribution under all the derived non-informative priors are of an unknown form, the propriety of the posterior distributions is assessed to ensure admissible results. For comparison purposes, estimates obtained via the method of maximum likelihood are also considered. Finding these estimates requires solving non-linear equations, hence the Newton-Raphson algorithm is used to obtain estimates. A simulation study based on the time-to-failure of accelerated data is conducted to compare results between maximum likelihood and Bayesian estimates. As a result of the Bayesian posterior distributions being analytically intractable, two methods to obtain Bayesian estimates are considered: Markov chain Monte Carlo methods and Lindley’s approximation technique. In the simulation study the posterior means and the root mean squared error values of the estimates under the symmetric squared error loss function and the two asymmetric loss functions: the LINEX loss function and general entropy loss function, are considered. Furthermore the coverage rates for the Bayesian Markov chain Monte Carlo and maximum likelihood estimates are found, and are compared by their average interval lengths. A case study using a dataset based on accelerated time-to-failure of an insulating fluid is considered. The fit of these data for the Weibull distribution is studied and is compared to that of other popular life distributions. A full simulation study is conducted to illustrate convergence of the proper posterior distributions. Both maximum likelihood and Bayesian estimates are found for these data. The deviance information criterion is used to compare Bayesian estimates between the prior distributions. The case study is concluded by finding reliability estimates of the data at use-stress levels.
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BEd foundation phase fourth year student teachers’ self-efficacy beliefs towards teaching mathematics and the self-reported factors that influence these self-efficacy beliefs
- Authors: Harrison, Chloe
- Date: 2020
- Subjects: Mathematics -- Study and teaching (Elementary) -- South Africa , Mathematics teachers -- Training of -- South Africa , Educational evaluation -- South Africa , Student teachers -- Training of -- South Africa , Student teachers -- Rating of -- South Africa , Social cognitive theory , Self-efficacy
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/147004 , vital:38584
- Description: The underperformance of mathematics teaching and learning is a pressing concern in South Africa. Many foundation phase in-service teachers show inadequate mathematics content knowledge which creates barriers to their learners acquiring adequate mathematics skills. Teacher training programmes offer a key opportunity to improve the instructional practices of teachers at foundation phase level. In order to improve the teaching skills of in-service teachers, one focus must be on teacher training programmes. Unfortunately, there are many foundation phase student teachers who are leaving the profession within the first few years of teaching reportedly due to low levels of motivation. This research investigates the self-efficacy beliefs of pre-service student teachers. It also focuses on foundation phase student teachers as they experience significant challenges to their self-efficacy beliefs in mathematics and mathematics teaching. Self-efficacy is the key theory of the study. It stems from Bandura’s social cognitive theory and is an individual’s judgments about their capabilities, skills and perceived performance. This qualitative research adopts an interpretivist approach which seeks to identify Bed foundation phase fourth year student teachers’ self-efficacy beliefs towards teaching mathematics and the self-reported factors influencing such beliefs. This research found that BEd foundation phase fourth year student teachers have low self-efficacy beliefs towards teaching mathematics. The purpose of this research is to raise awareness of the BEd student teachers’ low self-efficacy beliefs towards teaching mathematics. The results from this research will provide a platform for future intervention research, as well as potentially influencing student teacher training programmes.
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Between nationalism and transnationalism: entanglements of history, individual narrative, and memory in diaspora spaces in selected transnational fiction
- Authors: Bosman, Sean James
- Date: 2020
- Subjects: Literature and transnationalism , Gurnah, Abdulrazak, 1948- , Gurnah, Abdulrazak, 1948- -- By the sea , Gurnah, Abdulrazak, 1948- -- Gravel heart , Nguyen, Viet Thanh, 1971- , Nguyen, Viet Thanh, 1971- -- The sympathizer , Nguyen, Viet Thanh, 1971- -- The refugees , Urrea, Luis Alberto , Urrea, Luis Alberto -- The house of broken angels , Urrea, Luis Alberto -- The water museum
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/140932 , vital:37930
- Description: This thesis offers close readings and a comparative analysis of selected works by Abdulrazak Gurnah, Viet Thanh Nguyen, and Luis Alberto Urrea. The selected primary texts used are Gurnah’s By the Sea (2000) and Gravel Heart (2017), Nguyen’s The Sympathizer (2015) and The Refugees (2017), and Urrea’s The Water Museum (2015) and The House of Broken Angels (2018). Analyses are informed by a conceptual framework that draws on critical works by Avtar Brah, J. U. Jacobs, Sarah Nuttall, Homi K. Bhabha, Judith Butler, Stuart Hall, Paul Ricoeur, Viet Thanh Nguyen, and Christopher B. Patterson. These theories are deployed to analyse how the selected works engage with the entanglements of history, individual narratives, and memory in the diaspora spaces they articulate. The thesis argues that the selected works indicate an emerging subgenre within the broader category of transnational literature. This subgenre rejects disempowering interpolations of transnational identities. Instead, it prioritises ethical forms of memory. These acknowledge that transnational subjects share at least partial accountability for the precarity they experience in diaspora spaces. The selected literature limns how this may be accomplished by rejecting the label of victim. In so doing, the selected literature also suggests that the elevation of transnationals to full ethical agency would enable them to exercise power in their diaspora spaces. All three authorial projects studied here also give rise to uncomfortable juxtapositions that suggest a mounting fear that, as nationalisms become more pronounced in the UK and the USA, transnationals may have to re-experience conditions from which they have already fled. The thesis concludes by identifying four additional areas of confluence amongst the selected literature worthy of future study.
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Between past and future: memory and mourning in the stories of Okwiri Oduor and Ndinda Kioko
- Authors: Awuor, Nicholas Amol
- Date: 2020
- Subjects: Oduor, Okwiri -- Criticism and interpretation , Oduor, Okwiri -- The plea bargain , Oduor, Okwiri -- My father's head , Oduor, Okwiri -- Rag doll , Kioko, Ndinda -- Criticism and interpretation , Kioko, Ndinda -- Sometime Before Maulidi , Kioko, Ndinda -- Some Freedom Dreams , Authors, Kenyan -- Criticism and interpretation , Kenyan fiction (English) -- History and criticism , Kenyan literature (English) -- History and criticism
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/163168 , vital:41015
- Description: This study investigates the literary activities of two emerging female Kenyan writers, Claudette Okwiri Oduor and Jacqueline Ndinda Kioko, both of whom are award-winning authors. Oduor won the 2014 Caine Prize for African Writing while Kioko bagged the Wasafiri New Writing Fiction Award 2017. It examines specifically how the writers deal with memory and mourning in negotiating between the past and future. I explore how their fictional and non-fictional narratives assist individuals and groups to confront loss, reconstruct new identities, and renegotiate belonging amidst personal and social upheaval. The fictional narratives at the centre of this research are Oduor’s “The Plea Bargain” (2011), “My Father’s Head” (2013) and “Rag Doll” (2014), and Kioko’s “Sometime Before Maulidi” (2014) and “Some Freedom Dreams” (2017). The study explores the themes of mental illness, existential crisis, and fragmentation, and considers bereavement, queer relationships, cultural freedom, and social recognition. The research further considers the active participation of these two writers in Kenya’s contemporary literary-cultural conversations, which span different genres and various media platforms, including blogs, YouTube clips, online magazines, and social media networks in dialogue with other writers. I trace the significance of the literary-cultural link these authors have with their local, continental, and global counterparts in countries like Uganda, Nigeria, and South Africa. The link finds expression through their (in)direct association with some of the new online publishing outlets in Kenya like Jalada Africa, Enkare Review, and Kikwetu. More importantly, their shared participation in and association with such international awards and scholarships as the Commonwealth Short Story Prize, Kwani Trust Manuscript Project, and Miles Morland Foundation is integral in apprehending contemporary literary exchanges and multidirectional flows of publishing in Africa and beyond. I equally illustrate how mentorship of younger writers through local writers’ organisations and collectives like AMKA and Writivism help in the formation of an alternative canon other than the mainstream. The study affirms that the authors seem to transcend the boundaries of production and circulation by fluidly moving between electronic and non-electronic platforms, thus mimicking the memory production of remembering, repeating, and working through.
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Between past and future: memory and mourning in the stories of Okwiri Oduor and Ndinda Kioko
- Authors: Awuor, Nicholas Amol
- Date: 2020
- Subjects: Women authors, Kenyan , Oduor, Okwiri -- The plea bargain , Oduor, Okwiri -- My father's head , Oduor, Okwiri -- Rag doll , Kioko, Ndinda -- Sometime before Maulidi , Kioko, Ndinda -- Some freedom dreams , Women and literature -- Africa , Bereavement -- Fiction , Culture in literature , Liberty in literature
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/161229 , vital:40608
- Description: This study investigates the literary activities of two emerging female Kenyan writers, Claudette Okwiri Oduor and Jacqueline Ndinda Kioko, both of whom are award-winning authors. Oduor won the 2014 Caine Prize for African Writing while Kioko bagged the Wasafiri New Writing Fiction Award 2017. It examines specifically how the writers deal with memory and mourning in negotiating between the past and future. I explore how their fictional and non-fictional narratives assist individuals and groups to confront loss, reconstruct new identities, and renegotiate belonging amidst personal and social upheaval. The fictional narratives at the centre of this research are Oduor’s “The Plea Bargain” (2011), “My Father’s Head” (2013) and “Rag Doll” (2014), and Kioko’s “Sometime Before Maulidi” (2014) and “Some Freedom Dreams” (2017). The study explores the themes of mental illness, existential crisis, and fragmentation, and considers bereavement, queer relationships, cultural freedom, and social recognition. The research further considers the active participation of these two writers in Kenya’s contemporary literary-cultural conversations, which span different genres and various media platforms, including blogs, YouTube clips, online magazines, and social media networks in dialogue with other writers. . I trace the significance of the literary-cultural link these authors have with their local, continental, and global counterparts in countries like Uganda, Nigeria, and South Africa. The link finds expression through their (in)direct association with some of the new online publishing outlets in Kenya like Jalada Africa, Enkare Review, and Kikwetu. More importantly, their shared participation in and association with such international awards and scholarships as the Commonwealth Short Story Prize, Kwani Trust Manuscript Project, and Miles Morland Foundation is integral in apprehending contemporary literary exchanges and multidirectional flows of publishing in Africa and beyond. I equally illustrate how mentorship of younger writers through local writers’ organisations and collectives like AMKA and Writivism help in the formation of an alternative canon other than the mainstream. The study affirms that the authors seem to transcend the boundaries of production and circulation by fluidly moving between electronic and non-electronic platforms, thus mimicking the memory production of remembering, repeating, and working through.
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Biodiversity conservation and rural livelihoods across four nature reserves in the Eastern Cape Province, South Africa: Striving towards a balance between livelihoods and conservation
- Authors: Angwenyi, Daniel
- Date: 2020
- Subjects: National parks and reserves -- South Africa -- Eastern Cape , Nature conservation -- South Africa -- Eastern Cape , Biodiversity conservation -- South Africa -- Eastern Cape , Rural population -- South Africa -- Eastern Cape , Sustainable development -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/138551 , vital:37649
- Description: The realisation that biodiversity is being lost at alarming rates, and that intact ecosystems are essential for ecological functioning and sustenance of human life, has led to biodiversity taking centre stage in national and international agencies’ environmental talks agendas. Protected areas are viable option to stem biodiversity loss. However, the establishment of protected areas might have negative impacts on communities living adjacent to them, leading to poor relations and frequent conflicts between these communities and the managers of protected areas. The Eastern Cape Province has twenty-one nature reserves and three national parks. Since the province is rural, the assumption was likelihood that households in the province depended on natural resources, specifically non-timber forest products for their day-to-day needs. Therefore, it was hypothesised that conserving natural resources, was likely to negatively impact on the livelihoods of most households adjacent to these areas, which in turn would influence their perceptions towards these resources and eventually the effectiveness of conservation efforts. This study aimed at examining the relationship between biodiversity conservation and rural livelihoods in the Eastern Cape Province, South Africa, focusing on four nature reserves – Tsolwana, Hluleka, Mkambati and Great Fish River. The objectives of the study were to: I I. Compare the vegetation productivity inside and outside, as well as land cover change in four nature reserves, as an indicator of conservation effectiveness. II II. Evaluate the relationship between biodiversity conservation and livelihoods in four nature reserves. III III. Evaluate how people’s expectations of nature reserves and perceptions towards nature reserve influence their support of conservation activities. Four hundred semi-structured questionnaires were administered to household heads of communities living at various distances from the four nature reserves, using a gradient design (based on distance). The motive of using distance was to assess whether livelihood status varied with distance from the nature reserves, since data on livelihood before the reserves’ establishment could not be obtained. Through a questionnaire survey, data on demographic information, livelihood assets, livelihood activities, livelihood strategies, livelihood trends, and impacts of the reserves on local communities were gathered. Focus group interviews were also conducted to complement the household surveys. A chi-square test was used to test if there was a relationship between distance from the reserves’ boundaries and local communities’ state of livelihoods. NVivo was used to analyse qualitative data Themes substantiated using literature. The study finds that the reserves did not have any impact on livelihood assets because most households in the study area did not directly depend on the resources found in the reserves. These households depended mostly on government grants and remittances from relatives working in other areas in the country. The reserves, however, supplied some goods and services to local communities, including meat, jobs, water, building materials, security from wild animals, education, skills development, and recreation. There were also a number of negative impacts associated with the reserves including resource use restrictions, harassment by reserves management, killing of domestic animals, and attacks on humans by wild animals escaping from the reserve. The majority (60%) of locals had substantive knowledge of the reserves’ role because of this awareness, 79% were supportive of reserves. However, there were mixed views by locals on the best way to manage these reserves. The most dominant view was that natural resources should be preserved for future generations, while meeting the current generation’s livelihood needs. Other lesser views included that the reserves’ management should involve locals in the management structures, either as active members or through consultation. Similarly, there were people feeling that the reserve is an obstacle to their livelihoods and should be closed and the land returned to the rightful owners. The vegetation productivity was better inside as compared to the outside the reserves. This activity also improved in the sixteen (16) years under assessment. This imply that the ecological functionality of the reserves is better than the surrounding areas and is improving with time. The research recommended that local communities could be an asset in conservation since most of them were in favour of the reserves. This, however, will need reserve managers to form workable partnerships with these communities, where the rights and responsibilities for both parties are defined. Besides these partnerships, lease agreements between local communities and reserves management to enhance benefits to the communities could encourage local communities to take pride in the natural resources within the reserves. This will ultimately becoming stewards to these resources. Development of tourism infrastructure such as curio shops and convenience stores to enhance livelihood opportunities could also help. For the local communities to be well represented it is important that the committees representing them in the various reserve matters be expanded and democratically elected. Where necessary, community awareness programmes on the importance of the reserves and the roles of local communities should be implemented.
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Biogeographic patterns of endolithic cyanobacteria and their negative impacts on mussels along the South African coast
- Authors: Ndhlovu, Aldwin
- Date: 2020
- Subjects: Cyanobacteria -- South Africa , Cyanobacteria -- Geographical distribution , Prokaryotes -- South Africa , Mexilhao mussel -- South Africa , Mytilus galloprovincialis -- South Africa , Coastal biology -- South Africa , Coastal ecology -- South Africa , Mussels -- Geographical distribution , Mussels -- Predators of , Mussels -- Mortality -- South Africa , Mussels -- Ecology -- South Africa , Mussels -- Growth -- South Africa , Mussels -- Fertility -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/144656 , vital:38367
- Description: Endolithic cyanobacterial species occur in a wide range of environments including cold and hot deserts as well as marine systems where they attack biological material such as corals and the shells of molluscs including limpets, mussels and abalone. Endoliths live as parasites in mussel shells, where they erode and extract calcium carbonate leading to shell weakening, creating fracture holes that lead to shell collapse and death, but they also have positive effects when they lead to discolouration of mussel shells hence giving them the ability to reduce stressful heat gain during periods of extreme heat stress. Mussels are ecological engineers on which the abundance and diversity of associated species assemblages depend. Understanding how endolithic cyanobacteria affect mussels will not only help in predicting future patterns of mussel abundances, but also future patterns of the infauna that depend on them. Firstly, I identified endolithic species infesting mussels and assessed the prevalence of endolithic parasitism in two intertidal mussel species in South Africa, the native Perna perna and the invasive Mytilus galloprovincialis. Large-scale surveys of endolithic infestation of mussels were conducted along 2500 km of the South African coast, covering three biogeographic regions: the subtropical east coast, dominated by P. perna, the warm temperate south coast where the indigenous species coexists with M. galloprovincialis, and the cool temperate west coast which is dominated by M. galloprovincialis. The prevalence of endolithic infestation was higher in the cool temperate bioregion than in the warm temperate and subtropical bioregions which did not differ and for P. perna endolithic species assemblages revealed clear groupings by bioregion. Results for endolithic induced mortality followed the same trend, with no significant difference between the two mussel species where they coexist and these results attribute biogeography of endoliths to environmental factors rather than host identity. Secondly, I assessed energy budgets of infested and clean mussels, to evaluate the energetic cost of infestation. This involved measuring energy acquisition, expenditure, calculating scope for growth and lethal temperatures (LT50s). The results revealed that endolithic cyanobacteria have a negative effect on scope for growth due to increased metabolic rates for infested mussels, with no effect of endoliths on the rates or efficiency of energy acquisition through filtration and no effect on lethal temperatures. The effects of infestation were then examined in more detail through a qualitative and quantitative analysis of mussel gonads and byssal attachment strength to the substratum. Endolithic infestation was found to affect reproduction by affecting the size (mass) of gonads, but not the density of eggs within them. Attachment strength was affected by endolithic infestation with very infested mussels requiring much less force to detach them from the substratum compared to mussels with low or no infestation. These results show that endolithic infestation affects mussel fitness by directly affecting attachment strength and by reducing their reproductive output. Thirdly, endolithic succession within mussel shells was examined by assessing endolithic species composition in different regions of the shell and as a function of time. The results on the spatial distribution of endolith species within a shell supported those for temporal succession in shells deployed in the field. Endolithic species that were early colonists of clean shells were similar to those that were found in the distal edge, the new and growing region of the shell and species that arrived late in succession were similar to endolithic species found near the umbo, the oldest region of the shell. Overall, the study shows that endolithic cyanobacteria show the effects of biogeography on species distribution and clear patterns of succession within mussel shells. Cyanobacteria affect mussels negatively; they lead to low scope for growth and hence low growth rates, low reproductive output and reduced attachment strength for infested mussels. This, in turn is expected to have indirect consequences for other species that rely on mussels as ecological engineers for their survival.
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BODIPY dyes for application in the photo-oxidation of pollutants, photodynamic antimicrobial chemotherapy, and nonlinear optics
- Authors: Kelechi, Lebechi Augustus
- Date: 2020
- Subjects: Dyes and dyeing -- Chemistry , Fluorescent probes , Fluorescence spectroscopy
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/140298 , vital:37859
- Description: The synthesis and structural characterization of a series of BODIPY dyes to analyze both the effects of halogenations at the 2,6-positions and the introduction of styryl groups at the 3,5-positions. The photophysical properties of these dyes were investigated to determine their suitability as singlet oxygen-generating photosensitiser dyes for application in photocatalytic degradation of azo dyes and in photodynamic antimicrobial chemotherapy (PACT). Upon halogenation, the dyes showed high to moderate singlet oxygen quantum yields. The potential utility of electrospun polystyrene (PS) nanofibres embedded with halogenated BODIPY dyes for the photocatalytic degradation of Orange G and Methyl Orange from textile industry effluents were investigated. A comparison of the singlet oxygen quantum yield of the BODIPY dyes in solution and when embedded in the PS nanofibres support demonstrates that its photosensitiser properties are maintained in the nanofibre mats. The photocatalytic degradation properties of the PS nanofibres for Orange G and Methyl Orange were determined by using a 530 nm and 660 nm light-emitting diodes. The rate of photodegradation increases with both the Orange G and Methyl Orange concentrations and follows pseudo-first-order kinetics. The PACT activities of brominated BODIPYs on Escherichia coli and Staphylococcus aureus were investigated. Log reduction values of over 9 were obtained during the photoinactivation of Staphylococcus aureus. To be able to red-shift the main spectral band of the BODIPY dyes into the therapeutic window, styryl groups were introduced at the 3,5-positions through a modified Knoevenagel condensation reaction. Because the red-shifted spectral band lies above 532 nm, the second harmonic of the Nd:YAG laser, there is very minute absorption at this wavelength. One of the novel brominated BODIPY dyes was investigated for its potential utility as optical limiting materials in nonlinear optics (NLO), and the dyes demonstrated typical nonlinear absorption behaviour characterised by reverse saturable absorption (RSA) in Z-scan measurements. Excellent optical limiting parameters were obtained for third-order susceptibility and hyperpolarisability.
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Building a flexible and inexpensive multi-layer switch for software-defined networks
- Authors: Magwenzi, Tinashe
- Date: 2020
- Subjects: Software-defined networking (Computer network technology) , Telecommunication -- Switching systems , OpenFlow (Computer network protocol) , Local area networks (Computer networks)
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/142841 , vital:38122
- Description: Software-Defined Networking (SDN) is a paradigm which enables the realisation of programmable network through the separation of the control logic from the forwarding functions. This separation is a departure from the traditional architecture. Much of the work done in SDN enabled devices has concentrated on higher end, high speed networks (10s GBit/s 100s GBit/s), rather than the relatively low bandwidth links (10s MBit/s to a few GBit/s) which are seen, for example, in South Africa. As SDN is increasingly becoming more accepted, due to its advantages over the traditional networks, it has been adopted for industrial purposes such as networking in data centres and network providers. The demand for programmable networks is increasing but is limited by the ability of providers to upgrade their infrastructure. In addition, as access to the Internet has become less expensive, the use of Internet is increasing in academic institutions, NGOs, and small to medium enterprises. This thesis details a means of building and managing a small scale Software-Defined Network using commodity hardware and open source tools. Core to the SDN Network illustrated in this thesis is the prototype of a multi-layer SDN switch. The proposed device is targeted to serve lower bandwidth communication (in relation to commercially produced high speed SDN-enabled devices). The performance of the prototype multilayer switch had shown to achieve: data-rates of up to 99.998%, average latencies that are under 40µs during forwarding/switching and under 100µs during routing while using packet sizes between 64 bytes and 1518 bytes, and a jitter of less than 15µs during all tests. This research explores in detail the design, development, and management of a multi-layer switch and its placement and integration in small scale SDN network. This includes testing of Layer 2 forwarding and Layer 3 routing, OpenFlow compliance testing, the management of the switch using created SDN applications, and real life network functionality such as forwarding, routing and VLAN networking to demonstrate its real world applicability.
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Carnivore intra-guild competition in Selati Game Reserve, Limpopo Province, South Africa
- Authors: Comley, Jessica
- Date: 2020
- Subjects: Hyenas -- Behavior -- South Africa , Hyenas -- South Africa , Hyenas -- Ecology -- South Africa , Top predators -- South Africa , Top predators -- Ecology -- South Africa , Animal communities -- South Africa , Animal behavior -- South Africa , Mutualism (Biology) -- South Africa , Coexistence of species -- South Africa , Game farms -- South Africa , Selati Game Reserve (South Africa)
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115558 , vital:34163
- Description: Carnivore intra-guild interactions can be important drivers of carnivore community composition and ecosystem functioning. Large carnivores are particularly important since they occupy the highest trophic levels and can exert extensive influences on subordinate carnivores and prey species. Given Africa’s rapidly expanding human population, enclosed reserves such as those found in South Africa, may become increasingly important for carnivore conservation. A major concern, however, is that the interactions and co-existence of multiple carnivores in these systems is poorly understood. Additionally, the majority of reserves in South Africa are small ( 400km²), potentially increasing the likelihood of competition. My research aimed to provide insight into the interactions and co-existence of a multi-carnivore community within a small, enclosed reserve in South Africa (Selati Game Reserve). I tackled this task by using a combination of field techniques including camera trap surveys, ungulate transect surveys, aerial count surveys, location data collected from collared large carnivores and scat and kill site analyses. I found that carnivore-carnivore interactions, and their associated impacts, varied within the carnivore guild and that co-existence may be due to trade-offs between various risks (i.e. interference and exploitative competition) and benefits (i.e. resources such as food and space). My findings also revealed that large carnivores, such as lions (Panthera leo), spotted hyaenas (Crocuta crocuta) and leopards (Panthera pardus) do not have homogenous effects and that site-specific research on multiple-carnivores is integral for conserving biodiversity and ecosystem dynamics. Lions were the dominant large carnivore (in terms of intra-guild predation, space use and resource use) despite being outnumbered seven to one by spotted hyaenas. Leopard occupancy was negatively influenced by lions and leopard diet overlapped almost completely (91%) with spotted hyaenas, suggesting increased kleptoparasitism of leopard kills by spotted hyaenas. While my study provides valuable insight into the complexity of carnivore intra-guild competition in a small, enclosed reserve it also highlights major research gaps and emphasises the need for ecosystem-based research throughout southern Africa to fully understand how multiple sympatric carnivores co-exist in these systems.
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Chasing Eden: Margaret Atwood’s MaddAddam trilogy and the value of reading in a technological age
- Authors: Bosman, Zoë June
- Date: 2020
- Subjects: Atwood, Margaret, 1939- MaddAddam trilogy , Speculative fiction -- History and criticism , Capitalism in literature , Dystopias in literature , Science fiction -- History and criticism , Technology in literature
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/145796 , vital:38467
- Description: This thesis is focussed on Margaret Atwood’s MaddAddam trilogy: Oryx and Crake (2003) The Year of the Flood (2009) and MaddAddam (2013). Detailing Atwood’s own specifications as to why these texts should be categorised as works of speculative fiction, the thesis examines how this literary genre, and Atwood’s MaddAddam trilogy in particular, is uniquely capable of encouraging readers to interrogate critically the socio-economic, environmental, and ethical problems to which she, and the contemporary reader, bear witness in the present technological age. With reference to Atwood’s essays and critical writings, Darko Suvin’s Metamorphoses of Science Fiction, and Wolfgang Iser’s The Act of Reading, this project explores the value of reading speculative fiction and details how Atwood has constructed the fictional, yet plausible, possible future world of her trilogy by extrapolating our current scientific capabilities, environmental challenges, and political configurations to their logical conclusions. It explores the close relationship that exists between the near-future world of Atwood’s texts and the contemporary context from which she has drawn her subject matter, and argues that the trilogy demonstrates graphically the long-term consequences of capitalism, sustainability, and the doctrine of human exceptionalism, which this project, following Yuval Harari, defines as orthodox guiding narratives: fictions that humanity has created, and which structure our perception of reality and guide our behaviour. The project maintains that Atwood’s trilogy presents the reader with a hypothetical future that looks towards and beyond the end of contemporary technological society in order to urge her reader to imagine, and actualize, alternatives to the scenarios that these texts depict. The most significant question Atwood’s texts ask is whether contemporary technological society is willing and able to transform in order to avert the ecological apocalypse that is the logical conclusion to the Anthropocene?
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Chirema Chine Mazano Chinotamba Chakazendama Madziro
- Authors: Mapondera, Wallen
- Date: 2020
- Subjects: Art, Zimbabwean , Art -- Economic aspects -- Zimbabwe , Artists -- Zimbabwe , Takadiwa, Moffet , Nyandoro, Gareth , Clottey, Serge Attiku , Mapondera, Wallen -- Exhibitions
- Language: English
- Type: text , Thesis , Masters , MFA
- Identifier: http://hdl.handle.net/10962/147457 , vital:38638
- Description: This mini-thesis has developed as a practice-based supporting document to the exhibition Chirema Chine Mazano Chinotamba Chakazendama Madziro. The exhibition responds to how people become innovative in finding alternative means of survival and staying relevant in an economically depressed country. Zimbabwe is often the first country that comes to mind when people talk about hyperinflation; the situation was and still is intolerable, but somehow its citizens find means to pull through. Unemployment and poverty are the main causes of physical and mental problems for an individual. With this thesis, I highlight the innovations employed by Zimbabweans as a way of keeping themselves busy. I approach this through analysing the Zimbabwean general public’s creative reactions, and by tracing Zimbabwean visual artists’ use of found objects as a reaction to the country’s economic hardships. As people have been pushed to find alternative ways of survival, Zimbabwean artists in particular also shifted from using conventional art materials due to their unavailability. They began to redefine what art material is by employing objects in their artworks that previously had a non-art function. As such, there is a growing need to recognise, classify and document the shifts and establish platforms to generate growth of these innovations. In this minithesis I discuss my own practice, and I analyse the works of Moffat Takadiwa, Gareth Nyandoro and Serge Attiku Clottey.
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Choreographies of protest performance as recruitment to activism and the movement of perception during the 2015 re-emergence of student activism at Rhodes University
- Authors: Qoza, Phiwokazi
- Date: 2020
- Subjects: College students -- Political activity -- South Africa , Student protesters -- South Africa , Student movements -- South Africa , Higher education and state -- South Africa , Performance art -- Political aspects -- South Africa , Protest songs -- South Africa
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/141692 , vital:37997
- Description: It has been argued that individuals participate in activism due to an identification with the preferences and interests of an emerging group of actors or in solidarity with a pre-existing network that has resorted to a number of protest repertoires in order to make claims or demands. Additionally, an emerging instance of protest is often linked to an image of previous protest events through the employment of a combination of master frames which function as discursive articulation of the encounter in familiar terms, creating a frame resonance which recruits adherents and constituents. To understand why some bystanders to protest transcended to actors in protest and the development of frames within a protest cycle, a performance ethnography is employed to observe and analyse choreographies of protest which took place at an institution of higher education in South Africa during the 2015 re-emergence of wide-spread student activism. It is found that in encountering an atmosphere of protest there emerged a relation of feeling, referred to as “feeling the vibe or atmosphere”, which those who became protest performers resolved in ways which increased their capacity to act in favour of co-constituting that atmosphere. During the encounter between the bystander body and the atmosphere of protest, non-linear somatic communication, characterised by active and passive gestures and postures, occurred through which protest performers developed contact and connection with other bodies as a result of the displacement of space. This thesis suggests that participation in activism can be about going with the flow of movement in an uncertain and ambiguous moment and is not limited to an identification with the pre-existing organization of preferences and interests as a frame of resonance emerges to signify somatic communication which differentiated bodies in the duration of protest performance. Therefore, this thesis uses the theory of affect to situate student activism in-between the politics of performance and the performance of politics whereupon the rhythm of song creates an opening for the kinaesthetic to create form from spontaneous movement of the body as an event of the movement of perception and the perception of movement.
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Combination ecosystem green engineering and early life history processes to enhance the intertidal biodiversity in the Port of East London
- Authors: Mafanya, Sandisiwer
- Date: 2020
- Subjects: Biotic communities -- South Africa -- East London , Perna -- Ecology --South Africa -- South Africa-- East London , Mexilhao mussel -- Ecology -- South Africa -- East London , Habitat (Ecology) -- Modification -- South Africa -- East London , Benthic animals -- Effect of habitat modification on -- South Africa -- East London , Harbors -- Environmental aspects -- South Africa -- East London
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166376 , vital:41357
- Description: Marine coastal ecosystems are highly impacted by anthropogenic activities, including the development of, and practices within, harbours and/or ports. Artificial structures associated with harbours have a different chemical composition, texture and orientation than that of the natural benthic habitats they have replaced, and are therefore not generally favourable for the settlement and occurrence of indigenous species. Attempts are being made to identify what structures and materials can be used to aid in the rehabilitation of native species within harbours. The aim of this study was to investigate the effects of utilising environmentally-friendly artificial structures (tiles) with varying complexity (crevices and ridges with different depths) with ecological engineers (the indigenous bivalve Perna perna), on the associated benthic biodiversity within an international port in South Africa (Port of East London). The objectives of the study were to test the effects of artificial habitat complexity and the presence of bivalves on 1) the growth, mortality and biomass of a selected model species of ecosystem engineer (P. perna), and 2) the associated intertidal biodiversity. Tiles seeded with bivalves (P. perna) were deployed at two sites in the Port of East London and monitored monthly over a period of 12 months (November 2016-October 2017) to assess survival, growth and associated biodiversity. Environmental variables were also measured every month. The results of the three-way repeated measures ANOVAs indicated that tile treatment (especially high complexity of 2.5 and 5 cm) had an effect on the diversity of mobile species, length, height and biomass of the bivalves used as model ecosystem engineer, indicating the potentials for protection from wave dislodgement and refuge provision. Treatment (especially flat tiles) also had an effect on sessile/sedentary species diversity, indicating the greater proportion of space provided by these non-complex tiles. In addition, month had an effect on the mortality, height and biomass of the bivalves. Mortality was highest in October 2017, while the growth in height and biomass of P. perna were largest in January and October 2017 respectively. The use of artificial tiles also had a positive effect on the survival, growth, and biomass of bivalves (especially the length, weight and dry weight in 2.5 cm and 5 cm complexity). Additionally, this research investigated patterns of settlement and recruitment of the local bivalve population (P. perna) in the Port of East London and adjacent natural coastline to understand the early life history temporal and spatial dynamics of this model ecosystem engineer species. Settlement and recruitment were assessed every month by deploying and replacing artificial collectors for a total period of 19 months (November 2016-May 2018). The results of the two-way ANOVAs indicated that month and site (port vs natural) had an effect on settlement and recruitment of bivalves. Settlement and recruitment of bivalves were highest in July 2017 (port) and March 2018 (natural rocky shore). This study has highlighted that the use of artificial concrete tiles with increased complexity, as well as the investigation of the early stages of mussel populations could be important to consider in a framework of rehabilitation of urban coastal environments such as the Port of East London. Ecological engineering (in terms of increased complexity and heterogeneity) has indeed the potentials to be incorporated in South African programmes aiming at improving natural biodiversity in coastal urban environments. Nonetheless, the spatio-temporal variability of early driver of mussel populations (settlement and recruitment) is also an important feature to be closely monitored if biodiversity in South African coastal armouring is to be enhanced effectively and in the long term.
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Combining DNA barcoding and morphology to identify larval fishes from the nearshore environment off the south-east coast of South Africa
- Authors: Somana, Zinzi Sinazo
- Date: 2020
- Subjects: Fishes -- Larvae -- South Africa -- Identification , Fishes -- Genetics -- Research -- Technique , Fishes -- South Africa -- Classification , Genetic markers
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/144605 , vital:38362
- Description: The early life history stages of most marine fish species are undescribed. The problem is, most of these fishes have pelagic larvae which are minute, delicate forms. Linking the larval stage to an adult counterpart is extremely challenging as larvae are morphologically different from the adults. Historically, larval fish identification relied solely on distinguishing morphological characteristics and meristic measurements, which has resulted in taxonomic confusion and misidentification. The introduction of the deoxyribonucleic acid (DNA) barcoding technique as an alternative approach has been successful in positively identifying larval fishes. The correct identification of larval specimens is the key to a better understanding of larval ecology, which underpins the success of any adult fish population. This study aimed to positively identify larval fishes of the south-east coast of South Africa using morphological characteristics and DNA barcoding. Larval and eggs specimens for this study were collected from the shallow nearshore waters of the south-east coast of South Africa. A total of 177 larval specimens were used for morphological analysis. Body shape, gut shape, pigmentation and morphometric measurements (such as body depth, preanal length and total body length) were used to identify each specimen to the family level. In addition, a fragment of mitochondrial cytochrome c oxidase subunit 1 gene (COI) was adopted for sequencing to identify larval fish specimens and fish eggs. Sequences generated from this study were compared to those in the Barcode of Life Database (BOLD). When there were no close matches to a sequence, the GenBank nucleic acid sequence database, maintained by the National Center for Biotechnology Information (NCBI), was used as an alternative. A total of 18 different families were identified through morphology. Seventy-seven of the 177 larval specimens were not subjected to morphological identification due to physical damage. The majority of larvae identified using morphological characteristics belonged to either the Sparidae, Tripterygiidae or Gobiesocidae fish families. Through DNA barcoding, 12 fish families, 16 genera and 18 different species were identified. Ten DNA barcodes (categorised as ‘no match’) from 10 different larval specimens were not identified through any of the online databases. Therefore, the 2% threshold value was used to identify members of the same species. The K2P genetic distance relationships were calculated among the no match sequences and downloaded probability matches from NCBI. This resulted in two unknown specimens assigned to the Blenniidae and Gobiidae. All other taxa were identified to species level, except specimens representing the Gobiidae and Tripterygiidae families. Based on the K2P genetic distances Gobiidae representatives were categorised as members of the Caffrogobius genus. Twenty-eight barcodes represented specimens from the Tripterygiidae. DNA barcode data from COI was analysed using the standard phylogenetic procedures in MEGA6 to examine relationships and differentiation among sequences. These could not be identified to the lowest taxonomic rank due to limited sequence data to compare them with. The sequence data from these specimens gave different results in the two online databases. BOLD results were to family level (Tripterygiidae) and NCBI to the species level (Clinidae: Pavoclinus profundus). Results in this study confirmed the efficiency of the DNA barcoding technique in species level identification of fish larvae. The evidence from genetic barcodes of the Tripterygiidae specimens, supported by morphological characteristics, suggests the need for thorough research to identify the individuals to the species level. The fact that this study identified taxonomically problematic Gobiidae and Tripterygiidae specimens suggests that studies similar to this may highlight additional diversity and help to resolve the taxonomy of other species in these families. However, the lack of reference sequence data from the adult specimens, and especially those with cryptic diversity, were both shortcomings for the positive identification of larvae. With that being said, it shows the necessity for more research to be conducted on barcoding of larvae in general as to accommodate all kinds of species from biodiversity to economic perspectives.
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Come listen quickly
- Authors: Gouws, Leigh-Anne
- Date: 2020
- Subjects: South African fiction (English) -- 21st century
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/141559 , vital:37985
- Description: Creative work portfolio.
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Commonplaces
- Authors: Orsmond, Joseph Granger
- Date: 2020
- Subjects: South African fiction (English) -- 21st century
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/144061 , vital:38307
- Description: My thesis is a collection of short to medium length poems. All of the subject matter is sustained by reflections, anecdotes or stories. The pieces in the collection are concerned with experiences linked to the seemingly ordinary and mundane. In this regard, I am inspired by how Alan Ziegler (in “Tales of Teaching” and Love at First Sight) and Raymond Carver (All of Us: The collected Poems) find stories in subject matter which is so commonplace, that it is often ignored creatively. Likewise, the lyricism and modes of expression of William Carlos Williams, Federico García Lorca and Luis Cernuda have informed how I write and structure my poetry.
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Computer aided approaches against Human African Trypanosomiasis
- Authors: Kimuda, Magambo Phillip
- Date: 2020
- Subjects: African trypanosomiasis , African trypanosomiasis -- Chemotherapy , Genomics , Macrophage migration inhibitory factor , Trypanosoma brucei , Pteridines , Tetrahydrofolate dehydrogenase , Adenylic acid , Molecular dynamics , Principal components analysis , Bioinformatics , Single nucleotide polymorphisms , Single Nucleotide Variants , Candidate Gene Association Study (CGAS)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/142542 , vital:38089
- Description: The thesis presented here is divided into two parts under a common theme that is the use of computer based tools, genomics, and in vitro experiments to develop innovative ways of tackling Human African Trypanosomiasis (HAT). Part I of this thesis focused on the human host genetic determinants while Part II focused on the discovery of novel chemotherapeutics against the parasite. Part I is further sub-divided into two parts: The first involves a Candidate Gene Association Study (CGAS) on an African population to identify genetic determinants associated with disease and/or susceptibility to HAT. The second involves studying the effects of missense Single Nucleotide Variants (SNVs) on protein structure, dynamics, and function using Macrophage Migration Inhibitory Factor (MIF) as a case study. Part II is also sub-divided into two parts: The first involves a computer based rational drug discovery of potential inhibitors against the Trypanosoma the folate pathway; particularly by targeting Trypanosoma brucei Pteridine Reductase (TbPTR1) which is an enzyme used by trypanosomes to overcome T. brucei Dihydrofolate Reductase (TbDHFR) inhibition. Lastly the derivation of CHARMM force-field parameters that can be used to accurately model the geometry and dynamics of the T. brucei Phosphodiesterase B1 enzyme (TbrPDEB1) bimetallic active site center. The derived parameters were then used in MD simulations to characterise protein-ligand residue interactions that are important in TbrPDEB1 inhibition with the goal of targeting the cyclic Adenosine Monophosphate (cAMP) signalling pathway. In the CGAS we were unable to detect any genetic associations in the Ugandan cohort analysed that passed correction for multiple testing in spite of the study being sufficiently powered. Additionally, our study found no association of the Apo lipoprotein 1 (APOL1) G2 allele association with protection against acute HAT that has been previously reported. Future investigations for example, Genome Wide Association Studies using larger samples sizes (>3000 cases and controls) are required. Macrophage migration inhibitory factor (MIF) is a cytokine that is important in both innate and adaptive immunity that has been shown to play a role in T. brucei pathogenicity using murine models. A total of 27 missense SNVs were modelled using homology modelling to create MIF protein mutants that were investigated using in silico effect prediction tools, molecular dynamics (MD), Principal Component Analysis (PCA), and Dynamic Residue Network (DRN) analysis. Our results demonstrate that mutations P2Q, I5M, P16Q, L23F, T24S, T31I, Y37H, H41P, M48V, P44L, G52C, S54R, I65M, I68T, S75F, N106S, and T113S caused significant conformational changes. Further, DRN analysis showed that residues P2, T31, Y37, G52, I65, I68, S75, N106, and T113S are part of a similar local residue interaction network with functional significance. These results show how polymorphisms such as missense SNVs can affect protein conformation, dynamics, and function. Trypanosomes are auxotrophic for folates and pterins but require them for survival. They scavenge them from their hosts. PTR1 is a multifunctional enzyme that is unique to trypanosomatids that reduces both pterins and folates. In the presence of DHFR inhibitors, PTR1 is over-expressed thus providing an escape from the effects of DHFR inhibition. Both TbPTR1 and TbDHFR are pharmacologically and genetically validated drug targets. In this study 5742 compounds were screened using molecular docking, and 13 promising binding modes were further analysed using MD simulations. The trajectories were analysed using RMSD, Rg, RMSF, PCA, Essential Dynamics Analysis (EDA), Molecular Mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations, and DRN analysis. The computational screening approach allowed us to identify five of the compounds, named RUBi004, RUBi007, RUBi014, RUBi016 and RUBi018 that exhibited antitrypanosomal growth activities against trypanosomes in culture with IC50 values of 12.5 ± 4.8 μM, 32.4 ± 4.2 μM, 5.9 ± 1.4 μM, 28.2 ± 3.3 μM, and 9.7 ± 2.1 μM, respectively. Further when used in combination with WR99210 a known TbDHFR inhibitor RUBi004, RUBi007, RUBi014 and RUBi018 showed antagonism while RUBi016 showed an additive effect. These results indicate that the four compounds might be competing with TbDHFR while RUBi016 might be more specific for TbPTR1. These compounds provide scaffolds that can be further optimised to improve their potency and specificity. Lastly, using a systematic approach we derived CHARMM force-field parameters to accurately describe the TbrPDEB1 bi-metal catalytic center. For dynamics, we employed mixed bonded and non-bonded approach. We optimised the structure using a two-layer QM/MM ONIOM (B3LYP/6-31(g): UFF). The TbrPDEB1 bi-metallic center bonds, angles, and dihedrals were parameterized by fitting the energy profiles from Potential Energy Surface (PES) scans to the CHARMM potential energy function. The parameters were validated by means of MD simulations and analysed using RMSD, Rg, RMSF, hydrogen bonding, bond/angle/dihedral evaluations, EDA, PCA, and DRN analysis. The force-field parameters were able to accurately reproduce the geometry and dynamics of the TbrPDEB1 bi-metal catalytic center during MD simulations. Molecular docking was used to identify 6 potential hits, that inhibited trypanosome growth in vitro. The derived force-field parameters were used to simulate the 6 protein-ligand complexes with the aim of elucidating crucial protein-ligand residue interactions. Using the most potent ligand RUBi022 that had an IC50 of 14.96 μM we were able to identify key residue interactions that can be of use in in silico prediction of potential TbrPDEB1 inhibitors. Overall we demonstrate how bioinformatics tools can complement current disease eradication strategies. Future work will focus on identifying variants identified in Genome Wide Association Studies and partnering with wet labs to carry out further enzyme-ligand activity relationship studies, structure determination or characterisation of appropriate protein-ligand complexes by crystallography, and site specific mutation studies
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