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    Structural bioinformatics studies and tool development related to drug discovery

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    This thesis is divided into two distinct sections which can be combined under the broad umbrella of structural bioinformatics studies related to drug discovery. The first section involves the establishment of an online South African natural products database. Natural products (NPs) are chemical entities synthesised in nature and are unrivalled in their structural complexity, chemical diversity, and biological specificity, which has long made them crucial to the drug discovery process. South Africa is rich in both plant and marine biodiversity and a great deal of research has gone into isolating compounds from organisms found in this country. However, there is no official database containing this information, making it difficult to access for research purposes. This information was extracted manually from literature to create a database of South African natural products. In order to make the information accessible to the general research community, a website, named “SANCDB”, was built to enable compounds to be quickly and easily searched for and downloaded in a number of different chemical formats. The content of the database was assessed and compared to other established natural product databases. Currently, SANCDB is the only database of natural products in Africa with an online interface. The second section of the thesis was aimed at performing structural characterisation of proteins with the potential to be targeted for antimalarial drug therapy. This looked specifically at 1) The interactions between an exported heat shock protein (Hsp) from Plasmodium falciparum (P. falciparum), PfHsp70-x and various host and exported parasite J proteins, as well as 2) The interface between PfHsp90 and the heat shock organising protein (PfHop). The PfHsp70-x:J protein study provided additional insight into how these two proteins potentially interact. Analysis of the PfHsp90:PfHop also provided a structural insight into the interaction interface between these two proteins and identified residues that could be targeted due to their contribution to the stability of the Hsp90:Hop binding complex and differences between parasite and human proteins. These studies inspired the development of a homology modelling tool, which can be used to assist researchers with homology modelling, while providing them with step-by-step control over the entire process. This thesis presents the establishment of a South African NP database and the development of a homology modelling tool, inspired by protein structural studies. When combined, these two applications have the potential to contribute greatly towards in silico drug discovery research

    Mesoscale mechanisms of larval transport and settlement in relation to physical factors off the south coast of South Africa: a topographic approach

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    The majority of benthic marine invertebrate life cycles include a meroplanktonic phase. Most marine biologists recognise that this stage could play an important role in dispersal, especially for sedentary or sessile organisms. Recent studies on larval dispersal have found that dispersal does not occur to the extent that was previously believed. Some larvae instead remain close to their natal populations through larval nearshore retention mechanisms, both active and passive. This study attempted to a) describe nearshore distribution patterns of several intertidal larvae in relation to nearshore hydrodynamics, b) infer whether larvae are active or passive in the water column and whether this differs among taxa and c) compare pelagic mussel larval abundance with settlement rates, at 2 bay and 2 open coast sites on the south coast of South Africa to note any topographical effects. At each of the four sites, pelagic samples were collected along 2 transects. Larvae and current speed data were collected at various depths (surface, mid-depth and bottom) at distances of 200, 400, 900 and 2400m offshore of the coast. Settlement samples were collected at sites that were onshore of the pelagic transects using plastic souring pads following previous studies. Pelagic larval distribution showed no effect of topography. Instead larval abundance was highly variable among sample periods and among different taxa. Slow swimming D-stage mussel larvae were found to be positively correlated with both upwelling and turbulence indices suggesting that they behave as passive particles in the water column. The abundances of larval taxa with faster swimming speeds than the D-larvae were negatively correlated with upwelling and did not correlate with turbulence. This suggests that these larvae are more active within the water column than the D-larvae which would theoretically allow them to maintain their position in the water column. Further analysis revealed that mean larval depth correlated with mean depth of shoreward moving water masses regardless of the state of upwelling. These results suggest that larvae were actively selecting the depth at which they were found presumably in order to associate themselves with shoreward moving currents. This interpretation was supported by ontogenetic patterns in the behaviour of barnacle larvae, the nauplii of which were found further offshore as they aged, and closer onshore again once they reach the faster swimming cyprid stage. Although there was no detectable effect of topography on the abundances of planktonic larvae, the settlement section of this study revealed an effect of topography, with higher settlement and recruitment rates at bay sites than at the open coast sites. Settlement rates were seen to be negatively correlated with turbulence at bay sites but not open coast sites. Recruitment rates for each sample event were positively correlated with upwelling at each site. This study found pelagic larvae to be generally active within the water column which allowed them to remain close to the shore regardless of topography and upwelling/turbulence regimes. Although meaningful correlation analyses between pelagic larval supply and settlement rates could not be conducted due to loss of settlement collectors, settlement rates were affected by local topography with higher settlement and recruitment in bay sites

    Water supply development decision-making in South Africa

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    Balancing water demand and supply in South Africa involves high levels of uncertainty. The Department of Water and Sanitation (DWS) is responsible for making decisions to either increase water supply or decrease water demand so as to ensure that sufficient water is available, when and where it is needed. However, no retrospective analyses of such decisions have been found. One way to assess such decisions is to evaluate the associated costs and benefits thereof. Therefore the primary aim of this study is to evaluate the costs and benefits of selected water supply options, and of the decision-making associated with those options. In order to achieve this purpose, four case studies were analysed within a mixed-methods research paradigm, which used both quantitative and qualitative methods, including unit reference value (URV) analysis, inter- and intra-case analysis and content analysis to examine the success of the decisions made. The four case studies were conducted on the Inyaka, Nandoni, Berg and De Hoop dams and their catchments. Firstly, estimated and actual project costs were compared using unit reference analysis and inter-case analyses. Secondly, the reduction of mean annual runoff (MAR) caused by invasive alien plants (IAPs) and the cost of clearing them in the dam catchments were evaluated using inter-case analyses. Information thus gathered was used together with data from DWS documentation and the results of interviews with ten key specialists, to analyse the decision-making process that led to the decision to build De Hoop Dam (the most recent case study). The rational decision-making model (RDMM) was used as a framework within which to analyse and evaluate this decision-making process. This study has also demonstrated how the RDMM can be used to assess decision-making associated with water supply development. The results of this study show that there is considerable variation of estimated costs (at the time that the decision to build the dam was taken) in relation to the actual costs of building the dams and that Ministers were not put in a position to understand the full long-term costs or the opportunity costs of the proposed dams. Furthermore, the most recent IAP data (2008) shows that the impact on water security by IAPs could not offset the water security resulting from building each of the four dams. However, if IAP management is not continued in these catchments, the projected reduction of MAR by IAPs will compromise water security within 45 years. Given the almost exponential spread and densification of IAPs, together with their long-term impact on MAR and increased costs of controlling them, it is clear that IAP management should have been factored into water supply decision-making from the outset. In the analysis of the decision to build the De Hoop Dam, the results show that while the decision-making process that culminated in the decision to build the dam did not follow the steps of the RDMM, DWS appears to have followed a somewhat similar approach. It was found that while there was a need for the provision of additional water in the Olifants catchment, this need was overstated and the resulting overestimation caused the scale and size of the dam to be larger than it could and probably should have been. Additionally, it appears that DWS‘s decision to build the De Hoop Dam themselves, rather than having it built by the private sector, may have been less than optimal. It is recommended that, in future decision-making, DWS needs to incorporate multiple alternative options into the same solution, and to ensure that decision-makers are put into a position to make informed decisions, including adequate consideration of externalities. Furthermore, DWS needs to employ decision-making models such as the RDMM to facilitate retrospective analyses to improve their institutional knowledge. Keywords: water resources management, dams, invasive alien plants, decision-making, unit reference values, rational decision-making model

    Examining the Influence of Non-Governmental Organizations upon the Long Term Outcomes of the Involuntary Community Resettlement Processes: With Special Reference to the Kariba Case, Zambia.

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    Researchers have clearly demonstrated that Development‐Induced Displacement and Resettlement (DIDR) usually risks impoverishing people and that annually, millions are displaced as a result. Although the impacts and consequences of resettlement are known, over the next couple of decades, development projects will continue to be needed to meet the different demands of growing economies and populations, of especially developing countries, making relocation sometimes unavoidable. Hence, over the years, many scholars have developed conceptual frameworks to understand and explain the impoverishment risks inherent in the resettlement phenomenon; and how those can be anticipated so as to be positively counteracted through strategic interactions and the implementation of development activities. Generally, the majority of those development activities to improve resettlement outcomes have often been planned, funded, and executed by the government, albeit with mixed levels of success, yet the possibilities of other development institutions such as Non‐Governmental Organizations (NGOs) have not been fully understood. However, a great deal of what is known about NGOs relates to their work in advocacy and activism to pressure governments to, for example, change relocation plans or raise awareness on the negative impacts of development projects on people and environment. Therefore, this thesis examines the influence of NGOs upon the on‐going outcomes of the involuntary community resettlement processes. The empirical basis is ethnographic research, which integrated several resettlement conceptual frameworks and theories about NGOs to collect and analyse data. Fieldwork was carried out in four villages of Simamba i.e. Malata, Kafwakuduli, Nangoba and Hamukonde. Simamba is one of the riverine Gwembe chiefdoms resettled following the construction of the Kariba dam on the Zambezi River bordering Zambia and Zimbabwe. The ethnographic research for this thesis was conducted from 2013 to 2015. In this thesis, I demonstrate that spatial factors influenced the resettlement trajectory using evidence from Simamba’s pre and post resettlement situation. I conclude by arguing that sustained contributions of the NGO type of development can positively influence the long‐term outcomes of involuntary community resettlement processes, and that problems that occurred were largely related to the management of the community development activities by the NGO under study. Therefore, this thesis is relevant to resettlement and development studies in general

    Integrated Algae Pond Systems for the Treatment of Municipal Wastewater

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    Integrated algae pond systems are a derivation of the Oswald designed advanced integrated wastewater ponding system, and combine the use of anaerobic and aerobic bioprocesses to effect wastewater treatment. Integrated algae pond system technology was introduced to South Africa in 1996 and a pilot plant was designed and commissioned at the Belmont Valley wastewater treatment works in Grahamstown. Previous studies showed that this system delivered a final effluent superior to most pond systems deployed in South Africa but that it was unable to meet the general standard for nutrient removal and effluent discharge. This study was initiated to re-appraise integrated algae pond systems and to assess the potential of the technology as an effective municipal sewage treatment system. And more..

    An investigation of the practices employed by an environmental community-based organization to successfully sustain its school based and community based projects (A case study)

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    Community-based organizations (CBOs) play a crucial role in sustainable development and hence it is important that they are promoted, guided and supported by state agencies and the private sector. The South African government encourages communities to establish co-operatives as a tool or strategy to address local social issues and risks and act accordingly. The purpose of this case study was to determine what aspects of the establishment and operation of a successful community-based environmental organization are producing sustained school and community projects. The study set out to investigate and audit the activities of a successful environmental CBO so as to determine how it has successfully sustained its school and community environmental projects. The reason for this investigation was to inform other CBOs and the state environmental agencies that support them on how to sustain their environmental activities in community and school contexts. The investigation was designed as an interpretive case study, which used document analysis, semi-structured interviews and observations to gather data. The gathered data was analyzed through inductive analysis to interpret and audit reported activities. Analytical memos were used to represent key themes in relation to the successful operations of the organization. Through auditing and reporting the activities in the analytical memos, analytical statements were developed. Those statements guided the discussion and informed the study‟s findings and recommendations. After investigating this CBO, it was concluded that, their success is a result of the establishment of a networking forum with different stakeholders and parties, community involvement in different projects, partnerships with local schools to develop and expand their curriculum practice, CBO networking locally and internationally and finally, their participation in annual and continuous environmental competitions/projects/programs. The insights gained and lessons learned will be used to advice and support community based co-operatives in environmental learning activities in school and community contexts as part of my ongoing work

    A study of factors enhancing truck driver retention at Tanker Services, Imperial Logistics, South Africa

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    The aim of this qualitative study was to gain an understanding of the factors that enhance truck driver retention at Tanker Services, Imperial Logistics, South Africa. The specific objectives of the study were to (1) explore factors which influence the retention of truck drivers from the perspectives of immediate supervisors of these drivers at Tanker Services Branches in Durban, Johannesburg, and Cape Town; (2) to identify the means Tanker Services adopts in meeting factors influential to truck driver retention; and (3) to provide recommendations on how to successfully retain truck drivers in this logistics organisation in South Africa. The research methodology of this study involved interviewing ten immediate managers of truck drivers at Tanker Services, Imperial Logistics. Specifically, data was collected through the use of individual, in-depth and semi-structured interviews to investigate the most influential factors affecting truck driver retention. The results of this research outline factors important to the truck drivers at Tanker Services from the perspectives of their immediate supervisors - most of whom were previously truck drivers themselves. The findings of this research identified the general factors that affect Tanker Services Truck drivers as follows: formal and informal rewards, competitive compensation, a work environment of quality equipment, high safety standards and recreational facilities. Furthermore, interpersonal relations and company reputation were found most influential to truck drivers in this South African logistics context

    Active Layer Dynamics at Four Borehole Sites in Western Dronning Maud Land, Antarctica

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    Permafrost and active layer dynamics in the Antarctic play an important role within terrestrial landscapes and ecosystems and as a climate change indicator. However, they remain less thoroughly researched than their Northern-Hemispheric counterpart. Despite advancements made by ANTPAS on the permafrost and active layer monitoring network in the Antarctic, observational gaps still exist. Western Dronning Maud Land (WDML) has been identified as one of these gaps, necessitating further research on permafrost dynamics and the influence of climate parameters thereon. Such elucidation is critical to both the cryospheric and life sciences. Variations in the surface climate of Antarctica can be seen as a result of inter-annual variations in atmospheric circulation, enhancing permafrost degradation and active layer thickening which directly affects soil processes, such as sorting and cryoturbation. Ground temperatures from four permafrost boreholes from WDML were analysed from 2007 to 2014. The study sites exhibit seasonal freezing, periglacial landforms, and altitudinal variation, ranging between ca. 450masl to ca. 1300masl. Using ground thermal regime and regional climate data, the spatial and temporal variability of the active layer in the Ahlmannryggen and Jutulsessen areas of WDML were characterised. 137 Cs tracing has revealed that the active layer and associated landforms have been active over the past half century. Further results show that active layer depths at each site vary inter-annually and are particularly influenced by snow cover, altitude and distance to the ice-shelf. Moreover, a correlation between the SAO (Semi-Annual Oscillation) and measured ground temperatures was found, principally during the transitional season of the SAO in May and September. The relationship between climate and ground thermal regimes, especially the influence of teleconnections thereon, is essential to improving the understanding of permafrost dynamics and landform morphology in continental Antarctica

    Rural livelihood strategies of female headed households in former Bantustans of post apartheid South Africa: The case of Cala, Eastern Cape Province.

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    Communal areas in contemporary South Africa (that is, the former Bantustans of apartheid South Africa) continue to bear and endure, albeit in new forms, socio-economic and political vulnerabilities which are negatively affecting household livelihoods. Current studies on rural livelihoods have failed to keep pace in exploring and analysing the lived experiences and ever-changing challenges faced by these rural households. This thesis provides an understanding and explanation of the livelihood activities of specifically de facto and de jure female-headed households in the former Transkei Bantustan, with a specific focus on villages in Cala. This is framed analytically by feminist theories with their emphasis on systems of patriarchy and by a rural livelihoods framework. It uses a multiplicity of research methods, including focus group discussions, in-depth interviews, life histories and survey questionnaires. The major findings of the thesis show that the female-headed households in Cala depend upon agricultural-based activities and non-agriculturally-based activities and income (including social grants) but that they exist under conditions of extreme vulnerability which are subject to fluctuation. In the end, the livelihoods of female-headed households are precarious and unstable as they live under circumstances of poverty. However, the female heads are not mere passive victims of the rural crisis in post-apartheid South Africa, as they demonstrate qualities of ingenuity and resourcefulness including through a range of coping mechanisms. At the same time, rural communities continue to be marked by patriarchal norms and practices, including systems of chieftainship, which disempower women (including female heads), though this affects de jure heads and de facto heads differently. The thesis contributes to an understanding of rural livelihoods in communal areas (or former Bantustans) of present-day South Africa by way of ‘thick descriptions’ of the everyday lives of female heads in Cala. Further, in examining rural livelihoods, it highlights the importance of bringing to bear on the livelihoods framework a feminist perspective in pinpointing the additional livelihood burdens carried by rural women

    Epistemological access in a science foundation course: A social realist perspective

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    This dissertation examines how educational practices of a multidisciplinary, integrated science foundation course, Introduction to Science Concepts and Methods (ISCM), at Rhodes University in South Africa, enable and/or constrain epistemological access to a range of mainstream science disciplines. Students in the ISCM course are mainly African, working-class, first-generation higher education learners whose home language is seldom English. This study is motivated firstly by poor success of working-class African students in higher education in South Africa in general and in the sciences in particular, and secondly by the need for closely theorised, empirical work to guide necessary transformational change that will contribute to equity and, thus, to greater social justice. Since I teach in ISCM and coordinate the programme in which it is located, I also have a personal and professional interest in improving my own practice. Conceptually the study draws on Morrow’s (2007, 2009) and various literacy theorists interpretations of the concept of epistemological access, which in this study is about becoming and being a participant in an academic practice by virtue of learning both the knowledge as well as the norms, values and beliefs that constitute the practice. Theoretically and analytically the study draws on Maton’s (2014a) Legitimation Code Theory (LCT) and on various aspects of Bernstein’s (2000) code theory work. Codes are the organising principles or ‘rules of the game’ of practices and code theory is premised on the idea that power and control in education systems manifest themselves through the structural and interactional aspects of educational practices, and therefore have the capacity to include or exclude. Analysing educational practices using code theory enables characterisation of the practices, highlights their underpinning principles, and allows for their effects to be considered. This layered approach to analysis indicates that a critical realist depth ontology serves as an underlabourer to code theory. The desired ‘effect’ of educational practices in this study, is students gaining epistemological access to science, or science disciplines, in higher education. The overall approach is a single, in-depth, qualitative case study with a primary focus on what is legitimated in ISCM educational practices (curriculum, pedagogy, assessment) and how students respond to these practices. A lesser focus is how ex-ISCM students are responding to educational practices in the first-year, first-semester Cell Biology, Chemistry, Earth Sciences and Physics mainstream courses, and whether they are attaining epistemological access. To examine educational practices in ISCM and mainstream courses data from document analysis, interviews, observations and critical reflections are analysed through developing external languages of description. The two LCT code dimensions of Specialisation (what or who specialises a practice) and Semantics (how meaning relates to context and empirical referents) are used to examine curriculum, Bernstein’s (2000) framing of the regulative and instructional discourses are drawn on in considering pedagogy, and an adapted cognitive process level model assists in analysing assessment practices. To examine student responses to educational practices Bernstein’s (ibid.) concept of acquisition of recognition and realisation rules is used. Since ISCM serves the dual purpose of developing scientific conceptual knowledge, as well as supporting student learning in an academic context, a complex picture of practices and underpinning codes emerges. Based on epistemological concerns of developing students as scientists, ISCM legitimates an epistemic-context knowledge code and a rhizomatic/worldly curriculum code. If students produce the legitimated epistemic-context scientific ‘text’, they have attained epistemic access. Based on axiological concerns of the learning context, ISCM also legitimates a learning-context knower code. By producing the legitimate learning-context ‘text’ of an autonomous, self-regulated science learner, students demonstrate they have attained learning-context access. Both forms of access are key for student success, and combined they constitute epistemological access. The findings of the study indicate that framing and legitimation of educational practices in ISCM, by most accounts, should be promoting epistemological access. When epistemological access is not attained in ISCM it is suggested this is likely due to both a code clash at the learning-context level and competing code demands between epistemic-context and learning-context concerns. Poor access in mainstream courses appears to be exacerbated by both a narrow-based knowledge code and little or no support for a learning-context knower code. The study concludes by outlining a two-tiered conceptual model of epistemological access in the sciences based on the mutually integrative components of epistemic- and learning-context access. Because of inequitable outcomes in science mainstream courses at Rhodes University based on race and/or class I argue for far-reaching transformative pedagogies throughout the faculty, and in the broader South African science higher education sector, that address and accommodate issues of diversity and difference. This should include, amongst other things, a weakening of epistemic relations to create space for a strengthening of learning-context social relations. This is not a suggestion to move away from a science knowledge code, which I argue is based on powerful knowledge to which all students must gain access, but instead a shift in emphasis to better support previously educationally disenfranchised students and to understand in a more rigorous manner what epistemological access means to them as individuals. In light of the recent disruptive and angry student calls for decolonisation of the curriculum, this is an urgent imperative

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