A comparative study of conceptualisations and practices of inclusion as an aspect of social justice in three teacher education institutions in Canada, South Africa and Zimbabwe
- Authors: Musara, Ellison
- Date: 2020
- Subjects: Social justice and education , Teachers -- Training of -- Canada , Teachers -- Training of -- South Africa , Teachers -- Training of -- Zimbabwe , Educational sociology -- Canada , Educational sociology -- South Africa , Educational sociology -- Zimbabwe , Educational equalization , Inclusive education , Education -- Moral and ethical aspects , Critical realism
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/144138 , vital:38314
- Description: This study sought to examine understandings and practices of inclusion as social justice in teacher education programmes in three countries: Canada, South Africa and Zimbabwe. While inclusive education has become an issue of increasing importance globally, contemporary research shows that not much attention has been given to the preparation of teachers as a key element in developing inclusive education systems. Recognising that pre-service teacher education is vital to the success and continued development of inclusive educational practice, the purpose of this qualitative study was to better understand the ways in which inclusion is understood and practiced in the field of teacher education. Using Roy Bhaskar’s (1978) critical realism as a metatheory and drawing on Fraser’s substantive theory of social justice (2008, 2009) and Tronto’s ethic of care (1993, 2013), this study explored the extent to which teacher education faculty and teacher candidates understood and practiced inclusion as an aspect of social justice. The data used in this study was generated through individual and focus group interviews and document analysis in three higher education institutions, one in each of the three countries. In Canada, four teacher educators took part in the interviews while five teacher candidates participated in the focus group. Similarly, in South Africa, three teacher educators and eight teacher candidates participated, and in Zimbabwe, four teacher educators and eight teacher candidates took part in the study respectively. Findings from the study revealed that inclusion still means different things to different people, reflecting contrasting theoretical and ideological orientations from which inclusion is considered, while still remaining a major educational policy concern in all three countries. In the Canadian and South African institutions, inclusion is viewed more in terms of systemic educational change in pursuit of equity, social justice and equal educational opportunities for all learners. In the Zimbabwean institution, the primary focus of inclusion remains creating conditions that make it possible for students with disabilities to overcome barriers to learning and participation by providing specialist educational measures and interventions intended to respond to specific forms of impairment. As a comparative study, it is hoped that this study will contribute to the knowledge of variations and patterns in the ways in which inclusive education is shaped by societal forces such as political, economic and cultural conditions.
- Full Text:
- Authors: Musara, Ellison
- Date: 2020
- Subjects: Social justice and education , Teachers -- Training of -- Canada , Teachers -- Training of -- South Africa , Teachers -- Training of -- Zimbabwe , Educational sociology -- Canada , Educational sociology -- South Africa , Educational sociology -- Zimbabwe , Educational equalization , Inclusive education , Education -- Moral and ethical aspects , Critical realism
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/144138 , vital:38314
- Description: This study sought to examine understandings and practices of inclusion as social justice in teacher education programmes in three countries: Canada, South Africa and Zimbabwe. While inclusive education has become an issue of increasing importance globally, contemporary research shows that not much attention has been given to the preparation of teachers as a key element in developing inclusive education systems. Recognising that pre-service teacher education is vital to the success and continued development of inclusive educational practice, the purpose of this qualitative study was to better understand the ways in which inclusion is understood and practiced in the field of teacher education. Using Roy Bhaskar’s (1978) critical realism as a metatheory and drawing on Fraser’s substantive theory of social justice (2008, 2009) and Tronto’s ethic of care (1993, 2013), this study explored the extent to which teacher education faculty and teacher candidates understood and practiced inclusion as an aspect of social justice. The data used in this study was generated through individual and focus group interviews and document analysis in three higher education institutions, one in each of the three countries. In Canada, four teacher educators took part in the interviews while five teacher candidates participated in the focus group. Similarly, in South Africa, three teacher educators and eight teacher candidates participated, and in Zimbabwe, four teacher educators and eight teacher candidates took part in the study respectively. Findings from the study revealed that inclusion still means different things to different people, reflecting contrasting theoretical and ideological orientations from which inclusion is considered, while still remaining a major educational policy concern in all three countries. In the Canadian and South African institutions, inclusion is viewed more in terms of systemic educational change in pursuit of equity, social justice and equal educational opportunities for all learners. In the Zimbabwean institution, the primary focus of inclusion remains creating conditions that make it possible for students with disabilities to overcome barriers to learning and participation by providing specialist educational measures and interventions intended to respond to specific forms of impairment. As a comparative study, it is hoped that this study will contribute to the knowledge of variations and patterns in the ways in which inclusive education is shaped by societal forces such as political, economic and cultural conditions.
- Full Text:
A critical analysis of the de-peasantisation process in Nepal with specific reference to the role of state land policies since the 1950s
- Authors: Basnet, Jagat
- Date: 2020
- Subjects: Land tenure -- Nepal , Land reform -- Law and legislation -- Nepal , Nepal -- Politics and government , Peasants -- Nepal -- Economic conditions , Panchayat -- Nepal
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/138716 , vital:37667
- Description: The principal objective of this thesis is to offer a critical analysis of the process of de-peasantisation in Nepal since 1950, with a particular focus on the capitalist neo-liberal restructuring of the economy beginning in the early 1990s. The analysis begins by tracing the legacy of feudal land practices and landholdings from the pre-1950 Rana and Shah dynasties. It was under these feudal dynasties that economic and political institutions of extraction first emerged, leading to a landlord-peasant agrarian economy in which peasants (often as tenants/sharecroppers and smallholders) were subordinate to the power nexus between feudal landlords and the ruling dynasties. After 1950, a window of democratic opening was soon interrupted by the formation of the party-less Panchayat system, which lasted from 1960 to 1990. In 1964, a major land reform measure was enacted under the Lands Act, with the goal of enhancing the security and livelihood of the peasantry. However, this process was met with significant resistance by feudal landlords, and actually led to deepening insecurity and the loss of land by peasants, with farmers belonging to lower castes and indigenous groups experiencing this with a greater degree of intensity. The overall result of this period was the beginnings of what is referred to in this study as de-peasantisation. This line of analysis shows that the institutions of extraction remained firmly in place even after the reforms of this period. Finally, the neo-liberal period, which was marked by land titling, the marketisation of land, and the commercialisation of agriculture, represents the late entry of capitalism into Nepal. This period saw the deepening and widening of the process of de-peasantisation, including further loss of peasants’ access to land and a general turn to wage-labour. In this regard, despite propagating the slogan ‘land to the tillers’, the major political parties in Nepal (including the Maoist party) have failed to defend the interests of the peasantry. Some progressive civil society groups have recently sought to do better, but there is also evidence of peasant organisations themselves seeking to resist and oppose the de-peasantisation effects of neo-liberal restructuring. This thesis thus considers the form and extent of de-peasantisation in Nepal, and some responses to it, over an extended period. A broad Marxist-based political economy perspective has been adopted in pursuing the principal thesis objective, but one which argues that there is a symbiotic relationship between economic and political power, such that the latter is not reducible to the former. The thesis draws upon original fieldwork in twenty districts of Nepal, including through the use of a survey, interviews, observations, case studies, and focus group discussions, thus combining both quantitative and qualitative research methods. Based on this fieldwork, it becomes clear that (i) there are major social, economic, and political forces behind the processes of de-peasantisation in the studied districts (and in Nepal more broadly), and that (ii) the Nepali peasantry is becoming increasingly landless, or land-short, and subject to processes of proletarianisation.
- Full Text:
- Authors: Basnet, Jagat
- Date: 2020
- Subjects: Land tenure -- Nepal , Land reform -- Law and legislation -- Nepal , Nepal -- Politics and government , Peasants -- Nepal -- Economic conditions , Panchayat -- Nepal
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/138716 , vital:37667
- Description: The principal objective of this thesis is to offer a critical analysis of the process of de-peasantisation in Nepal since 1950, with a particular focus on the capitalist neo-liberal restructuring of the economy beginning in the early 1990s. The analysis begins by tracing the legacy of feudal land practices and landholdings from the pre-1950 Rana and Shah dynasties. It was under these feudal dynasties that economic and political institutions of extraction first emerged, leading to a landlord-peasant agrarian economy in which peasants (often as tenants/sharecroppers and smallholders) were subordinate to the power nexus between feudal landlords and the ruling dynasties. After 1950, a window of democratic opening was soon interrupted by the formation of the party-less Panchayat system, which lasted from 1960 to 1990. In 1964, a major land reform measure was enacted under the Lands Act, with the goal of enhancing the security and livelihood of the peasantry. However, this process was met with significant resistance by feudal landlords, and actually led to deepening insecurity and the loss of land by peasants, with farmers belonging to lower castes and indigenous groups experiencing this with a greater degree of intensity. The overall result of this period was the beginnings of what is referred to in this study as de-peasantisation. This line of analysis shows that the institutions of extraction remained firmly in place even after the reforms of this period. Finally, the neo-liberal period, which was marked by land titling, the marketisation of land, and the commercialisation of agriculture, represents the late entry of capitalism into Nepal. This period saw the deepening and widening of the process of de-peasantisation, including further loss of peasants’ access to land and a general turn to wage-labour. In this regard, despite propagating the slogan ‘land to the tillers’, the major political parties in Nepal (including the Maoist party) have failed to defend the interests of the peasantry. Some progressive civil society groups have recently sought to do better, but there is also evidence of peasant organisations themselves seeking to resist and oppose the de-peasantisation effects of neo-liberal restructuring. This thesis thus considers the form and extent of de-peasantisation in Nepal, and some responses to it, over an extended period. A broad Marxist-based political economy perspective has been adopted in pursuing the principal thesis objective, but one which argues that there is a symbiotic relationship between economic and political power, such that the latter is not reducible to the former. The thesis draws upon original fieldwork in twenty districts of Nepal, including through the use of a survey, interviews, observations, case studies, and focus group discussions, thus combining both quantitative and qualitative research methods. Based on this fieldwork, it becomes clear that (i) there are major social, economic, and political forces behind the processes of de-peasantisation in the studied districts (and in Nepal more broadly), and that (ii) the Nepali peasantry is becoming increasingly landless, or land-short, and subject to processes of proletarianisation.
- Full Text:
A critique of the language of record in South African courts in relation to selected university language policies
- Authors: Docrat, Zakeera
- Date: 2020
- Subjects: Language policy -- South Africa , Forensic linguistics -- South Africa , Communication in law -- South Africa , Language planning -- South Africa , Linguistic rights -- South Africa , Court interpreting and translating -- South Africa , Multilingual education -- South Africa , Language and education -- South Africa , Education, Higher -- Social aspects -- South Africa
- Language: English
- Type: text , Thesis , Doctoral , PHD
- Identifier: http://hdl.handle.net/10962/141394 , vital:37968
- Description: This interdisciplinary research located in the research area of forensic linguistics seeks to provide a critique of the monolingual language of record directive for courts in South Africa, while investigating how university language policies contribute the formulation of a monolingual language of record policy for courts, by graduating monolingual LLB students. The research commences with identifying the research problem, goals and objectives and how the language of record policy for courts is linked to university language planning. The research proceeds to an overview of scholarly literature concerning the historical developments of language planning in both the legal system and higher education in South Africa. The theoretical principles concerning the enacting of language legislation and policies is advanced in relation to the constitutional framework. This research furthermore provides a thorough critique of the constitutional framework where the language rights the other related language provisions are discussed in relation to the theory and the application thereof in case law. The research explicates that the language rights of African language speaking litigants is unfairly limited and that access to justice for these litigants is either unattainable or achieved to a lesser extent. The disparities between language, law and power are brought to the fore, where the relevant legislation and language policies fail to determine the language of record in courts as well as legislate the African language requirements for legal practitioners in giving meaning to the constitutional language rights. The language policies of six selected universities is discussed in relation to the legal system’s legislative and policy frameworks, outlining the need to transform the language of learning and teaching and develop the curriculum to support the legal system. In doing so, the shortcomings of the interpretation profession in South Africa are highlighted and the effects thereof on the language rights of litigants. This thesis advances seven African and international case studies, comprising Kenya, Morocco, Nigeria, Australia, Belgium, Canada and India. Each of the case studies provides an in-depth analysis of the language of record/proceedings in courts and the language competencies of legal practitioners and judicial officers in relation to their university education. The African case studies are illustrative that English on the African continent in courts and higher education is dominate and the resultant loss of indigenous languages marginalises people from mainstream society. The international case studies provide two models, Belgium and Canada, which South Africa can emulate, in enacting new legislation and policies and the amendment of current legislation, to ensure bilingual/ multilingual language policies are drafted for courts per province, where the language demographics present majority spoken languages alongside English. Furthermore, where courts interpret language rights and legislative and policy provisions in a purposive manner, where African language speakers are able to, fully realise their rights. Australia and India as multilingual models serve as important case studies where South Africa can learn from what to avoid, how to subvert challenges or adequately address these. These case studies highlight the dangers of a political elite who pursue an English only agenda at the expense of the indigenous languages and the speakers thereof. This thesis in conclusion provides interdisciplinary recommendations that need to be implemented in order to address the language question in South African courts and higher education.
- Full Text:
- Authors: Docrat, Zakeera
- Date: 2020
- Subjects: Language policy -- South Africa , Forensic linguistics -- South Africa , Communication in law -- South Africa , Language planning -- South Africa , Linguistic rights -- South Africa , Court interpreting and translating -- South Africa , Multilingual education -- South Africa , Language and education -- South Africa , Education, Higher -- Social aspects -- South Africa
- Language: English
- Type: text , Thesis , Doctoral , PHD
- Identifier: http://hdl.handle.net/10962/141394 , vital:37968
- Description: This interdisciplinary research located in the research area of forensic linguistics seeks to provide a critique of the monolingual language of record directive for courts in South Africa, while investigating how university language policies contribute the formulation of a monolingual language of record policy for courts, by graduating monolingual LLB students. The research commences with identifying the research problem, goals and objectives and how the language of record policy for courts is linked to university language planning. The research proceeds to an overview of scholarly literature concerning the historical developments of language planning in both the legal system and higher education in South Africa. The theoretical principles concerning the enacting of language legislation and policies is advanced in relation to the constitutional framework. This research furthermore provides a thorough critique of the constitutional framework where the language rights the other related language provisions are discussed in relation to the theory and the application thereof in case law. The research explicates that the language rights of African language speaking litigants is unfairly limited and that access to justice for these litigants is either unattainable or achieved to a lesser extent. The disparities between language, law and power are brought to the fore, where the relevant legislation and language policies fail to determine the language of record in courts as well as legislate the African language requirements for legal practitioners in giving meaning to the constitutional language rights. The language policies of six selected universities is discussed in relation to the legal system’s legislative and policy frameworks, outlining the need to transform the language of learning and teaching and develop the curriculum to support the legal system. In doing so, the shortcomings of the interpretation profession in South Africa are highlighted and the effects thereof on the language rights of litigants. This thesis advances seven African and international case studies, comprising Kenya, Morocco, Nigeria, Australia, Belgium, Canada and India. Each of the case studies provides an in-depth analysis of the language of record/proceedings in courts and the language competencies of legal practitioners and judicial officers in relation to their university education. The African case studies are illustrative that English on the African continent in courts and higher education is dominate and the resultant loss of indigenous languages marginalises people from mainstream society. The international case studies provide two models, Belgium and Canada, which South Africa can emulate, in enacting new legislation and policies and the amendment of current legislation, to ensure bilingual/ multilingual language policies are drafted for courts per province, where the language demographics present majority spoken languages alongside English. Furthermore, where courts interpret language rights and legislative and policy provisions in a purposive manner, where African language speakers are able to, fully realise their rights. Australia and India as multilingual models serve as important case studies where South Africa can learn from what to avoid, how to subvert challenges or adequately address these. These case studies highlight the dangers of a political elite who pursue an English only agenda at the expense of the indigenous languages and the speakers thereof. This thesis in conclusion provides interdisciplinary recommendations that need to be implemented in order to address the language question in South African courts and higher education.
- Full Text:
A gendered analysis of conditional cash based transfers: a case study of Puntland Technical Vocational Skills Training Programme, Somalia
- Authors: Chitombi, Rumbidzai
- Date: 2020
- Subjects: Puntland Technical Vocational Skills Training Programme , Transfer payments -- Somalia -- Case studies , Economic assistance, Domestic -- Somalia , Economic development -- Social aspects -- Somalia , Women -- Somalia -- Social conditions
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/167335 , vital:41469
- Description: As part of the worldwide development system, conditional cash transfer (CCT) programmes have become an increasingly popular policy and development approach in seeking to address poverty, especially in developing countries. Under the CCT programmes, beneficiaries are given assistance in the form of either cash or cash vouchers after fulfilling certain obligations of the development programme, such as attending training, enacting proper health care, or ensuring regular school attendance of children. The programmes have been described as a ‘double-edged sword’ since they aim to address poverty and, at the same time, reduce reliance on government largesse. In this regard, they are seen as potentially effective, and more empowering, alternatives to more traditional social assistance programmes whereby poor people receive welfare assistance in the form of ‘in kind’ and ‘unconditional’ assistance, receiving this as either food or shelter commodities, and without having to meet any conditions in doing so. This ‘traditional’ way of assisting poor people has largely been criticised for creating a dependency syndrome amongst the beneficiaries. In certain cases, CCT programmes focus specifically on women, either in receiving the cash transfer or in meeting the conditions attached to the programme, or both. In this context, considerable debate exists in the scholarly literature about the effects of such CCT programmes on the situation and status of women, specifically in terms of possibly empowering women. While some scholars claim that these programmes enhance the human and financial assets of women, others argue that focusing specifically on women, and as care-givers within households, tends to reproduce gender-based inequalities and subordination. Since gender equality and female empowerment are now key issues in global development spheres, and at national levels, this thesis aims to contribute to literature on the effects of CCTs on gender and women’s empowerment. This is pursued by way of a gendered perspective on CCTs as a development methodology for empowering women with reference to Somalia, using the Puntland Technical Vocational Skills Training programme as a case study. This programme focused, in the main, on internally-displaced people in Somalia, with a particular emphasis on women in meeting the programme conditions (i.e. participating in a training programme) and in being the cash recipients. The study used both quantitative and qualitative approaches for data collection and analysis, focusing on sixty selected beneficiaries who participated in the Puntland Technical Vocational skills training programme in Somalia from 2013. The thesis examines the prevailing structures (including cultural dynamics and socio-economic factors) in Somalia which lead to women’s subordination, notably in the light of significant internal displacement because of war and conflict and the emergence of internally-displaced camps. On this basis, from a gendered perspective, there is a critical appraisal of the manner in which the Puntland CCT programme affected women’s subordinate status, including how it may have led to the restructuring of gendered relations at both household and community levels. In offering this appraisal with reference to the Puntland programme, the thesis argues that women’s subordination and, by extension, women’s empowerment, is multi-faceted, and that continuity and change along the dimensions of subordination is often uneven and contradictory. Further, as also demonstrated in the Puntland case study, women’s subordination (as a social totality) is not a totalising system, such that women regularly make use of gaps in the system as opportunities to enhance their well-being without confronting the totality of the system.
- Full Text:
- Authors: Chitombi, Rumbidzai
- Date: 2020
- Subjects: Puntland Technical Vocational Skills Training Programme , Transfer payments -- Somalia -- Case studies , Economic assistance, Domestic -- Somalia , Economic development -- Social aspects -- Somalia , Women -- Somalia -- Social conditions
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/167335 , vital:41469
- Description: As part of the worldwide development system, conditional cash transfer (CCT) programmes have become an increasingly popular policy and development approach in seeking to address poverty, especially in developing countries. Under the CCT programmes, beneficiaries are given assistance in the form of either cash or cash vouchers after fulfilling certain obligations of the development programme, such as attending training, enacting proper health care, or ensuring regular school attendance of children. The programmes have been described as a ‘double-edged sword’ since they aim to address poverty and, at the same time, reduce reliance on government largesse. In this regard, they are seen as potentially effective, and more empowering, alternatives to more traditional social assistance programmes whereby poor people receive welfare assistance in the form of ‘in kind’ and ‘unconditional’ assistance, receiving this as either food or shelter commodities, and without having to meet any conditions in doing so. This ‘traditional’ way of assisting poor people has largely been criticised for creating a dependency syndrome amongst the beneficiaries. In certain cases, CCT programmes focus specifically on women, either in receiving the cash transfer or in meeting the conditions attached to the programme, or both. In this context, considerable debate exists in the scholarly literature about the effects of such CCT programmes on the situation and status of women, specifically in terms of possibly empowering women. While some scholars claim that these programmes enhance the human and financial assets of women, others argue that focusing specifically on women, and as care-givers within households, tends to reproduce gender-based inequalities and subordination. Since gender equality and female empowerment are now key issues in global development spheres, and at national levels, this thesis aims to contribute to literature on the effects of CCTs on gender and women’s empowerment. This is pursued by way of a gendered perspective on CCTs as a development methodology for empowering women with reference to Somalia, using the Puntland Technical Vocational Skills Training programme as a case study. This programme focused, in the main, on internally-displaced people in Somalia, with a particular emphasis on women in meeting the programme conditions (i.e. participating in a training programme) and in being the cash recipients. The study used both quantitative and qualitative approaches for data collection and analysis, focusing on sixty selected beneficiaries who participated in the Puntland Technical Vocational skills training programme in Somalia from 2013. The thesis examines the prevailing structures (including cultural dynamics and socio-economic factors) in Somalia which lead to women’s subordination, notably in the light of significant internal displacement because of war and conflict and the emergence of internally-displaced camps. On this basis, from a gendered perspective, there is a critical appraisal of the manner in which the Puntland CCT programme affected women’s subordinate status, including how it may have led to the restructuring of gendered relations at both household and community levels. In offering this appraisal with reference to the Puntland programme, the thesis argues that women’s subordination and, by extension, women’s empowerment, is multi-faceted, and that continuity and change along the dimensions of subordination is often uneven and contradictory. Further, as also demonstrated in the Puntland case study, women’s subordination (as a social totality) is not a totalising system, such that women regularly make use of gaps in the system as opportunities to enhance their well-being without confronting the totality of the system.
- Full Text:
A holistic approach in understanding the effects of dietary protein sources on the growth and reproductive development of farmed abalone, Haliotis midae
- Wu, Yu
- Authors: Wu, Yu
- Date: 2020
- Subjects: Abalones -- Nutrition , Abalones -- Reproduction , Abalones -- Growth , Abalone culture , Haliotis midae -- Nutrition , Haliotis midae -- Reproduction , Haliotis midae -- Growth , Haliotis midae fisheries
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/167719 , vital:41506
- Description: The combination of fishmeal and soya in the formulated feed of farmed South African abalone, Haliotis midae, not only improved abalone growth, but also the sustainability of the compound diets by reducing the reliance on fishmeal. However, the presence of soya produced larger gonads compared to those of abalone fed kelp or single-source protein diets. There is an increasing drive to control sexual maturation and reduce undesirable spawning events in farmed abalone. However, the reasons for the reported effects of soya inclusion on the reproductive development of farmed H. midae remain unresolved. The aim of this research was to use a combination of techniques to contribute to the understanding of the relationship between growth, reproductive and nutritional physiology of farmed H. midae fed diets of varying protein sources. These techniques included stable isotope analysis (SIA), fatty acid analysis, gonad histological assessments and haemolymph sexsteroid hormone analysis. The objectives were to examine the allocation of protein and nutritional components to somatic and reproductive tissues. This study also included the first attempt to investigate the role that sex steroid hormones play during gametogenesis. Abalone (40 – 50 g abalone-1) were fed one of four diets: either a single-source protein-based diet, i.e., (1) fishmeal-only (FM) or (2) soya-only (S), or a combination diet of (3) fishmeal-soya (FM S) or (4) fishmeal-sunflower meal (FM SM). Sampling occurred in 45-day intervals over one year. Dietary protein source had an effect on the growth of abalone, with enhancements in growth linked to the combination of fishmeal and a plant-protein source. The fishmeal ingredient was the most utilised protein source throughout the temporal changes in protein allocation into somatic and reproductive tissue, followed by soya and then sunflower meal. The mean whole- body mass of abalone was significantly influenced by an interaction between time and dietary treatment, with average whole-body mass changing differently over time between treatments (RM-ANOVA, F(24, 96) = 2.13, p = 0.005). Overall, abalone that were fed FM S had higher mean whole-body mass values than abalone that were fed the single-protein based diets, while abalone that were fed FM SM were similar to animals from all dietary treatments (RMANOVA, F(3, 12) = 5.75, p = 0.01). Male abalone had significantly higher gonad bulk index (GBI) values compared to females (RM-ANOVA, F(1, 24) = 49.03, p < 0.001) and this was independent of dietary treatment. Within each sex, female abalone fed the FM S diet (15.92 ± 1.88 mm3 g-1) had significantly higher GBI values than abalone fed S (9.76 ± 1.08 mm3 g-1), while abalone fed FM (11.96 ± 1.71 mm3 g-1) and FM SM (11.90 ± 0.80 mm3 g-1) were similar to abalone from all other dietary treatments (Tukey’s HSD, p < 0.05). Male abalone fed the FM S (21.59 ± 2.10 mm3 g-1) and FM SM diet (19.30 ± 2.63 mm3 g-1) had similar GBI values and they were significantly higher than in abalone fed the S diet (14.74 ± 1.27 mm3 g-1), while abalone fed FM S had significantly higher GBI values than abalone that consumed the FM diet (15.08 ±1.63mm3 g-1) ( Tukey’s HSD, p < 0.05). Although sunflower meal was poorly utilised, it produced similar overall growth to abalone that were fed the FM S diets. Yet, feed conversion ratio values were significantly lower for abalone fed FM S (1.30 ± 0.13) compared to those in the other three treatments, with ratios ranging from 1.65 – 1.72 over the one-year. The fatty acid compositions of the somatic and gonadal tissues were similar between treatments (PERMANOVA, p = 0.21), while fatty acid composition was influenced by sampling day, tissue type and abalone sex (PERMANOVA, p < 0.05). The essential fatty acids (EFAs) eicosadienoic acid and a-linolenic acid were present in abalone tissue, but they were not detected in the diets, suggesting the important role that an alternate food source (e.g. farmed abalone also had access to diatoms) may have played and the ability that H. midae may have in converting long-chain polyunsaturated fatty acids from C18 precursors. A change in the abundance of EFAs in the gonad tissue during highest and lowest GBI values suggested that arachidonic, eicosapentaenoic, g-linolenic and linoleic acid were important in females, while eicosapentaenoic, eicosadienoic and a-linolenic acid were important for male reproductive development. Dietary protein sources had an effect on the frequency distribution of maturity stages, where females that were fed FM S produced more ripe gonads and more males that were fed FM SM contained testes that showed signs of ripeness over the one-year study. Although dietary protein influenced the sex steroid concentrations in females and males, exhibiting fluctuations throughout the one-year period, no distinct pattern linked to gametogenesis were observed. The results from this study illustrate: (1) the importance of conducting laboratory studies when implementing SIA and mixing models in aquaculture nutrition; (2) conducting nutritional studies on mature, grow-out abalone; and (3) assessing the importance of naturally occurring diatoms in their diet and their contribution to growth and reproduction. The novel contribution of this research towards abalone nutritional physiology, the implications of these findings to industry as well as potential considerations for future studies were addressed.
- Full Text:
- Authors: Wu, Yu
- Date: 2020
- Subjects: Abalones -- Nutrition , Abalones -- Reproduction , Abalones -- Growth , Abalone culture , Haliotis midae -- Nutrition , Haliotis midae -- Reproduction , Haliotis midae -- Growth , Haliotis midae fisheries
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/167719 , vital:41506
- Description: The combination of fishmeal and soya in the formulated feed of farmed South African abalone, Haliotis midae, not only improved abalone growth, but also the sustainability of the compound diets by reducing the reliance on fishmeal. However, the presence of soya produced larger gonads compared to those of abalone fed kelp or single-source protein diets. There is an increasing drive to control sexual maturation and reduce undesirable spawning events in farmed abalone. However, the reasons for the reported effects of soya inclusion on the reproductive development of farmed H. midae remain unresolved. The aim of this research was to use a combination of techniques to contribute to the understanding of the relationship between growth, reproductive and nutritional physiology of farmed H. midae fed diets of varying protein sources. These techniques included stable isotope analysis (SIA), fatty acid analysis, gonad histological assessments and haemolymph sexsteroid hormone analysis. The objectives were to examine the allocation of protein and nutritional components to somatic and reproductive tissues. This study also included the first attempt to investigate the role that sex steroid hormones play during gametogenesis. Abalone (40 – 50 g abalone-1) were fed one of four diets: either a single-source protein-based diet, i.e., (1) fishmeal-only (FM) or (2) soya-only (S), or a combination diet of (3) fishmeal-soya (FM S) or (4) fishmeal-sunflower meal (FM SM). Sampling occurred in 45-day intervals over one year. Dietary protein source had an effect on the growth of abalone, with enhancements in growth linked to the combination of fishmeal and a plant-protein source. The fishmeal ingredient was the most utilised protein source throughout the temporal changes in protein allocation into somatic and reproductive tissue, followed by soya and then sunflower meal. The mean whole- body mass of abalone was significantly influenced by an interaction between time and dietary treatment, with average whole-body mass changing differently over time between treatments (RM-ANOVA, F(24, 96) = 2.13, p = 0.005). Overall, abalone that were fed FM S had higher mean whole-body mass values than abalone that were fed the single-protein based diets, while abalone that were fed FM SM were similar to animals from all dietary treatments (RMANOVA, F(3, 12) = 5.75, p = 0.01). Male abalone had significantly higher gonad bulk index (GBI) values compared to females (RM-ANOVA, F(1, 24) = 49.03, p < 0.001) and this was independent of dietary treatment. Within each sex, female abalone fed the FM S diet (15.92 ± 1.88 mm3 g-1) had significantly higher GBI values than abalone fed S (9.76 ± 1.08 mm3 g-1), while abalone fed FM (11.96 ± 1.71 mm3 g-1) and FM SM (11.90 ± 0.80 mm3 g-1) were similar to abalone from all other dietary treatments (Tukey’s HSD, p < 0.05). Male abalone fed the FM S (21.59 ± 2.10 mm3 g-1) and FM SM diet (19.30 ± 2.63 mm3 g-1) had similar GBI values and they were significantly higher than in abalone fed the S diet (14.74 ± 1.27 mm3 g-1), while abalone fed FM S had significantly higher GBI values than abalone that consumed the FM diet (15.08 ±1.63mm3 g-1) ( Tukey’s HSD, p < 0.05). Although sunflower meal was poorly utilised, it produced similar overall growth to abalone that were fed the FM S diets. Yet, feed conversion ratio values were significantly lower for abalone fed FM S (1.30 ± 0.13) compared to those in the other three treatments, with ratios ranging from 1.65 – 1.72 over the one-year. The fatty acid compositions of the somatic and gonadal tissues were similar between treatments (PERMANOVA, p = 0.21), while fatty acid composition was influenced by sampling day, tissue type and abalone sex (PERMANOVA, p < 0.05). The essential fatty acids (EFAs) eicosadienoic acid and a-linolenic acid were present in abalone tissue, but they were not detected in the diets, suggesting the important role that an alternate food source (e.g. farmed abalone also had access to diatoms) may have played and the ability that H. midae may have in converting long-chain polyunsaturated fatty acids from C18 precursors. A change in the abundance of EFAs in the gonad tissue during highest and lowest GBI values suggested that arachidonic, eicosapentaenoic, g-linolenic and linoleic acid were important in females, while eicosapentaenoic, eicosadienoic and a-linolenic acid were important for male reproductive development. Dietary protein sources had an effect on the frequency distribution of maturity stages, where females that were fed FM S produced more ripe gonads and more males that were fed FM SM contained testes that showed signs of ripeness over the one-year study. Although dietary protein influenced the sex steroid concentrations in females and males, exhibiting fluctuations throughout the one-year period, no distinct pattern linked to gametogenesis were observed. The results from this study illustrate: (1) the importance of conducting laboratory studies when implementing SIA and mixing models in aquaculture nutrition; (2) conducting nutritional studies on mature, grow-out abalone; and (3) assessing the importance of naturally occurring diatoms in their diet and their contribution to growth and reproduction. The novel contribution of this research towards abalone nutritional physiology, the implications of these findings to industry as well as potential considerations for future studies were addressed.
- Full Text:
A novel, improved throughput bioassay for determining the delative speed of antimalarial drug action using fluorescent vitality probes
- Authors: Laming, Dustin
- Date: 2020
- Subjects: Plasmodium falciparum , Malaria -- Treatment -- Africa , Antimalarials , Malaria vaccine
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/139902 , vital:37810
- Description: Malaria is one of the most prevalent diseases in Africa and Plasmodium falciparum is widely accepted as the most virulent of the malaria parasite species, with a fatality rate of 15 – 20 % of reported cases of infection. While various treatments have been accepted into early stage clinical trials, there has been little progress towards a proven vaccine. Pending a long-term solution, endemic countries rely heavily on the development of innovative drugs that are not only efficacious but are also quick acting. Traditional methods of evaluating antimalarial killing speeds via morphological assessments are inherently flawed by tedious, subjective interpretations of the heterogenous parasite morphology encountered in routine parasite culture conditions. This has led to the introduction of alternative assay formats to determine how rapidly compounds act on parasites in vitro: a parasite reduction ratio (PRR) assay that measures the recovery of parasite cultures from drug exposure; determining the shift in IC50 values of compounds when dose-response assays are carried out for different time periods; a bioluminescence relative rate of kill (BRRoK) assay that compares the extent to which compounds reduce firefly luciferase activity in transgenic parasites. Recent whole cell in vitro screening efforts have resulted in the generation of chemically diverse compound libraries such as the Medicines for Malaria Venture’s Pathogen Box, which houses 125 novel compounds with in vitro antiplasmodial activity. Assessing the relative killing speeds of these compounds would aid prioritizing fast-acting compounds that can be exploited as starting points for further development. This study aimed to develop a bioassay using the calcein-acetoxymethyl and propidium iodide fluorescent vitality probes, which would allow the relative speed of drug action on Plasmodium falciparum malaria parasites to be assessed and ranked in relation to each other using a quantitative, improved throughput approach. Initially applied to human (HeLa) cells, the assay was used to compare the relative speeds of action of 3 potential anti-cancer compounds by fluorescence microscopy. Subsequently adapted to P. falciparum, the assay was able to rank the relative speeds of action of standard antimalarials by fluorescence microscopy and two flow cytometry formats. Application of a multiwell flow cytometer increased throughput and enabled the assessment of experimental compounds, which included a set of artemisinin analogs and 125 antimalarial compounds in the MMV Pathogen Box. The latter culminated in the identification of five rapidly parasiticidal compounds in relation to the other compounds in the library, which may act as benchmark references for future studies and form the basis of the next generation of fast acting antimalarials that could be used to combat modern, resistant malaria.
- Full Text:
- Authors: Laming, Dustin
- Date: 2020
- Subjects: Plasmodium falciparum , Malaria -- Treatment -- Africa , Antimalarials , Malaria vaccine
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/139902 , vital:37810
- Description: Malaria is one of the most prevalent diseases in Africa and Plasmodium falciparum is widely accepted as the most virulent of the malaria parasite species, with a fatality rate of 15 – 20 % of reported cases of infection. While various treatments have been accepted into early stage clinical trials, there has been little progress towards a proven vaccine. Pending a long-term solution, endemic countries rely heavily on the development of innovative drugs that are not only efficacious but are also quick acting. Traditional methods of evaluating antimalarial killing speeds via morphological assessments are inherently flawed by tedious, subjective interpretations of the heterogenous parasite morphology encountered in routine parasite culture conditions. This has led to the introduction of alternative assay formats to determine how rapidly compounds act on parasites in vitro: a parasite reduction ratio (PRR) assay that measures the recovery of parasite cultures from drug exposure; determining the shift in IC50 values of compounds when dose-response assays are carried out for different time periods; a bioluminescence relative rate of kill (BRRoK) assay that compares the extent to which compounds reduce firefly luciferase activity in transgenic parasites. Recent whole cell in vitro screening efforts have resulted in the generation of chemically diverse compound libraries such as the Medicines for Malaria Venture’s Pathogen Box, which houses 125 novel compounds with in vitro antiplasmodial activity. Assessing the relative killing speeds of these compounds would aid prioritizing fast-acting compounds that can be exploited as starting points for further development. This study aimed to develop a bioassay using the calcein-acetoxymethyl and propidium iodide fluorescent vitality probes, which would allow the relative speed of drug action on Plasmodium falciparum malaria parasites to be assessed and ranked in relation to each other using a quantitative, improved throughput approach. Initially applied to human (HeLa) cells, the assay was used to compare the relative speeds of action of 3 potential anti-cancer compounds by fluorescence microscopy. Subsequently adapted to P. falciparum, the assay was able to rank the relative speeds of action of standard antimalarials by fluorescence microscopy and two flow cytometry formats. Application of a multiwell flow cytometer increased throughput and enabled the assessment of experimental compounds, which included a set of artemisinin analogs and 125 antimalarial compounds in the MMV Pathogen Box. The latter culminated in the identification of five rapidly parasiticidal compounds in relation to the other compounds in the library, which may act as benchmark references for future studies and form the basis of the next generation of fast acting antimalarials that could be used to combat modern, resistant malaria.
- Full Text:
A personality-based surveillance model for Facebook apps
- Authors: Van der Schyff, Karl Izak
- Date: 2020
- Subjects: Facebook (Electronic resource) , Electronic surveillance -- Psychological aspects , Online social networks -- Psychological aspects , Social media -- Psychological aspects , Personality
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/145534 , vital:38447
- Description: The surveillance of data through the use of Facebook Apps is an ongoing and persistent problem that impacts millions of users. Nonetheless, limited research has been conducted investigating to what extent a Facebook user’s personality influences their awareness of such surveillance practices. Thus, to understand this situation better, the current study inductively developed four propositions from secondary data sources as part of a detailed content analysis. Spanning three search and analysis phases the content analysis led to the development of the research model. Guided by the propositions and research questions, a questionnaire was developed based on the relevant constructs prescribed by the Theory of Planned Behaviour. This questionnaire was used, and a total of 651 responses were collected from Facebook users over the age of 18 years old and residing in the United States of America. Primary data took place at both a univariate and multivariate level with a specific focus on the development of a structural model. Interpretation of the structural model revealed that out of all the Big Five personality traits, Conscientiousness exhibited the strongest relationship with information security awareness followed by Openness to Experience and Neuroticism, respectively. The results further indicated that the model constructs based on attitude, social norms and awareness significantly influenced the intended use of Facebook Apps. The study also contributes by indicating which personality traits are most vulnerable to Facebook App surveillance. For example, it was found that individuals high in Conscientiousness are the least vulnerable with individuals high in Extraversion being the most vulnerable. Since the results indicate that not all the personality traits are significantly related to the model constructs, additional factors may contribute to App surveillance in this context. Concerning this, factors such as user apathy, information privacy, privacy concerns, control and Facebook dependency are discussed as a means to argue why this might be the case.
- Full Text:
- Authors: Van der Schyff, Karl Izak
- Date: 2020
- Subjects: Facebook (Electronic resource) , Electronic surveillance -- Psychological aspects , Online social networks -- Psychological aspects , Social media -- Psychological aspects , Personality
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/145534 , vital:38447
- Description: The surveillance of data through the use of Facebook Apps is an ongoing and persistent problem that impacts millions of users. Nonetheless, limited research has been conducted investigating to what extent a Facebook user’s personality influences their awareness of such surveillance practices. Thus, to understand this situation better, the current study inductively developed four propositions from secondary data sources as part of a detailed content analysis. Spanning three search and analysis phases the content analysis led to the development of the research model. Guided by the propositions and research questions, a questionnaire was developed based on the relevant constructs prescribed by the Theory of Planned Behaviour. This questionnaire was used, and a total of 651 responses were collected from Facebook users over the age of 18 years old and residing in the United States of America. Primary data took place at both a univariate and multivariate level with a specific focus on the development of a structural model. Interpretation of the structural model revealed that out of all the Big Five personality traits, Conscientiousness exhibited the strongest relationship with information security awareness followed by Openness to Experience and Neuroticism, respectively. The results further indicated that the model constructs based on attitude, social norms and awareness significantly influenced the intended use of Facebook Apps. The study also contributes by indicating which personality traits are most vulnerable to Facebook App surveillance. For example, it was found that individuals high in Conscientiousness are the least vulnerable with individuals high in Extraversion being the most vulnerable. Since the results indicate that not all the personality traits are significantly related to the model constructs, additional factors may contribute to App surveillance in this context. Concerning this, factors such as user apathy, information privacy, privacy concerns, control and Facebook dependency are discussed as a means to argue why this might be the case.
- Full Text:
A reappraisal of the origin of the Hotazel Fe-Mn Formation in an evolving early Earth system through the application of mineral-specific geochemistry, speciation techniques and stable isotope systematics
- Authors: Mhlanga, Xolane Reginald
- Date: 2020
- Subjects: Manganese ores -- South Africa -- Hotazel , Manganese ores -- Geology , Iron ores -- South Africa -- Hotazel , Iron ores -- Geology , Geochemistry -- South Africa -- Hotazel , Isotope geology -- South Africa -- Hotazel , Geology, Stratigraphic -- Archaean , Geology, Stratigraphic -- Proterozoic , Transvaal Supergroup (South Africa) , Great Oxidation Event
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/146123 , vital:38497
- Description: Marine chemical sediments such as Banded Iron Formations deposited during the Archean-Palaeoproterozoic are studied extensively because they represent a period in the development of the Earth’s early history where the atmospheric O₂ content was below the present levels (PAL) of 21%. Prior to the Great Oxidation Event (GOE) at ca. 2.4 Ga, highly ferruginous and anoxic marine environments were dominated by extensive BIF deposition such as that of the Griqualand West Basin of the Transvaal Supergroup in South Africa. This basin is also thought to record the transition into the first rise of atmospheric O₂ in our planet, from the Koegas Subgroup to the Hotazel Formation dated at ca. 2.43 Ga (Gumsley et al., 2017). Two drill cores from the north eastern part of the Kalahari Manganese Field characterized by a well-preserved and complete intersection of the cyclic Mn-Fe Hotazel Formation were studied at a high resolution (sampled at approximately one-meter interval). Such high-resolution approach is being employed for the first time in this project, capturing in detail the three manganese rich layers intercalated with BIF and the transitions between these lithofacies. The micro-banded BIF is made up of three major phases, namely Fe-Ca-Mg carbonates (ankerite, siderite and calcite), magnetite, and silicates (chert and minor Fe-silicates); laminated transitional lutite consist of mainly hematite, chert and Mn-carbonates, whereas the manganese ore layers are made up of mostly calcic carbonates (Mn-calcite and Ca-kutnahorite) in the form of laminations and ovoids, while Mn-silicates include dominant braunite and lesser friedelite. All three lithofacies are very fine grained (sub-mm scale) and so petrographic and mineralogical observations were obtained mostly through scanning electron microscope analysis for detailed textural relationships with focus on the carbonate fraction. Bulk geochemical studies of the entire stratigraphy of the Hotazel Formation have previously provided great insights into the cyclic nature of the deposit but have not adequately considered the potential of the carbonate fraction of the rocks as a valuable proxy for understanding the chemistry of the primary depositional environment and insights into the redox processes that were at play. This is because these carbonates have always been attributed to diagenetic processes below the sediment-water interface such as microbially-mediated dissimilatory iron/manganese reduction (DIR/DMR) where the precursor/primary Fe-Mn oxyhydroxides have been reduced to result in the minerals observed today. The carbonate fraction of the BIF is made up of ankerite and siderite which co-exist in a chert matrix as anhedral to subhedral grains with no apparent replacement textures. This suggests co-precipitation of the two species which is at apparent odds with classic diagenetic models. Similarly, Mn-carbonates in the hematite lutite and manganese ore (Mn-calcite, kutnahorite, and minor rhodocrosite) co-exist in laminae and ovoids with no textures observed that would suggest an obvious sequential mode of formation during diagenesis. In this light, a carbonate-specific geochemical analysis based on the sequential Fe extraction technique of Poulton and Canfield (2005) was employed to decipher further the cyclic nature of the Hotazel Formation and its primary versus diagenetic controls. Results from the carbonate fraction analysis of the three lithofacies show a clear fractionation of iron and manganese during primary – rather than diagenetic - carbonate precipitation, suggesting a decoupling between DIR and DMR which is ultimately interpreted to have taken place in the water column. Bulk-rock concentration results for minor and trace elements such as Zr, Ti, Sc and Al have been used for the determination of either siliciclastic or volcanic detrital inputs as they are generally immobile in most natural aqueous solutions. These elements are in very low concentrations in all three lithofacies suggesting that the depositional environment had vanishingly small contributions from terrigenous or volcanic detritus. In terms of redox-sensitive transition metals, only Mo and Co appear to show an affinity for high Mn facies in the Hotazel sequence. Cobalt in particular attains a very low abundance in the Hotazel BIF layers at an average of ~ 4 ppm. This is similar to average pre-GOE BIF in South Africa and worldwide. Maxima in Co abundance are associated with transitional hematite lutite and Mn ore layers, but maxima over 100ppm are seen in within the hematite lutite and not within the Mn ore proper where maxima in Mn are recorded. This suggests a clear and direct association with the hematite fraction in the rocks, which is modally much higher in the lutites but drops substantially in the Mn layers themselves. The similarities of bulk-rock BIF and modern-day seawater REE patterns has been used as a key argument for primary controls in REE behaviour and minimal diagenetic modification. Likewise, the three lithofacies of the Hotazel Formation analysed in this study all share similar characteristics with a clear seawater signal through gentle positive slopes in the normalised abundance of LREE versus HREE. Negative Ce anomalies prevail in the entire sample set analysed, which has been interpreted before as a proxy for oxic seawater conditions. However, positive Ce anomalies that are traditionally linked to scavenging and deposition of primary tetravalent Mn oxyhydroxides (e.g., as observed in modern day ferromanganese nodules) are completely absent from the current dataset. The lack of a positive Ce anomaly in the manganese ore and peak Co association with ferric oxides and not with peak Mn, suggests that primary deposition must have occurred within an environment that was not fully oxidizing with respect to manganese. The use of stable isotopes (i.e., C and Fe) was employed to gain insights into redox processes, whether these are thought to have happened below the sediment-water interface or in contemporaneous seawater. At a small scale, all lithofacies of the Hotazel Formation record bulk-rock δ¹³C values that are low and essentially invariant about the average value of -9.5 per mil. This is independent of sharp variations in overall modal mineralogy, relative carbonate abundance and carbonate chemistry, which is clearly difficult to reconcile with in-situ diagenetic processes that predict highly variable δ¹³C signals in response to complex combinations of precursor sediment mineralogy, pore-fluid chemistry, organic carbon supply and open vs closed system diagenesis. At a stratigraphic scale, the carbonate δ¹³C (-5 to -13‰) variations between the different lithologies could instead represent temporal changes in water-column chemistry against well-developed physico-chemical gradients, depth of deposition and biological processes. The low iron isotope values recorded in the hematite lutite and manganese ore samples can be attributed to fractionation effects of initial oxidation of ferrous iron to form Fe-oxyhydroxides in the shallow parts of the basin, from an already isotopically highly depleted aqueous Fe-pool as proposed previously. The slightly higher but still negative bulk-rock δ⁵⁶Fe values of the host BIF can be attributed to water-column Fe isotopic effects at deeper levels between primary Fe oxyhydroxides and an isotopically heavier Fe(II) pool, which was subsequently preserved during diagenetic recrystallization. All above findings were combined into a conceptual model of deposition for the three different lithologies of the Hotazel Formation. The model predicts that free molecular oxygen must have been present within the shallow oceanic environment and implicates both Mn and Fe as active redox “players” compared to classic models that apply to the origin of worldwide BIF prior to the GOE. The deposition of the Hotazel strata is interpreted to have occurred through the following three stages: (1) BIF deposition occurred in a relatively deep oceanic environment above the Ongeluk lavas during marine transgression, where a redoxcline and seawater stratification separated hydrothermally sourced iron and manganese, in response to an active Mn-shuttle mechanism linked to Mn redox cycling. Abundant ferrous iron must have been oxidized by available oxygen but also by oxidised Mn species (MnOOH) and possibly even some soluble Mn(III) complexes. Through this process, Mn(III) was being effectively reduced back into solution along with cobalt(III), as Mn(II) and Co(II) respectively, thus creating maxima in their concentrations. A drawdown of Fe(OH)₃ particles was therefore the only net precipitation mechanism at this stage. Carbonate species of Fe and the abundant magnetite would possibly have formed by reaction between the ferric hydroxides and the deeper Fe(II) pool, while organic matter would also have reacted in the water-column via DIR, accounting for the low δ¹³C signature of Fe carbonate minerals. (2) Hematite lutite formation would have occurred at a relatively shallower environment during marine regression. At this stage, reductive cycling of Fe was minimal in the absence of a deeper Fe(II) reservoir reacting with the ferric primary precipitates. Therefore, DIR progressively gave way to manganese reduction and organic carbon oxidation (DMR), which reduced MnOOH to form Mn(II)-rich carbonates in the form of kutnahorite and Mn-calcite. Co-bearing Fe(OH)₃ would have precipitated and was ultimately preserved as Co-bearing hematite during diagenesis. (3) Deposition of manganese-rich sediment occurred at even shallower oceanic depths (maximum regression) where aerobic organic carbon oxidation replaced DMR, resulting in Ca-rich carbonates such as Mn-bearing calcite and Ca-kutnahorite, yet with a low carbon isotope signature recording aerobic conditions of organic carbon cycling. Mn(III) reduction at this stage was curtailed, leading to massive precipitation of MnOOH which was diagenetically transformed into braunite and friedelite. Simultaneous precipitation of Co-bearing Fe(OH)₃ would have continued but at much more subdued rates. Repeated transgressive-regressive cycles resulted in the cyclic BIF-hematite lutite- manganese ore nature of the Hotazel Formation in an oxidized oceanic environment at the onset of the Great Oxidation Event, which was nonetheless never oxic enough to drive Mn(II) oxidation fully to its tetravalent state. The mineralogy and species-specific geochemistry of the Hotazel strata, and more specifically the carbonate fraction thereof, appear to faithfully capture the chemistry of the primary depositional environment in a progressively evolving Earth System. This project opens the door for more studies focusing on better constraining primary versus diagenetic depositional 2020 Hotazel Fe and Mn deposition mechanisms of iron and manganese during the period leading up to the GOE, and possibly re-defining the significance of Fe and Mn as invaluable redox proxies in a rapidly changing planet.
- Full Text:
- Authors: Mhlanga, Xolane Reginald
- Date: 2020
- Subjects: Manganese ores -- South Africa -- Hotazel , Manganese ores -- Geology , Iron ores -- South Africa -- Hotazel , Iron ores -- Geology , Geochemistry -- South Africa -- Hotazel , Isotope geology -- South Africa -- Hotazel , Geology, Stratigraphic -- Archaean , Geology, Stratigraphic -- Proterozoic , Transvaal Supergroup (South Africa) , Great Oxidation Event
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/146123 , vital:38497
- Description: Marine chemical sediments such as Banded Iron Formations deposited during the Archean-Palaeoproterozoic are studied extensively because they represent a period in the development of the Earth’s early history where the atmospheric O₂ content was below the present levels (PAL) of 21%. Prior to the Great Oxidation Event (GOE) at ca. 2.4 Ga, highly ferruginous and anoxic marine environments were dominated by extensive BIF deposition such as that of the Griqualand West Basin of the Transvaal Supergroup in South Africa. This basin is also thought to record the transition into the first rise of atmospheric O₂ in our planet, from the Koegas Subgroup to the Hotazel Formation dated at ca. 2.43 Ga (Gumsley et al., 2017). Two drill cores from the north eastern part of the Kalahari Manganese Field characterized by a well-preserved and complete intersection of the cyclic Mn-Fe Hotazel Formation were studied at a high resolution (sampled at approximately one-meter interval). Such high-resolution approach is being employed for the first time in this project, capturing in detail the three manganese rich layers intercalated with BIF and the transitions between these lithofacies. The micro-banded BIF is made up of three major phases, namely Fe-Ca-Mg carbonates (ankerite, siderite and calcite), magnetite, and silicates (chert and minor Fe-silicates); laminated transitional lutite consist of mainly hematite, chert and Mn-carbonates, whereas the manganese ore layers are made up of mostly calcic carbonates (Mn-calcite and Ca-kutnahorite) in the form of laminations and ovoids, while Mn-silicates include dominant braunite and lesser friedelite. All three lithofacies are very fine grained (sub-mm scale) and so petrographic and mineralogical observations were obtained mostly through scanning electron microscope analysis for detailed textural relationships with focus on the carbonate fraction. Bulk geochemical studies of the entire stratigraphy of the Hotazel Formation have previously provided great insights into the cyclic nature of the deposit but have not adequately considered the potential of the carbonate fraction of the rocks as a valuable proxy for understanding the chemistry of the primary depositional environment and insights into the redox processes that were at play. This is because these carbonates have always been attributed to diagenetic processes below the sediment-water interface such as microbially-mediated dissimilatory iron/manganese reduction (DIR/DMR) where the precursor/primary Fe-Mn oxyhydroxides have been reduced to result in the minerals observed today. The carbonate fraction of the BIF is made up of ankerite and siderite which co-exist in a chert matrix as anhedral to subhedral grains with no apparent replacement textures. This suggests co-precipitation of the two species which is at apparent odds with classic diagenetic models. Similarly, Mn-carbonates in the hematite lutite and manganese ore (Mn-calcite, kutnahorite, and minor rhodocrosite) co-exist in laminae and ovoids with no textures observed that would suggest an obvious sequential mode of formation during diagenesis. In this light, a carbonate-specific geochemical analysis based on the sequential Fe extraction technique of Poulton and Canfield (2005) was employed to decipher further the cyclic nature of the Hotazel Formation and its primary versus diagenetic controls. Results from the carbonate fraction analysis of the three lithofacies show a clear fractionation of iron and manganese during primary – rather than diagenetic - carbonate precipitation, suggesting a decoupling between DIR and DMR which is ultimately interpreted to have taken place in the water column. Bulk-rock concentration results for minor and trace elements such as Zr, Ti, Sc and Al have been used for the determination of either siliciclastic or volcanic detrital inputs as they are generally immobile in most natural aqueous solutions. These elements are in very low concentrations in all three lithofacies suggesting that the depositional environment had vanishingly small contributions from terrigenous or volcanic detritus. In terms of redox-sensitive transition metals, only Mo and Co appear to show an affinity for high Mn facies in the Hotazel sequence. Cobalt in particular attains a very low abundance in the Hotazel BIF layers at an average of ~ 4 ppm. This is similar to average pre-GOE BIF in South Africa and worldwide. Maxima in Co abundance are associated with transitional hematite lutite and Mn ore layers, but maxima over 100ppm are seen in within the hematite lutite and not within the Mn ore proper where maxima in Mn are recorded. This suggests a clear and direct association with the hematite fraction in the rocks, which is modally much higher in the lutites but drops substantially in the Mn layers themselves. The similarities of bulk-rock BIF and modern-day seawater REE patterns has been used as a key argument for primary controls in REE behaviour and minimal diagenetic modification. Likewise, the three lithofacies of the Hotazel Formation analysed in this study all share similar characteristics with a clear seawater signal through gentle positive slopes in the normalised abundance of LREE versus HREE. Negative Ce anomalies prevail in the entire sample set analysed, which has been interpreted before as a proxy for oxic seawater conditions. However, positive Ce anomalies that are traditionally linked to scavenging and deposition of primary tetravalent Mn oxyhydroxides (e.g., as observed in modern day ferromanganese nodules) are completely absent from the current dataset. The lack of a positive Ce anomaly in the manganese ore and peak Co association with ferric oxides and not with peak Mn, suggests that primary deposition must have occurred within an environment that was not fully oxidizing with respect to manganese. The use of stable isotopes (i.e., C and Fe) was employed to gain insights into redox processes, whether these are thought to have happened below the sediment-water interface or in contemporaneous seawater. At a small scale, all lithofacies of the Hotazel Formation record bulk-rock δ¹³C values that are low and essentially invariant about the average value of -9.5 per mil. This is independent of sharp variations in overall modal mineralogy, relative carbonate abundance and carbonate chemistry, which is clearly difficult to reconcile with in-situ diagenetic processes that predict highly variable δ¹³C signals in response to complex combinations of precursor sediment mineralogy, pore-fluid chemistry, organic carbon supply and open vs closed system diagenesis. At a stratigraphic scale, the carbonate δ¹³C (-5 to -13‰) variations between the different lithologies could instead represent temporal changes in water-column chemistry against well-developed physico-chemical gradients, depth of deposition and biological processes. The low iron isotope values recorded in the hematite lutite and manganese ore samples can be attributed to fractionation effects of initial oxidation of ferrous iron to form Fe-oxyhydroxides in the shallow parts of the basin, from an already isotopically highly depleted aqueous Fe-pool as proposed previously. The slightly higher but still negative bulk-rock δ⁵⁶Fe values of the host BIF can be attributed to water-column Fe isotopic effects at deeper levels between primary Fe oxyhydroxides and an isotopically heavier Fe(II) pool, which was subsequently preserved during diagenetic recrystallization. All above findings were combined into a conceptual model of deposition for the three different lithologies of the Hotazel Formation. The model predicts that free molecular oxygen must have been present within the shallow oceanic environment and implicates both Mn and Fe as active redox “players” compared to classic models that apply to the origin of worldwide BIF prior to the GOE. The deposition of the Hotazel strata is interpreted to have occurred through the following three stages: (1) BIF deposition occurred in a relatively deep oceanic environment above the Ongeluk lavas during marine transgression, where a redoxcline and seawater stratification separated hydrothermally sourced iron and manganese, in response to an active Mn-shuttle mechanism linked to Mn redox cycling. Abundant ferrous iron must have been oxidized by available oxygen but also by oxidised Mn species (MnOOH) and possibly even some soluble Mn(III) complexes. Through this process, Mn(III) was being effectively reduced back into solution along with cobalt(III), as Mn(II) and Co(II) respectively, thus creating maxima in their concentrations. A drawdown of Fe(OH)₃ particles was therefore the only net precipitation mechanism at this stage. Carbonate species of Fe and the abundant magnetite would possibly have formed by reaction between the ferric hydroxides and the deeper Fe(II) pool, while organic matter would also have reacted in the water-column via DIR, accounting for the low δ¹³C signature of Fe carbonate minerals. (2) Hematite lutite formation would have occurred at a relatively shallower environment during marine regression. At this stage, reductive cycling of Fe was minimal in the absence of a deeper Fe(II) reservoir reacting with the ferric primary precipitates. Therefore, DIR progressively gave way to manganese reduction and organic carbon oxidation (DMR), which reduced MnOOH to form Mn(II)-rich carbonates in the form of kutnahorite and Mn-calcite. Co-bearing Fe(OH)₃ would have precipitated and was ultimately preserved as Co-bearing hematite during diagenesis. (3) Deposition of manganese-rich sediment occurred at even shallower oceanic depths (maximum regression) where aerobic organic carbon oxidation replaced DMR, resulting in Ca-rich carbonates such as Mn-bearing calcite and Ca-kutnahorite, yet with a low carbon isotope signature recording aerobic conditions of organic carbon cycling. Mn(III) reduction at this stage was curtailed, leading to massive precipitation of MnOOH which was diagenetically transformed into braunite and friedelite. Simultaneous precipitation of Co-bearing Fe(OH)₃ would have continued but at much more subdued rates. Repeated transgressive-regressive cycles resulted in the cyclic BIF-hematite lutite- manganese ore nature of the Hotazel Formation in an oxidized oceanic environment at the onset of the Great Oxidation Event, which was nonetheless never oxic enough to drive Mn(II) oxidation fully to its tetravalent state. The mineralogy and species-specific geochemistry of the Hotazel strata, and more specifically the carbonate fraction thereof, appear to faithfully capture the chemistry of the primary depositional environment in a progressively evolving Earth System. This project opens the door for more studies focusing on better constraining primary versus diagenetic depositional 2020 Hotazel Fe and Mn deposition mechanisms of iron and manganese during the period leading up to the GOE, and possibly re-defining the significance of Fe and Mn as invaluable redox proxies in a rapidly changing planet.
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A sociological understanding of contemporary child marriage in Mabvuku, Harare, Zimbabwe
- Authors: Madzivire, Shamso Christine
- Date: 2020
- Subjects: Child marriage -- Zimbabwe -- Mabvuku , Child marriage -- Zimbabwe -- Case studies , Shona (African people) -- Social life and customs , Marriage customs and rites -- Zimbabwe , Shona (African people) -- Marriage customs and rites , Marriage -- Zimbabwe
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/142566 , vital:38091
- Description: Child marriage is a phenomenon that has been increasingly recognised as a global problem since the late nineteenth century. Since then, scholars across many disciplines along with various agencies such as government bodies and non-governmental organisations have tirelessly engaged in research exploring the causes and consequences of this practice and in developing prevention and mitigation strategies. These research efforts have been concentrated in some parts of the world and not others, with the findings in many cases being generalised problematically across different geographical areas. This thesis stands as a response to the dearth of academic research on child marriage in present-day Zimbabwe and simultaneously highlights the significance of studying the specificities of child marriage under particular historical and spatial conditions. The main objective of this thesis is to explore and understand child marriage as a part of modernday marriage practices in Zimbabwe, through a case study of child marriage in Mabvuku in Harare. In addressing this objective, it is hoped that new ways of thinking around this phenomenon will become evident. In addressing this main objective, the thesis considers the experiences of child brides, the drivers and consequences of child and post-child marriage experiences. It does this seeking to understand child marriage with reference to the types of marital unions which exist amongst Shona people in pre-colonial times and in post-colonial Zimbabwe. The thesis adopts a qualitative research methodology which involved in-depth semistructured interviews with 25 women in Mabvuku who were married before the age of 18, along with focus group discussions with community workers and interviews with pertinent government and non-government representatives. Due to certain challenges with current theorising about child marriage, there is an attempt to build theory by drawing upon in particular the Zimbabwean notion and practice of hunhu. A key conclusion is that child marriage in present-day Zimbabwe is in part a result of family transitions which arose during the time of colonialism and continue to this day.
- Full Text:
- Authors: Madzivire, Shamso Christine
- Date: 2020
- Subjects: Child marriage -- Zimbabwe -- Mabvuku , Child marriage -- Zimbabwe -- Case studies , Shona (African people) -- Social life and customs , Marriage customs and rites -- Zimbabwe , Shona (African people) -- Marriage customs and rites , Marriage -- Zimbabwe
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/142566 , vital:38091
- Description: Child marriage is a phenomenon that has been increasingly recognised as a global problem since the late nineteenth century. Since then, scholars across many disciplines along with various agencies such as government bodies and non-governmental organisations have tirelessly engaged in research exploring the causes and consequences of this practice and in developing prevention and mitigation strategies. These research efforts have been concentrated in some parts of the world and not others, with the findings in many cases being generalised problematically across different geographical areas. This thesis stands as a response to the dearth of academic research on child marriage in present-day Zimbabwe and simultaneously highlights the significance of studying the specificities of child marriage under particular historical and spatial conditions. The main objective of this thesis is to explore and understand child marriage as a part of modernday marriage practices in Zimbabwe, through a case study of child marriage in Mabvuku in Harare. In addressing this objective, it is hoped that new ways of thinking around this phenomenon will become evident. In addressing this main objective, the thesis considers the experiences of child brides, the drivers and consequences of child and post-child marriage experiences. It does this seeking to understand child marriage with reference to the types of marital unions which exist amongst Shona people in pre-colonial times and in post-colonial Zimbabwe. The thesis adopts a qualitative research methodology which involved in-depth semistructured interviews with 25 women in Mabvuku who were married before the age of 18, along with focus group discussions with community workers and interviews with pertinent government and non-government representatives. Due to certain challenges with current theorising about child marriage, there is an attempt to build theory by drawing upon in particular the Zimbabwean notion and practice of hunhu. A key conclusion is that child marriage in present-day Zimbabwe is in part a result of family transitions which arose during the time of colonialism and continue to this day.
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A theory-based approach to evaluating a Continuing Teacher Professional Development Programme aimed at strengthening environment and sustainability education
- Authors: Songqwaru, Nonyameko Zintle
- Date: 2020
- Subjects: Fundisa for Change , Environmental education -- South Africa , Teachers -- Training of -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/145267 , vital:38423
- Description: This study uses a theory-based approach to evaluate the Fundisa for Change training programme, a continuing teacher professional development programme aimed at strengthening environment and sustainability education. The aim of the study was to surface assumptions that underpin the design and implementation of the Fundisa for Change training programme. The Fundisa for Change Teacher Education programme is a national collaborative programme that is implemented in all the nine provinces of South Africa. The study reports on the implementation of the programme in five provinces. The study aimed to surface the Fundisa for Change training programme’s implementation theory and programme theory as these affect programme delivery. The Fundisa for Change training programme was implemented in diverse contexts by different facilitators to different participants. To determine how training programme outcomes were achieved, use was made of context-mechanism-outcome (CMO) configurations for each site where the programme was implemented. Data used to construct CMO configurations was generated through document analysis of Fundisa for Change documents, interviews with stakeholders and participants, as well as observations of programme implementation at five sites. There were three phases to data analysis: content analysis of Fundisa for Change documents, content analysis of observation transcripts and use of the CMO configuration, an analytical tool used in realist evaluation. An initial CMO configuration was constructed prior to observing implementation of the programme and a refined CMO configuration for the Fundisa for Change training programme was constructed based on similarities between the CMO configurations constructed for each of the five sites under study. The partnership model of the Fundisa for Change training programme brought diverse expertise and resources (material, cognitive, social and emotional) which were conducive to the achievement of programme outcomes. The programme’s action context (structure, culture, agency and relations) contributed to the achievement of programme outcomes by participants. Participants’ subject content knowledge, teaching practice and assessment practice was enhanced through attending the Fundisa for Change training. On-course tasks were mediated during training and this created opportunities for participants to discuss and reflect on current practice in ways that could lead to a change in practice. In evaluating professional development programmes, an elaborated definition of context in terms of structure, culture, agency and relations enables a comprehensive exploration of potential programme mechanisms that can be activated when programmes are implemented. It is also important to disaggregate resources and reasons when identifying mechanisms as this assists with differentiating between context and mechanisms. The study offers insights into the professional learning of teachers grappling with new content and pedagogical content knowledges related to environment in the context of recent curriculum changes where the South African national school curriculum has come into focus. Environmental education programmes in South Africa have implicitly used a realist approach. This study offers the first substantive professional learning evaluation that develops this approach explicitly using Theory of Change and Realist Evaluation in combination.
- Full Text:
- Authors: Songqwaru, Nonyameko Zintle
- Date: 2020
- Subjects: Fundisa for Change , Environmental education -- South Africa , Teachers -- Training of -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/145267 , vital:38423
- Description: This study uses a theory-based approach to evaluate the Fundisa for Change training programme, a continuing teacher professional development programme aimed at strengthening environment and sustainability education. The aim of the study was to surface assumptions that underpin the design and implementation of the Fundisa for Change training programme. The Fundisa for Change Teacher Education programme is a national collaborative programme that is implemented in all the nine provinces of South Africa. The study reports on the implementation of the programme in five provinces. The study aimed to surface the Fundisa for Change training programme’s implementation theory and programme theory as these affect programme delivery. The Fundisa for Change training programme was implemented in diverse contexts by different facilitators to different participants. To determine how training programme outcomes were achieved, use was made of context-mechanism-outcome (CMO) configurations for each site where the programme was implemented. Data used to construct CMO configurations was generated through document analysis of Fundisa for Change documents, interviews with stakeholders and participants, as well as observations of programme implementation at five sites. There were three phases to data analysis: content analysis of Fundisa for Change documents, content analysis of observation transcripts and use of the CMO configuration, an analytical tool used in realist evaluation. An initial CMO configuration was constructed prior to observing implementation of the programme and a refined CMO configuration for the Fundisa for Change training programme was constructed based on similarities between the CMO configurations constructed for each of the five sites under study. The partnership model of the Fundisa for Change training programme brought diverse expertise and resources (material, cognitive, social and emotional) which were conducive to the achievement of programme outcomes. The programme’s action context (structure, culture, agency and relations) contributed to the achievement of programme outcomes by participants. Participants’ subject content knowledge, teaching practice and assessment practice was enhanced through attending the Fundisa for Change training. On-course tasks were mediated during training and this created opportunities for participants to discuss and reflect on current practice in ways that could lead to a change in practice. In evaluating professional development programmes, an elaborated definition of context in terms of structure, culture, agency and relations enables a comprehensive exploration of potential programme mechanisms that can be activated when programmes are implemented. It is also important to disaggregate resources and reasons when identifying mechanisms as this assists with differentiating between context and mechanisms. The study offers insights into the professional learning of teachers grappling with new content and pedagogical content knowledges related to environment in the context of recent curriculum changes where the South African national school curriculum has come into focus. Environmental education programmes in South Africa have implicitly used a realist approach. This study offers the first substantive professional learning evaluation that develops this approach explicitly using Theory of Change and Realist Evaluation in combination.
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Activity of diverse chalcones against several targets: statistical analysis of a high-throughput virtual screen of a custom chalcone library
- Authors: Sarron, Arthur F D
- Date: 2020
- Subjects: Acetophenone , Benzaldehyde , Ketones , Pyruvate kinase , Drug development , Aromatic compounds , Heat shock proteins
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/116028 , vital:34291
- Description: Chalcone family molecules are well known to have therapeutic proprieties (anti-inflammatory, anti-microbial or anti-cancer, etc). However the mechanism of action in some cases is not well known. A virtual library of this family of compounds was constructed using custom scripts, based on the aldol condensation, and this library was modified further to analogues by expansion of the α,β-unsaturated ketone linker. Acetophenone and benzaldehyde derivatives which are available and purchasable were used as a base to design the chalcone virtual library. 8063 chalcones were constructed and geometrically optimized with Gaussian 09. Their physicochemical characteristics linked to the Lipinski rules were analyzed with Knime and CDK. The entire library was after docked against several targets including HIV-1 integrase, MRSA pyruvate kinase, HSP90, COX-1, COX-2, ALR2, MAOA, MAOB, acetylcholinesterase, butyrylcholinesterase and PLA2. With the exception of MAOA, which does not have a crystal structure ligand, all dockings were validated by redocking the original ligand provided by the literature. These targets are known in the literature to be inhibited by chalcone-derivatives. However, specificity of the particular known chalcone inhibitors to the particular targets is not known. To this end the performance of the generated chalcone library against the list of targets was of interest. The binding energy of ligand-protein complexes was generally good across the library. Statistical analysis including principal component analysis and hierarchical clustering analysis were made in order to investigate for any physical/chemical characteristics which might explain what chalcone features affect the binding energy of the ligand-protein complexes. The spherical polar coordinates defining the orientation of the binding poses were also calculated and used in the statistical analysis. The statistical analysis has allowed us to hypothesize the importance of these radial distances and the polar angles of key atoms in the chalcones in binding to the pyruvate kinase crystal structure. This was validated by the docking of another small library of compound models in which the α,β-unsaturated ketone chain of the chalcone was replaced by incrementally longer conjugated chains. Further studies on the chalcones themselves reveal rotameric systems in both cis and trans-configurations (which may impact binding), and also studied was the effect of Topliss-based modification and its impact of binding to HSP90. Molecular dynamics confirmed good binding of identified chalcone hits.
- Full Text:
- Authors: Sarron, Arthur F D
- Date: 2020
- Subjects: Acetophenone , Benzaldehyde , Ketones , Pyruvate kinase , Drug development , Aromatic compounds , Heat shock proteins
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/116028 , vital:34291
- Description: Chalcone family molecules are well known to have therapeutic proprieties (anti-inflammatory, anti-microbial or anti-cancer, etc). However the mechanism of action in some cases is not well known. A virtual library of this family of compounds was constructed using custom scripts, based on the aldol condensation, and this library was modified further to analogues by expansion of the α,β-unsaturated ketone linker. Acetophenone and benzaldehyde derivatives which are available and purchasable were used as a base to design the chalcone virtual library. 8063 chalcones were constructed and geometrically optimized with Gaussian 09. Their physicochemical characteristics linked to the Lipinski rules were analyzed with Knime and CDK. The entire library was after docked against several targets including HIV-1 integrase, MRSA pyruvate kinase, HSP90, COX-1, COX-2, ALR2, MAOA, MAOB, acetylcholinesterase, butyrylcholinesterase and PLA2. With the exception of MAOA, which does not have a crystal structure ligand, all dockings were validated by redocking the original ligand provided by the literature. These targets are known in the literature to be inhibited by chalcone-derivatives. However, specificity of the particular known chalcone inhibitors to the particular targets is not known. To this end the performance of the generated chalcone library against the list of targets was of interest. The binding energy of ligand-protein complexes was generally good across the library. Statistical analysis including principal component analysis and hierarchical clustering analysis were made in order to investigate for any physical/chemical characteristics which might explain what chalcone features affect the binding energy of the ligand-protein complexes. The spherical polar coordinates defining the orientation of the binding poses were also calculated and used in the statistical analysis. The statistical analysis has allowed us to hypothesize the importance of these radial distances and the polar angles of key atoms in the chalcones in binding to the pyruvate kinase crystal structure. This was validated by the docking of another small library of compound models in which the α,β-unsaturated ketone chain of the chalcone was replaced by incrementally longer conjugated chains. Further studies on the chalcones themselves reveal rotameric systems in both cis and trans-configurations (which may impact binding), and also studied was the effect of Topliss-based modification and its impact of binding to HSP90. Molecular dynamics confirmed good binding of identified chalcone hits.
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Addressing flux suppression, radio frequency interference, and selection of optimal solution intervals during radio interferometric calibration
- Authors: Sob, Ulrich Armel Mbou
- Date: 2020
- Subjects: CubiCal (Software) , Radio -- Interference , Imaging systems in astronomy , Algorithms , Astronomical instruments -- Calibration , Astronomy -- Data processing
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/147714 , vital:38663
- Description: The forthcoming Square Kilometre Array is expected to provide answers to some of the most intriguing questions about our Universe. However, as it is already noticeable from MeerKAT and other precursors, the amounts of data produced by these new instruments are significantly challenging to calibrate and image. Calibration of radio interferometric data is usually biased by incomplete sky models and radio frequency interference (RFI) resulting in calibration artefacts that limit the dynamic range and image fidelity of the resulting images. One of the most noticeable of these artefacts is the formation of spurious sources which causes suppression of real emissions. Fortunately, it has been shown that calibration algorithms employing heavy-tailed likelihood functions are less susceptible to this due to their robustness against outliers. Leveraging on recent developments in the field of complex optimisation, we implement a robust calibration algorithm using a Student’s t likelihood function and Wirtinger derivatives. The new algorithm, dubbed the robust solver, is incorporated as a subroutine into the newly released calibration software package CubiCal. We perform statistical analysis on the distribution of visibilities and provide an insight into the functioning of the robust solver and describe different scenarios where it will improve calibration. We use simulations to show that the robust solver effectively reduces the amount of flux suppressed from unmodelled sources both in direction independent and direction dependent calibration. Furthermore, the robust solver is shown to successfully mitigate the effects of low-level RFI when applied to a simulated and a real VLA dataset. Finally, we demonstrate that there are close links between the amount of flux suppressed from sources, the effects of the RFI and the employed solution interval during radio interferometric calibration. Hence, we investigate the effects of solution intervals and the different factors to consider in order to select adequate solution intervals. Furthermore, we propose a practical brute force method for selecting optimal solution intervals. The proposed method is successfully applied to a VLA dataset.
- Full Text:
- Authors: Sob, Ulrich Armel Mbou
- Date: 2020
- Subjects: CubiCal (Software) , Radio -- Interference , Imaging systems in astronomy , Algorithms , Astronomical instruments -- Calibration , Astronomy -- Data processing
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/147714 , vital:38663
- Description: The forthcoming Square Kilometre Array is expected to provide answers to some of the most intriguing questions about our Universe. However, as it is already noticeable from MeerKAT and other precursors, the amounts of data produced by these new instruments are significantly challenging to calibrate and image. Calibration of radio interferometric data is usually biased by incomplete sky models and radio frequency interference (RFI) resulting in calibration artefacts that limit the dynamic range and image fidelity of the resulting images. One of the most noticeable of these artefacts is the formation of spurious sources which causes suppression of real emissions. Fortunately, it has been shown that calibration algorithms employing heavy-tailed likelihood functions are less susceptible to this due to their robustness against outliers. Leveraging on recent developments in the field of complex optimisation, we implement a robust calibration algorithm using a Student’s t likelihood function and Wirtinger derivatives. The new algorithm, dubbed the robust solver, is incorporated as a subroutine into the newly released calibration software package CubiCal. We perform statistical analysis on the distribution of visibilities and provide an insight into the functioning of the robust solver and describe different scenarios where it will improve calibration. We use simulations to show that the robust solver effectively reduces the amount of flux suppressed from unmodelled sources both in direction independent and direction dependent calibration. Furthermore, the robust solver is shown to successfully mitigate the effects of low-level RFI when applied to a simulated and a real VLA dataset. Finally, we demonstrate that there are close links between the amount of flux suppressed from sources, the effects of the RFI and the employed solution interval during radio interferometric calibration. Hence, we investigate the effects of solution intervals and the different factors to consider in order to select adequate solution intervals. Furthermore, we propose a practical brute force method for selecting optimal solution intervals. The proposed method is successfully applied to a VLA dataset.
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An analysis of how visualisation capabilities in dynamic geometric software develop meaning-making of mathematical concepts in selected Grade 11 learners
- Authors: Mavani, Deepack Pravin
- Date: 2020
- Subjects: Mathematics -- Study and teaching (Secondary) -- South Africa , Mathematics -- Computer programs , Mathematics -- Study and teaching (Secondary) -- South Africa -- Case studies , Mathematics -- Study and teaching -- Activity programs , Educational technology , Visualization
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/143213 , vital:38211
- Description: Visualisation plays a central role in developing mathematical ideas because it can be used to make these ideas explicit and visible, and thus has the potential to advance understanding. This study centred around the GeoGebra Literacy Initiative Project (GLIP), a teacher development initiative in Mthatha that aimed to grow and develop appropriate Information and Communication Technology (ICT) skills in teachers, to harness the teaching and learning potential of GeoGebra. GeoGebra is a dynamic geometric software package that is very interactive and makes use of powerful features to create images which can be moved around the computer screen for mathematical exploration. This research project was located within GLIP and analysed how GeoGebra applets develop conceptual and procedural understanding in selected Grade 11 learners. One aspect of GLIP was for teachers to use GeoGebra applets that they had developed themselves and implemented in their classrooms in pre-determined cycles that were aligned to the curriculum. My study specifically focused on how the selected learners made use of these applets and explored how learning had taken place in terms of developing mathematical meaning-making. This interpretive research study was designed as a case study. The case was a cohort of selected Grade 11 learners who had been taught by GLIP teachers, and my unit of analysis was the learners’ interaction with the applets. A screen capturing software package was used to capture learners’ interactions with the GeoGebra. My data consisted mainly of recorded observations and interviews. An analytical framework derived from the works of Kilpatrick, Swafford, and Findell (2001) and Carter et al. (2009) guided and informed the data analysis of the learners’ activities with the GeoGebra. The theoretical orientation of this study was constructivist learning. An in-depth analysis and detailed descriptions of the participants’ interactions enabled me to gain a comprehensive understanding of their meaning-making processes in a technological classroom context. An analysis across the participants identified distinguishable patterns or differences in the development of the learners’ mathematical proficiency and making sense of mathematical ideas. The research argued that technology enabled visualisation was a powerful tool to not only enrich mathematically activities, but to also enrich conceptual and procedural understanding. The findings recognised that exploration of, or manipulation on mathematical objects in GeoGebra was a key activity in the participants’ meaning-making process. It also enabled learners to offer self-proclaimed theories
- Full Text:
- Authors: Mavani, Deepack Pravin
- Date: 2020
- Subjects: Mathematics -- Study and teaching (Secondary) -- South Africa , Mathematics -- Computer programs , Mathematics -- Study and teaching (Secondary) -- South Africa -- Case studies , Mathematics -- Study and teaching -- Activity programs , Educational technology , Visualization
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/143213 , vital:38211
- Description: Visualisation plays a central role in developing mathematical ideas because it can be used to make these ideas explicit and visible, and thus has the potential to advance understanding. This study centred around the GeoGebra Literacy Initiative Project (GLIP), a teacher development initiative in Mthatha that aimed to grow and develop appropriate Information and Communication Technology (ICT) skills in teachers, to harness the teaching and learning potential of GeoGebra. GeoGebra is a dynamic geometric software package that is very interactive and makes use of powerful features to create images which can be moved around the computer screen for mathematical exploration. This research project was located within GLIP and analysed how GeoGebra applets develop conceptual and procedural understanding in selected Grade 11 learners. One aspect of GLIP was for teachers to use GeoGebra applets that they had developed themselves and implemented in their classrooms in pre-determined cycles that were aligned to the curriculum. My study specifically focused on how the selected learners made use of these applets and explored how learning had taken place in terms of developing mathematical meaning-making. This interpretive research study was designed as a case study. The case was a cohort of selected Grade 11 learners who had been taught by GLIP teachers, and my unit of analysis was the learners’ interaction with the applets. A screen capturing software package was used to capture learners’ interactions with the GeoGebra. My data consisted mainly of recorded observations and interviews. An analytical framework derived from the works of Kilpatrick, Swafford, and Findell (2001) and Carter et al. (2009) guided and informed the data analysis of the learners’ activities with the GeoGebra. The theoretical orientation of this study was constructivist learning. An in-depth analysis and detailed descriptions of the participants’ interactions enabled me to gain a comprehensive understanding of their meaning-making processes in a technological classroom context. An analysis across the participants identified distinguishable patterns or differences in the development of the learners’ mathematical proficiency and making sense of mathematical ideas. The research argued that technology enabled visualisation was a powerful tool to not only enrich mathematically activities, but to also enrich conceptual and procedural understanding. The findings recognised that exploration of, or manipulation on mathematical objects in GeoGebra was a key activity in the participants’ meaning-making process. It also enabled learners to offer self-proclaimed theories
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An exploration of how Grade 3 Foundation Phase teachers develop basic scientific process skills using an inquiry-based approach in their classrooms
- Authors: Nhase, Zukiswa
- Date: 2020
- Subjects: Elementary school teaching-- South Africa , Elementary school teachers -- South Africa , Elementary school teachers -- In-service training -- South Africa , Science -- Study and teaching (Elementary) -- South Africa , Learning, Psychology of , Cognition in children , Inquiry-based learning -- South Africa , Active learning -- South Africa , Pedagogical content knowledge -- South Africa , Educational change -- South Africa , Socio-cultural theory
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/145181 , vital:38416
- Description: Some studies have looked at Foundation Phase teachers’ perspectives on the teaching of science in this phase. Such studies have highlighted various challenges on the teaching of science in the Foundation Phase. They pointed out issues such as large class numbers, lack of resources and lack of science knowledge from Foundation Phase teachers. However, none of these studies have looked at how Foundation Phase teachers are using an Inquiry-Based Approach in their classrooms instead few studies have looked at the Foundation Phase teachers’ perspectives about scientific inquiry in this phase. Even though many scholars have presented several challenges to the teaching of science both at secondary and primary level, the argument is strongly made that Foundation Phase learners should be exposed to the learning of science. Generally, children at the Foundation Phase level naturally enjoy observing and thinking about nature; exposing learners to science develops positive attitudes towards science; the use of scientifically informed language at an early age influences the eventual development of scientific concepts; children can understand scientific concepts and reason scientifically; and science is an efficient means for developing scientific thinking. It is within these arguments and discussions that this interpretive case study research sought to explore the Pedagogical Content Knowledge of four Foundation Phase teachers in developing the Scientific Process Skills using an Inquiry-Based Approach in their classrooms and subsequently, the significance of this research study. The socio-cultural theory, Topic Specific Pedagogical Content Knowledge, Zaretskii’s six conditions for development during mediation and the principles of an Inquiry-Based Approach were used as analytical lenses in this research. To use an Inquiry-Based Approach, generally teachers have to understand its principles and know how to develop basic Scientific Process Skills while teaching the science content. In the Foundation Phase, the Natural Sciences component or content is embedded in the Beginning Knowledge study area of the Life Skills subject and this can create difficulties for teachers to even recognise the scientific concepts in the Life Skills. The four IsiXhosa female teachers used the home language of learners as the language of instruction to implement an Inquiry-Based Approach in their classrooms. Data were generated in four phases. Phase one was baseline data through document analysis. Three of the phases were directed by the research question asked. Data were generated using questionnaires, interviews (semi-structured and stimulated recall), lesson observations (videotaped) and group reflections and discussions. From the work of Vygotsky, Zaretskii formulated six conditions that can be used to develop learners’ zone of proximal development in learning and these were used as analytical lenses to analyse data to understand how teachers mediated learning and development of Scientific Inquiry in their Grade 3 classrooms. In addition, the principles of an Inquiry-Based Approach were used as analytical lenses as to how teachers implemented the scientific inquiry approach. The categories or components of Topic Specific Pedagogical Content Knowledge were used as analytical lenses as to how these teachers dealt with science concepts or content when using an inquiry-based Approach in their classrooms. Using the home language of learners as an instructional tool, data showed that learners were afforded the opportunity to freely engage in activities and as a result, the context of learning was non-threatening for both teachers and learners. Although learning activities could be improved, teachers created social spaces for learners to take part in learning. In addition, the use of learners’ environments in the observed lessons made it comfortable for learners to act as young scientists. The new knowledge in this research was presented by the use of the adapted analytical tool, which combined diverse components of theory and literature that aligned with each other. The reflection space for the participants did not only afford the participants to discuss about each other’s lessons or experiences in this research, it allowed the participants to engage with the research objectives. The reflection space strengthened the research ethics if this study. Hence, the concept that says, ‘Absenting the absences’. In conclusion, the study thus recommends further professional development spaces that promote community of practice in using an Inquiry-Based Approach in the Foundation Phase.
- Full Text:
- Authors: Nhase, Zukiswa
- Date: 2020
- Subjects: Elementary school teaching-- South Africa , Elementary school teachers -- South Africa , Elementary school teachers -- In-service training -- South Africa , Science -- Study and teaching (Elementary) -- South Africa , Learning, Psychology of , Cognition in children , Inquiry-based learning -- South Africa , Active learning -- South Africa , Pedagogical content knowledge -- South Africa , Educational change -- South Africa , Socio-cultural theory
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/145181 , vital:38416
- Description: Some studies have looked at Foundation Phase teachers’ perspectives on the teaching of science in this phase. Such studies have highlighted various challenges on the teaching of science in the Foundation Phase. They pointed out issues such as large class numbers, lack of resources and lack of science knowledge from Foundation Phase teachers. However, none of these studies have looked at how Foundation Phase teachers are using an Inquiry-Based Approach in their classrooms instead few studies have looked at the Foundation Phase teachers’ perspectives about scientific inquiry in this phase. Even though many scholars have presented several challenges to the teaching of science both at secondary and primary level, the argument is strongly made that Foundation Phase learners should be exposed to the learning of science. Generally, children at the Foundation Phase level naturally enjoy observing and thinking about nature; exposing learners to science develops positive attitudes towards science; the use of scientifically informed language at an early age influences the eventual development of scientific concepts; children can understand scientific concepts and reason scientifically; and science is an efficient means for developing scientific thinking. It is within these arguments and discussions that this interpretive case study research sought to explore the Pedagogical Content Knowledge of four Foundation Phase teachers in developing the Scientific Process Skills using an Inquiry-Based Approach in their classrooms and subsequently, the significance of this research study. The socio-cultural theory, Topic Specific Pedagogical Content Knowledge, Zaretskii’s six conditions for development during mediation and the principles of an Inquiry-Based Approach were used as analytical lenses in this research. To use an Inquiry-Based Approach, generally teachers have to understand its principles and know how to develop basic Scientific Process Skills while teaching the science content. In the Foundation Phase, the Natural Sciences component or content is embedded in the Beginning Knowledge study area of the Life Skills subject and this can create difficulties for teachers to even recognise the scientific concepts in the Life Skills. The four IsiXhosa female teachers used the home language of learners as the language of instruction to implement an Inquiry-Based Approach in their classrooms. Data were generated in four phases. Phase one was baseline data through document analysis. Three of the phases were directed by the research question asked. Data were generated using questionnaires, interviews (semi-structured and stimulated recall), lesson observations (videotaped) and group reflections and discussions. From the work of Vygotsky, Zaretskii formulated six conditions that can be used to develop learners’ zone of proximal development in learning and these were used as analytical lenses to analyse data to understand how teachers mediated learning and development of Scientific Inquiry in their Grade 3 classrooms. In addition, the principles of an Inquiry-Based Approach were used as analytical lenses as to how teachers implemented the scientific inquiry approach. The categories or components of Topic Specific Pedagogical Content Knowledge were used as analytical lenses as to how these teachers dealt with science concepts or content when using an inquiry-based Approach in their classrooms. Using the home language of learners as an instructional tool, data showed that learners were afforded the opportunity to freely engage in activities and as a result, the context of learning was non-threatening for both teachers and learners. Although learning activities could be improved, teachers created social spaces for learners to take part in learning. In addition, the use of learners’ environments in the observed lessons made it comfortable for learners to act as young scientists. The new knowledge in this research was presented by the use of the adapted analytical tool, which combined diverse components of theory and literature that aligned with each other. The reflection space for the participants did not only afford the participants to discuss about each other’s lessons or experiences in this research, it allowed the participants to engage with the research objectives. The reflection space strengthened the research ethics if this study. Hence, the concept that says, ‘Absenting the absences’. In conclusion, the study thus recommends further professional development spaces that promote community of practice in using an Inquiry-Based Approach in the Foundation Phase.
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An integrative approach to understanding vulnerability of an alpine range-restricted bird to climate warming
- Authors: Oswald, Krista Natasha
- Date: 2020
- Subjects: Passeriformes -- South Africa -- Western Cape , Passeriformes -- Physiology -- South Africa -- Western Cape , Passeriformes -- Behavior -- Climatic factors -- South Africa -- Western Cape , Passeriformes -- Reproduction -- Climatic factors -- South Africa -- Western Cape , Passeriformes -- Dispersal -- South Africa -- Western Cape , Passeriformes -- Food -- South Africa -- Western Cape , Passeriformes -- Nests-- South Africa -- Western Cape , Blue Hill Nature Reserve , Cape Rockjumper -- Climatic factors , Chaetops frenatus
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/148517 , vital:38746
- Description: Understanding species' vulnerability to climate change requires an integrative ecological approach involving, at minimum, physiology, behaviour, reproductive success, and limitations on dispersal. In this thesis I determined potential negative effects of increasing temperatures on behaviour, reproduction, and ability to disperse in an alpine-restricted bird, the Cape Rockjumper Chaetops frenatus ("Rockjumper"). Here I provide a comprehensive ecological set of data for understanding the link between Rockjumper population declines and warming habitats. I tested whether Rockjumper microsite-use at high temperatures resulted in decreased time spent on important behaviours, such as foraging. I found Rockjumpers made increased use of rock-shade as air temperature increased and so spent less time panting, but birds in rock-shade foraged less. Birds may be constrained to foraging in sun at high temperatures to sustain energy or water requirements, despite risks of high thermal load, or else face lost foraging opportunities by remaining in rock-shade. I determined if adult nest attendance and causes of nest failure were related to high temperatures. I filmed nests over two breeding seasons to examine temperature-effects on adult time in nests, provisioning rate, and resultant nestling daily mass gain. The only temperature effect I found was decreased percent daily change in body mass for older nestlings at hotter temperatures. I also examined causes of nest failure over three breeding seasons in relation to nest concealment and habitat openness by observing failure/success. Nests in more open territories (i.e. early post-fire habitat) had greater success, and the main cause of predation came from Boomslang Dispholydus typus. Importantly, the probability of Boomslang predation increased significantly at hotter temperatures. These findings show there may be direct negative effects of increasing temperatures on reproductive success and population recruitment, and so hotter temperature during the breeding season may be at least partly responsible for observed population declines. Lastly, I examined genetic structure of populations across mountain ranges separated from one another by lowland habitat unsuitable for Rockjumpers. I predicted I would find little evidence for dispersal between mountain ranges separated by unsuitable lowland habitat, but instead found Rockjumpers show little evidence for inbreeding. I also found evidence for a past bottleneck event or founder effect, and little overall genetic diversity (possibly as their specialized niche exerts selective pressure). Low diversity may limit Rockjumpers' ability to adapt to a changing environment. Adult physiological and behavioural thresholds to increasing temperatures are often used to create predictions of climate change effects. My past physiological research and current behavioural research suggest no particularly strong evidence that temperature-related population declines are driven by poor physiological capacity to tolerate heat or negative behaviour trade-offs. Instead, my current research shows that understanding negative effects of increasing temperatures may require a more in-depth approach involving investigation of fine-scale ecological interactions. No single one of my chapters provides the insight necessary for understanding Rockjumper population declines at warming temperatures. Instead, I show how an integrative approach may be necessary for assessing species' vulnerability to climate change by examining multiple ecological aspects of a single sentinel species, using an alpine species with a narrow thermal range and highly specialized habitat niche.
- Full Text:
- Authors: Oswald, Krista Natasha
- Date: 2020
- Subjects: Passeriformes -- South Africa -- Western Cape , Passeriformes -- Physiology -- South Africa -- Western Cape , Passeriformes -- Behavior -- Climatic factors -- South Africa -- Western Cape , Passeriformes -- Reproduction -- Climatic factors -- South Africa -- Western Cape , Passeriformes -- Dispersal -- South Africa -- Western Cape , Passeriformes -- Food -- South Africa -- Western Cape , Passeriformes -- Nests-- South Africa -- Western Cape , Blue Hill Nature Reserve , Cape Rockjumper -- Climatic factors , Chaetops frenatus
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/148517 , vital:38746
- Description: Understanding species' vulnerability to climate change requires an integrative ecological approach involving, at minimum, physiology, behaviour, reproductive success, and limitations on dispersal. In this thesis I determined potential negative effects of increasing temperatures on behaviour, reproduction, and ability to disperse in an alpine-restricted bird, the Cape Rockjumper Chaetops frenatus ("Rockjumper"). Here I provide a comprehensive ecological set of data for understanding the link between Rockjumper population declines and warming habitats. I tested whether Rockjumper microsite-use at high temperatures resulted in decreased time spent on important behaviours, such as foraging. I found Rockjumpers made increased use of rock-shade as air temperature increased and so spent less time panting, but birds in rock-shade foraged less. Birds may be constrained to foraging in sun at high temperatures to sustain energy or water requirements, despite risks of high thermal load, or else face lost foraging opportunities by remaining in rock-shade. I determined if adult nest attendance and causes of nest failure were related to high temperatures. I filmed nests over two breeding seasons to examine temperature-effects on adult time in nests, provisioning rate, and resultant nestling daily mass gain. The only temperature effect I found was decreased percent daily change in body mass for older nestlings at hotter temperatures. I also examined causes of nest failure over three breeding seasons in relation to nest concealment and habitat openness by observing failure/success. Nests in more open territories (i.e. early post-fire habitat) had greater success, and the main cause of predation came from Boomslang Dispholydus typus. Importantly, the probability of Boomslang predation increased significantly at hotter temperatures. These findings show there may be direct negative effects of increasing temperatures on reproductive success and population recruitment, and so hotter temperature during the breeding season may be at least partly responsible for observed population declines. Lastly, I examined genetic structure of populations across mountain ranges separated from one another by lowland habitat unsuitable for Rockjumpers. I predicted I would find little evidence for dispersal between mountain ranges separated by unsuitable lowland habitat, but instead found Rockjumpers show little evidence for inbreeding. I also found evidence for a past bottleneck event or founder effect, and little overall genetic diversity (possibly as their specialized niche exerts selective pressure). Low diversity may limit Rockjumpers' ability to adapt to a changing environment. Adult physiological and behavioural thresholds to increasing temperatures are often used to create predictions of climate change effects. My past physiological research and current behavioural research suggest no particularly strong evidence that temperature-related population declines are driven by poor physiological capacity to tolerate heat or negative behaviour trade-offs. Instead, my current research shows that understanding negative effects of increasing temperatures may require a more in-depth approach involving investigation of fine-scale ecological interactions. No single one of my chapters provides the insight necessary for understanding Rockjumper population declines at warming temperatures. Instead, I show how an integrative approach may be necessary for assessing species' vulnerability to climate change by examining multiple ecological aspects of a single sentinel species, using an alpine species with a narrow thermal range and highly specialized habitat niche.
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An intervention on supporting teachers’ understanding of and mediation of learning of stoichiometry in selected schools in the Zambezi Region
- Authors: Denuga, Desalu Dedayo
- Date: 2020
- Subjects: Stoichiometry -- Study and teaching (Secondary) -- Namibia , Chemistry -- Study and teaching (Secondary) -- Namibia , Participant observation -- Namibia , Constructivism (Education) -- Namibia , Pedagogical content knowledge -- Namibia , Continuing education -- Namibia , Teachers -- In-service training -- Namibia
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/103855 , vital:32315
- Description: This study has been triggered by the results on stoichiometry questions in the Directorate of Namibian Examination Assessment’s (DNEA) scripts. As highlighted in the examiners’ reports, stoichiometry is an ongoing annual problem for most students in Namibia. It is against this background that I decided to explore the possibility of an intervention in the form of continuing professional development (CPD) and collaboration workshops to improve the understanding and the mediation of learning of stoichiometry by Physical Science teachers in the Zambezi Region of Namibia. The study was underpinned by an interpretive paradigm and within this paradigm a qualitative case study approach was adopted. Since this study was in a form of an intervention, a participatory action research (PAR) approach was employed within the community of practice (CoP). I used document analysis, workshop discussions, observations and videotaped lessons, interviews (semi-structured and stimulated recall interviews) and reflections to gather data. The study was carried out at three senior secondary schools and six Physical Science teachers were involved. The study drew on the theory of constructivism as a theoretical framework, namely, Piaget’s cognitive constructivism and Vygotsky‘s social constructivism as well as Shulman’s pedagogical content knowledge (PCK). Within PCK, Mavhunga and Rollnick’s Topic Specific Pedagogical Content Knowledge (TSPCK) was used as an analytical lens (Appendix L) in this study. The findings reveal that the use of a diagnostic test on learners made the Physical Science teachers aware of the learners’ challenges and what was difficult for them to understand in stoichiometry. It also helped in their understanding of the use of prior knowledge, one of the tenets of TSPCK, to access what learners knew about stoichiometry. Further findings of the study illuminate that the Physical Science teachers’ subject matter knowledge, pedagogical content knowledge and skills had shifted as a result of their participation in the intervention workshops. The findings of this study indicate that the CoP members acquired the professional transformations which were important breakthroughs in their careers. The study thus recommends that teachers should develop effective teacher professional development activities such as study teams, exemplary lessons, cluster teaching, and peer coaching where teachers are expected to examine their assumptions and practices continuously. The implication of my study is that the developed exemplary lesson during the intervention workshops by CoP members could be useful to other Physical Science teachers in the teaching of stoichiometry in all the schools in the Zambezi Region.
- Full Text:
- Authors: Denuga, Desalu Dedayo
- Date: 2020
- Subjects: Stoichiometry -- Study and teaching (Secondary) -- Namibia , Chemistry -- Study and teaching (Secondary) -- Namibia , Participant observation -- Namibia , Constructivism (Education) -- Namibia , Pedagogical content knowledge -- Namibia , Continuing education -- Namibia , Teachers -- In-service training -- Namibia
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/103855 , vital:32315
- Description: This study has been triggered by the results on stoichiometry questions in the Directorate of Namibian Examination Assessment’s (DNEA) scripts. As highlighted in the examiners’ reports, stoichiometry is an ongoing annual problem for most students in Namibia. It is against this background that I decided to explore the possibility of an intervention in the form of continuing professional development (CPD) and collaboration workshops to improve the understanding and the mediation of learning of stoichiometry by Physical Science teachers in the Zambezi Region of Namibia. The study was underpinned by an interpretive paradigm and within this paradigm a qualitative case study approach was adopted. Since this study was in a form of an intervention, a participatory action research (PAR) approach was employed within the community of practice (CoP). I used document analysis, workshop discussions, observations and videotaped lessons, interviews (semi-structured and stimulated recall interviews) and reflections to gather data. The study was carried out at three senior secondary schools and six Physical Science teachers were involved. The study drew on the theory of constructivism as a theoretical framework, namely, Piaget’s cognitive constructivism and Vygotsky‘s social constructivism as well as Shulman’s pedagogical content knowledge (PCK). Within PCK, Mavhunga and Rollnick’s Topic Specific Pedagogical Content Knowledge (TSPCK) was used as an analytical lens (Appendix L) in this study. The findings reveal that the use of a diagnostic test on learners made the Physical Science teachers aware of the learners’ challenges and what was difficult for them to understand in stoichiometry. It also helped in their understanding of the use of prior knowledge, one of the tenets of TSPCK, to access what learners knew about stoichiometry. Further findings of the study illuminate that the Physical Science teachers’ subject matter knowledge, pedagogical content knowledge and skills had shifted as a result of their participation in the intervention workshops. The findings of this study indicate that the CoP members acquired the professional transformations which were important breakthroughs in their careers. The study thus recommends that teachers should develop effective teacher professional development activities such as study teams, exemplary lessons, cluster teaching, and peer coaching where teachers are expected to examine their assumptions and practices continuously. The implication of my study is that the developed exemplary lesson during the intervention workshops by CoP members could be useful to other Physical Science teachers in the teaching of stoichiometry in all the schools in the Zambezi Region.
- Full Text:
An investigation into the nature and adequacy of tax compliance tools available to assist small businesses in the state of Oklahoma in the United States of America
- Authors: Cary, Cindi L
- Date: 2020
- Subjects: Tax administration and procedure -- United States , United States. Internal Revenue Service , Small business -- Oklahoma , Small business -- United States , Taxpayer compliance -- Oklahoma , Taxpayer compliance -- United States
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/141015 , vital:37937
- Description: This study identifies and analyses the effectiveness of the tax tools available to the small businesses that make up more than 99 per cent of all businesses in the United States and the state of Oklahoma through an extensive investigation of the small business resources offered by federal and state government agencies, higher education institutions and the professional accounting community. The study uses numerous measurements in order to acquire multiple perspectives and relies on the examination of government websites and documents, interviews, experiments, surveys, and questionnaires to determine the existing small business tax tools and their limitations. The research offers an in-depth analysis of the facts and limitations of the small business services offered by the Internal Revenue Service (IRS). The IRS is determined the largest source of small business tax tools, but limitations plague their effectiveness. Higher education is found guilty of not providing small business education in business or accounting disciplines, leaving college graduates ill-prepared to assist small businesses. Higher education is urged to implement a small business accounting curriculum that couples field experience with classroom lectures and textbooks. This study finds the accounting profession apathetic with regard to informing small businesses of accounting services and presses certified public accountants to be more involved in the education of future small business accountants. The study concludes with recommendations to reduce the small business tax burden by improving the existing small business tax tools.
- Full Text:
- Authors: Cary, Cindi L
- Date: 2020
- Subjects: Tax administration and procedure -- United States , United States. Internal Revenue Service , Small business -- Oklahoma , Small business -- United States , Taxpayer compliance -- Oklahoma , Taxpayer compliance -- United States
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/141015 , vital:37937
- Description: This study identifies and analyses the effectiveness of the tax tools available to the small businesses that make up more than 99 per cent of all businesses in the United States and the state of Oklahoma through an extensive investigation of the small business resources offered by federal and state government agencies, higher education institutions and the professional accounting community. The study uses numerous measurements in order to acquire multiple perspectives and relies on the examination of government websites and documents, interviews, experiments, surveys, and questionnaires to determine the existing small business tax tools and their limitations. The research offers an in-depth analysis of the facts and limitations of the small business services offered by the Internal Revenue Service (IRS). The IRS is determined the largest source of small business tax tools, but limitations plague their effectiveness. Higher education is found guilty of not providing small business education in business or accounting disciplines, leaving college graduates ill-prepared to assist small businesses. Higher education is urged to implement a small business accounting curriculum that couples field experience with classroom lectures and textbooks. This study finds the accounting profession apathetic with regard to informing small businesses of accounting services and presses certified public accountants to be more involved in the education of future small business accountants. The study concludes with recommendations to reduce the small business tax burden by improving the existing small business tax tools.
- Full Text:
An investigation of the experiences of psychotherapists regarding Ubuntu in their psychotherapy practice: an interpretative phenomenological analysis
- Authors: Qangule, Lumka Sybil
- Date: 2020
- Subjects: Ubuntu (Philosophy) , Psychotherapy -- Cross-cultural studies , Psychoanalysis and culture -- South Africa , Xhosa (African people) -- Psychology , Xhosa (African people) -- Mental health , Black people -- South Africa -- Psychology , Black people -- South Africa -- Mental health , Psychotherapists -- South Africa
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/146923 , vital:38577
- Description: Psychotherapy is a Eurocentric concept and practice that has migrated to South Africa with technology, as part of the general transfer of knowledge (Mkhize, 2003). It has embedded Eurocentric principles that sometimes do not easily accommodate working with Africans. It has been practised by psychotherapists of African origin with clients of African origin, but is based upon Eurocentric ideas and guidelines for practice. Many African people consider their core values to be uBuntu, rooted in a principle ‘umntu ngumntu ngabantu’ (translated as ‘a human being is a human being because of other human beings’). Some important features of uBuntu are interdependence, respect, spirituality and the primacy of communality as an approach to life. Some of the ways in which these impact on daily functioning are not foregrounded by adherence to Western principles. The use of only Eurocentric principles when working with clients of African origin may thus not lead to the desired outcomes in psychotherapy. However, these Eurocentric principles are recognised and enforced by the authoritative bodies in the field of psychology, such as the Health Professions Council of South Africa. A distinction will be made between the more inflexible ethical principles of psychology and the ideas of therapy frames. Therapy frames are not seen as being as rigid as ethical codes and they could be augmented, to be appropriate for the context, particularly in the commonly multicultural settings that are found here. Psychotherapists of African origin are torn between abiding by the ethical principles that they have been taught and practising in the way that they, together with their clients, have been socialised. Abiding by the principles as described in the codes is safe because it does not pose any threat of being sanctioned by the regulator of practice, but clients may be let down and there may be limited success with certain clients. This clash of ideas of ways of practice poses dissonance and many dilemmas among psychotherapists of African origin. Due to the nature of this study, Interpretative Phenomenological Analysis (IPA) was adopted as a suitable methodology, where eight practising amaXhosa psychotherapists were interviewed about their experiences of incorporating uBuntu in their psychotherapy practice. The raw data from initial interviews were analysed and the findings concluded that although psychotherapists were trained in Western ways of practice, they included some practices of uBuntu in their practice as well as upholding some Eurocentric principles that seemed to be helpful for their clientele. Subsequently a summary of the findings were discussed with participants in a focus group setting, where participants endorsed and expanded upon their original responses. With the above in mind, a psychotherapy model called uBuntu-Centred Psychotherapy was created, which reflects the principles and therapy frames that have been found to be useful in treating clients of African origin. This modality is more congruent with the worldviews and style of living of many South Africans, in the post-apartheid era. It embraces some Eurocentric principles that are relevant for Africans, while it is embedded in the phenomena and way of life reflected in uBuntu, a predominant mode of functioning for the group that was the focus of this study, the amaXhosa. The study ends by making recommendations for practice, as well as highlighting the need for further and more extensive research to contribute to the project of Africanising psychotherapy.
- Full Text:
- Authors: Qangule, Lumka Sybil
- Date: 2020
- Subjects: Ubuntu (Philosophy) , Psychotherapy -- Cross-cultural studies , Psychoanalysis and culture -- South Africa , Xhosa (African people) -- Psychology , Xhosa (African people) -- Mental health , Black people -- South Africa -- Psychology , Black people -- South Africa -- Mental health , Psychotherapists -- South Africa
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/146923 , vital:38577
- Description: Psychotherapy is a Eurocentric concept and practice that has migrated to South Africa with technology, as part of the general transfer of knowledge (Mkhize, 2003). It has embedded Eurocentric principles that sometimes do not easily accommodate working with Africans. It has been practised by psychotherapists of African origin with clients of African origin, but is based upon Eurocentric ideas and guidelines for practice. Many African people consider their core values to be uBuntu, rooted in a principle ‘umntu ngumntu ngabantu’ (translated as ‘a human being is a human being because of other human beings’). Some important features of uBuntu are interdependence, respect, spirituality and the primacy of communality as an approach to life. Some of the ways in which these impact on daily functioning are not foregrounded by adherence to Western principles. The use of only Eurocentric principles when working with clients of African origin may thus not lead to the desired outcomes in psychotherapy. However, these Eurocentric principles are recognised and enforced by the authoritative bodies in the field of psychology, such as the Health Professions Council of South Africa. A distinction will be made between the more inflexible ethical principles of psychology and the ideas of therapy frames. Therapy frames are not seen as being as rigid as ethical codes and they could be augmented, to be appropriate for the context, particularly in the commonly multicultural settings that are found here. Psychotherapists of African origin are torn between abiding by the ethical principles that they have been taught and practising in the way that they, together with their clients, have been socialised. Abiding by the principles as described in the codes is safe because it does not pose any threat of being sanctioned by the regulator of practice, but clients may be let down and there may be limited success with certain clients. This clash of ideas of ways of practice poses dissonance and many dilemmas among psychotherapists of African origin. Due to the nature of this study, Interpretative Phenomenological Analysis (IPA) was adopted as a suitable methodology, where eight practising amaXhosa psychotherapists were interviewed about their experiences of incorporating uBuntu in their psychotherapy practice. The raw data from initial interviews were analysed and the findings concluded that although psychotherapists were trained in Western ways of practice, they included some practices of uBuntu in their practice as well as upholding some Eurocentric principles that seemed to be helpful for their clientele. Subsequently a summary of the findings were discussed with participants in a focus group setting, where participants endorsed and expanded upon their original responses. With the above in mind, a psychotherapy model called uBuntu-Centred Psychotherapy was created, which reflects the principles and therapy frames that have been found to be useful in treating clients of African origin. This modality is more congruent with the worldviews and style of living of many South Africans, in the post-apartheid era. It embraces some Eurocentric principles that are relevant for Africans, while it is embedded in the phenomena and way of life reflected in uBuntu, a predominant mode of functioning for the group that was the focus of this study, the amaXhosa. The study ends by making recommendations for practice, as well as highlighting the need for further and more extensive research to contribute to the project of Africanising psychotherapy.
- Full Text:
Analysing emergent time within an isolated Universe through the application of interactions in the conditional probability approach
- Authors: Bryan, Kate Louise Halse
- Date: 2020
- Subjects: Space and time , Quantum gravity , Quantum theory , Relativity (Physics)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/146676 , vital:38547
- Description: Time remains a frequently discussed issue in physics and philosophy. One interpretation of growing popularity is the ‘timeless’ view which states that our experience of time is only an illusion. The isolated Universe model, provided by the Wheeler-DeWitt equation, supports this interpretation by describing time using clocks in the conditional probability interpretation (CPI). However, the CPI customarily dismisses interaction effects as negligible creating a potential blind spot which overlooks the potential influence of interaction effects. Accounting for interactions opens up a new avenue of analysis and a potential challenge to the interpretation of time. In aid of our assessment of the impact interaction effects have on the CPI, we present rudimentary definitions of time and its associated concepts. Defined in a minimalist manner, time is argued to require a postulate of causality as a means of accounting for temporal ordering in physical theories. Several of these theories are discussed here in terms of their respective approaches to time and, despite their differences, there are indications that the accounts of time are unified in a more fundamental theory. An analytic analysis of the CPI, incorporating two different clock choices, and a qualitative analysis both confirm that interactions have a necessary role within the CPI. The consequence of removing interactions is a maximised uncertainty in any measurement of the clock and a restriction to a two-state system, as indicated by the results of the toy models and qualitative argument respectively. The philosophical implication is that we are not restricted to the timeless view since including interactions as agents of causal interventions between systems provides an account of time as a real phenomenon. This result highlights the reliance on a postulate of causality which forms a pressing problem in explaining our experience of time.
- Full Text:
- Authors: Bryan, Kate Louise Halse
- Date: 2020
- Subjects: Space and time , Quantum gravity , Quantum theory , Relativity (Physics)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/146676 , vital:38547
- Description: Time remains a frequently discussed issue in physics and philosophy. One interpretation of growing popularity is the ‘timeless’ view which states that our experience of time is only an illusion. The isolated Universe model, provided by the Wheeler-DeWitt equation, supports this interpretation by describing time using clocks in the conditional probability interpretation (CPI). However, the CPI customarily dismisses interaction effects as negligible creating a potential blind spot which overlooks the potential influence of interaction effects. Accounting for interactions opens up a new avenue of analysis and a potential challenge to the interpretation of time. In aid of our assessment of the impact interaction effects have on the CPI, we present rudimentary definitions of time and its associated concepts. Defined in a minimalist manner, time is argued to require a postulate of causality as a means of accounting for temporal ordering in physical theories. Several of these theories are discussed here in terms of their respective approaches to time and, despite their differences, there are indications that the accounts of time are unified in a more fundamental theory. An analytic analysis of the CPI, incorporating two different clock choices, and a qualitative analysis both confirm that interactions have a necessary role within the CPI. The consequence of removing interactions is a maximised uncertainty in any measurement of the clock and a restriction to a two-state system, as indicated by the results of the toy models and qualitative argument respectively. The philosophical implication is that we are not restricted to the timeless view since including interactions as agents of causal interventions between systems provides an account of time as a real phenomenon. This result highlights the reliance on a postulate of causality which forms a pressing problem in explaining our experience of time.
- Full Text:
Application of machine learning, molecular modelling and structural data mining against antiretroviral drug resistance in HIV-1
- Sheik Amamuddy, Olivier Serge André
- Authors: Sheik Amamuddy, Olivier Serge André
- Date: 2020
- Subjects: Machine learning , Molecules -- Models , Data mining , Neural networks (Computer science) , Antiretroviral agents , Protease inhibitors , Drug resistance , Multidrug resistance , Molecular dynamics , Renin-angiotensin system , HIV (Viruses) -- South Africa , HIV (Viruses) -- Social aspects -- South Africa , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115964 , vital:34282
- Description: Millions are affected with the Human Immunodeficiency Virus (HIV) world wide, even though the death toll is on the decline. Antiretrovirals (ARVs), more specifically protease inhibitors have shown tremendous success since their introduction into therapy since the mid 1990’s by slowing down progression to the Acquired Immune Deficiency Syndrome (AIDS). However, Drug Resistance Mutations (DRMs) are constantly selected for due to viral adaptation, making drugs less effective over time. The current challenge is to manage the infection optimally with a limited set of drugs, with differing associated levels of toxicities in the face of a virus that (1) exists as a quasispecies, (2) may transmit acquired DRMs to drug-naive individuals and (3) that can manifest class-wide resistance due to similarities in design. The presence of latent reservoirs, unawareness of infection status, education and various socio-economic factors make the problem even more complex. Adequate timing and choice of drug prescription together with treatment adherence are very important as drug toxicities, drug failure and sub-optimal treatment regimens leave room for further development of drug resistance. While CD4 cell count and the determination of viral load from patients in resource-limited settings are very helpful to track how well a patient’s immune system is able to keep the virus in check, they can be lengthy in determining whether an ARV is effective. Phenosense assay kits answer this problem using viruses engineered to contain the patient sequences and evaluating their growth in the presence of different ARVs, but this can be expensive and too involved for routine checks. As a cheaper and faster alternative, genotypic assays provide similar information from HIV pol sequences obtained from blood samples, inferring ARV efficacy on the basis of drug resistance mutation patterns. However, these are inherently complex and the various methods of in silico prediction, such as Geno2pheno, REGA and Stanford HIVdb do not always agree in every case, even though this gap decreases as the list of resistance mutations is updated. A major gap in HIV treatment is that the information used for predicting drug resistance is mainly computed from data containing an overwhelming majority of B subtype HIV, when these only comprise about 12% of the worldwide HIV infections. In addition to growing evidence that drug resistance is subtype-related, it is intuitive to hypothesize that as subtyping is a phylogenetic classification, the more divergent a subtype is from the strains used in training prediction models, the less their resistance profiles would correlate. For the aforementioned reasons, we used a multi-faceted approach to attack the virus in multiple ways. This research aimed to (1) improve resistance prediction methods by focusing solely on the available subtype, (2) mine structural information pertaining to resistance in order to find any exploitable weak points and increase knowledge of the mechanistic processes of drug resistance in HIV protease. Finally, (3) we screen for protease inhibitors amongst a database of natural compounds [the South African natural compound database (SANCDB)] to find molecules or molecular properties usable to come up with improved inhibition against the drug target. In this work, structural information was mined using the Anisotropic Network Model, Dynamics Cross-Correlation, Perturbation Response Scanning, residue contact network analysis and the radius of gyration. These methods failed to give any resistance-associated patterns in terms of natural movement, internal correlated motions, residue perturbation response, relational behaviour and global compaction respectively. Applications of drug docking, homology-modelling and energy minimization for generating features suitable for machine-learning were not very promising, and rather suggest that the value of binding energies by themselves from Vina may not be very reliable quantitatively. All these failures lead to a refinement that resulted in a highly sensitive statistically-guided network construction and analysis, which leads to key findings in the early dynamics associated with resistance across all PI drugs. The latter experiment unravelled a conserved lateral expansion motion occurring at the flap elbows, and an associated contraction that drives the base of the dimerization domain towards the catalytic site’s floor in the case of drug resistance. Interestingly, we found that despite the conserved movement, bond angles were degenerate. Alongside, 16 Artificial Neural Network models were optimised for HIV proteases and reverse transcriptase inhibitors, with performances on par with Stanford HIVdb. Finally, we prioritised 9 compounds with potential protease inhibitory activity using virtual screening and molecular dynamics (MD) to additionally suggest a promising modification to one of the compounds. This yielded another molecule inhibiting equally well both opened and closed receptor target conformations, whereby each of the compounds had been selected against an array of multi-drug-resistant receptor variants. While a main hurdle was a lack of non-B subtype data, our findings, especially from the statistically-guided network analysis, may extrapolate to a certain extent to them as the level of conservation was very high within subtype B, despite all the present variations. This network construction method lays down a sensitive approach for analysing a pair of alternate phenotypes for which complex patterns prevail, given a sufficient number of experimental units. During the course of research a weighted contact mapping tool was developed to compare renin-angiotensinogen variants and packaged as part of the MD-TASK tool suite. Finally the functionality, compatibility and performance of the MODE-TASK tool were evaluated and confirmed for both Python2.7.x and Python3.x, for the analysis of normals modes from single protein structures and essential modes from MD trajectories. These techniques and tools collectively add onto the conventional means of MD analysis.
- Full Text:
- Authors: Sheik Amamuddy, Olivier Serge André
- Date: 2020
- Subjects: Machine learning , Molecules -- Models , Data mining , Neural networks (Computer science) , Antiretroviral agents , Protease inhibitors , Drug resistance , Multidrug resistance , Molecular dynamics , Renin-angiotensin system , HIV (Viruses) -- South Africa , HIV (Viruses) -- Social aspects -- South Africa , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115964 , vital:34282
- Description: Millions are affected with the Human Immunodeficiency Virus (HIV) world wide, even though the death toll is on the decline. Antiretrovirals (ARVs), more specifically protease inhibitors have shown tremendous success since their introduction into therapy since the mid 1990’s by slowing down progression to the Acquired Immune Deficiency Syndrome (AIDS). However, Drug Resistance Mutations (DRMs) are constantly selected for due to viral adaptation, making drugs less effective over time. The current challenge is to manage the infection optimally with a limited set of drugs, with differing associated levels of toxicities in the face of a virus that (1) exists as a quasispecies, (2) may transmit acquired DRMs to drug-naive individuals and (3) that can manifest class-wide resistance due to similarities in design. The presence of latent reservoirs, unawareness of infection status, education and various socio-economic factors make the problem even more complex. Adequate timing and choice of drug prescription together with treatment adherence are very important as drug toxicities, drug failure and sub-optimal treatment regimens leave room for further development of drug resistance. While CD4 cell count and the determination of viral load from patients in resource-limited settings are very helpful to track how well a patient’s immune system is able to keep the virus in check, they can be lengthy in determining whether an ARV is effective. Phenosense assay kits answer this problem using viruses engineered to contain the patient sequences and evaluating their growth in the presence of different ARVs, but this can be expensive and too involved for routine checks. As a cheaper and faster alternative, genotypic assays provide similar information from HIV pol sequences obtained from blood samples, inferring ARV efficacy on the basis of drug resistance mutation patterns. However, these are inherently complex and the various methods of in silico prediction, such as Geno2pheno, REGA and Stanford HIVdb do not always agree in every case, even though this gap decreases as the list of resistance mutations is updated. A major gap in HIV treatment is that the information used for predicting drug resistance is mainly computed from data containing an overwhelming majority of B subtype HIV, when these only comprise about 12% of the worldwide HIV infections. In addition to growing evidence that drug resistance is subtype-related, it is intuitive to hypothesize that as subtyping is a phylogenetic classification, the more divergent a subtype is from the strains used in training prediction models, the less their resistance profiles would correlate. For the aforementioned reasons, we used a multi-faceted approach to attack the virus in multiple ways. This research aimed to (1) improve resistance prediction methods by focusing solely on the available subtype, (2) mine structural information pertaining to resistance in order to find any exploitable weak points and increase knowledge of the mechanistic processes of drug resistance in HIV protease. Finally, (3) we screen for protease inhibitors amongst a database of natural compounds [the South African natural compound database (SANCDB)] to find molecules or molecular properties usable to come up with improved inhibition against the drug target. In this work, structural information was mined using the Anisotropic Network Model, Dynamics Cross-Correlation, Perturbation Response Scanning, residue contact network analysis and the radius of gyration. These methods failed to give any resistance-associated patterns in terms of natural movement, internal correlated motions, residue perturbation response, relational behaviour and global compaction respectively. Applications of drug docking, homology-modelling and energy minimization for generating features suitable for machine-learning were not very promising, and rather suggest that the value of binding energies by themselves from Vina may not be very reliable quantitatively. All these failures lead to a refinement that resulted in a highly sensitive statistically-guided network construction and analysis, which leads to key findings in the early dynamics associated with resistance across all PI drugs. The latter experiment unravelled a conserved lateral expansion motion occurring at the flap elbows, and an associated contraction that drives the base of the dimerization domain towards the catalytic site’s floor in the case of drug resistance. Interestingly, we found that despite the conserved movement, bond angles were degenerate. Alongside, 16 Artificial Neural Network models were optimised for HIV proteases and reverse transcriptase inhibitors, with performances on par with Stanford HIVdb. Finally, we prioritised 9 compounds with potential protease inhibitory activity using virtual screening and molecular dynamics (MD) to additionally suggest a promising modification to one of the compounds. This yielded another molecule inhibiting equally well both opened and closed receptor target conformations, whereby each of the compounds had been selected against an array of multi-drug-resistant receptor variants. While a main hurdle was a lack of non-B subtype data, our findings, especially from the statistically-guided network analysis, may extrapolate to a certain extent to them as the level of conservation was very high within subtype B, despite all the present variations. This network construction method lays down a sensitive approach for analysing a pair of alternate phenotypes for which complex patterns prevail, given a sufficient number of experimental units. During the course of research a weighted contact mapping tool was developed to compare renin-angiotensinogen variants and packaged as part of the MD-TASK tool suite. Finally the functionality, compatibility and performance of the MODE-TASK tool were evaluated and confirmed for both Python2.7.x and Python3.x, for the analysis of normals modes from single protein structures and essential modes from MD trajectories. These techniques and tools collectively add onto the conventional means of MD analysis.
- Full Text: