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An investigation of how selected Namibian grade 9 geography textbooks are reorienting school geography to education for sustainable development
- Authors: Uusiku, Naftal Amutenya
- Date: 2020
- Subjects: Geography -- Study and teaching -- Namibia , Geography -- Study and teaching -- Namibia -- Textbooks , Sustainable development -- Study and teaching -- Namibia , Environmental education -- Namibia
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/145524 , vital:38446
- Description: The World Social Science Report (UNESCO, 2013) describes environmental issues and challenges, many of which are driven by human activities. These include: changing consumption patterns, climate change, deforestation, desertification, water, population growth, poverty, food security, waste products and cultural diversity and globalization. Education for sustainable development [ESD], a vital tool for achieving the Sustainable Development Goals, requires a rethinking and reorienting of education to address sustainability (UNESCO, 2016). The International Geographical Union Commission on Geographical Education (2007, 2016) acknowledges the importance of reorienting of school geography to ESD. In Namibia, ESD has been embedded in the national curriculum. However, teachers play a critical role in reorienting school geography to ESD at the level of the classroom. They need appropriate resources to do so, the most widely used of which is the textbook. This study addresses the need for empirical research on how Namibian textbooks are reorienting geography to ESD. Using a qualitative interpretive research design, the study had the goals of understanding how selected Grade 9 textbooks are reorienting geography to ESD in what is taught (content) and how it is taught and learned (pedagogy), and how textbook authors perceive the reorienting of geography to ESD. Data were gathered through an online questionnaire of authors’ perceptions of their educational goals, important ESD content, the teaching strategies they use and the challenges they face. Document analysis was done on two causes of environmental deterioration — deforestation and population explosion in the theme Ecology — in three approved Grade 9 textbooks. The study provides evidence of how the selected textbooks are helping to reorientate school geography to the ESD content prescribed by the Namibian geography syllabus in a way that emphasizes knowing about, as opposed to critically engaging with the environmental challenges and issues at hand. With the exception of one textbook, the textbooks generally do not help to reorientate pedagogy to the transformative, change-oriented, futures-focused pedagogy advocated by the literature. Furthermore, the authors’ responses do not contain evidence that suggests their thinking is informed by contemporary perspectives on ESD or geography education. The findings provide insights for understanding how textbooks are helping to reorient Namibian school geography that may be of value to textbook authors and curriculum developers. Furthermore, it illuminates the need for theoretically informed curriculum and textbook writing workshops.
- Full Text:
- Authors: Uusiku, Naftal Amutenya
- Date: 2020
- Subjects: Geography -- Study and teaching -- Namibia , Geography -- Study and teaching -- Namibia -- Textbooks , Sustainable development -- Study and teaching -- Namibia , Environmental education -- Namibia
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/145524 , vital:38446
- Description: The World Social Science Report (UNESCO, 2013) describes environmental issues and challenges, many of which are driven by human activities. These include: changing consumption patterns, climate change, deforestation, desertification, water, population growth, poverty, food security, waste products and cultural diversity and globalization. Education for sustainable development [ESD], a vital tool for achieving the Sustainable Development Goals, requires a rethinking and reorienting of education to address sustainability (UNESCO, 2016). The International Geographical Union Commission on Geographical Education (2007, 2016) acknowledges the importance of reorienting of school geography to ESD. In Namibia, ESD has been embedded in the national curriculum. However, teachers play a critical role in reorienting school geography to ESD at the level of the classroom. They need appropriate resources to do so, the most widely used of which is the textbook. This study addresses the need for empirical research on how Namibian textbooks are reorienting geography to ESD. Using a qualitative interpretive research design, the study had the goals of understanding how selected Grade 9 textbooks are reorienting geography to ESD in what is taught (content) and how it is taught and learned (pedagogy), and how textbook authors perceive the reorienting of geography to ESD. Data were gathered through an online questionnaire of authors’ perceptions of their educational goals, important ESD content, the teaching strategies they use and the challenges they face. Document analysis was done on two causes of environmental deterioration — deforestation and population explosion in the theme Ecology — in three approved Grade 9 textbooks. The study provides evidence of how the selected textbooks are helping to reorientate school geography to the ESD content prescribed by the Namibian geography syllabus in a way that emphasizes knowing about, as opposed to critically engaging with the environmental challenges and issues at hand. With the exception of one textbook, the textbooks generally do not help to reorientate pedagogy to the transformative, change-oriented, futures-focused pedagogy advocated by the literature. Furthermore, the authors’ responses do not contain evidence that suggests their thinking is informed by contemporary perspectives on ESD or geography education. The findings provide insights for understanding how textbooks are helping to reorient Namibian school geography that may be of value to textbook authors and curriculum developers. Furthermore, it illuminates the need for theoretically informed curriculum and textbook writing workshops.
- Full Text:
An investigation of learning and emerging knowledge in the Mpophomeni Sanitation Education Project, Howick, KwaZulu-Natal
- Authors: Boothway, Reinetta Louina
- Date: 2020
- Subjects: Environmental education -- South Africa , Mpophomeni Sanitation Education Project (South Africa) , Water quality management -- Study and teaching -- South Africa , Knowledge and learning
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/115377 , vital:34121
- Description: This study took place within the broader context of water resources management in South Africa. With the democratisation of water stewardship through an enabling international and South African water policy landscape, an opportunity opened up for citizens to participate in the effective management of their own water resources. In this context, a community-engaged citizen science project known as the Mpophomeni Sanitation Education Project emerged to demonstrate how a diverse range of knowledge agents can work and learn together to better manage their water resources and address problems of sewage pollution threatening their provincial water source. The following study aimed to shed light on the learning and emerging knowledge in the MSEP. The study was conducted in three phases. Wenger’s Communities of Practice (CoP) theory provided a lens to look at Phase One, which aimed to answer the following sub-question: Is the MSEP a CoP? Wenger’s CoP theory also assisted with the investigation during Phase Two, which looked at the following question: What is the nature of learning in the MSEP? Social realist theories of knowledge and education, and Tàbara and Chabay with their Ideal Type (IT) worldviews, provided suitable lenses for Phase Three’s investigation of the following question: What is the nature of emerging knowledge in the MSEP? The main finding for Phase One is that the MSEP does function as a CoP. With its strong focus on relationships, it’s clearly defined joint enterprise of solving the problem of sewage pollution, individual and joint commitment to engage with the problem and the sharing of a repertoire of tools, ideas and practices it is cultivating a culture conducive to purposeful learning. Regarding the exploration of the nature of learning in Phase Two, findings confirming the engagement of identity with learning and the importance of context for meaning-making emerged. Finally, study findings about the nature of knowledge in the MSEP found that the knowledge practices in the MSEP that are both social and epistemic in nature are produced by a diverse range of knowledge agents in an open knowledge space.
- Full Text:
- Authors: Boothway, Reinetta Louina
- Date: 2020
- Subjects: Environmental education -- South Africa , Mpophomeni Sanitation Education Project (South Africa) , Water quality management -- Study and teaching -- South Africa , Knowledge and learning
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/115377 , vital:34121
- Description: This study took place within the broader context of water resources management in South Africa. With the democratisation of water stewardship through an enabling international and South African water policy landscape, an opportunity opened up for citizens to participate in the effective management of their own water resources. In this context, a community-engaged citizen science project known as the Mpophomeni Sanitation Education Project emerged to demonstrate how a diverse range of knowledge agents can work and learn together to better manage their water resources and address problems of sewage pollution threatening their provincial water source. The following study aimed to shed light on the learning and emerging knowledge in the MSEP. The study was conducted in three phases. Wenger’s Communities of Practice (CoP) theory provided a lens to look at Phase One, which aimed to answer the following sub-question: Is the MSEP a CoP? Wenger’s CoP theory also assisted with the investigation during Phase Two, which looked at the following question: What is the nature of learning in the MSEP? Social realist theories of knowledge and education, and Tàbara and Chabay with their Ideal Type (IT) worldviews, provided suitable lenses for Phase Three’s investigation of the following question: What is the nature of emerging knowledge in the MSEP? The main finding for Phase One is that the MSEP does function as a CoP. With its strong focus on relationships, it’s clearly defined joint enterprise of solving the problem of sewage pollution, individual and joint commitment to engage with the problem and the sharing of a repertoire of tools, ideas and practices it is cultivating a culture conducive to purposeful learning. Regarding the exploration of the nature of learning in Phase Two, findings confirming the engagement of identity with learning and the importance of context for meaning-making emerged. Finally, study findings about the nature of knowledge in the MSEP found that the knowledge practices in the MSEP that are both social and epistemic in nature are produced by a diverse range of knowledge agents in an open knowledge space.
- 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 , Blacks -- South Africa -- Psychology , Blacks -- 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 , Blacks -- South Africa -- Psychology , Blacks -- 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:
An investigation of the influence of knowledge-production and learning processes on complex practices in a community-driven citizen science initiative: A nature conservation case study
- Authors: Alexander, Jaclyn
- Date: 2020
- Subjects: Science -- Citizen participation , Western Leopard Toad Conservation Committee , Environmental education , Frogs -- South Africa
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/138173 , vital:37603
- Description: Community-driven citizen science initiatives have become an increasingly popular tool for combating social-ecological challenges that arise within communities. Scientific protocols have been designed to strengthen and support the accuracy and reliability of data collection and information sharing; however, little is understood of the dynamic social processes that reinforce and co-ordinate such community-driven action. This qualitative case study was undertaken to identify and understand complex organisational, political and socio-cultural processes (in particular knowledge-production and learning processes) that have guided, sustained and informed complex practices in a community driven citizen science initiative. The study aimed to inform the development of a social protocol that might be transferable to other citizen science contexts. The study drew on the theory of ‘Landscapes of Practice’, which highlights how multiple communities of practice overlap, interrelate, share knowledge and cross boundaries to create potential learning across a landscape. Additionally, ideas and typologies in recent citizen science literature offered perspective on the community-driven citizen science practices. This qualitative case study focused on the bounded case of the Western Leopard Toad Conservation Committee. Specific data generation tools (interviews, observations, document analysis and diagrams) were used from multiple perspectives over time to provide rigor and depth to the data. The study demonstrated how multiple ‘nexes of practice’ co-engaged in collective knowledge creation practices, which helped to enhance ‘knowledgeability’ across the landscape. This coordinated effort, however, was sporadic and inconsistent. Recommendations are made for the development of social protocols that could assist collaborators in citizen science initiatives to scrutinise and rethink their practices and to examine both their successes and shortfalls towards their shared interest.
- Full Text:
- Authors: Alexander, Jaclyn
- Date: 2020
- Subjects: Science -- Citizen participation , Western Leopard Toad Conservation Committee , Environmental education , Frogs -- South Africa
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/138173 , vital:37603
- Description: Community-driven citizen science initiatives have become an increasingly popular tool for combating social-ecological challenges that arise within communities. Scientific protocols have been designed to strengthen and support the accuracy and reliability of data collection and information sharing; however, little is understood of the dynamic social processes that reinforce and co-ordinate such community-driven action. This qualitative case study was undertaken to identify and understand complex organisational, political and socio-cultural processes (in particular knowledge-production and learning processes) that have guided, sustained and informed complex practices in a community driven citizen science initiative. The study aimed to inform the development of a social protocol that might be transferable to other citizen science contexts. The study drew on the theory of ‘Landscapes of Practice’, which highlights how multiple communities of practice overlap, interrelate, share knowledge and cross boundaries to create potential learning across a landscape. Additionally, ideas and typologies in recent citizen science literature offered perspective on the community-driven citizen science practices. This qualitative case study focused on the bounded case of the Western Leopard Toad Conservation Committee. Specific data generation tools (interviews, observations, document analysis and diagrams) were used from multiple perspectives over time to provide rigor and depth to the data. The study demonstrated how multiple ‘nexes of practice’ co-engaged in collective knowledge creation practices, which helped to enhance ‘knowledgeability’ across the landscape. This coordinated effort, however, was sporadic and inconsistent. Recommendations are made for the development of social protocols that could assist collaborators in citizen science initiatives to scrutinise and rethink their practices and to examine both their successes and shortfalls towards their shared interest.
- Full Text:
An investigation of the internal challenges that hinder sustainability of the Furntech Nyanga incubates
- Authors: Sakuba, Siyasanga
- Date: 2020
- Subjects: Business incubators -- South Africa -- Cape Town , Business incubators -- Training of -- South Africa -- Cape Town , Entrepreneurship -- South Africa – Cape Town , Unemployment -- South Africa , Rate of return -- South Africa , Economic development -- South Africa , Training needs -- South Africa -- Cape Town , Furntech (Nyanga)
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/142830 , vital:38121
- Description: The South African unemployment rate is currently at 27.6 per cent (Statistics South Africa, 2019). In an effort to combat unemployment, the South African government has implemented various mechanisms to provide opportunities to the people and combat unemployment. One of these mechanisms is to invest in the establishment of entrepreneurship incubators while the Furntech incubator is one of the incubators established for this purpose. It is imperative that the government spending on these mechanisms is justified by a return on investment which, in this case, should be to reduce unemployment and increase the overall entrepreneurial activity. In view of Furntech, with specific reference to the Nyanga incubation centre, there is a high failure rate with very little output of sustainable enterprises from the two-year incubation period. This study seeks to investigate the internal challenges that hinder the sustainability of these entrepreneurs to either drop out before the end of the two-year incubation period or to furnish the two years without becoming sustainable entrepreneurs. This study seeks to investigate this matter by using a semi -structured interview schedule that was geared towards investigating the research problem from the view of the incubates. The findings of the study showed that Furntech can be commended in respect of the transfer of technical skills. Furntech, however, failed to support the entrepreneurs with the other business support services that are part of their services, namely the business advisory, financial support and business skills. These findings provide a guideline of where Furntech needs to improve its service offering to gain a higher output of sustainable entrepreneurs. It is important to note that even though Furntech has representation in three provinces with two incubators in the Western Cape (Cape Town and Nyanga), however, this study was limited to the Furntech Nyanga incubates.
- Full Text:
- Authors: Sakuba, Siyasanga
- Date: 2020
- Subjects: Business incubators -- South Africa -- Cape Town , Business incubators -- Training of -- South Africa -- Cape Town , Entrepreneurship -- South Africa – Cape Town , Unemployment -- South Africa , Rate of return -- South Africa , Economic development -- South Africa , Training needs -- South Africa -- Cape Town , Furntech (Nyanga)
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/142830 , vital:38121
- Description: The South African unemployment rate is currently at 27.6 per cent (Statistics South Africa, 2019). In an effort to combat unemployment, the South African government has implemented various mechanisms to provide opportunities to the people and combat unemployment. One of these mechanisms is to invest in the establishment of entrepreneurship incubators while the Furntech incubator is one of the incubators established for this purpose. It is imperative that the government spending on these mechanisms is justified by a return on investment which, in this case, should be to reduce unemployment and increase the overall entrepreneurial activity. In view of Furntech, with specific reference to the Nyanga incubation centre, there is a high failure rate with very little output of sustainable enterprises from the two-year incubation period. This study seeks to investigate the internal challenges that hinder the sustainability of these entrepreneurs to either drop out before the end of the two-year incubation period or to furnish the two years without becoming sustainable entrepreneurs. This study seeks to investigate this matter by using a semi -structured interview schedule that was geared towards investigating the research problem from the view of the incubates. The findings of the study showed that Furntech can be commended in respect of the transfer of technical skills. Furntech, however, failed to support the entrepreneurs with the other business support services that are part of their services, namely the business advisory, financial support and business skills. These findings provide a guideline of where Furntech needs to improve its service offering to gain a higher output of sustainable entrepreneurs. It is important to note that even though Furntech has representation in three provinces with two incubators in the Western Cape (Cape Town and Nyanga), however, this study was limited to the Furntech Nyanga incubates.
- Full Text:
An investigation of the morphological and electrochemical properties of anode titanate materials used in li-ion batteries
- Authors: Gelant, Charmaine
- Date: 2020
- Subjects: Electrodes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/48346 , vital:40851
- Description: The chemistry involved in the synthesis of lithium titanium oxide (Li4Ti5O12) for lithium ion battery applications is critical for understanding and optimizing the most cost-efficient manufacturing route. This study investigates the sol-gel synthesis technique of Li4Ti5O12 using triethanolamine (TEOA) as complexing agent by means of in-situ Powder X-ray Diffraction (PXRD). The influence of doping with various metals such as Al3+, Mg2+ , Co3+ and Ni2+ that were made as precursors was considered for comparison purposes due to literature showing improved electrochemical performance using the molecular formula of Li4Ti4.95M0.05O12. The in-situ PXRD technique was used to identify the phase changes that occurred in the thermal synthesis process from the sol-gel precursors to the final crystalline oxides. The materials’ decomposition mechanisms were characterized by thermal gravimetric analysis (TGA) as the precursors were gradually heated to obtain the final oxides. BET surface area analysis and scanning electron microscopy (SEM) were used in order to obtain a morphological understanding of the materials during the synthetic route at specific temperature regions. The in-situ studies have shown that the precursor materials are amorphous at room temperature to about 550 °C, after which the spinel and anatase formed, with relatively small crystallites and a large surface area. The study also showed that a crystalline intermediate phase formed at around 150-200 °C, which then disappeared above 250 °C and was speculated to be a titanium acid (H2Ti2O5.H2O). Upon further heating above 250 °C, the anatase phase converted to the high temperature stable TiO2 phase, rutile, also with an increased formation of the expected LTO spinel phase around 850 °C. Keeping the material at 850 °C, isothermally, did show further conversion of the rutile into the desired spinel phase Li4Ti5O12 (LTO) with an increase in the crystallite size and a decrease in surface area. SEM analysis of the material at 850 °C did show some extensive sintering of the particles with some samples indicating the presence of an additional β-Li2TiO3 phase that formed at the high temperatures. Upon cooling, the βLi2TiO3 phase showed a distinctive powder diffraction pattern besides the typical spinel II LTO phase. The study showed that in comparison to the oxide formed at 850 °C, a mixed phase material of the spinel LTO, anatase and rutile could be achieved at temperatures close to 650 °C with very small crystallites and a relatively large surface area that showed desirable electrochemical properties. Suitable Li-ion coin cells were built with the undoped spinel and doped materials that were isothermally made at 650 °C and 850 °C, whereby their electrochemical properties were tested in the form of cell capacity, electrochemical impedance spectroscopy (EIS) and differential capacity (dQ/dV) studies. The cells made with the materials at 850 °C provided reasonable capacity where the dQ/dV plots did show a single step redox reaction at around 1.5V vs Li/Li+ . These were compared to cells made with commercially available LTO and highlighted the importance of high surface area and small particle size of the active material in order to achieve acceptable electrochemical performances. The cells with the materials made at 650 °C showed to have good capacity upon the first discharge with a number of irreversible phase transitions that were subsequently not observed upon recharging. The dQ/dV graphs showed that the phase transitions were unique to the mixed phase composition of the material made at low temperatures and the cells made with the doped spinel materials were on average better performing than the undoped LTO material. Subsequent grinding steps of the active material made at 850 °C improved the capacity performance of the cells but were still lower when compared to the commercially available material. Hence, significantly longer grinding and processing time would be required to achieve battery active materials that are acceptable for commercial use. This study highlights the importance of understanding the phase transitions that occur during the synthesis route of making battery active material, where doping with different elements and using lower temperatures during synthesis could lead to electroactive materials that do not require additional excessive processing steps such as grinding.
- Full Text:
- Authors: Gelant, Charmaine
- Date: 2020
- Subjects: Electrodes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/48346 , vital:40851
- Description: The chemistry involved in the synthesis of lithium titanium oxide (Li4Ti5O12) for lithium ion battery applications is critical for understanding and optimizing the most cost-efficient manufacturing route. This study investigates the sol-gel synthesis technique of Li4Ti5O12 using triethanolamine (TEOA) as complexing agent by means of in-situ Powder X-ray Diffraction (PXRD). The influence of doping with various metals such as Al3+, Mg2+ , Co3+ and Ni2+ that were made as precursors was considered for comparison purposes due to literature showing improved electrochemical performance using the molecular formula of Li4Ti4.95M0.05O12. The in-situ PXRD technique was used to identify the phase changes that occurred in the thermal synthesis process from the sol-gel precursors to the final crystalline oxides. The materials’ decomposition mechanisms were characterized by thermal gravimetric analysis (TGA) as the precursors were gradually heated to obtain the final oxides. BET surface area analysis and scanning electron microscopy (SEM) were used in order to obtain a morphological understanding of the materials during the synthetic route at specific temperature regions. The in-situ studies have shown that the precursor materials are amorphous at room temperature to about 550 °C, after which the spinel and anatase formed, with relatively small crystallites and a large surface area. The study also showed that a crystalline intermediate phase formed at around 150-200 °C, which then disappeared above 250 °C and was speculated to be a titanium acid (H2Ti2O5.H2O). Upon further heating above 250 °C, the anatase phase converted to the high temperature stable TiO2 phase, rutile, also with an increased formation of the expected LTO spinel phase around 850 °C. Keeping the material at 850 °C, isothermally, did show further conversion of the rutile into the desired spinel phase Li4Ti5O12 (LTO) with an increase in the crystallite size and a decrease in surface area. SEM analysis of the material at 850 °C did show some extensive sintering of the particles with some samples indicating the presence of an additional β-Li2TiO3 phase that formed at the high temperatures. Upon cooling, the βLi2TiO3 phase showed a distinctive powder diffraction pattern besides the typical spinel II LTO phase. The study showed that in comparison to the oxide formed at 850 °C, a mixed phase material of the spinel LTO, anatase and rutile could be achieved at temperatures close to 650 °C with very small crystallites and a relatively large surface area that showed desirable electrochemical properties. Suitable Li-ion coin cells were built with the undoped spinel and doped materials that were isothermally made at 650 °C and 850 °C, whereby their electrochemical properties were tested in the form of cell capacity, electrochemical impedance spectroscopy (EIS) and differential capacity (dQ/dV) studies. The cells made with the materials at 850 °C provided reasonable capacity where the dQ/dV plots did show a single step redox reaction at around 1.5V vs Li/Li+ . These were compared to cells made with commercially available LTO and highlighted the importance of high surface area and small particle size of the active material in order to achieve acceptable electrochemical performances. The cells with the materials made at 650 °C showed to have good capacity upon the first discharge with a number of irreversible phase transitions that were subsequently not observed upon recharging. The dQ/dV graphs showed that the phase transitions were unique to the mixed phase composition of the material made at low temperatures and the cells made with the doped spinel materials were on average better performing than the undoped LTO material. Subsequent grinding steps of the active material made at 850 °C improved the capacity performance of the cells but were still lower when compared to the commercially available material. Hence, significantly longer grinding and processing time would be required to achieve battery active materials that are acceptable for commercial use. This study highlights the importance of understanding the phase transitions that occur during the synthesis route of making battery active material, where doping with different elements and using lower temperatures during synthesis could lead to electroactive materials that do not require additional excessive processing steps such as grinding.
- Full Text:
An investigation of the security of passwords derived from African languages
- Authors: Sishi, Sibusiso
- Date: 2020
- Subjects: Computers -- Access control -- Passwords , Computer users -- Attitudes , Internet -- Access control , Internet -- Security measures , Internet -- Management , Data protection
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163273 , vital:41024
- Description: Password authentication has become ubiquitous in the cyber age. To-date, there have been several studies on country based passwords by authors who studied, amongst others, English, Finnish, Italian and Chinese based passwords. However, there has been a lack of focused study on the type of passwords that are being created in Africa and whether there are benefits in creating passwords in an African language. For this research, password databases containing LAN Manager (LM) and NT LAN Manager (NTLM) hashes extracted from South African organisations in a variety of sectors in the economy, were obtained to gain an understanding of user behaviour in creating passwords. Analysis of the passwords obtained from these hashes (using several cracking methods) showed that many organisational passwords are based on the English language. This is understandable considering that the business language in South Africa is English even though South Africa has 11 official languages. African language based passwords were derived from known English weak passwords and some of the passwords were appended with numbers and special characters. The African based passwords created using eight Southern African languages were then uploaded to the Internet to test the security around using passwords based on African languages. Since most of the passwords were able to be cracked by third party researchers, we conclude that any password that is derived from known weak English words marked no improvement in the security of a password written in an African language, especially the more widely spoken languages, namely, isiZulu, isiXhosa and Setswana.
- Full Text:
- Authors: Sishi, Sibusiso
- Date: 2020
- Subjects: Computers -- Access control -- Passwords , Computer users -- Attitudes , Internet -- Access control , Internet -- Security measures , Internet -- Management , Data protection
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163273 , vital:41024
- Description: Password authentication has become ubiquitous in the cyber age. To-date, there have been several studies on country based passwords by authors who studied, amongst others, English, Finnish, Italian and Chinese based passwords. However, there has been a lack of focused study on the type of passwords that are being created in Africa and whether there are benefits in creating passwords in an African language. For this research, password databases containing LAN Manager (LM) and NT LAN Manager (NTLM) hashes extracted from South African organisations in a variety of sectors in the economy, were obtained to gain an understanding of user behaviour in creating passwords. Analysis of the passwords obtained from these hashes (using several cracking methods) showed that many organisational passwords are based on the English language. This is understandable considering that the business language in South Africa is English even though South Africa has 11 official languages. African language based passwords were derived from known English weak passwords and some of the passwords were appended with numbers and special characters. The African based passwords created using eight Southern African languages were then uploaded to the Internet to test the security around using passwords based on African languages. Since most of the passwords were able to be cracked by third party researchers, we conclude that any password that is derived from known weak English words marked no improvement in the security of a password written in an African language, especially the more widely spoken languages, namely, isiZulu, isiXhosa and Setswana.
- Full Text:
An update on the indigenous vascular flora of sub-Antarctic Marion Island: taxonomic changes, sequences for DNA barcode loci, and genome size data
- Chau, John H, Mtsi, Nasipi I S, Münbergová, Zuzana, Greve, Michelle, le Roux, Peter C, Mairal, Mario, Le Roux, Johannes J, Dorrington, Rosemanry A, van Vuuren, Bettine
- Authors: Chau, John H , Mtsi, Nasipi I S , Münbergová, Zuzana , Greve, Michelle , le Roux, Peter C , Mairal, Mario , Le Roux, Johannes J , Dorrington, Rosemanry A , van Vuuren, Bettine
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/160344 , vital:40437 , https://0-doi.org.wam.seals.ac.za/10.1007/s00300-020-02747-7
- Description: The flora of sub-Antarctic Marion Island forms part of the unique South Indian Ocean Biogeographic Province, and is under threat from climate change and invasive species. Current information on the flora is necessary to rapidly identify and manage future changes. We conducted a literature search on the taxonomy of indigenous vascular plant species on Marion Island and found nomenclatural changes following taxonomic revisions for Austroblechnum penna-marina (Poir.) Gasper and V.A.O.Dittrich, Carex dikei (Nelmes) K.L.Wilson, Leptinella plumosa Hook.f., Notogrammitis crassior (Kirk) Parris, Phlegmariurus saururus (Lam.) B.Øllg., and Polypogon magellanicus (Lam.) Finot. Additionally, Ranunculus moseleyi Hook.f. was removed from our species checklist due to its long absence in floristic surveys, leaving 21 species in the indigenous vascular plant flora present on Marion Island. We also amplified and sequenced the universal plant barcoding loci rbcL and matK for 19 and 13 species, respectively, and found that ample interspecific genetic distance and minimal intraspecific genetic distance allowed for easy discrimination between species.
- Full Text:
- Authors: Chau, John H , Mtsi, Nasipi I S , Münbergová, Zuzana , Greve, Michelle , le Roux, Peter C , Mairal, Mario , Le Roux, Johannes J , Dorrington, Rosemanry A , van Vuuren, Bettine
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/160344 , vital:40437 , https://0-doi.org.wam.seals.ac.za/10.1007/s00300-020-02747-7
- Description: The flora of sub-Antarctic Marion Island forms part of the unique South Indian Ocean Biogeographic Province, and is under threat from climate change and invasive species. Current information on the flora is necessary to rapidly identify and manage future changes. We conducted a literature search on the taxonomy of indigenous vascular plant species on Marion Island and found nomenclatural changes following taxonomic revisions for Austroblechnum penna-marina (Poir.) Gasper and V.A.O.Dittrich, Carex dikei (Nelmes) K.L.Wilson, Leptinella plumosa Hook.f., Notogrammitis crassior (Kirk) Parris, Phlegmariurus saururus (Lam.) B.Øllg., and Polypogon magellanicus (Lam.) Finot. Additionally, Ranunculus moseleyi Hook.f. was removed from our species checklist due to its long absence in floristic surveys, leaving 21 species in the indigenous vascular plant flora present on Marion Island. We also amplified and sequenced the universal plant barcoding loci rbcL and matK for 19 and 13 species, respectively, and found that ample interspecific genetic distance and minimal intraspecific genetic distance allowed for easy discrimination between species.
- 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:
Analysis of bacterial Mur amide ligase enzymes for the identification of inhibitory compounds by in silico methods
- Chamboko, Chiratidzo Respina
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Pathogenic microorganisms -- Analysis , Drug resistance in microorganisms , Microorganisms -- Effect of drugs on , Antibiotics -- Effectiveness , Pathogenic bacteria , Drug tolerance , Enzymes -- Analysis , Peptide antibiotics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161911 , vital:40690
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Pathogenic microorganisms -- Analysis , Drug resistance in microorganisms , Microorganisms -- Effect of drugs on , Antibiotics -- Effectiveness , Pathogenic bacteria , Drug tolerance , Enzymes -- Analysis , Peptide antibiotics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161911 , vital:40690
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
Analysis of bacterial Mur amide ligase enzymes for the identification of inhibitory compounds by in silico methods
- Chamboko, Chiratidzo Respina
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Mur amide ligases , Ligases , Ligand binding (Biochemistry) , Antibacterial agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163430 , vital:41036
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Mur amide ligases , Ligases , Ligand binding (Biochemistry) , Antibacterial agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163430 , vital:41036
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
Analysis of the regulation of HSP90α expression upon differentiation of C2C12 cells
- Authors: Holm, Nathan Christopher
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163318 , vital:41028
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Authors: Holm, Nathan Christopher
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163318 , vital:41028
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
Analysis of the relationship between changes in macroeconomic variables and various sector price indices of JSE
- Mapanda, Tungamirai Chisvuvo
- Authors: Mapanda, Tungamirai Chisvuvo
- Date: 2020
- Subjects: Johannesburg Stock Exchange , Stock price indexes -- South Africa , Interest rates -- South Africa
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/147445 , vital:38637
- Description: Purpose- The purpose of this paper is to analyse the relationship between changes in domestic macroeconomic variables and various indices of the JSE during the full time period, June 1995 to December 2018 and the sub-periods, June 1995 to June 2007 and July 2007 to December 2018. Design/ methodology/ approach- The paper employs the Autoregressive Distributed Lag (ARDL) model approach to cointegration using monthly data from June 1995 to December 2018. Findings- In terms of the long run, the results show that the coincident indicator measure of domestic economic activity is positively and significantly related to the various JSE indices for all study periods. In terms of inflation, the results show no relationship between inflation rate and the various indices for both whole period and June 1995 to June 2007 sub period. However for the July 2007 to December 2018 sub period, JSE All Share Index and JSE Top 40 Index are negatively related. For the real effective exchange rate, only the Consumer Services Index is positively related to the exchange rate in terms of June 1995 to June 2007 sub period. However, JSE All Share Index and JSE Top 40 Index are negatively related to the exchange rate in all study periods. In terms of the short term interest rate, for the whole period, JSE All Share Index, JSE Top 40 Index, Health Care Index and Telecommunications Index are negatively related to interest rate. In terms of the June 1995 to June 2007 sub period, JSE All Share Index and Industrials Index are negatively related to the short term interest rate. For the July 2007 to December 2018 sub period, Telecommunications Index and Technology Index are negatively related. In terms of the short run, the coincident indicator is positively and significantly related to the various JSE indices for all study periods. Inflation is not significantly related to any index in the whole period. In terms of the June 1995 to June 2007 sub period, Industrials Index and Financials Index are positively related to inflation and in the July 2007 to December 2018 sub period, Consumer Goods Index, Health Index and Consumer Services Index are negatively related to the inflation rate. The real effective exchange rate is positively and significantly related to the various JSE indices in the different study periods. In terms of the short term interest rate, for the whole period and the June 1995 to June 2007 sub period only the Technology Index is not significantly and negatively related to the short term interest rate, but for the July 2007 to December 2018 sub period, Top 40 Index, Telecommunications Index and Technology Index are positively related to the interest rate. Only the Financial Index is negatively related to short term interest rates during this sub period. Research Limitations- Not a lot literature was found on the relationship between macroeconomic variables and the various sector indices of the JSE. Most previous work, in the South African context focused just on the JSE All Share Index. Practical Implications- The findings can help investors diversify their portfolios into indices that benefit from expected changes in macroeconomic variables, such as recessions, rising interest rates, rising inflation or a weakening exchange rate. Alternatively, they can hedge themselves against the negative implications of such macroeconomic changes on portfolio performance. In addition, the findings are important for the monetary authorities to better understand the implications of their policy changes on financial markets.
- Full Text:
- Authors: Mapanda, Tungamirai Chisvuvo
- Date: 2020
- Subjects: Johannesburg Stock Exchange , Stock price indexes -- South Africa , Interest rates -- South Africa
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/147445 , vital:38637
- Description: Purpose- The purpose of this paper is to analyse the relationship between changes in domestic macroeconomic variables and various indices of the JSE during the full time period, June 1995 to December 2018 and the sub-periods, June 1995 to June 2007 and July 2007 to December 2018. Design/ methodology/ approach- The paper employs the Autoregressive Distributed Lag (ARDL) model approach to cointegration using monthly data from June 1995 to December 2018. Findings- In terms of the long run, the results show that the coincident indicator measure of domestic economic activity is positively and significantly related to the various JSE indices for all study periods. In terms of inflation, the results show no relationship between inflation rate and the various indices for both whole period and June 1995 to June 2007 sub period. However for the July 2007 to December 2018 sub period, JSE All Share Index and JSE Top 40 Index are negatively related. For the real effective exchange rate, only the Consumer Services Index is positively related to the exchange rate in terms of June 1995 to June 2007 sub period. However, JSE All Share Index and JSE Top 40 Index are negatively related to the exchange rate in all study periods. In terms of the short term interest rate, for the whole period, JSE All Share Index, JSE Top 40 Index, Health Care Index and Telecommunications Index are negatively related to interest rate. In terms of the June 1995 to June 2007 sub period, JSE All Share Index and Industrials Index are negatively related to the short term interest rate. For the July 2007 to December 2018 sub period, Telecommunications Index and Technology Index are negatively related. In terms of the short run, the coincident indicator is positively and significantly related to the various JSE indices for all study periods. Inflation is not significantly related to any index in the whole period. In terms of the June 1995 to June 2007 sub period, Industrials Index and Financials Index are positively related to inflation and in the July 2007 to December 2018 sub period, Consumer Goods Index, Health Index and Consumer Services Index are negatively related to the inflation rate. The real effective exchange rate is positively and significantly related to the various JSE indices in the different study periods. In terms of the short term interest rate, for the whole period and the June 1995 to June 2007 sub period only the Technology Index is not significantly and negatively related to the short term interest rate, but for the July 2007 to December 2018 sub period, Top 40 Index, Telecommunications Index and Technology Index are positively related to the interest rate. Only the Financial Index is negatively related to short term interest rates during this sub period. Research Limitations- Not a lot literature was found on the relationship between macroeconomic variables and the various sector indices of the JSE. Most previous work, in the South African context focused just on the JSE All Share Index. Practical Implications- The findings can help investors diversify their portfolios into indices that benefit from expected changes in macroeconomic variables, such as recessions, rising interest rates, rising inflation or a weakening exchange rate. Alternatively, they can hedge themselves against the negative implications of such macroeconomic changes on portfolio performance. In addition, the findings are important for the monetary authorities to better understand the implications of their policy changes on financial markets.
- Full Text:
Anger, Pain and the Body in the Public Sphere:
- Authors: Garman, Anthea
- Date: 2020
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/158459 , vital:40188 , ISBN 9781776145898
- Description: In this timely, original and sophisticated collection, writers from the Global South demonstrate that forms of publicness are multiple, mobile and varied. The notion that societies mediate issues through certain kinds of engagement is at the heart of imaginings of democracy and often centers on the ideal of the public sphere. But this imagined foundation of how we live collectively appears to have suffered a dramatic collapse across the world, with many democracies apparently unable to solve problems through talk – or even to agree on who speaks, in what ways and where. In the 10 essays in this timely, original and sophisticated collection, writers from southern Africa combine theoretical analysis with the examination of historical cases and contemporary developments to demonstrate that forms of publicness are multiple, mobile and varied. They propose new concepts and methodologies to analyse how public engagements work in society.
- Full Text:
- Authors: Garman, Anthea
- Date: 2020
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/158459 , vital:40188 , ISBN 9781776145898
- Description: In this timely, original and sophisticated collection, writers from the Global South demonstrate that forms of publicness are multiple, mobile and varied. The notion that societies mediate issues through certain kinds of engagement is at the heart of imaginings of democracy and often centers on the ideal of the public sphere. But this imagined foundation of how we live collectively appears to have suffered a dramatic collapse across the world, with many democracies apparently unable to solve problems through talk – or even to agree on who speaks, in what ways and where. In the 10 essays in this timely, original and sophisticated collection, writers from southern Africa combine theoretical analysis with the examination of historical cases and contemporary developments to demonstrate that forms of publicness are multiple, mobile and varied. They propose new concepts and methodologies to analyse how public engagements work in society.
- 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:
Application of quality by design principles for optimizing process variables of Extrusion and Spheronization of a Captopril Pellet Formulation:
- Authors: Veerubhotla, K , Walker, R B
- Date: 2020
- Language: English
- Type: text , article
- Identifier: vital:40098 , DOI: 10.36468/pharmaceutical-sciences.624
- Description: Product development using quality by design is a proactive and risk-based approach that shifts the manufacturing process from empirical to science-based. Risk assessment was performed to identify and analyse risk areas for the manufacture of captopril pellets. Twelve experimental runs were performed using a Plackett-Burman screening design. Pareto plots revealed the effect of formulation and process variables on the responses monitored and facilitated the identification of the most critical parameters for optimization of the formulation. A response surface methodology approach in conjunction with a central composite design was used to optimize the Eudragit® RL 30D (15-30 ml), microcrystalline cellulose (20-40 % w/w), sodium starch glycolate (2-5 % w/w) and spheronizer speed (650-1050 rpm).
- Full Text:
- Authors: Veerubhotla, K , Walker, R B
- Date: 2020
- Language: English
- Type: text , article
- Identifier: vital:40098 , DOI: 10.36468/pharmaceutical-sciences.624
- Description: Product development using quality by design is a proactive and risk-based approach that shifts the manufacturing process from empirical to science-based. Risk assessment was performed to identify and analyse risk areas for the manufacture of captopril pellets. Twelve experimental runs were performed using a Plackett-Burman screening design. Pareto plots revealed the effect of formulation and process variables on the responses monitored and facilitated the identification of the most critical parameters for optimization of the formulation. A response surface methodology approach in conjunction with a central composite design was used to optimize the Eudragit® RL 30D (15-30 ml), microcrystalline cellulose (20-40 % w/w), sodium starch glycolate (2-5 % w/w) and spheronizer speed (650-1050 rpm).
- Full Text:
Application of quality by design to the manufacture of a multiparticulate prednisone dosage form
- Authors: Manda, Arthur
- Date: 2020
- Subjects: Drugs -- Quality control , Drugs -- Design -- Quality control , Drugs -- Dosage forms , Drug development -- Quality control , Pharmaceutical industry -- Quality control , Prednisone , High throughput screening (Drug development)
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/117986 , vital:34583
- Description: For many years, quality by testing was the only approach to guarantee quality of drug products before the Food and Drug Administration launched the concept of current Good Manufacturing Practice. In order to gain more knowledge of the manufacturing process, a new system known as Quality by Design was introduced into the pharmaceutical industry. Quality by Design is based on thorough understanding of how materials, process parameters and interaction thereof impact final product quality. Quality by Design is a systematic approach to product development which ensures that quality is built into a product during product development and not just tested into it. The aim of Quality by Design is to achieve optimum product quality with consistent dosage form performance and minimal risk of failure in patients. The objective of these studies was to implement a Quality by Design approach to establish a design space for the development and manufacture of a safe, effective and stable multi-partite solid oral dosage form for prednisone as an alternative to currently marketed prednisone formulations. Multi-particulate dosage forms offer significant advantages over conventional technologies. In addition to lowering the incidence of gastrointestinal irritation they exhibit a reduced risk of dose dumping and a large surface area which favours dissolution. Furthermore, their free flowing nature facilitates reproducible capsule filling and consequently uniformity of dosing. Different multi-particulate dosage forms exist however a multiple-unit pellet system was investigated during these studies. Quality by Design principles were used to develop and establish a reversed-phase high performance liquid chromatographic method for quantifying prednisone from solid oral dosage forms. A Central Composite Design was used to generate multivariate experiments and to investigate the impact of input variables on the quality and performance of the analytical method. The optimized method was validated according to International Council for Harmonization guidelines and was found to be linear, precise, accurate and specific for the quantitation of prednisone. Pre-formulation studies were conducted and included the assessment of particle size, particle shape, powder flow properties and compatibility studies. Carr’s index, Hausner ratio and the Angle of Repose were used to evaluate powder flow properties and results generated from all studies suggest the need for adding a glidant and lubricant to improve pellet flow. The images generated from Scanning Electron Microscopy were used to analyze particle shape and size. Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy were used to evaluate API-excipient compatibility. All excipients investigated were found to be compatible with prednisone and suitable for formulation development studies. Extrusion-spheronization was used to manufacture prednisone pellets. Extrusion-spheronization is a multi-step process involving many factors. Quality risk management tools particularly an Ishikawa Fishbone (cause and effect) diagram and failure mode and effects analysis were used to narrow down potentially significant factors to a reasonable number that could be investigated experimentally. Risk priority numbers were used to quantify risk and factors above a set threshold value were considered to be of high risk. A total of eleven risk factors were identified as high. A Plackett-Burman study was conducted to narrow down the eleven high risk factors to identify the most impactful factors viz., microcrystalline cellulose content, sodium starch glycolate content, extrusion speed and spheronization time. Evaluation of four factors was carried over to optimization studies using a Box-Behnken Design and following identifaction of the optimum process settings and excipient content a design space for the manufacture of a multi-partite dosage form containing prednisone was established.
- Full Text:
- Authors: Manda, Arthur
- Date: 2020
- Subjects: Drugs -- Quality control , Drugs -- Design -- Quality control , Drugs -- Dosage forms , Drug development -- Quality control , Pharmaceutical industry -- Quality control , Prednisone , High throughput screening (Drug development)
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/117986 , vital:34583
- Description: For many years, quality by testing was the only approach to guarantee quality of drug products before the Food and Drug Administration launched the concept of current Good Manufacturing Practice. In order to gain more knowledge of the manufacturing process, a new system known as Quality by Design was introduced into the pharmaceutical industry. Quality by Design is based on thorough understanding of how materials, process parameters and interaction thereof impact final product quality. Quality by Design is a systematic approach to product development which ensures that quality is built into a product during product development and not just tested into it. The aim of Quality by Design is to achieve optimum product quality with consistent dosage form performance and minimal risk of failure in patients. The objective of these studies was to implement a Quality by Design approach to establish a design space for the development and manufacture of a safe, effective and stable multi-partite solid oral dosage form for prednisone as an alternative to currently marketed prednisone formulations. Multi-particulate dosage forms offer significant advantages over conventional technologies. In addition to lowering the incidence of gastrointestinal irritation they exhibit a reduced risk of dose dumping and a large surface area which favours dissolution. Furthermore, their free flowing nature facilitates reproducible capsule filling and consequently uniformity of dosing. Different multi-particulate dosage forms exist however a multiple-unit pellet system was investigated during these studies. Quality by Design principles were used to develop and establish a reversed-phase high performance liquid chromatographic method for quantifying prednisone from solid oral dosage forms. A Central Composite Design was used to generate multivariate experiments and to investigate the impact of input variables on the quality and performance of the analytical method. The optimized method was validated according to International Council for Harmonization guidelines and was found to be linear, precise, accurate and specific for the quantitation of prednisone. Pre-formulation studies were conducted and included the assessment of particle size, particle shape, powder flow properties and compatibility studies. Carr’s index, Hausner ratio and the Angle of Repose were used to evaluate powder flow properties and results generated from all studies suggest the need for adding a glidant and lubricant to improve pellet flow. The images generated from Scanning Electron Microscopy were used to analyze particle shape and size. Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy were used to evaluate API-excipient compatibility. All excipients investigated were found to be compatible with prednisone and suitable for formulation development studies. Extrusion-spheronization was used to manufacture prednisone pellets. Extrusion-spheronization is a multi-step process involving many factors. Quality risk management tools particularly an Ishikawa Fishbone (cause and effect) diagram and failure mode and effects analysis were used to narrow down potentially significant factors to a reasonable number that could be investigated experimentally. Risk priority numbers were used to quantify risk and factors above a set threshold value were considered to be of high risk. A total of eleven risk factors were identified as high. A Plackett-Burman study was conducted to narrow down the eleven high risk factors to identify the most impactful factors viz., microcrystalline cellulose content, sodium starch glycolate content, extrusion speed and spheronization time. Evaluation of four factors was carried over to optimization studies using a Box-Behnken Design and following identifaction of the optimum process settings and excipient content a design space for the manufacture of a multi-partite dosage form containing prednisone was established.
- Full Text:
Application of section 197 of the Labour Relations Act in an insourcing context
- Authors: Mahlati, Nomphelo Miliswa
- Date: 2020
- Subjects: Labor laws and legislation -- South Africa
- Language: English
- Type: Thesis , Masters , LLM
- Identifier: http://hdl.handle.net/10948/47392 , vital:39974
- Description: The last two decades have been characterised by a phenomenal rise in the outsourcing of services to external service providers. The driver of this trend has been largely economic, since outsourcing offers more competitive price points for the same service at a comparable service level. Beyond the cost saving objective, the rationale for outsourcing has been to drive core strategy. However, with the economic slowdown, declining consumption and production are forcing entrepreneurs to change their way of thinking about the management of companies. Notably, in recent years there has been a small but a growing reversal of this trend where companies that have previously outsourced functions are being brought back in-house. One of the major concerns surrounding these changes of business strategies is the extent to which the employee rights are safeguarded.
- Full Text:
- Authors: Mahlati, Nomphelo Miliswa
- Date: 2020
- Subjects: Labor laws and legislation -- South Africa
- Language: English
- Type: Thesis , Masters , LLM
- Identifier: http://hdl.handle.net/10948/47392 , vital:39974
- Description: The last two decades have been characterised by a phenomenal rise in the outsourcing of services to external service providers. The driver of this trend has been largely economic, since outsourcing offers more competitive price points for the same service at a comparable service level. Beyond the cost saving objective, the rationale for outsourcing has been to drive core strategy. However, with the economic slowdown, declining consumption and production are forcing entrepreneurs to change their way of thinking about the management of companies. Notably, in recent years there has been a small but a growing reversal of this trend where companies that have previously outsourced functions are being brought back in-house. One of the major concerns surrounding these changes of business strategies is the extent to which the employee rights are safeguarded.
- Full Text:
Applied phylogeography : mapping the genetic resource of Honeybush across the Cape Floristic Region
- Authors: Galuszynski, Nicholas C
- Date: 2020
- Subjects: Phylogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46771 , vital:39655
- Description: Aim: Honeybush tea is a herbal infusion made from members of the Cape Floristic Region (CFR) endemic Cyclopia Vent. Consting of 21 extant species, six are anthropogenically redistributed across the CFR for Honeybush cultivation. However, with no information regarding the distribution and levels of genetic diversity among wild Honeybush populations, anthropogenic translocation of cultivated genotypes may risk disrupting natural genetic diversity patterns. In this thesis, an applied phylogeographic approach is used to provide baseline insights into the spatial structuring of Honeybush genetic diversity. Location: The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods: Spatial structuring of evolutionary lineages within Cyclopia are explored at a genus level using data generated from the combination of Anchored Hybrid Enrichment library preparation and high through put sequencing. A High Resolution Melt analysis (HRM) toolkit is then developed to screen haplotype variation across three non-coding chloroplast loci. This HRM toolkit coupled with haplotype confirmation Sanger sequencing is then applied to describe the spatial structuring of genetic diversity in wild populations for two Honeybush species (C. intermedia and C. subternata) and to compare genetic diversity among wild and cultivated populations of three Honeybush species (C. intermedia, C. subternata, and C. longifolia). A reanalysis of published phylogeographic data focusing on CFR plant taxa is used to test if phylogeographic breaks occur across the boundaries among adjacent Centers of Endemism (CoEs). Finally, the low-copy nuclear data set generated via AHE and high throughput sequencing is summarized. Results: Phylogeographic structuring was detected at the inter- and intraspecific levels in Cyclopia. The genus level analysis revealed a strong phylogenetic split between western CFR and eastern CFR endemic species in the nuclear and chloroplast genomes. At the intraspecific level, HRM proved to be a high throughput and accurate tool for haplotype detection, revealing phylogeographic structuring of genetic diversity in C.intermediaand C.subternata. This genetic diversity and structuring was not detected in cultivated Honeybush populations, which appear to have originated from a small number of founding individuals and have experienced a genetic bottleneck. Spatial structuring of genetic lineages is common among CFR plant taxa and the reanalysis of existing data found a significant trend for phylogeographic breaks tooccuracrosstheboundariesamongadjacentCoEs. Finally, over200000baseswere sequenced across 445 low-copy nuclear loci for 14 Cyclopia species. Conclusions: This thesis provides important baseline information on the spatial distribution of wild Honeybush genetic diversity. Phylogeographic structuring is present in wild Honeybush populations. This however is not accounted for in cultivated populations, which may place wild genetic diversity at risk of being disrupted if geneflow among wild and cultivated populations occurs. The results from this thesis should therefore be used to develop precautionary guidelines for the anthropogenic redistribution of Honeybush genetic material for cultivation. Furthermore, the novel insights into regional patterns of phylogeohraphic structuring of plant populations should encourage more efficient and hypothesis driven sampling designs in future phylogeographic work in the CFR. The high throughput sequence data generated in this thesis should transform Cyclopia to a model organism for the study of molecular evolution in the CFR.
- Full Text:
- Authors: Galuszynski, Nicholas C
- Date: 2020
- Subjects: Phylogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46771 , vital:39655
- Description: Aim: Honeybush tea is a herbal infusion made from members of the Cape Floristic Region (CFR) endemic Cyclopia Vent. Consting of 21 extant species, six are anthropogenically redistributed across the CFR for Honeybush cultivation. However, with no information regarding the distribution and levels of genetic diversity among wild Honeybush populations, anthropogenic translocation of cultivated genotypes may risk disrupting natural genetic diversity patterns. In this thesis, an applied phylogeographic approach is used to provide baseline insights into the spatial structuring of Honeybush genetic diversity. Location: The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods: Spatial structuring of evolutionary lineages within Cyclopia are explored at a genus level using data generated from the combination of Anchored Hybrid Enrichment library preparation and high through put sequencing. A High Resolution Melt analysis (HRM) toolkit is then developed to screen haplotype variation across three non-coding chloroplast loci. This HRM toolkit coupled with haplotype confirmation Sanger sequencing is then applied to describe the spatial structuring of genetic diversity in wild populations for two Honeybush species (C. intermedia and C. subternata) and to compare genetic diversity among wild and cultivated populations of three Honeybush species (C. intermedia, C. subternata, and C. longifolia). A reanalysis of published phylogeographic data focusing on CFR plant taxa is used to test if phylogeographic breaks occur across the boundaries among adjacent Centers of Endemism (CoEs). Finally, the low-copy nuclear data set generated via AHE and high throughput sequencing is summarized. Results: Phylogeographic structuring was detected at the inter- and intraspecific levels in Cyclopia. The genus level analysis revealed a strong phylogenetic split between western CFR and eastern CFR endemic species in the nuclear and chloroplast genomes. At the intraspecific level, HRM proved to be a high throughput and accurate tool for haplotype detection, revealing phylogeographic structuring of genetic diversity in C.intermediaand C.subternata. This genetic diversity and structuring was not detected in cultivated Honeybush populations, which appear to have originated from a small number of founding individuals and have experienced a genetic bottleneck. Spatial structuring of genetic lineages is common among CFR plant taxa and the reanalysis of existing data found a significant trend for phylogeographic breaks tooccuracrosstheboundariesamongadjacentCoEs. Finally, over200000baseswere sequenced across 445 low-copy nuclear loci for 14 Cyclopia species. Conclusions: This thesis provides important baseline information on the spatial distribution of wild Honeybush genetic diversity. Phylogeographic structuring is present in wild Honeybush populations. This however is not accounted for in cultivated populations, which may place wild genetic diversity at risk of being disrupted if geneflow among wild and cultivated populations occurs. The results from this thesis should therefore be used to develop precautionary guidelines for the anthropogenic redistribution of Honeybush genetic material for cultivation. Furthermore, the novel insights into regional patterns of phylogeohraphic structuring of plant populations should encourage more efficient and hypothesis driven sampling designs in future phylogeographic work in the CFR. The high throughput sequence data generated in this thesis should transform Cyclopia to a model organism for the study of molecular evolution in the CFR.
- Full Text:
Applying blockchain technology to aspects of electronic health records in South Africa: lessons learnt
- Authors: Adlam, Ryno
- Date: 2020
- Subjects: Blockchains (Databases) , Database security , Data protection , Medical records -- Data processing
- Language: English
- Type: Thesis , Masters , MIT
- Identifier: http://hdl.handle.net/10948/45996 , vital:39405
- Description: The purpose of this study was to explore the applicability of blockchain technology as a viable alternative for the secure storage and distribution of electronic health records in a South African context. The adoption of electronic health records (EHRs) has grown over recent years. Electronic health records (EHRs) can be seen as electronic versions of patients’ medical history. EHRs promise benefits such as improving the quality of care, reducing medical errors, reducing costs, saving time, and enhancing the availability and sharing of medical records. Blockchain, in simple terms, could be seen as a distributed database controlled by a group of individuals. Blockchain technology differs from other distributed ledger technology by bundling unrelated data into blocks that are chained together in a linked-list manner, hence the name blockchain. Blockchain technology strives to provide desirable features, such as decentralization, immutability, audibility, and transparency. EHRs are traditionally constructed with a cloud-based infrastructure to promote the storing and distribution of medical records. These medical records are commonly stored in a centralized architecture, such as a relational database. The centralized architecture employed by EHRs may present a single point of failure. These kinds of failures may lead to data-breaches. The cloud-based infrastructure is effective and efficient from an availability standpoint. The increased availability of electronic health records has brought forth challenges related to the security and privacy of the patient’s medical records. The sensitive nature of EHRs attracts the attention of cyber-criminals. There has been a rise in the number of data breaches related to electronic health records. The traditional infrastructure used by electronic health records can no longer ensure the privacy and security of patient’s medical records. To determine whether blockchain is a viable alternative to these approaches, the main objective of this study was to compile a technical report on the applicability of aspects of blockchain technology to the secure storage and distribution of electronic health records. The study first conducted a literature review to gather background on the current state of electronic health records and blockchain technology. The results of the literature review were used to compile an initial report. Experiments were conducted with various aspects of blockchain technology to build a technical baseline and to ultimately validate the initial report. The insights gained from the experiments served to refine the initial report into a final technical report. The final deliverable of this study was to devise a technical report. The technical report serves as a generalized overview of the applicability of blockchain technology as a secure storage and distribution mechanism for electronic health records. The main topics covered by the technical report to outline the applicability of blockchain technology to EHRs are as follows: authentication, authorization, audit log, storage and transactions. The insights gained from the study illustrate that permissioned blockchain technology can enhance the traditional AAA security scheme employed by traditional EHRs. The AAA security scheme entails the use of certificate-based authentication and attributebased access control for authorization. Audit logs can be stored in a semi-decentralized architecture that can enhance the security and privacy of audit logs. Using blockchain technology for storing electronic health records might not be a viable alternative to traditional EHRs architecture. Blockchain technology violates certain privacy regulations as information is stored in a permanent manner. Furthermore, blockchain technology is not optimized for dealing with large volumes of data. However, blockchain technology could be used to store a cryptographic hash of electronic health records to ensure the integrity of records. Permissioned blockchain technology can enhance the EHRs transaction process by transacting health records in a peer-to-peer infrastructure. In doing so, the above-mentioned AAA security scheme can enhance the security, confidentiality, and integrity of electronic health records shared across organizational bounds.
- Full Text:
- Authors: Adlam, Ryno
- Date: 2020
- Subjects: Blockchains (Databases) , Database security , Data protection , Medical records -- Data processing
- Language: English
- Type: Thesis , Masters , MIT
- Identifier: http://hdl.handle.net/10948/45996 , vital:39405
- Description: The purpose of this study was to explore the applicability of blockchain technology as a viable alternative for the secure storage and distribution of electronic health records in a South African context. The adoption of electronic health records (EHRs) has grown over recent years. Electronic health records (EHRs) can be seen as electronic versions of patients’ medical history. EHRs promise benefits such as improving the quality of care, reducing medical errors, reducing costs, saving time, and enhancing the availability and sharing of medical records. Blockchain, in simple terms, could be seen as a distributed database controlled by a group of individuals. Blockchain technology differs from other distributed ledger technology by bundling unrelated data into blocks that are chained together in a linked-list manner, hence the name blockchain. Blockchain technology strives to provide desirable features, such as decentralization, immutability, audibility, and transparency. EHRs are traditionally constructed with a cloud-based infrastructure to promote the storing and distribution of medical records. These medical records are commonly stored in a centralized architecture, such as a relational database. The centralized architecture employed by EHRs may present a single point of failure. These kinds of failures may lead to data-breaches. The cloud-based infrastructure is effective and efficient from an availability standpoint. The increased availability of electronic health records has brought forth challenges related to the security and privacy of the patient’s medical records. The sensitive nature of EHRs attracts the attention of cyber-criminals. There has been a rise in the number of data breaches related to electronic health records. The traditional infrastructure used by electronic health records can no longer ensure the privacy and security of patient’s medical records. To determine whether blockchain is a viable alternative to these approaches, the main objective of this study was to compile a technical report on the applicability of aspects of blockchain technology to the secure storage and distribution of electronic health records. The study first conducted a literature review to gather background on the current state of electronic health records and blockchain technology. The results of the literature review were used to compile an initial report. Experiments were conducted with various aspects of blockchain technology to build a technical baseline and to ultimately validate the initial report. The insights gained from the experiments served to refine the initial report into a final technical report. The final deliverable of this study was to devise a technical report. The technical report serves as a generalized overview of the applicability of blockchain technology as a secure storage and distribution mechanism for electronic health records. The main topics covered by the technical report to outline the applicability of blockchain technology to EHRs are as follows: authentication, authorization, audit log, storage and transactions. The insights gained from the study illustrate that permissioned blockchain technology can enhance the traditional AAA security scheme employed by traditional EHRs. The AAA security scheme entails the use of certificate-based authentication and attributebased access control for authorization. Audit logs can be stored in a semi-decentralized architecture that can enhance the security and privacy of audit logs. Using blockchain technology for storing electronic health records might not be a viable alternative to traditional EHRs architecture. Blockchain technology violates certain privacy regulations as information is stored in a permanent manner. Furthermore, blockchain technology is not optimized for dealing with large volumes of data. However, blockchain technology could be used to store a cryptographic hash of electronic health records to ensure the integrity of records. Permissioned blockchain technology can enhance the EHRs transaction process by transacting health records in a peer-to-peer infrastructure. In doing so, the above-mentioned AAA security scheme can enhance the security, confidentiality, and integrity of electronic health records shared across organizational bounds.
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