Free space in the academy
- Authors: Janz, Bruce B
- Date: 2015
- Subjects: Academic Freedom -- South Africa Universities and colleges -- South Africa Equality Liberty Education and state -- South Africa Education, Higher -- South Africa
- Language: English
- Type: text
- Identifier: http://hdl.handle.net/10962/848 , vital:19996
- Description: “Academic freedom” does not mean the same thing to everyone. There are, to be sure, a few who argue against it. Sandra Korn, in the Harvard Crimson last year, argued that we should abandon academic freedom in favor of academic justice. She argues that we have reached a consensus on issues such as racism, classism and sexism, and so to promote racist or classist or sexist views under the guise of “academic freedom” is to ignore a higher standard and more importantly to ignore the fact that academic freedom is always couched in political realities, and is never the dispassionate exercise of reason and the pursuit of knowledge. It always serves an agenda, and so if that is the case, it should serve the agenda of justice, particularly justice for disadvantaged and marginalized people. Her online article, when I last looked, had almost 1300 comments, and had inspired commentary from a number of other publications. You can imagine the range of these comments and reactions: everything from “this is long overdue” to the newest favorite insult circulating the internet, “she’s just another Social Justice Warrior (SJW).”
- Full Text:
- Date Issued: 2015
- Authors: Janz, Bruce B
- Date: 2015
- Subjects: Academic Freedom -- South Africa Universities and colleges -- South Africa Equality Liberty Education and state -- South Africa Education, Higher -- South Africa
- Language: English
- Type: text
- Identifier: http://hdl.handle.net/10962/848 , vital:19996
- Description: “Academic freedom” does not mean the same thing to everyone. There are, to be sure, a few who argue against it. Sandra Korn, in the Harvard Crimson last year, argued that we should abandon academic freedom in favor of academic justice. She argues that we have reached a consensus on issues such as racism, classism and sexism, and so to promote racist or classist or sexist views under the guise of “academic freedom” is to ignore a higher standard and more importantly to ignore the fact that academic freedom is always couched in political realities, and is never the dispassionate exercise of reason and the pursuit of knowledge. It always serves an agenda, and so if that is the case, it should serve the agenda of justice, particularly justice for disadvantaged and marginalized people. Her online article, when I last looked, had almost 1300 comments, and had inspired commentary from a number of other publications. You can imagine the range of these comments and reactions: everything from “this is long overdue” to the newest favorite insult circulating the internet, “she’s just another Social Justice Warrior (SJW).”
- Full Text:
- Date Issued: 2015
A constructivist deconstruction of post-apartheid South Africa’s trade negotiation strategies: the politics of development and global value chains
- Authors: Pillay, Morgenie
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64731 , vital:28596
- Description: Expected release date-May 2020
- Full Text:
- Date Issued: 2015
- Authors: Pillay, Morgenie
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64731 , vital:28596
- Description: Expected release date-May 2020
- Full Text:
- Date Issued: 2015
Isolation and structure elucidation of halogenated metabolites from Portieria hornemannii and Portieria tripinnata
- Authors: Adam, Mohammed
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/64674 , vital:28591
- Description: The red marine algal genus, Portieria, is known to produce a number of potent cytotoxic compounds with anticancer potential. The most important anticancer lead produced by this genus is the compound halomon. Unfortunately, the lack of sufficient quantities of this compound hampered its further development. Two Portieria species, Portieria hornemannii and Portieria tripinnata, are found along the South African coastline. Recent studies, based on DNA analysis, suggest that Portieria hornemannii may in fact be divided into several cryptic species. The current project is part of a larger study designed to investigate the use of secondary metabolites to identify new marine algal species. In this study 1H NMR profiles of the organic extracts of selected Portieria spp were compared in order to identify new species. Selected compounds were then isolated and characterised as potential chemotaxonomic markers. Four halogenated monoterpenes were isolated from Portieria hornemannii. Two of these were new compounds 4-(3-bromo-4-chloro-4-methylpentyl)-3-chlorofuran-2(5H)-one, which were isomers of each other. The two known compounds had been previously isolated from Portieria hornemannii samples off the Madagascar coast. These compounds could prove to be useful as chemotaxonomic marker compounds, as they have never been isolated from any other species of marine algae. Three known halogenated monoterpenes were isolated from Portieria tripinnata. These compounds had been previously isolated from different species of marine algae and therefore, could not serve as chemotaxonomic marker compounds for this species of marine alga. Further work needs to be done on Portieria tripinnata, with regards to its chemistry, as it is a species of marine algae that has not been previously researched.
- Full Text:
- Date Issued: 2015
- Authors: Adam, Mohammed
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/64674 , vital:28591
- Description: The red marine algal genus, Portieria, is known to produce a number of potent cytotoxic compounds with anticancer potential. The most important anticancer lead produced by this genus is the compound halomon. Unfortunately, the lack of sufficient quantities of this compound hampered its further development. Two Portieria species, Portieria hornemannii and Portieria tripinnata, are found along the South African coastline. Recent studies, based on DNA analysis, suggest that Portieria hornemannii may in fact be divided into several cryptic species. The current project is part of a larger study designed to investigate the use of secondary metabolites to identify new marine algal species. In this study 1H NMR profiles of the organic extracts of selected Portieria spp were compared in order to identify new species. Selected compounds were then isolated and characterised as potential chemotaxonomic markers. Four halogenated monoterpenes were isolated from Portieria hornemannii. Two of these were new compounds 4-(3-bromo-4-chloro-4-methylpentyl)-3-chlorofuran-2(5H)-one, which were isomers of each other. The two known compounds had been previously isolated from Portieria hornemannii samples off the Madagascar coast. These compounds could prove to be useful as chemotaxonomic marker compounds, as they have never been isolated from any other species of marine algae. Three known halogenated monoterpenes were isolated from Portieria tripinnata. These compounds had been previously isolated from different species of marine algae and therefore, could not serve as chemotaxonomic marker compounds for this species of marine alga. Further work needs to be done on Portieria tripinnata, with regards to its chemistry, as it is a species of marine algae that has not been previously researched.
- Full Text:
- Date Issued: 2015
Addressing local level food insecurity amongst small-holder communities in transition
- Shackleton, Charlie M, Hamer, Nicholas G, Swallow, Brent M, Ncube, K
- Authors: Shackleton, Charlie M , Hamer, Nicholas G , Swallow, Brent M , Ncube, K
- Date: 2015
- Subjects: Food security -- South Africa Economic development -- South Africa Rural development -- South Africa
- Language: English
- Type: text
- Identifier: http://hdl.handle.net/10962/50090 , vital:25958
- Description: Food insecurity affects as significant proportion of the world's population and hence it typically receives priority attention in global policies associated with poverty, equity and sustainable development. For example, it is the first of the Millennium Development Goals and the second of their successor, the Sustainable Development Goals. Access to sufficient and nutritious food is deemed a basic human right. The latest FAO analysis of the “State of Food Insecurity in the World 2014” reports that 805 million people (approximately 11-12% of the world's population) are chronically undernourished (i.e. do not have sufficient energy intake over a period of at least one year). In sub-Saharan Africa the prevalence remains stubbornly high at 24%, the highest in the world. Whilst most interpret food insecurity to mean an insufficient quantity of food (as measured by the number of calories consumed), the widely accepted FAO definition considers four dimensions of food security, namely quantity, quality or diversity, access and use. Provision of enough calories on a daily basis is not sufficient if the diet lacks diversity and appropriate balance to provide the full range of minerals and vitamins necessary for proper health, or if the food available is culturally unacceptable. Thus, there is a pressing need for more nuanced analyses of food security against all four of the dimensions embedded in the concept. Additionally, it is important that these be measured at more local or regional levels because national statistics can mask alarming regional discrepancies in food security, or amongst particular sectors of society, such as recent migrants, refugees, female- or child-headed households, those vulnerable to HIV/AIDS or the landless, to mention just a few. For example, at a national level South Africa is considered a food secure nation with respect to staple requirements, and access to sufficient food is enshrined in the Constitution (Section 27, subsection 1b), but nationally one in twenty (i.e. approx. 2.5 million people) go to bed hungry most nights, and 23% of children below the age of 15 are physically stunted, severely stunted or wasted, due to the long-term ill effects of insufficient food or of inadequate diversity and quality. At a subnational level, there are marked differences between rural and urban populations and even between geographic areas (for example, the prevalence of stunting amongst boys less than 15 years old is 23% in the Eastern Cape, compared to 12% in Gauteng). Once again, despite being a food secure nation, nationally 40% of the population have a dietary diversity score of four or less, which is a cut-off point signifying poor dietary diversity which makes people more vulnerable to malnutrition and ill health, and in Limpopo and Northwest provinces it is as high as 66% and 61%, respectively.
- Full Text:
- Date Issued: 2015
- Authors: Shackleton, Charlie M , Hamer, Nicholas G , Swallow, Brent M , Ncube, K
- Date: 2015
- Subjects: Food security -- South Africa Economic development -- South Africa Rural development -- South Africa
- Language: English
- Type: text
- Identifier: http://hdl.handle.net/10962/50090 , vital:25958
- Description: Food insecurity affects as significant proportion of the world's population and hence it typically receives priority attention in global policies associated with poverty, equity and sustainable development. For example, it is the first of the Millennium Development Goals and the second of their successor, the Sustainable Development Goals. Access to sufficient and nutritious food is deemed a basic human right. The latest FAO analysis of the “State of Food Insecurity in the World 2014” reports that 805 million people (approximately 11-12% of the world's population) are chronically undernourished (i.e. do not have sufficient energy intake over a period of at least one year). In sub-Saharan Africa the prevalence remains stubbornly high at 24%, the highest in the world. Whilst most interpret food insecurity to mean an insufficient quantity of food (as measured by the number of calories consumed), the widely accepted FAO definition considers four dimensions of food security, namely quantity, quality or diversity, access and use. Provision of enough calories on a daily basis is not sufficient if the diet lacks diversity and appropriate balance to provide the full range of minerals and vitamins necessary for proper health, or if the food available is culturally unacceptable. Thus, there is a pressing need for more nuanced analyses of food security against all four of the dimensions embedded in the concept. Additionally, it is important that these be measured at more local or regional levels because national statistics can mask alarming regional discrepancies in food security, or amongst particular sectors of society, such as recent migrants, refugees, female- or child-headed households, those vulnerable to HIV/AIDS or the landless, to mention just a few. For example, at a national level South Africa is considered a food secure nation with respect to staple requirements, and access to sufficient food is enshrined in the Constitution (Section 27, subsection 1b), but nationally one in twenty (i.e. approx. 2.5 million people) go to bed hungry most nights, and 23% of children below the age of 15 are physically stunted, severely stunted or wasted, due to the long-term ill effects of insufficient food or of inadequate diversity and quality. At a subnational level, there are marked differences between rural and urban populations and even between geographic areas (for example, the prevalence of stunting amongst boys less than 15 years old is 23% in the Eastern Cape, compared to 12% in Gauteng). Once again, despite being a food secure nation, nationally 40% of the population have a dietary diversity score of four or less, which is a cut-off point signifying poor dietary diversity which makes people more vulnerable to malnutrition and ill health, and in Limpopo and Northwest provinces it is as high as 66% and 61%, respectively.
- Full Text:
- Date Issued: 2015
Characterization of the co-chaperones of Hsp70 and Hsp90 in Trypanosoma brucei and their potential partnerships
- Authors: Mokoena, Fortunate
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54543 , vital:26583
- Description: African Trypanosomiasis, which is caused by Trypanosoma brucei, is one of the crippling agents of social and economic development in Africa. T. brucei cycles between the cold-blooded insect vector, the tsetse fly (Glossina spp), and warm-blooded mammalian hosts. T. brucei, T. cruzi and L. major are mammal infecting kinetoplastid parasites that are collectively referred to as TriTryps. These parasites experience extreme environments as they move between their warm-blooded mammalian hosts and cold-blooded insect vectors which trigger extensive morphological transformations during the life-cycle of the parasite. Molecular chaperones have been implicated in parasite differentiation. TriTryps display significant expansions and diversity in the gene complements encoding molecular chaperones, especially J-proteins. Generally, J-proteins function as co-chaperones of Hsp70s, forming part of vital protein homeostasis processes. Hsp70s show a high degree of conservation, while J-proteins appear to be an extreme case of taxonomic radiation. Although several studies have focused on the molecular and cell biology of Hsp70s in some kinetoplastid parasites, knowledge is still lacking pertaining to J-proteins and their partnerships with Hsp70s. This thesis focused on the classification of kinetoplastid Jproteins into the four types by examining the domain organizations using T. brucei as a guide. The potential partnership of J-proteins and Hsp70s were postulated based on predicted subcellular localization. Kinetoplastid parasites, particularly T. brucei, have evolved an expanded and specialized J-protein machinery, likely to be a consequence of an evolutionary fitness/trait to adapt to diverse environment present in hosts and vectors. These analyses will yield insight into the process of parasite differentiation as well as provide new leads for chemotherapeutic treatments. The presence of the STI1 mediated Hsp90 hetero-complex formation has not been confirmed in T. brucei. To this end, in silico and biochemical techniques were used to characterize the role of TbSTI1, as an adaptor protein of Hsp70 and Hsp90. Through domain architecture analysis, sequence alignments, phylogenetic analysis and three-dimensional structure prediction, TbSTI1 was demonstrated to be the most conserved TPR containing co-chaperone of Hsp70 and Hsp83 in T. brucei and also shown to be highly similar to its eukaryotic homologues. Recombinant TbSTI1 was overproduced and purified in E.coli cells and subsequently shown to associate with TcHsp70 in a concentration dependent manner and associate weakly with TbHsp70.4. TbSTI1 and TbHsp83 were also demonstrated to be expressed and upregulated upon exposure to heat shock at the bloodstream stage of parasite development. In conclusion, this study is the first to report the interaction of TbSTI1 with a chaperone. Interactions between TbSTI1 and Hsp70s were demonstrated and therefore, the formation of the hetero-complex is predicted based the similarity of TbSTI1 to other STI1 proteins.
- Full Text:
- Date Issued: 2015
- Authors: Mokoena, Fortunate
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54543 , vital:26583
- Description: African Trypanosomiasis, which is caused by Trypanosoma brucei, is one of the crippling agents of social and economic development in Africa. T. brucei cycles between the cold-blooded insect vector, the tsetse fly (Glossina spp), and warm-blooded mammalian hosts. T. brucei, T. cruzi and L. major are mammal infecting kinetoplastid parasites that are collectively referred to as TriTryps. These parasites experience extreme environments as they move between their warm-blooded mammalian hosts and cold-blooded insect vectors which trigger extensive morphological transformations during the life-cycle of the parasite. Molecular chaperones have been implicated in parasite differentiation. TriTryps display significant expansions and diversity in the gene complements encoding molecular chaperones, especially J-proteins. Generally, J-proteins function as co-chaperones of Hsp70s, forming part of vital protein homeostasis processes. Hsp70s show a high degree of conservation, while J-proteins appear to be an extreme case of taxonomic radiation. Although several studies have focused on the molecular and cell biology of Hsp70s in some kinetoplastid parasites, knowledge is still lacking pertaining to J-proteins and their partnerships with Hsp70s. This thesis focused on the classification of kinetoplastid Jproteins into the four types by examining the domain organizations using T. brucei as a guide. The potential partnership of J-proteins and Hsp70s were postulated based on predicted subcellular localization. Kinetoplastid parasites, particularly T. brucei, have evolved an expanded and specialized J-protein machinery, likely to be a consequence of an evolutionary fitness/trait to adapt to diverse environment present in hosts and vectors. These analyses will yield insight into the process of parasite differentiation as well as provide new leads for chemotherapeutic treatments. The presence of the STI1 mediated Hsp90 hetero-complex formation has not been confirmed in T. brucei. To this end, in silico and biochemical techniques were used to characterize the role of TbSTI1, as an adaptor protein of Hsp70 and Hsp90. Through domain architecture analysis, sequence alignments, phylogenetic analysis and three-dimensional structure prediction, TbSTI1 was demonstrated to be the most conserved TPR containing co-chaperone of Hsp70 and Hsp83 in T. brucei and also shown to be highly similar to its eukaryotic homologues. Recombinant TbSTI1 was overproduced and purified in E.coli cells and subsequently shown to associate with TcHsp70 in a concentration dependent manner and associate weakly with TbHsp70.4. TbSTI1 and TbHsp83 were also demonstrated to be expressed and upregulated upon exposure to heat shock at the bloodstream stage of parasite development. In conclusion, this study is the first to report the interaction of TbSTI1 with a chaperone. Interactions between TbSTI1 and Hsp70s were demonstrated and therefore, the formation of the hetero-complex is predicted based the similarity of TbSTI1 to other STI1 proteins.
- Full Text:
- Date Issued: 2015
The economics of institutions, institutional governance and efficiency: the case of water distribution in Lower Sundays River Valley
- Authors: Madigele, Patricia Kefilwe
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/54777 , vital:26611
- Description: The institutional dynamics, policies and legislation that were prevalent during the apartheid era have left imprints that are difficult to ignore as they still dictate the interaction between different elements in the water sector to date. During the apartheid era, the formulation of policies was informed by racial segregation, resulting in a socio-economic pattern that dictated the distribution and access of resources for the people of different races in the country. Post-apartheid, the National Water Act has established the basis for management of water resources on a catchment basis (for equity, efficiency and sustainability), and the Water Services Act aims to ensure everybody has access to basic water supply and sanitation services. Regardless of the improvements in water supply to the rural sector made by the South African government, many of the current patterns of water use are still characterised by inequality, inefficiency, and inadequacy. The poor remain marginalised, and emerging farmers and poor rural communities have limited access to water resources while water continues to be used inefficiently by some farmers in the agricultural sector with few incentives to improve its water use efficiency. Despite the existence of the thriving citrus industry in the area, around 60% of people in the Sundays River Valley Municipality (SRVM) live below the poverty datum line. The inequality between the municipal populace and the commercial citrus industry is noticeable and the inequitable water redistribution is prevalent in the Lower Sundays River Valley (LSRV). The problem of disrupted water supply is prevalent in the catchment. However, there is also currently no physical shortage of water in the catchment. Therefore, the currently experienced problems with water supply in the LSRV are consequence of a lack of effective institutions and infrastructure, not of physical water scarcity. It is argued in this paper that there is a notable lack of understanding about the design of institutions for water management in developing countries. The vast majority of research on water management and access is premised on neoclassical economics ideas related to water markets and pricing among others. The neoclassical economics approach, however, does not adequately define the role of institutions in shaping the direction of water access and supply. This study uses new institutional economics (NIE) arguments to define the institutional arrangements and dynamics defining the water sector in South Africa, using the Lower Sunday River Water Users Association (LSR-WUA) as the case study. It aims at analysing the institutional governance and performance of the using equity, efficiency and effectiveness as key indicators. The various research methods employed in this study include; interpretive and post-positivist paradigms, quantitative and qualitative research, the case study research method and in-depth key informant interviews. It is concluded that that the current and future decisions made by the LSR-WUA are not entirely independent of those made in the past under Sundays River Irrigation Board (SRIB). The thesis argues that such factors as old effective networks, vested interests of commercial farmers, sunk costs towards the building of canals, among other factors, may have influenced the dependence of the LSR-WUA on the SRIB’s set path. It is further concluded that the absence of contractual agreement between the LRS-WUA which acts as the bulk water supplier, and the SRVM which acts as both the water services authority (WSA) and the water service provider (WSP) creates an institutional arrangement deficiency. Such an institutional arrangement vacuum can lead to a failure of the water institutions in the catchment to provide water resources effectively. The study further argues that because the post-apartheid National Water Policy of South Africa is largely influenced by neoclassical economics foundations, the desired results in the water sector, such as equitable distribution of water resources, have not yet been fulfilled completely.
- Full Text:
- Date Issued: 2015
- Authors: Madigele, Patricia Kefilwe
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/54777 , vital:26611
- Description: The institutional dynamics, policies and legislation that were prevalent during the apartheid era have left imprints that are difficult to ignore as they still dictate the interaction between different elements in the water sector to date. During the apartheid era, the formulation of policies was informed by racial segregation, resulting in a socio-economic pattern that dictated the distribution and access of resources for the people of different races in the country. Post-apartheid, the National Water Act has established the basis for management of water resources on a catchment basis (for equity, efficiency and sustainability), and the Water Services Act aims to ensure everybody has access to basic water supply and sanitation services. Regardless of the improvements in water supply to the rural sector made by the South African government, many of the current patterns of water use are still characterised by inequality, inefficiency, and inadequacy. The poor remain marginalised, and emerging farmers and poor rural communities have limited access to water resources while water continues to be used inefficiently by some farmers in the agricultural sector with few incentives to improve its water use efficiency. Despite the existence of the thriving citrus industry in the area, around 60% of people in the Sundays River Valley Municipality (SRVM) live below the poverty datum line. The inequality between the municipal populace and the commercial citrus industry is noticeable and the inequitable water redistribution is prevalent in the Lower Sundays River Valley (LSRV). The problem of disrupted water supply is prevalent in the catchment. However, there is also currently no physical shortage of water in the catchment. Therefore, the currently experienced problems with water supply in the LSRV are consequence of a lack of effective institutions and infrastructure, not of physical water scarcity. It is argued in this paper that there is a notable lack of understanding about the design of institutions for water management in developing countries. The vast majority of research on water management and access is premised on neoclassical economics ideas related to water markets and pricing among others. The neoclassical economics approach, however, does not adequately define the role of institutions in shaping the direction of water access and supply. This study uses new institutional economics (NIE) arguments to define the institutional arrangements and dynamics defining the water sector in South Africa, using the Lower Sunday River Water Users Association (LSR-WUA) as the case study. It aims at analysing the institutional governance and performance of the using equity, efficiency and effectiveness as key indicators. The various research methods employed in this study include; interpretive and post-positivist paradigms, quantitative and qualitative research, the case study research method and in-depth key informant interviews. It is concluded that that the current and future decisions made by the LSR-WUA are not entirely independent of those made in the past under Sundays River Irrigation Board (SRIB). The thesis argues that such factors as old effective networks, vested interests of commercial farmers, sunk costs towards the building of canals, among other factors, may have influenced the dependence of the LSR-WUA on the SRIB’s set path. It is further concluded that the absence of contractual agreement between the LRS-WUA which acts as the bulk water supplier, and the SRVM which acts as both the water services authority (WSA) and the water service provider (WSP) creates an institutional arrangement deficiency. Such an institutional arrangement vacuum can lead to a failure of the water institutions in the catchment to provide water resources effectively. The study further argues that because the post-apartheid National Water Policy of South Africa is largely influenced by neoclassical economics foundations, the desired results in the water sector, such as equitable distribution of water resources, have not yet been fulfilled completely.
- Full Text:
- Date Issued: 2015
Establishment of human OCT4 as a putative HSP90 client protein: a case for HSP90 chaperoning pluripotency
- Authors: Sterrenberg, Jason Neville
- Date: 2015
- Subjects: Induced pluripotent stem cells , Heat shock proteins , Stem cells , Transcription factors , Molecular chaperones
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/194010 , vital:45415 , 10.21504/10962/194010
- Description: The therapeutic potential of stem cells is already being harnessed in clinical trails. Of even greater therapeutic potential has been the discovery of mechanisms to reprogram differentiated cells into a pluripotent stem cell-like state known as induced pluripotent stem cells (iPSCs). Stem cell nature is governed and maintained by a hierarchy of transcription factors, the apex of which is OCT4. Although much research has elucidated the transcriptional regulation of OCT4, OCT4 regulated gene expression profiles and OCT4 transcriptional activation mechanisms in both stem cell biology and cellular reprogramming to iPSCs, the fundamental biochemistry surrounding the OCT4 transcription factor remains largely unknown. In order to analyze the biochemical relationship between HSP90 and human OCT4 we developed an exogenous active human OCT4 expression model with human OCT4 under transcriptional control of a constitutive promoter. We identified the direct interaction between HSP90 and human OCT4 despite the fact that the proteins predominantly display differential subcellular localizations. We show that HSP90 inhibition resulted in degradation of human OCT4 via the ubiquitin proteasome degradation pathway. As human OCT4 and HSP90 did not interact in the nucleus, we suggest that HSP90 functions in the cytoplasmic stabilization of human OCT4. Our analysis suggests HSP90 inhibition inhibits the transcriptional activity of human OCT4 dimers without affecting monomeric OCT4 activity. Additionally our data suggests that the HSP90 and human OCT4 complex is modulated by phosphorylation events either promoting or abrogating the interaction between HSP90 and human OCT4. Our data suggest that human OCT4 displays the characteristics describing HSP90 client proteins, therefore we identify human OCT4 as a putative HSP90 client protein. The regulation of the transcription factor OCT4 by HSP90 provides fundamental insights into the complex biochemistry of stem cell biology. This may also be suggestive that HSP90 not only regulates stem cell biology by maintaining routine cellular homeostasis but additionally through the direct regulation of pluripotency factors. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2015
- Full Text:
- Date Issued: 2015
- Authors: Sterrenberg, Jason Neville
- Date: 2015
- Subjects: Induced pluripotent stem cells , Heat shock proteins , Stem cells , Transcription factors , Molecular chaperones
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/194010 , vital:45415 , 10.21504/10962/194010
- Description: The therapeutic potential of stem cells is already being harnessed in clinical trails. Of even greater therapeutic potential has been the discovery of mechanisms to reprogram differentiated cells into a pluripotent stem cell-like state known as induced pluripotent stem cells (iPSCs). Stem cell nature is governed and maintained by a hierarchy of transcription factors, the apex of which is OCT4. Although much research has elucidated the transcriptional regulation of OCT4, OCT4 regulated gene expression profiles and OCT4 transcriptional activation mechanisms in both stem cell biology and cellular reprogramming to iPSCs, the fundamental biochemistry surrounding the OCT4 transcription factor remains largely unknown. In order to analyze the biochemical relationship between HSP90 and human OCT4 we developed an exogenous active human OCT4 expression model with human OCT4 under transcriptional control of a constitutive promoter. We identified the direct interaction between HSP90 and human OCT4 despite the fact that the proteins predominantly display differential subcellular localizations. We show that HSP90 inhibition resulted in degradation of human OCT4 via the ubiquitin proteasome degradation pathway. As human OCT4 and HSP90 did not interact in the nucleus, we suggest that HSP90 functions in the cytoplasmic stabilization of human OCT4. Our analysis suggests HSP90 inhibition inhibits the transcriptional activity of human OCT4 dimers without affecting monomeric OCT4 activity. Additionally our data suggests that the HSP90 and human OCT4 complex is modulated by phosphorylation events either promoting or abrogating the interaction between HSP90 and human OCT4. Our data suggest that human OCT4 displays the characteristics describing HSP90 client proteins, therefore we identify human OCT4 as a putative HSP90 client protein. The regulation of the transcription factor OCT4 by HSP90 provides fundamental insights into the complex biochemistry of stem cell biology. This may also be suggestive that HSP90 not only regulates stem cell biology by maintaining routine cellular homeostasis but additionally through the direct regulation of pluripotency factors. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2015
- Full Text:
- Date Issued: 2015
The reform of world order?: BRICS in an Interpolar world
- Authors: Phyllis, Yvonne
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193520 , vital:45339
- Description: International relations has recently seen new developments which are unpredictable and in their infant stage. The causes of these developments are plentiful, the consequences stemming from waning unipolarity to the emergence of new fora creating their own spaces. Whatever the case, international relations is not as it was in the period just after the Cold War. As a result, the terms of global governance established after 1990 have come under serious scrutiny. This transition has the makings of a new world order, an interpolar world order. This study asserts that we no longer live in a unipolar world, nor do we live in a world which can only be described as multipolar. It makes the argument that although multipolarity is a crucial element of the world, it only offers a partial description of today’s order. The study asserts that it is interpolarity which is closest in accounting for today’s world. Not only does it describe the world as multipolar, it also describes it as interdependent. To this end, the study provides a detailed account of what is meant by an interpolar world order and how differently it explains international events. It also provides an account of factors which can develop in an interpolar world. One of these includes allowing room for emerging powers to create their own spaces in efforts of avoiding co-option while continuing to realise the importance of operating within a context of continuity. This means that emerging countries create their own spaces but they also realise the importance of working with already established regimes such as the G20. BRICS (Brazil, Russia, India, China and South Africa) is used as a case study to indicate one of the new developments afforded by an interpolar order-the emergence of new fora. The study asserts that although BRICS is rife with internal dissimilarities, it has indicated some degree of political will in one aspect; that is; advocating for the reform of the terms of global governance, advocating for more representative forms of global governance. The study thus explores factors of a world whose contours are gradually changing but which are unpredictable and in flux. , Thesis (MA) -- Faculty of Humanities, Political and International Studies, 2015
- Full Text:
- Date Issued: 2015
- Authors: Phyllis, Yvonne
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193520 , vital:45339
- Description: International relations has recently seen new developments which are unpredictable and in their infant stage. The causes of these developments are plentiful, the consequences stemming from waning unipolarity to the emergence of new fora creating their own spaces. Whatever the case, international relations is not as it was in the period just after the Cold War. As a result, the terms of global governance established after 1990 have come under serious scrutiny. This transition has the makings of a new world order, an interpolar world order. This study asserts that we no longer live in a unipolar world, nor do we live in a world which can only be described as multipolar. It makes the argument that although multipolarity is a crucial element of the world, it only offers a partial description of today’s order. The study asserts that it is interpolarity which is closest in accounting for today’s world. Not only does it describe the world as multipolar, it also describes it as interdependent. To this end, the study provides a detailed account of what is meant by an interpolar world order and how differently it explains international events. It also provides an account of factors which can develop in an interpolar world. One of these includes allowing room for emerging powers to create their own spaces in efforts of avoiding co-option while continuing to realise the importance of operating within a context of continuity. This means that emerging countries create their own spaces but they also realise the importance of working with already established regimes such as the G20. BRICS (Brazil, Russia, India, China and South Africa) is used as a case study to indicate one of the new developments afforded by an interpolar order-the emergence of new fora. The study asserts that although BRICS is rife with internal dissimilarities, it has indicated some degree of political will in one aspect; that is; advocating for the reform of the terms of global governance, advocating for more representative forms of global governance. The study thus explores factors of a world whose contours are gradually changing but which are unpredictable and in flux. , Thesis (MA) -- Faculty of Humanities, Political and International Studies, 2015
- Full Text:
- Date Issued: 2015
Evaluation of microinsurance distribution strategy at the bottom of the pyramid by Liberty Life Swaziland
- Authors: Lukhele, Mlungisi Reginald
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/54474 , vital:26568
- Description: This is a qualitative study which focuses on how Liberty Life Swaziland distributes microinsurance to the bottom of the pyramid within Swaziland. Using stratified purposive sampling, this study identified 5 managers within Liberty Life and 4 managers from brokerages and affinity partners who had a minimum of 3 years’ experience in distribution of microinsurance. Semi-structured and in-depth interviews were conducted by the researcher with these managers. Interviews were stopped when there was data saturation. To induce emerging themes from the data, open-coding and constant comparison technique was used. Findings in this study reveal that to distribute microinsurance to low income households, Liberty Life objectives are to; (1) provide relevant solutions in a cost effective manner, thus keeping premiums as affordable as possible, (2) provide simple products which are easy to understand by customers, (3) make services accessible, and (4) make doing business easy. In this regard, Liberty Life distribution strategy is to partner with bulk retailing entities that have a client base they already service and benefit from nationwide presence and infrastructure. Lastly, the perspectives of both internal and external stakeholders in microinsurance are discussed to evaluate the challenges and successes experienced in implementing the distribution strategy. This study is valuable to critically understand the current distribution strategy from the viewpoint of key intermediaries, but also pinpoint how efforts to achieve microinsurance distribution objectives can be enhanced. Lastly, the study recommends that; a selection criteria be set for distribution partners, partnership with mobile network operators, investment in continuous training of distribution partners and knowledge sharing between Liberty and intermediaries to cease the opportunity at the bottom of the pyramid.
- Full Text:
- Date Issued: 2015
- Authors: Lukhele, Mlungisi Reginald
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/54474 , vital:26568
- Description: This is a qualitative study which focuses on how Liberty Life Swaziland distributes microinsurance to the bottom of the pyramid within Swaziland. Using stratified purposive sampling, this study identified 5 managers within Liberty Life and 4 managers from brokerages and affinity partners who had a minimum of 3 years’ experience in distribution of microinsurance. Semi-structured and in-depth interviews were conducted by the researcher with these managers. Interviews were stopped when there was data saturation. To induce emerging themes from the data, open-coding and constant comparison technique was used. Findings in this study reveal that to distribute microinsurance to low income households, Liberty Life objectives are to; (1) provide relevant solutions in a cost effective manner, thus keeping premiums as affordable as possible, (2) provide simple products which are easy to understand by customers, (3) make services accessible, and (4) make doing business easy. In this regard, Liberty Life distribution strategy is to partner with bulk retailing entities that have a client base they already service and benefit from nationwide presence and infrastructure. Lastly, the perspectives of both internal and external stakeholders in microinsurance are discussed to evaluate the challenges and successes experienced in implementing the distribution strategy. This study is valuable to critically understand the current distribution strategy from the viewpoint of key intermediaries, but also pinpoint how efforts to achieve microinsurance distribution objectives can be enhanced. Lastly, the study recommends that; a selection criteria be set for distribution partners, partnership with mobile network operators, investment in continuous training of distribution partners and knowledge sharing between Liberty and intermediaries to cease the opportunity at the bottom of the pyramid.
- Full Text:
- Date Issued: 2015
Spatio-temporal variation in the phytobenthos and phytoplankton community structure and composition of particulate matter along a river-estuary continuum assessed using microscopic and stable isotope analyses
- Authors: Dalu, Tatenda
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54416 , vital:26563
- Description: Phytoplankton and phytobenthos communities play an important role in lotic systems as primary producers providing essential biomolecules to higher trophic oganisms and are important indicators for environmental or ecological change. In this thesis, field studies (observational and experimental) along a river–estuary continuum were conducted to assess the spatio-temporal variation and development of phytobenthos and phytoplankton communities using a combination of stable isotope and community analyses in a temperate southern African system across four study periods: September (early spring) and November/December (late spring) 2012, and February (summer) and May/June (winter) 2013. Additionally, the sources and composition of the particulate organic matter were also analysed using stable isotope (δ15N and δ13C) analysis. The effects of substrate type and flood occurrence were assessed through experimental studies at an up- and downstream site of the river after a major flood event that occurred between October and November 2012. Common household tiles were used as artificial substrates to study the development/succession of phytobenthos communities after the flood disturbance. Distinct diatom communities were observed between upstream and downstream sites and at each site, community structure changed with time indicating succession. In addition to recording diatom characteristics on three natural substrates, namely; macrophytes, rocks and sediment, artificial substrates observations were also made on three different types of artificial substrates, namely; brick, brown clay and grey clay tiles. The natural (species richness 78) and artificial substrates (sp. richness 93) had different communities with the latter having greater species richness. Common phytobenthos taxa were not restricted to a single substrate but preference was generally high for the artificial substrates, especially brown tiles (mean sp. richness 47). Results of the redundancy analysis (RDA) analysis indicated that ammonium, conductivity, total dissolved solids, salinity, pH, oxygen reduction potential, phosphate and water depth were the major determinants of the phytobenthos composition at the two sites. The spatio–temporal variation of phytoplankton and phytobenthos communities and allochthonous organic matter along the river–estuary continuum was assessed at 8 sites using a combination of community and stable isotope analyses. A total of 178 species belonging to 78 genera were recorded with diatoms being predominant, accounting for 81.9 % of the total abundance. The total chl-a concentration along the river-estuary continuum increased from spring to a high in summer before decreasing to a low in winter. Periphyton communities were observed to be significantly different across sites (p < 0.05) in terms of species richness, abundances and isotopically The high periphytic δ15N values (range 7.9–15.2 ‰) recorded at the downstream sites compared to the pristine upstream sites (δ15N values range 4–7 ‰) suggest nutrient enrichment most likely derived from anthropogenic sources. Overall, our results reveal general patterns of periphyton communities and stable isotopes and provide improved information in the use of periphyton δ15N as an excellent indicator of anthropogenic nitrogen pollution. Ecologists are interested in the factors that control, and the variability in, the contributions of different sources to mixed organic materials traveling through lotic systems. We hypothesized that the source matter fuelling mixed organic pools in a river-estuary continuum varies over space and time, with the upper reaches of a system characterized by allochthonous-dominated material and autochthonous contributions becoming more important in the lower reaches. Samples of the mixed organic pools and allochthonous and autochthonous source materials were collected during the four study periods. The C:N ratios of suspended particulate matter (SPM) collected during summer and winter indicated that the lower reaches of the system had similar organic matter contributions from the freshwater and terrestrial sources. Stable isotope analysis in R revealed that the contributions of autochthonous organic matter were high in SPM along the entire continuum, and aquatic macrophytes were significant contributors to SPM specifically in the upper reaches. The terrestrial leaves made major contributions to the SPM in the middle regions of the system (i.e. downstream sites of the river, particularly in early and late spring). Bulk detritus had large allochthonous matter components in the lower reaches (estuary), and the contributions of aquatic macrophytes and benthic algae to bulk detritus were high (> 50 %) in the upper to middle reaches (river), but low (< 20 %) in the lower reaches (estuary). The current investigation represents the first attempt to assess the validity of the River Continuum Concept (RCC) in a southern African temperate river. The phytoplankton and phytobenthos communities, and chl-a concentration followed a trend similar to that proposed for the river continuum concept (RCC). The middle reaches based on the phytobenthos or phytoplankton communities and chl-a concentrations which were employed as proxies for primary production, were the most productive, while the upper reaches were the least primary productive. The evaluation of organic matter contributions to the SPM and detritus along the river–estuary continuum provided a baseline assessment of the nature and sources of potential food for consumers inhabiting different locations during different times of the year. Incorporating such spatio-temporal variations in SPM and detritus into food web studies will improve our understanding of the flow of carbon through aquatic systems.
- Full Text:
- Date Issued: 2015
- Authors: Dalu, Tatenda
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54416 , vital:26563
- Description: Phytoplankton and phytobenthos communities play an important role in lotic systems as primary producers providing essential biomolecules to higher trophic oganisms and are important indicators for environmental or ecological change. In this thesis, field studies (observational and experimental) along a river–estuary continuum were conducted to assess the spatio-temporal variation and development of phytobenthos and phytoplankton communities using a combination of stable isotope and community analyses in a temperate southern African system across four study periods: September (early spring) and November/December (late spring) 2012, and February (summer) and May/June (winter) 2013. Additionally, the sources and composition of the particulate organic matter were also analysed using stable isotope (δ15N and δ13C) analysis. The effects of substrate type and flood occurrence were assessed through experimental studies at an up- and downstream site of the river after a major flood event that occurred between October and November 2012. Common household tiles were used as artificial substrates to study the development/succession of phytobenthos communities after the flood disturbance. Distinct diatom communities were observed between upstream and downstream sites and at each site, community structure changed with time indicating succession. In addition to recording diatom characteristics on three natural substrates, namely; macrophytes, rocks and sediment, artificial substrates observations were also made on three different types of artificial substrates, namely; brick, brown clay and grey clay tiles. The natural (species richness 78) and artificial substrates (sp. richness 93) had different communities with the latter having greater species richness. Common phytobenthos taxa were not restricted to a single substrate but preference was generally high for the artificial substrates, especially brown tiles (mean sp. richness 47). Results of the redundancy analysis (RDA) analysis indicated that ammonium, conductivity, total dissolved solids, salinity, pH, oxygen reduction potential, phosphate and water depth were the major determinants of the phytobenthos composition at the two sites. The spatio–temporal variation of phytoplankton and phytobenthos communities and allochthonous organic matter along the river–estuary continuum was assessed at 8 sites using a combination of community and stable isotope analyses. A total of 178 species belonging to 78 genera were recorded with diatoms being predominant, accounting for 81.9 % of the total abundance. The total chl-a concentration along the river-estuary continuum increased from spring to a high in summer before decreasing to a low in winter. Periphyton communities were observed to be significantly different across sites (p < 0.05) in terms of species richness, abundances and isotopically The high periphytic δ15N values (range 7.9–15.2 ‰) recorded at the downstream sites compared to the pristine upstream sites (δ15N values range 4–7 ‰) suggest nutrient enrichment most likely derived from anthropogenic sources. Overall, our results reveal general patterns of periphyton communities and stable isotopes and provide improved information in the use of periphyton δ15N as an excellent indicator of anthropogenic nitrogen pollution. Ecologists are interested in the factors that control, and the variability in, the contributions of different sources to mixed organic materials traveling through lotic systems. We hypothesized that the source matter fuelling mixed organic pools in a river-estuary continuum varies over space and time, with the upper reaches of a system characterized by allochthonous-dominated material and autochthonous contributions becoming more important in the lower reaches. Samples of the mixed organic pools and allochthonous and autochthonous source materials were collected during the four study periods. The C:N ratios of suspended particulate matter (SPM) collected during summer and winter indicated that the lower reaches of the system had similar organic matter contributions from the freshwater and terrestrial sources. Stable isotope analysis in R revealed that the contributions of autochthonous organic matter were high in SPM along the entire continuum, and aquatic macrophytes were significant contributors to SPM specifically in the upper reaches. The terrestrial leaves made major contributions to the SPM in the middle regions of the system (i.e. downstream sites of the river, particularly in early and late spring). Bulk detritus had large allochthonous matter components in the lower reaches (estuary), and the contributions of aquatic macrophytes and benthic algae to bulk detritus were high (> 50 %) in the upper to middle reaches (river), but low (< 20 %) in the lower reaches (estuary). The current investigation represents the first attempt to assess the validity of the River Continuum Concept (RCC) in a southern African temperate river. The phytoplankton and phytobenthos communities, and chl-a concentration followed a trend similar to that proposed for the river continuum concept (RCC). The middle reaches based on the phytobenthos or phytoplankton communities and chl-a concentrations which were employed as proxies for primary production, were the most productive, while the upper reaches were the least primary productive. The evaluation of organic matter contributions to the SPM and detritus along the river–estuary continuum provided a baseline assessment of the nature and sources of potential food for consumers inhabiting different locations during different times of the year. Incorporating such spatio-temporal variations in SPM and detritus into food web studies will improve our understanding of the flow of carbon through aquatic systems.
- Full Text:
- Date Issued: 2015
The isolation, characterisation and chemotaxonomic significance of secondary metabolites from selected South African Laurencia spp. Rhodophyta
- Authors: Fakee, Jameel
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64696 , vital:28593
- Description: Bioprospection of marine organisms as a potential source for lead drugs is becoming increasingly popular. The secondary metabolome of these organisms consists of structurally diverse molecules possessing unprecedented carbon skeletons, the biosynthesis of which occurs via complex metabolomic pathways driven by specialist enzymes. This structural novelty is highly influential on the favourable bioactivity these compounds display. A prominent example of such a compound is trabectedin marketed as Yondelis®. Registered for the treatment of soft tissue sarcomas, this marine drug was developed from extracts of the tunicate Ecteinascidia turbinata. South Africa is renowned for possessing a highly diverse marine biota including several endemic species of marine red algae belonging to the Laurencia sensu stricto genus, which falls within the Laurencia complex. Despite having a good reputation for fascinating secondary metabolites, the taxonomy of Laurencia natural products is proving challenging for reasons including the presence of cryptic species, as well as individual species displaying morphological variability. The aim of this study was thus to isolate secondary metabolites from various South African Laurencia spp. and subsequently assess their chemotaxonomic significance by analysis of a parallel plastid rbcL phylogeny study of Laurencia spp. This study reports the first phycochemical investigation into Laurencia natalensis Kylin, Laurencia cf. corymbosa J.Agardh, Laurencia complanata (Suhr) Kützing, Laurencia sodwaniensis Francis, Bolton, Mattio and Anderson submitted, Laurencia multiclavata Francis, Bolton, Mattio and Anderson submitted, and a South African specimen of Laurenciella marilzae Gil-Rodríguez, Sentíes, Díaz-Larrea, Cassano and M.T. Fujii (basionym: Laurencia marilzae) originally described from Spain. Additionally, the chemical profiles of previously explored species Laurencia flexuosa Kützing and Laurencia glomerata Kützing were re-investigated. The organic extracts of the above species afforded 31 compounds belonging to a wide array of structural classes including halo-chamigranes, linear C15 acetogenins, indole alkaloids, cuparanes and cyclic bromo-ethers. A new tri-cyclic keto-cuparane (4.4) was isolated from L.cf. corymbosa alongside the new cuparanes 4.1 and 4.7. Algoane (5.9), a unique marker compound isolated from L. natalensis, was previously only reported from a sea-hare. Such marker compounds which are exclusive to an individual algal species increase the ease of their subsequent identification. The feasibility of chemotaxonomy as an additional tool to classify Laurencia spp. Was established as broad predictions of a specimen’s phylogeny, based on representatives of its secondary metabolome, proved viable. The study specimens were shown to possess similar chemical profiles to their sister species e.g. L. complanata, L. sodwaniensis and L. multiclavata produced similar metabolites to their sister species as inferred by an rbcL phylogeny tree. Finally, a 1H NMR profiling study on the crude organic extracts of various Laurencia spp. generated distinctive, reproducible spectra, exposing the value of NMR spectroscopy as a rudimentary species discernment tool.
- Full Text:
- Date Issued: 2015
- Authors: Fakee, Jameel
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64696 , vital:28593
- Description: Bioprospection of marine organisms as a potential source for lead drugs is becoming increasingly popular. The secondary metabolome of these organisms consists of structurally diverse molecules possessing unprecedented carbon skeletons, the biosynthesis of which occurs via complex metabolomic pathways driven by specialist enzymes. This structural novelty is highly influential on the favourable bioactivity these compounds display. A prominent example of such a compound is trabectedin marketed as Yondelis®. Registered for the treatment of soft tissue sarcomas, this marine drug was developed from extracts of the tunicate Ecteinascidia turbinata. South Africa is renowned for possessing a highly diverse marine biota including several endemic species of marine red algae belonging to the Laurencia sensu stricto genus, which falls within the Laurencia complex. Despite having a good reputation for fascinating secondary metabolites, the taxonomy of Laurencia natural products is proving challenging for reasons including the presence of cryptic species, as well as individual species displaying morphological variability. The aim of this study was thus to isolate secondary metabolites from various South African Laurencia spp. and subsequently assess their chemotaxonomic significance by analysis of a parallel plastid rbcL phylogeny study of Laurencia spp. This study reports the first phycochemical investigation into Laurencia natalensis Kylin, Laurencia cf. corymbosa J.Agardh, Laurencia complanata (Suhr) Kützing, Laurencia sodwaniensis Francis, Bolton, Mattio and Anderson submitted, Laurencia multiclavata Francis, Bolton, Mattio and Anderson submitted, and a South African specimen of Laurenciella marilzae Gil-Rodríguez, Sentíes, Díaz-Larrea, Cassano and M.T. Fujii (basionym: Laurencia marilzae) originally described from Spain. Additionally, the chemical profiles of previously explored species Laurencia flexuosa Kützing and Laurencia glomerata Kützing were re-investigated. The organic extracts of the above species afforded 31 compounds belonging to a wide array of structural classes including halo-chamigranes, linear C15 acetogenins, indole alkaloids, cuparanes and cyclic bromo-ethers. A new tri-cyclic keto-cuparane (4.4) was isolated from L.cf. corymbosa alongside the new cuparanes 4.1 and 4.7. Algoane (5.9), a unique marker compound isolated from L. natalensis, was previously only reported from a sea-hare. Such marker compounds which are exclusive to an individual algal species increase the ease of their subsequent identification. The feasibility of chemotaxonomy as an additional tool to classify Laurencia spp. Was established as broad predictions of a specimen’s phylogeny, based on representatives of its secondary metabolome, proved viable. The study specimens were shown to possess similar chemical profiles to their sister species e.g. L. complanata, L. sodwaniensis and L. multiclavata produced similar metabolites to their sister species as inferred by an rbcL phylogeny tree. Finally, a 1H NMR profiling study on the crude organic extracts of various Laurencia spp. generated distinctive, reproducible spectra, exposing the value of NMR spectroscopy as a rudimentary species discernment tool.
- Full Text:
- Date Issued: 2015
Bacterial degradation of fossil fuel waste in aqueous and solid media
- Authors: Edeki, Oghenekume Gerald
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54565 , vital:26588
- Description: The generation of environmental pollutants worldwide is mainly due to over reliance on fossil fuels as a source of energy. As a result of the negative impacts of these pollutants on the health of humans, animals, plants and microorganisms, global attention has been directed towards ways of containing this problem. Biodegradation of fossil fuel is one of the most effective methods used to remediate contaminated systems. However with regard to coal waste, much of what is known is based on the ability of fungal species to biosolubilize this material under enrichment conditions in a laboratory setting. For effective biodegradation as a remediation technique, there is an immediate need to source, isolate, enrich and incorporate other microorganisms such as bacteria into bioremediation technologies. The goal of this dissertation was to isolate bacteria from fossil fuel contaminated environments and to demonstrate competence for petroleum hydrocarbon degradation which was achieved using a combination of analytical methods such as spectrophotometry, FT-IR, SEM and GC-MS. Screening for biodegradation of coal and petroleum hydrocarbon waste resulted in the isolation of 75 bacterial strains of which 15 showed good potential for use in developing remedial biotechnologies. Spectrophotometric analysis of bacteria both in coal and petroleum hydrocarbons (all in aqueous media) revealed a high proliferation of bacteria in these media suggesting that these microbes can effectively utilize the various substrates as a source of carbon. The isolated bacteria effectively degraded and converted waste coal to humic and fulvic acids; products required to enrich coal mine dumps to support re-vegetation. Scanning electron microscopy showed the attachment of bacteria to waste coal surfaces and the disintegration of coal structures while FT-IR analysis of extracted humic-like substances from biodegraded waste coal revealed these to have the same functional groups as commercial humic acid. Specific consortia which were established using the isolated bacterial strains, showed greater potential to biodegrade coal than did individual isolates. This was evident in experiments carried out on coal and hydrocarbons where the efficient colonization and utilization of these substrates by each bacterial consortium was observed due to the effect of added nutrients such as algae. The biodegradation of liquid petroleum hydrocarbons (diesel and BTEX) was also achieved using the 15 bacterial isolates. GC-MS analysis of extracted residual PHC from aqueous and solid media revealed rapid breakdown of these contaminants by bacteria. Different bacterial consortia established from the individual isolates were shown to be more efficient than single isolates indicating that formulated consortia are the biocatalysts of choice for fossil fuel biodegradation. This study represents one of the most detailed screenings for bacteria from fossil fuel contaminated sites and the isolation of strains with potential to biodegrade coal and petroleum hydrocarbon wastes. Several consortia have been developed and these show potential for further development as biocatalysts for use in bioremediation technology development. An evaluation of efficiency of each established bacterial consortium for biodegradation in a commercial and/or industrial setting at pilot scale is now needed.
- Full Text:
- Date Issued: 2015
- Authors: Edeki, Oghenekume Gerald
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/54565 , vital:26588
- Description: The generation of environmental pollutants worldwide is mainly due to over reliance on fossil fuels as a source of energy. As a result of the negative impacts of these pollutants on the health of humans, animals, plants and microorganisms, global attention has been directed towards ways of containing this problem. Biodegradation of fossil fuel is one of the most effective methods used to remediate contaminated systems. However with regard to coal waste, much of what is known is based on the ability of fungal species to biosolubilize this material under enrichment conditions in a laboratory setting. For effective biodegradation as a remediation technique, there is an immediate need to source, isolate, enrich and incorporate other microorganisms such as bacteria into bioremediation technologies. The goal of this dissertation was to isolate bacteria from fossil fuel contaminated environments and to demonstrate competence for petroleum hydrocarbon degradation which was achieved using a combination of analytical methods such as spectrophotometry, FT-IR, SEM and GC-MS. Screening for biodegradation of coal and petroleum hydrocarbon waste resulted in the isolation of 75 bacterial strains of which 15 showed good potential for use in developing remedial biotechnologies. Spectrophotometric analysis of bacteria both in coal and petroleum hydrocarbons (all in aqueous media) revealed a high proliferation of bacteria in these media suggesting that these microbes can effectively utilize the various substrates as a source of carbon. The isolated bacteria effectively degraded and converted waste coal to humic and fulvic acids; products required to enrich coal mine dumps to support re-vegetation. Scanning electron microscopy showed the attachment of bacteria to waste coal surfaces and the disintegration of coal structures while FT-IR analysis of extracted humic-like substances from biodegraded waste coal revealed these to have the same functional groups as commercial humic acid. Specific consortia which were established using the isolated bacterial strains, showed greater potential to biodegrade coal than did individual isolates. This was evident in experiments carried out on coal and hydrocarbons where the efficient colonization and utilization of these substrates by each bacterial consortium was observed due to the effect of added nutrients such as algae. The biodegradation of liquid petroleum hydrocarbons (diesel and BTEX) was also achieved using the 15 bacterial isolates. GC-MS analysis of extracted residual PHC from aqueous and solid media revealed rapid breakdown of these contaminants by bacteria. Different bacterial consortia established from the individual isolates were shown to be more efficient than single isolates indicating that formulated consortia are the biocatalysts of choice for fossil fuel biodegradation. This study represents one of the most detailed screenings for bacteria from fossil fuel contaminated sites and the isolation of strains with potential to biodegrade coal and petroleum hydrocarbon wastes. Several consortia have been developed and these show potential for further development as biocatalysts for use in bioremediation technology development. An evaluation of efficiency of each established bacterial consortium for biodegradation in a commercial and/or industrial setting at pilot scale is now needed.
- Full Text:
- Date Issued: 2015
If I Stay Right Here
- Authors: Ngamlana, Chwayita
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193498 , vital:45337
- Description: My novella concerns the dynamics of a relationship between two girls. It shows the heterosexual‐like nature of the relationship rather than dwelling on the pressures on lesbians from society as a whole. At its core is the raw emotion and passion of the relationship, which is at the same time toxic, destructive and volatile because of their class differences and other insecurities. The work is influenced by the grit, openness, and innovation of several contemporary writers. , Thesis (MA) -- Faculty of Humanities, Institute for the Study of English in Africa, 2015
- Full Text:
- Date Issued: 2015
- Authors: Ngamlana, Chwayita
- Date: 2015
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/193498 , vital:45337
- Description: My novella concerns the dynamics of a relationship between two girls. It shows the heterosexual‐like nature of the relationship rather than dwelling on the pressures on lesbians from society as a whole. At its core is the raw emotion and passion of the relationship, which is at the same time toxic, destructive and volatile because of their class differences and other insecurities. The work is influenced by the grit, openness, and innovation of several contemporary writers. , Thesis (MA) -- Faculty of Humanities, Institute for the Study of English in Africa, 2015
- Full Text:
- Date Issued: 2015
An exploration of business level strategy at the bottom of the pyramid: a case study of Twizza, Eastern Cape
- Authors: Sityoshwana, Ludwe Lusu
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/54486 , vital:26569
- Description: This qualitative study focuses on business level strategy adopted by Twizza to compete in the bottom of the pyramid market in the Eastern Cape, South Africa. Twizza enjoyed huge success between the years 2010 - 2014 as a medium to large sized manufacturer of carbonated soft drinks in the Eastern Cape. In light of this, the current study seeks to answer the following: What business level strategy did top management at Twizza adopt to compete and grow in the BoP market in the Eastern Cape, South Africa? The study takes the form of a case study to explore and understand the patterns of decisions adopted by Twizza’s top management in competing at the bottom of the pyramid. As such, the main objective of the study was to identify the business level strategy adopted by Twizza which enabled their superior performance within the BoP market. The study adopts Porter`s typology to explore business level strategy. Stratified, purposive sampling was used to identify 4 top managers as participants in this study. A total of 7, semi-structured, interviews were used to collect critical incidents from top management of Twizza. This was the primary data used in this study. This type of data was combined with relevant information which was gathered via published press articles and on-line commentary. The study found that central to Twizza’s business strategy were four pillars, namely, strict control and management of manufacturing costs, product quality equal to that of market leaders, the ability of the organisation to manufacture its own raw materials and ability to ensure product availability to the market to the market. These findings reveal that Twizza employed a hybrid strategy, anchored by cost leadership. Thus, Twizza incorporated elements of differentiation and best value strategies to offer its customers affordable quality.
- Full Text:
- Date Issued: 2015
- Authors: Sityoshwana, Ludwe Lusu
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/54486 , vital:26569
- Description: This qualitative study focuses on business level strategy adopted by Twizza to compete in the bottom of the pyramid market in the Eastern Cape, South Africa. Twizza enjoyed huge success between the years 2010 - 2014 as a medium to large sized manufacturer of carbonated soft drinks in the Eastern Cape. In light of this, the current study seeks to answer the following: What business level strategy did top management at Twizza adopt to compete and grow in the BoP market in the Eastern Cape, South Africa? The study takes the form of a case study to explore and understand the patterns of decisions adopted by Twizza’s top management in competing at the bottom of the pyramid. As such, the main objective of the study was to identify the business level strategy adopted by Twizza which enabled their superior performance within the BoP market. The study adopts Porter`s typology to explore business level strategy. Stratified, purposive sampling was used to identify 4 top managers as participants in this study. A total of 7, semi-structured, interviews were used to collect critical incidents from top management of Twizza. This was the primary data used in this study. This type of data was combined with relevant information which was gathered via published press articles and on-line commentary. The study found that central to Twizza’s business strategy were four pillars, namely, strict control and management of manufacturing costs, product quality equal to that of market leaders, the ability of the organisation to manufacture its own raw materials and ability to ensure product availability to the market to the market. These findings reveal that Twizza employed a hybrid strategy, anchored by cost leadership. Thus, Twizza incorporated elements of differentiation and best value strategies to offer its customers affordable quality.
- Full Text:
- Date Issued: 2015
Challenges of post-apartheid state-owned company pension fund reform: a case study of the controversy around the Transnet-Transport Pension Fund
- Authors: Goqoza, Noluyolo Juliet
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSocSc
- Identifier: http://hdl.handle.net/10962/54766 , vital:26610
- Description: This thesis examines the restructuring of the pension funds of Transnet, a South African state-owned company involved in transportation, from the 1990s. Two of its main pension funds, the Transport-Transnet Pension sub-Fund (TTPF) and the Transnet Second Defined Benefit Fund (TSDBF), have been surrounded by controversy, with major court actions brought by aggrieved pensioners in 2006-2012 and again from 2013, and smaller cases in 1997-1999 and 2004. (There were also a number of smaller cases, mostly unsuccessful, but the thesis will not examine them). The case that started in 2013 is the biggest class action in the country‟s history, and makes claims of serious mismanagement and bad faith against the Transnet management. But the fundamental grievance is that (according to the 2013 legal case) “more than 80% of pensioners earn less than R4 000.00 a month… 62 % earn less than R2 500.00… 45% of the pensioners earn less than the state‟s ordinary old-age pension” grant for the poor. Although that case is ongoing, this thesis examines the background and controversies that frame the case. It provides an overview of the history and development of the South African pensions system and South African state-owned companies; it examines how these have been shaped by the apartheid and post-apartheid periods, and by the rise of neo-liberalism; it examines the evolution of Transnet and its pensions systems, from the early days of the South African Railways and Harbours Administration (SAR&H, formed 1910), to its restructuring into the South African Transport Services (SATS) in 1982, and then into Transnet in 1990. The thesis shows that the operations of the TTPF and TSDBF, which are closed to new members, have had serious effects on pensioners that rely upon them. Pensions are very low (the main reason for the various court cases), and this is for a range of reasons. Annual increases in pensions are formally set at below-inflation levels, leading to falling real incomes. More pressure on pensioners‟ livelihoods has arisen from Transnet‟s cuts to other benefits, like the medical aid Transmed, provided to pensioners. While the schemes are solvent, the pensions generally started at a low base, partly because most pensioners were relatively poorly paid workers before retirement (and the pensions were linked to former salaries). There is also a racial dimension: while most white workers at SAR&H/ SATS and Transnet were poorly paid, black, Coloured and Indian workers were paid even worse, and, further, were only brought into the pension schemes late. Both TTPF and TSDBF are defined benefit funds, which means members are guaranteed specific benefits at retirement, with the employer obligated to inject funds to meet shortfalls where needed. Yet neither the state nor Transnet has been willing to take actions to lift the basic pensions, such as investments into the funds, or to make systematic ex gratia payments to bring the pensions to a reasonable level, to remove historic racial inequalities between pensioners, to increase medical aid co-payments or coverage or to otherwise address the pensioners‟ situation. It does not seem that the reason for the problems is that the two funds have been severely mismanaged or asset-stripped, as alleged in the 2013 class action: it must be noted that both funds report surpluses. But the surpluses are possible because the pensions are low and falling in real terms, and the numbers of pensioners declining due to deaths. It seems clear that Transnet is unable or unwilling to act to decisively improve the situation of the pensioners: ensuring a surplus on existing pension funds is a major goal. This is partly because Transnet itself has ongoing financial problems, and partly because it operates in the context of neo-liberal restructuring, like corporatisation, commercialisation and privatisation, which places limits on the additional funding of the funds. At the same time, the pensioners have very little real, as opposed to a nominal, say in the administration of the pension schemes, limiting their ability to affect the rules and administration or raise issues. The thesis seeks to use historical institutionalism, which sees policies and major institutions, including state-owned companies, as shaped by power and conflict, especially between classes. This is used to try and explain changing state policies and the changing role and actions of state-owned companies, as a way of understanding Transnet‟s actions, as well as its treatment of its pensioners.
- Full Text:
- Date Issued: 2015
- Authors: Goqoza, Noluyolo Juliet
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSocSc
- Identifier: http://hdl.handle.net/10962/54766 , vital:26610
- Description: This thesis examines the restructuring of the pension funds of Transnet, a South African state-owned company involved in transportation, from the 1990s. Two of its main pension funds, the Transport-Transnet Pension sub-Fund (TTPF) and the Transnet Second Defined Benefit Fund (TSDBF), have been surrounded by controversy, with major court actions brought by aggrieved pensioners in 2006-2012 and again from 2013, and smaller cases in 1997-1999 and 2004. (There were also a number of smaller cases, mostly unsuccessful, but the thesis will not examine them). The case that started in 2013 is the biggest class action in the country‟s history, and makes claims of serious mismanagement and bad faith against the Transnet management. But the fundamental grievance is that (according to the 2013 legal case) “more than 80% of pensioners earn less than R4 000.00 a month… 62 % earn less than R2 500.00… 45% of the pensioners earn less than the state‟s ordinary old-age pension” grant for the poor. Although that case is ongoing, this thesis examines the background and controversies that frame the case. It provides an overview of the history and development of the South African pensions system and South African state-owned companies; it examines how these have been shaped by the apartheid and post-apartheid periods, and by the rise of neo-liberalism; it examines the evolution of Transnet and its pensions systems, from the early days of the South African Railways and Harbours Administration (SAR&H, formed 1910), to its restructuring into the South African Transport Services (SATS) in 1982, and then into Transnet in 1990. The thesis shows that the operations of the TTPF and TSDBF, which are closed to new members, have had serious effects on pensioners that rely upon them. Pensions are very low (the main reason for the various court cases), and this is for a range of reasons. Annual increases in pensions are formally set at below-inflation levels, leading to falling real incomes. More pressure on pensioners‟ livelihoods has arisen from Transnet‟s cuts to other benefits, like the medical aid Transmed, provided to pensioners. While the schemes are solvent, the pensions generally started at a low base, partly because most pensioners were relatively poorly paid workers before retirement (and the pensions were linked to former salaries). There is also a racial dimension: while most white workers at SAR&H/ SATS and Transnet were poorly paid, black, Coloured and Indian workers were paid even worse, and, further, were only brought into the pension schemes late. Both TTPF and TSDBF are defined benefit funds, which means members are guaranteed specific benefits at retirement, with the employer obligated to inject funds to meet shortfalls where needed. Yet neither the state nor Transnet has been willing to take actions to lift the basic pensions, such as investments into the funds, or to make systematic ex gratia payments to bring the pensions to a reasonable level, to remove historic racial inequalities between pensioners, to increase medical aid co-payments or coverage or to otherwise address the pensioners‟ situation. It does not seem that the reason for the problems is that the two funds have been severely mismanaged or asset-stripped, as alleged in the 2013 class action: it must be noted that both funds report surpluses. But the surpluses are possible because the pensions are low and falling in real terms, and the numbers of pensioners declining due to deaths. It seems clear that Transnet is unable or unwilling to act to decisively improve the situation of the pensioners: ensuring a surplus on existing pension funds is a major goal. This is partly because Transnet itself has ongoing financial problems, and partly because it operates in the context of neo-liberal restructuring, like corporatisation, commercialisation and privatisation, which places limits on the additional funding of the funds. At the same time, the pensioners have very little real, as opposed to a nominal, say in the administration of the pension schemes, limiting their ability to affect the rules and administration or raise issues. The thesis seeks to use historical institutionalism, which sees policies and major institutions, including state-owned companies, as shaped by power and conflict, especially between classes. This is used to try and explain changing state policies and the changing role and actions of state-owned companies, as a way of understanding Transnet‟s actions, as well as its treatment of its pensioners.
- Full Text:
- Date Issued: 2015
Appraising the appraisal framework: evidence from Grahamstown property advertisements
- Authors: Beangstrom, Tracy
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/54744 , vital:26608
- Description: This thesis considers how interpersonal meaning choices in property advertisements are best reflected in a context of constraint in Grahamstown, South Africa, using and appraising Martin & White’s (2005) APPRAISAL Framework. The study is comparative in two senses since the data is analysed using Martin & White’s (2005) APPRAISAL Framework and a revision to it, and property advertisements from two competing estate agencies are analysed: Remax Frontier Properties and Pam Golding Properties. An initial strict application of Martin & White’s (2005) framework is followed by a second, based on analyst difficulties and framework limitations experienced in the first analysis, as well as those experienced by other researchers. Revisions to the original framework include added ‘local’, context-driven features and sub-categories: Exclusivity and Convenience in Attitude, a Scale of Intensity in Graduation, and a category ‘Invite’ in Engagement. These enable a richer, more detailed account of the alignment strategies and interpersonal micro-politics at play in the property advertisements than is possible using the original framework. Findings from the analyses reveal four facts of note. Firstly, that while the original Martin & White (2005) APPRAISAL Framework captures a general level of interpersonal meaning in the data, it does so more fully when it includes contextual and contextually-driven categories that are informed by local knowledge. Secondly, two levels of meaning are expressed in the data. One is aimed at an ‘external’ audience; the other, truer, fuller and more contentious, is aimed at what appears to be the intended audience only. Thirdly, and relatedly, specific contextual and cultural knowledge is needed by the intended audience to access the intended meaning. Fourthly, both estate agencies promote values of high prestige, exclusivity, elitism and wealth as their intended meaning to align a like-minded audience, although Remax Frontier Properties attribute these values to location and features of the home to a greater extent than Pam Golding Properties, who place greater emphasis on the size of the home. The thesis suggests further avenues for research into the discourse of property advertising, as well as into overcoming certain context-specific limitations of the APPRAISAL Framework.
- Full Text:
- Date Issued: 2015
- Authors: Beangstrom, Tracy
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/54744 , vital:26608
- Description: This thesis considers how interpersonal meaning choices in property advertisements are best reflected in a context of constraint in Grahamstown, South Africa, using and appraising Martin & White’s (2005) APPRAISAL Framework. The study is comparative in two senses since the data is analysed using Martin & White’s (2005) APPRAISAL Framework and a revision to it, and property advertisements from two competing estate agencies are analysed: Remax Frontier Properties and Pam Golding Properties. An initial strict application of Martin & White’s (2005) framework is followed by a second, based on analyst difficulties and framework limitations experienced in the first analysis, as well as those experienced by other researchers. Revisions to the original framework include added ‘local’, context-driven features and sub-categories: Exclusivity and Convenience in Attitude, a Scale of Intensity in Graduation, and a category ‘Invite’ in Engagement. These enable a richer, more detailed account of the alignment strategies and interpersonal micro-politics at play in the property advertisements than is possible using the original framework. Findings from the analyses reveal four facts of note. Firstly, that while the original Martin & White (2005) APPRAISAL Framework captures a general level of interpersonal meaning in the data, it does so more fully when it includes contextual and contextually-driven categories that are informed by local knowledge. Secondly, two levels of meaning are expressed in the data. One is aimed at an ‘external’ audience; the other, truer, fuller and more contentious, is aimed at what appears to be the intended audience only. Thirdly, and relatedly, specific contextual and cultural knowledge is needed by the intended audience to access the intended meaning. Fourthly, both estate agencies promote values of high prestige, exclusivity, elitism and wealth as their intended meaning to align a like-minded audience, although Remax Frontier Properties attribute these values to location and features of the home to a greater extent than Pam Golding Properties, who place greater emphasis on the size of the home. The thesis suggests further avenues for research into the discourse of property advertising, as well as into overcoming certain context-specific limitations of the APPRAISAL Framework.
- Full Text:
- Date Issued: 2015
Formulation, development and assessment of tenofovir disoproxil fumarate-loaded pellets
- Authors: Dube, Tawanda
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54690 , vital:26600
- Description: Tenofovir disoproxil fumarate (TDF) is a novel nucleotide analog reverse transcriptase inhibitor that is recommended by the WHO for use in first line treatment of HIV infections. Due to the high dose of TDF for anti-retroviral treatment the formulation of a pellet dosage form may improve patient adherence by incorporation of a large dose in a relatively small dosage form. TDF is currently only available in tablet form. A simple, sensitive, selective, rapid, accurate, precise, stability indicating reversed-phase HPLC method was developed and validated in accordance with ICH guidelines and was successfully used for the analysis of TDF raw material and pharmaceutical dosage forms. Preformulation studies included an investigation of TDF-excipient and excipient-excipient interactions with all materials that could potentially be used to produce extruded and spheronized pellets. Nuclear Magnetic Resonance spectroscopy (NMR), Infrared Spectroscopy (IR), Differential Scanning Colorimetry (DSC) and Thermogravimetric analysis were used for identification and purity testing of TDF and all excipients. DSC data revealed that no potential interactions between TDF and the excipients occurred suggesting that incompatibility reactions were unlikely during manufacture and storage. These findings were confirmed by IR analysis that revealed that no physical interaction was likely between any of the excipients used and TDF. DSC data also reveal the existence of the α and β-polymorphs of TDF as evidenced by two enthalpy changes observed on the resultant thermograms. The existence of two polymorphs is unlikely to result in incompatibility and was confirmed by IR analysis. The IR spectra reveal that all characteristic peaks for TDF were present in 1:1 binary mixtures. Therefore TDF is compatible with all excipients tested and thermal analysis confirmed the stability of TDF under manufacturing conditions. The temperature of degradation temperature established through DSC analysis confirmed that degradation during manufacture is unlikely as the temperature of manufacture is lower than that at which degradation occurs. Extrusion and spheronization were the processes used to manufacture TDF pellets as it is a simple and economic approach for production. The effects of extruder and spheronizer speed, amount of spheronization aid and diluents on the pellet size, shape, flow properties and TDF release characteristics were examined. In order to decrease the complexity of analysis and reduce the cost of development a Taguchi orthogonal array design of experiments was successfully applied to evaluate the impact of formulation variables on product characteristics and predict an optimized formulation with a minimum number of experiments. The use of Response Surface Methodology for the development and optimization of pharmaceutical systems, including the optimization of formulation composition, manufacturing processes and/or analytical methods is well established. However the application of RSM requires that accurate, precise and reproducible experimental conditions are used for the generation of reliable data and RSM use is limited due to sensitivity to experimental variability. The benefits of using RSM for formulation optimization include the fact that more than one variable can be investigated at a time and large amounts of information can be generated at the same time ensuring a more efficient process with respect to time and cost. An added advantage of this approach is that mathematical relationships can be generated for the models that are produced and provide formulation scientists with an indication of whether the effect(s) between factors are synergistic or antagonistic. There are several statistical design approaches that use RSM and a Taguchi orthogonal array design was selected for use in this optimization process as fewer experiments are required to generate data for the same number of factors to be investigated when compared to other statistical designs such as Central Composite (CCD) and Box-Behnken designs. The use of RSM clearly demonstrates the impact of different input variables on the % TDF released at 45 min and % TDF loaded into the particles. The amount of sorbitol and Kollidon® CL-M were the only significant variables that affected the % TDF released at 45 min and both excipients had an overall synergistic effect on the in vitro release of TDF. The prediction and manufacture of an optimized formulation led to the production of pellets that met predetermined specifications which was successfully achieved using RSM. The development of a TDF containing pellet dosage form has been achieved and the formulation, manufacture and characterization of the dosage form reveal that the product has the potential to be further developed.
- Full Text:
- Date Issued: 2015
- Authors: Dube, Tawanda
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54690 , vital:26600
- Description: Tenofovir disoproxil fumarate (TDF) is a novel nucleotide analog reverse transcriptase inhibitor that is recommended by the WHO for use in first line treatment of HIV infections. Due to the high dose of TDF for anti-retroviral treatment the formulation of a pellet dosage form may improve patient adherence by incorporation of a large dose in a relatively small dosage form. TDF is currently only available in tablet form. A simple, sensitive, selective, rapid, accurate, precise, stability indicating reversed-phase HPLC method was developed and validated in accordance with ICH guidelines and was successfully used for the analysis of TDF raw material and pharmaceutical dosage forms. Preformulation studies included an investigation of TDF-excipient and excipient-excipient interactions with all materials that could potentially be used to produce extruded and spheronized pellets. Nuclear Magnetic Resonance spectroscopy (NMR), Infrared Spectroscopy (IR), Differential Scanning Colorimetry (DSC) and Thermogravimetric analysis were used for identification and purity testing of TDF and all excipients. DSC data revealed that no potential interactions between TDF and the excipients occurred suggesting that incompatibility reactions were unlikely during manufacture and storage. These findings were confirmed by IR analysis that revealed that no physical interaction was likely between any of the excipients used and TDF. DSC data also reveal the existence of the α and β-polymorphs of TDF as evidenced by two enthalpy changes observed on the resultant thermograms. The existence of two polymorphs is unlikely to result in incompatibility and was confirmed by IR analysis. The IR spectra reveal that all characteristic peaks for TDF were present in 1:1 binary mixtures. Therefore TDF is compatible with all excipients tested and thermal analysis confirmed the stability of TDF under manufacturing conditions. The temperature of degradation temperature established through DSC analysis confirmed that degradation during manufacture is unlikely as the temperature of manufacture is lower than that at which degradation occurs. Extrusion and spheronization were the processes used to manufacture TDF pellets as it is a simple and economic approach for production. The effects of extruder and spheronizer speed, amount of spheronization aid and diluents on the pellet size, shape, flow properties and TDF release characteristics were examined. In order to decrease the complexity of analysis and reduce the cost of development a Taguchi orthogonal array design of experiments was successfully applied to evaluate the impact of formulation variables on product characteristics and predict an optimized formulation with a minimum number of experiments. The use of Response Surface Methodology for the development and optimization of pharmaceutical systems, including the optimization of formulation composition, manufacturing processes and/or analytical methods is well established. However the application of RSM requires that accurate, precise and reproducible experimental conditions are used for the generation of reliable data and RSM use is limited due to sensitivity to experimental variability. The benefits of using RSM for formulation optimization include the fact that more than one variable can be investigated at a time and large amounts of information can be generated at the same time ensuring a more efficient process with respect to time and cost. An added advantage of this approach is that mathematical relationships can be generated for the models that are produced and provide formulation scientists with an indication of whether the effect(s) between factors are synergistic or antagonistic. There are several statistical design approaches that use RSM and a Taguchi orthogonal array design was selected for use in this optimization process as fewer experiments are required to generate data for the same number of factors to be investigated when compared to other statistical designs such as Central Composite (CCD) and Box-Behnken designs. The use of RSM clearly demonstrates the impact of different input variables on the % TDF released at 45 min and % TDF loaded into the particles. The amount of sorbitol and Kollidon® CL-M were the only significant variables that affected the % TDF released at 45 min and both excipients had an overall synergistic effect on the in vitro release of TDF. The prediction and manufacture of an optimized formulation led to the production of pellets that met predetermined specifications which was successfully achieved using RSM. The development of a TDF containing pellet dosage form has been achieved and the formulation, manufacture and characterization of the dosage form reveal that the product has the potential to be further developed.
- Full Text:
- Date Issued: 2015
The effect of extracellular Hsp90β and TGF-β1 on colon cancer biology
- Authors: Perks, Tamarin
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55896 , vital:26753
- Description: The TGF-β signaling pathway is known to be one of the most commonly mutated pathways in human cancers, while Hsp90 is a bone fide drug target that is involved in regulating the conformation and activity of many oncoproteins. The role of intracellular Hsp90 in cancer has thus far been established and there is a growing link between extracellular Hsp90 and cancer metastasis, as well as the role of TGF-β in metastasis. This study aimed to analyse the interaction between Hsp90 (both intracellular and extracellular) and the TGF-β machinery in cancer cells, as well as to determine the effect of these proteins on cellular responses on the biology of cancer cells. This was achieved by studying the expression of Hsp90; TGF-βRII and TGF-β1 in cancer cell lines of various origins using flow cytometry, ELISA, and western blot analysis. The genetically paired SW480 and SW620 colon cancer cell lines, derived from a primary tumour and lymph node metastasis, respectively, were selected for further study due to differences in expression levels and activation of the TGF-β1 pathway. SW480 cells expressed double the level of TGF-βRII compared to SW620 cells, while SW620 expressed two times more extracellular TGF-β1 than SW480 cells. A direct interaction between TGF-β1 and Hsp90β was determined in vitro, and confirmed in vivo in SW620 cells. Growth, adhesion and migration were analysed in SW480 and SW620 cells. SW480 cells adhered significantly faster than SW620 cells, while SW620 cells had a greater rate of migration. Inhibiting the TGF-β pathway, specifically TGF-βRI, using SB 431542, as well as inhibiting Hsp90 with novobiocin, caused an increase in migration in SW480 cells. Only the addition of TGF-β1 in combination with Hsp90 as well as SB 431542 caused an increase in migration in SW620 cells. The canonical TGF-β1/TGF-βRI/TGF-βRII pathway may be constitutively active in SW620 cells and the inhibition of TGF-βRI may suggest an alternate pathway or receptor in both SW480 and SW620 cells.
- Full Text:
- Date Issued: 2015
- Authors: Perks, Tamarin
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55896 , vital:26753
- Description: The TGF-β signaling pathway is known to be one of the most commonly mutated pathways in human cancers, while Hsp90 is a bone fide drug target that is involved in regulating the conformation and activity of many oncoproteins. The role of intracellular Hsp90 in cancer has thus far been established and there is a growing link between extracellular Hsp90 and cancer metastasis, as well as the role of TGF-β in metastasis. This study aimed to analyse the interaction between Hsp90 (both intracellular and extracellular) and the TGF-β machinery in cancer cells, as well as to determine the effect of these proteins on cellular responses on the biology of cancer cells. This was achieved by studying the expression of Hsp90; TGF-βRII and TGF-β1 in cancer cell lines of various origins using flow cytometry, ELISA, and western blot analysis. The genetically paired SW480 and SW620 colon cancer cell lines, derived from a primary tumour and lymph node metastasis, respectively, were selected for further study due to differences in expression levels and activation of the TGF-β1 pathway. SW480 cells expressed double the level of TGF-βRII compared to SW620 cells, while SW620 expressed two times more extracellular TGF-β1 than SW480 cells. A direct interaction between TGF-β1 and Hsp90β was determined in vitro, and confirmed in vivo in SW620 cells. Growth, adhesion and migration were analysed in SW480 and SW620 cells. SW480 cells adhered significantly faster than SW620 cells, while SW620 cells had a greater rate of migration. Inhibiting the TGF-β pathway, specifically TGF-βRI, using SB 431542, as well as inhibiting Hsp90 with novobiocin, caused an increase in migration in SW480 cells. Only the addition of TGF-β1 in combination with Hsp90 as well as SB 431542 caused an increase in migration in SW620 cells. The canonical TGF-β1/TGF-βRI/TGF-βRII pathway may be constitutively active in SW620 cells and the inhibition of TGF-βRI may suggest an alternate pathway or receptor in both SW480 and SW620 cells.
- Full Text:
- Date Issued: 2015
An investigation into the feasibility of incorporating ketoconazole into solid lipid microparticles
- Authors: Jhundoo, Henusha Devi
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54701 , vital:26601
- Description: One of the major challenges of the oral administration of ketoconazole (KTZ), an inhibitor of sterol 14α demethylase, used in the management of systemic and topical mycoses in immuno-compromised and paediatric patients is the lack of availability of liquid dosage forms. In order to overcome this challenge, extemporaneous preparations have been manufactured by care-givers and health care providers by crushing or breaking solid oral dosage forms of KTZ and mixing with a vehicle to produce a liquid dosage form that can be swallowed by patients. However, the use of extemporaneous preparations may lead to under or over-dosing if the care-givers are not guided accordingly. Furthermore, the dearth of information on the stability of these KTZ-containing extemporaneous preparations may lead to ineffective antifungal therapy and complicate the problems of resistance as it is difficult to estimate the shelf-lives of these extemporaneous products under varying storage conditions due to the susceptibility of KTZ to chemical degradation. Therefore, there is a need for formulation scientists to develop novel drug delivery systems that avoid the need for extemporaneous preparations, possess well-established limits of stability and minimize the risks of systemic adverse effects to facilitate KTZ therapy. The use of solid lipid microparticles (SLM) as potential carriers for the oral administration of KTZ was investigated since solid lipid carriers are known to exhibit the advantages of traditional colloidal carriers. The research undertaken in these studies aimed to investigate the feasibility of developing and manufacturing solid lipid microparticles (SLM), using a simple micro-emulsion technique, as a carrier for KTZ. Prior to pre-formulation, formulation development and optimization studies of KTZ-loaded SLM, it was necessary to develop and validate an analytical method for the in vitro quantitation and characterization of KTZ in aqueous dispersions of SLM during development and assessment studies. An accurate, precise, specific and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) method coupled with UV detection at 206 nm was developed, optimized and validated for the analysis of KTZ in formulations. Formulation development studies were preceded by solubility studies of KTZ in different lipids. Labrafil® M2130 CS was found to exhibit the best solubilising potential for KTZ. Pre-formulation studies were also designed to determine the polymorphic behavior and the crystallinity of KTZ and Labrafil® M2130 CS that was used for subsequent manufacture of the solid lipid carriers. DSC and FTIR studies revealed that there were no changes in the crystallinity of KTZ or Labrafil® M2130 CS following exposure to a temperature of 60°C for 1 hour. In addition the potential for physicochemical interaction of KTZ with the lipid Labrafil® M2130 CS was investigated using DSC and FTIR and the results revealed that KTZ was molecularly dispersed in Labrafil® M2130 CS and that it is unlikely that KTZ would interact with the lipid. It was therefore established that KTZ and Labrafil® M2130 CS were thermo-stable at a temperature of 60°C and thus a micro-emulsion technique could be used to manufacture the KTZ-loaded SLM. Drug-free and KTZ-loaded SLM were prepared using a modified micro-emulsion technique that required the use of an Ultra-Turrax® homogenizer set at 24 000 rpm for 5 minutes followed by the use of the Erweka GmbH homogenizer. SLM were characterized in terms of particle size (PS), zeta potential (ZP), shape and surface morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition drug loading capacity (DLC) and encapsulation efficiency (EE) of SLM for KTZ were assessed using RP-HPLC. Formulation development and optimization studies of KTZ-loaded SLM were initially aimed at selecting an emulsifying system that was able to stabilize the SLM in an aqueous dispersion. Successful formulations were selected based on their ability to remain physically stable on the day of manufacture. Pluronic® F68 used in combination with Lutrol® E40, Soluphor® P, Soluplus® produced unstable dispersions on the day of manufacture and these combinations were not investigated further. However, the formulation of a stable KTZ-loaded SLM dispersion was accomplished by use of a combination of Pluronic® F68, Tween 80 and sodium cholate as the surfactant system. Increasing amounts of Labrafil® M2130 CS resulted in the production of particles with low DLC and EE, a large PS and a relatively unchanged ZP. An optimum concentration of 10% w/v Labrafil® M2130 CS was selected to manufacture the KTZ-loaded SLM. Studies to determine the influence of KTZ loading on the quality of SLM revealed that concentrations of KTZ > 5% w/v led to a reduction in DLC and EE and an increase in PS with minimal impact on the ZP. Stability studies conducted at 25°C/65% RH and 40°C/75% RH for up to 30 days following manufacture revealed that batch SLM 15 manufactured using 10% w/v Labrafil® M2130 CS, 5% w/v KTZ and a combination of 4% w/v Pluronic® F-68, 2% w/v Tween 80 and 1% w/v sodium cholate produced the most stable dosage form when stored at 25°C/65% RH for up to 30 days. However, storage at 40°C/75% RH resulted in instability of the formulation. An aqueous dispersion of KTZ-loaded SLM has been developed and assessed and may offer an alternative to extemporaneous preparations used for KTZ therapy in paediatric and immuno-compromised patients.
- Full Text:
- Date Issued: 2015
- Authors: Jhundoo, Henusha Devi
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54701 , vital:26601
- Description: One of the major challenges of the oral administration of ketoconazole (KTZ), an inhibitor of sterol 14α demethylase, used in the management of systemic and topical mycoses in immuno-compromised and paediatric patients is the lack of availability of liquid dosage forms. In order to overcome this challenge, extemporaneous preparations have been manufactured by care-givers and health care providers by crushing or breaking solid oral dosage forms of KTZ and mixing with a vehicle to produce a liquid dosage form that can be swallowed by patients. However, the use of extemporaneous preparations may lead to under or over-dosing if the care-givers are not guided accordingly. Furthermore, the dearth of information on the stability of these KTZ-containing extemporaneous preparations may lead to ineffective antifungal therapy and complicate the problems of resistance as it is difficult to estimate the shelf-lives of these extemporaneous products under varying storage conditions due to the susceptibility of KTZ to chemical degradation. Therefore, there is a need for formulation scientists to develop novel drug delivery systems that avoid the need for extemporaneous preparations, possess well-established limits of stability and minimize the risks of systemic adverse effects to facilitate KTZ therapy. The use of solid lipid microparticles (SLM) as potential carriers for the oral administration of KTZ was investigated since solid lipid carriers are known to exhibit the advantages of traditional colloidal carriers. The research undertaken in these studies aimed to investigate the feasibility of developing and manufacturing solid lipid microparticles (SLM), using a simple micro-emulsion technique, as a carrier for KTZ. Prior to pre-formulation, formulation development and optimization studies of KTZ-loaded SLM, it was necessary to develop and validate an analytical method for the in vitro quantitation and characterization of KTZ in aqueous dispersions of SLM during development and assessment studies. An accurate, precise, specific and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) method coupled with UV detection at 206 nm was developed, optimized and validated for the analysis of KTZ in formulations. Formulation development studies were preceded by solubility studies of KTZ in different lipids. Labrafil® M2130 CS was found to exhibit the best solubilising potential for KTZ. Pre-formulation studies were also designed to determine the polymorphic behavior and the crystallinity of KTZ and Labrafil® M2130 CS that was used for subsequent manufacture of the solid lipid carriers. DSC and FTIR studies revealed that there were no changes in the crystallinity of KTZ or Labrafil® M2130 CS following exposure to a temperature of 60°C for 1 hour. In addition the potential for physicochemical interaction of KTZ with the lipid Labrafil® M2130 CS was investigated using DSC and FTIR and the results revealed that KTZ was molecularly dispersed in Labrafil® M2130 CS and that it is unlikely that KTZ would interact with the lipid. It was therefore established that KTZ and Labrafil® M2130 CS were thermo-stable at a temperature of 60°C and thus a micro-emulsion technique could be used to manufacture the KTZ-loaded SLM. Drug-free and KTZ-loaded SLM were prepared using a modified micro-emulsion technique that required the use of an Ultra-Turrax® homogenizer set at 24 000 rpm for 5 minutes followed by the use of the Erweka GmbH homogenizer. SLM were characterized in terms of particle size (PS), zeta potential (ZP), shape and surface morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition drug loading capacity (DLC) and encapsulation efficiency (EE) of SLM for KTZ were assessed using RP-HPLC. Formulation development and optimization studies of KTZ-loaded SLM were initially aimed at selecting an emulsifying system that was able to stabilize the SLM in an aqueous dispersion. Successful formulations were selected based on their ability to remain physically stable on the day of manufacture. Pluronic® F68 used in combination with Lutrol® E40, Soluphor® P, Soluplus® produced unstable dispersions on the day of manufacture and these combinations were not investigated further. However, the formulation of a stable KTZ-loaded SLM dispersion was accomplished by use of a combination of Pluronic® F68, Tween 80 and sodium cholate as the surfactant system. Increasing amounts of Labrafil® M2130 CS resulted in the production of particles with low DLC and EE, a large PS and a relatively unchanged ZP. An optimum concentration of 10% w/v Labrafil® M2130 CS was selected to manufacture the KTZ-loaded SLM. Studies to determine the influence of KTZ loading on the quality of SLM revealed that concentrations of KTZ > 5% w/v led to a reduction in DLC and EE and an increase in PS with minimal impact on the ZP. Stability studies conducted at 25°C/65% RH and 40°C/75% RH for up to 30 days following manufacture revealed that batch SLM 15 manufactured using 10% w/v Labrafil® M2130 CS, 5% w/v KTZ and a combination of 4% w/v Pluronic® F-68, 2% w/v Tween 80 and 1% w/v sodium cholate produced the most stable dosage form when stored at 25°C/65% RH for up to 30 days. However, storage at 40°C/75% RH resulted in instability of the formulation. An aqueous dispersion of KTZ-loaded SLM has been developed and assessed and may offer an alternative to extemporaneous preparations used for KTZ therapy in paediatric and immuno-compromised patients.
- Full Text:
- Date Issued: 2015
Towards a Mobile Bioethanol Unit for point of source conversion of sugar sources to bioethanol: design and feasibility study for South Africa
- Authors: Cech, Alexandra Louise
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/59141 , vital:27439
- Description: Restricted access-thesis embargoed for 5 years
- Full Text:
- Date Issued: 2015
- Authors: Cech, Alexandra Louise
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/59141 , vital:27439
- Description: Restricted access-thesis embargoed for 5 years
- Full Text:
- Date Issued: 2015