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
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
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
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
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
Biotechnology from bench to market: the design, scale-up and commercialisation strategy development of a disruptive bioprocess for potable ethanol production
- Authors: Dhanani, Karim Colin Hassan
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55863 , vital:26750
- Description: The capacity of research institutions to engage in technology transfer activities has important implications on both economic development and technological advancement. This thesis explores the developmental and commercialisation processes involved in the transfer of a potentially disruptive bioprocessing technology for beverage alcohol production. Ethanolic fermentation strategies are of interest due to their global economic importance and their potential to produce clean renewable fuels in the future. Currently used methods are both energetically wasteful and economically inefficient. To this end more effective bioprocessing methods and implementation strategies are required to enable commercially viable decentralised small-scale ethanol production. Perfusion reactors have a number of advantages over batch and other continuous fermentation strategies. This study aimed to develop and study the fermentative efficiency of a perfusion tower bioreactor system at the bench scale, and subsequently through a scale up process to a low level commercial capacity. An HPLC method was developed for the Simultaneous quantification of common fermentation analytes; this was used to determine bench scale fermentation efficacies over an operational period. At steady state the ethanol volumetric productivity of the bench scale bioreactor system was 3.40 g. L-1.h-1, the average yield of ethanol to consumed sugar was 0.467 g.g -1, with an average sugar conversion percentage of 96%. Results showed that the tower perfusion bioreactor was appropriate for high performance ethyl alcohol fermentations. This reactor design was then scaled up to pilot scale and then commercial scale ca pacity. Similar efficienCies were achieved with these larger systems. Based on the process performance data obtained, a commercialisation strategy was developed and market performance was projected. It was found that productivity rates per unit volume were favourable, and the bioreactor system was determined to be very cost effective for a decentralised ethanolic beverage manufacturing model.
- Full Text:
- Date Issued: 2015
- Authors: Dhanani, Karim Colin Hassan
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55863 , vital:26750
- Description: The capacity of research institutions to engage in technology transfer activities has important implications on both economic development and technological advancement. This thesis explores the developmental and commercialisation processes involved in the transfer of a potentially disruptive bioprocessing technology for beverage alcohol production. Ethanolic fermentation strategies are of interest due to their global economic importance and their potential to produce clean renewable fuels in the future. Currently used methods are both energetically wasteful and economically inefficient. To this end more effective bioprocessing methods and implementation strategies are required to enable commercially viable decentralised small-scale ethanol production. Perfusion reactors have a number of advantages over batch and other continuous fermentation strategies. This study aimed to develop and study the fermentative efficiency of a perfusion tower bioreactor system at the bench scale, and subsequently through a scale up process to a low level commercial capacity. An HPLC method was developed for the Simultaneous quantification of common fermentation analytes; this was used to determine bench scale fermentation efficacies over an operational period. At steady state the ethanol volumetric productivity of the bench scale bioreactor system was 3.40 g. L-1.h-1, the average yield of ethanol to consumed sugar was 0.467 g.g -1, with an average sugar conversion percentage of 96%. Results showed that the tower perfusion bioreactor was appropriate for high performance ethyl alcohol fermentations. This reactor design was then scaled up to pilot scale and then commercial scale ca pacity. Similar efficienCies were achieved with these larger systems. Based on the process performance data obtained, a commercialisation strategy was developed and market performance was projected. It was found that productivity rates per unit volume were favourable, and the bioreactor system was determined to be very cost effective for a decentralised ethanolic beverage manufacturing model.
- 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
Characterisation of the HSP70-HSP90 organising protein gene and its link to cancer
- Authors: Weeks, Stacey
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56006 , vital:26764
- Description: HOP (Heat shock protein 70/ Heat shock protein 90 organising protein) is a co-chaperone essential for client protein transfer from HSP70 to HSP90 within the HSP90 chaperone machine and has been found to be up-regulated in various cancers. However, minimal in vitro information can be found on the regulation of HOP expression. The aim of this study was to analyse the HOP gene structure across known orthologues, identify and characterise the HOP promoter, and identify the regulatory mechanisms influencing the expression of HOP in cancer. We hypothesized that the expression of HOP in cancer cells is likely regulated by oncogenic signalling pathways linked to cis-elements within the HOP promoter. An initial study of the evolution of the HOP gene speciation was performed across identified orthologues using Mega5.2. The evolutionary pathway of the HOP gene was traced from the unicellular organisms to fish, to amphibian and then to land mammal. The synteny across the orthologues was identified and the co-expression profile of HOP analysed. We identified the putative promoter region for HOP in silico and in vitro. Luciferase reporter assays were utilized to demonstrate promoter activity of the upstream region in vitro. Bioinformatic analysis of the active promoter region identified a large CpG island and a range of putative cis-elements. Many of the cis-elements interact with transcription factors which are activated by oncogenic pathways. We therefore tested the regulation of HOP levels by rat sarcoma viral oncogene homologue (RAS). Cancer cell lines were transfected with mutated RAS to observe the effect of constitutively active RAS expression on the production of HOP using qRT-PCR and Western Blot analyses. Additionally, inhibitors of the RAS signalling pathway were utilised to confirm the regulatory effect of mutated RAS on HOP expression. In cancer cell lines containing mutated RAS (Hs578T), HOP was up-regulated via a mechanism involving the MAPK signalling pathway and the ETS-1 and C/EBPβ cis-elements within the HOP promoter. These findings suggest for the first time that Hop expression in cancer may be regulated by RAS activation of the HOP promoter. Additionally, this study allowed us to determine the murine system to be the most suited genetic model organism with which to study the function of human HOP.
- Full Text:
- Date Issued: 2015
- Authors: Weeks, Stacey
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56006 , vital:26764
- Description: HOP (Heat shock protein 70/ Heat shock protein 90 organising protein) is a co-chaperone essential for client protein transfer from HSP70 to HSP90 within the HSP90 chaperone machine and has been found to be up-regulated in various cancers. However, minimal in vitro information can be found on the regulation of HOP expression. The aim of this study was to analyse the HOP gene structure across known orthologues, identify and characterise the HOP promoter, and identify the regulatory mechanisms influencing the expression of HOP in cancer. We hypothesized that the expression of HOP in cancer cells is likely regulated by oncogenic signalling pathways linked to cis-elements within the HOP promoter. An initial study of the evolution of the HOP gene speciation was performed across identified orthologues using Mega5.2. The evolutionary pathway of the HOP gene was traced from the unicellular organisms to fish, to amphibian and then to land mammal. The synteny across the orthologues was identified and the co-expression profile of HOP analysed. We identified the putative promoter region for HOP in silico and in vitro. Luciferase reporter assays were utilized to demonstrate promoter activity of the upstream region in vitro. Bioinformatic analysis of the active promoter region identified a large CpG island and a range of putative cis-elements. Many of the cis-elements interact with transcription factors which are activated by oncogenic pathways. We therefore tested the regulation of HOP levels by rat sarcoma viral oncogene homologue (RAS). Cancer cell lines were transfected with mutated RAS to observe the effect of constitutively active RAS expression on the production of HOP using qRT-PCR and Western Blot analyses. Additionally, inhibitors of the RAS signalling pathway were utilised to confirm the regulatory effect of mutated RAS on HOP expression. In cancer cell lines containing mutated RAS (Hs578T), HOP was up-regulated via a mechanism involving the MAPK signalling pathway and the ETS-1 and C/EBPβ cis-elements within the HOP promoter. These findings suggest for the first time that Hop expression in cancer may be regulated by RAS activation of the HOP promoter. Additionally, this study allowed us to determine the murine system to be the most suited genetic model organism with which to study the function of human HOP.
- 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
Contributions to the study of a class of optimal control problems on the orthogonal groups SO(3) and SO(4)
- Authors: Adams, Ross Montague
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64826 , vital:28608
- Description: In this thesis we investigate a class of invariant optimal control problems, and their associated quadratic Hamilton-Poisson systems, on the orthogonal groups SO(3) and SO(4). Specifically, we are concerned with the class of left-invariant control affine systems. We begin by classifying all cost-extended systems on SO(3) under cost equivalence. (Cost-extended systems are closely related to optimal control problems.) A classification of all quadratic Hamilton-Poisson systems on the (minus) Lie-Poisson space so(3)*, under affine equivalence, is also obtained. For the normal forms obtained in our classification (of Hamilton-Poisson systems) we investigate the (Lyapunov) stability nature of the equilibria using spectral and energy-Casimir methods. For a subclass of these systems, we obtain analytic expressions for the integral curves of the associated Hamiltonian vector fields in terms of (basic) Jacobi elliptic functions. The explicit relationship between the classification of cost-extended systems on SO(3) and the classification of quadratic Hamilton- Poisson systems on so(3)* is provided. On SO(4), a classification of all left-invariant control affine systems under L-equivalence is obtained. We then determine which of these representatives are controllable, thus obtaining a classification under detached feedback equivalence. We also obtain a partial classification of quadratic Hamilton-Poisson systems on the Lie-Poisson space so(4)*. An investigation of the stability nature of the equilibria for a subclass of these systems is also done. Several illustrative examples of optimal control problems on the orthogonal group SO(3) are provided. More specifically, we consider an optimal control problem corresponding to a representative of our classification (of cost-extended system) for each possible number of control inputs. For each of these problems, we obtain explicit expressions for the extremal trajectories on the homogeneous space S2 by projecting the extremal trajectories on the group SO(3). The examples provided show how our classifications of cost-extended systems and Hamilton-Poisson systems can be used to obtain the optimal controls and the extremal trajectories corresponding to a large class of optimal control problems on SO(3). An example of a four-input optimal control problem on SO(4) is also provided. This example is provided to show how the solutions of certain problems on SO(4) can be related to the solutions of certain optimal control problems on SO(3).
- Full Text:
- Date Issued: 2015
- Authors: Adams, Ross Montague
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64826 , vital:28608
- Description: In this thesis we investigate a class of invariant optimal control problems, and their associated quadratic Hamilton-Poisson systems, on the orthogonal groups SO(3) and SO(4). Specifically, we are concerned with the class of left-invariant control affine systems. We begin by classifying all cost-extended systems on SO(3) under cost equivalence. (Cost-extended systems are closely related to optimal control problems.) A classification of all quadratic Hamilton-Poisson systems on the (minus) Lie-Poisson space so(3)*, under affine equivalence, is also obtained. For the normal forms obtained in our classification (of Hamilton-Poisson systems) we investigate the (Lyapunov) stability nature of the equilibria using spectral and energy-Casimir methods. For a subclass of these systems, we obtain analytic expressions for the integral curves of the associated Hamiltonian vector fields in terms of (basic) Jacobi elliptic functions. The explicit relationship between the classification of cost-extended systems on SO(3) and the classification of quadratic Hamilton- Poisson systems on so(3)* is provided. On SO(4), a classification of all left-invariant control affine systems under L-equivalence is obtained. We then determine which of these representatives are controllable, thus obtaining a classification under detached feedback equivalence. We also obtain a partial classification of quadratic Hamilton-Poisson systems on the Lie-Poisson space so(4)*. An investigation of the stability nature of the equilibria for a subclass of these systems is also done. Several illustrative examples of optimal control problems on the orthogonal group SO(3) are provided. More specifically, we consider an optimal control problem corresponding to a representative of our classification (of cost-extended system) for each possible number of control inputs. For each of these problems, we obtain explicit expressions for the extremal trajectories on the homogeneous space S2 by projecting the extremal trajectories on the group SO(3). The examples provided show how our classifications of cost-extended systems and Hamilton-Poisson systems can be used to obtain the optimal controls and the extremal trajectories corresponding to a large class of optimal control problems on SO(3). An example of a four-input optimal control problem on SO(4) is also provided. This example is provided to show how the solutions of certain problems on SO(4) can be related to the solutions of certain optimal control problems on SO(3).
- Full Text:
- Date Issued: 2015
Development and manufacture of sustained release captopril beads
- Authors: Mhaka, Farai Arthur
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54712 , vital:26602
- Description: Hypertension has a high mortality rate in developing countries such as South Africa. Although the prevention and control of hypertension is a health priority, efforts to decrease the global burden of hypertension and improve control over the condition are inadequate. The use of angiotensin converting enzyme (ACE) inhibitors such as captopril (CPT) have been effective for the management of hypertension when used as first line therapy alone or in combination. Commercially available immediate release dosage forms containing 12.5, 25 and 50 mg of CPT are administered two or three times a day to treat hypertension. CPT degrades in aqueous media with the sulfhydryl functional moiety responsible for adverse effects such as hypersensitivity, taste disturbances and/or presenting with a dry hacking cough. CPT has a short elimination half-life of between 1.6 and 1.9 hours, which means that the compound is a suitable candidate for inclusion in sustained release (SR) dosage forms. Manufacturing a SR dosage form of coated beads for twice daily dosing may reduce the incidence and intensity of undesirable adverse effects, improve the stability of CPT and improve patient adherence. A stability indicating reversed-phase high performance liquid chromatographic (RP-HPLC) method was developed and optimised using a central composite design approach. As part of this approach the interactive effects of input factors, viz. pH, methanol (MeOH) content and column temperature on retention time, were investigated to achieve a separation with well-resolved and symmetrical peaks for CPT and salicylic acid. The method was validated using ICH guidelines and was found to be simple, linear, precise, accurate, selective and rapid for the in vitro quantitation of CPT. The method was successfully applied for the analysis of both commercially available and test formulations. Preformulation studies were undertaken to establish the physical and chemical properties of CPT, excipients and dosage forms to ensure the production of stabile and bioavailable products. Powder blends were assessed for flow properties using angle of repose (AOR), and bulk and tapped density, which were subsequently used to calculate Carr’s Index (CI) and the Hausner ratio (HR). The addition of talc resulted in the most powder blends with AOR, CI and HR that were within a range indicative of satisfactory to good flow properties. The use of talc was necessary to ensure that blending prior to wet granulation and extrusion-spheronisation would produce homogenous powders. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FT-IR) were used for the identification and purity of CPT alone and 1:1 binary mixtures with excipients in an effort to establish if CPT was likely to undergo physical and/or chemical modification during production. The DSC thermograms for all CPT-excipient mixtures revealed the presence of a melting endotherm that was wider, occurring at 110.93 °C (Tpeak for pure CPT). The characteristic peaks for specific functional groups were present in the FT-IR spectra for powder mixtures, indicating the absence of incompatibilities. Dialysis studies were used to investigate if the ammonium oleate present in Surelease® E-7-19010 interacted with CPT. The results suggests that an interaction between CPT and Surelease® E-7-19010 during processing of CPT beads was unlikely to occur. Preliminary investigations reveal that Methocel® K100M, Methocel® E4M, Avicel® PH102, Eudragit® RS PO, Surelease® E-7-19010 and talc are compatible with CPT and could be used for the manufacture of SR CPT beads. CPT beads were manufactured using extrusion-spheronisation and coated using a fluidised bed drier fitted with a Wurster insert. The amount of granulating fluid, coating levels, curing time and formulation composition were varied to achieve CPT release with specific criteria to develop a preliminary formulation. The coated beads met all desired quality attributes in respect of micromeritic and flow properties, content uniformity and friability. Response Surface Methodology was used to further optimise the SR CPT formulation. The Plackett-Burman design was used for this process to produce an SR dosage form with desirable quality attributes achieved by altering formulation composition, extrusion-spheronisation variables and coating parameters. ANOVA data revealed significant responses for yield, aspect ratio, sphericity, coating efficiency and cumulative percent CPT released at 2 and 12 hours. Formulations in which the high molecular weight HPMC were used in increased concentrations resulted in the formation of a sticky wet mass and extrudate, resulting in a decrease in yield. The application of a permeable, but insoluble Surelease® coat onto the surface of the beads formed a barrier that complements the activity of the hydrophilic matrix in preventing rapid dissolution and retarding the release of CPT from the beads. The amount of CPT released over 12 hours revealed that increasing the Methocel® K100M content entrapped CPT and retained it more efficiently in the hydrated matrix, resulting in a slow rate of CPT release. In vitro release data were fitted to a number of models in an attempt to elucidate mechanistic aspects of transport processes specific to CPT from the coated bead formulations. The results of fitting data from optimised batches revealed that the goodness of fit based on the adjusted correlation coefficient ranged between 0.953 and 0.976 for the Higuchi model, indicating that diffusion is a predominant factor that controls CPT release from the coated beads. The results of fitting data to the Korsmeyer-Peppas model suggest that the mechanism of CPT release includes transport of the dissolution medium from the vessel reservoir into the core of the bead due to osmotic potential, dissolution of CPT, mass transfer of the dissolved CPT within the core, partitioning between the solution and polymeric film, mass transfer of dissolved CPT through the film to ultimately reach the bulk dissolution fluid. A SR CPT bead formulation that has potential for further development and optimisation for scaled-up production using RSM approaches and Design of Experiments such as CCD or Box-Behnken has been successfully developed and manufactured using extrusion, spheronisation and coating processes. Assessment of all batches of beads manufactured exhibited satisfactory to good flow properties and demonstrated SR profiles over 12 hours that met USP criteria for SR dosage forms.
- Full Text:
- Date Issued: 2015
- Authors: Mhaka, Farai Arthur
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54712 , vital:26602
- Description: Hypertension has a high mortality rate in developing countries such as South Africa. Although the prevention and control of hypertension is a health priority, efforts to decrease the global burden of hypertension and improve control over the condition are inadequate. The use of angiotensin converting enzyme (ACE) inhibitors such as captopril (CPT) have been effective for the management of hypertension when used as first line therapy alone or in combination. Commercially available immediate release dosage forms containing 12.5, 25 and 50 mg of CPT are administered two or three times a day to treat hypertension. CPT degrades in aqueous media with the sulfhydryl functional moiety responsible for adverse effects such as hypersensitivity, taste disturbances and/or presenting with a dry hacking cough. CPT has a short elimination half-life of between 1.6 and 1.9 hours, which means that the compound is a suitable candidate for inclusion in sustained release (SR) dosage forms. Manufacturing a SR dosage form of coated beads for twice daily dosing may reduce the incidence and intensity of undesirable adverse effects, improve the stability of CPT and improve patient adherence. A stability indicating reversed-phase high performance liquid chromatographic (RP-HPLC) method was developed and optimised using a central composite design approach. As part of this approach the interactive effects of input factors, viz. pH, methanol (MeOH) content and column temperature on retention time, were investigated to achieve a separation with well-resolved and symmetrical peaks for CPT and salicylic acid. The method was validated using ICH guidelines and was found to be simple, linear, precise, accurate, selective and rapid for the in vitro quantitation of CPT. The method was successfully applied for the analysis of both commercially available and test formulations. Preformulation studies were undertaken to establish the physical and chemical properties of CPT, excipients and dosage forms to ensure the production of stabile and bioavailable products. Powder blends were assessed for flow properties using angle of repose (AOR), and bulk and tapped density, which were subsequently used to calculate Carr’s Index (CI) and the Hausner ratio (HR). The addition of talc resulted in the most powder blends with AOR, CI and HR that were within a range indicative of satisfactory to good flow properties. The use of talc was necessary to ensure that blending prior to wet granulation and extrusion-spheronisation would produce homogenous powders. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FT-IR) were used for the identification and purity of CPT alone and 1:1 binary mixtures with excipients in an effort to establish if CPT was likely to undergo physical and/or chemical modification during production. The DSC thermograms for all CPT-excipient mixtures revealed the presence of a melting endotherm that was wider, occurring at 110.93 °C (Tpeak for pure CPT). The characteristic peaks for specific functional groups were present in the FT-IR spectra for powder mixtures, indicating the absence of incompatibilities. Dialysis studies were used to investigate if the ammonium oleate present in Surelease® E-7-19010 interacted with CPT. The results suggests that an interaction between CPT and Surelease® E-7-19010 during processing of CPT beads was unlikely to occur. Preliminary investigations reveal that Methocel® K100M, Methocel® E4M, Avicel® PH102, Eudragit® RS PO, Surelease® E-7-19010 and talc are compatible with CPT and could be used for the manufacture of SR CPT beads. CPT beads were manufactured using extrusion-spheronisation and coated using a fluidised bed drier fitted with a Wurster insert. The amount of granulating fluid, coating levels, curing time and formulation composition were varied to achieve CPT release with specific criteria to develop a preliminary formulation. The coated beads met all desired quality attributes in respect of micromeritic and flow properties, content uniformity and friability. Response Surface Methodology was used to further optimise the SR CPT formulation. The Plackett-Burman design was used for this process to produce an SR dosage form with desirable quality attributes achieved by altering formulation composition, extrusion-spheronisation variables and coating parameters. ANOVA data revealed significant responses for yield, aspect ratio, sphericity, coating efficiency and cumulative percent CPT released at 2 and 12 hours. Formulations in which the high molecular weight HPMC were used in increased concentrations resulted in the formation of a sticky wet mass and extrudate, resulting in a decrease in yield. The application of a permeable, but insoluble Surelease® coat onto the surface of the beads formed a barrier that complements the activity of the hydrophilic matrix in preventing rapid dissolution and retarding the release of CPT from the beads. The amount of CPT released over 12 hours revealed that increasing the Methocel® K100M content entrapped CPT and retained it more efficiently in the hydrated matrix, resulting in a slow rate of CPT release. In vitro release data were fitted to a number of models in an attempt to elucidate mechanistic aspects of transport processes specific to CPT from the coated bead formulations. The results of fitting data from optimised batches revealed that the goodness of fit based on the adjusted correlation coefficient ranged between 0.953 and 0.976 for the Higuchi model, indicating that diffusion is a predominant factor that controls CPT release from the coated beads. The results of fitting data to the Korsmeyer-Peppas model suggest that the mechanism of CPT release includes transport of the dissolution medium from the vessel reservoir into the core of the bead due to osmotic potential, dissolution of CPT, mass transfer of the dissolved CPT within the core, partitioning between the solution and polymeric film, mass transfer of dissolved CPT through the film to ultimately reach the bulk dissolution fluid. A SR CPT bead formulation that has potential for further development and optimisation for scaled-up production using RSM approaches and Design of Experiments such as CCD or Box-Behnken has been successfully developed and manufactured using extrusion, spheronisation and coating processes. Assessment of all batches of beads manufactured exhibited satisfactory to good flow properties and demonstrated SR profiles over 12 hours that met USP criteria for SR dosage forms.
- Full Text:
- Date Issued: 2015
Environmental conflict resolution: a critical analysis of the role of interests and value
- Authors: Mweshi, John
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/55842 , vital:26740
- Description: This thesis intends to contribute to an enhanced understanding of environmental conflicts and their resolution. To accomplish this task the thesis will ascertain the role that value and interests play in environmental conflicts in order to establish an adequate basis upon which they can be resolved. In the process, the thesis will also examine three different approaches, namely, the Standard Approach; the Environmental Impact Assessment (EIA) framework; and the Structured Decision Making (SDM) approach. First, the standard approach is informed by the understanding that focusing on interests instead of human values makes the resolution of conflicts more tractable. In contrast, this thesis argues that an exclusive focus on interests, in the context of environmental conflict resolution, is inadequate in some important respects because there are other factors to be considered such as the environmental impacts at the root of the conflict. Second, the thesis examines the focus on impacts that characterises EIAs. It argues that this approach remedies the limitations of the standard approach insofar as impacts are understood in terms of object value. However, the EIA approach does not provide much guidance on how to deal with conflicting human values. Third, taking into account the fact that the standard approach does not address the question of object value, while the EIA addresses object value but does not deal directly with human values, the thesis examines the SDM approach to environmental risk decisions. The thesis argues that while the SDM approach claims to deal with conflicts involving human values head-on, it does not provide a viable alternative in terms of environmental conflict resolution. This is because it fails to recognise the key distinction between human values and object value despite acknowledging the presence of multiple value dimensions as a major obstacle to value trade-offs and therefore to the resolution of value conflicts. Finally, the thesis recommends an adequate basis upon which environmental conflicts can be resolved.
- Full Text:
- Date Issued: 2015
- Authors: Mweshi, John
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/55842 , vital:26740
- Description: This thesis intends to contribute to an enhanced understanding of environmental conflicts and their resolution. To accomplish this task the thesis will ascertain the role that value and interests play in environmental conflicts in order to establish an adequate basis upon which they can be resolved. In the process, the thesis will also examine three different approaches, namely, the Standard Approach; the Environmental Impact Assessment (EIA) framework; and the Structured Decision Making (SDM) approach. First, the standard approach is informed by the understanding that focusing on interests instead of human values makes the resolution of conflicts more tractable. In contrast, this thesis argues that an exclusive focus on interests, in the context of environmental conflict resolution, is inadequate in some important respects because there are other factors to be considered such as the environmental impacts at the root of the conflict. Second, the thesis examines the focus on impacts that characterises EIAs. It argues that this approach remedies the limitations of the standard approach insofar as impacts are understood in terms of object value. However, the EIA approach does not provide much guidance on how to deal with conflicting human values. Third, taking into account the fact that the standard approach does not address the question of object value, while the EIA addresses object value but does not deal directly with human values, the thesis examines the SDM approach to environmental risk decisions. The thesis argues that while the SDM approach claims to deal with conflicts involving human values head-on, it does not provide a viable alternative in terms of environmental conflict resolution. This is because it fails to recognise the key distinction between human values and object value despite acknowledging the presence of multiple value dimensions as a major obstacle to value trade-offs and therefore to the resolution of value conflicts. Finally, the thesis recommends an adequate basis upon which environmental conflicts can be resolved.
- Full Text:
- Date Issued: 2015
Evaluating coverage of the environment: a comparative study of the observations of academics and journalists
- Authors: Koro, Emmanuel
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/64888 , vital:28628
- Description: This study is a comparative analysis of the way that academics and journalists evaluate media coverage of news about the environment. The purpose is to gain insight into the kind of contributions that each of these groups can make to debates about the role that such coverage should play within processes of public deliberations about the environment. The dissertation begins by establishing theoretical terms of reference for assessing discussions of the journalistic coverage of the environment. It proposes that it is of value to consider the conceptualisation, within such discussions, of credible knowledge about the environment and, more particularly, to establish whether such conceptualisation is based within a positivist, interpretive, or critical realist paradigm. It is demonstrated that each of these epistemological traditions brings valuable perspectives to the discussion of journalism about the environment within such literature. It is, however, the positivist perspective that remains dominant, and this limits the extent to which the potential of the other two epistemological positions are fully realized. It is also demonstrated that there is a tendency, within this literature, to focus on the performance of individual journalists with minimal attention to the particularities of institutional and social context. It is proposed that this tendency results from the adherence to a positivist approach to the evaluation of journalism. The dissertation then describes the design and implementation of the empirical component of the study - dealing with decisions made about the overall methodological framing, the choice of method, the fieldwork plan and the approach to analysis. It is explained that the aim of the empirical component was to examine South African print journalists’ discussions of coverage of the environment in their own publications, and to compare such discussion to that which is represented in the academic literature. The dissertation then presents a summary of the themes that emerged from the analysis of the interview material that formed part of this empirical work. It is demonstrated that the evaluation of coverage of the environment, as articulated by the research participants, is informed by many of the assumptions and values that can be identified within academic literature. Such evaluation is, furthermore, similarly informed by a positivist, interpretive and critical treatment of knowledge - with, again, a tendency for the positivist position to dominate. One important difference is that the research participants include more references to institutional context. It is proposed, however, that the tendency to prioritise a positivist epistemological framing continues to place limitations on the extent to which the participants are able to fully articulate their knowledge about such context.
- Full Text:
- Date Issued: 2015
- Authors: Koro, Emmanuel
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/64888 , vital:28628
- Description: This study is a comparative analysis of the way that academics and journalists evaluate media coverage of news about the environment. The purpose is to gain insight into the kind of contributions that each of these groups can make to debates about the role that such coverage should play within processes of public deliberations about the environment. The dissertation begins by establishing theoretical terms of reference for assessing discussions of the journalistic coverage of the environment. It proposes that it is of value to consider the conceptualisation, within such discussions, of credible knowledge about the environment and, more particularly, to establish whether such conceptualisation is based within a positivist, interpretive, or critical realist paradigm. It is demonstrated that each of these epistemological traditions brings valuable perspectives to the discussion of journalism about the environment within such literature. It is, however, the positivist perspective that remains dominant, and this limits the extent to which the potential of the other two epistemological positions are fully realized. It is also demonstrated that there is a tendency, within this literature, to focus on the performance of individual journalists with minimal attention to the particularities of institutional and social context. It is proposed that this tendency results from the adherence to a positivist approach to the evaluation of journalism. The dissertation then describes the design and implementation of the empirical component of the study - dealing with decisions made about the overall methodological framing, the choice of method, the fieldwork plan and the approach to analysis. It is explained that the aim of the empirical component was to examine South African print journalists’ discussions of coverage of the environment in their own publications, and to compare such discussion to that which is represented in the academic literature. The dissertation then presents a summary of the themes that emerged from the analysis of the interview material that formed part of this empirical work. It is demonstrated that the evaluation of coverage of the environment, as articulated by the research participants, is informed by many of the assumptions and values that can be identified within academic literature. Such evaluation is, furthermore, similarly informed by a positivist, interpretive and critical treatment of knowledge - with, again, a tendency for the positivist position to dominate. One important difference is that the research participants include more references to institutional context. It is proposed, however, that the tendency to prioritise a positivist epistemological framing continues to place limitations on the extent to which the participants are able to fully articulate their knowledge about such context.
- 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
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
Identification of novel SNPSTRs by 454 sequencing in Nguni and Sotho-Tswana populations
- Authors: Laurence, Jo-Anne Elizabeth
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55885 , vital:26752
- Description: DNA profiling is currently performed by analysis of the electropherogram that results following the amplification of a panel of Short Tandem Repeat (STR) loci. A need has arisen, however, for the development of a typing method that generates results which are compatible and comparable with existing databases, but that have a higher discrimination power by supplying sequence data as well as repeat-number data. Recent studies that explore these alternative typing methodologies have revealed the existence of a number of STR variants. There is, however, little information about the exact nature and prevalence of these sub-alleles. There have also been limited population studies of the genetic profiles of sub-Saharan African populations, despite the fact that evidence suggests that there is greater genetic structure and genetic diversity in these populations. In this study, a processing protocol for the generation of 454 sequencing-ready amplicons of vWA, D2S441, D3S1358, D13S317, D21S11 and D7S820 loci was developed. This protocol was applied to buccal swabs collected from 144 individuals of the Nguni and Sotho-Tswana population groups. A total of 145 485 reads were obtained from the sequencing of these amplicons, of which 97 400 and 48 085 reads were obtained for the Nguni and Sotho-Tswana populations respectively. The proportional representation for each locus ranged from 8-20%, and the allele calls and observed frequencies of these alleles suggested a high degree of relatedness between population groups. The sequencing results, furthermore, enabled the identification of a number of previously undescribed STR variants and SNPSTRs; with allele 13´ for D13S317 representing a SNP that may be predictive of Nguni-ancestry. The results also demonstrated the usefulness of next generation sequencing for increasing the number of discernible alleles for STR profiling.
- Full Text:
- Date Issued: 2015
- Authors: Laurence, Jo-Anne Elizabeth
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/55885 , vital:26752
- Description: DNA profiling is currently performed by analysis of the electropherogram that results following the amplification of a panel of Short Tandem Repeat (STR) loci. A need has arisen, however, for the development of a typing method that generates results which are compatible and comparable with existing databases, but that have a higher discrimination power by supplying sequence data as well as repeat-number data. Recent studies that explore these alternative typing methodologies have revealed the existence of a number of STR variants. There is, however, little information about the exact nature and prevalence of these sub-alleles. There have also been limited population studies of the genetic profiles of sub-Saharan African populations, despite the fact that evidence suggests that there is greater genetic structure and genetic diversity in these populations. In this study, a processing protocol for the generation of 454 sequencing-ready amplicons of vWA, D2S441, D3S1358, D13S317, D21S11 and D7S820 loci was developed. This protocol was applied to buccal swabs collected from 144 individuals of the Nguni and Sotho-Tswana population groups. A total of 145 485 reads were obtained from the sequencing of these amplicons, of which 97 400 and 48 085 reads were obtained for the Nguni and Sotho-Tswana populations respectively. The proportional representation for each locus ranged from 8-20%, and the allele calls and observed frequencies of these alleles suggested a high degree of relatedness between population groups. The sequencing results, furthermore, enabled the identification of a number of previously undescribed STR variants and SNPSTRs; with allele 13´ for D13S317 representing a SNP that may be predictive of Nguni-ancestry. The results also demonstrated the usefulness of next generation sequencing for increasing the number of discernible alleles for STR profiling.
- Full Text:
- Date Issued: 2015
Invariant control systems and sub-Riemannian structures on lie groups: equivalence and isometries
- Authors: Biggs, Rory
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64815 , vital:28607
- Description: In this thesis we consider invariant optimal control problems and invariant sub-Riemannian structures on Lie groups. Primarily, we are concerned with the equivalence and classification of problems (resp. structures). In the first chapter, both the class of invariant optimal control problems and the class of invariant sub-Riemannian structures are organised as categories. The latter category is shown to be functorially equivalent to a subcategory of the former category. Via the Pontryagin Maximum Principle, we associate to each invariant optimal control problem (resp. invariant sub-Riemannian structure) a quadratic Hamilton-Poisson system on the associated Lie-Poisson space. These Hamiltonian systems are also organised as a category and hence the Pontryagin lift is realised as a contravariant functor. Basic properties of these categories are investigated. The rest of this thesis is concerned with the classification (and investigation) of certain subclasses of structures and systems. In the second chapter, the homogeneous positive semidefinite quadratic Hamilton-Poisson systems on three-dimensional Lie-Poisson spaces are classified up to compatibility with a linear isomorphism; a list of 23 normal forms is exhibited. In the third chapter, we classify the invariant sub-Riemannian structures in three dimensions and calculate the isometry group for each normal form. By comparing our results with known results, we show that most isometries (in three dimensions) are in fact the composition of a left translation and a Lie group isomorphism. In the fourth and last chapter of this thesis, we classify the sub-Riemannian and Riemannian structures on the (2n + 1)-dimensional Heisenberg groups. Furthermore, we find the isometry group and geodesics of each normal form.
- Full Text:
- Date Issued: 2015
- Authors: Biggs, Rory
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/64815 , vital:28607
- Description: In this thesis we consider invariant optimal control problems and invariant sub-Riemannian structures on Lie groups. Primarily, we are concerned with the equivalence and classification of problems (resp. structures). In the first chapter, both the class of invariant optimal control problems and the class of invariant sub-Riemannian structures are organised as categories. The latter category is shown to be functorially equivalent to a subcategory of the former category. Via the Pontryagin Maximum Principle, we associate to each invariant optimal control problem (resp. invariant sub-Riemannian structure) a quadratic Hamilton-Poisson system on the associated Lie-Poisson space. These Hamiltonian systems are also organised as a category and hence the Pontryagin lift is realised as a contravariant functor. Basic properties of these categories are investigated. The rest of this thesis is concerned with the classification (and investigation) of certain subclasses of structures and systems. In the second chapter, the homogeneous positive semidefinite quadratic Hamilton-Poisson systems on three-dimensional Lie-Poisson spaces are classified up to compatibility with a linear isomorphism; a list of 23 normal forms is exhibited. In the third chapter, we classify the invariant sub-Riemannian structures in three dimensions and calculate the isometry group for each normal form. By comparing our results with known results, we show that most isometries (in three dimensions) are in fact the composition of a left translation and a Lie group isomorphism. In the fourth and last chapter of this thesis, we classify the sub-Riemannian and Riemannian structures on the (2n + 1)-dimensional Heisenberg groups. Furthermore, we find the isometry group and geodesics of each normal form.
- 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
Love in a cold war
- Authors: Christenson, Anna
- Date: 2015
- Subjects: South African fiction (English) -- 21st century
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: vital:5988
- Description: A collection of short stories in two parts written in realist and fabulist styles. The first part looks at the post-war generation of baby boomers growing up in the American Midwest. The second half follows an American abroad and explores themes of disintegration, the shifting power balance in relationships and the terrible hole at the core of expatriate identity.
- Full Text:
- Date Issued: 2015
- Authors: Christenson, Anna
- Date: 2015
- Subjects: South African fiction (English) -- 21st century
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: vital:5988
- Description: A collection of short stories in two parts written in realist and fabulist styles. The first part looks at the post-war generation of baby boomers growing up in the American Midwest. The second half follows an American abroad and explores themes of disintegration, the shifting power balance in relationships and the terrible hole at the core of expatriate identity.
- Full Text:
- Date Issued: 2015
Modification and application of the decentralised wastewater treatment technology for greywater treatment to reduce water needs
- Authors: Ngqwala, Nosiphiwe P
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/103714 , vital:32290
- Description: Expected release date-April 2017
- Full Text: false
- Date Issued: 2015
- Authors: Ngqwala, Nosiphiwe P
- Date: 2015
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/103714 , vital:32290
- Description: Expected release date-April 2017
- Full Text: false
- Date Issued: 2015