Regional application of the Pitman monthly rainfall-runoff model in Southern Africa incorporating uncertainty
- Authors: Kapangaziwiri, Evison
- Date: 2011
- Subjects: Water supply -- Africa, Southern Water supply -- Measurement -- Africa, Southern Hydrology -- Mathematical models -- Africa, Southern Hydrologic models Rain and rainfall -- Mathematical models -- Africa, Southern Runoff -- Mathematical models
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:6037 , http://hdl.handle.net/10962/d1006178
- Description: Climate change and a growing demand for freshwater resources due to population increases and socio-economic changes will make water a limiting factor (in terms of both quantity and quality) in development. The need for reliable quantitative estimates of water availability cannot be over-emphasised. However, there is frequently a paucity of the data required for this quantification as many basins, especially in the developing world, are inadequately equipped with monitoring networks. Existing networks are also shrinking due mainly to shortages in human and financial resources. Over the past few decades mathematical models have been used to bridge the data gap by generating datasets for use in management and policy making. In southern Africa, the Pitman monthly rainfall-runoff model has enjoyed relatively popular use as a water resources estimation tool. However, it is acknowledged that models are abstractions of reality and the data used to drive them is imperfect, making the model outputs uncertain. While there is acknowledgement of the limitations of modelled data in the southern African region among water practitioners, there has been little effort to explicitly quantify and account for this uncertainty in water resources estimation tools and explore how it affects the decision making process. Uncertainty manifests itself in three major areas of the modelling chain; the input data used to force the model, the parameter estimation process and the model structural errors. A previous study concluded that the parameter estimation process for the Pitman model contributed more to the global uncertainty of the model than other sources. While the literature abounds with uncertainty estimation techniques, many of these are dependent on observations and are therefore unlikely to be easily applicable to the southern African region where there is an acute shortage of such data. This study focuses on two aspects of making hydrologic predictions in ungauged basins. Firstly, the study advocates the development of an a priori parameter estimation process for the Pitman model and secondly, uses indices of hydrological functional behaviour to condition and reduce predictive uncertainty in both gauged and ungauged basins. In this approach all the basins are treated as ungauged, while the historical records in the gauged basins are used to develop regional indices of expected hydrological behaviour and assess the applicability of these methods. Incorporating uncertainty into the hydrologic estimation tools used in southern Africa entails rethinking the way the uncertain results can be used in further analysis and how they will be interpreted by stakeholders. An uncertainty framework is proposed. The framework is made up of a number of components related to the estimation of the prior distribution of the parameters, used to generate output ensembles which are then assessed and constrained using regionalised indices of basin behavioural responses. This is premised on such indices being based on the best available knowledge covering different regions. This framework is flexible enough to be used with any model structure to ensure consistent and comparable results. While the aim is to eventually apply the uncertainty framework in the southern African region, this study reports on the preliminary work on the development and testing of the framework components based on South African basins. This is necessitated by the variations in the availability and quality of the data across the region. Uncertainty in the parameter estimation process was incorporated by assuming uncertainty in the physical and hydro-meteorological data used to directly quantify the parameter. This uncertainty was represented by the range of variability of these basin characteristics and probability distribution functions were developed to account for this uncertainty and propagate it through the estimation process to generate posterior distributions for the parameters. The results show that the framework has a great deal of potential but can still be improved. In general, the estimated uncertain parameters managed to produce hydrologically realistic model outputs capturing the expected regimes across the different hydro-climatic and geo-physical gradients examined. The regional relationships for the three indices developed and tested in this study were in general agreement with existing knowledge and managed to successfully provide a multi-criteria conditioning of the model output ensembles. The feedback loop included in the framework enabled a systematic re-examination of the estimation procedures for both the parameters and the indices when inconsistencies in the results were identified. This improved results. However, there is need to carefully examine the issues and problems that may arise within other basins outside South Africa and develop guidelines for the use of the framework. , iText 1.4.6 (by lowagie.com)
- Full Text:
- Date Issued: 2011
- Authors: Kapangaziwiri, Evison
- Date: 2011
- Subjects: Water supply -- Africa, Southern Water supply -- Measurement -- Africa, Southern Hydrology -- Mathematical models -- Africa, Southern Hydrologic models Rain and rainfall -- Mathematical models -- Africa, Southern Runoff -- Mathematical models
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:6037 , http://hdl.handle.net/10962/d1006178
- Description: Climate change and a growing demand for freshwater resources due to population increases and socio-economic changes will make water a limiting factor (in terms of both quantity and quality) in development. The need for reliable quantitative estimates of water availability cannot be over-emphasised. However, there is frequently a paucity of the data required for this quantification as many basins, especially in the developing world, are inadequately equipped with monitoring networks. Existing networks are also shrinking due mainly to shortages in human and financial resources. Over the past few decades mathematical models have been used to bridge the data gap by generating datasets for use in management and policy making. In southern Africa, the Pitman monthly rainfall-runoff model has enjoyed relatively popular use as a water resources estimation tool. However, it is acknowledged that models are abstractions of reality and the data used to drive them is imperfect, making the model outputs uncertain. While there is acknowledgement of the limitations of modelled data in the southern African region among water practitioners, there has been little effort to explicitly quantify and account for this uncertainty in water resources estimation tools and explore how it affects the decision making process. Uncertainty manifests itself in three major areas of the modelling chain; the input data used to force the model, the parameter estimation process and the model structural errors. A previous study concluded that the parameter estimation process for the Pitman model contributed more to the global uncertainty of the model than other sources. While the literature abounds with uncertainty estimation techniques, many of these are dependent on observations and are therefore unlikely to be easily applicable to the southern African region where there is an acute shortage of such data. This study focuses on two aspects of making hydrologic predictions in ungauged basins. Firstly, the study advocates the development of an a priori parameter estimation process for the Pitman model and secondly, uses indices of hydrological functional behaviour to condition and reduce predictive uncertainty in both gauged and ungauged basins. In this approach all the basins are treated as ungauged, while the historical records in the gauged basins are used to develop regional indices of expected hydrological behaviour and assess the applicability of these methods. Incorporating uncertainty into the hydrologic estimation tools used in southern Africa entails rethinking the way the uncertain results can be used in further analysis and how they will be interpreted by stakeholders. An uncertainty framework is proposed. The framework is made up of a number of components related to the estimation of the prior distribution of the parameters, used to generate output ensembles which are then assessed and constrained using regionalised indices of basin behavioural responses. This is premised on such indices being based on the best available knowledge covering different regions. This framework is flexible enough to be used with any model structure to ensure consistent and comparable results. While the aim is to eventually apply the uncertainty framework in the southern African region, this study reports on the preliminary work on the development and testing of the framework components based on South African basins. This is necessitated by the variations in the availability and quality of the data across the region. Uncertainty in the parameter estimation process was incorporated by assuming uncertainty in the physical and hydro-meteorological data used to directly quantify the parameter. This uncertainty was represented by the range of variability of these basin characteristics and probability distribution functions were developed to account for this uncertainty and propagate it through the estimation process to generate posterior distributions for the parameters. The results show that the framework has a great deal of potential but can still be improved. In general, the estimated uncertain parameters managed to produce hydrologically realistic model outputs capturing the expected regimes across the different hydro-climatic and geo-physical gradients examined. The regional relationships for the three indices developed and tested in this study were in general agreement with existing knowledge and managed to successfully provide a multi-criteria conditioning of the model output ensembles. The feedback loop included in the framework enabled a systematic re-examination of the estimation procedures for both the parameters and the indices when inconsistencies in the results were identified. This improved results. However, there is need to carefully examine the issues and problems that may arise within other basins outside South Africa and develop guidelines for the use of the framework. , iText 1.4.6 (by lowagie.com)
- Full Text:
- Date Issued: 2011
Relations of family and school attachment to forms of learner violence in secondary school communities in Amathole education district, Eastern Cape
- Authors: Ncube, Thembinkosi
- Date: 2011
- Subjects: School violence -- South Africa -- Eastern Cape , School discipline -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD (Education)
- Identifier: vital:16166 , http://hdl.handle.net/10353/504 , School violence -- South Africa -- Eastern Cape , School discipline -- South Africa -- Eastern Cape
- Description: Adolescents in the schools in South Africa have been victims of many social problems such as violence and crime as a result of background influence. They have been both victims and perpetrators of this violence. Problems of attachment to both school and home have always been blamed for the adolescents’ deviance. South African schools are affected by this verbal and physical violence which presumably emanates from learners poor connections with school and home. The background of societies such as economic deprivation has also been presumed to have an impact on the way adolescents conduct themselves in schools. There is no research that has verified the correlation between violence and attachment to bases of attachment - home and school in South Africa, especially in the Eastern Cape Province. A survey was conducted in more than ten schools in the Amathole District where 317 learners’ opinions on their observation of cases of verbal and physical violence in their schools, and on their attachment to both home and school were collected through a 40 item questionnaire. The questionnaire had five sections (a) to (e). The first section (a) required learners to enter their biographical information; gender, age, grade, and quintile classification. The second section (b) required learners to rate their attachment to their homes and to their care givers. The third section (c) required learners to rate their connectedness to their schools. The fourth section (d) required learners to supply information on their observation and involvement in verbal violence. The final section (e) with items adopted from section (d) and customised required learners to rate their observation and involvement in physical violence. Descriptive statistics were used to glean frequencies and the overall levels of attachment and violence amongst learners. The study also looked at significant differences in attachment (both family and school) and violence (both verbal and physical) using gender and socio-economic profiles of the learners and schools (quintile system) as sorting or categorising variables. One major finding which is contrary to most theory and may be as a result of social dynamics is that statistics suggested that gender and socio-economic variables had little bearing on violence and attachment. Through the use of SPSS, the Spearman’s rho correlation coefficients were calculated to answer the sub-questions on the relationship between family and school attachment, and school violence (both verbal and physical). There were notable negative and positive correlations between school attachment and verbal violence; for example there was a positive correlation between teachers making learners hate school and learner-involvement in swearing. There was also a negative correlation between school buildings making learners proud and schools and homes being to blame for the frequency of verbal violence in the schools. There were also notable correlations between attachment to family and verbal violence such as the correlation between the frustration by parents’ lack of concern and learners’ involvement in verbal violence without any clear reason. With regard to physical violence there was a negative correlation between parents having time to discuss life with their children and the frequency of physical violence in the schools. There was however a negative correlation between one’s pride in one’s school and the blame on schools for instigating school violence. From these correlations implications for school violence prevention could be drawn. The study reveals that a lot needs to be done by the schools, parents, the government, and the community to enhance learner attachment to both school and home. However, for all the stake holders to succeed government must take the leading role in speeding up the process of reducing poverty in the communities. This is premised on the fact that some findings reveal that frequency of violence increases in an environment of frustration and anger. Schools as care-givers can also introduce many interventions such as counselling workshops to equip teachers with professional crisis management. The research may encourage the Department of Education and schools to adopt violence prevention programs implemented in countries (like United States of America’s Olweus bullying and violence prevention program) for use in bringing communities together to work against school violence. These findings might strengthen the South African Department of Education’s Safe Schools Programs.
- Full Text:
- Date Issued: 2011
- Authors: Ncube, Thembinkosi
- Date: 2011
- Subjects: School violence -- South Africa -- Eastern Cape , School discipline -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Doctoral , PhD (Education)
- Identifier: vital:16166 , http://hdl.handle.net/10353/504 , School violence -- South Africa -- Eastern Cape , School discipline -- South Africa -- Eastern Cape
- Description: Adolescents in the schools in South Africa have been victims of many social problems such as violence and crime as a result of background influence. They have been both victims and perpetrators of this violence. Problems of attachment to both school and home have always been blamed for the adolescents’ deviance. South African schools are affected by this verbal and physical violence which presumably emanates from learners poor connections with school and home. The background of societies such as economic deprivation has also been presumed to have an impact on the way adolescents conduct themselves in schools. There is no research that has verified the correlation between violence and attachment to bases of attachment - home and school in South Africa, especially in the Eastern Cape Province. A survey was conducted in more than ten schools in the Amathole District where 317 learners’ opinions on their observation of cases of verbal and physical violence in their schools, and on their attachment to both home and school were collected through a 40 item questionnaire. The questionnaire had five sections (a) to (e). The first section (a) required learners to enter their biographical information; gender, age, grade, and quintile classification. The second section (b) required learners to rate their attachment to their homes and to their care givers. The third section (c) required learners to rate their connectedness to their schools. The fourth section (d) required learners to supply information on their observation and involvement in verbal violence. The final section (e) with items adopted from section (d) and customised required learners to rate their observation and involvement in physical violence. Descriptive statistics were used to glean frequencies and the overall levels of attachment and violence amongst learners. The study also looked at significant differences in attachment (both family and school) and violence (both verbal and physical) using gender and socio-economic profiles of the learners and schools (quintile system) as sorting or categorising variables. One major finding which is contrary to most theory and may be as a result of social dynamics is that statistics suggested that gender and socio-economic variables had little bearing on violence and attachment. Through the use of SPSS, the Spearman’s rho correlation coefficients were calculated to answer the sub-questions on the relationship between family and school attachment, and school violence (both verbal and physical). There were notable negative and positive correlations between school attachment and verbal violence; for example there was a positive correlation between teachers making learners hate school and learner-involvement in swearing. There was also a negative correlation between school buildings making learners proud and schools and homes being to blame for the frequency of verbal violence in the schools. There were also notable correlations between attachment to family and verbal violence such as the correlation between the frustration by parents’ lack of concern and learners’ involvement in verbal violence without any clear reason. With regard to physical violence there was a negative correlation between parents having time to discuss life with their children and the frequency of physical violence in the schools. There was however a negative correlation between one’s pride in one’s school and the blame on schools for instigating school violence. From these correlations implications for school violence prevention could be drawn. The study reveals that a lot needs to be done by the schools, parents, the government, and the community to enhance learner attachment to both school and home. However, for all the stake holders to succeed government must take the leading role in speeding up the process of reducing poverty in the communities. This is premised on the fact that some findings reveal that frequency of violence increases in an environment of frustration and anger. Schools as care-givers can also introduce many interventions such as counselling workshops to equip teachers with professional crisis management. The research may encourage the Department of Education and schools to adopt violence prevention programs implemented in countries (like United States of America’s Olweus bullying and violence prevention program) for use in bringing communities together to work against school violence. These findings might strengthen the South African Department of Education’s Safe Schools Programs.
- Full Text:
- Date Issued: 2011
Repulsive-attractive models for the impact of two predators on prey species varying in anti-predator response
- Authors: Ddumba, Hassan
- Date: 2011
- Subjects: Predation (Biology) -- Mathematical models , Wildlife management -- Mathematical models , Pattern formation (Biology) , Predatory animals -- Ecology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10506 , http://hdl.handle.net/10948/d1010995 , Predation (Biology) -- Mathematical models , Wildlife management -- Mathematical models , Pattern formation (Biology) , Predatory animals -- Ecology
- Description: This study considers the dynamical interaction of two predatory carnivores (Lions (Panthera leo) and Spotted Hyaenas (Crocuta crocuta)) and three of their common prey (Buffalo (Syncerus caffer), Warthog (Phacochoerus africanus) and Kudu (Tragelaphus strepsiceros)). The dependence on spatial structure of species’ interaction stimulated the author to formulate reaction-diffusion models to explain the dynamics of predator-prey relationships in ecology. These models were used to predict and explain the effect of threshold populations, predator additional food and prey refuge on the general species’ dynamics. Vital parameters that model additional food to predators, prey refuge and population thresholds were given due attention in the analyses. The stability of a predator-prey model for an ecosystem faced with a prey out-flux which is analogous to and modelled as an Allee effect was investigated. The results highlight the bounds for the conversion efficiency of prey biomass to predator biomass (fertility gain) for which stability of the three species ecosystem model can be attained. Global stability analysis results showed that the prey (warthog) population density should exceed the sum of its carrying capacity and threshold value minus its equilibrium value i.e., W >(Kw + $) −W . This result shows that the warthog’s equilibrium population density is bounded above by population thresholds, i.e., W < (Kw+$). Besides showing the occurrence under parameter space of the so-called paradox of enrichment, early indicators of chaos can also be deduced. In addition, numerical results revealed stable oscillatory behaviour and stable spirals of the species as predator fertility rate, mortality rate and prey threshold were varied. The stabilising effect of prey refuge due to variations in predator fertility and proportion of prey in the refuge was studied. Formulation and analysis of a robust mathematical model for two predators having an overlapping dietary niche were also done. The Beddington-DeAngelis functional and numerical responses which are relevant in addressing the Principle of Competitive Exclusion as species interact were incorporated in the model. The stabilizing effect of additional food in relation to the relative diffusivity D, and wave number k, was investigated. Stability, dissipativity, permanence, persistence and periodicity of the model were studied using the routine and limit cycle perturbation methods. The periodic solutions (b 1 and b 3), which influence the dispersal rate (') of the interacting species, have been shown to be controlled by the wave number. For stability, and in order to overcome predator natural mortality, the nutritional value of predator additional food has been shown to be of high quality that can enhance predator fertility gain. The threshold relationships between various ecosystem parameters and the carrying capacity of the game park for the prey species were also deduced to ensure ecosystem persistence. Besides revealing irregular periodic travelling wave behaviour due to predator interference, numerical results also show oscillatory temporal dynamics resulting from additional food supplements combined with high predation rates.
- Full Text:
- Date Issued: 2011
- Authors: Ddumba, Hassan
- Date: 2011
- Subjects: Predation (Biology) -- Mathematical models , Wildlife management -- Mathematical models , Pattern formation (Biology) , Predatory animals -- Ecology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10506 , http://hdl.handle.net/10948/d1010995 , Predation (Biology) -- Mathematical models , Wildlife management -- Mathematical models , Pattern formation (Biology) , Predatory animals -- Ecology
- Description: This study considers the dynamical interaction of two predatory carnivores (Lions (Panthera leo) and Spotted Hyaenas (Crocuta crocuta)) and three of their common prey (Buffalo (Syncerus caffer), Warthog (Phacochoerus africanus) and Kudu (Tragelaphus strepsiceros)). The dependence on spatial structure of species’ interaction stimulated the author to formulate reaction-diffusion models to explain the dynamics of predator-prey relationships in ecology. These models were used to predict and explain the effect of threshold populations, predator additional food and prey refuge on the general species’ dynamics. Vital parameters that model additional food to predators, prey refuge and population thresholds were given due attention in the analyses. The stability of a predator-prey model for an ecosystem faced with a prey out-flux which is analogous to and modelled as an Allee effect was investigated. The results highlight the bounds for the conversion efficiency of prey biomass to predator biomass (fertility gain) for which stability of the three species ecosystem model can be attained. Global stability analysis results showed that the prey (warthog) population density should exceed the sum of its carrying capacity and threshold value minus its equilibrium value i.e., W >(Kw + $) −W . This result shows that the warthog’s equilibrium population density is bounded above by population thresholds, i.e., W < (Kw+$). Besides showing the occurrence under parameter space of the so-called paradox of enrichment, early indicators of chaos can also be deduced. In addition, numerical results revealed stable oscillatory behaviour and stable spirals of the species as predator fertility rate, mortality rate and prey threshold were varied. The stabilising effect of prey refuge due to variations in predator fertility and proportion of prey in the refuge was studied. Formulation and analysis of a robust mathematical model for two predators having an overlapping dietary niche were also done. The Beddington-DeAngelis functional and numerical responses which are relevant in addressing the Principle of Competitive Exclusion as species interact were incorporated in the model. The stabilizing effect of additional food in relation to the relative diffusivity D, and wave number k, was investigated. Stability, dissipativity, permanence, persistence and periodicity of the model were studied using the routine and limit cycle perturbation methods. The periodic solutions (b 1 and b 3), which influence the dispersal rate (') of the interacting species, have been shown to be controlled by the wave number. For stability, and in order to overcome predator natural mortality, the nutritional value of predator additional food has been shown to be of high quality that can enhance predator fertility gain. The threshold relationships between various ecosystem parameters and the carrying capacity of the game park for the prey species were also deduced to ensure ecosystem persistence. Besides revealing irregular periodic travelling wave behaviour due to predator interference, numerical results also show oscillatory temporal dynamics resulting from additional food supplements combined with high predation rates.
- Full Text:
- Date Issued: 2011
Risk-based assessment of environmental asbestos contamination in the Northern Cape and North West provinces of South Africa
- Authors: Jones, Robert Ryan
- Date: 2011
- Subjects: Asbestos industry -- Health aspects -- South Africa -- Northern Cape Asbestos industry -- Health aspects -- South Africa -- North West Environmental risk assessment -- South Africa-- Northern Cape Environmental risk assessment -- North West Asbestos -- Toxicology -- South Africa -- Northern Cape Asbestos -- Toxicology -- South Africa -- North West Tailings (Metallurgy) -- Waste disposal -- South Africa -- Northern Cape Tailings (Metallurgy) -- Waste disposal -- South Africa -- North West
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4780 , http://hdl.handle.net/10962/d1012612
- Description: The commercial mining of asbestos occurred in four Provinces of South Africa (Northern Cape, North West, Limpopo and Mpumalanga). It was initiated in the late 1800's and lasted for over a hundred years into the beginning of this century. As a producer of amphibole asbestos, South Africa far outpaced every other country being responsible for 97% of global production. The last crocidolite mine closed in 1996 and chrysotile in 2002. Anecdotal information concerning environmental contamination as a result of the former mining activities and the improper disposal of mine waste tailings has been reported by a variety of authors. Few comprehensive or systematic surveys have been conducted to date to document this issue and very little quantifiable research has been completed on the communities located in close proximity to the former mine sites to determine the extent of contamination. In 2004-2006 communities were surveyed within the Northern Cape and North West Provinces to determine the extent and severity of environmental contamination. This research developed and applied a methodology to select those communities suspected of environmental contamination, a targeted survey methodology, and a protocol for rapid sample laboratory analysis. A total of 41 communities were initially predicted by the model to be suspected for environmental asbestos contamination. Based on the inclusion of local knowledge, a final 36 communities were selected for a screening-level field assessment, 34 of which were found to contain environmental asbestos contamination at rates ranging from 20 to 100% of the surveyed locations. A total of 1 843 samples of soil and building material were collected in the screening level assessment. One community (Ga-Mopedi) was selected as being representative of the total cohort and a more detailed house to house survey was completed. A total of 1 486 samples were collected during the detailed survey. Results of the detailed survey revealed 26.2% of the homes were contaminated with asbestos containing soil and/or building material. A theoretical quantitative cumulative exposure assessment was developed to estimate the disease burden within the study area population of 126,130 individuals within the surveyed communities resulting in a predicted range of 25-52.4 excess deaths per year from lung cancer and mesothelioma due solely to environmental exposures to asbestos pollution.
- Full Text:
- Date Issued: 2011
- Authors: Jones, Robert Ryan
- Date: 2011
- Subjects: Asbestos industry -- Health aspects -- South Africa -- Northern Cape Asbestos industry -- Health aspects -- South Africa -- North West Environmental risk assessment -- South Africa-- Northern Cape Environmental risk assessment -- North West Asbestos -- Toxicology -- South Africa -- Northern Cape Asbestos -- Toxicology -- South Africa -- North West Tailings (Metallurgy) -- Waste disposal -- South Africa -- Northern Cape Tailings (Metallurgy) -- Waste disposal -- South Africa -- North West
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4780 , http://hdl.handle.net/10962/d1012612
- Description: The commercial mining of asbestos occurred in four Provinces of South Africa (Northern Cape, North West, Limpopo and Mpumalanga). It was initiated in the late 1800's and lasted for over a hundred years into the beginning of this century. As a producer of amphibole asbestos, South Africa far outpaced every other country being responsible for 97% of global production. The last crocidolite mine closed in 1996 and chrysotile in 2002. Anecdotal information concerning environmental contamination as a result of the former mining activities and the improper disposal of mine waste tailings has been reported by a variety of authors. Few comprehensive or systematic surveys have been conducted to date to document this issue and very little quantifiable research has been completed on the communities located in close proximity to the former mine sites to determine the extent of contamination. In 2004-2006 communities were surveyed within the Northern Cape and North West Provinces to determine the extent and severity of environmental contamination. This research developed and applied a methodology to select those communities suspected of environmental contamination, a targeted survey methodology, and a protocol for rapid sample laboratory analysis. A total of 41 communities were initially predicted by the model to be suspected for environmental asbestos contamination. Based on the inclusion of local knowledge, a final 36 communities were selected for a screening-level field assessment, 34 of which were found to contain environmental asbestos contamination at rates ranging from 20 to 100% of the surveyed locations. A total of 1 843 samples of soil and building material were collected in the screening level assessment. One community (Ga-Mopedi) was selected as being representative of the total cohort and a more detailed house to house survey was completed. A total of 1 486 samples were collected during the detailed survey. Results of the detailed survey revealed 26.2% of the homes were contaminated with asbestos containing soil and/or building material. A theoretical quantitative cumulative exposure assessment was developed to estimate the disease burden within the study area population of 126,130 individuals within the surveyed communities resulting in a predicted range of 25-52.4 excess deaths per year from lung cancer and mesothelioma due solely to environmental exposures to asbestos pollution.
- Full Text:
- Date Issued: 2011
Secondary school children's experiences of bereavement: implications for school counselling in Harare Metropolitan Province
- Authors: Shumba, Jenn
- Date: 2011
- Subjects: Bereavement , Counseling in secondary education -- Zimbabwe -- Harare , Schools -- Zimbabwe -- Harare -- Social conditions , Teachers -- Zimbabwe -- Harare -- Attitudes , Teachers -- Training -- Zimbabwe -- Harare , School children -- Zimbabwe -- Harare
- Language: English
- Type: Thesis , Doctoral , PhD (Education)
- Identifier: vital:16196 , http://hdl.handle.net/10353/d1007237 , Bereavement , Counseling in secondary education -- Zimbabwe -- Harare , Schools -- Zimbabwe -- Harare -- Social conditions , Teachers -- Zimbabwe -- Harare -- Attitudes , Teachers -- Training -- Zimbabwe -- Harare , School children -- Zimbabwe -- Harare
- Description: Death and bereavement are prevalent in Zimbabwe due to HIV/AIDS and other illnesses. It is estimated that a large population of school going learners have lost one or both parents and have become orphans. The aim of the study was two-fold: to understand the bereavement experiences of orphaned learners and to examine how such experiences can inform school counselling services. A multiple case study involving 13 school children and four school counsellors from two secondary schools in Harare Metropolitan Region was conducted. Each of the 17 participants was viewed as a bounded case due to his or her individual unique experiences. An interpretive phenomenological approach was employed to collect and analyse the data. All the cases were purposively selected as they were bearers of crucial information on bereavement experiences and bereavement counselling. The study established nine (9) key findings. First, it was found that the type of attachments and support systems the child had were contributory to the way the child experienced bereavement. Second, it was established that although learners manifested emotional pain, they found it difficult to verbalise it. Third, the study found that cultural practices either exacerbate or work for the better for bereaved children as some were seen to enhance their livelihood whilst some were detrimental and oppressive. Fourth, it was established that bereavement triggered philosophical and reflexive reactions on the part of bereaved children. The deaths of the parents resulted in them reflecting on the three phases of their life trajectories: life before death; at the time of death; and after death. Fifth, it was also established in the study that there was a mismatch in what children and counsellors claimed to be happening in secondary schools pertaining bereavement counselling provisioning. Sixth, the study found that most children did not receive any bereavement counselling in schools. Only three out of the 13 learner cases interviewed in this study had a teacher in the school talk to them about loss of their parents. In some instances, a child’s bereavement was only discovered through the grapevine or when this researcher got to the school. Seventh, it was established that although counsellors were qualified as both teachers and counsellors, they lacked confidence in dealing with sensitive issues such as bereavement. Eighth, the study also found that although there is a lot of death in Zimbabwe the counselling syllabi lacked focus on bereavement counselling. Ninth, it was also discovered that teachers who were not assigned to counselling duties had negative attitudes towards counselling, a matter which has serious consequences for the bereaved learners. Based on the above findings, the study concludes that bereaved children experienced a variety of circumstances that impacted both positively and negatively on their schooling and rendered them in need of bereavement counselling. It also concludes that bereaved learners in selected Harare schools were not receiving adequate bereavement counselling; schools neither had policies nor laid down procedures on bereavement counselling. For further research, the study recommends that there should be research focusing on methodologies designed to access children’s innermost feelings of emotional pain. There should be further research on the nature of the relationship between a child’s bereavement and educational experiences. Studies involving other bereaved populations, such as, children from rural areas and primary school children should be carried out in order to gain insights on how the phenomenon is experienced by different age groups in different contexts. To improve counselling practice in schools, the study recommends that there should be capacity building programmes aimed at assisting teachers to deal with bereavement counselling. School bereavement counselling should explore collaboration with other stakeholders such as peers, care givers and government as well as non-governmental organisations. Above all, the study recommends that schools should be proactive and have school bereavement policies and procedures on bereavement counselling.
- Full Text:
- Date Issued: 2011
- Authors: Shumba, Jenn
- Date: 2011
- Subjects: Bereavement , Counseling in secondary education -- Zimbabwe -- Harare , Schools -- Zimbabwe -- Harare -- Social conditions , Teachers -- Zimbabwe -- Harare -- Attitudes , Teachers -- Training -- Zimbabwe -- Harare , School children -- Zimbabwe -- Harare
- Language: English
- Type: Thesis , Doctoral , PhD (Education)
- Identifier: vital:16196 , http://hdl.handle.net/10353/d1007237 , Bereavement , Counseling in secondary education -- Zimbabwe -- Harare , Schools -- Zimbabwe -- Harare -- Social conditions , Teachers -- Zimbabwe -- Harare -- Attitudes , Teachers -- Training -- Zimbabwe -- Harare , School children -- Zimbabwe -- Harare
- Description: Death and bereavement are prevalent in Zimbabwe due to HIV/AIDS and other illnesses. It is estimated that a large population of school going learners have lost one or both parents and have become orphans. The aim of the study was two-fold: to understand the bereavement experiences of orphaned learners and to examine how such experiences can inform school counselling services. A multiple case study involving 13 school children and four school counsellors from two secondary schools in Harare Metropolitan Region was conducted. Each of the 17 participants was viewed as a bounded case due to his or her individual unique experiences. An interpretive phenomenological approach was employed to collect and analyse the data. All the cases were purposively selected as they were bearers of crucial information on bereavement experiences and bereavement counselling. The study established nine (9) key findings. First, it was found that the type of attachments and support systems the child had were contributory to the way the child experienced bereavement. Second, it was established that although learners manifested emotional pain, they found it difficult to verbalise it. Third, the study found that cultural practices either exacerbate or work for the better for bereaved children as some were seen to enhance their livelihood whilst some were detrimental and oppressive. Fourth, it was established that bereavement triggered philosophical and reflexive reactions on the part of bereaved children. The deaths of the parents resulted in them reflecting on the three phases of their life trajectories: life before death; at the time of death; and after death. Fifth, it was also established in the study that there was a mismatch in what children and counsellors claimed to be happening in secondary schools pertaining bereavement counselling provisioning. Sixth, the study found that most children did not receive any bereavement counselling in schools. Only three out of the 13 learner cases interviewed in this study had a teacher in the school talk to them about loss of their parents. In some instances, a child’s bereavement was only discovered through the grapevine or when this researcher got to the school. Seventh, it was established that although counsellors were qualified as both teachers and counsellors, they lacked confidence in dealing with sensitive issues such as bereavement. Eighth, the study also found that although there is a lot of death in Zimbabwe the counselling syllabi lacked focus on bereavement counselling. Ninth, it was also discovered that teachers who were not assigned to counselling duties had negative attitudes towards counselling, a matter which has serious consequences for the bereaved learners. Based on the above findings, the study concludes that bereaved children experienced a variety of circumstances that impacted both positively and negatively on their schooling and rendered them in need of bereavement counselling. It also concludes that bereaved learners in selected Harare schools were not receiving adequate bereavement counselling; schools neither had policies nor laid down procedures on bereavement counselling. For further research, the study recommends that there should be research focusing on methodologies designed to access children’s innermost feelings of emotional pain. There should be further research on the nature of the relationship between a child’s bereavement and educational experiences. Studies involving other bereaved populations, such as, children from rural areas and primary school children should be carried out in order to gain insights on how the phenomenon is experienced by different age groups in different contexts. To improve counselling practice in schools, the study recommends that there should be capacity building programmes aimed at assisting teachers to deal with bereavement counselling. School bereavement counselling should explore collaboration with other stakeholders such as peers, care givers and government as well as non-governmental organisations. Above all, the study recommends that schools should be proactive and have school bereavement policies and procedures on bereavement counselling.
- Full Text:
- Date Issued: 2011
Sedimentology of plio-pleistocene gravel barrier deposits in the palaeo-Orange River mouth, Namibia : depositional history and diamond mineralisation
- Authors: Spaggiari, Renato Igino
- Date: 2011 , 2013-08-19
- Subjects: Diamond mines and mining -- Namibia Sediments (Geology) -- South Africa and Namibia -- Orange River Estuary Diamond deposits -- Namibia Orange River Estuary (Namibia and South Africa)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4927 , http://hdl.handle.net/10962/d1004636
- Description: The largest known marine diamond placer, the Namibian mega-placer, lies along the Atlantic coast of south-western Africa from the Orange River mouth 1,000 km northwards to the Namibian-Angolan border. The most economically viable portion of the Namibian mega-placer (>75 million carats recovered at >95% gem quality) comprises onshore and offshore marine deposits that are developed within ∼100km of the Orange River outfall. For much of the Cainozoic, this long-lived fluvial system has been the main conduit transporting diamonds from kimberlitic and secondary sources in the cratonic hinterland of southern Africa to the Atlantic shelf that has been neutrally buoyant over this period. Highly energetic marine processes, driven in part, by southerly winds with an attendant northward-directed longshore drift, have generated terminal placers that are preserved both onshore and offshore. This study, through detailed field sedimentological and diamond analyses, investigates the development and mineralisation of gravel barrier deposits within the ancestral Orange River mouth area during a major ∼30 m regional transgression ('30 m Package') in the Late Pliocene. At that time, diamond supply from this fluvial conduit was minimal, yet the corresponding onshore marine deposits to the north of the Orange River mouth were significantly diamond enriched, enabling large-scale alluvial diamond mining to take place for over 75 years. Of the entire coastline of south-western Africa, the most complete accumulation of the '30 m Package' is preserved within the palaeo-Orange River mouth as barrier spit and barrier beach deposits. Arranged vertically and laterally in a 16m thick succession, these are deposits of: (1) intertidal beach, (2) lagoon and washover, (3) tidal inlet and spit recurve and (4) storm-dominated subtidal settings. These were parts of larger barrier features, the bulk of which are preserved as highstand deposits that are diamond-bearing with varying, but generally low grades (<13 stones (diamonds) per hundred tons, spht). Intertidal beach and spit recurve deposits have higher economic grades (12-13 spht) due to the energetic sieving and mobile trapping mechanisms associated with their emplacement. In contrast, the less reworked and more sandy subtidal, tidal inlet and washover deposits have un-economic grades (<2 spht). Despite these low grades, the barrier deposits have the largest average stone (diamond) size (1-2 carats/stone, cts/stn) of the entire Namibian mega-placer, given their proximity to the ancestral Orange River outfall. This study demonstrates that barrier shoreline evolution at the fluvial/marine interface was controlled by: (1) a strong and coarse fluvial sediment supply that sustained shoreline growth on a highly energetic coast, (2) accommodation space facilitating sediment preservation and (3) short-duration, high-frequency sea-level cycles superimposed on the∼30 m regional transgression, promoting hierarchal stacking of progradational deposits. During these sea-level fluctuations, diamonds were 'farmed' from older, shelf sequences in the offshore and driven landward to accumulate in '30 m Package' highstand barrier deposits. In spite of the large supply of diamonds, their retention in these deposits was poor due to an incompetent footwall of ancestral Orange River mouth sediment and the inherent cobble-boulder size of the barrier gravels. Thus the principal process controlling diamond entrapment in these barrier deposits was kinetic sieving in a coarse-grained framework. Consequently, at the marine/fluvial interface and down-drift for ∼5 km, larger diamonds (1-2 cts/stn) were retained in low-grade (<2 spht), coarse-gravel barrier shorelines. Smaller diamonds (mostly < I cts/stn) were rejected into the northward-driven littoral sediments and further size-sorted along ∼95 km of Namibian coast to accumulate in finer, high-grade beach placers (> 100 spht) where bedrock footwall promoted such high concentrations. The gravel-dominated palaeo-Orange River mouth is considered to be the ' heart' of the Namibian mega-placer, controlling sediment and diamond supply to the littoral zone further north. Although coarse gravel is retained at the river mouth, the incompetence of this highly energetic setting to trap diamonds renders it sub-economic. This ineffectiveness at the fluvial/marine interface is thus fundamental in enriching the coastal tract farther down-drift and developing highly economic coastal placers along the Atlantic coast of south-western Africa. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 2011
- Authors: Spaggiari, Renato Igino
- Date: 2011 , 2013-08-19
- Subjects: Diamond mines and mining -- Namibia Sediments (Geology) -- South Africa and Namibia -- Orange River Estuary Diamond deposits -- Namibia Orange River Estuary (Namibia and South Africa)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4927 , http://hdl.handle.net/10962/d1004636
- Description: The largest known marine diamond placer, the Namibian mega-placer, lies along the Atlantic coast of south-western Africa from the Orange River mouth 1,000 km northwards to the Namibian-Angolan border. The most economically viable portion of the Namibian mega-placer (>75 million carats recovered at >95% gem quality) comprises onshore and offshore marine deposits that are developed within ∼100km of the Orange River outfall. For much of the Cainozoic, this long-lived fluvial system has been the main conduit transporting diamonds from kimberlitic and secondary sources in the cratonic hinterland of southern Africa to the Atlantic shelf that has been neutrally buoyant over this period. Highly energetic marine processes, driven in part, by southerly winds with an attendant northward-directed longshore drift, have generated terminal placers that are preserved both onshore and offshore. This study, through detailed field sedimentological and diamond analyses, investigates the development and mineralisation of gravel barrier deposits within the ancestral Orange River mouth area during a major ∼30 m regional transgression ('30 m Package') in the Late Pliocene. At that time, diamond supply from this fluvial conduit was minimal, yet the corresponding onshore marine deposits to the north of the Orange River mouth were significantly diamond enriched, enabling large-scale alluvial diamond mining to take place for over 75 years. Of the entire coastline of south-western Africa, the most complete accumulation of the '30 m Package' is preserved within the palaeo-Orange River mouth as barrier spit and barrier beach deposits. Arranged vertically and laterally in a 16m thick succession, these are deposits of: (1) intertidal beach, (2) lagoon and washover, (3) tidal inlet and spit recurve and (4) storm-dominated subtidal settings. These were parts of larger barrier features, the bulk of which are preserved as highstand deposits that are diamond-bearing with varying, but generally low grades (<13 stones (diamonds) per hundred tons, spht). Intertidal beach and spit recurve deposits have higher economic grades (12-13 spht) due to the energetic sieving and mobile trapping mechanisms associated with their emplacement. In contrast, the less reworked and more sandy subtidal, tidal inlet and washover deposits have un-economic grades (<2 spht). Despite these low grades, the barrier deposits have the largest average stone (diamond) size (1-2 carats/stone, cts/stn) of the entire Namibian mega-placer, given their proximity to the ancestral Orange River outfall. This study demonstrates that barrier shoreline evolution at the fluvial/marine interface was controlled by: (1) a strong and coarse fluvial sediment supply that sustained shoreline growth on a highly energetic coast, (2) accommodation space facilitating sediment preservation and (3) short-duration, high-frequency sea-level cycles superimposed on the∼30 m regional transgression, promoting hierarchal stacking of progradational deposits. During these sea-level fluctuations, diamonds were 'farmed' from older, shelf sequences in the offshore and driven landward to accumulate in '30 m Package' highstand barrier deposits. In spite of the large supply of diamonds, their retention in these deposits was poor due to an incompetent footwall of ancestral Orange River mouth sediment and the inherent cobble-boulder size of the barrier gravels. Thus the principal process controlling diamond entrapment in these barrier deposits was kinetic sieving in a coarse-grained framework. Consequently, at the marine/fluvial interface and down-drift for ∼5 km, larger diamonds (1-2 cts/stn) were retained in low-grade (<2 spht), coarse-gravel barrier shorelines. Smaller diamonds (mostly < I cts/stn) were rejected into the northward-driven littoral sediments and further size-sorted along ∼95 km of Namibian coast to accumulate in finer, high-grade beach placers (> 100 spht) where bedrock footwall promoted such high concentrations. The gravel-dominated palaeo-Orange River mouth is considered to be the ' heart' of the Namibian mega-placer, controlling sediment and diamond supply to the littoral zone further north. Although coarse gravel is retained at the river mouth, the incompetence of this highly energetic setting to trap diamonds renders it sub-economic. This ineffectiveness at the fluvial/marine interface is thus fundamental in enriching the coastal tract farther down-drift and developing highly economic coastal placers along the Atlantic coast of south-western Africa. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 2011
Social policy and the state in South Africa: pathways for human capability development
- Authors: Monyai, Priscilla B
- Date: 2011
- Subjects: Human capital -- South Africa , Apartheid -- South Africa , Equality -- South Africa , Poverty -- South Africa , Political participation -- South Africa , South Africa -- Economic conditions , South Africa -- Social conditions
- Language: English
- Type: Thesis , Doctoral , PhD (Social Science Dev)
- Identifier: vital:11439 , http://hdl.handle.net/10353/d1007230 , Human capital -- South Africa , Apartheid -- South Africa , Equality -- South Africa , Poverty -- South Africa , Political participation -- South Africa , South Africa -- Economic conditions , South Africa -- Social conditions
- Description: The main focus of this thesis is the challenges that are facing social policy development and implementation in South Africa in relation to the enhancement of human capability. The study adopted a historical approach to assess the model of social policy in South Africa and identified that social relations of domination inherited from the apartheid era continuing to produce inequalities in opportunities. Social policy under the democratic government has not managed to address social inequalities and the main drivers of poverty in the form of income poverty, asset poverty and capability poverty which are the underlying factors reproducing deprivation and destitution of the majority of the population Although South Africa prides itself of a stable democracy, social inequalities continue to undermine the benefits of social citizenship because political participation in the midst of unequal access to economic and social resources undermine the value of citizenship. Also, inequalities in the distribution of income and wealth, and in the control of economic production undermine political equality which is an ethic upon which social rights are predicated. As a result, state interventions are lacking inherent potential to build human capability for people to live the life that they have reason to value. The paradox of social policy in South Africa is that the majority of those who are marginalised are those who were excluded by the apartheid regime even though state intervention is claimed to be targeting them. This points to the failure of incremental equalisation of opportunities within a context of stark social inequities. It is also an indication that the economic growth path delivered by the political transition is working to reinforce the inherited legacy of deprivation and it is avoiding questions related to the structural nature of poverty and inequalities. Therefore, a transformative social policy is an imperative for South Africa. Such a framework of social policy should be premised upon a notion of human security in order to built human capability. Human security focuses on the security of individuals and communities to strengthen human development. It emphasises on civil, political and socioeconomic rights for individual citizens to participate fully in the process of governance. Although this thesis is a case study of social policy in South Africa, it can be used to appreciate the role of social policy in other developing countries, particularly the impact of political decision making on social distribution. Poverty and social inequalities are growing problems in developing countries and so is the importance of putting these problems under the spotlight for political attention.
- Full Text:
- Date Issued: 2011
- Authors: Monyai, Priscilla B
- Date: 2011
- Subjects: Human capital -- South Africa , Apartheid -- South Africa , Equality -- South Africa , Poverty -- South Africa , Political participation -- South Africa , South Africa -- Economic conditions , South Africa -- Social conditions
- Language: English
- Type: Thesis , Doctoral , PhD (Social Science Dev)
- Identifier: vital:11439 , http://hdl.handle.net/10353/d1007230 , Human capital -- South Africa , Apartheid -- South Africa , Equality -- South Africa , Poverty -- South Africa , Political participation -- South Africa , South Africa -- Economic conditions , South Africa -- Social conditions
- Description: The main focus of this thesis is the challenges that are facing social policy development and implementation in South Africa in relation to the enhancement of human capability. The study adopted a historical approach to assess the model of social policy in South Africa and identified that social relations of domination inherited from the apartheid era continuing to produce inequalities in opportunities. Social policy under the democratic government has not managed to address social inequalities and the main drivers of poverty in the form of income poverty, asset poverty and capability poverty which are the underlying factors reproducing deprivation and destitution of the majority of the population Although South Africa prides itself of a stable democracy, social inequalities continue to undermine the benefits of social citizenship because political participation in the midst of unequal access to economic and social resources undermine the value of citizenship. Also, inequalities in the distribution of income and wealth, and in the control of economic production undermine political equality which is an ethic upon which social rights are predicated. As a result, state interventions are lacking inherent potential to build human capability for people to live the life that they have reason to value. The paradox of social policy in South Africa is that the majority of those who are marginalised are those who were excluded by the apartheid regime even though state intervention is claimed to be targeting them. This points to the failure of incremental equalisation of opportunities within a context of stark social inequities. It is also an indication that the economic growth path delivered by the political transition is working to reinforce the inherited legacy of deprivation and it is avoiding questions related to the structural nature of poverty and inequalities. Therefore, a transformative social policy is an imperative for South Africa. Such a framework of social policy should be premised upon a notion of human security in order to built human capability. Human security focuses on the security of individuals and communities to strengthen human development. It emphasises on civil, political and socioeconomic rights for individual citizens to participate fully in the process of governance. Although this thesis is a case study of social policy in South Africa, it can be used to appreciate the role of social policy in other developing countries, particularly the impact of political decision making on social distribution. Poverty and social inequalities are growing problems in developing countries and so is the importance of putting these problems under the spotlight for political attention.
- Full Text:
- Date Issued: 2011
Strategies to create a post-merged organisational culture conducive to effective performance management
- Authors: Paul, Gary William
- Date: 2011
- Subjects: Corporate culture , Organizational change , Organizational effectiveness
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:9385 , http://hdl.handle.net/10948/d1010857 , Corporate culture , Organizational change , Organizational effectiveness
- Description: Mergers have been described as the most complex business process that an organisation can be faced with, requiring executives and other stakeholders to discharge the promise of a more successful merged organisation. However, several studies have highlighted the factors that led to the demise of the merged organisations. One of the often quoted and frequently blamed aspects related to merger failure has been the lack of effective post-merged organisational culture integration and alignment. Where mergers have been successful, it was attributed to a structured approach to integrating and aligning all aspects related to organisational culture thus ensuring the creation of a high performing organisation, conducive to effective performance management. The main research problem in this study centred around the identification of strategies that could be used to design an integrated model for creating a post-merged organisational culture which is conducive to effectively managing performance. To achieve this objective, the following approaches were adopted: A literature study was conducted with the view to identifying the challenges facing merged organisations in general and post-merged South African Higher Education institutions in particular. The researcher also conducted interviews with senior HR practitioner at the institutions participating in this study to gain insights into their experiences of performance within their merged institutions. The institutions involved in this study were Nelson Mandela Metropolitan University (NMMU), Cape Peninsula University of Technology (CPUT and Durban University of Technology (DUT). The insights gleaned from these interviews were incorporated into the survey questionnaire. The literature study also concerned itself with the identification of strategies that merged organisations could use in its pursuit of organisational culture alignment and integration. These strategies included conducting critical pre-merger assessments or due-diligence studies, adopting structured approaches to dealing with resistance to change, employee engagement, the design, implementation and communication of monitoring and evaluation of merger success measures as well as several other moderating variables referred to in figure 1.2. In terms of sub-problem six of the study, the findings of sub-problems one, two and five were used to develop an eight-step integrated theoretical model to create an organisational culture conducive to effective performance management in a post-merged environment. The model served as a basis for the design of a survey questionnaire. The questionnaire was used to ascertain the extent to which respondents from the three participating institutions (NMMU, CPUT and DUT), perceived the various strategies as being important in establishing a post-merged organisational culture conducive to effective performance management. The results that emerged from the empirical study showed a strong concurrence with the strategies identified in the literature study and included in the integrated theoretical model. The quantitative and qualitative results from the empirical study where incorporated into the integrated theoretical model, which lead to a refined Eight-Step Integrated Post-merged Organisational Culture Creation Model as depicted in Figure 7.1 with associated details in Figure 7.2.
- Full Text:
- Date Issued: 2011
- Authors: Paul, Gary William
- Date: 2011
- Subjects: Corporate culture , Organizational change , Organizational effectiveness
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:9385 , http://hdl.handle.net/10948/d1010857 , Corporate culture , Organizational change , Organizational effectiveness
- Description: Mergers have been described as the most complex business process that an organisation can be faced with, requiring executives and other stakeholders to discharge the promise of a more successful merged organisation. However, several studies have highlighted the factors that led to the demise of the merged organisations. One of the often quoted and frequently blamed aspects related to merger failure has been the lack of effective post-merged organisational culture integration and alignment. Where mergers have been successful, it was attributed to a structured approach to integrating and aligning all aspects related to organisational culture thus ensuring the creation of a high performing organisation, conducive to effective performance management. The main research problem in this study centred around the identification of strategies that could be used to design an integrated model for creating a post-merged organisational culture which is conducive to effectively managing performance. To achieve this objective, the following approaches were adopted: A literature study was conducted with the view to identifying the challenges facing merged organisations in general and post-merged South African Higher Education institutions in particular. The researcher also conducted interviews with senior HR practitioner at the institutions participating in this study to gain insights into their experiences of performance within their merged institutions. The institutions involved in this study were Nelson Mandela Metropolitan University (NMMU), Cape Peninsula University of Technology (CPUT and Durban University of Technology (DUT). The insights gleaned from these interviews were incorporated into the survey questionnaire. The literature study also concerned itself with the identification of strategies that merged organisations could use in its pursuit of organisational culture alignment and integration. These strategies included conducting critical pre-merger assessments or due-diligence studies, adopting structured approaches to dealing with resistance to change, employee engagement, the design, implementation and communication of monitoring and evaluation of merger success measures as well as several other moderating variables referred to in figure 1.2. In terms of sub-problem six of the study, the findings of sub-problems one, two and five were used to develop an eight-step integrated theoretical model to create an organisational culture conducive to effective performance management in a post-merged environment. The model served as a basis for the design of a survey questionnaire. The questionnaire was used to ascertain the extent to which respondents from the three participating institutions (NMMU, CPUT and DUT), perceived the various strategies as being important in establishing a post-merged organisational culture conducive to effective performance management. The results that emerged from the empirical study showed a strong concurrence with the strategies identified in the literature study and included in the integrated theoretical model. The quantitative and qualitative results from the empirical study where incorporated into the integrated theoretical model, which lead to a refined Eight-Step Integrated Post-merged Organisational Culture Creation Model as depicted in Figure 7.1 with associated details in Figure 7.2.
- Full Text:
- Date Issued: 2011
Structural and functional characterisation of the protein inhibitor of activated STAT3 (PIAS3)
- Authors: Mautsa, Nicodemus
- Date: 2011
- Subjects: Cytokines Immune response Proteins Cancer cells -- Growth -- Regulation
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3991 , http://hdl.handle.net/10962/d1004050
- Description: The signal transducer and activator of transcription (STAT) and protein inhibitor of STAT(PIAS) system represent an elegant regulatory mechanism of transcriptional control IN mammalian cytokine signalling. Abnormal activation of the system is associated with immune disorders and a large group of diverse tumours. PIAS3 is a multiple domain protein with distinct functions involved in regulation of cytokine-mediated gene activation pathways.Its over-expression significantly inhibits cell growth and renders cancer cells more sensitive to drugs. The objective of this study was to structurally and biochemically characterise the function of the PIAS3 protein using in silico, in vivo and in vitro analysis approaches.The conservation pattern of the PIAS protein family and critical conserved residues in the PINIT (Proline, Isoleucine, Asparagine, Isoleucine, Tyrosine) domain were identified. The PINIT domain model was generated based on the PINIT domain structure of yeast PIAS3 homologue Siz1 and structural determinants in the PIAS3-STAT3 interaction were evaluated.Guided by the in silico findings, in vivo analysis of the localisation of the PIAS3, mutantderivatives of PIAS3 (PIAS3-L97A, PIAS3-R99N, PIAS3-R99Q), PINIT and acidic domain was conducted. PIAS3 was completely localised in the nucleus while PIAS3 mutants appeared to exhibit diffuse cytoplasmic distribution. The PINIT domain was predominantly localised in the nucleus with some apparent perinuclear staining while the acidic domain exhibited a predominantly perinuclear staining pattern. Further analysis of the PINIT domain and the effect of the mutants on PIAS3-STAT3 interaction were assessed by in vitro analysis. Guided by in silico analysis, the PINIT domain and mutant derivatives of PINIT domain (PINIT-L97A, PINIT-R99N, and PINIT-R99Q) were heterologously expressed in Escherichia coli and subsequently purified using a combination of immobilized metal affinity and size exclusion based chromatography. The size and structural elements of the PINIT domain and its mutants were characterised. The 23 kDa PINIT domain was found to exist as a monomer in solution and its secondary structure was shown to consist of 66 % β-sheets by fourier transformed infrared spectroscopy consistent with the generated homology model.Using surface plasmonresonance spectroscopy (SPR) the PINIT domain was shown to bind to STAT3 in a specific concentration dependent manner. Recombinant PINIT-L97A,PINITR99N and PINIT-R99Q mutants, which exhibited similar structural integrity to the wildtype, were found to abrogate binding to STAT3. These findings suggest that these residues form part of a potential binding surface for stat3. In conclusion, this study has provided evidence that the PINIT domain is an important determinant of PIAS3 interaction with STAT3 and that the interaction is mediated by defined conserved residues directly involved in the PINITSTAT3 interaction.
- Full Text:
- Date Issued: 2011
- Authors: Mautsa, Nicodemus
- Date: 2011
- Subjects: Cytokines Immune response Proteins Cancer cells -- Growth -- Regulation
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3991 , http://hdl.handle.net/10962/d1004050
- Description: The signal transducer and activator of transcription (STAT) and protein inhibitor of STAT(PIAS) system represent an elegant regulatory mechanism of transcriptional control IN mammalian cytokine signalling. Abnormal activation of the system is associated with immune disorders and a large group of diverse tumours. PIAS3 is a multiple domain protein with distinct functions involved in regulation of cytokine-mediated gene activation pathways.Its over-expression significantly inhibits cell growth and renders cancer cells more sensitive to drugs. The objective of this study was to structurally and biochemically characterise the function of the PIAS3 protein using in silico, in vivo and in vitro analysis approaches.The conservation pattern of the PIAS protein family and critical conserved residues in the PINIT (Proline, Isoleucine, Asparagine, Isoleucine, Tyrosine) domain were identified. The PINIT domain model was generated based on the PINIT domain structure of yeast PIAS3 homologue Siz1 and structural determinants in the PIAS3-STAT3 interaction were evaluated.Guided by the in silico findings, in vivo analysis of the localisation of the PIAS3, mutantderivatives of PIAS3 (PIAS3-L97A, PIAS3-R99N, PIAS3-R99Q), PINIT and acidic domain was conducted. PIAS3 was completely localised in the nucleus while PIAS3 mutants appeared to exhibit diffuse cytoplasmic distribution. The PINIT domain was predominantly localised in the nucleus with some apparent perinuclear staining while the acidic domain exhibited a predominantly perinuclear staining pattern. Further analysis of the PINIT domain and the effect of the mutants on PIAS3-STAT3 interaction were assessed by in vitro analysis. Guided by in silico analysis, the PINIT domain and mutant derivatives of PINIT domain (PINIT-L97A, PINIT-R99N, and PINIT-R99Q) were heterologously expressed in Escherichia coli and subsequently purified using a combination of immobilized metal affinity and size exclusion based chromatography. The size and structural elements of the PINIT domain and its mutants were characterised. The 23 kDa PINIT domain was found to exist as a monomer in solution and its secondary structure was shown to consist of 66 % β-sheets by fourier transformed infrared spectroscopy consistent with the generated homology model.Using surface plasmonresonance spectroscopy (SPR) the PINIT domain was shown to bind to STAT3 in a specific concentration dependent manner. Recombinant PINIT-L97A,PINITR99N and PINIT-R99Q mutants, which exhibited similar structural integrity to the wildtype, were found to abrogate binding to STAT3. These findings suggest that these residues form part of a potential binding surface for stat3. In conclusion, this study has provided evidence that the PINIT domain is an important determinant of PIAS3 interaction with STAT3 and that the interaction is mediated by defined conserved residues directly involved in the PINITSTAT3 interaction.
- Full Text:
- Date Issued: 2011
Studies in marine quinone chemistry
- Authors: Sunassee, Suthananda Naidu
- Date: 2011
- Subjects: Quinone Marine natural products Marine invertebrates Marine pharmacology Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4355 , http://hdl.handle.net/10962/d1005020
- Description: This thesis is divided into two parts and the rationale of the research conducted is based on the cytotoxicity of the prenylated quinones 1.24-1.29, isolated from the South African nudibranch Leminda millecra, against oesophageal cancer cells. The first part (Chapters 2 and 3) of the thesis initially documents the distribution of cytotoxic and antioxidant prenylated quinones and hydroquinones in the marine environment. We have been able to show, for the first time, that these compounds can be divided into eight structural classes closely related to their phyletic distribution. Secondly, we attempted to synthesize the two marine natural products 1.24 and 1.26 in an effort to contribute to an ongoing collaborative search with the Division of Medical Biochemistry at the University of Cape Town for new compounds with anti-oesophageal cancer activity. Accordingly, we followed the published synthetic procedure for 1.26 and, although we were unable to reproduce the reported results, we have generated five new prenylated quinone analogues 3.53-3.55, 3.63 and 3.71, which are a potentially viable addition to our ongoing structure-activity relationship (SAR) studies. Moreover, we embarked on a 7Li NMR mechanistic study for the synthesis of 3.2 from 3.1 which rewarded us with an improved and reproducible methodology for this crucial reaction that is detailed in Chapter 3. The second part of this thesis (Chapters 4 and 5) is concerned with a synthetic, structural, electrochemical and biological exploration of the 1,4-naphthoquinone nucleus as a primary pharmacophore in our search for new chemical entities which can induce apoptosis in oesophageal cancer cells, thus contributing to our overall ongoing SAR study in this class of compounds. Seven new naphthoquinone derivatves (4.19, 4.30, 4.31, 4.33 and 4.46-4.48) of the natural products 2-deoxylapachol (2.44), lapachol (4.1) and β-lapachone (5.2) were synthesized and 2-(1`-hydroxy-`-phenylmethyl)-1,4-naphthoquinone (4.29) was found to be the most cytotoxic (IC50 1.5 μM) against the oesophageal cancer cell line WHCO1, while 5.2, which is currently in phase II clinical trials as an anticancer drug, was found to be similarly active (IC50 1.6 μM). Electrochemical investigations of the redox properties of the benzylic alcohol derivatives 4.29-4.31 indicated a higher reduction potential compared to their oxidized counterparts 4.45-4.48, and this finding has been correlated to the increased activity of 4.29-4.31 against the WHCO1 cell line. Additionally, 4.29 is synthetically more accessible than either 1.26 or 5.2 and potentially a lead compound in our search for new and more effective chemotherapeutic agents against oesophageal cancer
- Full Text:
- Date Issued: 2011
- Authors: Sunassee, Suthananda Naidu
- Date: 2011
- Subjects: Quinone Marine natural products Marine invertebrates Marine pharmacology Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4355 , http://hdl.handle.net/10962/d1005020
- Description: This thesis is divided into two parts and the rationale of the research conducted is based on the cytotoxicity of the prenylated quinones 1.24-1.29, isolated from the South African nudibranch Leminda millecra, against oesophageal cancer cells. The first part (Chapters 2 and 3) of the thesis initially documents the distribution of cytotoxic and antioxidant prenylated quinones and hydroquinones in the marine environment. We have been able to show, for the first time, that these compounds can be divided into eight structural classes closely related to their phyletic distribution. Secondly, we attempted to synthesize the two marine natural products 1.24 and 1.26 in an effort to contribute to an ongoing collaborative search with the Division of Medical Biochemistry at the University of Cape Town for new compounds with anti-oesophageal cancer activity. Accordingly, we followed the published synthetic procedure for 1.26 and, although we were unable to reproduce the reported results, we have generated five new prenylated quinone analogues 3.53-3.55, 3.63 and 3.71, which are a potentially viable addition to our ongoing structure-activity relationship (SAR) studies. Moreover, we embarked on a 7Li NMR mechanistic study for the synthesis of 3.2 from 3.1 which rewarded us with an improved and reproducible methodology for this crucial reaction that is detailed in Chapter 3. The second part of this thesis (Chapters 4 and 5) is concerned with a synthetic, structural, electrochemical and biological exploration of the 1,4-naphthoquinone nucleus as a primary pharmacophore in our search for new chemical entities which can induce apoptosis in oesophageal cancer cells, thus contributing to our overall ongoing SAR study in this class of compounds. Seven new naphthoquinone derivatves (4.19, 4.30, 4.31, 4.33 and 4.46-4.48) of the natural products 2-deoxylapachol (2.44), lapachol (4.1) and β-lapachone (5.2) were synthesized and 2-(1`-hydroxy-`-phenylmethyl)-1,4-naphthoquinone (4.29) was found to be the most cytotoxic (IC50 1.5 μM) against the oesophageal cancer cell line WHCO1, while 5.2, which is currently in phase II clinical trials as an anticancer drug, was found to be similarly active (IC50 1.6 μM). Electrochemical investigations of the redox properties of the benzylic alcohol derivatives 4.29-4.31 indicated a higher reduction potential compared to their oxidized counterparts 4.45-4.48, and this finding has been correlated to the increased activity of 4.29-4.31 against the WHCO1 cell line. Additionally, 4.29 is synthetically more accessible than either 1.26 or 5.2 and potentially a lead compound in our search for new and more effective chemotherapeutic agents against oesophageal cancer
- Full Text:
- Date Issued: 2011
Surface properties and electrocatalytic applications of metallophthalocyanines confined on electrode surfaces
- Authors: Akinbulu, Isaac Adebayo
- Date: 2011
- Subjects: Phthalocyanines Electrochemistry Electrocatalysis Pesticides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4365 , http://hdl.handle.net/10962/d1005030
- Description: New cobalt (13, 16 19 and 22), manganese (14, 17, 20 and 23) and iron (15, 18, 21 and 24)phthalocyanine complexes were synthesized and characterized. The UV-Vis spectral properties of the complexes were typical of the nature of central metal and position of substituent on the Pc ligand. Their electrochemical behaviors were signatures of the central metals, with varying influences of the nature and position of substituents. Nanocomposite of complex 18 and single walled carbon nanotubes (SWCNTs) (SWCNT-18)was fabricated. Formation of this nano-composite was confirmed by infrared (IR)spectroscopy, X-ray diffraction (XRD) spectroscopy and transmission electron microscopy (TEM). Self-assembled monolayers (SAMs) of SWCNT-18, complexes 13-15, and 20 were electropolymerized on glassy carbon electrodes (GCE). Complex 14 was also electrodeposited on GCE. Surface properties of the SAMs were consistent with the molecular feature of the substituent and the nature of central metal in the adsorbed species, while those of the MnPc modified GCEs were dependent on point of substitution and number of substituent. The SAM-modified gold electrodes were used for the electrocatalytic oxidation of the carbamate insecticide, carbofuran. Amplification of the current signal of the insecticide, at more energetically feasible oxidation potentials, on the SAM-modified gold electrodes, relative to bare gold electrode,justified electrocatalysis. There was enhanced sensitivity (attributed to the presence of SWCNT) of the SWCNT-18-SAM-modified gold electrode towards carbofuran, relative to the signals observed on the other SAMs. Current response of the insecticide,bendiocarb, was also intensified, at more favorable oxidation potentials, on the MnPc (14 and 17) modified GCEs, relative to the response on bare GCE, substantiating electrocatalysis. Also, catalysis of the oxidation of the herbicide, bentazon, was observed on polymeric film of complex 20. The current response of the herbicide on this film was better than that observed on bare GCE. Electrocatalysis of the analytes, on the respective modified electrodes, occurred via closely related mechanisms.
- Full Text:
- Date Issued: 2011
- Authors: Akinbulu, Isaac Adebayo
- Date: 2011
- Subjects: Phthalocyanines Electrochemistry Electrocatalysis Pesticides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4365 , http://hdl.handle.net/10962/d1005030
- Description: New cobalt (13, 16 19 and 22), manganese (14, 17, 20 and 23) and iron (15, 18, 21 and 24)phthalocyanine complexes were synthesized and characterized. The UV-Vis spectral properties of the complexes were typical of the nature of central metal and position of substituent on the Pc ligand. Their electrochemical behaviors were signatures of the central metals, with varying influences of the nature and position of substituents. Nanocomposite of complex 18 and single walled carbon nanotubes (SWCNTs) (SWCNT-18)was fabricated. Formation of this nano-composite was confirmed by infrared (IR)spectroscopy, X-ray diffraction (XRD) spectroscopy and transmission electron microscopy (TEM). Self-assembled monolayers (SAMs) of SWCNT-18, complexes 13-15, and 20 were electropolymerized on glassy carbon electrodes (GCE). Complex 14 was also electrodeposited on GCE. Surface properties of the SAMs were consistent with the molecular feature of the substituent and the nature of central metal in the adsorbed species, while those of the MnPc modified GCEs were dependent on point of substitution and number of substituent. The SAM-modified gold electrodes were used for the electrocatalytic oxidation of the carbamate insecticide, carbofuran. Amplification of the current signal of the insecticide, at more energetically feasible oxidation potentials, on the SAM-modified gold electrodes, relative to bare gold electrode,justified electrocatalysis. There was enhanced sensitivity (attributed to the presence of SWCNT) of the SWCNT-18-SAM-modified gold electrode towards carbofuran, relative to the signals observed on the other SAMs. Current response of the insecticide,bendiocarb, was also intensified, at more favorable oxidation potentials, on the MnPc (14 and 17) modified GCEs, relative to the response on bare GCE, substantiating electrocatalysis. Also, catalysis of the oxidation of the herbicide, bentazon, was observed on polymeric film of complex 20. The current response of the herbicide on this film was better than that observed on bare GCE. Electrocatalysis of the analytes, on the respective modified electrodes, occurred via closely related mechanisms.
- Full Text:
- Date Issued: 2011
Synthesis and evaluation of novel HIV-1 enzyme inhibitors
- Olomola, Temitope Oloruntoba
- Authors: Olomola, Temitope Oloruntoba
- Date: 2011
- Subjects: HIV infections -- Treatment HIV infections -- Chemotherapy HIV (Viruses) Enzyme inhibitors AZT (Drug) Reverse transcriptase Proteolytic enzymes Ligands Psoralens Resorcinol
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4369 , http://hdl.handle.net/10962/d1005034
- Description: This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.
- Full Text:
- Date Issued: 2011
- Authors: Olomola, Temitope Oloruntoba
- Date: 2011
- Subjects: HIV infections -- Treatment HIV infections -- Chemotherapy HIV (Viruses) Enzyme inhibitors AZT (Drug) Reverse transcriptase Proteolytic enzymes Ligands Psoralens Resorcinol
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4369 , http://hdl.handle.net/10962/d1005034
- Description: This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.
- Full Text:
- Date Issued: 2011
Synthesis of novel inhibitors of 1-Deoxy-D-xylulose-5-phosphate reductoisomerase as potential anti-malarial lead compounds
- Authors: Mutorwa, Marius Kudumo
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Malaria -- Chemotherapy Drug development Lead compounds Phosphonates Phosphonic acids Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4372 , http://hdl.handle.net/10962/d1005037
- Description: This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
- Full Text:
- Date Issued: 2011
- Authors: Mutorwa, Marius Kudumo
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Malaria -- Chemotherapy Drug development Lead compounds Phosphonates Phosphonic acids Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4372 , http://hdl.handle.net/10962/d1005037
- Description: This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
- Full Text:
- Date Issued: 2011
Systematics, morphology, phylogeny and historical biogeography of the Mayfly family Prosopistomatidae (Ephemeroptera: Insecta) of the world
- Barber-James, Helen Margaret
- Authors: Barber-James, Helen Margaret
- Date: 2011
- Subjects: Mayflies Mayflies -- Classification Mayflies -- Morphology Mayflies -- Phylogeny Mayflies -- Geographical distribution Ephemeridae
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5785 , http://hdl.handle.net/10962/d1005473
- Description: The diversity, classification and historical biogeography of the mayfly family Prosopistomatidae are explored. First, the higher classification of the Ephemeroptera is reviewed, focussing on the phylogenetic placement of the Prosopistomatidae relative to other mayfly families. All relevant literature from 1762 to 2010 is synthesized. Baetiscidae are established as the probable sister lineage of Prosopistomatidae, the two constituting the superfamily Baetiscoidea. Next, qualitative morphological variation within the Prosopistomatidae is reviewed and revised, emphasizing nymphs because imaginal specimens are few. The labium and associated structures and the hypopharynx of nymphs, and the highly-derived wing venation of the imaginal stages, are re-interpreted. The structure of the male tarsal claws changes considerably between subimago and imago, which, together with deeply scalloped ridges on male imaginal forelegs and unusual pits on the female thorax, are interpreted as providing an unusual mating mechanism. These structures provide morphological characters for species definition and phylogenetic analyses. Two approaches to species delimitation are explored. First, morphometric variation is analysed using Principal Component Analysis, revealing groupings that can be interpreted as species, although there is some overlap between them. Discriminant Function Analysis shows that head width and carapace shape have the most value in identifying nymphs of different species. The carapace of Prosopistoma nymphs is shown to grow allometrically and gradually, in contrast with that of Baetisca, indicating a difference in early ontogeny. Second, an Artificial Neural Network algorithm applied to nymphal morphological characters accurately identified species. This computer-driven artificial intelligence method has power to provide future easy-to-use electronic identification aids. Phylogenetic analysis of nymphal morphology using the parsimony method shows two clades of Prosopistomatidae, one sharing characters with the type species, Prosopistoma variegatum and the other predominating in Africa, although also occurring in Asia; these clades are named the “P. variegatum” and “African” clades, respectively. Parsimony analysis of adult morphology supports these two clades, but supertree analysis obscures the relationships, nesting the “P. variegatum” lineage within the other clade. Preliminary molecular phylogenetic analysis of the 16S rRNA, (mitochondrial) 18S rRNA and Histone-3 genes using Bayesian Inference methods does not support the two clades shown by morphology. Instead, there is a strong relationship between the European species and one African species, with the single Asian representative being most distantly related. These results are limited by lack of fresh material, patchy taxon sampling, and problems with finding suitable primers. A molecular clock program, BEAST, calibrated using fossils, suggests divergence times for the oldest crown-group Prosopistoma clade, represented by the Asian P. wouterae, of about 131 Ma, with the youngest species, the African P. crassi, of 1.21 Ma. Stem-group relationships are analysed using parsimony analysis, focussing on wing characters of the Baetiscoidea, other extant mayfly lineages, and extinct stem-group lineages. This suggests that the Baetiscoidea diverged from main-line Ephemeroptera earlier than any other extant mayfly lineage. This approach expands upon ideas hinted at by earlier scientists. Finally, historical biogeographical analysis of the distribution of known Baetiscoidea s.s. stem-group fossils implies a once Pangean distribution of the lineage. Changing palaeo-climate, catastrophic extinction events and plate tectonic movements in relation to the distribution of crown-group species are reviewed. Other approaches to historical biogeography that build on both morphological and molecular phylogenies are used to interpret disperalist and vacarianist arguments. Distribution patterns of eight unrelated freshwater organisms which share a similar distribution pattern are compared, assuming that shared patterns indicate similar historic biogeographic processes. The distribution of recent Prosopistoma species is seen to be the product of evolution resulting from both vicariance and dispersal. In conclusion, this thesis encompasses a variety of disciplines. It successfully recognises new characters and distinguishes previously unknown species. It uses new approaches to delimiting species and known methods to determine phylogeny from several angles. The analysis of stem-group relationships offers an insight into possible early lineage splitting within Ephemeroptera. Interpretation of historical biogeography allows for both a Gondwanan origin of Prosopistomatidae, with rafting of species on the Deccan plate to Asia, and for subsequent dispersal from Asia down to Australia and across to Europe, and possibly back to Africa.
- Full Text:
- Date Issued: 2011
- Authors: Barber-James, Helen Margaret
- Date: 2011
- Subjects: Mayflies Mayflies -- Classification Mayflies -- Morphology Mayflies -- Phylogeny Mayflies -- Geographical distribution Ephemeridae
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:5785 , http://hdl.handle.net/10962/d1005473
- Description: The diversity, classification and historical biogeography of the mayfly family Prosopistomatidae are explored. First, the higher classification of the Ephemeroptera is reviewed, focussing on the phylogenetic placement of the Prosopistomatidae relative to other mayfly families. All relevant literature from 1762 to 2010 is synthesized. Baetiscidae are established as the probable sister lineage of Prosopistomatidae, the two constituting the superfamily Baetiscoidea. Next, qualitative morphological variation within the Prosopistomatidae is reviewed and revised, emphasizing nymphs because imaginal specimens are few. The labium and associated structures and the hypopharynx of nymphs, and the highly-derived wing venation of the imaginal stages, are re-interpreted. The structure of the male tarsal claws changes considerably between subimago and imago, which, together with deeply scalloped ridges on male imaginal forelegs and unusual pits on the female thorax, are interpreted as providing an unusual mating mechanism. These structures provide morphological characters for species definition and phylogenetic analyses. Two approaches to species delimitation are explored. First, morphometric variation is analysed using Principal Component Analysis, revealing groupings that can be interpreted as species, although there is some overlap between them. Discriminant Function Analysis shows that head width and carapace shape have the most value in identifying nymphs of different species. The carapace of Prosopistoma nymphs is shown to grow allometrically and gradually, in contrast with that of Baetisca, indicating a difference in early ontogeny. Second, an Artificial Neural Network algorithm applied to nymphal morphological characters accurately identified species. This computer-driven artificial intelligence method has power to provide future easy-to-use electronic identification aids. Phylogenetic analysis of nymphal morphology using the parsimony method shows two clades of Prosopistomatidae, one sharing characters with the type species, Prosopistoma variegatum and the other predominating in Africa, although also occurring in Asia; these clades are named the “P. variegatum” and “African” clades, respectively. Parsimony analysis of adult morphology supports these two clades, but supertree analysis obscures the relationships, nesting the “P. variegatum” lineage within the other clade. Preliminary molecular phylogenetic analysis of the 16S rRNA, (mitochondrial) 18S rRNA and Histone-3 genes using Bayesian Inference methods does not support the two clades shown by morphology. Instead, there is a strong relationship between the European species and one African species, with the single Asian representative being most distantly related. These results are limited by lack of fresh material, patchy taxon sampling, and problems with finding suitable primers. A molecular clock program, BEAST, calibrated using fossils, suggests divergence times for the oldest crown-group Prosopistoma clade, represented by the Asian P. wouterae, of about 131 Ma, with the youngest species, the African P. crassi, of 1.21 Ma. Stem-group relationships are analysed using parsimony analysis, focussing on wing characters of the Baetiscoidea, other extant mayfly lineages, and extinct stem-group lineages. This suggests that the Baetiscoidea diverged from main-line Ephemeroptera earlier than any other extant mayfly lineage. This approach expands upon ideas hinted at by earlier scientists. Finally, historical biogeographical analysis of the distribution of known Baetiscoidea s.s. stem-group fossils implies a once Pangean distribution of the lineage. Changing palaeo-climate, catastrophic extinction events and plate tectonic movements in relation to the distribution of crown-group species are reviewed. Other approaches to historical biogeography that build on both morphological and molecular phylogenies are used to interpret disperalist and vacarianist arguments. Distribution patterns of eight unrelated freshwater organisms which share a similar distribution pattern are compared, assuming that shared patterns indicate similar historic biogeographic processes. The distribution of recent Prosopistoma species is seen to be the product of evolution resulting from both vicariance and dispersal. In conclusion, this thesis encompasses a variety of disciplines. It successfully recognises new characters and distinguishes previously unknown species. It uses new approaches to delimiting species and known methods to determine phylogeny from several angles. The analysis of stem-group relationships offers an insight into possible early lineage splitting within Ephemeroptera. Interpretation of historical biogeography allows for both a Gondwanan origin of Prosopistomatidae, with rafting of species on the Deccan plate to Asia, and for subsequent dispersal from Asia down to Australia and across to Europe, and possibly back to Africa.
- Full Text:
- Date Issued: 2011
Tailoring a lean product development framework for the South African automotive industry
- Authors: Mund, Klaudia
- Date: 2011
- Subjects: Lean manufacturing , Automobile industry and trade -- South Africa , Production management -- South Africa , Globalization
- Language: English
- Type: Thesis , Doctoral , DTech
- Identifier: vital:8792 , http://hdl.handle.net/10948/d1015737
- Description: Globalization in the automotive industry exerts enormous pressure on automotive manufacturers and forces many global companies to expand into emerging markets, which results in adopting new ways to manage product design and development. Excellence in product design and development offers an opportunity to gain competitive advantage and can be achieved by implementing Toyota´s Lean Product Development System (LPDS). Although in the last three years Toyota has been severely challenged by the global economic crisis, by a series of recalls resulting in reputation damage and also by natural disasters such as the recent tsunamis - the world can still learn from Toyota´s successes embodied in the lean concept and practices, which are integral to Toyota´s ‘way of life’. The LPDS model (Morgan & Liker 2006) has captured the attention of academics worldwide (including this researcher) thanks to the following key characteristics: shorter development times, less engineering hours involved in development, lower manufacturing costs, higher customer satisfaction and fewer defects reported. In the academic world, lean product development (LPD) is a new field of exploration and thus relevant literature and numbers of studies available are limited. However, scientists are asking questions about successful adaptation and adoption of this model to other environments beyond Toyota. Similarly, the researcher aimed in this thesis to find answers to its main research question, namely: ‘What would be a suitable LPD model for the South African automotive industry?’ South Africa (SA) is a country with a strong manufacturing tradition and although the automotive sector is the third-largest segment in the South African economy and its vehicle market is the largest on the African continent in a global perspective SA´s contribution is relatively small as it produces only 0.61percent of the global motor vehicle volume (OICA 2011). While the country strives to secure sustainable development for the automotive industry and seeks to improve its global competitiveness, companies operating in SA are currently faced with several unique challenges and problems. Lean has been expanding slowly in SA and some companies in the local automotive industry have implemented the lean concept into production areas to improve their operational excellence and performance. However, it is a search for excellence in product development (PD) that could best contribute to improved sustainability for the automotive industry and also provide an important strategic spur towards global competitiveness. The primary intention of this research was to develop an integrated LPD framework tailored for SA´s automotive industry. Considering this, it was necessary to determine current PD capabilities at domestic and international companies operating in SA´s automotive industry so as to examine levels of adaptation of LPD practices. A questionnaire survey and personal interviews involving all seven locally operating Original Equipment Manufacturers (OEMs), including Toyota, as well as 36 local automotive suppliers provided an empirical base for this investigation. This study indicates that SA plays an important supportive role in the global PD context. In spite of a strong manufacturing focus and very limited PD capabilities, SA´s automotive companies have already achieved a high level of ‘leanness’ in product engineering processes. However, on the downside, it appears that industry leaders and senior managers are sceptical about current and future capabilities and opportunities for SA in the designing and developing of global products.
- Full Text:
- Date Issued: 2011
- Authors: Mund, Klaudia
- Date: 2011
- Subjects: Lean manufacturing , Automobile industry and trade -- South Africa , Production management -- South Africa , Globalization
- Language: English
- Type: Thesis , Doctoral , DTech
- Identifier: vital:8792 , http://hdl.handle.net/10948/d1015737
- Description: Globalization in the automotive industry exerts enormous pressure on automotive manufacturers and forces many global companies to expand into emerging markets, which results in adopting new ways to manage product design and development. Excellence in product design and development offers an opportunity to gain competitive advantage and can be achieved by implementing Toyota´s Lean Product Development System (LPDS). Although in the last three years Toyota has been severely challenged by the global economic crisis, by a series of recalls resulting in reputation damage and also by natural disasters such as the recent tsunamis - the world can still learn from Toyota´s successes embodied in the lean concept and practices, which are integral to Toyota´s ‘way of life’. The LPDS model (Morgan & Liker 2006) has captured the attention of academics worldwide (including this researcher) thanks to the following key characteristics: shorter development times, less engineering hours involved in development, lower manufacturing costs, higher customer satisfaction and fewer defects reported. In the academic world, lean product development (LPD) is a new field of exploration and thus relevant literature and numbers of studies available are limited. However, scientists are asking questions about successful adaptation and adoption of this model to other environments beyond Toyota. Similarly, the researcher aimed in this thesis to find answers to its main research question, namely: ‘What would be a suitable LPD model for the South African automotive industry?’ South Africa (SA) is a country with a strong manufacturing tradition and although the automotive sector is the third-largest segment in the South African economy and its vehicle market is the largest on the African continent in a global perspective SA´s contribution is relatively small as it produces only 0.61percent of the global motor vehicle volume (OICA 2011). While the country strives to secure sustainable development for the automotive industry and seeks to improve its global competitiveness, companies operating in SA are currently faced with several unique challenges and problems. Lean has been expanding slowly in SA and some companies in the local automotive industry have implemented the lean concept into production areas to improve their operational excellence and performance. However, it is a search for excellence in product development (PD) that could best contribute to improved sustainability for the automotive industry and also provide an important strategic spur towards global competitiveness. The primary intention of this research was to develop an integrated LPD framework tailored for SA´s automotive industry. Considering this, it was necessary to determine current PD capabilities at domestic and international companies operating in SA´s automotive industry so as to examine levels of adaptation of LPD practices. A questionnaire survey and personal interviews involving all seven locally operating Original Equipment Manufacturers (OEMs), including Toyota, as well as 36 local automotive suppliers provided an empirical base for this investigation. This study indicates that SA plays an important supportive role in the global PD context. In spite of a strong manufacturing focus and very limited PD capabilities, SA´s automotive companies have already achieved a high level of ‘leanness’ in product engineering processes. However, on the downside, it appears that industry leaders and senior managers are sceptical about current and future capabilities and opportunities for SA in the designing and developing of global products.
- Full Text:
- Date Issued: 2011
Tailoring a lean product development framework for the South African automotive industry
- Authors: Mund, Klaudia
- Date: 2011
- Subjects: Lean manufacturing , Automobile industry and trade -- South Africa , Production management -- South Africa , Globalization
- Language: English
- Type: Thesis , Doctoral , DTech (Operations Management)
- Identifier: vital:9605 , http://hdl.handle.net/10948/1660 , Lean manufacturing , Automobile industry and trade -- South Africa , Production management -- South Africa , Globalization
- Description: Globalization in the automotive industry exerts enormous pressure on automotive manufacturers and forces many global companies to expand into emerging markets, which results in adopting new ways to manage product design and development. Excellence in product design and development offers an opportunity to gain competitive advantage and can be achieved by implementing Toyota´s Lean Product Development System (LPDS). Although in the last three years Toyota has been severely challenged by the global economic crisis, by a series of recalls resulting in reputation damage and also by natural disasters such as the recent tsunamis - the world can still learn from Toyota´s successes embodied in the lean concept and practices, which are integral to Toyota´s ‘way of life’. The LPDS model (Morgan & Liker 2006) has captured the attention of academics worldwide (including this researcher) thanks to the following key characteristics: shorter development times, less engineering hours involved in development, lower manufacturing costs, higher customer satisfaction and fewer defects reported. In the academic world, lean product development (LPD) is a new field of exploration and thus relevant literature and numbers of studies available are limited. However, scientists are asking questions about successful adaptation and adoption of this model to other environments beyond Toyota. Similarly, the researcher aimed in this thesis to find answers to its main research question, namely: ‘What would be a suitable LPD model for the South African automotive industry?’ South Africa (SA) is a country with a strong manufacturing tradition and although the automotive sector is the third-largest segment in the South African economy and its vehicle market is the largest on the African continent in a global perspective SA´s contribution is relatively small as it produces only 0.61% of the global motor vehicle volume (OICA 2011). While the country strives to secure sustainable development for the automotive industry and seeks to improve its global competitiveness, companies operating in SA are currently faced with several unique challenges and problems. Lean has been expanding slowly in SA and some companies in the local automotive industry have implemented the lean concept into production areas to improve their operational excellence and performance. However, it is a search for excellence in product development (PD) that could best contribute to improved sustainability for the iv automotive industry and also provide an important strategic spur towards global competitiveness. The primary intention of this research was to develop an integrated LPD framework tailored for SA´s automotive industry. Considering this, it was necessary to determine current PD capabilities at domestic and international companies operating in SA´s automotive industry so as to examine levels of adaptation of LPD practices. A questionnaire survey and personal interviews involving all seven locally operating Original Equipment Manufacturers (OEMs), including Toyota, as well as 36 local automotive suppliers provided an empirical base for this investigation. This study indicates that SA plays an important supportive role in the global PD context. In spite of a strong manufacturing focus and very limited PD capabilities, SA´s automotive companies have already achieved a high level of ‘leanness’ in product engineering processes. However, on the downside, it appears that industry leaders and senior managers are sceptical about current and future capabilities and opportunities for SA in the designing and developing of global products.
- Full Text:
- Date Issued: 2011
- Authors: Mund, Klaudia
- Date: 2011
- Subjects: Lean manufacturing , Automobile industry and trade -- South Africa , Production management -- South Africa , Globalization
- Language: English
- Type: Thesis , Doctoral , DTech (Operations Management)
- Identifier: vital:9605 , http://hdl.handle.net/10948/1660 , Lean manufacturing , Automobile industry and trade -- South Africa , Production management -- South Africa , Globalization
- Description: Globalization in the automotive industry exerts enormous pressure on automotive manufacturers and forces many global companies to expand into emerging markets, which results in adopting new ways to manage product design and development. Excellence in product design and development offers an opportunity to gain competitive advantage and can be achieved by implementing Toyota´s Lean Product Development System (LPDS). Although in the last three years Toyota has been severely challenged by the global economic crisis, by a series of recalls resulting in reputation damage and also by natural disasters such as the recent tsunamis - the world can still learn from Toyota´s successes embodied in the lean concept and practices, which are integral to Toyota´s ‘way of life’. The LPDS model (Morgan & Liker 2006) has captured the attention of academics worldwide (including this researcher) thanks to the following key characteristics: shorter development times, less engineering hours involved in development, lower manufacturing costs, higher customer satisfaction and fewer defects reported. In the academic world, lean product development (LPD) is a new field of exploration and thus relevant literature and numbers of studies available are limited. However, scientists are asking questions about successful adaptation and adoption of this model to other environments beyond Toyota. Similarly, the researcher aimed in this thesis to find answers to its main research question, namely: ‘What would be a suitable LPD model for the South African automotive industry?’ South Africa (SA) is a country with a strong manufacturing tradition and although the automotive sector is the third-largest segment in the South African economy and its vehicle market is the largest on the African continent in a global perspective SA´s contribution is relatively small as it produces only 0.61% of the global motor vehicle volume (OICA 2011). While the country strives to secure sustainable development for the automotive industry and seeks to improve its global competitiveness, companies operating in SA are currently faced with several unique challenges and problems. Lean has been expanding slowly in SA and some companies in the local automotive industry have implemented the lean concept into production areas to improve their operational excellence and performance. However, it is a search for excellence in product development (PD) that could best contribute to improved sustainability for the iv automotive industry and also provide an important strategic spur towards global competitiveness. The primary intention of this research was to develop an integrated LPD framework tailored for SA´s automotive industry. Considering this, it was necessary to determine current PD capabilities at domestic and international companies operating in SA´s automotive industry so as to examine levels of adaptation of LPD practices. A questionnaire survey and personal interviews involving all seven locally operating Original Equipment Manufacturers (OEMs), including Toyota, as well as 36 local automotive suppliers provided an empirical base for this investigation. This study indicates that SA plays an important supportive role in the global PD context. In spite of a strong manufacturing focus and very limited PD capabilities, SA´s automotive companies have already achieved a high level of ‘leanness’ in product engineering processes. However, on the downside, it appears that industry leaders and senior managers are sceptical about current and future capabilities and opportunities for SA in the designing and developing of global products.
- Full Text:
- Date Issued: 2011
The business sustainability of an automotive refinish paint distributor
- Authors: Msuthwana, Vusumzi M
- Date: 2011
- Subjects: Business enterprises -- Development , Business enterprises -- Marketing , Business -- Sustainability
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: vital:9371 , http://hdl.handle.net/10948/d1012376 , Business enterprises -- Development , Business enterprises -- Marketing , Business -- Sustainability
- Description: From a broad overview of business management literature, the proposition emerged that strategic conditions within an organisation can translate into sustainable business development outcomes. However, in the rapidly evolving business environment, the quest to grow or sustain competitive advantage demands that business practices become more proactive, creative and innovative. Globalisation and technological advances drive the need for innovation within a business context and the resultant rapid pace of change demands that businesses adopt a customer-focused entrepreneurial orientation to accommodate this need for innovation. This study investigated whether the principles of marketing, business management tools and management of the customer-base could be incorporated as key drivers to develop innovative and creative tactics that could serve as viable solutions to sustain business development strategies of automotive refinish paint distributors. An initial step in this research comprised a theoretical overview of the internal business environment as a system of the enterprise that aims to provide an in-depth understanding of the organisation, which could be applied to support strategic business goals and objectives. The literature review further entailed an investigation and explorations regarding best practices that automotive refinish paint distributors could follow in order to identify, focus on and develop their source of competitive advantage, sustainability and profitability. From the literature review, a methodological framework was developed that could be applied to specific success indicators, moulded to produce distinctive competencies in the automotive refinish paint industry; defining a significant foundation from which the objectives of this study could be researched. The study adopted the qualitative research approach and focused on a single case of a refinish paint distributor. The reason for selecting the case study method is that an entire organisation could be investigated in depth with particular attention to detail. A detailed questionnaire was drawn up in order to conduct face-to-face interviews with selected respondents, based on the profound expertise of the selected personnel. This was done to enable the researcher to assess the prevalent elements of business sustainability applied by the automotive refinish distributor to enhance their competitive advantage. The design of the empirical element of this study, aimed at providing a blueprint that would enable the researcher to structure the research problem in such a way that the outcome of the study would be valid, objective and reliable. Due to the qualitative nature of this study, the results are interpreted through inductive reasoning, observations, projective and participatory approaches all of which are integrated into a comprehensive model indicating key drivers to promote, improve and facilitate the business sustainability of the automotive refinish paint distributor. A range of recommendations and managerial implications extracted from the results of the empirical study are presented in the final chapter.
- Full Text:
- Date Issued: 2011
- Authors: Msuthwana, Vusumzi M
- Date: 2011
- Subjects: Business enterprises -- Development , Business enterprises -- Marketing , Business -- Sustainability
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: vital:9371 , http://hdl.handle.net/10948/d1012376 , Business enterprises -- Development , Business enterprises -- Marketing , Business -- Sustainability
- Description: From a broad overview of business management literature, the proposition emerged that strategic conditions within an organisation can translate into sustainable business development outcomes. However, in the rapidly evolving business environment, the quest to grow or sustain competitive advantage demands that business practices become more proactive, creative and innovative. Globalisation and technological advances drive the need for innovation within a business context and the resultant rapid pace of change demands that businesses adopt a customer-focused entrepreneurial orientation to accommodate this need for innovation. This study investigated whether the principles of marketing, business management tools and management of the customer-base could be incorporated as key drivers to develop innovative and creative tactics that could serve as viable solutions to sustain business development strategies of automotive refinish paint distributors. An initial step in this research comprised a theoretical overview of the internal business environment as a system of the enterprise that aims to provide an in-depth understanding of the organisation, which could be applied to support strategic business goals and objectives. The literature review further entailed an investigation and explorations regarding best practices that automotive refinish paint distributors could follow in order to identify, focus on and develop their source of competitive advantage, sustainability and profitability. From the literature review, a methodological framework was developed that could be applied to specific success indicators, moulded to produce distinctive competencies in the automotive refinish paint industry; defining a significant foundation from which the objectives of this study could be researched. The study adopted the qualitative research approach and focused on a single case of a refinish paint distributor. The reason for selecting the case study method is that an entire organisation could be investigated in depth with particular attention to detail. A detailed questionnaire was drawn up in order to conduct face-to-face interviews with selected respondents, based on the profound expertise of the selected personnel. This was done to enable the researcher to assess the prevalent elements of business sustainability applied by the automotive refinish distributor to enhance their competitive advantage. The design of the empirical element of this study, aimed at providing a blueprint that would enable the researcher to structure the research problem in such a way that the outcome of the study would be valid, objective and reliable. Due to the qualitative nature of this study, the results are interpreted through inductive reasoning, observations, projective and participatory approaches all of which are integrated into a comprehensive model indicating key drivers to promote, improve and facilitate the business sustainability of the automotive refinish paint distributor. A range of recommendations and managerial implications extracted from the results of the empirical study are presented in the final chapter.
- Full Text:
- Date Issued: 2011
The development of novel cancer targeting agents
- Authors: Knoetze, Steyn
- Date: 2011
- Subjects: Cancer -- Research , Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: vital:10397 , http://hdl.handle.net/10948/d1010636 , Cancer -- Research , Cancer -- Treatment
- Description: The search for the cure for cancer is currently a multi-billion dollar industry and the search for the elusive “magic bullet”, i.e. the perfect cancer drug that would interact therapeutically with cancerous tissues while having a minimal effect on healthy cells, is the topic of many research studies in the world today. A large number of novel drugs or drug complexes and conjugates are being synthesized and subjected to rigorous evaluation in the race to find the perfect cure. ECDG (Ethylene diCysteine DeoxyGlucose) seems to have promising cancer targeting ability. Even though this compound has been described in a few publications, we could not find any reference to the current use of ECDG in oncology clinics, either as a therapeutic agent, or as a diagnostic tool for imaging purposes. It was also not possible to purchase pure ECDG anywhere in the world. This prompted us to further investigate ECDG as a possible candidate for cancer targeting research, either as an imaging agent for cancer diagnosis or complexed with an anti-cancer agent for therapeutic purposes. Detailed investigations done in our laboratory can be divided into the following categories: - Development of a synthetic method for ECDG on a multigram scale ; - Purification of prepared ECDG not using the described dialysis method that only allows the purification of small quantities of ECDG (mg scale) ; Detailed investigation of the chemistry involved in the preparation of pure ECDG and its metal complexes ; - Investigation of the stability of ECDG and its metal complexes that is essential data required for any pharmaceutical agent ; - Preparation of ECDG complexes for use as a diagnostic tool, i.e. complexation with 99mTc ; Investigation of the bio distribution of ECDG-ReO complexes ; - Preparation of an ECDG kit as a diagnostic tool for use in oncology clinics. The development of novel aromatic ligands having similar characteristics compared to ECDG, containing an N2S2 chromophore as donor atoms, to further investigate their targeting capabilities, have also been investigated. All intermediates and final compounds were characterized mainly by ESI MS, in some cases IR and NMR whenever available. Successful preparation and purification of ECDG ands its metal complexes was achieved and extensively characterized and evaluated. Efforts directed towards the development of ECDG at NECSA, South Africa, were also rewarded with significant success. Furthermore, significant development regarding the synthesis of two novel compounds with ECDG-like characteristics was also completed.
- Full Text:
- Date Issued: 2011
- Authors: Knoetze, Steyn
- Date: 2011
- Subjects: Cancer -- Research , Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: vital:10397 , http://hdl.handle.net/10948/d1010636 , Cancer -- Research , Cancer -- Treatment
- Description: The search for the cure for cancer is currently a multi-billion dollar industry and the search for the elusive “magic bullet”, i.e. the perfect cancer drug that would interact therapeutically with cancerous tissues while having a minimal effect on healthy cells, is the topic of many research studies in the world today. A large number of novel drugs or drug complexes and conjugates are being synthesized and subjected to rigorous evaluation in the race to find the perfect cure. ECDG (Ethylene diCysteine DeoxyGlucose) seems to have promising cancer targeting ability. Even though this compound has been described in a few publications, we could not find any reference to the current use of ECDG in oncology clinics, either as a therapeutic agent, or as a diagnostic tool for imaging purposes. It was also not possible to purchase pure ECDG anywhere in the world. This prompted us to further investigate ECDG as a possible candidate for cancer targeting research, either as an imaging agent for cancer diagnosis or complexed with an anti-cancer agent for therapeutic purposes. Detailed investigations done in our laboratory can be divided into the following categories: - Development of a synthetic method for ECDG on a multigram scale ; - Purification of prepared ECDG not using the described dialysis method that only allows the purification of small quantities of ECDG (mg scale) ; Detailed investigation of the chemistry involved in the preparation of pure ECDG and its metal complexes ; - Investigation of the stability of ECDG and its metal complexes that is essential data required for any pharmaceutical agent ; - Preparation of ECDG complexes for use as a diagnostic tool, i.e. complexation with 99mTc ; Investigation of the bio distribution of ECDG-ReO complexes ; - Preparation of an ECDG kit as a diagnostic tool for use in oncology clinics. The development of novel aromatic ligands having similar characteristics compared to ECDG, containing an N2S2 chromophore as donor atoms, to further investigate their targeting capabilities, have also been investigated. All intermediates and final compounds were characterized mainly by ESI MS, in some cases IR and NMR whenever available. Successful preparation and purification of ECDG ands its metal complexes was achieved and extensively characterized and evaluated. Efforts directed towards the development of ECDG at NECSA, South Africa, were also rewarded with significant success. Furthermore, significant development regarding the synthesis of two novel compounds with ECDG-like characteristics was also completed.
- Full Text:
- Date Issued: 2011
The discoursal construction of female physical identity in selected works in children's literature
- Authors: Hunt, Sally Ann
- Date: 2011 , 2013-09-20
- Subjects: Rowling, J K -- Criticism and interpretation Lewis, C S (Clive Staples), 1898-1963 -- Criticism and interpretation Girls in literature Girls -- Identity Human body in literature Gender identity in literature Sex role in literature Children's stories, English -- History and criticism Young women in literature Women in literature
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:2377 , http://hdl.handle.net/10962/d1005965
- Description: This thesis reports on an analysis of the discursive construction of female and male physical identity in children’s literature and explicitly combines corpus linguistic methods with a critical discourse approach. Based on three novels from each of the Chronicles of Narnia and the Harry Potter series, it shows clear gendering of body parts, not only in terms of the purely quantitative preferences for certain body parts to be associated with one or other gender, but in terms of discourse prosody, or the uses to which the body parts are put. Human body parts in these series are mostly used in the following four ways, all of which show differences in realisation in terms of gender: · to describe individuals, physically, in order to distinguish one from the other; · to convey emotion, unintentionally as well as consciously; · for physical interaction between people and · for interaction with the world more broadly: responses to danger and agency, i.e. the ability to act on the world and the nature of what is achieved. The use of body parts by characters to express emotion and act agentively on the world is revealed to be strongly gendered in the two series. I characterise the most prominent patterns in terms of the bodily products blood, sweat and tears, of which the last is strongly connected to female characters, who are generally associated with emotion. The other two, referring to active participation in fighting and injury, as well as agency, are almost exclusively reserved for males, with female characters rendered unable to act on the physical world as a result of overwhelming feelings. The females’ response to danger suggests stereotyped discourses of inequality which see women and girls as requiring protection and being physically incapable. Thus gender is still a particularly salient aspect in these widely-read examples of children’s literature, despite plots which appear to be fairly positive towards women. The strength of the inclusion of a corpus approach in this study lies in its capacity to reveal objective, and often fairly covert, trends in language use. These in turn enrich the critical analysis of discourses in these influential texts, which facilitates social change through linguistic analysis.
- Full Text:
- Date Issued: 2011
- Authors: Hunt, Sally Ann
- Date: 2011 , 2013-09-20
- Subjects: Rowling, J K -- Criticism and interpretation Lewis, C S (Clive Staples), 1898-1963 -- Criticism and interpretation Girls in literature Girls -- Identity Human body in literature Gender identity in literature Sex role in literature Children's stories, English -- History and criticism Young women in literature Women in literature
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:2377 , http://hdl.handle.net/10962/d1005965
- Description: This thesis reports on an analysis of the discursive construction of female and male physical identity in children’s literature and explicitly combines corpus linguistic methods with a critical discourse approach. Based on three novels from each of the Chronicles of Narnia and the Harry Potter series, it shows clear gendering of body parts, not only in terms of the purely quantitative preferences for certain body parts to be associated with one or other gender, but in terms of discourse prosody, or the uses to which the body parts are put. Human body parts in these series are mostly used in the following four ways, all of which show differences in realisation in terms of gender: · to describe individuals, physically, in order to distinguish one from the other; · to convey emotion, unintentionally as well as consciously; · for physical interaction between people and · for interaction with the world more broadly: responses to danger and agency, i.e. the ability to act on the world and the nature of what is achieved. The use of body parts by characters to express emotion and act agentively on the world is revealed to be strongly gendered in the two series. I characterise the most prominent patterns in terms of the bodily products blood, sweat and tears, of which the last is strongly connected to female characters, who are generally associated with emotion. The other two, referring to active participation in fighting and injury, as well as agency, are almost exclusively reserved for males, with female characters rendered unable to act on the physical world as a result of overwhelming feelings. The females’ response to danger suggests stereotyped discourses of inequality which see women and girls as requiring protection and being physically incapable. Thus gender is still a particularly salient aspect in these widely-read examples of children’s literature, despite plots which appear to be fairly positive towards women. The strength of the inclusion of a corpus approach in this study lies in its capacity to reveal objective, and often fairly covert, trends in language use. These in turn enrich the critical analysis of discourses in these influential texts, which facilitates social change through linguistic analysis.
- Full Text:
- Date Issued: 2011
The druggable antimalarial target 1-deoxy-D-xylulose-5-phosphate reductoisomerase: purfication, kinetic characterization and inhibition studies
- Authors: Goble, Jessica Leigh
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Drug development Plasmodium falciparum -- Purification Plasmodium falciparum -- Inhibitors Enzyme kinetics Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3949 , http://hdl.handle.net/10962/d1004008
- Description: Plasmodium falciparum 1–deoxy–D–xylulose–5 phosphatereductoisomerase (PfDXR) plays a role in isoprenoid biosynthesis in the malaria parasite and is absent in the human host, making this parasite enzyme an attractive target for antimalarial drug design. To characterize PfDXR, it is necessary to produce large quantities of the enzyme in a soluble and functional form. However, the over–production of malarial proteins in prokaryotic host systems often results in the formation of truncated proteins or insoluble protein aggregates. A heterologous expression system was developed for the production of active PfDXR using codon harmonization and tight control of expression in the presence of lac repressor. Yields of up to 2 mg/l of enzyme were reported using the optimised expression system, which is 8 to 10– fold greater than previously reported yields. The kinetic parameters Km, Vmax and kcat were determined for PfDXR; values reported in this study were consistent with those reported in the literature for other DXR enzymes. A three–dimensional model of the malarial drug target protein PfDXR was generated, and validated using structure–checking programs and protein docking studies. Structural and functional features unique to PfDXR were identified using the model and comparative sequence analyses with apicomplexan and non–apicomplexan DXR proteins. Residues Val44 and Asn45, essential for NADPH binding; and catalytic hatch residues Lys224 and Lys226, which are unique to the species of Plasmodium, were mutated to resemble those of E. coli DXR. Interestingly,these mutations resulted in significant reductions in substrate affinity, when compared to the unmutated PfDXR. Mutant enzymes PfDXR(VN43,44AG) and PfDXR(KK224,226NS) also demonstrated a decreased ability to turnover substrate by 4–fold and 2–fold respectively. This study indicates a difference in the role of the catalytic hatch of PfDXR with regards to the way in which it captures substrates. The study also highlights subtle differences in cofactor binding to PfDXR, compared with the well characterized EcDXR enzyme. The validated PfDXR model was also used to develop a novel efficient in silico screening method for potential tool compounds for use in the rational design of novel DXR inhibitors. Following in silico screening of 46 potential DXR inhibitors, a two–tiered in vitro screening approach was undertaken. DXR inhibition was assessed for the 46 novel compounds using an NADPH– ependant DXP enzyme inhibition assay and antimalarial potential was assessed using P.falciparum–infected erythrocyte growth assays. Select compounds were tested in human cells in order to determine whether they were toxic to the host. From the parallel in silico and in vitro drug screening, it was evident that only a single compound demonstrated reasonable potential binding to DXR (determined using in silico docking), inhibited DXR in vitro and inhibited P. falciparum growth, without being toxic to human cells. Its potential as a lead compound in antimalarial drug development is therefore feasible. Two outcomes were evident from this work. Firstly, analogues of known antimalarial natural products can be screened against malaria, which may then lead towards the rational design of novel compounds that are effective against a specific antimalarial drug target enzyme, such as PfDXR. Secondly, the rational design of novel compounds against a specific antimalarial drug target enzyme can be untaken by adopting a coupled in silico and in vitro approach to drug discovery.
- Full Text:
- Date Issued: 2011
- Authors: Goble, Jessica Leigh
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Drug development Plasmodium falciparum -- Purification Plasmodium falciparum -- Inhibitors Enzyme kinetics Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3949 , http://hdl.handle.net/10962/d1004008
- Description: Plasmodium falciparum 1–deoxy–D–xylulose–5 phosphatereductoisomerase (PfDXR) plays a role in isoprenoid biosynthesis in the malaria parasite and is absent in the human host, making this parasite enzyme an attractive target for antimalarial drug design. To characterize PfDXR, it is necessary to produce large quantities of the enzyme in a soluble and functional form. However, the over–production of malarial proteins in prokaryotic host systems often results in the formation of truncated proteins or insoluble protein aggregates. A heterologous expression system was developed for the production of active PfDXR using codon harmonization and tight control of expression in the presence of lac repressor. Yields of up to 2 mg/l of enzyme were reported using the optimised expression system, which is 8 to 10– fold greater than previously reported yields. The kinetic parameters Km, Vmax and kcat were determined for PfDXR; values reported in this study were consistent with those reported in the literature for other DXR enzymes. A three–dimensional model of the malarial drug target protein PfDXR was generated, and validated using structure–checking programs and protein docking studies. Structural and functional features unique to PfDXR were identified using the model and comparative sequence analyses with apicomplexan and non–apicomplexan DXR proteins. Residues Val44 and Asn45, essential for NADPH binding; and catalytic hatch residues Lys224 and Lys226, which are unique to the species of Plasmodium, were mutated to resemble those of E. coli DXR. Interestingly,these mutations resulted in significant reductions in substrate affinity, when compared to the unmutated PfDXR. Mutant enzymes PfDXR(VN43,44AG) and PfDXR(KK224,226NS) also demonstrated a decreased ability to turnover substrate by 4–fold and 2–fold respectively. This study indicates a difference in the role of the catalytic hatch of PfDXR with regards to the way in which it captures substrates. The study also highlights subtle differences in cofactor binding to PfDXR, compared with the well characterized EcDXR enzyme. The validated PfDXR model was also used to develop a novel efficient in silico screening method for potential tool compounds for use in the rational design of novel DXR inhibitors. Following in silico screening of 46 potential DXR inhibitors, a two–tiered in vitro screening approach was undertaken. DXR inhibition was assessed for the 46 novel compounds using an NADPH– ependant DXP enzyme inhibition assay and antimalarial potential was assessed using P.falciparum–infected erythrocyte growth assays. Select compounds were tested in human cells in order to determine whether they were toxic to the host. From the parallel in silico and in vitro drug screening, it was evident that only a single compound demonstrated reasonable potential binding to DXR (determined using in silico docking), inhibited DXR in vitro and inhibited P. falciparum growth, without being toxic to human cells. Its potential as a lead compound in antimalarial drug development is therefore feasible. Two outcomes were evident from this work. Firstly, analogues of known antimalarial natural products can be screened against malaria, which may then lead towards the rational design of novel compounds that are effective against a specific antimalarial drug target enzyme, such as PfDXR. Secondly, the rational design of novel compounds against a specific antimalarial drug target enzyme can be untaken by adopting a coupled in silico and in vitro approach to drug discovery.
- Full Text:
- Date Issued: 2011