Analysis of bacterial Mur amide ligase enzymes for the identification of inhibitory compounds by in silico methods
- Chamboko, Chiratidzo Respina
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Mur amide ligases , Ligases , Ligand binding (Biochemistry) , Antibacterial agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163430 , vital:41036
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Mur amide ligases , Ligases , Ligand binding (Biochemistry) , Antibacterial agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163430 , vital:41036
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
Analysis of bacterial Mur amide ligase enzymes for the identification of inhibitory compounds by in silico methods
- Chamboko, Chiratidzo Respina
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Pathogenic microorganisms -- Analysis , Drug resistance in microorganisms , Microorganisms -- Effect of drugs on , Antibiotics -- Effectiveness , Pathogenic bacteria , Drug tolerance , Enzymes -- Analysis , Peptide antibiotics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161911 , vital:40690
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
- Authors: Chamboko, Chiratidzo Respina
- Date: 2020
- Subjects: Pathogenic microorganisms -- Analysis , Drug resistance in microorganisms , Microorganisms -- Effect of drugs on , Antibiotics -- Effectiveness , Pathogenic bacteria , Drug tolerance , Enzymes -- Analysis , Peptide antibiotics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/161911 , vital:40690
- Description: An increased emergence of resistant pathogenic bacterial strains over the years has resulted in many people dying of untreatable infections. This has become one of the most critical global public health problems, as resistant strains are complicating treatment of infectious diseases, increasing human morbidity, mortality, and health care costs. A very limited amount of effective antibiotics is currently available, but the development of novel classes of antibacterial agents is becoming a priority. Mur amide ligases are enzymes that have been identified as potentially good targets for antibiotics, as they are uniquely found in bacteria. They are responsible for the formation of peptide bonds in a growing peptidoglycan structure for bacterial cell walls. The current work presented here focused on characterizing these Mur amide ligase enzymes and obtaining inhibitory compounds that could potentially be of use in drug discovery of antibacterial agents. To do this, multiple sequence alignment, motif analysis and phylogenetic tree constructions were carried out, followed by docking studies and molecular dynamic simulations. Prior to docking, homology modelling of missing residues in the MurF structure (PDB 1GG4) was performed. Characterization results revealed the Mur amide ligase enzymes contained defined conservation in limited regions, that ultimately mapped towards the central domain responsible for ATP binding (presence of a conserved GKT motif). Further analysis of results further unraveled the unique patterns observed within each group of the family of enzymes. As a result of these findings, docking studies were carried out on each Mur amide ligase structure. At most, two ligands were identified to be sufficiently inhibiting each Mur amide ligase. The ligands obtained were SANC00574 and SANC00575 for MurC, SANC00290 and SANC00438 for MurD, SANC00290 and SANC00525 for MurE and SANC00290 and SANC00434 for MurF. The two best ligands identified for each enzyme had docked in the active site of their respective proteins, passed Lipinski’s rule of five and had substantially low binding energies. Molecular dynamic simulations were then performed to analyze the behavior of the proteins and protein-ligand complexes, to confirm the lead compounds as good inhibitors of the Mur amide ligases. In the case of MurC, MurD and MurE complexes, the identified ligands clearly impacted the behavior of the protein, as the ligand bound proteins became more compact and stable, while flexibility decreased. There was however an opposite effect on MurF complexes, that resulted in identified inhibitors being discarded. As a potential next step, in vivo and in vitro experiments can be performed with identified ligands from this research, to further support the information presented.
- Full Text:
- Date Issued: 2020
Analysis of maximum power point tracking data for obtaining photovoltaic parameters
- Authors: Chitura, Anesu Godfrey
- Date: 2020
- Subjects: Photovoltaic power system
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/18576 , vital:42610
- Description: As a standard, photovoltaic (PV) modules are rated by the use of standard test conditions (STC). Such details entail current and voltage (I-V) measurements for modules under an irradiance of 1000 W/m2 an air mass ration of 1.5 global spectrum and 25˚C cell temperature. Outdoor weather conditions continuously vary with time and from one location to the other. This further offset the expected operational power outputs as outdoor conditions are generally characterized by high cell temperatures. The technology one uses will also complicate the power output prediction since different module technologies respond to these outdoor conditions differently. I-V tracers are able to measure the full I-V curve of the module thus can give the operational PV parameters at any given time. However, these tracers are sold at exorbitant prices and they require skilled personnel in order to operate them. Most if not all tracers require isolation of the module under test thereby disrupting the power production function of the module._________________________________________________________________________________________________________________________________________ In this study a method to obtain photovoltaic (PV) parameters using the maximum power point tracking (MPPT) data is presented and tested under natural outdoor conditions. The method features a customized data acquisition system (DAS) designed for the measurement and storage of meteorological and MPPT data. The DAS is capable of extracting parameters from any combination of modules with an open circuit voltage 〖(V〗_oc) less than or equal to 120 Volts and a short circuit current 〖(I〗_sc) of 100 Amps. The system used is capable of extracting MPPT data using a reliable, improved storage and a programmable data logger. In order to match the sampling operational speeds of internal charge controller switches a computer interfaced Peripheral Component Interconnect (PCI) card was also used. Data collection and characterization of the MPPT data was done in such a way that the power generation process remained uninterrupted throughout the whole process. The regression nonlinear least squares method was used to fit MPPT crests and obtain the knee part of the I-V curve. This was then extrapolated to obtain the full I-V curve, which then produces the operational PV parameters. The resultant parameters from the characterization process were logged and accessible at any time. The end result was a method that can be incorporated within a charge controller for quick, hands-free PV parameter extraction, using only the MPPT scanned data.
- Full Text:
- Date Issued: 2020
- Authors: Chitura, Anesu Godfrey
- Date: 2020
- Subjects: Photovoltaic power system
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/18576 , vital:42610
- Description: As a standard, photovoltaic (PV) modules are rated by the use of standard test conditions (STC). Such details entail current and voltage (I-V) measurements for modules under an irradiance of 1000 W/m2 an air mass ration of 1.5 global spectrum and 25˚C cell temperature. Outdoor weather conditions continuously vary with time and from one location to the other. This further offset the expected operational power outputs as outdoor conditions are generally characterized by high cell temperatures. The technology one uses will also complicate the power output prediction since different module technologies respond to these outdoor conditions differently. I-V tracers are able to measure the full I-V curve of the module thus can give the operational PV parameters at any given time. However, these tracers are sold at exorbitant prices and they require skilled personnel in order to operate them. Most if not all tracers require isolation of the module under test thereby disrupting the power production function of the module._________________________________________________________________________________________________________________________________________ In this study a method to obtain photovoltaic (PV) parameters using the maximum power point tracking (MPPT) data is presented and tested under natural outdoor conditions. The method features a customized data acquisition system (DAS) designed for the measurement and storage of meteorological and MPPT data. The DAS is capable of extracting parameters from any combination of modules with an open circuit voltage 〖(V〗_oc) less than or equal to 120 Volts and a short circuit current 〖(I〗_sc) of 100 Amps. The system used is capable of extracting MPPT data using a reliable, improved storage and a programmable data logger. In order to match the sampling operational speeds of internal charge controller switches a computer interfaced Peripheral Component Interconnect (PCI) card was also used. Data collection and characterization of the MPPT data was done in such a way that the power generation process remained uninterrupted throughout the whole process. The regression nonlinear least squares method was used to fit MPPT crests and obtain the knee part of the I-V curve. This was then extrapolated to obtain the full I-V curve, which then produces the operational PV parameters. The resultant parameters from the characterization process were logged and accessible at any time. The end result was a method that can be incorporated within a charge controller for quick, hands-free PV parameter extraction, using only the MPPT scanned data.
- Full Text:
- Date Issued: 2020
Analysis of the contribution of socio-economic factors on poor academic performance of grade 12 learners: the case of Butterworth education district, Eastern Cape Province South Africa
- Authors: Lubisi, Anathi
- Date: 2020
- Subjects: Performance standards -- South Africa Teacher effectiveness -- South Africa
- Language: English
- Type: Thesis , Masters , MSoc (Sociology)
- Identifier: http://hdl.handle.net/10353/18141 , vital:42236
- Description: The drive of this research project was to discover factors contributing to the poor academic performance of Grade 12 learners at two selected schools in the Butterworth Education District, Eastern Cape province South Africa. The participants were Grade 12 learners, Grade 12 teachers and parents of Grade 12 learners in both schools. Both schools are located in rural areas of Mnquma municipality under the Butterworth education district. The study used both qualitative and quantitative research methods. The motivation behind using triangulation was to decrease or offset the deficiency of a specific methodology and for deeper understanding of the discoveries of the study. Use of triangulation in this study was aimed at expanding the legitimacy, dependability and generalizability of the results of the study. The findings of the study revealed that the most determining factor that contributes to the poor academic performance of Grade 12 learners in the Butterworth Education District is the unavailability and inadequacy of instructional resources. This is the most critical school resource which the parents cannot afford to buy for their children. Both teachers and Grade 12 learners indicated that they do not have a school library or a community library. The majority of learners also indicated that they do not have enough textbooks in all subjects and their parents concurred that their children end up sharing textbooks with their peers. Furthermore, the three groups of participants agreed that learners do not have access to computers, and the school does not have a science lab for Grade 12 learners doing science. The core argument of this study is that a poor socio-economic background is a primary contributor to low academic performance of Grade 12 learners at the Butterworth Education District. The findings of this study support this thesis as they indicate that instructional resources are inadequate, a school or community library is vii non-existent, and there is not enough textbooks at the selected schools. With parents from low socio-economic background, the Butterworth community is also not in a position to supplement these insufficient instructional resources. This study utilized the cultural reproduction theory of Bourdieu (1977) to explore a system of education in industrialized communities and the way it works to illuminate class differences in academic performance and achievement of Grade 12 learners. The study made recommendations that should be put in place to improve the academic performance of Grade 12 learners in the Butterworth Education District. The most important of these recommendations is that government officials should provide educational resources (teaching and learning resources). Furthermore, the researcher suggest that for further research, it would be interesting to find out about learners that perform well, regardless of identified factors that cause other learners to perform poorly to help them improve their academic performance.
- Full Text:
- Date Issued: 2020
- Authors: Lubisi, Anathi
- Date: 2020
- Subjects: Performance standards -- South Africa Teacher effectiveness -- South Africa
- Language: English
- Type: Thesis , Masters , MSoc (Sociology)
- Identifier: http://hdl.handle.net/10353/18141 , vital:42236
- Description: The drive of this research project was to discover factors contributing to the poor academic performance of Grade 12 learners at two selected schools in the Butterworth Education District, Eastern Cape province South Africa. The participants were Grade 12 learners, Grade 12 teachers and parents of Grade 12 learners in both schools. Both schools are located in rural areas of Mnquma municipality under the Butterworth education district. The study used both qualitative and quantitative research methods. The motivation behind using triangulation was to decrease or offset the deficiency of a specific methodology and for deeper understanding of the discoveries of the study. Use of triangulation in this study was aimed at expanding the legitimacy, dependability and generalizability of the results of the study. The findings of the study revealed that the most determining factor that contributes to the poor academic performance of Grade 12 learners in the Butterworth Education District is the unavailability and inadequacy of instructional resources. This is the most critical school resource which the parents cannot afford to buy for their children. Both teachers and Grade 12 learners indicated that they do not have a school library or a community library. The majority of learners also indicated that they do not have enough textbooks in all subjects and their parents concurred that their children end up sharing textbooks with their peers. Furthermore, the three groups of participants agreed that learners do not have access to computers, and the school does not have a science lab for Grade 12 learners doing science. The core argument of this study is that a poor socio-economic background is a primary contributor to low academic performance of Grade 12 learners at the Butterworth Education District. The findings of this study support this thesis as they indicate that instructional resources are inadequate, a school or community library is vii non-existent, and there is not enough textbooks at the selected schools. With parents from low socio-economic background, the Butterworth community is also not in a position to supplement these insufficient instructional resources. This study utilized the cultural reproduction theory of Bourdieu (1977) to explore a system of education in industrialized communities and the way it works to illuminate class differences in academic performance and achievement of Grade 12 learners. The study made recommendations that should be put in place to improve the academic performance of Grade 12 learners in the Butterworth Education District. The most important of these recommendations is that government officials should provide educational resources (teaching and learning resources). Furthermore, the researcher suggest that for further research, it would be interesting to find out about learners that perform well, regardless of identified factors that cause other learners to perform poorly to help them improve their academic performance.
- Full Text:
- Date Issued: 2020
Analysis of the effectiveness of Tulbaghia Violacea extracts as devulcanizing agents for synthetic CIS-1,4-polyisoprene vulcanizates
- Authors: Gxakuma, Lutho
- Date: 2020
- Subjects: Plant extracts , Plant products -- South Africa Medicinal plants -- South Africa Plants -- Analysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/49093 , vital:41600
- Description: Tulbaghia violacea is an indigenous plant commonly known as wild garlic, wilde knoffel in Afrikaans, isihaqa in Zulu or itswele lomlambo in Xhosa. Its leaves and bulbs are widely used as herbal remedies for various ailments and its medicinal uses include fever and colds, asthma, tuberculosis and stomach problems. Like all other members of the Alliacea family, Tulbaghia violacea produces a distinctive garlic-like odour when its leaves or rhizomes are damaged, resulting in the release of cysteine-derived sulphur compounds which include the oil-soluble organo-sulphur compounds and water-soluble cysteine derivatives. Chemically synthesized sulphur containing compounds have been reported to be effective devulcanizing agents and many industries prefer to perform devulcanization using them. Most commonly applied devulcanizing agents include disulphides, thiophenols and their zinc salts, and mercaptans which are mixed with the rubber scrap powder under specific reaction conditions. In this study, instead of performing devulcanization by using industrial synthesized sulphur containing compounds, the effectiveness of the extracts of organo-sulphur containing compounds from Tulbaghia violacea are evaluated as potential devulcanizing agents for synthetic cis-1,4-polyisoprene vulcanizates. This is a new, cheap and greener practice of rubber devulcanization. Diallyl disulphide, which is one of the organo-sulphur containing compounds present in Tulbaghia violacea, is the devulcanizing agent of interest to this study. The organo-sulphur containing compounds were extracted from the bulbs, roots and leaves of the plant using the soxhlet and ultrasonic bath extraction method. The solvent system used in the soxhlet extraction method was 2% of 2-propanol in n-hexane whereas in ultrasonic bath extraction method the solvent system used was 100% ethanol. An essential oil extract was obtained from the plant organs. The yield of the essential oil extracts obtained using the soxhlet extraction method was higher compared to the yield of the essential oil extracts obtained using the ultrasonic bath extraction method. According to the Fourier-Transform Infrared spectroscopy, the organo-sulphur containing compounds were present in the essential oil extracts of the plant. The essential oil extracts that were extracted using the soxhlet extraction method were chosen for further analysis. It was found out that the allyl sulphide and diallyl disulphide have the same retention time from the High Performance Liquid Chromatography (using a normal phase column). The Differential Scanning Calorimeter indicated that the allyl sulphide was not present in the essential oil extracts whereas the diallyl disulphide was present in the essential oil extract of the roots and leaves. The High Performance Liquid Chromatography was used to quantify the presence of the diallyl disulphide in the essential oil extract of roots and leaves. The quantity of diallyl disulphide was 23% in the dry mass of the essential oil extract of roots. In the essential oil extract of leaves the diallyl disulphide was very low concentrated and the High Performance Liquid Chromatography was less sensitive to detect it. According to the Thermogravimetric Analyser, it was found that the essential oil extracts begin to degrade at 120 °C and experience a multistage degradation. The softening temperature of the essential oil extracts was 60 °C from the Simultaneous Differential Scanning Calorimeter-Thermogravimetric Analyser. Conventional vulcanization of synthetic cis-1,4-polyisoprene was prepared with the vulcanization ingredients of zinc oxide, sulphur, stearic acid and N-tert-butyl-2-benzothiazole sulphenamide. The vulcanized synthetic cis-1,4-polyisoprene produced, under the heating temperature of 160 °C, was mixed with the essential oil extracts using the internal mixer at 60 °C and the two-roll mill. The overall torque, tan delta and the total crosslink density were the properties of interest of synthetic cis-1,4-polyisoprene vulcanizate in this study. The devulcanization temperature for the treated synthetic cis-1,4-polyisoprene vulcanizate with the essential oil extracts was optimized using the Dynamic Moving Die Rheometer and Dynamic Rubber Process Analyser. The amount of essential oil extracts at which they are effective devulcanizing agents for synthetic cis-1,4-polyisoprene vulcanizate was also optimized. During optimization a change on the latter mentioned properties of synthetic cis-1,4-polyisoprene vulcanizate was observed, indicating that the essential oil extracts have an effect as potential devulcanizing agents. The essential oil extracts increased the tan delta and reduced the overall torque, and total crosslink density of synthetic cis-1,4-polyisoprene vulcanizate as expected from devulcanizing agents. 200 °C was a preferable devulcanization temperature whereas essential oil extracts were effective as devulcanizing agent at 1.4%. However, the essential oil extracts influenced the overall torque and tan delta of synthetic cis-1,4-polyisoprene vulcanizate during the mixing process in the internal mixer at 60 °C, which was before heating at 200 °C. The essential oil extracts had a higher influence on the overall torque of synthetic cis-1,4-polyisoprene vulcanizate under heating at 200 °C whereas at 60 °C, during the mixing process, they had a higher influence on the tan delta of synthetic cis-1,4-polyisoprene vulcanizate. The essential oil extract of leaves had a higher influence on the overall torque whereas the essential oil extract of bulbs had a higher influence on the tan delta of synthetic cis-1,4-polyisoprene vulcanizate at 200 °C. The essential oil extract of roots shown a greater influence on the overall torque and tan delta of synthetic cis-1,4-polyisoprene vulcanizate at 60 °C during the mixing process. The effect of the essential oil extracts on the reversing heat capacity of synthetic cis-1,4-polyisoprene vulcanizate was also investigated using the Modulated Differential Scanning Calorimetry method. The essential oil extract of bulbs and roots influenced the reversing heat capacity of synthetic cis-1,4-polyisoprene vulcanizate by reducing it whereas the essential oil extract of leaves caused a temperature shift of the reversing heat capacity curve from the Modulated Differential Scanning Calorimeter thermogram of synthetic cis-1,4-polyisoprene vulcanizate. Therefore, the results indicated that the essential oil extracts of Tulbaghia violacea have an effect as an alternative potential devulcanizing agents for conventional vulcanized synthetic cis-1,4-polyisoprene whether the diallyl disulphide compound is present or not in them.
- Full Text:
- Date Issued: 2020
- Authors: Gxakuma, Lutho
- Date: 2020
- Subjects: Plant extracts , Plant products -- South Africa Medicinal plants -- South Africa Plants -- Analysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/49093 , vital:41600
- Description: Tulbaghia violacea is an indigenous plant commonly known as wild garlic, wilde knoffel in Afrikaans, isihaqa in Zulu or itswele lomlambo in Xhosa. Its leaves and bulbs are widely used as herbal remedies for various ailments and its medicinal uses include fever and colds, asthma, tuberculosis and stomach problems. Like all other members of the Alliacea family, Tulbaghia violacea produces a distinctive garlic-like odour when its leaves or rhizomes are damaged, resulting in the release of cysteine-derived sulphur compounds which include the oil-soluble organo-sulphur compounds and water-soluble cysteine derivatives. Chemically synthesized sulphur containing compounds have been reported to be effective devulcanizing agents and many industries prefer to perform devulcanization using them. Most commonly applied devulcanizing agents include disulphides, thiophenols and their zinc salts, and mercaptans which are mixed with the rubber scrap powder under specific reaction conditions. In this study, instead of performing devulcanization by using industrial synthesized sulphur containing compounds, the effectiveness of the extracts of organo-sulphur containing compounds from Tulbaghia violacea are evaluated as potential devulcanizing agents for synthetic cis-1,4-polyisoprene vulcanizates. This is a new, cheap and greener practice of rubber devulcanization. Diallyl disulphide, which is one of the organo-sulphur containing compounds present in Tulbaghia violacea, is the devulcanizing agent of interest to this study. The organo-sulphur containing compounds were extracted from the bulbs, roots and leaves of the plant using the soxhlet and ultrasonic bath extraction method. The solvent system used in the soxhlet extraction method was 2% of 2-propanol in n-hexane whereas in ultrasonic bath extraction method the solvent system used was 100% ethanol. An essential oil extract was obtained from the plant organs. The yield of the essential oil extracts obtained using the soxhlet extraction method was higher compared to the yield of the essential oil extracts obtained using the ultrasonic bath extraction method. According to the Fourier-Transform Infrared spectroscopy, the organo-sulphur containing compounds were present in the essential oil extracts of the plant. The essential oil extracts that were extracted using the soxhlet extraction method were chosen for further analysis. It was found out that the allyl sulphide and diallyl disulphide have the same retention time from the High Performance Liquid Chromatography (using a normal phase column). The Differential Scanning Calorimeter indicated that the allyl sulphide was not present in the essential oil extracts whereas the diallyl disulphide was present in the essential oil extract of the roots and leaves. The High Performance Liquid Chromatography was used to quantify the presence of the diallyl disulphide in the essential oil extract of roots and leaves. The quantity of diallyl disulphide was 23% in the dry mass of the essential oil extract of roots. In the essential oil extract of leaves the diallyl disulphide was very low concentrated and the High Performance Liquid Chromatography was less sensitive to detect it. According to the Thermogravimetric Analyser, it was found that the essential oil extracts begin to degrade at 120 °C and experience a multistage degradation. The softening temperature of the essential oil extracts was 60 °C from the Simultaneous Differential Scanning Calorimeter-Thermogravimetric Analyser. Conventional vulcanization of synthetic cis-1,4-polyisoprene was prepared with the vulcanization ingredients of zinc oxide, sulphur, stearic acid and N-tert-butyl-2-benzothiazole sulphenamide. The vulcanized synthetic cis-1,4-polyisoprene produced, under the heating temperature of 160 °C, was mixed with the essential oil extracts using the internal mixer at 60 °C and the two-roll mill. The overall torque, tan delta and the total crosslink density were the properties of interest of synthetic cis-1,4-polyisoprene vulcanizate in this study. The devulcanization temperature for the treated synthetic cis-1,4-polyisoprene vulcanizate with the essential oil extracts was optimized using the Dynamic Moving Die Rheometer and Dynamic Rubber Process Analyser. The amount of essential oil extracts at which they are effective devulcanizing agents for synthetic cis-1,4-polyisoprene vulcanizate was also optimized. During optimization a change on the latter mentioned properties of synthetic cis-1,4-polyisoprene vulcanizate was observed, indicating that the essential oil extracts have an effect as potential devulcanizing agents. The essential oil extracts increased the tan delta and reduced the overall torque, and total crosslink density of synthetic cis-1,4-polyisoprene vulcanizate as expected from devulcanizing agents. 200 °C was a preferable devulcanization temperature whereas essential oil extracts were effective as devulcanizing agent at 1.4%. However, the essential oil extracts influenced the overall torque and tan delta of synthetic cis-1,4-polyisoprene vulcanizate during the mixing process in the internal mixer at 60 °C, which was before heating at 200 °C. The essential oil extracts had a higher influence on the overall torque of synthetic cis-1,4-polyisoprene vulcanizate under heating at 200 °C whereas at 60 °C, during the mixing process, they had a higher influence on the tan delta of synthetic cis-1,4-polyisoprene vulcanizate. The essential oil extract of leaves had a higher influence on the overall torque whereas the essential oil extract of bulbs had a higher influence on the tan delta of synthetic cis-1,4-polyisoprene vulcanizate at 200 °C. The essential oil extract of roots shown a greater influence on the overall torque and tan delta of synthetic cis-1,4-polyisoprene vulcanizate at 60 °C during the mixing process. The effect of the essential oil extracts on the reversing heat capacity of synthetic cis-1,4-polyisoprene vulcanizate was also investigated using the Modulated Differential Scanning Calorimetry method. The essential oil extract of bulbs and roots influenced the reversing heat capacity of synthetic cis-1,4-polyisoprene vulcanizate by reducing it whereas the essential oil extract of leaves caused a temperature shift of the reversing heat capacity curve from the Modulated Differential Scanning Calorimeter thermogram of synthetic cis-1,4-polyisoprene vulcanizate. Therefore, the results indicated that the essential oil extracts of Tulbaghia violacea have an effect as an alternative potential devulcanizing agents for conventional vulcanized synthetic cis-1,4-polyisoprene whether the diallyl disulphide compound is present or not in them.
- Full Text:
- Date Issued: 2020
Analysis of the existence of the Phillips curve, Okun’s law and Taylor rule in the Zambian economy
- Authors: Chella, Siame Nampasa
- Date: 2020
- Subjects: Unemployment -- Effect of inflation -- Mathematical models --Zambia
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10948/49783 , vital:41800
- Description: The objective for this study was to explore the relationship between inflation and growth with an understanding of the effects of unemployment on growth. The primary objective of this paper was to investigate the existence of Phillips Curve, Okun’s Law, and Taylor Rule in Zambia on the basis that Zambia is a youthful economy, with a growing population, which is expected to temper with unemployment rates, as an increase in the supply of labour might be too high for the demand for jobs available. To be specific, the study aims at determining the relationship between inflation and growth and seeks to understand what policy measures have been undertaken to curb inflation and reduce unemployment in Zambia. To achieve this, a quantitative research was undertaken using the ARDL cointegration model in conjunction with sensitivity tests to cater for structural changes in the economy with 2007 standing as the break point, as well as paying attention to the fact that different policy regimes employed during the course of the data covered, that being, 1996 to 2017, would affect that rates of unemployment, inflation and growth of the country, across period under review. The study revealed that Zambia faces a Hybrid New Keynesian Phillips Curve during the period under study which is dominated by a mixture of both back-ward and forward-looking aspects of inflation. This specifically, paints the effects of inflation persistence as well future expectations of inflation on growth. Further, a cointegration relationship was established between unemployment and output, while Taylor principles were found not to apply to the Zambian economy, which have proved in other economies to be foundation blocks for good economic growth and as such significant to both fiscal and monetary policy authorities of the economy. The researcher therefore recommends that Zambian policy makers, that is, both the fiscal and the monetary authorities, work together in order to attain minimal and optimal levels of inflation to help achieve a conducive economic environment for the country.
- Full Text:
- Date Issued: 2020
- Authors: Chella, Siame Nampasa
- Date: 2020
- Subjects: Unemployment -- Effect of inflation -- Mathematical models --Zambia
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10948/49783 , vital:41800
- Description: The objective for this study was to explore the relationship between inflation and growth with an understanding of the effects of unemployment on growth. The primary objective of this paper was to investigate the existence of Phillips Curve, Okun’s Law, and Taylor Rule in Zambia on the basis that Zambia is a youthful economy, with a growing population, which is expected to temper with unemployment rates, as an increase in the supply of labour might be too high for the demand for jobs available. To be specific, the study aims at determining the relationship between inflation and growth and seeks to understand what policy measures have been undertaken to curb inflation and reduce unemployment in Zambia. To achieve this, a quantitative research was undertaken using the ARDL cointegration model in conjunction with sensitivity tests to cater for structural changes in the economy with 2007 standing as the break point, as well as paying attention to the fact that different policy regimes employed during the course of the data covered, that being, 1996 to 2017, would affect that rates of unemployment, inflation and growth of the country, across period under review. The study revealed that Zambia faces a Hybrid New Keynesian Phillips Curve during the period under study which is dominated by a mixture of both back-ward and forward-looking aspects of inflation. This specifically, paints the effects of inflation persistence as well future expectations of inflation on growth. Further, a cointegration relationship was established between unemployment and output, while Taylor principles were found not to apply to the Zambian economy, which have proved in other economies to be foundation blocks for good economic growth and as such significant to both fiscal and monetary policy authorities of the economy. The researcher therefore recommends that Zambian policy makers, that is, both the fiscal and the monetary authorities, work together in order to attain minimal and optimal levels of inflation to help achieve a conducive economic environment for the country.
- Full Text:
- Date Issued: 2020
Analysis of the regulation of HSP90α expression upon differentiation of C2C12 cells
- Authors: Holm, Nathan Christopher
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163318 , vital:41028
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Holm, Nathan Christopher
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163318 , vital:41028
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
Analysis of the relationship between changes in macroeconomic variables and various sector price indices of JSE
- Mapanda, Tungamirai Chisvuvo
- Authors: Mapanda, Tungamirai Chisvuvo
- Date: 2020
- Subjects: Johannesburg Stock Exchange , Stock price indexes -- South Africa , Interest rates -- South Africa
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/147445 , vital:38637
- Description: Purpose- The purpose of this paper is to analyse the relationship between changes in domestic macroeconomic variables and various indices of the JSE during the full time period, June 1995 to December 2018 and the sub-periods, June 1995 to June 2007 and July 2007 to December 2018. Design/ methodology/ approach- The paper employs the Autoregressive Distributed Lag (ARDL) model approach to cointegration using monthly data from June 1995 to December 2018. Findings- In terms of the long run, the results show that the coincident indicator measure of domestic economic activity is positively and significantly related to the various JSE indices for all study periods. In terms of inflation, the results show no relationship between inflation rate and the various indices for both whole period and June 1995 to June 2007 sub period. However for the July 2007 to December 2018 sub period, JSE All Share Index and JSE Top 40 Index are negatively related. For the real effective exchange rate, only the Consumer Services Index is positively related to the exchange rate in terms of June 1995 to June 2007 sub period. However, JSE All Share Index and JSE Top 40 Index are negatively related to the exchange rate in all study periods. In terms of the short term interest rate, for the whole period, JSE All Share Index, JSE Top 40 Index, Health Care Index and Telecommunications Index are negatively related to interest rate. In terms of the June 1995 to June 2007 sub period, JSE All Share Index and Industrials Index are negatively related to the short term interest rate. For the July 2007 to December 2018 sub period, Telecommunications Index and Technology Index are negatively related. In terms of the short run, the coincident indicator is positively and significantly related to the various JSE indices for all study periods. Inflation is not significantly related to any index in the whole period. In terms of the June 1995 to June 2007 sub period, Industrials Index and Financials Index are positively related to inflation and in the July 2007 to December 2018 sub period, Consumer Goods Index, Health Index and Consumer Services Index are negatively related to the inflation rate. The real effective exchange rate is positively and significantly related to the various JSE indices in the different study periods. In terms of the short term interest rate, for the whole period and the June 1995 to June 2007 sub period only the Technology Index is not significantly and negatively related to the short term interest rate, but for the July 2007 to December 2018 sub period, Top 40 Index, Telecommunications Index and Technology Index are positively related to the interest rate. Only the Financial Index is negatively related to short term interest rates during this sub period. Research Limitations- Not a lot literature was found on the relationship between macroeconomic variables and the various sector indices of the JSE. Most previous work, in the South African context focused just on the JSE All Share Index. Practical Implications- The findings can help investors diversify their portfolios into indices that benefit from expected changes in macroeconomic variables, such as recessions, rising interest rates, rising inflation or a weakening exchange rate. Alternatively, they can hedge themselves against the negative implications of such macroeconomic changes on portfolio performance. In addition, the findings are important for the monetary authorities to better understand the implications of their policy changes on financial markets.
- Full Text:
- Date Issued: 2020
- Authors: Mapanda, Tungamirai Chisvuvo
- Date: 2020
- Subjects: Johannesburg Stock Exchange , Stock price indexes -- South Africa , Interest rates -- South Africa
- Language: English
- Type: text , Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10962/147445 , vital:38637
- Description: Purpose- The purpose of this paper is to analyse the relationship between changes in domestic macroeconomic variables and various indices of the JSE during the full time period, June 1995 to December 2018 and the sub-periods, June 1995 to June 2007 and July 2007 to December 2018. Design/ methodology/ approach- The paper employs the Autoregressive Distributed Lag (ARDL) model approach to cointegration using monthly data from June 1995 to December 2018. Findings- In terms of the long run, the results show that the coincident indicator measure of domestic economic activity is positively and significantly related to the various JSE indices for all study periods. In terms of inflation, the results show no relationship between inflation rate and the various indices for both whole period and June 1995 to June 2007 sub period. However for the July 2007 to December 2018 sub period, JSE All Share Index and JSE Top 40 Index are negatively related. For the real effective exchange rate, only the Consumer Services Index is positively related to the exchange rate in terms of June 1995 to June 2007 sub period. However, JSE All Share Index and JSE Top 40 Index are negatively related to the exchange rate in all study periods. In terms of the short term interest rate, for the whole period, JSE All Share Index, JSE Top 40 Index, Health Care Index and Telecommunications Index are negatively related to interest rate. In terms of the June 1995 to June 2007 sub period, JSE All Share Index and Industrials Index are negatively related to the short term interest rate. For the July 2007 to December 2018 sub period, Telecommunications Index and Technology Index are negatively related. In terms of the short run, the coincident indicator is positively and significantly related to the various JSE indices for all study periods. Inflation is not significantly related to any index in the whole period. In terms of the June 1995 to June 2007 sub period, Industrials Index and Financials Index are positively related to inflation and in the July 2007 to December 2018 sub period, Consumer Goods Index, Health Index and Consumer Services Index are negatively related to the inflation rate. The real effective exchange rate is positively and significantly related to the various JSE indices in the different study periods. In terms of the short term interest rate, for the whole period and the June 1995 to June 2007 sub period only the Technology Index is not significantly and negatively related to the short term interest rate, but for the July 2007 to December 2018 sub period, Top 40 Index, Telecommunications Index and Technology Index are positively related to the interest rate. Only the Financial Index is negatively related to short term interest rates during this sub period. Research Limitations- Not a lot literature was found on the relationship between macroeconomic variables and the various sector indices of the JSE. Most previous work, in the South African context focused just on the JSE All Share Index. Practical Implications- The findings can help investors diversify their portfolios into indices that benefit from expected changes in macroeconomic variables, such as recessions, rising interest rates, rising inflation or a weakening exchange rate. Alternatively, they can hedge themselves against the negative implications of such macroeconomic changes on portfolio performance. In addition, the findings are important for the monetary authorities to better understand the implications of their policy changes on financial markets.
- Full Text:
- Date Issued: 2020
Analytical Detection and Electrocatalysis of Paracetamol in Aqueous Media Using Rare‐Earth Double‐Decker Phthalocyaninato Chelates as Electrochemically Active Materials
- Sekhosana, Kutloana E, Nkhahle, Reitumetse, Nyokong, Tebello
- Authors: Sekhosana, Kutloana E , Nkhahle, Reitumetse , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/190840 , vital:45033 , xlink:href="https://doi.org/10.1002/slct.202002268"
- Description: Paracetamol (PA), being an analgesic and antipyretic medicine, can cause fatal hepatotoxicity and nephrotoxicity when overdosed. It is therefore important to develop electrochemical sensors that can monitor and quantify it in aquatic environments. In this study, rare-earth sandwich-type phthalocyaninato chelates based on neodymium (1 a) and samarium (1 b) were employed as electrocatalysts to modify glassy carbon electrodes (GCE) for the first time. It was found that 1 a-modified GCE (herein referred to as 1 a-GCE) is less conductive than 1 b-modified counterpart (1 b-GCE). A larger rate constant was also obtained for 1 b-GCE. It was established that a faster oxidation rate efficiency was responsible for lower limit of detection value obtained for 1 b-GCE as compared to 1 a-GCE.
- Full Text:
- Date Issued: 2020
- Authors: Sekhosana, Kutloana E , Nkhahle, Reitumetse , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/190840 , vital:45033 , xlink:href="https://doi.org/10.1002/slct.202002268"
- Description: Paracetamol (PA), being an analgesic and antipyretic medicine, can cause fatal hepatotoxicity and nephrotoxicity when overdosed. It is therefore important to develop electrochemical sensors that can monitor and quantify it in aquatic environments. In this study, rare-earth sandwich-type phthalocyaninato chelates based on neodymium (1 a) and samarium (1 b) were employed as electrocatalysts to modify glassy carbon electrodes (GCE) for the first time. It was found that 1 a-modified GCE (herein referred to as 1 a-GCE) is less conductive than 1 b-modified counterpart (1 b-GCE). A larger rate constant was also obtained for 1 b-GCE. It was established that a faster oxidation rate efficiency was responsible for lower limit of detection value obtained for 1 b-GCE as compared to 1 a-GCE.
- Full Text:
- Date Issued: 2020
Analytical evaluation of the effect of aggregate variation on Asphalt Mixture Properties
- Authors: Van Eck, Elandre
- Date: 2020
- Subjects: Aggregates (Building materials)
- Language: English
- Type: Thesis , Masters , MEng
- Identifier: http://hdl.handle.net/10948/49639 , vital:41743
- Description: This research study aimed to conduct an analytical evaluation of the effect of aggregate grading on the properties of asphalt mixtures. This was achieved by obtaining asphalt mix designs from approved civil engineering organisations and determining the relationship between the aggregate grading and the corresponding properties of the asphalt mix designs.
- Full Text: false
- Date Issued: 2020
- Authors: Van Eck, Elandre
- Date: 2020
- Subjects: Aggregates (Building materials)
- Language: English
- Type: Thesis , Masters , MEng
- Identifier: http://hdl.handle.net/10948/49639 , vital:41743
- Description: This research study aimed to conduct an analytical evaluation of the effect of aggregate grading on the properties of asphalt mixtures. This was achieved by obtaining asphalt mix designs from approved civil engineering organisations and determining the relationship between the aggregate grading and the corresponding properties of the asphalt mix designs.
- Full Text: false
- Date Issued: 2020
Anger, Pain and the Body in the Public Sphere:
- Authors: Garman, Anthea
- Date: 2020
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/158459 , vital:40188 , ISBN 9781776145898
- Description: In this timely, original and sophisticated collection, writers from the Global South demonstrate that forms of publicness are multiple, mobile and varied. The notion that societies mediate issues through certain kinds of engagement is at the heart of imaginings of democracy and often centers on the ideal of the public sphere. But this imagined foundation of how we live collectively appears to have suffered a dramatic collapse across the world, with many democracies apparently unable to solve problems through talk – or even to agree on who speaks, in what ways and where. In the 10 essays in this timely, original and sophisticated collection, writers from southern Africa combine theoretical analysis with the examination of historical cases and contemporary developments to demonstrate that forms of publicness are multiple, mobile and varied. They propose new concepts and methodologies to analyse how public engagements work in society.
- Full Text:
- Date Issued: 2020
- Authors: Garman, Anthea
- Date: 2020
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/158459 , vital:40188 , ISBN 9781776145898
- Description: In this timely, original and sophisticated collection, writers from the Global South demonstrate that forms of publicness are multiple, mobile and varied. The notion that societies mediate issues through certain kinds of engagement is at the heart of imaginings of democracy and often centers on the ideal of the public sphere. But this imagined foundation of how we live collectively appears to have suffered a dramatic collapse across the world, with many democracies apparently unable to solve problems through talk – or even to agree on who speaks, in what ways and where. In the 10 essays in this timely, original and sophisticated collection, writers from southern Africa combine theoretical analysis with the examination of historical cases and contemporary developments to demonstrate that forms of publicness are multiple, mobile and varied. They propose new concepts and methodologies to analyse how public engagements work in society.
- Full Text:
- Date Issued: 2020
Anti-cancer and anti-trypanosomal properties of alkaloids from the root bark of Zanthoxylum leprieurii Guill and Perr
- Eze, Fabian I, Siwe-Noundou, Xavier, Isaacs, Michelle, Patala, Srivinas, Osadebe, Patience O, Krause, Rui W M
- Authors: Eze, Fabian I , Siwe-Noundou, Xavier , Isaacs, Michelle , Patala, Srivinas , Osadebe, Patience O , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193352 , vital:45324 , xlink:href="http://dx.doi.org/10.4314/tjpr.v19i11.19"
- Description: Purpose: To isolate the anti-cancer and anti-trypanosomal principles of Zanthoxylum leprieurii, a medicinally versatile wild tropical plant used for managing tumours, African trypanosomiasis, and inflammation in southeastern Nigeria. Methods: The pure compounds were isolated using chromatographic methods. The structural elucidation of the pure compounds was based on their NMR (1D and 2D) and mass spectral data as well as chemical test results. Structure-activity relationships were based on the structural differences among the compounds. The cytotoxicity of the extracts and compounds (1, 2, 3, and 4) was evaluated in HeLa (human cervix adenocarcinoma) cell line while the trypanocidal activities were evaluated on Trypanosoma brucei brucei. Results: Two acridone alkaloids, 1-hydroxy-3-methoxy-10-methylacridin-9 (10H)-one, named fabiocinine (1), and 1-hydroxy-2,3-dimethoxy-10-methylacridin-9 (10H)-one (arborinine, 2), together with a furoquinoline alkaloid, skimmianine (3), and a chelerythrine derivative, 6-acetonyl-5,6-dihydrochelerythrine (4) were isolated from the root bark of Zanthoxylum leprieurii. Skimmianine (3) exhibited cytotoxicity and anti-trypanosomal IC50 of 12.8 and 13.2 µg/mL respectively (p less than 0.05). Compound (1) and arborinine (2) were selectively cytotoxic to HeLa cells with cytotoxicity IC50 of 28.49 and 62.71 µg/mL, respectively, while (4) did not show significant activity (p less than 0.05). Conclusion: Zanthoxylum leprieurii root bark contains cytotoxic and trypanocidal compounds, and is thus a potential source of anti-cancer and anti-trypanosomal leads.
- Full Text:
- Date Issued: 2020
- Authors: Eze, Fabian I , Siwe-Noundou, Xavier , Isaacs, Michelle , Patala, Srivinas , Osadebe, Patience O , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193352 , vital:45324 , xlink:href="http://dx.doi.org/10.4314/tjpr.v19i11.19"
- Description: Purpose: To isolate the anti-cancer and anti-trypanosomal principles of Zanthoxylum leprieurii, a medicinally versatile wild tropical plant used for managing tumours, African trypanosomiasis, and inflammation in southeastern Nigeria. Methods: The pure compounds were isolated using chromatographic methods. The structural elucidation of the pure compounds was based on their NMR (1D and 2D) and mass spectral data as well as chemical test results. Structure-activity relationships were based on the structural differences among the compounds. The cytotoxicity of the extracts and compounds (1, 2, 3, and 4) was evaluated in HeLa (human cervix adenocarcinoma) cell line while the trypanocidal activities were evaluated on Trypanosoma brucei brucei. Results: Two acridone alkaloids, 1-hydroxy-3-methoxy-10-methylacridin-9 (10H)-one, named fabiocinine (1), and 1-hydroxy-2,3-dimethoxy-10-methylacridin-9 (10H)-one (arborinine, 2), together with a furoquinoline alkaloid, skimmianine (3), and a chelerythrine derivative, 6-acetonyl-5,6-dihydrochelerythrine (4) were isolated from the root bark of Zanthoxylum leprieurii. Skimmianine (3) exhibited cytotoxicity and anti-trypanosomal IC50 of 12.8 and 13.2 µg/mL respectively (p less than 0.05). Compound (1) and arborinine (2) were selectively cytotoxic to HeLa cells with cytotoxicity IC50 of 28.49 and 62.71 µg/mL, respectively, while (4) did not show significant activity (p less than 0.05). Conclusion: Zanthoxylum leprieurii root bark contains cytotoxic and trypanocidal compounds, and is thus a potential source of anti-cancer and anti-trypanosomal leads.
- Full Text:
- Date Issued: 2020
Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives
- Waleguele, Christine C, Mba'ning, Brice M, Awantu, Angelbert F, Bankeu, Jean J, Fongang, Yannick S F, Ngouela, Augustin S, Tsamo, Etienne, Sewald, Norbert, Lenta, Bruno N, Krause, Rui W M
- Authors: Waleguele, Christine C , Mba'ning, Brice M , Awantu, Angelbert F , Bankeu, Jean J , Fongang, Yannick S F , Ngouela, Augustin S , Tsamo, Etienne , Sewald, Norbert , Lenta, Bruno N , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193364 , vital:45325 , xlink:href="https://doi.org/10.3390/molecules25122862"
- Description: The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4–15). In addition, four new derivatives (11a–11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 μM.
- Full Text:
- Date Issued: 2020
- Authors: Waleguele, Christine C , Mba'ning, Brice M , Awantu, Angelbert F , Bankeu, Jean J , Fongang, Yannick S F , Ngouela, Augustin S , Tsamo, Etienne , Sewald, Norbert , Lenta, Bruno N , Krause, Rui W M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193364 , vital:45325 , xlink:href="https://doi.org/10.3390/molecules25122862"
- Description: The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4–15). In addition, four new derivatives (11a–11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 μM.
- Full Text:
- Date Issued: 2020
Application of In Vitro Release Testing (IVRT) and a dermatopharmacokinetic approach (tape stripping) for the assessment of Metronidazole topical formulations
- Rath, Seeprarani Prabirkumar
- Authors: Rath, Seeprarani Prabirkumar
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164617 , vital:41148 , doi:10.21504/10962/164617
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Rath, Seeprarani Prabirkumar
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164617 , vital:41148 , doi:10.21504/10962/164617
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
Application of machine learning, molecular modelling and structural data mining against antiretroviral drug resistance in HIV-1
- Sheik Amamuddy, Olivier Serge André
- Authors: Sheik Amamuddy, Olivier Serge André
- Date: 2020
- Subjects: Machine learning , Molecules -- Models , Data mining , Neural networks (Computer science) , Antiretroviral agents , Protease inhibitors , Drug resistance , Multidrug resistance , Molecular dynamics , Renin-angiotensin system , HIV (Viruses) -- South Africa , HIV (Viruses) -- Social aspects -- South Africa , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115964 , vital:34282
- Description: Millions are affected with the Human Immunodeficiency Virus (HIV) world wide, even though the death toll is on the decline. Antiretrovirals (ARVs), more specifically protease inhibitors have shown tremendous success since their introduction into therapy since the mid 1990’s by slowing down progression to the Acquired Immune Deficiency Syndrome (AIDS). However, Drug Resistance Mutations (DRMs) are constantly selected for due to viral adaptation, making drugs less effective over time. The current challenge is to manage the infection optimally with a limited set of drugs, with differing associated levels of toxicities in the face of a virus that (1) exists as a quasispecies, (2) may transmit acquired DRMs to drug-naive individuals and (3) that can manifest class-wide resistance due to similarities in design. The presence of latent reservoirs, unawareness of infection status, education and various socio-economic factors make the problem even more complex. Adequate timing and choice of drug prescription together with treatment adherence are very important as drug toxicities, drug failure and sub-optimal treatment regimens leave room for further development of drug resistance. While CD4 cell count and the determination of viral load from patients in resource-limited settings are very helpful to track how well a patient’s immune system is able to keep the virus in check, they can be lengthy in determining whether an ARV is effective. Phenosense assay kits answer this problem using viruses engineered to contain the patient sequences and evaluating their growth in the presence of different ARVs, but this can be expensive and too involved for routine checks. As a cheaper and faster alternative, genotypic assays provide similar information from HIV pol sequences obtained from blood samples, inferring ARV efficacy on the basis of drug resistance mutation patterns. However, these are inherently complex and the various methods of in silico prediction, such as Geno2pheno, REGA and Stanford HIVdb do not always agree in every case, even though this gap decreases as the list of resistance mutations is updated. A major gap in HIV treatment is that the information used for predicting drug resistance is mainly computed from data containing an overwhelming majority of B subtype HIV, when these only comprise about 12% of the worldwide HIV infections. In addition to growing evidence that drug resistance is subtype-related, it is intuitive to hypothesize that as subtyping is a phylogenetic classification, the more divergent a subtype is from the strains used in training prediction models, the less their resistance profiles would correlate. For the aforementioned reasons, we used a multi-faceted approach to attack the virus in multiple ways. This research aimed to (1) improve resistance prediction methods by focusing solely on the available subtype, (2) mine structural information pertaining to resistance in order to find any exploitable weak points and increase knowledge of the mechanistic processes of drug resistance in HIV protease. Finally, (3) we screen for protease inhibitors amongst a database of natural compounds [the South African natural compound database (SANCDB)] to find molecules or molecular properties usable to come up with improved inhibition against the drug target. In this work, structural information was mined using the Anisotropic Network Model, Dynamics Cross-Correlation, Perturbation Response Scanning, residue contact network analysis and the radius of gyration. These methods failed to give any resistance-associated patterns in terms of natural movement, internal correlated motions, residue perturbation response, relational behaviour and global compaction respectively. Applications of drug docking, homology-modelling and energy minimization for generating features suitable for machine-learning were not very promising, and rather suggest that the value of binding energies by themselves from Vina may not be very reliable quantitatively. All these failures lead to a refinement that resulted in a highly sensitive statistically-guided network construction and analysis, which leads to key findings in the early dynamics associated with resistance across all PI drugs. The latter experiment unravelled a conserved lateral expansion motion occurring at the flap elbows, and an associated contraction that drives the base of the dimerization domain towards the catalytic site’s floor in the case of drug resistance. Interestingly, we found that despite the conserved movement, bond angles were degenerate. Alongside, 16 Artificial Neural Network models were optimised for HIV proteases and reverse transcriptase inhibitors, with performances on par with Stanford HIVdb. Finally, we prioritised 9 compounds with potential protease inhibitory activity using virtual screening and molecular dynamics (MD) to additionally suggest a promising modification to one of the compounds. This yielded another molecule inhibiting equally well both opened and closed receptor target conformations, whereby each of the compounds had been selected against an array of multi-drug-resistant receptor variants. While a main hurdle was a lack of non-B subtype data, our findings, especially from the statistically-guided network analysis, may extrapolate to a certain extent to them as the level of conservation was very high within subtype B, despite all the present variations. This network construction method lays down a sensitive approach for analysing a pair of alternate phenotypes for which complex patterns prevail, given a sufficient number of experimental units. During the course of research a weighted contact mapping tool was developed to compare renin-angiotensinogen variants and packaged as part of the MD-TASK tool suite. Finally the functionality, compatibility and performance of the MODE-TASK tool were evaluated and confirmed for both Python2.7.x and Python3.x, for the analysis of normals modes from single protein structures and essential modes from MD trajectories. These techniques and tools collectively add onto the conventional means of MD analysis.
- Full Text:
- Date Issued: 2020
- Authors: Sheik Amamuddy, Olivier Serge André
- Date: 2020
- Subjects: Machine learning , Molecules -- Models , Data mining , Neural networks (Computer science) , Antiretroviral agents , Protease inhibitors , Drug resistance , Multidrug resistance , Molecular dynamics , Renin-angiotensin system , HIV (Viruses) -- South Africa , HIV (Viruses) -- Social aspects -- South Africa , South African Natural Compounds Database
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/115964 , vital:34282
- Description: Millions are affected with the Human Immunodeficiency Virus (HIV) world wide, even though the death toll is on the decline. Antiretrovirals (ARVs), more specifically protease inhibitors have shown tremendous success since their introduction into therapy since the mid 1990’s by slowing down progression to the Acquired Immune Deficiency Syndrome (AIDS). However, Drug Resistance Mutations (DRMs) are constantly selected for due to viral adaptation, making drugs less effective over time. The current challenge is to manage the infection optimally with a limited set of drugs, with differing associated levels of toxicities in the face of a virus that (1) exists as a quasispecies, (2) may transmit acquired DRMs to drug-naive individuals and (3) that can manifest class-wide resistance due to similarities in design. The presence of latent reservoirs, unawareness of infection status, education and various socio-economic factors make the problem even more complex. Adequate timing and choice of drug prescription together with treatment adherence are very important as drug toxicities, drug failure and sub-optimal treatment regimens leave room for further development of drug resistance. While CD4 cell count and the determination of viral load from patients in resource-limited settings are very helpful to track how well a patient’s immune system is able to keep the virus in check, they can be lengthy in determining whether an ARV is effective. Phenosense assay kits answer this problem using viruses engineered to contain the patient sequences and evaluating their growth in the presence of different ARVs, but this can be expensive and too involved for routine checks. As a cheaper and faster alternative, genotypic assays provide similar information from HIV pol sequences obtained from blood samples, inferring ARV efficacy on the basis of drug resistance mutation patterns. However, these are inherently complex and the various methods of in silico prediction, such as Geno2pheno, REGA and Stanford HIVdb do not always agree in every case, even though this gap decreases as the list of resistance mutations is updated. A major gap in HIV treatment is that the information used for predicting drug resistance is mainly computed from data containing an overwhelming majority of B subtype HIV, when these only comprise about 12% of the worldwide HIV infections. In addition to growing evidence that drug resistance is subtype-related, it is intuitive to hypothesize that as subtyping is a phylogenetic classification, the more divergent a subtype is from the strains used in training prediction models, the less their resistance profiles would correlate. For the aforementioned reasons, we used a multi-faceted approach to attack the virus in multiple ways. This research aimed to (1) improve resistance prediction methods by focusing solely on the available subtype, (2) mine structural information pertaining to resistance in order to find any exploitable weak points and increase knowledge of the mechanistic processes of drug resistance in HIV protease. Finally, (3) we screen for protease inhibitors amongst a database of natural compounds [the South African natural compound database (SANCDB)] to find molecules or molecular properties usable to come up with improved inhibition against the drug target. In this work, structural information was mined using the Anisotropic Network Model, Dynamics Cross-Correlation, Perturbation Response Scanning, residue contact network analysis and the radius of gyration. These methods failed to give any resistance-associated patterns in terms of natural movement, internal correlated motions, residue perturbation response, relational behaviour and global compaction respectively. Applications of drug docking, homology-modelling and energy minimization for generating features suitable for machine-learning were not very promising, and rather suggest that the value of binding energies by themselves from Vina may not be very reliable quantitatively. All these failures lead to a refinement that resulted in a highly sensitive statistically-guided network construction and analysis, which leads to key findings in the early dynamics associated with resistance across all PI drugs. The latter experiment unravelled a conserved lateral expansion motion occurring at the flap elbows, and an associated contraction that drives the base of the dimerization domain towards the catalytic site’s floor in the case of drug resistance. Interestingly, we found that despite the conserved movement, bond angles were degenerate. Alongside, 16 Artificial Neural Network models were optimised for HIV proteases and reverse transcriptase inhibitors, with performances on par with Stanford HIVdb. Finally, we prioritised 9 compounds with potential protease inhibitory activity using virtual screening and molecular dynamics (MD) to additionally suggest a promising modification to one of the compounds. This yielded another molecule inhibiting equally well both opened and closed receptor target conformations, whereby each of the compounds had been selected against an array of multi-drug-resistant receptor variants. While a main hurdle was a lack of non-B subtype data, our findings, especially from the statistically-guided network analysis, may extrapolate to a certain extent to them as the level of conservation was very high within subtype B, despite all the present variations. This network construction method lays down a sensitive approach for analysing a pair of alternate phenotypes for which complex patterns prevail, given a sufficient number of experimental units. During the course of research a weighted contact mapping tool was developed to compare renin-angiotensinogen variants and packaged as part of the MD-TASK tool suite. Finally the functionality, compatibility and performance of the MODE-TASK tool were evaluated and confirmed for both Python2.7.x and Python3.x, for the analysis of normals modes from single protein structures and essential modes from MD trajectories. These techniques and tools collectively add onto the conventional means of MD analysis.
- Full Text:
- Date Issued: 2020
Application of quality by design principles for optimizing process variables of Extrusion and Spheronization of a Captopril Pellet Formulation:
- Veerubhotla, Krishna, Walker, Roderick B
- Authors: Veerubhotla, Krishna , Walker, Roderick B
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/178312 , vital:40098 , DOI: 10.36468/pharmaceutical-sciences.624
- Description: Product development using quality by design is a proactive and risk-based approach that shifts the manufacturing process from empirical to science-based. Risk assessment was performed to identify and analyse risk areas for the manufacture of captopril pellets. Twelve experimental runs were performed using a Plackett-Burman screening design. Pareto plots revealed the effect of formulation and process variables on the responses monitored and facilitated the identification of the most critical parameters for optimization of the formulation. A response surface methodology approach in conjunction with a central composite design was used to optimize the Eudragit® RL 30D (15-30 ml), microcrystalline cellulose (20-40 % w/w), sodium starch glycolate (2-5 % w/w) and spheronizer speed (650-1050 rpm).
- Full Text:
- Date Issued: 2020
- Authors: Veerubhotla, Krishna , Walker, Roderick B
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/178312 , vital:40098 , DOI: 10.36468/pharmaceutical-sciences.624
- Description: Product development using quality by design is a proactive and risk-based approach that shifts the manufacturing process from empirical to science-based. Risk assessment was performed to identify and analyse risk areas for the manufacture of captopril pellets. Twelve experimental runs were performed using a Plackett-Burman screening design. Pareto plots revealed the effect of formulation and process variables on the responses monitored and facilitated the identification of the most critical parameters for optimization of the formulation. A response surface methodology approach in conjunction with a central composite design was used to optimize the Eudragit® RL 30D (15-30 ml), microcrystalline cellulose (20-40 % w/w), sodium starch glycolate (2-5 % w/w) and spheronizer speed (650-1050 rpm).
- Full Text:
- Date Issued: 2020
Application of section 197 of the Labour Relations Act in an insourcing context
- Authors: Mahlati, Nomphelo Miliswa
- Date: 2020
- Subjects: Labor laws and legislation -- South Africa
- Language: English
- Type: Thesis , Masters , LLM
- Identifier: http://hdl.handle.net/10948/47392 , vital:39974
- Description: The last two decades have been characterised by a phenomenal rise in the outsourcing of services to external service providers. The driver of this trend has been largely economic, since outsourcing offers more competitive price points for the same service at a comparable service level. Beyond the cost saving objective, the rationale for outsourcing has been to drive core strategy. However, with the economic slowdown, declining consumption and production are forcing entrepreneurs to change their way of thinking about the management of companies. Notably, in recent years there has been a small but a growing reversal of this trend where companies that have previously outsourced functions are being brought back in-house. One of the major concerns surrounding these changes of business strategies is the extent to which the employee rights are safeguarded.
- Full Text:
- Date Issued: 2020
- Authors: Mahlati, Nomphelo Miliswa
- Date: 2020
- Subjects: Labor laws and legislation -- South Africa
- Language: English
- Type: Thesis , Masters , LLM
- Identifier: http://hdl.handle.net/10948/47392 , vital:39974
- Description: The last two decades have been characterised by a phenomenal rise in the outsourcing of services to external service providers. The driver of this trend has been largely economic, since outsourcing offers more competitive price points for the same service at a comparable service level. Beyond the cost saving objective, the rationale for outsourcing has been to drive core strategy. However, with the economic slowdown, declining consumption and production are forcing entrepreneurs to change their way of thinking about the management of companies. Notably, in recent years there has been a small but a growing reversal of this trend where companies that have previously outsourced functions are being brought back in-house. One of the major concerns surrounding these changes of business strategies is the extent to which the employee rights are safeguarded.
- Full Text:
- Date Issued: 2020
Applied phylogeography : mapping the genetic resource of Honeybush across the Cape Floristic Region
- Authors: Galuszynski, Nicholas C
- Date: 2020
- Subjects: Phylogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46771 , vital:39655
- Description: Aim: Honeybush tea is a herbal infusion made from members of the Cape Floristic Region (CFR) endemic Cyclopia Vent. Consting of 21 extant species, six are anthropogenically redistributed across the CFR for Honeybush cultivation. However, with no information regarding the distribution and levels of genetic diversity among wild Honeybush populations, anthropogenic translocation of cultivated genotypes may risk disrupting natural genetic diversity patterns. In this thesis, an applied phylogeographic approach is used to provide baseline insights into the spatial structuring of Honeybush genetic diversity. Location: The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods: Spatial structuring of evolutionary lineages within Cyclopia are explored at a genus level using data generated from the combination of Anchored Hybrid Enrichment library preparation and high through put sequencing. A High Resolution Melt analysis (HRM) toolkit is then developed to screen haplotype variation across three non-coding chloroplast loci. This HRM toolkit coupled with haplotype confirmation Sanger sequencing is then applied to describe the spatial structuring of genetic diversity in wild populations for two Honeybush species (C. intermedia and C. subternata) and to compare genetic diversity among wild and cultivated populations of three Honeybush species (C. intermedia, C. subternata, and C. longifolia). A reanalysis of published phylogeographic data focusing on CFR plant taxa is used to test if phylogeographic breaks occur across the boundaries among adjacent Centers of Endemism (CoEs). Finally, the low-copy nuclear data set generated via AHE and high throughput sequencing is summarized. Results: Phylogeographic structuring was detected at the inter- and intraspecific levels in Cyclopia. The genus level analysis revealed a strong phylogenetic split between western CFR and eastern CFR endemic species in the nuclear and chloroplast genomes. At the intraspecific level, HRM proved to be a high throughput and accurate tool for haplotype detection, revealing phylogeographic structuring of genetic diversity in C.intermediaand C.subternata. This genetic diversity and structuring was not detected in cultivated Honeybush populations, which appear to have originated from a small number of founding individuals and have experienced a genetic bottleneck. Spatial structuring of genetic lineages is common among CFR plant taxa and the reanalysis of existing data found a significant trend for phylogeographic breaks tooccuracrosstheboundariesamongadjacentCoEs. Finally, over200000baseswere sequenced across 445 low-copy nuclear loci for 14 Cyclopia species. Conclusions: This thesis provides important baseline information on the spatial distribution of wild Honeybush genetic diversity. Phylogeographic structuring is present in wild Honeybush populations. This however is not accounted for in cultivated populations, which may place wild genetic diversity at risk of being disrupted if geneflow among wild and cultivated populations occurs. The results from this thesis should therefore be used to develop precautionary guidelines for the anthropogenic redistribution of Honeybush genetic material for cultivation. Furthermore, the novel insights into regional patterns of phylogeohraphic structuring of plant populations should encourage more efficient and hypothesis driven sampling designs in future phylogeographic work in the CFR. The high throughput sequence data generated in this thesis should transform Cyclopia to a model organism for the study of molecular evolution in the CFR.
- Full Text:
- Date Issued: 2020
- Authors: Galuszynski, Nicholas C
- Date: 2020
- Subjects: Phylogeography -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/46771 , vital:39655
- Description: Aim: Honeybush tea is a herbal infusion made from members of the Cape Floristic Region (CFR) endemic Cyclopia Vent. Consting of 21 extant species, six are anthropogenically redistributed across the CFR for Honeybush cultivation. However, with no information regarding the distribution and levels of genetic diversity among wild Honeybush populations, anthropogenic translocation of cultivated genotypes may risk disrupting natural genetic diversity patterns. In this thesis, an applied phylogeographic approach is used to provide baseline insights into the spatial structuring of Honeybush genetic diversity. Location: The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods: Spatial structuring of evolutionary lineages within Cyclopia are explored at a genus level using data generated from the combination of Anchored Hybrid Enrichment library preparation and high through put sequencing. A High Resolution Melt analysis (HRM) toolkit is then developed to screen haplotype variation across three non-coding chloroplast loci. This HRM toolkit coupled with haplotype confirmation Sanger sequencing is then applied to describe the spatial structuring of genetic diversity in wild populations for two Honeybush species (C. intermedia and C. subternata) and to compare genetic diversity among wild and cultivated populations of three Honeybush species (C. intermedia, C. subternata, and C. longifolia). A reanalysis of published phylogeographic data focusing on CFR plant taxa is used to test if phylogeographic breaks occur across the boundaries among adjacent Centers of Endemism (CoEs). Finally, the low-copy nuclear data set generated via AHE and high throughput sequencing is summarized. Results: Phylogeographic structuring was detected at the inter- and intraspecific levels in Cyclopia. The genus level analysis revealed a strong phylogenetic split between western CFR and eastern CFR endemic species in the nuclear and chloroplast genomes. At the intraspecific level, HRM proved to be a high throughput and accurate tool for haplotype detection, revealing phylogeographic structuring of genetic diversity in C.intermediaand C.subternata. This genetic diversity and structuring was not detected in cultivated Honeybush populations, which appear to have originated from a small number of founding individuals and have experienced a genetic bottleneck. Spatial structuring of genetic lineages is common among CFR plant taxa and the reanalysis of existing data found a significant trend for phylogeographic breaks tooccuracrosstheboundariesamongadjacentCoEs. Finally, over200000baseswere sequenced across 445 low-copy nuclear loci for 14 Cyclopia species. Conclusions: This thesis provides important baseline information on the spatial distribution of wild Honeybush genetic diversity. Phylogeographic structuring is present in wild Honeybush populations. This however is not accounted for in cultivated populations, which may place wild genetic diversity at risk of being disrupted if geneflow among wild and cultivated populations occurs. The results from this thesis should therefore be used to develop precautionary guidelines for the anthropogenic redistribution of Honeybush genetic material for cultivation. Furthermore, the novel insights into regional patterns of phylogeohraphic structuring of plant populations should encourage more efficient and hypothesis driven sampling designs in future phylogeographic work in the CFR. The high throughput sequence data generated in this thesis should transform Cyclopia to a model organism for the study of molecular evolution in the CFR.
- Full Text:
- Date Issued: 2020
Applying blockchain technology to aspects of electronic health records in South Africa: lessons learnt
- Authors: Adlam, Ryno
- Date: 2020
- Subjects: Blockchains (Databases) , Database security Data protection Medical records -- Data processing
- Language: English
- Type: Thesis , Masters , MIT
- Identifier: http://hdl.handle.net/10948/45996 , vital:39405
- Description: The purpose of this study was to explore the applicability of blockchain technology as a viable alternative for the secure storage and distribution of electronic health records in a South African context. The adoption of electronic health records (EHRs) has grown over recent years. Electronic health records (EHRs) can be seen as electronic versions of patients’ medical history. EHRs promise benefits such as improving the quality of care, reducing medical errors, reducing costs, saving time, and enhancing the availability and sharing of medical records. Blockchain, in simple terms, could be seen as a distributed database controlled by a group of individuals. Blockchain technology differs from other distributed ledger technology by bundling unrelated data into blocks that are chained together in a linked-list manner, hence the name blockchain. Blockchain technology strives to provide desirable features, such as decentralization, immutability, audibility, and transparency. EHRs are traditionally constructed with a cloud-based infrastructure to promote the storing and distribution of medical records. These medical records are commonly stored in a centralized architecture, such as a relational database. The centralized architecture employed by EHRs may present a single point of failure. These kinds of failures may lead to data-breaches. The cloud-based infrastructure is effective and efficient from an availability standpoint. The increased availability of electronic health records has brought forth challenges related to the security and privacy of the patient’s medical records. The sensitive nature of EHRs attracts the attention of cyber-criminals. There has been a rise in the number of data breaches related to electronic health records. The traditional infrastructure used by electronic health records can no longer ensure the privacy and security of patient’s medical records. To determine whether blockchain is a viable alternative to these approaches, the main objective of this study was to compile a technical report on the applicability of aspects of blockchain technology to the secure storage and distribution of electronic health records. The study first conducted a literature review to gather background on the current state of electronic health records and blockchain technology. The results of the literature review were used to compile an initial report. Experiments were conducted with various aspects of blockchain technology to build a technical baseline and to ultimately validate the initial report. The insights gained from the experiments served to refine the initial report into a final technical report. The final deliverable of this study was to devise a technical report. The technical report serves as a generalized overview of the applicability of blockchain technology as a secure storage and distribution mechanism for electronic health records. The main topics covered by the technical report to outline the applicability of blockchain technology to EHRs are as follows: authentication, authorization, audit log, storage and transactions. The insights gained from the study illustrate that permissioned blockchain technology can enhance the traditional AAA security scheme employed by traditional EHRs. The AAA security scheme entails the use of certificate-based authentication and attributebased access control for authorization. Audit logs can be stored in a semi-decentralized architecture that can enhance the security and privacy of audit logs. Using blockchain technology for storing electronic health records might not be a viable alternative to traditional EHRs architecture. Blockchain technology violates certain privacy regulations as information is stored in a permanent manner. Furthermore, blockchain technology is not optimized for dealing with large volumes of data. However, blockchain technology could be used to store a cryptographic hash of electronic health records to ensure the integrity of records. Permissioned blockchain technology can enhance the EHRs transaction process by transacting health records in a peer-to-peer infrastructure. In doing so, the above-mentioned AAA security scheme can enhance the security, confidentiality, and integrity of electronic health records shared across organizational bounds.
- Full Text:
- Date Issued: 2020
- Authors: Adlam, Ryno
- Date: 2020
- Subjects: Blockchains (Databases) , Database security Data protection Medical records -- Data processing
- Language: English
- Type: Thesis , Masters , MIT
- Identifier: http://hdl.handle.net/10948/45996 , vital:39405
- Description: The purpose of this study was to explore the applicability of blockchain technology as a viable alternative for the secure storage and distribution of electronic health records in a South African context. The adoption of electronic health records (EHRs) has grown over recent years. Electronic health records (EHRs) can be seen as electronic versions of patients’ medical history. EHRs promise benefits such as improving the quality of care, reducing medical errors, reducing costs, saving time, and enhancing the availability and sharing of medical records. Blockchain, in simple terms, could be seen as a distributed database controlled by a group of individuals. Blockchain technology differs from other distributed ledger technology by bundling unrelated data into blocks that are chained together in a linked-list manner, hence the name blockchain. Blockchain technology strives to provide desirable features, such as decentralization, immutability, audibility, and transparency. EHRs are traditionally constructed with a cloud-based infrastructure to promote the storing and distribution of medical records. These medical records are commonly stored in a centralized architecture, such as a relational database. The centralized architecture employed by EHRs may present a single point of failure. These kinds of failures may lead to data-breaches. The cloud-based infrastructure is effective and efficient from an availability standpoint. The increased availability of electronic health records has brought forth challenges related to the security and privacy of the patient’s medical records. The sensitive nature of EHRs attracts the attention of cyber-criminals. There has been a rise in the number of data breaches related to electronic health records. The traditional infrastructure used by electronic health records can no longer ensure the privacy and security of patient’s medical records. To determine whether blockchain is a viable alternative to these approaches, the main objective of this study was to compile a technical report on the applicability of aspects of blockchain technology to the secure storage and distribution of electronic health records. The study first conducted a literature review to gather background on the current state of electronic health records and blockchain technology. The results of the literature review were used to compile an initial report. Experiments were conducted with various aspects of blockchain technology to build a technical baseline and to ultimately validate the initial report. The insights gained from the experiments served to refine the initial report into a final technical report. The final deliverable of this study was to devise a technical report. The technical report serves as a generalized overview of the applicability of blockchain technology as a secure storage and distribution mechanism for electronic health records. The main topics covered by the technical report to outline the applicability of blockchain technology to EHRs are as follows: authentication, authorization, audit log, storage and transactions. The insights gained from the study illustrate that permissioned blockchain technology can enhance the traditional AAA security scheme employed by traditional EHRs. The AAA security scheme entails the use of certificate-based authentication and attributebased access control for authorization. Audit logs can be stored in a semi-decentralized architecture that can enhance the security and privacy of audit logs. Using blockchain technology for storing electronic health records might not be a viable alternative to traditional EHRs architecture. Blockchain technology violates certain privacy regulations as information is stored in a permanent manner. Furthermore, blockchain technology is not optimized for dealing with large volumes of data. However, blockchain technology could be used to store a cryptographic hash of electronic health records to ensure the integrity of records. Permissioned blockchain technology can enhance the EHRs transaction process by transacting health records in a peer-to-peer infrastructure. In doing so, the above-mentioned AAA security scheme can enhance the security, confidentiality, and integrity of electronic health records shared across organizational bounds.
- Full Text:
- Date Issued: 2020
Applying high-resolution remote sensing to quantify baboon damage at a sub-compartment level in pine stands in the Mpumalanga escarpment region of South Africa
- Authors: Ferreira, Regardt
- Date: 2020
- Subjects: Environmental sciences -- Remote sensing , Geographic information systems Remote sensing
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/49082 , vital:41599
- Description: Managing risk in intensively managed monoculture plantation forests is an essential task to ensure sustainable yield and a continuous flow of forest products. However, since risks can be either biotic or abiotic, not all of them have a predictable pattern of spread, which can cause severe losses if management does not have the chance to implement mitigation action. Monitoring the change in forest health is vital as this provides the opportunity for preventative management and quantifies the amount of damage that management has to deal with. To provide this window of opportunity for appropriate action, constant monitoring is required. Until recently, forest health was measured through field surveys which provided adequate data. This procedure, however, is time consuming. Remote sensing has become very popular as a monitoring tool, due to its ability to provide assessment data in a fraction of the time. In this study, baboon damage in plantations along the Mpumalanga escarpment area of South Africa was monitored using remote sensing methods. While there are many methods of forest health monitoring using remote sensing, some approaches are less suitable as they either monitor damage caused at a plantation level, use lower spatial resolution (>10m) datasets or map damage using one available time period. The purpose of this study was first to establish the impact of baboon damage through time, using Sentinel-2 satellite imagery with all vegetation indices available, and the Extreme Gradient Boosting (XGboost) algorithm. The second part focused on analysing the damage at a tree level using PlanetScope imagery using a deep Learning approach. Overall, the study found that the use of Sentinel-2 data and PlanetScope data could accurately distinguish between the varying severity of baboon damage, achieving an accuracy of 95% and 82%. The processing time of the deep learning Artificial Neural Network (ANN) was greatly affected by the number of hidden layers and neurons used. Implementation of techniques used in this study has the potential to improve the accuracy of forest health monitoring in compartment forestry in South Africa.
- Full Text:
- Date Issued: 2020
- Authors: Ferreira, Regardt
- Date: 2020
- Subjects: Environmental sciences -- Remote sensing , Geographic information systems Remote sensing
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/49082 , vital:41599
- Description: Managing risk in intensively managed monoculture plantation forests is an essential task to ensure sustainable yield and a continuous flow of forest products. However, since risks can be either biotic or abiotic, not all of them have a predictable pattern of spread, which can cause severe losses if management does not have the chance to implement mitigation action. Monitoring the change in forest health is vital as this provides the opportunity for preventative management and quantifies the amount of damage that management has to deal with. To provide this window of opportunity for appropriate action, constant monitoring is required. Until recently, forest health was measured through field surveys which provided adequate data. This procedure, however, is time consuming. Remote sensing has become very popular as a monitoring tool, due to its ability to provide assessment data in a fraction of the time. In this study, baboon damage in plantations along the Mpumalanga escarpment area of South Africa was monitored using remote sensing methods. While there are many methods of forest health monitoring using remote sensing, some approaches are less suitable as they either monitor damage caused at a plantation level, use lower spatial resolution (>10m) datasets or map damage using one available time period. The purpose of this study was first to establish the impact of baboon damage through time, using Sentinel-2 satellite imagery with all vegetation indices available, and the Extreme Gradient Boosting (XGboost) algorithm. The second part focused on analysing the damage at a tree level using PlanetScope imagery using a deep Learning approach. Overall, the study found that the use of Sentinel-2 data and PlanetScope data could accurately distinguish between the varying severity of baboon damage, achieving an accuracy of 95% and 82%. The processing time of the deep learning Artificial Neural Network (ANN) was greatly affected by the number of hidden layers and neurons used. Implementation of techniques used in this study has the potential to improve the accuracy of forest health monitoring in compartment forestry in South Africa.
- Full Text:
- Date Issued: 2020