The relationship between OCT4 and an aggressive phenotype in triple negative breast cancer (TNBC)
- Authors: Jackson, Hayley Claire
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59209 , vital:27477
- Description: Expected release date-April 2019
- Full Text:
- Date Issued: 2017
- Authors: Jackson, Hayley Claire
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59209 , vital:27477
- Description: Expected release date-April 2019
- Full Text:
- Date Issued: 2017
Chemical weathering on selected nunataks in western Dronning Maud Land, Antarctica
- Authors: Knox, Jenna Tracy
- Date: 2018
- Subjects: Glacial climates -- Antarctica -- Queen Maud Land , Glaciology -- Antarctica -- Queen Maud Land , Chemical weathering -- Antarctica -- Queen Maud Land , Atmospheric carbon dioxide -- Environmental aspects , Climatic changes -- Antarctica -- Queen Maud Land , Nunataks -- Antarctica -- Queen Maud Land
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/61658 , vital:28046
- Description: High latitude areas are sensitive to the impacts of climate change, and it is expected that the impact of greenhouse warming will be much higher in the polar regions than in any other climatic zones, with the most highly affected area being that of the Antarctic rim (Barsch, 1993). Weathering and pedogenic processes respond to variations in climate, with models predicting that chemical weathering may increase synchronously with global carbon dioxide levels increase, due to dissolution rates and the erosional impact of hydrological cycles in warming climates (Anderson & Anderson, 2010). As liquid water becomes more available in Antarctica the potential for chemical weathering, due to a less moisture-limited environment and increased temperatures, increases (Convey et al., 2009). Weathering processes are important for soil formation and the production of fine-grained material, with chemical weathering being an active constituent of this. Increased rates of soil formation are likely to occur, with global climate changes resulting in greater chemical weathering occurring in Antarctica. Opportunistic sampling was conducted during the Austral summer of 2016/2017, whereby rock, snow and meltwater samples were taken at various sites within the western portion of Dronning Maud Land of Antarctica. Rock samples were placed in resin, and cut with a diamond saw to create thin sections. Optical microscopy and scanning transmission electron microscopy (STEM) were used to analyse mineral weight percentage with depth. Twelve soil samples were dried and weighed, sieved and statistically represented according to particle size. Inductively coupled plasma mass spectrometry (ICP-MS) determined the geochemical analysis for 10 water and snow samples. Rock hardness was inferred through the use of an Equotip, with rebound values recorded for multiple rock faces and samples. Thermal regimes of rock temperature was further recorded using a FLIR infrared camera, and documented for each rock face over a 24 hour period at 2 hourly intervals. The products of increased chemical weathering were evident from particle size analysis; samples were very poorly sorted in nature, and undergo in situ weathering, whereby products were not removed by erosional processes. Weathering rinds were found to be siliceous and ferric, depending on parent lithology. Ferric ratios increased in wt.% from the substrate rock to the external surface, creating the red, iron rich crusts noted on the hand specimens. The observable chemical weathering was found adjacent to intrusions through Precambrian dolerites. Geochemical analysis revealed thin, carbonaceous features, with impurity-rich layers, characteristic of speleothem formation. Carbonaceous layers did not follow underlying substrate features, rather deposited at the external surface, upon which, further precipitation growth could occur, creating karst features. Extensive gypsum coatings (>2mm) under BSE imagery were identified, with the abundance of gypsum salts (below surface level) and rock coatings indicating active sulphuric acid weathering, in western Dronning Maud Land, Antarctica. Were mechanical processes faster than chemical, weathering rinds and solution features on silicate rocks would be uncommon in the Antarctic, periglacial landscape. However, this is not the case as the existence of these landforms implies that chemical weathering may occur faster than mechanical weathering processes (Pope et al., 1995). In a changing world, one needs to monitor these processes at a micro-scale in order to fully understand how periglacial environments react to global climatic changes, and the subsequent impacts on these sensitive environments.
- Full Text:
- Date Issued: 2018
- Authors: Knox, Jenna Tracy
- Date: 2018
- Subjects: Glacial climates -- Antarctica -- Queen Maud Land , Glaciology -- Antarctica -- Queen Maud Land , Chemical weathering -- Antarctica -- Queen Maud Land , Atmospheric carbon dioxide -- Environmental aspects , Climatic changes -- Antarctica -- Queen Maud Land , Nunataks -- Antarctica -- Queen Maud Land
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/61658 , vital:28046
- Description: High latitude areas are sensitive to the impacts of climate change, and it is expected that the impact of greenhouse warming will be much higher in the polar regions than in any other climatic zones, with the most highly affected area being that of the Antarctic rim (Barsch, 1993). Weathering and pedogenic processes respond to variations in climate, with models predicting that chemical weathering may increase synchronously with global carbon dioxide levels increase, due to dissolution rates and the erosional impact of hydrological cycles in warming climates (Anderson & Anderson, 2010). As liquid water becomes more available in Antarctica the potential for chemical weathering, due to a less moisture-limited environment and increased temperatures, increases (Convey et al., 2009). Weathering processes are important for soil formation and the production of fine-grained material, with chemical weathering being an active constituent of this. Increased rates of soil formation are likely to occur, with global climate changes resulting in greater chemical weathering occurring in Antarctica. Opportunistic sampling was conducted during the Austral summer of 2016/2017, whereby rock, snow and meltwater samples were taken at various sites within the western portion of Dronning Maud Land of Antarctica. Rock samples were placed in resin, and cut with a diamond saw to create thin sections. Optical microscopy and scanning transmission electron microscopy (STEM) were used to analyse mineral weight percentage with depth. Twelve soil samples were dried and weighed, sieved and statistically represented according to particle size. Inductively coupled plasma mass spectrometry (ICP-MS) determined the geochemical analysis for 10 water and snow samples. Rock hardness was inferred through the use of an Equotip, with rebound values recorded for multiple rock faces and samples. Thermal regimes of rock temperature was further recorded using a FLIR infrared camera, and documented for each rock face over a 24 hour period at 2 hourly intervals. The products of increased chemical weathering were evident from particle size analysis; samples were very poorly sorted in nature, and undergo in situ weathering, whereby products were not removed by erosional processes. Weathering rinds were found to be siliceous and ferric, depending on parent lithology. Ferric ratios increased in wt.% from the substrate rock to the external surface, creating the red, iron rich crusts noted on the hand specimens. The observable chemical weathering was found adjacent to intrusions through Precambrian dolerites. Geochemical analysis revealed thin, carbonaceous features, with impurity-rich layers, characteristic of speleothem formation. Carbonaceous layers did not follow underlying substrate features, rather deposited at the external surface, upon which, further precipitation growth could occur, creating karst features. Extensive gypsum coatings (>2mm) under BSE imagery were identified, with the abundance of gypsum salts (below surface level) and rock coatings indicating active sulphuric acid weathering, in western Dronning Maud Land, Antarctica. Were mechanical processes faster than chemical, weathering rinds and solution features on silicate rocks would be uncommon in the Antarctic, periglacial landscape. However, this is not the case as the existence of these landforms implies that chemical weathering may occur faster than mechanical weathering processes (Pope et al., 1995). In a changing world, one needs to monitor these processes at a micro-scale in order to fully understand how periglacial environments react to global climatic changes, and the subsequent impacts on these sensitive environments.
- Full Text:
- Date Issued: 2018
Quantification of water resources uncertainties in two sub-basins of the Limpopo River basin
- Authors: Oosthuizen, Nadia
- Date: 2018
- Subjects: Hydrologic models -- Limpopo River Watershed , Water-supply -- Limpopo River Watershed , Water-supply -- Management , Sustainable development , Rain and rainfall -- Mathematical models , Runoff -- Mathematical models , Reservoirs -- Limpopo River Watershed
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63267 , vital:28388
- Description: The demand for water is rapidly growing, placing more strain on access to the resources and subsequently its management. For sustainable management, there is a need to accurately quantify the available water resources. Unfortunately, the data required for such assessments are frequently far from sufficient in terms of availability and quality, especially in southern Africa. In the absence of historical observed data, models are generally used to describe the different hydrological processes and generate data and information that will inform management and policy decision making. Ideally, any hydrological model should be based on a sound conceptual understanding of the processes in the basin and be backed by quantitative information for the parameterization of the model. Such data is however, often inadequate in many sub-basins necessitating the incorporation of the uncertainty related to the estimation process. Model parameter estimation and input data are significant sources of uncertainty that should be quantified. Also, in southern Africa water use data are unreliable because available databases consist of licensed information and actual use is generally unknown. In this study, the water resources of two sub-basins of the Limpopo River basin – the Mogalakwena in South Africa and the Shashe shared between Botswana and Zimbabwe – are estimated. The study assessed how uncertainties in the Pitman model parameterisation and input water use data affect the estimation of surface water resources of the selected sub-basins. Farm reservoirs and irrigated areas data from various sources were collected and used to run the Pitman model. Results indicate that the total model output uncertainty is higher for the Shashe sub-basin which is more data scarce than the Mogalakwena sub-basin. The study illustrates the importance of including uncertainty in the water resources assessment process to provide baseline data for decision making in resource management and planning. The study reviews existing information sources associated with the quantification of water balance components and gives an update of water resources of the sub-basin. The flows generated by the model at the outlet of the basin were between 22.6 Mm3 and 24.7 Mm3 per month when incorporating uncertainty to the main physical runoff generating parameters. The total predictive uncertainty of the model increased to between 22.2 Mm3 and 25.0 Mm3 when anthropogenic water use data such as small farm and large reservoirs and irrigation were included. The flows generated for Shashe was between 11.7 Mm3 and 14.5 Mm3 per month when incorporating uncertainty to the main physical runoff generating parameters. The predictive uncertainty of the model changed to 11.7 Mm3 and 17.7 Mm3 after the water use uncertainty was added. However, it is expected that the uncertainty could be reduced by using higher resolution remote sensing imagery.
- Full Text:
- Date Issued: 2018
- Authors: Oosthuizen, Nadia
- Date: 2018
- Subjects: Hydrologic models -- Limpopo River Watershed , Water-supply -- Limpopo River Watershed , Water-supply -- Management , Sustainable development , Rain and rainfall -- Mathematical models , Runoff -- Mathematical models , Reservoirs -- Limpopo River Watershed
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63267 , vital:28388
- Description: The demand for water is rapidly growing, placing more strain on access to the resources and subsequently its management. For sustainable management, there is a need to accurately quantify the available water resources. Unfortunately, the data required for such assessments are frequently far from sufficient in terms of availability and quality, especially in southern Africa. In the absence of historical observed data, models are generally used to describe the different hydrological processes and generate data and information that will inform management and policy decision making. Ideally, any hydrological model should be based on a sound conceptual understanding of the processes in the basin and be backed by quantitative information for the parameterization of the model. Such data is however, often inadequate in many sub-basins necessitating the incorporation of the uncertainty related to the estimation process. Model parameter estimation and input data are significant sources of uncertainty that should be quantified. Also, in southern Africa water use data are unreliable because available databases consist of licensed information and actual use is generally unknown. In this study, the water resources of two sub-basins of the Limpopo River basin – the Mogalakwena in South Africa and the Shashe shared between Botswana and Zimbabwe – are estimated. The study assessed how uncertainties in the Pitman model parameterisation and input water use data affect the estimation of surface water resources of the selected sub-basins. Farm reservoirs and irrigated areas data from various sources were collected and used to run the Pitman model. Results indicate that the total model output uncertainty is higher for the Shashe sub-basin which is more data scarce than the Mogalakwena sub-basin. The study illustrates the importance of including uncertainty in the water resources assessment process to provide baseline data for decision making in resource management and planning. The study reviews existing information sources associated with the quantification of water balance components and gives an update of water resources of the sub-basin. The flows generated by the model at the outlet of the basin were between 22.6 Mm3 and 24.7 Mm3 per month when incorporating uncertainty to the main physical runoff generating parameters. The total predictive uncertainty of the model increased to between 22.2 Mm3 and 25.0 Mm3 when anthropogenic water use data such as small farm and large reservoirs and irrigation were included. The flows generated for Shashe was between 11.7 Mm3 and 14.5 Mm3 per month when incorporating uncertainty to the main physical runoff generating parameters. The predictive uncertainty of the model changed to 11.7 Mm3 and 17.7 Mm3 after the water use uncertainty was added. However, it is expected that the uncertainty could be reduced by using higher resolution remote sensing imagery.
- Full Text:
- Date Issued: 2018
In silico identification of selective novel hits against the active site of wild type mycobacterium tuberculosis pyrazinamidase and its mutants
- Authors: Gowo, Prudence
- Date: 2021-04
- Subjects: Mycobacterium tuberculosis , Pyrazinamide , Multidrug resistance , Antitubercular agents , Molecular dynamics , Hydrogen bonding , Ligand binding (Biochemistry) , Dynamic Residue Network
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/178007 , vital:42898
- Description: The World Health Organization declared Tuberculosis a global health emergency and has set a goal to eradicate it by 2035. However, effective treatment and control of the disease is being hindered by the emerging Multi-Drug Resistant and Extensively Drug Resistant strains on the most effective first line prodrug, Pyrazinamide (PZA). Studies have shown that the main cause of PZA resistance is due to mutations in the pncA gene that codes for the target protein Pyrazinamidase (PZase). Therefore, this study aimed to identify novel drug compounds that bind to the active site of wild type PZase and study the dynamics of these potential anti-TB drugs in the mutant systems of PZase. This approach will aid in identifying drugs that may be repurposed for TB therapy and/or designed to counteract PZA resistance. This was achieved by screening 2089 DrugBank compounds against the whole wild type (WT) PZase protein in molecular docking using AutoDOCK4.2. Compound screening based on docking binding energy, hydrogen bonds, molecular weight and active site proximity identified 47 compounds meeting all the set selection criteria. The stability of these compounds were analysed in Molecular Dynamic (MD) simulations and were further studied in PZase mutant systems of A3P, A134V, A146V, D8G, D49A, D49G, D63G, H51P, H137R, L85R, L116R, Q10P, R140S, T61P, V139M and Y103S. Generally, mutant-ligand systems displayed little deviation from the WT systems. The compound systems remained compact, with less fluctuations and more hydrogen bond interactions throughout the simulation (DB00255, DB00655, DB00672, DB00782, DB00977, DB01196, DB04573, DB06414, DB08981, DB11181, DB11760, DB13867, DB13952). From this research study, potential drugs that may be repurposed for TB therapy were identified. Majority of these drugs are currently used in the treatment of hypertension, menopause disorders and inflammation. To further understand the mutant-ligand dynamic systems, calculations such as Dynamic Residue Network (DRN) may be done. Also, the bioactivity of these drugs on Mycobacterium tuberculosis may be studied in wet laboratory, to understand their clinical impart in vivo experiments. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-04
- Authors: Gowo, Prudence
- Date: 2021-04
- Subjects: Mycobacterium tuberculosis , Pyrazinamide , Multidrug resistance , Antitubercular agents , Molecular dynamics , Hydrogen bonding , Ligand binding (Biochemistry) , Dynamic Residue Network
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/178007 , vital:42898
- Description: The World Health Organization declared Tuberculosis a global health emergency and has set a goal to eradicate it by 2035. However, effective treatment and control of the disease is being hindered by the emerging Multi-Drug Resistant and Extensively Drug Resistant strains on the most effective first line prodrug, Pyrazinamide (PZA). Studies have shown that the main cause of PZA resistance is due to mutations in the pncA gene that codes for the target protein Pyrazinamidase (PZase). Therefore, this study aimed to identify novel drug compounds that bind to the active site of wild type PZase and study the dynamics of these potential anti-TB drugs in the mutant systems of PZase. This approach will aid in identifying drugs that may be repurposed for TB therapy and/or designed to counteract PZA resistance. This was achieved by screening 2089 DrugBank compounds against the whole wild type (WT) PZase protein in molecular docking using AutoDOCK4.2. Compound screening based on docking binding energy, hydrogen bonds, molecular weight and active site proximity identified 47 compounds meeting all the set selection criteria. The stability of these compounds were analysed in Molecular Dynamic (MD) simulations and were further studied in PZase mutant systems of A3P, A134V, A146V, D8G, D49A, D49G, D63G, H51P, H137R, L85R, L116R, Q10P, R140S, T61P, V139M and Y103S. Generally, mutant-ligand systems displayed little deviation from the WT systems. The compound systems remained compact, with less fluctuations and more hydrogen bond interactions throughout the simulation (DB00255, DB00655, DB00672, DB00782, DB00977, DB01196, DB04573, DB06414, DB08981, DB11181, DB11760, DB13867, DB13952). From this research study, potential drugs that may be repurposed for TB therapy were identified. Majority of these drugs are currently used in the treatment of hypertension, menopause disorders and inflammation. To further understand the mutant-ligand dynamic systems, calculations such as Dynamic Residue Network (DRN) may be done. Also, the bioactivity of these drugs on Mycobacterium tuberculosis may be studied in wet laboratory, to understand their clinical impart in vivo experiments. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-04