Identification of SANCDB compounds against G2019S and I2020T variants of leucine-rich repeat Kinase 2 (LRRK2) for the development of drugs against Parkinson’s Disease
- Authors: Baye, Bertha Cinthia
- Date: 2020
- Subjects: Antiparkinsonian agents , Parkinson's disease -- Treatment , Protein kinases , Parkinson's disease -- Chemotherapy , Molecules -- Models
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138764 , vital:37671
- Description: Parkinson’s disease is a type of movement disorder that occurs when nerve cells in the brain stop producing dopamine. It is the second neurodegenerative disease affecting 1-2% of people above the ages of 65 years old. There is a worldwide prevalence of 7 to 10 million affected people of all cultures and race. Studies have shown that mutation that causes Parkinson’s disease result in increased kinase activity. The c.6055 G > A in exon 41 is the most prevalent LRRK2 variation which causes a substitution of glycine to serine in G2019S in the highly activated loop of its MAP kinase domain. The LRRK2 G2019S variant is the most common genetic determinant of Parkinson’s disease identified to date. This work focused on building accurate 3D models of the LRRK2 kinase domain, that were used for large-scale in silico docking against South African natural compounds from the South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/). Molecular docking was performed to identify compounds that formed interactions with the active site of the protein and had the lowest binding energy scores. Molecular dynamics simulations showed different movements of the protein-ligand complexes and behavioural difference of the wildtype and the variants, all three structures proved to be compact. Network analysis was done to study residue interactions, contact maps, dynamic cross correlations, average BC and average L were used to study the residue interactions and general residue contribution to the functioning of the protein..
- Full Text:
- Date Issued: 2020
- Authors: Baye, Bertha Cinthia
- Date: 2020
- Subjects: Antiparkinsonian agents , Parkinson's disease -- Treatment , Protein kinases , Parkinson's disease -- Chemotherapy , Molecules -- Models
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/138764 , vital:37671
- Description: Parkinson’s disease is a type of movement disorder that occurs when nerve cells in the brain stop producing dopamine. It is the second neurodegenerative disease affecting 1-2% of people above the ages of 65 years old. There is a worldwide prevalence of 7 to 10 million affected people of all cultures and race. Studies have shown that mutation that causes Parkinson’s disease result in increased kinase activity. The c.6055 G > A in exon 41 is the most prevalent LRRK2 variation which causes a substitution of glycine to serine in G2019S in the highly activated loop of its MAP kinase domain. The LRRK2 G2019S variant is the most common genetic determinant of Parkinson’s disease identified to date. This work focused on building accurate 3D models of the LRRK2 kinase domain, that were used for large-scale in silico docking against South African natural compounds from the South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.ac.za/). Molecular docking was performed to identify compounds that formed interactions with the active site of the protein and had the lowest binding energy scores. Molecular dynamics simulations showed different movements of the protein-ligand complexes and behavioural difference of the wildtype and the variants, all three structures proved to be compact. Network analysis was done to study residue interactions, contact maps, dynamic cross correlations, average BC and average L were used to study the residue interactions and general residue contribution to the functioning of the protein..
- Full Text:
- Date Issued: 2020
Performance of an integrated algal pond for treatment of domestic sewage: a process audit
- Authors: Dube, Anele
- Date: 2020
- Subjects: Water -- Purification , Sewage -- Purification -- Anaerobic treatment , Algae -- Biotechnology , Waste disposal -- South Africa , Integrated algae pond systems (IAPS)
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167043 , vital:41432
- Description: Integrated algae pond systems (IAPS) are energy efficient, robust, passive systems that use the principles of fermentation, photosynthesis and microbial metabolism to remediate wastewater, producing a good quality effluent with reuse potential. In addition to the treatment of wastewater, IAPS have the ability to generate two additional product streams viz. biogas and biomass. The latter adds to the attractiveness of the system. However, the implementation of this technology, like many passive systems, has remained limited at a commercial scale, and the inclination is still towards grey technologies. The aim of this research was to investigate the capabilities and potential of a demonstration-scale IAPS and use results obtained to establish a process audit framework. The aspects considered for the audit included performance efficiency, effluent water quality, biomass composition, quantity and productivity within the ponds, and cost analysis of operation and maintenance over a 9-year period. Plant performance was closely monitored during the course of the study and this led to a review of previously adopted plant management strategies. Troubleshooting exercises were also carried out when plant performance declined. Results showed that IAPS efficiently reduced standard water parameters with the exception of pH, dissolved oxygen, and nitrate whose values increased from raw influent to final effluent. The following water quality parameters were established for the final effluent: total suspended solids 55 ± 7.1 mg. L-1 (n = 28); chemical oxygen demand 94.1 ± 10.6 mg. L-1 (n = 28) (after removal of algae); pH 9.9 ± 0.01 (n = 26); ammonium nitrogen 1.7 ± 0.3 mg. L-1 (n = 25); nitrate 3.3 ± 0.6 mg. L-1 (n = 25); ortho-phosphate 1.6 ± 0.2 mg. L-1 (n = 25); electrical conductivity 98.7 ± 2.0 mS m-1 (n = 26) and faecal coliforms (per 100 mL) 1482.6 ± 636.0 (n = 24). The final effluent measured consistently high chemical oxygen demand and total suspended solids, however close analysis showed that total suspended solids could be controlled by increasing the frequency of removal of settled biomass within the settling ponds. Biomass produced contained microalgae, bacteria, metazoa, and protozoa. The biomass productivity achieved was as high as 130.6 kg ha-1 d-1; however, about 33% was lost to the final effluent due to inadequate settling. Results obtained during the course of this study and outcomes of earlier work on IAPS are taken as the baseline to determine parameters needed for the development of the process audit framework. Techniques utilised to derive the blue print process audit protocol for IAPS included a turtle diagram, a flow diagram and a checklist. Attention to plant management proved vital in determining overall performance. Cost, including operating and maintenance, of treating water using the demonstration scale system on a per person equivalent per year basis was determined as ZAR 123.87 (where, ZAR to USD = 0.07).
- Full Text:
- Date Issued: 2020
- Authors: Dube, Anele
- Date: 2020
- Subjects: Water -- Purification , Sewage -- Purification -- Anaerobic treatment , Algae -- Biotechnology , Waste disposal -- South Africa , Integrated algae pond systems (IAPS)
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167043 , vital:41432
- Description: Integrated algae pond systems (IAPS) are energy efficient, robust, passive systems that use the principles of fermentation, photosynthesis and microbial metabolism to remediate wastewater, producing a good quality effluent with reuse potential. In addition to the treatment of wastewater, IAPS have the ability to generate two additional product streams viz. biogas and biomass. The latter adds to the attractiveness of the system. However, the implementation of this technology, like many passive systems, has remained limited at a commercial scale, and the inclination is still towards grey technologies. The aim of this research was to investigate the capabilities and potential of a demonstration-scale IAPS and use results obtained to establish a process audit framework. The aspects considered for the audit included performance efficiency, effluent water quality, biomass composition, quantity and productivity within the ponds, and cost analysis of operation and maintenance over a 9-year period. Plant performance was closely monitored during the course of the study and this led to a review of previously adopted plant management strategies. Troubleshooting exercises were also carried out when plant performance declined. Results showed that IAPS efficiently reduced standard water parameters with the exception of pH, dissolved oxygen, and nitrate whose values increased from raw influent to final effluent. The following water quality parameters were established for the final effluent: total suspended solids 55 ± 7.1 mg. L-1 (n = 28); chemical oxygen demand 94.1 ± 10.6 mg. L-1 (n = 28) (after removal of algae); pH 9.9 ± 0.01 (n = 26); ammonium nitrogen 1.7 ± 0.3 mg. L-1 (n = 25); nitrate 3.3 ± 0.6 mg. L-1 (n = 25); ortho-phosphate 1.6 ± 0.2 mg. L-1 (n = 25); electrical conductivity 98.7 ± 2.0 mS m-1 (n = 26) and faecal coliforms (per 100 mL) 1482.6 ± 636.0 (n = 24). The final effluent measured consistently high chemical oxygen demand and total suspended solids, however close analysis showed that total suspended solids could be controlled by increasing the frequency of removal of settled biomass within the settling ponds. Biomass produced contained microalgae, bacteria, metazoa, and protozoa. The biomass productivity achieved was as high as 130.6 kg ha-1 d-1; however, about 33% was lost to the final effluent due to inadequate settling. Results obtained during the course of this study and outcomes of earlier work on IAPS are taken as the baseline to determine parameters needed for the development of the process audit framework. Techniques utilised to derive the blue print process audit protocol for IAPS included a turtle diagram, a flow diagram and a checklist. Attention to plant management proved vital in determining overall performance. Cost, including operating and maintenance, of treating water using the demonstration scale system on a per person equivalent per year basis was determined as ZAR 123.87 (where, ZAR to USD = 0.07).
- Full Text:
- Date Issued: 2020
Graphite: origin, deposits and economics : an exploration study of the Orom Graphite project
- Van den Berg, Jacobus Petrus
- Authors: Van den Berg, Jacobus Petrus
- Date: 2018
- Subjects: Graphite , Ore deposits , Geophysics , Graphite mines and mining Economic aspects Africa, East , Trenches , Project management
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63786 , vital:28489
- Description: Developing exploration projects successfully requires that the Reasonable Prospects for Eventual Economic Extraction (RPEEE) be confirmed and based on the global market perception and trend. The exploration methods applied in the attempt to establish this RPEEE must be based on a key management framework that assures the results, and eventually the conclusion, are obtained with best practical and technical approaches whilst managing the risks and capitalizing on each result. The Orom Graphite project is located within the East African Orogenic belt, a suture zone between the Congo craton and the SLAMIN shield, formed during the formation of Gondwana during the late Proterozoic to early-Phanerozoic era. The closing of the Mozambique ocean, and the eventual collision between the craton and shield, occurred along the paleo-earths equator and migrated towards lower latitudes. This, along with the period’s biodiversity boom, provided the perfect deposition environment for carbonaceous sediments which were later metamorphosed to amphibolite and granulites grade metamorphism, resulting in the carbonization and the eventual graphitization of these carbonaceous sediments. The project is located within a poorly developed part of Uganda with the closest port situated some 1 500 km to the east in Kenya. The poorly developed infrastructure along with probable high logistical cost assigns a low competitivity index if compared to the economic costs of peer projects. However, the potential resources of the Orom Graphite project suggest that the Life of Mine (LOM) can rival the largest resource currently reported within the market. The current market conditions suggest that a possible oversupply of graphite concentrate will dominate the market within the next 4 to 10 years. This suggests that new graphite projects such as the Orom Graphite project are likely to develop into the production phase once the global supply and demand stabilize. This requires the Orom Graphite project to develop from its current scoping study level to a project development study level associated with a definitive feasibility study. To date, the project developed through mapping, reconnaissance drilling, geophysical survey and trenching programs increasing the Net Present Value (NPV) considerably based upon a Cost-Based Valuation approach using Prospectivity Enhancement Multiplier (PEM). The metallurgical studies could however not produce a graphite concentrate product within industrial grade standards. The risk associated with developing the project further into the Mineral Resource Estimation (MRE) phase was quantified and risk was evaluated by implementing a point decision tree and calculating the Expected Monetary Value (EMV). Due to the unfavourable metallurgical results obtained to date, the risk associated with undertaking an additional metallurgical test is considerable with a slight chance of producing a negative project value estimated at 65%. JP van den Berg Rhodes University Overall, the Orom Graphite project contains favourable geological formations with a potential large resource. Market trends indicate that a considerable resource is currently being developed and can supply the global market for the next 4 to 10 years. The project’s location within a landlocked country decreases its economic competitiveness with peer project and the unfavourable, but not conclusive, metallurgical results obtained during the scoping phase do not instil confidence that the project will develop into a productive mine soon. Managing the project development with future graphite demand in mind is the key to determining whether the project still has future value.
- Full Text:
- Date Issued: 2018
- Authors: Van den Berg, Jacobus Petrus
- Date: 2018
- Subjects: Graphite , Ore deposits , Geophysics , Graphite mines and mining Economic aspects Africa, East , Trenches , Project management
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63786 , vital:28489
- Description: Developing exploration projects successfully requires that the Reasonable Prospects for Eventual Economic Extraction (RPEEE) be confirmed and based on the global market perception and trend. The exploration methods applied in the attempt to establish this RPEEE must be based on a key management framework that assures the results, and eventually the conclusion, are obtained with best practical and technical approaches whilst managing the risks and capitalizing on each result. The Orom Graphite project is located within the East African Orogenic belt, a suture zone between the Congo craton and the SLAMIN shield, formed during the formation of Gondwana during the late Proterozoic to early-Phanerozoic era. The closing of the Mozambique ocean, and the eventual collision between the craton and shield, occurred along the paleo-earths equator and migrated towards lower latitudes. This, along with the period’s biodiversity boom, provided the perfect deposition environment for carbonaceous sediments which were later metamorphosed to amphibolite and granulites grade metamorphism, resulting in the carbonization and the eventual graphitization of these carbonaceous sediments. The project is located within a poorly developed part of Uganda with the closest port situated some 1 500 km to the east in Kenya. The poorly developed infrastructure along with probable high logistical cost assigns a low competitivity index if compared to the economic costs of peer projects. However, the potential resources of the Orom Graphite project suggest that the Life of Mine (LOM) can rival the largest resource currently reported within the market. The current market conditions suggest that a possible oversupply of graphite concentrate will dominate the market within the next 4 to 10 years. This suggests that new graphite projects such as the Orom Graphite project are likely to develop into the production phase once the global supply and demand stabilize. This requires the Orom Graphite project to develop from its current scoping study level to a project development study level associated with a definitive feasibility study. To date, the project developed through mapping, reconnaissance drilling, geophysical survey and trenching programs increasing the Net Present Value (NPV) considerably based upon a Cost-Based Valuation approach using Prospectivity Enhancement Multiplier (PEM). The metallurgical studies could however not produce a graphite concentrate product within industrial grade standards. The risk associated with developing the project further into the Mineral Resource Estimation (MRE) phase was quantified and risk was evaluated by implementing a point decision tree and calculating the Expected Monetary Value (EMV). Due to the unfavourable metallurgical results obtained to date, the risk associated with undertaking an additional metallurgical test is considerable with a slight chance of producing a negative project value estimated at 65%. JP van den Berg Rhodes University Overall, the Orom Graphite project contains favourable geological formations with a potential large resource. Market trends indicate that a considerable resource is currently being developed and can supply the global market for the next 4 to 10 years. The project’s location within a landlocked country decreases its economic competitiveness with peer project and the unfavourable, but not conclusive, metallurgical results obtained during the scoping phase do not instil confidence that the project will develop into a productive mine soon. Managing the project development with future graphite demand in mind is the key to determining whether the project still has future value.
- Full Text:
- Date Issued: 2018
Economic consequences of ecological change: restoration options for the Mfolozi floodplain and implications for Lake St. Lucia, South Africa
- Authors: Collings, Sandy Lyn
- Date: 2010
- Subjects: Lake ecology -- South Africa -- Saint Lucia, Lake , Ecology -- Economic aspects -- South Africa -- Kwazulu-Natal , Wetland ecology -- South Africa -- Kwazulu-Natal , Ecosystem services -- South Africa -- Kwazulu-Natal
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4744 , http://hdl.handle.net/10962/d1006950 , Lake ecology -- South Africa -- Saint Lucia, Lake , Ecology -- Economic aspects -- South Africa -- Kwazulu-Natal , Wetland ecology -- South Africa -- Kwazulu-Natal , Ecosystem services -- South Africa -- Kwazulu-Natal
- Description: Lake St Lucia in northern KwaZulu-Natal, South Africa, experiences severe ecological stress during dry periods largely as a result of diminishing freshwater supplies and conditions of hypersalinity. Possible intervention involves diverting the Mfolozi River to the St Lucia Lake system. However, due to high sediment loading, water from the Mfolozi river requires considerable filtration before a link can be established. A suggested option considered in this study is to restore the existing sugarcane farmlands on the Mfolozi Floodplain (~20 800 ha) to previous wetland conditions to reinstate a sediment removal function amongst other benefits. Proposed restoration will have a direct impact on the industries currently supported by the iSimangaliso Wetland Park and the Mfolozi Floodplain (tourism, sugar, conservation). to understand a measure of such impacts, ecosystem services for both Lake St Lucia and the Mfolozi Floodplain were analysed (flood alleviation, water provision, water purification, sediment regulation, tourism, fisheries, vegetation for harvest, existence, cultural and research). Annual economic values for each ecosystem service were determined by means of valuation methods that included benefit transfer and replacement cost. Results showed a current annual minimum value of the Mfolozi Floodplain and Lake St Lucia as greater than R21 million and R1.1 billion respectively. Partial restoration of the floodplain (~6 000 ha) is expected to increase the sum of all ecosystem services values by approximately 26% for the Mfolozi Floodplain and by 23% for the St Lucia System. Full restoration (~20 800 ha) increases the total ecosystem services value by 88% and 50% for the Mfolozi Floodplain and St Lucia System respectively. Results showed that economic values for existence, fisheries, tourism and water provision increase by the greatest percentage for the St Lucia System under both restoration scenarios. Partial and full restoration of the floodplain will result in the greatest increases in economic value for the services existence, tourism, fisheries and the harvesting of vegetation on the Mfolozi Floodplain.
- Full Text:
- Date Issued: 2010
- Authors: Collings, Sandy Lyn
- Date: 2010
- Subjects: Lake ecology -- South Africa -- Saint Lucia, Lake , Ecology -- Economic aspects -- South Africa -- Kwazulu-Natal , Wetland ecology -- South Africa -- Kwazulu-Natal , Ecosystem services -- South Africa -- Kwazulu-Natal
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4744 , http://hdl.handle.net/10962/d1006950 , Lake ecology -- South Africa -- Saint Lucia, Lake , Ecology -- Economic aspects -- South Africa -- Kwazulu-Natal , Wetland ecology -- South Africa -- Kwazulu-Natal , Ecosystem services -- South Africa -- Kwazulu-Natal
- Description: Lake St Lucia in northern KwaZulu-Natal, South Africa, experiences severe ecological stress during dry periods largely as a result of diminishing freshwater supplies and conditions of hypersalinity. Possible intervention involves diverting the Mfolozi River to the St Lucia Lake system. However, due to high sediment loading, water from the Mfolozi river requires considerable filtration before a link can be established. A suggested option considered in this study is to restore the existing sugarcane farmlands on the Mfolozi Floodplain (~20 800 ha) to previous wetland conditions to reinstate a sediment removal function amongst other benefits. Proposed restoration will have a direct impact on the industries currently supported by the iSimangaliso Wetland Park and the Mfolozi Floodplain (tourism, sugar, conservation). to understand a measure of such impacts, ecosystem services for both Lake St Lucia and the Mfolozi Floodplain were analysed (flood alleviation, water provision, water purification, sediment regulation, tourism, fisheries, vegetation for harvest, existence, cultural and research). Annual economic values for each ecosystem service were determined by means of valuation methods that included benefit transfer and replacement cost. Results showed a current annual minimum value of the Mfolozi Floodplain and Lake St Lucia as greater than R21 million and R1.1 billion respectively. Partial restoration of the floodplain (~6 000 ha) is expected to increase the sum of all ecosystem services values by approximately 26% for the Mfolozi Floodplain and by 23% for the St Lucia System. Full restoration (~20 800 ha) increases the total ecosystem services value by 88% and 50% for the Mfolozi Floodplain and St Lucia System respectively. Results showed that economic values for existence, fisheries, tourism and water provision increase by the greatest percentage for the St Lucia System under both restoration scenarios. Partial and full restoration of the floodplain will result in the greatest increases in economic value for the services existence, tourism, fisheries and the harvesting of vegetation on the Mfolozi Floodplain.
- Full Text:
- Date Issued: 2010
- «
- ‹
- 1
- ›
- »