Foreign reference products in the registration of generic medicines in South Africa a case study
- Authors: Hwengwere, Eldinah
- Date: 2012
- Subjects: Generic drugs -- Law and legislation -- South Africa Case studies Generic drugs -- South Africa Case studies Drugs -- Law and legislation -- South Africa Case studies Pharmacy -- Law and legislation -- South Africa Case studies
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3762 , http://hdl.handle.net/10962/d1003240
- Description: Introduction: Due to the increase in healthcare costs, generic medicines have been adopted for used in both developed and developing countries. When a generic or ‘multisource interchangeable medicine’ is to be registered, studies that prove that the generic is equivalent to the Innovator Product (IP) are used. The generic medicine is required to prove that it will mirror the IP in terms of safety, quality and efficacy and, in South Africa, the Medicines Control Council (MCC) ensures that generic medicines meet these requirements. Generic medicines may be registered using bioequivalence data obtained from comparison with a domestic reference product (usually the local innovator product) or in certain cases, a foreign reference product (FRP). The bioequivalence data can either be from in vivo or in vitro studies. The MCC guidelines require that for modified release preparations, in vivo bioequivalence studies are done for approval of registration; the exception being if a proportionally higher dose has already been registered. No information is currently given to prescribers and dispensers or to the public about whether a generic product was registered against a foreign or domestic reference product. Aims and Objectives: 1.) To determine the number of generic medicines in a predetermined sample registered using a FRP as comparator and to document the transparency of pharmaceutical companies when approached to disclose information regarding the registration of these products. 2.) To describe and document the use of the Promotion of Access to Information Act (Act 2 of 2000) [PAIA] from the perspective of a ‘layperson’ in the context of medicines’ regulation, in both private and public bodies. Methods: 20 modified release and Biopharmaceutics Classification System (BCS) class IV products were selected from the ‘generics dictionary’ – a commercial publication – and letters were sent to the manufacturers of the products requesting information about the tests done to prove equivalence and whether they were performed against a domestic or foreign reference product. The same information was also requested from the MCC. The requests were all made using the Promotion of Access to Information Act (PAIA). Results: Nine companies were represented by the 20 products chosen. Information was obtained about thirteen products. Ten of these products were registered using FRPs. Four products were registered based only on comparative dissolution studies. Four companies provided the requested information, two companies responded by refusing the requests and three did not respond at all. The MCC refused the request for information even after an internal appeal was lodged. Conclusions: The Promotion of Access to information Act was unsuccessful in obtaining information from the public body, and partly successful in obtaining it from the private bodies. While the title of the Act seems to indicate that the Act can be used to obtain information as such, it only provides for access to specified records. The MCC and the pharmaceutical companies involved in the study were under no obligation to provide the information as the request had not complied with PAIA requirements. The use of FRPs for registration is a reality in the pharmaceutical industry in South Africa. Neither the public nor healthcare professionals who prescribe medicines or who are involved in dispensing generic medicines as substitutes are aware of whether or not a FRP has been used to register a generic. Interchangeability cannot necessarily be guaranteed if the reference product was not proven equivalent to the local innovator product. It is debatable as to whether or not this information would be of any particular benefit to members of the public. Prescribers may choose to write ‘no substitution’ on their prescriptions if they were unconvinced that an FRP is acceptable. This could have consequences for healthcare costs. Dispensers are the most vulnerable in South Africa as they are obliged by law to substitute generic medicines when innovator medicines have been prescribed. Dispensers’ views on the acceptability of the use of FRPs can be seen as irrelevant. In the end, as this study demonstrates, the only option in the present situation is to rely entirely on the MCC’s rigour in assessing applications for registration of generic medicines.
- Full Text:
- Authors: Hwengwere, Eldinah
- Date: 2012
- Subjects: Generic drugs -- Law and legislation -- South Africa Case studies Generic drugs -- South Africa Case studies Drugs -- Law and legislation -- South Africa Case studies Pharmacy -- Law and legislation -- South Africa Case studies
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3762 , http://hdl.handle.net/10962/d1003240
- Description: Introduction: Due to the increase in healthcare costs, generic medicines have been adopted for used in both developed and developing countries. When a generic or ‘multisource interchangeable medicine’ is to be registered, studies that prove that the generic is equivalent to the Innovator Product (IP) are used. The generic medicine is required to prove that it will mirror the IP in terms of safety, quality and efficacy and, in South Africa, the Medicines Control Council (MCC) ensures that generic medicines meet these requirements. Generic medicines may be registered using bioequivalence data obtained from comparison with a domestic reference product (usually the local innovator product) or in certain cases, a foreign reference product (FRP). The bioequivalence data can either be from in vivo or in vitro studies. The MCC guidelines require that for modified release preparations, in vivo bioequivalence studies are done for approval of registration; the exception being if a proportionally higher dose has already been registered. No information is currently given to prescribers and dispensers or to the public about whether a generic product was registered against a foreign or domestic reference product. Aims and Objectives: 1.) To determine the number of generic medicines in a predetermined sample registered using a FRP as comparator and to document the transparency of pharmaceutical companies when approached to disclose information regarding the registration of these products. 2.) To describe and document the use of the Promotion of Access to Information Act (Act 2 of 2000) [PAIA] from the perspective of a ‘layperson’ in the context of medicines’ regulation, in both private and public bodies. Methods: 20 modified release and Biopharmaceutics Classification System (BCS) class IV products were selected from the ‘generics dictionary’ – a commercial publication – and letters were sent to the manufacturers of the products requesting information about the tests done to prove equivalence and whether they were performed against a domestic or foreign reference product. The same information was also requested from the MCC. The requests were all made using the Promotion of Access to Information Act (PAIA). Results: Nine companies were represented by the 20 products chosen. Information was obtained about thirteen products. Ten of these products were registered using FRPs. Four products were registered based only on comparative dissolution studies. Four companies provided the requested information, two companies responded by refusing the requests and three did not respond at all. The MCC refused the request for information even after an internal appeal was lodged. Conclusions: The Promotion of Access to information Act was unsuccessful in obtaining information from the public body, and partly successful in obtaining it from the private bodies. While the title of the Act seems to indicate that the Act can be used to obtain information as such, it only provides for access to specified records. The MCC and the pharmaceutical companies involved in the study were under no obligation to provide the information as the request had not complied with PAIA requirements. The use of FRPs for registration is a reality in the pharmaceutical industry in South Africa. Neither the public nor healthcare professionals who prescribe medicines or who are involved in dispensing generic medicines as substitutes are aware of whether or not a FRP has been used to register a generic. Interchangeability cannot necessarily be guaranteed if the reference product was not proven equivalent to the local innovator product. It is debatable as to whether or not this information would be of any particular benefit to members of the public. Prescribers may choose to write ‘no substitution’ on their prescriptions if they were unconvinced that an FRP is acceptable. This could have consequences for healthcare costs. Dispensers are the most vulnerable in South Africa as they are obliged by law to substitute generic medicines when innovator medicines have been prescribed. Dispensers’ views on the acceptability of the use of FRPs can be seen as irrelevant. In the end, as this study demonstrates, the only option in the present situation is to rely entirely on the MCC’s rigour in assessing applications for registration of generic medicines.
- Full Text:
Forty years of historical research in South Africa: some general trends and personal recollections
- Authors: Maylam, Paul
- Date: 2012
- Language: English
- Type: Text
- Identifier: vital:590 , http://hdl.handle.net/10962/d1019739
- Description: Vice Chancellor's Distinguished Research Award Lecture, Rhodes University, 15 October 2012
- Full Text:
- Authors: Maylam, Paul
- Date: 2012
- Language: English
- Type: Text
- Identifier: vital:590 , http://hdl.handle.net/10962/d1019739
- Description: Vice Chancellor's Distinguished Research Award Lecture, Rhodes University, 15 October 2012
- Full Text:
From the grave to the cradle : the possibility of post-mortem gamete retrieval and reproduction in South Africa
- Authors: Kruuse, Helen
- Date: 2012
- Language: English
- Type: Article
- Identifier: vital:24533 , http://hdl.handle.net/10962/36254 , http://www.tandfonline.com/doi/abs/10.1080/19962126.2012.11865059
- Description: The development of reproductive technologies in the last century, such as effective contraceptive methods, artificial insemination, pre-implantation genetic diagnosis, amongst others, has fundamentally reshaped traditional concepts of reproduction parenthood and has raised practical and ethical concerns. This article describes one such development, namely, post-mortem gamete retrieval (PMGR) for the purposes of posthumous reproduction. In exploring the particular concerns arising from this technology, I argue that South Africa lacks a coherent, considered approach to the issue. In considering models adopted in overseas jurisdictions, and the various bases for the legalisation of such a procedure, I adopt an interest theory of rights to argue for restricted access to such a technology in suitable circumstances.
- Full Text:
- Authors: Kruuse, Helen
- Date: 2012
- Language: English
- Type: Article
- Identifier: vital:24533 , http://hdl.handle.net/10962/36254 , http://www.tandfonline.com/doi/abs/10.1080/19962126.2012.11865059
- Description: The development of reproductive technologies in the last century, such as effective contraceptive methods, artificial insemination, pre-implantation genetic diagnosis, amongst others, has fundamentally reshaped traditional concepts of reproduction parenthood and has raised practical and ethical concerns. This article describes one such development, namely, post-mortem gamete retrieval (PMGR) for the purposes of posthumous reproduction. In exploring the particular concerns arising from this technology, I argue that South Africa lacks a coherent, considered approach to the issue. In considering models adopted in overseas jurisdictions, and the various bases for the legalisation of such a procedure, I adopt an interest theory of rights to argue for restricted access to such a technology in suitable circumstances.
- Full Text:
Functional programming and security
- Authors: Motara, Yusuf, M
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/428985 , vital:72551 , https://doi.org/10.48550/arXiv.1201.5728
- Description: This paper analyses the security contribution of typical functional-language features by examining them in the light of accepted information security principles. Imperative and functional code are compared to illustrate various cases. In conclusion, there may be an excellent case for the use of functional languages on the grounds of better security; however, empirical research should be done to validate this possibility.
- Full Text:
- Authors: Motara, Yusuf, M
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/428985 , vital:72551 , https://doi.org/10.48550/arXiv.1201.5728
- Description: This paper analyses the security contribution of typical functional-language features by examining them in the light of accepted information security principles. Imperative and functional code are compared to illustrate various cases. In conclusion, there may be an excellent case for the use of functional languages on the grounds of better security; however, empirical research should be done to validate this possibility.
- Full Text:
Futures studies for the southern African region : ‘from Africa’ not ‘on Africa’
- Fox, Roddy C, Rowntree, Kate M, Kaskinen, J
- Authors: Fox, Roddy C , Rowntree, Kate M , Kaskinen, J
- Date: 2012
- Language: English
- Type: Conference paper
- Identifier: vital:6668 , http://hdl.handle.net/10962/d1006685
- Description: Futures studies is well established in the Nordic region and its history can be readily charted, but in Africa it barely exists in an institutional form and its evolution and impact is little known or understood. The first two sections of our paper briefly examine the history of futures studies, spending most attention on the African experience. We go on to show that the Higher Education landscape in the Southern African Development Community (SADC) region is very different to that in the Nordic region. Recent futures reports present forecasts and scenarios that show a differentiated Higher Education landscape in the SADC; there are few Higher Education Institutions (HEIs) and even the most optimistic forecasts show that the region as a whole will not meet the international enrollment norm of 30% by 2050. The last part of the paper examines our experience of collaboration with Finland and its well developed linkages between state and Universities. One outcome of three years of collaboration from 2007 to 2009 between two SANORD members, the Finland Futures Research Centre (now a part of the University of Turku) and Rhodes University, was a proposal to develop a multi-disciplinary, inter-institutional futures studies program intended to help Africa find its own voice in futures studies. The final part of our presentation reflects on the unsuccessful experiences that we have had to date in finding funding. We conclude by asking whether our experience can be seen as highlighting some of the challenges SANORD may be positioned to overcome if the SADC region’s HEIs are to achieve the Knowledge Village scenario and begin to match their Nordic counterparts.
- Full Text:
- Authors: Fox, Roddy C , Rowntree, Kate M , Kaskinen, J
- Date: 2012
- Language: English
- Type: Conference paper
- Identifier: vital:6668 , http://hdl.handle.net/10962/d1006685
- Description: Futures studies is well established in the Nordic region and its history can be readily charted, but in Africa it barely exists in an institutional form and its evolution and impact is little known or understood. The first two sections of our paper briefly examine the history of futures studies, spending most attention on the African experience. We go on to show that the Higher Education landscape in the Southern African Development Community (SADC) region is very different to that in the Nordic region. Recent futures reports present forecasts and scenarios that show a differentiated Higher Education landscape in the SADC; there are few Higher Education Institutions (HEIs) and even the most optimistic forecasts show that the region as a whole will not meet the international enrollment norm of 30% by 2050. The last part of the paper examines our experience of collaboration with Finland and its well developed linkages between state and Universities. One outcome of three years of collaboration from 2007 to 2009 between two SANORD members, the Finland Futures Research Centre (now a part of the University of Turku) and Rhodes University, was a proposal to develop a multi-disciplinary, inter-institutional futures studies program intended to help Africa find its own voice in futures studies. The final part of our presentation reflects on the unsuccessful experiences that we have had to date in finding funding. We conclude by asking whether our experience can be seen as highlighting some of the challenges SANORD may be positioned to overcome if the SADC region’s HEIs are to achieve the Knowledge Village scenario and begin to match their Nordic counterparts.
- Full Text:
Gender Policy: discussion document 27-29 March 2012
- Congress of South African Trade Unions (COSATU)
- Authors: Congress of South African Trade Unions (COSATU)
- Date: 2012
- Subjects: Uncatalogued
- Language: English
- Type: book , text
- Identifier: http://hdl.handle.net/10962/68759 , vital:29312
- Description: The Gender policy draws together existing COSATU resolutions into a coherent document, while further enriching these resolutions. This document aims to combine the vision and principles that we aspire towards, with practical relations in the working workplace and economy, in trade unions and in broader society. The issue of gender equality has been on our agenda since the formation of COSATU. However, we require a policy framework to guide our struggles to transform gender relations in the current period. It is therefore important that we reflect on progress in taking forward the vision and programmes adopted on several Congresses since COSATU inception. In broad terms, progress to realise these resolutions has been uneven and varies between affiliates. COSATU and its affiliates are guided by a vision of a society free of sexism, racism, class exploitation, and other forms of oppression. We envisage a future where women participate equally in the economy and society without barriers, and where women are emancipated from all forms of oppression in the household, the workplace and in broader society. We have a vision of a trade union movement as a home for women workers. This policy document was debated and adopted and the National Gender Conference (held on 5-7 July 2000). It is tabled at Congress for discussion and adoption. Once it has been adopted by the Congress all affiliates will have to give expression to this broad framework in their own policies.
- Full Text:
- Authors: Congress of South African Trade Unions (COSATU)
- Date: 2012
- Subjects: Uncatalogued
- Language: English
- Type: book , text
- Identifier: http://hdl.handle.net/10962/68759 , vital:29312
- Description: The Gender policy draws together existing COSATU resolutions into a coherent document, while further enriching these resolutions. This document aims to combine the vision and principles that we aspire towards, with practical relations in the working workplace and economy, in trade unions and in broader society. The issue of gender equality has been on our agenda since the formation of COSATU. However, we require a policy framework to guide our struggles to transform gender relations in the current period. It is therefore important that we reflect on progress in taking forward the vision and programmes adopted on several Congresses since COSATU inception. In broad terms, progress to realise these resolutions has been uneven and varies between affiliates. COSATU and its affiliates are guided by a vision of a society free of sexism, racism, class exploitation, and other forms of oppression. We envisage a future where women participate equally in the economy and society without barriers, and where women are emancipated from all forms of oppression in the household, the workplace and in broader society. We have a vision of a trade union movement as a home for women workers. This policy document was debated and adopted and the National Gender Conference (held on 5-7 July 2000). It is tabled at Congress for discussion and adoption. Once it has been adopted by the Congress all affiliates will have to give expression to this broad framework in their own policies.
- Full Text:
Geo-spatial autocorrelation as a metric for the detection of fast-flux botnet domains
- Stalmans, Etienne, Hunter, Samuel O, Irwin, Barry V W
- Authors: Stalmans, Etienne , Hunter, Samuel O , Irwin, Barry V W
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429799 , vital:72640 , 10.1109/ISSA.2012.6320433
- Description: Botnets consist of thousands of hosts infected with malware. Botnet owners communicate with these hosts using Command and Control (C2) servers. These C2 servers are usually infected hosts which the botnet owners do not have physical access to. For this reason botnets can be shut down by taking over or blocking the C2 servers. Botnet owners have employed numerous shutdown avoidance techniques. One of these techniques, DNS Fast-Flux, relies on rapidly changing address records. The addresses returned by the Fast-Flux DNS servers consist of geographically widely distributed hosts. The distributed nature of Fast-Flux botnets differs from legitimate domains, which tend to have geographically clustered server locations. This paper examines the use of spatial autocorrelation techniques based on the geographic distribution of domain servers to detect Fast-Flux domains. Moran's I and Geary's C are used to produce classifiers using multiple geographic co-ordinate systems to produce efficient and accurate results. It is shown how Fast-Flux domains can be detected reliably while only a small percentage of false positives are produced.
- Full Text:
- Authors: Stalmans, Etienne , Hunter, Samuel O , Irwin, Barry V W
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429799 , vital:72640 , 10.1109/ISSA.2012.6320433
- Description: Botnets consist of thousands of hosts infected with malware. Botnet owners communicate with these hosts using Command and Control (C2) servers. These C2 servers are usually infected hosts which the botnet owners do not have physical access to. For this reason botnets can be shut down by taking over or blocking the C2 servers. Botnet owners have employed numerous shutdown avoidance techniques. One of these techniques, DNS Fast-Flux, relies on rapidly changing address records. The addresses returned by the Fast-Flux DNS servers consist of geographically widely distributed hosts. The distributed nature of Fast-Flux botnets differs from legitimate domains, which tend to have geographically clustered server locations. This paper examines the use of spatial autocorrelation techniques based on the geographic distribution of domain servers to detect Fast-Flux domains. Moran's I and Geary's C are used to produce classifiers using multiple geographic co-ordinate systems to produce efficient and accurate results. It is shown how Fast-Flux domains can be detected reliably while only a small percentage of false positives are produced.
- Full Text:
GPF : a framework for general packet classification on GPU co-processors
- Authors: Nottingham, Alastair
- Date: 2012
- Subjects: Graphics processing units , Coprocessors , Computer network protocols , Computer networks -- Security measures , NVIDIA Corporation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4661 , http://hdl.handle.net/10962/d1006662 , Graphics processing units , Coprocessors , Computer network protocols , Computer networks -- Security measures , NVIDIA Corporation
- Description: This thesis explores the design and experimental implementation of GPF, a novel protocol-independent, multi-match packet classification framework. This framework is targeted and optimised for flexible, efficient execution on NVIDIA GPU platforms through the CUDA API, but should not be difficult to port to other platforms, such as OpenCL, in the future. GPF was conceived and developed in order to accelerate classification of large packet capture files, such as those collected by Network Telescopes. It uses a multiphase SIMD classification process which exploits both the parallelism of packet sets and the redundancy in filter programs, in order to classify packet captures against multiple filters at extremely high rates. The resultant framework - comprised of classification, compilation and buffering components - efficiently leverages GPU resources to classify arbitrary protocols, and return multiple filter results for each packet. The classification functions described were verified and evaluated by testing an experimental prototype implementation against several filter programs, of varying complexity, on devices from three GPU platform generations. In addition to the significant speedup achieved in processing results, analysis indicates that the prototype classification functions perform predictably, and scale linearly with respect to both packet count and filter complexity. Furthermore, classification throughput (packets/s) remained essentially constant regardless of the underlying packet data, and thus the effective data rate when classifying a particular filter was heavily influenced by the average size of packets in the processed capture. For example: in the trivial case of classifying all IPv4 packets ranging in size from 70 bytes to 1KB, the observed data rate achieved by the GPU classification kernels ranged from 60Gbps to 900Gbps on a GTX 275, and from 220Gbps to 3.3Tbps on a GTX 480. In the less trivial case of identifying all ARP, TCP, UDP and ICMP packets for both IPv4 and IPv6 protocols, the effective data rates ranged from 15Gbps to 220Gbps (GTX 275), and from 50Gbps to 740Gbps (GTX 480), for 70B and 1KB packets respectively. , LaTeX with hyperref package
- Full Text:
- Authors: Nottingham, Alastair
- Date: 2012
- Subjects: Graphics processing units , Coprocessors , Computer network protocols , Computer networks -- Security measures , NVIDIA Corporation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4661 , http://hdl.handle.net/10962/d1006662 , Graphics processing units , Coprocessors , Computer network protocols , Computer networks -- Security measures , NVIDIA Corporation
- Description: This thesis explores the design and experimental implementation of GPF, a novel protocol-independent, multi-match packet classification framework. This framework is targeted and optimised for flexible, efficient execution on NVIDIA GPU platforms through the CUDA API, but should not be difficult to port to other platforms, such as OpenCL, in the future. GPF was conceived and developed in order to accelerate classification of large packet capture files, such as those collected by Network Telescopes. It uses a multiphase SIMD classification process which exploits both the parallelism of packet sets and the redundancy in filter programs, in order to classify packet captures against multiple filters at extremely high rates. The resultant framework - comprised of classification, compilation and buffering components - efficiently leverages GPU resources to classify arbitrary protocols, and return multiple filter results for each packet. The classification functions described were verified and evaluated by testing an experimental prototype implementation against several filter programs, of varying complexity, on devices from three GPU platform generations. In addition to the significant speedup achieved in processing results, analysis indicates that the prototype classification functions perform predictably, and scale linearly with respect to both packet count and filter complexity. Furthermore, classification throughput (packets/s) remained essentially constant regardless of the underlying packet data, and thus the effective data rate when classifying a particular filter was heavily influenced by the average size of packets in the processed capture. For example: in the trivial case of classifying all IPv4 packets ranging in size from 70 bytes to 1KB, the observed data rate achieved by the GPU classification kernels ranged from 60Gbps to 900Gbps on a GTX 275, and from 220Gbps to 3.3Tbps on a GTX 480. In the less trivial case of identifying all ARP, TCP, UDP and ICMP packets for both IPv4 and IPv6 protocols, the effective data rates ranged from 15Gbps to 220Gbps (GTX 275), and from 50Gbps to 740Gbps (GTX 480), for 70B and 1KB packets respectively. , LaTeX with hyperref package
- Full Text:
Gravitational entropy and thermodynamics away from the horizon
- Brustein, Ram, Medved, Allan J M
- Authors: Brustein, Ram , Medved, Allan J M
- Date: 2012
- Language: English
- Type: Article
- Identifier: vital:6818 , http://hdl.handle.net/10962/d1004328
- Description: We define, by an integral of geometric quantities over a spherical shell of arbitrary radius, an invariant gravitational entropy. This definition relies on defining a gravitational energy and pressure, and it reduces at the horizon of both black branes and black holes to Wald's Noether charge entropy. We support the thermodynamic interpretation of the proposed entropy by showing that, for some cases, the field theory duals of the entropy, energy and pressure are the same as the corresponding quantities in the field theory. In this context, the Einstein equations are equivalent to the field theory thermodynamic relation TdS=dE+PdV supplemented by an equation of state
- Full Text:
- Authors: Brustein, Ram , Medved, Allan J M
- Date: 2012
- Language: English
- Type: Article
- Identifier: vital:6818 , http://hdl.handle.net/10962/d1004328
- Description: We define, by an integral of geometric quantities over a spherical shell of arbitrary radius, an invariant gravitational entropy. This definition relies on defining a gravitational energy and pressure, and it reduces at the horizon of both black branes and black holes to Wald's Noether charge entropy. We support the thermodynamic interpretation of the proposed entropy by showing that, for some cases, the field theory duals of the entropy, energy and pressure are the same as the corresponding quantities in the field theory. In this context, the Einstein equations are equivalent to the field theory thermodynamic relation TdS=dE+PdV supplemented by an equation of state
- Full Text:
Graviton n-point functions for UV-complete theories in Anti-de Sitter space
- Brustein, Ram, Medved, Allan J M
- Authors: Brustein, Ram , Medved, Allan J M
- Date: 2012
- Language: English
- Type: text , Article
- Identifier: vital:6820 , http://hdl.handle.net/10962/d1004427
- Description: We calculate graviton n-point functions in an anti-de Sitter black brane background for effective gravity theories whose linearized equations of motion have at most two time derivatives. We compare the n-point functions in Einstein gravity to those in theories whose leading correction is quadratic in the Riemann tensor. The comparison is made for any number of gravitons and for all physical graviton modes in a kinematic region for which the leading correction can significantly modify the Einstein result. We find that the n-point functions of Einstein gravity depend on at most a single angle, whereas those of the corrected theories may depend on two angles. For the four-point functions, Einstein gravity exhibits linear dependence on the Mandelstam variable s versus a quadratic dependence on s for the corrected theory.
- Full Text:
- Authors: Brustein, Ram , Medved, Allan J M
- Date: 2012
- Language: English
- Type: text , Article
- Identifier: vital:6820 , http://hdl.handle.net/10962/d1004427
- Description: We calculate graviton n-point functions in an anti-de Sitter black brane background for effective gravity theories whose linearized equations of motion have at most two time derivatives. We compare the n-point functions in Einstein gravity to those in theories whose leading correction is quadratic in the Riemann tensor. The comparison is made for any number of gravitons and for all physical graviton modes in a kinematic region for which the leading correction can significantly modify the Einstein result. We find that the n-point functions of Einstein gravity depend on at most a single angle, whereas those of the corrected theories may depend on two angles. For the four-point functions, Einstein gravity exhibits linear dependence on the Mandelstam variable s versus a quadratic dependence on s for the corrected theory.
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Guy Butler’s South Africanism: ‘Being present where you are’
- Authors: Wright, Laurence
- Date: 2012
- Language: English
- Type: text , article
- Identifier: vital:7069 , http://hdl.handle.net/10962/d1007460 , https://doi.org/10.1080/10131752.2012.730182
- Description: preprint , A peer-reviewed lecture delivered at Rhodes University on the occasion of the presentation to Professor Wright of the English Academy's Gold Medal, 16 November 2011. Guy Butler (1918-2001) has been gone some ten years. This lecture sets out to illuminate the thinking behind his important role in South Africa's national life. The institutions he created continue to make vital cultural contributions in South Africa's efforts to make sense of its own complex historical make-up, working towards a happier, richer, and more equal future. However, despite what he achieved, there is little surety that today the rationale informing his massive effort to foster processes of artistic and cultural endeavour has been appreciated or accurately understood.
- Full Text:
- Authors: Wright, Laurence
- Date: 2012
- Language: English
- Type: text , article
- Identifier: vital:7069 , http://hdl.handle.net/10962/d1007460 , https://doi.org/10.1080/10131752.2012.730182
- Description: preprint , A peer-reviewed lecture delivered at Rhodes University on the occasion of the presentation to Professor Wright of the English Academy's Gold Medal, 16 November 2011. Guy Butler (1918-2001) has been gone some ten years. This lecture sets out to illuminate the thinking behind his important role in South Africa's national life. The institutions he created continue to make vital cultural contributions in South Africa's efforts to make sense of its own complex historical make-up, working towards a happier, richer, and more equal future. However, despite what he achieved, there is little surety that today the rationale informing his massive effort to foster processes of artistic and cultural endeavour has been appreciated or accurately understood.
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Haul Music : transnationalism and musical performance in the Saharaui refugee camps of Tindouf, Algeria
- Authors: Gimenez Amoros, Luis
- Date: 2012
- Subjects: Bedouins -- Music -- Research Sahrawi (African people) -- Migrations Social change -- Arab countries Arab countries -- Social life and customs Civilization, Arab
- Language: English
- Type: Thesis , Masters , MMus
- Identifier: vital:2637 , http://hdl.handle.net/10962/d1002302
- Description: The thesis presents ethnographic data and musical analysis (in the form of transcriptions) of Haul music which is the music style performed by Bedouin societies in Trab el Bidan region (Mauritania, Western Sahara, northern Mali, southern Algeria and northern Morocco). It is based on field research undertaken in Algeria in 2004-05 in the refugee camps of Tindouf, Algeria, where Saharaui people (a Bedouin society)live in exile. This research is unique and original as Haul has not, until now, been explored in depth by any scholar. My research on Haul reveals that the changes in Saharaui music in the refugee camps of Tindouf reflect changes in the musical traditions of Bedouin societies as whole; changes that can be traced to the revolution which occurred in Western Sahara in 1975, and changes that are a result of the migrations and life in exile that followed. I argue that these changes occurred due to the transnational experiences undergone by Saharaui people in their forced exile (caused by the Moroccan state) from their homeland in Western Sahara to Algeria. Further, I assert that the invocation of memory in Bedouin musical styles is evidence of past musical practices being retained in contemporary Haul performance, although other musical changes are similarly in progress.
- Full Text:
- Authors: Gimenez Amoros, Luis
- Date: 2012
- Subjects: Bedouins -- Music -- Research Sahrawi (African people) -- Migrations Social change -- Arab countries Arab countries -- Social life and customs Civilization, Arab
- Language: English
- Type: Thesis , Masters , MMus
- Identifier: vital:2637 , http://hdl.handle.net/10962/d1002302
- Description: The thesis presents ethnographic data and musical analysis (in the form of transcriptions) of Haul music which is the music style performed by Bedouin societies in Trab el Bidan region (Mauritania, Western Sahara, northern Mali, southern Algeria and northern Morocco). It is based on field research undertaken in Algeria in 2004-05 in the refugee camps of Tindouf, Algeria, where Saharaui people (a Bedouin society)live in exile. This research is unique and original as Haul has not, until now, been explored in depth by any scholar. My research on Haul reveals that the changes in Saharaui music in the refugee camps of Tindouf reflect changes in the musical traditions of Bedouin societies as whole; changes that can be traced to the revolution which occurred in Western Sahara in 1975, and changes that are a result of the migrations and life in exile that followed. I argue that these changes occurred due to the transnational experiences undergone by Saharaui people in their forced exile (caused by the Moroccan state) from their homeland in Western Sahara to Algeria. Further, I assert that the invocation of memory in Bedouin musical styles is evidence of past musical practices being retained in contemporary Haul performance, although other musical changes are similarly in progress.
- Full Text:
Having a phone, having style:
- Authors: Schoon, Alette
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159506 , vital:40303 , https://hdl.handle.net/10520/EJC135828
- Description: It was dusk, and a group of young men with a dog trailing behind them, were walking past on a dusty township road in Hooggenoeg, an RDP village on the rim of the Grahamstown bowl. While they ambled along, one was holding up a mobile phone on which music was playing, dancing while he walked. This was exactly the kind of thing I was hoping to observe in my new identity as researcher and participant observer, and was why I had agreed to judge the Hooggenoeg fashion show which turned out to be more of a beauty competition. While I'm not generally fond of these kind of shows and the way they essentialise beauty, I agreed because I wanted to get more of a sense of how mobile phones are integrated into the everyday lives of these young adults.
- Full Text:
- Authors: Schoon, Alette
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/159506 , vital:40303 , https://hdl.handle.net/10520/EJC135828
- Description: It was dusk, and a group of young men with a dog trailing behind them, were walking past on a dusty township road in Hooggenoeg, an RDP village on the rim of the Grahamstown bowl. While they ambled along, one was holding up a mobile phone on which music was playing, dancing while he walked. This was exactly the kind of thing I was hoping to observe in my new identity as researcher and participant observer, and was why I had agreed to judge the Hooggenoeg fashion show which turned out to be more of a beauty competition. While I'm not generally fond of these kind of shows and the way they essentialise beauty, I agreed because I wanted to get more of a sense of how mobile phones are integrated into the everyday lives of these young adults.
- Full Text:
Henry Williams : The Glasbury Bellfounder, and the production and tuning of bells
- Authors: Lewis, Colin A
- Date: 2012
- Language: English
- Type: Book chapter
- Identifier: vital:6159 , http://hdl.handle.net/10962/d1004779 , Full text available to the end of Chapter 2
- Description: The production and tuning of church bells is described before attention is paid to Henry Williams, the Glasbury bellfounder who died in 1722, and his bells. The bells of TP, his apparent successor are also described. Henry Williams was probably a member of the Williams family of Gwernyfed and was born c 1635. His presumed family connections are described. Bells known to have been cast by Henry Williams between 1677 and 1719 are listed; their distribution depicted; and their qualities assessed. The inventory of Williams' possessions at the time of his death is presented and discussed. Bells cast by TP during a brief foray into bell founding, apparently 1738-40, are described and their qualities assessed. TP was probably Benjamin Tanner (T), the industrialist specialising in iron production who succeeded Williams at the Pipton forge (P) in Aberllynfi parish near Glasbury, or Tanner (T) and Samuel Prichard (P). Prichard was the grandson of Henry Williams and his sole executor. , A complete copy of this book is available at The Whiting Society of Ringers at: http://www.whitingsociety.org.uk
- Full Text:
- Authors: Lewis, Colin A
- Date: 2012
- Language: English
- Type: Book chapter
- Identifier: vital:6159 , http://hdl.handle.net/10962/d1004779 , Full text available to the end of Chapter 2
- Description: The production and tuning of church bells is described before attention is paid to Henry Williams, the Glasbury bellfounder who died in 1722, and his bells. The bells of TP, his apparent successor are also described. Henry Williams was probably a member of the Williams family of Gwernyfed and was born c 1635. His presumed family connections are described. Bells known to have been cast by Henry Williams between 1677 and 1719 are listed; their distribution depicted; and their qualities assessed. The inventory of Williams' possessions at the time of his death is presented and discussed. Bells cast by TP during a brief foray into bell founding, apparently 1738-40, are described and their qualities assessed. TP was probably Benjamin Tanner (T), the industrialist specialising in iron production who succeeded Williams at the Pipton forge (P) in Aberllynfi parish near Glasbury, or Tanner (T) and Samuel Prichard (P). Prichard was the grandson of Henry Williams and his sole executor. , A complete copy of this book is available at The Whiting Society of Ringers at: http://www.whitingsociety.org.uk
- Full Text:
High pressure liquid chromatographic quantification of nitrile biocatalysis
- Authors: Mathiba, Kgama
- Date: 2012
- Subjects: High performance liquid chromatography , Rhodococcus , Biocatalysis , Organic compounds -- Industrial applications
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4129 , http://hdl.handle.net/10962/d1015710
- Description: Nitrile biocatalysts are of use in the chemical and pharmaceutical industries for the synthesis of carboxyamides and carboxylic acids. In particular, the application of biocatalysts in the synthesis of single enantiomer compounds is of increasing interest, but requires novel substrate specific highly stereoselective biocatalysts. Addition to the limited toolbox of known nitrile biocatalysts requires definitive characterisation of the biocatalysts through accurate determination of the substrate profiles and quantification of activity. The accurate quantification of stereoisomers chiral mixtures to determine biocatalyst stereoselectivity remains a significant challenge due to the difficulty in separating stereoisomers by physical methods. The known nitrile metabolising organism, Rhodococcus rhodochrous ATCC BAA-870, was grown in a defined medium and harvested, providing whole cell biocatalyst. Additional biomass was disrupted to provide a cell free enzyme extract, which was put through an enzyme purification protocol to provide a solution with specific activity of 351 U.mg⁻¹. A portion of the enzyme was self immobilised using the SphereZyme™ technique. The nitrile hydratase SphereZymes™ (1.2 U.mg⁻¹ initial activity) that were prepared had pH and temperature optima of 6 and 30°C respectively, and could be recovered by repeated washing. The particles retained activity in the presence of the organic solvents isooctane and n-hexadecane saturated with 50 mM phosphate buffer (pH 7.5). An initial analytical system was devised for quantification of the nitrile hydratase activity using the non-chiral substrate benzonitrile. An improved reversed phase high performance liquid chromatography method was developed to separate and quantify benzamide, benzoic acid and benzonitrile. The mobile phase consisting of 0.1% trifluoroacetic acid in H₂O and acetonitrile (70:30, %v/v), at a flow rate of 0.5 ml.ml⁻¹, 25°C, resolved all three analytes in 3.5 minutes on a Waters X-Terra MS C18 3.5μm column. UV detection was carried out at 210 nm. Analytical methods to determine activity and enantioselectivity of the whole cell biocatalyst were subsequently developed for both β-amino nitriles and β-hydroxy nitrile substrates and hydrolysis products.
- Full Text:
- Authors: Mathiba, Kgama
- Date: 2012
- Subjects: High performance liquid chromatography , Rhodococcus , Biocatalysis , Organic compounds -- Industrial applications
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4129 , http://hdl.handle.net/10962/d1015710
- Description: Nitrile biocatalysts are of use in the chemical and pharmaceutical industries for the synthesis of carboxyamides and carboxylic acids. In particular, the application of biocatalysts in the synthesis of single enantiomer compounds is of increasing interest, but requires novel substrate specific highly stereoselective biocatalysts. Addition to the limited toolbox of known nitrile biocatalysts requires definitive characterisation of the biocatalysts through accurate determination of the substrate profiles and quantification of activity. The accurate quantification of stereoisomers chiral mixtures to determine biocatalyst stereoselectivity remains a significant challenge due to the difficulty in separating stereoisomers by physical methods. The known nitrile metabolising organism, Rhodococcus rhodochrous ATCC BAA-870, was grown in a defined medium and harvested, providing whole cell biocatalyst. Additional biomass was disrupted to provide a cell free enzyme extract, which was put through an enzyme purification protocol to provide a solution with specific activity of 351 U.mg⁻¹. A portion of the enzyme was self immobilised using the SphereZyme™ technique. The nitrile hydratase SphereZymes™ (1.2 U.mg⁻¹ initial activity) that were prepared had pH and temperature optima of 6 and 30°C respectively, and could be recovered by repeated washing. The particles retained activity in the presence of the organic solvents isooctane and n-hexadecane saturated with 50 mM phosphate buffer (pH 7.5). An initial analytical system was devised for quantification of the nitrile hydratase activity using the non-chiral substrate benzonitrile. An improved reversed phase high performance liquid chromatography method was developed to separate and quantify benzamide, benzoic acid and benzonitrile. The mobile phase consisting of 0.1% trifluoroacetic acid in H₂O and acetonitrile (70:30, %v/v), at a flow rate of 0.5 ml.ml⁻¹, 25°C, resolved all three analytes in 3.5 minutes on a Waters X-Terra MS C18 3.5μm column. UV detection was carried out at 210 nm. Analytical methods to determine activity and enantioselectivity of the whole cell biocatalyst were subsequently developed for both β-amino nitriles and β-hydroxy nitrile substrates and hydrolysis products.
- Full Text:
Higher education, academic communities, and the intellectual virtues
- Authors: Jones, Ward E
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/275647 , vital:55066 , xlink:href="https://doi.org/10.1111/edth.12005"
- Description: Because higher education brings members of academic communities in direct contact with students, the reflective higher education student is in an excellent position for developing two important intellectual virtues: confidence and humility. However, academic communities differ as to whether their members reach consensus, and their teaching practices reflect this difference. In this essay, Ward Jones argues that both consensus-reaching and non-consensus-reaching communities can encourage the development of intellectual confidence and humility in their students, although each will do so in very different ways.
- Full Text:
- Authors: Jones, Ward E
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/275647 , vital:55066 , xlink:href="https://doi.org/10.1111/edth.12005"
- Description: Because higher education brings members of academic communities in direct contact with students, the reflective higher education student is in an excellent position for developing two important intellectual virtues: confidence and humility. However, academic communities differ as to whether their members reach consensus, and their teaching practices reflect this difference. In this essay, Ward Jones argues that both consensus-reaching and non-consensus-reaching communities can encourage the development of intellectual confidence and humility in their students, although each will do so in very different ways.
- Full Text:
How do HIV and AIDS impact the use of natural resources by poor rural populations?: The case of wild animal products
- Kaschula, Sarah A H, Shackleton, Charlie M
- Authors: Kaschula, Sarah A H , Shackleton, Charlie M
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/182344 , vital:43822 , xlink:href="https://hdl.handle.net/10520/EJC97203"
- Description: As a result of heightened financial and food insecurity, populations adversely affected by HIV and/or AIDS may be more likely to utilise wild natural resources to supplement their diet and livelihoods. Should this effect be pronounced, HIV and AIDS may pose a serious environmental threat. We explored the hypothesis that the presence of factors in the household, such as chronic illness in and recent mortality of individuals in a high HIV-risk age group, as well as the fostering of orphans, are associated with increased utilisation of wild animal products (WAPs) at the household level. We randomly surveyed 519 households from four sites in rural South Africa, recording household socio-economic status, the utilisation of wild animal products and health and demographic factors attributed to HIV or AIDS. Binary logistic regressions were used to test if households with markers of HIV and/or AIDS affliction were more likely to have a higher incidence and frequency of WAP utilisation relative to non-afflicted households, after adjusting for socio-economic and demographic variables. We found that, although households with markers of HIV and/or AIDS were generally poorer and had higher dependency ratios, there was no evidence to support the hypothesis that WAP harvesting was associated with either poverty, or markers of HIV and/or AIDS affliction. Our findings suggest that generalisations about a possible interaction between HIV and/or AIDS and the environment may not uniformly apply to all categories of natural resources or to all user groups.
- Full Text:
- Authors: Kaschula, Sarah A H , Shackleton, Charlie M
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/182344 , vital:43822 , xlink:href="https://hdl.handle.net/10520/EJC97203"
- Description: As a result of heightened financial and food insecurity, populations adversely affected by HIV and/or AIDS may be more likely to utilise wild natural resources to supplement their diet and livelihoods. Should this effect be pronounced, HIV and AIDS may pose a serious environmental threat. We explored the hypothesis that the presence of factors in the household, such as chronic illness in and recent mortality of individuals in a high HIV-risk age group, as well as the fostering of orphans, are associated with increased utilisation of wild animal products (WAPs) at the household level. We randomly surveyed 519 households from four sites in rural South Africa, recording household socio-economic status, the utilisation of wild animal products and health and demographic factors attributed to HIV or AIDS. Binary logistic regressions were used to test if households with markers of HIV and/or AIDS affliction were more likely to have a higher incidence and frequency of WAP utilisation relative to non-afflicted households, after adjusting for socio-economic and demographic variables. We found that, although households with markers of HIV and/or AIDS were generally poorer and had higher dependency ratios, there was no evidence to support the hypothesis that WAP harvesting was associated with either poverty, or markers of HIV and/or AIDS affliction. Our findings suggest that generalisations about a possible interaction between HIV and/or AIDS and the environment may not uniformly apply to all categories of natural resources or to all user groups.
- Full Text:
Human rights and post-conflict peace building in the Democratic Republic of Congo
- Authors: Juma, Laurence
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/128438 , vital:36109 , https://0-hdl.handle.net.wam.seals.ac.za/10520/EJC192855
- Description: This article deals with normative issues that arose in the post-conflict peace-building processes in the Democratic Republic of Congo (DRC). It undertakes an historical review of the major episodes in the DRC peace process and highlights how these episodes yielded to the establishment of the interim government in 2003 and the enactment of the current constitution. It mainly highlights the proprietary consequences of the Lusaka peace Accord, the transformative aspects of the 2005 Constitution and the role that international organs, especially the ICC, have played in consolidating peace in the DRC.
- Full Text: false
- Authors: Juma, Laurence
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/128438 , vital:36109 , https://0-hdl.handle.net.wam.seals.ac.za/10520/EJC192855
- Description: This article deals with normative issues that arose in the post-conflict peace-building processes in the Democratic Republic of Congo (DRC). It undertakes an historical review of the major episodes in the DRC peace process and highlights how these episodes yielded to the establishment of the interim government in 2003 and the enactment of the current constitution. It mainly highlights the proprietary consequences of the Lusaka peace Accord, the transformative aspects of the 2005 Constitution and the role that international organs, especially the ICC, have played in consolidating peace in the DRC.
- Full Text: false
Hydrological uncertainty analysis and scenario-based streamflow modelling for the Congo River Basin
- Authors: Tshimanga, Raphael Muamba
- Date: 2012
- Subjects: Congo River -- Regulation Hydrological surveys -- Congo River Watershed Water resources development -- Congo River Watershed Water resources development -- Environmental aspects -- Congo River Watershed Water supply -- Congo River Watershed River engineering -- Congo River Watershed
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:6029 , http://hdl.handle.net/10962/d1006158
- Description: The effects of climate and environmental change are likely to exacerbate water stress in Africa over the next five decades. It appears obvious, therefore, that large river basins with considerable total renewable water resources will play a prominent role in regional cooperation to alleviate the pressure of water scarcity within Africa. However, managing water resources in the large river basins of Africa involves problems of data paucity, lack of technical resources and the sheer scale of the problem. These river basins are located in regions that are characterized by poverty, low levels of economic development and little food security. The rivers provide multiple goods and services that include hydro-power, water supply, fisheries, agriculture, transportation, and maintenance of aquatic ecosystems. Sustainable water resources management is a critical issue, but there is almost always insufficient data available to formulate adequate management strategies. These basins therefore represent some of the best test cases for the practical application of the science associated with the Predictions in Ungauged Basins (PUB). The thesis presents the results of a process-based hydrological modelling study in the Congo Basin. One of the primary objectives of this study was to establish a hydrological model for the whole Congo Basin, using available historical data. The secondary objective of the study was to use the model and assess the impacts of future environmental change on water resources of the Congo Basin. Given the lack of adequate data on the basin physical characteristics, the preliminary work consisted of assessing available global datasets and building a database of the basin physical characteristics. The database was used for both assessing relationships of similarities between features of physiographic settings in the basin (Chapters 3 and 4), and establishing models that adequately represent the basin hydrology (Chapters 5, 6, and 7). The representative model of the Congo Basin hydrology was then used to assess the impacts of future environmental changes on water resources availability of the Congo Basin (Chapter 8). Through assessment of the physical characteristics of the basin, relationships of similarities were used to determine homogenous regions with regard to rainfall variability, physiographic settings, and hydrological responses. The first observation that comes from this study is that these three categories of regional groups of homogenous characteristics are sensible with regards to their geographical settings, but the overlap and apparent relationships between them are weak. An explanation of this observation is that there are insufficient data, particularly associated with defining sub-surface processes, and it is possible that additional data would have assisted in the discrimination of more homogenous groups and better links between the different datasets. The model application in this study consisted of two phases: model calibration, using a manual approach, and the application of a physically-based a priori parameter estimation approach. While the first approach was designed to assess the general applicability of the model and identify major errors with regard to input data and model structure, the second approach aimed to establish an understanding of the processes and identify useful relationships between the model parameters and the variations in real hydrological processes. The second approach was also designed to quantify the sensitivity of the model outputs to the parameters of the model and to encompass information sharing between the basin physical characteristics and quantifying the parameters of the model. Collectively, the study’s findings show that these two approaches work well and are appropriate to represent the real hydrological processes of Congo Basin. The secondary objective of this study was achieved by forcing the hydrological model developed for the Congo Basin with downscaled Global Climate Model (GCMs) data in order to assess scenarios of change and future possible impacts on water resources availability within the basin. The results provide useful lessons in terms of basin-wide adaptation measures to future climates. The lessons suggest that there is a risk of developing inappropriate adaptation measures to future climate change based on large scale hydrological response, as the response at small scales shows a completely different picture from that which is based on large scale predictions. While the study has concluded that the application of the hydrological model has been successful and can be used with some degree of confidence for enhanced decision making, there remain a number of uncertainties and opportunities to improve the methods used for water resources assessment within the basin. The focus of future activities from the perspective of practical application should be on improved access to data collection to increase confidence in model predictions, on dissemination of the knowledge generated by this study, and on training in the use of the developed water resources assessment techniques.
- Full Text:
- Authors: Tshimanga, Raphael Muamba
- Date: 2012
- Subjects: Congo River -- Regulation Hydrological surveys -- Congo River Watershed Water resources development -- Congo River Watershed Water resources development -- Environmental aspects -- Congo River Watershed Water supply -- Congo River Watershed River engineering -- Congo River Watershed
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:6029 , http://hdl.handle.net/10962/d1006158
- Description: The effects of climate and environmental change are likely to exacerbate water stress in Africa over the next five decades. It appears obvious, therefore, that large river basins with considerable total renewable water resources will play a prominent role in regional cooperation to alleviate the pressure of water scarcity within Africa. However, managing water resources in the large river basins of Africa involves problems of data paucity, lack of technical resources and the sheer scale of the problem. These river basins are located in regions that are characterized by poverty, low levels of economic development and little food security. The rivers provide multiple goods and services that include hydro-power, water supply, fisheries, agriculture, transportation, and maintenance of aquatic ecosystems. Sustainable water resources management is a critical issue, but there is almost always insufficient data available to formulate adequate management strategies. These basins therefore represent some of the best test cases for the practical application of the science associated with the Predictions in Ungauged Basins (PUB). The thesis presents the results of a process-based hydrological modelling study in the Congo Basin. One of the primary objectives of this study was to establish a hydrological model for the whole Congo Basin, using available historical data. The secondary objective of the study was to use the model and assess the impacts of future environmental change on water resources of the Congo Basin. Given the lack of adequate data on the basin physical characteristics, the preliminary work consisted of assessing available global datasets and building a database of the basin physical characteristics. The database was used for both assessing relationships of similarities between features of physiographic settings in the basin (Chapters 3 and 4), and establishing models that adequately represent the basin hydrology (Chapters 5, 6, and 7). The representative model of the Congo Basin hydrology was then used to assess the impacts of future environmental changes on water resources availability of the Congo Basin (Chapter 8). Through assessment of the physical characteristics of the basin, relationships of similarities were used to determine homogenous regions with regard to rainfall variability, physiographic settings, and hydrological responses. The first observation that comes from this study is that these three categories of regional groups of homogenous characteristics are sensible with regards to their geographical settings, but the overlap and apparent relationships between them are weak. An explanation of this observation is that there are insufficient data, particularly associated with defining sub-surface processes, and it is possible that additional data would have assisted in the discrimination of more homogenous groups and better links between the different datasets. The model application in this study consisted of two phases: model calibration, using a manual approach, and the application of a physically-based a priori parameter estimation approach. While the first approach was designed to assess the general applicability of the model and identify major errors with regard to input data and model structure, the second approach aimed to establish an understanding of the processes and identify useful relationships between the model parameters and the variations in real hydrological processes. The second approach was also designed to quantify the sensitivity of the model outputs to the parameters of the model and to encompass information sharing between the basin physical characteristics and quantifying the parameters of the model. Collectively, the study’s findings show that these two approaches work well and are appropriate to represent the real hydrological processes of Congo Basin. The secondary objective of this study was achieved by forcing the hydrological model developed for the Congo Basin with downscaled Global Climate Model (GCMs) data in order to assess scenarios of change and future possible impacts on water resources availability within the basin. The results provide useful lessons in terms of basin-wide adaptation measures to future climates. The lessons suggest that there is a risk of developing inappropriate adaptation measures to future climate change based on large scale hydrological response, as the response at small scales shows a completely different picture from that which is based on large scale predictions. While the study has concluded that the application of the hydrological model has been successful and can be used with some degree of confidence for enhanced decision making, there remain a number of uncertainties and opportunities to improve the methods used for water resources assessment within the basin. The focus of future activities from the perspective of practical application should be on improved access to data collection to increase confidence in model predictions, on dissemination of the knowledge generated by this study, and on training in the use of the developed water resources assessment techniques.
- Full Text:
Identification of novel marine algal compounds with differential anti-cancer activity: towards a cancer stem-cell specific chemotherapy
- Authors: De la Mare, Jo-Anne
- Date: 2012
- Subjects: Breast -- Cancer , Stem cells -- Research , Chemotherapy , Algae -- Biotechnology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4143 , http://hdl.handle.net/10962/d1016250
- Description: Breast cancer remains the leading cause of cancer-related death in women worldwide. Furthermore, it has been demonstrated that the treatment-resistant ER-PR-HER2/neu- sub-type is more common among women of African descent, necessitating the search for novel chemotherapies for this form of the disease. The secondary metabolites produced by marine algae represent a rich source of structurally unique compounds with chemotherapeutic potential, particularly in South Africa, whose oceans allegedly host 15 % of the total number of species in the world. Indeed, a recent study reported the isolation of a range of novel compounds from South African red and brown algae of the Plocamium, Portiera and Sargassum genera which displayed cytotoxicity against oesophageal cancer cells in vitro. The molecular mechanisms mediating this toxicity were unknown, as was the effect of these and similar compounds on metastatic ER-PR-HER2/neu- breast cancer cell lines or breast cancer stem cells. The current study aimed to address these questions by screening a library of twenty-two novel marine algal compounds for the ability to inhibit MDA-MB-231 and Hs578T breast cancer cells, while having no adverse effects on non-cancerous MCF12A breast epithelial cells. While twelve of these were toxic in the micromolar range against breast cancer cells, only the polyhalogenated monoterpenes RU004 and RU007, and the tetraprenylated quinone sargaquinoic acid (SQA) were identified as hit compounds based on the criteria that their cytotoxicity was specific to breast cancer and not healthy breast cells in vitro. On the other hand, the halogenated monoterpene RU015 was found to be highly toxic to both breast cancer and non-cancerous breast cell lines, while the halogenated monoterpene stereoisomers RU017 and RU018 were non-toxic to either of these cell lines. The mode of action of RU004, RU007, RU015 and SQA, together with the previously characterized carotenoid fucoxanthin (FXN), was assessed in terms of the type of cell death induced and the effect on cell cycle distribution of these compounds. Flow cytometric analysis of the extent of Hoescht 33342 and propidium iodide staining along with PARP cleavage studies suggested that SQA induced apoptosis in MDA-MB-231 cells. On the other hand, the highly toxic compound RU015 appeared to induce necrosis as evidenced by 50 kDa PARP cleavage product in MDA-MB-231 cells. The flow cytometry profiles of MDA-MB-231 and Hst578T cells treated with the hit compounds RU004 and RU007 were suggestive of the induction of apoptosis by these compounds. Cell cycle analysis by flow cytometry with propidium iodide staining revealed that both SQA and FXN induced G0-G1 arrest together with an increase in the apoptotic sub-G0 population, which agreed with previous reports in the literature. The molecular mechanism of action of SQA and FXN were further investigated by the identification of specific signal transducer molecules involved in mediating their anti-cancer activities. SQA was found to require the activity of numerous caspases, including caspase-3, -6, -8, -9, -10 and -13, for its cytotoxicity and was demonstrated to decrease the level of the antiapoptotic protein Bcl-2. On the other hand, FXN was shown to require caspase-1, -2, -3, -9 and - 10 for its toxicity. This, together with the ability to decrease the levels of Bcl-2, pointed to the involvement of the intrinsic pathway in particular in mediating the activity of FXN. The screening of algal compounds against non-cancerous breast epithelial cells carried out in this study, together with the investigation into their mechanisms of action, represent one of the few reports in which characterization of algal metabolites goes beyond the initial cytotoxicity assays. Finally, in order to assess the potential anti-cancer stem cell activity of the marine algal compounds, a subset of these was screened using a mammosphere assay technique developed in this study. The cancer stem cell (CSC) theory proposes that cancers arise from and are maintained by a specific subpopulation of cells able to undergo asymmetric cell division and termed CSCs. These CSCs are capable of anchorage-independent growth in serum-free culture conditions, such as those in the mammosphere assay. Using this assay, the novel halogenated monoterpene stereoisomers RU017 and RU018 were demonstrated to possess putative anti- CSC activity as evidenced by their ability to completely eliminate mammosphere formation in vitro. Furthermore, since RU017 and RU018 were non-toxic to both breast cancer and healthy breast cells, it appeared that the activity of the compounds was potentially specific to the CSCs. The results require further validation, but represent the first report of selective anti-CSC activity.
- Full Text:
- Authors: De la Mare, Jo-Anne
- Date: 2012
- Subjects: Breast -- Cancer , Stem cells -- Research , Chemotherapy , Algae -- Biotechnology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4143 , http://hdl.handle.net/10962/d1016250
- Description: Breast cancer remains the leading cause of cancer-related death in women worldwide. Furthermore, it has been demonstrated that the treatment-resistant ER-PR-HER2/neu- sub-type is more common among women of African descent, necessitating the search for novel chemotherapies for this form of the disease. The secondary metabolites produced by marine algae represent a rich source of structurally unique compounds with chemotherapeutic potential, particularly in South Africa, whose oceans allegedly host 15 % of the total number of species in the world. Indeed, a recent study reported the isolation of a range of novel compounds from South African red and brown algae of the Plocamium, Portiera and Sargassum genera which displayed cytotoxicity against oesophageal cancer cells in vitro. The molecular mechanisms mediating this toxicity were unknown, as was the effect of these and similar compounds on metastatic ER-PR-HER2/neu- breast cancer cell lines or breast cancer stem cells. The current study aimed to address these questions by screening a library of twenty-two novel marine algal compounds for the ability to inhibit MDA-MB-231 and Hs578T breast cancer cells, while having no adverse effects on non-cancerous MCF12A breast epithelial cells. While twelve of these were toxic in the micromolar range against breast cancer cells, only the polyhalogenated monoterpenes RU004 and RU007, and the tetraprenylated quinone sargaquinoic acid (SQA) were identified as hit compounds based on the criteria that their cytotoxicity was specific to breast cancer and not healthy breast cells in vitro. On the other hand, the halogenated monoterpene RU015 was found to be highly toxic to both breast cancer and non-cancerous breast cell lines, while the halogenated monoterpene stereoisomers RU017 and RU018 were non-toxic to either of these cell lines. The mode of action of RU004, RU007, RU015 and SQA, together with the previously characterized carotenoid fucoxanthin (FXN), was assessed in terms of the type of cell death induced and the effect on cell cycle distribution of these compounds. Flow cytometric analysis of the extent of Hoescht 33342 and propidium iodide staining along with PARP cleavage studies suggested that SQA induced apoptosis in MDA-MB-231 cells. On the other hand, the highly toxic compound RU015 appeared to induce necrosis as evidenced by 50 kDa PARP cleavage product in MDA-MB-231 cells. The flow cytometry profiles of MDA-MB-231 and Hst578T cells treated with the hit compounds RU004 and RU007 were suggestive of the induction of apoptosis by these compounds. Cell cycle analysis by flow cytometry with propidium iodide staining revealed that both SQA and FXN induced G0-G1 arrest together with an increase in the apoptotic sub-G0 population, which agreed with previous reports in the literature. The molecular mechanism of action of SQA and FXN were further investigated by the identification of specific signal transducer molecules involved in mediating their anti-cancer activities. SQA was found to require the activity of numerous caspases, including caspase-3, -6, -8, -9, -10 and -13, for its cytotoxicity and was demonstrated to decrease the level of the antiapoptotic protein Bcl-2. On the other hand, FXN was shown to require caspase-1, -2, -3, -9 and - 10 for its toxicity. This, together with the ability to decrease the levels of Bcl-2, pointed to the involvement of the intrinsic pathway in particular in mediating the activity of FXN. The screening of algal compounds against non-cancerous breast epithelial cells carried out in this study, together with the investigation into their mechanisms of action, represent one of the few reports in which characterization of algal metabolites goes beyond the initial cytotoxicity assays. Finally, in order to assess the potential anti-cancer stem cell activity of the marine algal compounds, a subset of these was screened using a mammosphere assay technique developed in this study. The cancer stem cell (CSC) theory proposes that cancers arise from and are maintained by a specific subpopulation of cells able to undergo asymmetric cell division and termed CSCs. These CSCs are capable of anchorage-independent growth in serum-free culture conditions, such as those in the mammosphere assay. Using this assay, the novel halogenated monoterpene stereoisomers RU017 and RU018 were demonstrated to possess putative anti- CSC activity as evidenced by their ability to completely eliminate mammosphere formation in vitro. Furthermore, since RU017 and RU018 were non-toxic to both breast cancer and healthy breast cells, it appeared that the activity of the compounds was potentially specific to the CSCs. The results require further validation, but represent the first report of selective anti-CSC activity.
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