Ethics in transdisciplinary research: reflections on the implications of ‘Science with Society’
- Cockburn, Jessica J, Cundill, Georgina
- Authors: Cockburn, Jessica J , Cundill, Georgina
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , book chapter
- Identifier: http://hdl.handle.net/10962/436187 , vital:73236 , ISBN 978-3-319-74721-7 , https://doi.org/10.1007/978-3-319-74721-7_6
- Description: Transdisciplinarity is a reflexive, participatory research approach that addresses societal problems by transcending the boundaries between science and society through knowledge co-production. Research ethics clearance procedures are of-ten out of step with such forms of engaged research. Through a case study of a transdisciplinary PhD, we share our experiences of the ethical challenges involved in research that takes place beyond the bounds of procedural ethics. Our research aims to co-produce knowledge on environmental stewardship. In this chapter we consider what strategies transdisciplinary scholars can employ to ensure they fulfil the requirements of ethical research in the absence of suitably aligned institutional processes, and what changes need to be made to research ethics clearance procedures to ensure they are able to account for transdisciplinary research.
- Full Text:
- Authors: Cockburn, Jessica J , Cundill, Georgina
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , book chapter
- Identifier: http://hdl.handle.net/10962/436187 , vital:73236 , ISBN 978-3-319-74721-7 , https://doi.org/10.1007/978-3-319-74721-7_6
- Description: Transdisciplinarity is a reflexive, participatory research approach that addresses societal problems by transcending the boundaries between science and society through knowledge co-production. Research ethics clearance procedures are of-ten out of step with such forms of engaged research. Through a case study of a transdisciplinary PhD, we share our experiences of the ethical challenges involved in research that takes place beyond the bounds of procedural ethics. Our research aims to co-produce knowledge on environmental stewardship. In this chapter we consider what strategies transdisciplinary scholars can employ to ensure they fulfil the requirements of ethical research in the absence of suitably aligned institutional processes, and what changes need to be made to research ethics clearance procedures to ensure they are able to account for transdisciplinary research.
- Full Text:
Eti zōsa phlox
- Authors: Van Schoor, David J
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/468457 , vital:77062 , https://www.jstor.org/stable/26945033?seq=1
- Description: Myths of the god typically recount a divine presence undiscerned or misdiagnosed by mortals, with tragic consequences. The vengeful Dionysus of Euripides’ Bacchae comes amongst humans disguised, ironically, to make them learn and recognise his divine identity and that they are in the presence of the truly, if not at first apparently, immortal. The kind of inference that it seems mortals are expected to rely upon in the vicinity of Dionysus in order to secure that all-important knowledge and recognition, is explored in this paper, which is offered as a contribution towards the development of a contemporary anthropology of Greek tragedy and its god. The anthropology of art and agency of Alfred Gell is mobilised in order to explore how different modes of inference are implicitly compared and evaluated in the drama and to suggest what this has to do with the nature of Dionysiac experience as represented by the tragic poet.
- Full Text:
- Authors: Van Schoor, David J
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/468457 , vital:77062 , https://www.jstor.org/stable/26945033?seq=1
- Description: Myths of the god typically recount a divine presence undiscerned or misdiagnosed by mortals, with tragic consequences. The vengeful Dionysus of Euripides’ Bacchae comes amongst humans disguised, ironically, to make them learn and recognise his divine identity and that they are in the presence of the truly, if not at first apparently, immortal. The kind of inference that it seems mortals are expected to rely upon in the vicinity of Dionysus in order to secure that all-important knowledge and recognition, is explored in this paper, which is offered as a contribution towards the development of a contemporary anthropology of Greek tragedy and its god. The anthropology of art and agency of Alfred Gell is mobilised in order to explore how different modes of inference are implicitly compared and evaluated in the drama and to suggest what this has to do with the nature of Dionysiac experience as represented by the tragic poet.
- Full Text:
Evaluating metabolism-induced toxicity using a non-hepatic cell line
- Authors: Weyers, Carli
- Date: 2018
- Subjects: Cytochrome P-450 , Drugs Metabolism , Drugs Design
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/61950 , vital:28087
- Description: The drug discovery pipeline is a complicated process taking roughly 15 years to complete, costing in excess of $1 billion per new chemical entity. It has been estimated that for every 100, 000 promising hit or lead compounds, only one will make it onto the market due to numerous drug candidates being discarded because of many complications. One such complication is metabolism-induced toxicity. Accordingly, an early understanding of the metabolism of any new chemical entity is becoming an integral part of the pipeline. In order to explore this, various methods have been developed including in silico and in vitro techniques. One such method involves performing cell viability assays on human liver cancer cell lines, which overexpress specific metabolic cytochrome P450 enzymes. If a toxic metabolite is produced it would result in reduced cell viability of the transformed cell line in comparison to a control. Since the liver is the primary site of metabolism in the human body, we were curious as to the extent to which background metabolism may play a role in the degree to which toxic metabolites would be produced in these cell lines. The aim of this project, therefore, was to establish if a non-hepatic cell-based system which overexpresses CYP3A4 could be used to detect the metabolism and any subsequent toxicity of compounds which have been reported to be substrates of the CYP450 enzyme. The HEK293 cell line was stably transfected with a plasmid vector for human CYP3A4 to create a model overexpression system for our metabolism studies. The activity of the enzyme was confirmed using the substrate, 7-benzyloxy-4-trifluoromethyl-coumarin. Subsequently, cytotoxicity testing was done on four known pharmaceuticals reported to generate toxic metabolites in hepatic cell-based assays. In silico metabolic predictions on the four known compounds were performed and compared to the results of published literature. Finally, the metabolism of one compound was studied using a combination of high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) in order to detect predicted metabolites. We observed no change in cellular toxicity nor did we detect the formation of metabolites, even though the overexpressed CYP3A4 enzyme was active. The results suggest that caution should be taken when interpreting the results of cell-based metabolism studies, and background metabolism may play a significant role in the data. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
- Authors: Weyers, Carli
- Date: 2018
- Subjects: Cytochrome P-450 , Drugs Metabolism , Drugs Design
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/61950 , vital:28087
- Description: The drug discovery pipeline is a complicated process taking roughly 15 years to complete, costing in excess of $1 billion per new chemical entity. It has been estimated that for every 100, 000 promising hit or lead compounds, only one will make it onto the market due to numerous drug candidates being discarded because of many complications. One such complication is metabolism-induced toxicity. Accordingly, an early understanding of the metabolism of any new chemical entity is becoming an integral part of the pipeline. In order to explore this, various methods have been developed including in silico and in vitro techniques. One such method involves performing cell viability assays on human liver cancer cell lines, which overexpress specific metabolic cytochrome P450 enzymes. If a toxic metabolite is produced it would result in reduced cell viability of the transformed cell line in comparison to a control. Since the liver is the primary site of metabolism in the human body, we were curious as to the extent to which background metabolism may play a role in the degree to which toxic metabolites would be produced in these cell lines. The aim of this project, therefore, was to establish if a non-hepatic cell-based system which overexpresses CYP3A4 could be used to detect the metabolism and any subsequent toxicity of compounds which have been reported to be substrates of the CYP450 enzyme. The HEK293 cell line was stably transfected with a plasmid vector for human CYP3A4 to create a model overexpression system for our metabolism studies. The activity of the enzyme was confirmed using the substrate, 7-benzyloxy-4-trifluoromethyl-coumarin. Subsequently, cytotoxicity testing was done on four known pharmaceuticals reported to generate toxic metabolites in hepatic cell-based assays. In silico metabolic predictions on the four known compounds were performed and compared to the results of published literature. Finally, the metabolism of one compound was studied using a combination of high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) in order to detect predicted metabolites. We observed no change in cellular toxicity nor did we detect the formation of metabolites, even though the overexpressed CYP3A4 enzyme was active. The results suggest that caution should be taken when interpreting the results of cell-based metabolism studies, and background metabolism may play a significant role in the data. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
Evaluating the effects of catch-and-release angling on Cape stumpnose Rhabdosargus holubi in a South African estuary
- Arkert, N K, Childs, Amber-Robyn, Parkinson, Matthew C, Winkler, Alexander C, Butler, Edward C, Mannheim, Samantha L, Potts, Warren M
- Authors: Arkert, N K , Childs, Amber-Robyn , Parkinson, Matthew C , Winkler, Alexander C , Butler, Edward C , Mannheim, Samantha L , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124439 , vital:35613 , https://doi.10.2989/1814232x.2018.1494041
- Description: Fisheries managers are increasingly promoting catch and release (C&R) as a means to manage recreational fish stocks. Several commonly used output regulations, including bag and size limits, require the mandatory release of captured fishes by anglers. In addition to mandatory C&R, conservation-conscious anglers have adopted voluntary C&R behaviour as a result of the noticeable declines in the populations of many fishery species and this behaviour is becoming increasingly popular among recreational anglers (Cooke et al. 2013a). The combination of mandatory and voluntary C&R behaviour is substantial, as Raby et al. (2014) estimated that 60% of fish captured in global recreational fisheries are released. In South Africa, Cowley et al. (2013) found that a large proportion (mean 74% [SD 7.3]) of the five most-dominant fishery species captured in the Sundays Estuary recreational fishery were released.
- Full Text:
- Authors: Arkert, N K , Childs, Amber-Robyn , Parkinson, Matthew C , Winkler, Alexander C , Butler, Edward C , Mannheim, Samantha L , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124439 , vital:35613 , https://doi.10.2989/1814232x.2018.1494041
- Description: Fisheries managers are increasingly promoting catch and release (C&R) as a means to manage recreational fish stocks. Several commonly used output regulations, including bag and size limits, require the mandatory release of captured fishes by anglers. In addition to mandatory C&R, conservation-conscious anglers have adopted voluntary C&R behaviour as a result of the noticeable declines in the populations of many fishery species and this behaviour is becoming increasingly popular among recreational anglers (Cooke et al. 2013a). The combination of mandatory and voluntary C&R behaviour is substantial, as Raby et al. (2014) estimated that 60% of fish captured in global recreational fisheries are released. In South Africa, Cowley et al. (2013) found that a large proportion (mean 74% [SD 7.3]) of the five most-dominant fishery species captured in the Sundays Estuary recreational fishery were released.
- Full Text:
Evaluating the efficacy of Hypogeococcus sp. as a biological control agent of the cactaceous weed Cereus jamacaru in South Africa
- Sutton, Guy F, Klein, Hildegard, Paterson, Iain D
- Authors: Sutton, Guy F , Klein, Hildegard , Paterson, Iain D
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/423350 , vital:72051 , xlink:href="https://doi.org/10.1007/s10526-018-9887-3"
- Description: We evaluated the efficacy of Hypogeococcus sp. (Hemiptera: Pseudococcidae) as a biological control agent of the cactaceous weed Cereus jamacaru De Candolle (Queen of the Night cactus) in South Africa. This weed has been described as being under complete biological control due to the action of Hypogeococcus sp., although no formal post-release evaluation had been conducted prior to this study. Biological control was associated with significant reductions in fruiting, plant survival and plant densities, while plant population age structures were negatively affected. Weed populations infected by Hypogeococcus sp. were typified by low or non-existent recruitment and are expected to diminish with time. Populations where Hypogeococcus sp. was absent displayed extensive recruitment, and are predicted to expand or self-replace, if left unchecked. These data indicate that Hypogeococcus sp. has a significant negative effect on C. jamacaru at the individual plant and population level, and given sufficient time provides complete biological control over this weed in South Africa.
- Full Text:
- Authors: Sutton, Guy F , Klein, Hildegard , Paterson, Iain D
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/423350 , vital:72051 , xlink:href="https://doi.org/10.1007/s10526-018-9887-3"
- Description: We evaluated the efficacy of Hypogeococcus sp. (Hemiptera: Pseudococcidae) as a biological control agent of the cactaceous weed Cereus jamacaru De Candolle (Queen of the Night cactus) in South Africa. This weed has been described as being under complete biological control due to the action of Hypogeococcus sp., although no formal post-release evaluation had been conducted prior to this study. Biological control was associated with significant reductions in fruiting, plant survival and plant densities, while plant population age structures were negatively affected. Weed populations infected by Hypogeococcus sp. were typified by low or non-existent recruitment and are expected to diminish with time. Populations where Hypogeococcus sp. was absent displayed extensive recruitment, and are predicted to expand or self-replace, if left unchecked. These data indicate that Hypogeococcus sp. has a significant negative effect on C. jamacaru at the individual plant and population level, and given sufficient time provides complete biological control over this weed in South Africa.
- Full Text:
Evaluation of the photophysicochemical properties and photodynamic therapy activity of nanoconjugates of zinc phthalocyanine linked to glutathione capped Au and Au3Ag1 nanoparticles
- Oluwole, David O, Manoto, Sello L, Malabi, Rudzani, Maphanga, Charles, Ombinda-Lemboumba, Saturnin, Mthunzi-Kufa, Patience, Nyokong, Tebello
- Authors: Oluwole, David O , Manoto, Sello L , Malabi, Rudzani , Maphanga, Charles , Ombinda-Lemboumba, Saturnin , Mthunzi-Kufa, Patience , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/237886 , vital:50563 , xlink:href="https://doi.org/10.1016/j.dyepig.2017.11.019"
- Description: We report on the synthesis of glutathione capped gold (AuNPs–GSH) and gold–silver (Au3Ag1NPs–GSH) nanoparticles and their covalent attachment to Zn monocarboxyphenoxy phthalocyanine (1) via amide bond formation. The photophysicochemical properties and photodynamic therapy (PDT) activity of the complex and its nanoconjugates were assessed. The conjugates afforded improved triplet and singlet oxygen quantum yield as well as PDT activity (except for 1-Au3Ag1NPs which afforded decreased activity) in comparison to complex 1.
- Full Text:
- Authors: Oluwole, David O , Manoto, Sello L , Malabi, Rudzani , Maphanga, Charles , Ombinda-Lemboumba, Saturnin , Mthunzi-Kufa, Patience , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/237886 , vital:50563 , xlink:href="https://doi.org/10.1016/j.dyepig.2017.11.019"
- Description: We report on the synthesis of glutathione capped gold (AuNPs–GSH) and gold–silver (Au3Ag1NPs–GSH) nanoparticles and their covalent attachment to Zn monocarboxyphenoxy phthalocyanine (1) via amide bond formation. The photophysicochemical properties and photodynamic therapy (PDT) activity of the complex and its nanoconjugates were assessed. The conjugates afforded improved triplet and singlet oxygen quantum yield as well as PDT activity (except for 1-Au3Ag1NPs which afforded decreased activity) in comparison to complex 1.
- Full Text:
Evidence for a new regime shift between floating and submerged invasive plant dominance in South Africa
- Strange, Emily F, Hill, Martin P, Coetzee, Julie A
- Authors: Strange, Emily F , Hill, Martin P , Coetzee, Julie A
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/423993 , vital:72114 , xlink:href="https://doi.org/10.1007/s10750-018-3506-2"
- Description: Classical biological control for the management of floating invasive plants has been highly successful in South Africa. However, restoring ecosystem services has been compromised by a new suite of submerged invasive plants. This study proposes that biological control of floating invasive macrophytes acts as a catalyst in a regime shift between floating and submerged invasive plant dominance. Regime shifts are large and sudden changes in the structure and functioning of ecosystems. The proposed shift is driven by the rapid decomposition of floating plants and subsequent increase in availability of nutrients and light. A mesocosm experiment explored the effect of biological control on floating Pistia stratiotes L. (Araceae) upon the growth of invasive submerged Egeria densa Planch. (Hydrocharitaceae), and native submerged plant species of the same family; Lagarosiphon major (Ridl.) Moss (Hydrocharitaceae). The results revealed a cascade effect of biological control of P. stratiotes on the availability of nitrogen, resulting in increased relative growth rates and invasive capacity for E. densa. In contrast, the native L. major could not compete with healthy or damaged P. stratiotes. These findings highlight the vulnerability of South African freshwater systems to submerged plant invasions and demonstrate the importance of a more holistic approach to invasive plant management.
- Full Text:
- Authors: Strange, Emily F , Hill, Martin P , Coetzee, Julie A
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/423993 , vital:72114 , xlink:href="https://doi.org/10.1007/s10750-018-3506-2"
- Description: Classical biological control for the management of floating invasive plants has been highly successful in South Africa. However, restoring ecosystem services has been compromised by a new suite of submerged invasive plants. This study proposes that biological control of floating invasive macrophytes acts as a catalyst in a regime shift between floating and submerged invasive plant dominance. Regime shifts are large and sudden changes in the structure and functioning of ecosystems. The proposed shift is driven by the rapid decomposition of floating plants and subsequent increase in availability of nutrients and light. A mesocosm experiment explored the effect of biological control on floating Pistia stratiotes L. (Araceae) upon the growth of invasive submerged Egeria densa Planch. (Hydrocharitaceae), and native submerged plant species of the same family; Lagarosiphon major (Ridl.) Moss (Hydrocharitaceae). The results revealed a cascade effect of biological control of P. stratiotes on the availability of nitrogen, resulting in increased relative growth rates and invasive capacity for E. densa. In contrast, the native L. major could not compete with healthy or damaged P. stratiotes. These findings highlight the vulnerability of South African freshwater systems to submerged plant invasions and demonstrate the importance of a more holistic approach to invasive plant management.
- Full Text:
Evidence for protandry in Polydactylus quadrifilis in the Kwanza Estuary, Angola, and its implications for local fisheries
- Butler, Edward C, Childs, Amber-Robyn, Winkler, Alexander C, Milner, Marianne V, Potts, Warren M
- Authors: Butler, Edward C , Childs, Amber-Robyn , Winkler, Alexander C , Milner, Marianne V , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124451 , vital:35614 , https://doi.10.1007/s10641-017-0699-6
- Description: A total of 141 Polydactylus quadrifilis were sampled from the Kwanza Estuary in Angola ranging in size from 436 to 1360 mm fork-length (FL). Of these, 124 were male, six intersex and 11 female. Female fish were significantly longer (mm, FL) and heavier (kg) than males and had significantly higher gonadosomatic indices (GSI’s) than those of males and intersex fish. Transitional (intersex) gonads were delimited, with testicular and ovarian regions separated by connective tissue. The first signs of ovarian tissue appeared on the outer ventral surface of the gonad. A second layer of ovarian tissue was first noticeable at either end of the initial ovarian region and developed back towards the centre of the ventral wall to form a luminal space. Early-stage oocytes were commonly found in the outer area of male regions and residual late-stage spermatids and spermatozoa were found in the luminal space of ovarian regions, suggesting a process of sex change from the outside inwards. A loss of male function was noted with increased ovarian prevalence. Based on this evidence it is suggested that P. quadrifilis in the Kwanza Estuary are protandrous. Owing to the reliance of P. quadrifilis on large highly fecund females for egg production, it is likely that they will be sensitive to fishing practices that target larger individuals within the population.
- Full Text:
- Authors: Butler, Edward C , Childs, Amber-Robyn , Winkler, Alexander C , Milner, Marianne V , Potts, Warren M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124451 , vital:35614 , https://doi.10.1007/s10641-017-0699-6
- Description: A total of 141 Polydactylus quadrifilis were sampled from the Kwanza Estuary in Angola ranging in size from 436 to 1360 mm fork-length (FL). Of these, 124 were male, six intersex and 11 female. Female fish were significantly longer (mm, FL) and heavier (kg) than males and had significantly higher gonadosomatic indices (GSI’s) than those of males and intersex fish. Transitional (intersex) gonads were delimited, with testicular and ovarian regions separated by connective tissue. The first signs of ovarian tissue appeared on the outer ventral surface of the gonad. A second layer of ovarian tissue was first noticeable at either end of the initial ovarian region and developed back towards the centre of the ventral wall to form a luminal space. Early-stage oocytes were commonly found in the outer area of male regions and residual late-stage spermatids and spermatozoa were found in the luminal space of ovarian regions, suggesting a process of sex change from the outside inwards. A loss of male function was noted with increased ovarian prevalence. Based on this evidence it is suggested that P. quadrifilis in the Kwanza Estuary are protandrous. Owing to the reliance of P. quadrifilis on large highly fecund females for egg production, it is likely that they will be sensitive to fishing practices that target larger individuals within the population.
- Full Text:
Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers:
- Lunga, Mayibongwe J, Chisango, Ruramai L, Weyers, Carli, Isaacs, Michelle, Taylor, Dale, Edkins, Adrienne L, Khanye, Setshaba D, Hoppe, Heinrich C, Veale, Clinton G L
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai L , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164389 , vital:41114 , DOI: 10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain.
- Full Text:
- Authors: Lunga, Mayibongwe J , Chisango, Ruramai L , Weyers, Carli , Isaacs, Michelle , Taylor, Dale , Edkins, Adrienne L , Khanye, Setshaba D , Hoppe, Heinrich C , Veale, Clinton G L
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/164389 , vital:41114 , DOI: 10.1002/cmdc.201800235
- Description: Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain.
- Full Text:
Exploration and design of a synchronous message passing framework for a CPU-NPU heterogeneous architecture
- Pennefather, Sean, Bradshaw, Karen L, Irwin, Barry V W
- Authors: Pennefather, Sean , Bradshaw, Karen L , Irwin, Barry V W
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429537 , vital:72620 , https://ieeexplore.ieee.org/abstract/document/8425384
- Description: In this paper we present the development of a framework for communication between an NPU (network processing unit) and CPU through synchronous message passing that is compliant with the synchronous communication events of the CSP formalisms. This framework is designed to be used for passing generic information between application components operating on both architectures and is intended to operate in conjunction with existing datapaths present on the NPU which in turn are responsible for network traffic transmission. An investigation of different message passing topologies is covered before the proposed message passing fabric is presented. As a proof of concept, an initial implementation of the fabric is developed and tested to determine its viability and correctness. Through testing it is shown that the implemented framework operates as intended. However, it is noted the throughput of the exploratory implementation is not considered suitable for high-performance applications and further evaluation is required.
- Full Text:
- Authors: Pennefather, Sean , Bradshaw, Karen L , Irwin, Barry V W
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429537 , vital:72620 , https://ieeexplore.ieee.org/abstract/document/8425384
- Description: In this paper we present the development of a framework for communication between an NPU (network processing unit) and CPU through synchronous message passing that is compliant with the synchronous communication events of the CSP formalisms. This framework is designed to be used for passing generic information between application components operating on both architectures and is intended to operate in conjunction with existing datapaths present on the NPU which in turn are responsible for network traffic transmission. An investigation of different message passing topologies is covered before the proposed message passing fabric is presented. As a proof of concept, an initial implementation of the fabric is developed and tested to determine its viability and correctness. Through testing it is shown that the implemented framework operates as intended. However, it is noted the throughput of the exploratory implementation is not considered suitable for high-performance applications and further evaluation is required.
- Full Text:
Exploration potential for copperbelt - style mineralisation in NW Province, Zambia; soil geochemistry as a targeting tool
- Authors: Mwamba, John
- Date: 2018
- Subjects: Mineralogy -- Zambia -- Copperbelt Province , River sediments -- Zambia -- Copperbelt Province , Soils -- Sampling -- Zambia -- Copperbelt Province , Prospecting -- Geophysical methods , Landsat satellites , Lufilian fold belt
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62538 , vital:28204
- Description: The NW Province of Zambia is fast becoming a major significant mining district challenging to usurp the economic importance of the traditional Copperbelt Province that has been mined for nearly a century. With latest developments at Kansanshi, Lumwana and Kalumbila mines exploration efforts in the search for Copperbelt style mineralisation have doubled up in the province in recent months. Traditional methods of stream sediment and soil sampling, geophysics, aerial photo and Landsat imagery interpretations have been employed in exploration targeting campaigns. This thesis asks the question: Can we use the Copperbelt geochemical footprint as a proxy to finding new copper deposits in NW Province? The challenge faced in such studies is that few geochemical datasets for old mines exist and the little that does is proprietary information. In some mines this dataset is entirely nonexistent - at least not in the public domain. Attempting to run orientation geochemical trials on such mines is not feasible at present due to maturity of mining and the levels of contamination of the natural environment that have occurred over several decades of mining. However, in tackling this question few Copperbelt geochemical datasets from Baluba, Nkana, Mimbula, Nchanga, Bwana Mkubwa, Mufulira West and Lufubu North were used. The findings presented in this report are that for Copperbelt style mineralisation Cu/Co, Cu/Ni, Cu/Ag ratios in soil geochemistry data should be in the ranges of 0.25 to 0.48 provided geochemical studies occurred in residual soils. These ratios hold true for sediment hosted copper-cobalt mineralisation hosted at various stratigraphic levels within the Roan Group or in upper levels elsewhere on the Central African Copperbelt. Geochemical dataset for the study areas presented in this report show that the soil geochemistry footprint in the province is not dissimilar to the soil geochemistry footprint of the traditional Copperbelt Province. This means there is great potential for finding Copperbelt style mineralisation in the province and other styles of mineralisation in which copper is associated with cobalt, lead, zinc, nickel, vanadium and molybdenum. The areas of study also possess requisite geological factors that are conducive to hosting Copperbelt style deposits. These factors include: favourable structural traps with similar trends to existing mines in the province, geophysical characteristics comparable to other deposits in the province, right geological package known to host multi-type deposits in the Katangan stratigraphic sequence, and similar geochemical footprints observed on other deposits within the Lufilian fold belt. For this reason, geochemical dataset must not be looked at in isolation but should be treated in considerations with other factors and geological environment.
- Full Text:
- Authors: Mwamba, John
- Date: 2018
- Subjects: Mineralogy -- Zambia -- Copperbelt Province , River sediments -- Zambia -- Copperbelt Province , Soils -- Sampling -- Zambia -- Copperbelt Province , Prospecting -- Geophysical methods , Landsat satellites , Lufilian fold belt
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62538 , vital:28204
- Description: The NW Province of Zambia is fast becoming a major significant mining district challenging to usurp the economic importance of the traditional Copperbelt Province that has been mined for nearly a century. With latest developments at Kansanshi, Lumwana and Kalumbila mines exploration efforts in the search for Copperbelt style mineralisation have doubled up in the province in recent months. Traditional methods of stream sediment and soil sampling, geophysics, aerial photo and Landsat imagery interpretations have been employed in exploration targeting campaigns. This thesis asks the question: Can we use the Copperbelt geochemical footprint as a proxy to finding new copper deposits in NW Province? The challenge faced in such studies is that few geochemical datasets for old mines exist and the little that does is proprietary information. In some mines this dataset is entirely nonexistent - at least not in the public domain. Attempting to run orientation geochemical trials on such mines is not feasible at present due to maturity of mining and the levels of contamination of the natural environment that have occurred over several decades of mining. However, in tackling this question few Copperbelt geochemical datasets from Baluba, Nkana, Mimbula, Nchanga, Bwana Mkubwa, Mufulira West and Lufubu North were used. The findings presented in this report are that for Copperbelt style mineralisation Cu/Co, Cu/Ni, Cu/Ag ratios in soil geochemistry data should be in the ranges of 0.25 to 0.48 provided geochemical studies occurred in residual soils. These ratios hold true for sediment hosted copper-cobalt mineralisation hosted at various stratigraphic levels within the Roan Group or in upper levels elsewhere on the Central African Copperbelt. Geochemical dataset for the study areas presented in this report show that the soil geochemistry footprint in the province is not dissimilar to the soil geochemistry footprint of the traditional Copperbelt Province. This means there is great potential for finding Copperbelt style mineralisation in the province and other styles of mineralisation in which copper is associated with cobalt, lead, zinc, nickel, vanadium and molybdenum. The areas of study also possess requisite geological factors that are conducive to hosting Copperbelt style deposits. These factors include: favourable structural traps with similar trends to existing mines in the province, geophysical characteristics comparable to other deposits in the province, right geological package known to host multi-type deposits in the Katangan stratigraphic sequence, and similar geochemical footprints observed on other deposits within the Lufilian fold belt. For this reason, geochemical dataset must not be looked at in isolation but should be treated in considerations with other factors and geological environment.
- Full Text:
Exploring grade 3 teachers’ resistance to ‘take up’progressive mathematics teaching roles
- Graven, Mellony, Westaway, Lise
- Authors: Graven, Mellony , Westaway, Lise
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/69700 , vital:29568 , https://DOI: 10.1007/s13394-018-0237-7
- Description: This article addresses the question: Why teachers of mathematics have yet to ‘take up’ progressive roles? Drawing on the philosophy of critical realism and its methodological equivalent, social realism, we analyse interview and observation data of four grade 3 teachers, with the view to identifying the mechanisms conditioning the expression of teachers’ identities. In so doing, we show how post-apartheid changes in systemic roles of teachers create contradictory tensions for teachers as these bring their own mathematical learning and teaching experiences into contradiction with the new post-apartheid roles they are mandated to enact. We examine how this contradiction, together with beliefs about mathematics, pedagogy and learners, is expressed in the teaching of grade 3 mathematics. We maintain that the complementarity between teachers’ beliefs and old systemic roles provides an explanation for why teachers of grade 3 mathematics have yet to ‘take-up’ progressive roles. The implications point to the need for teacher development that creates enablers that lead to changes in classroom practices that align with policy-designated, progressive roles in teaching mathematics.
- Full Text:
- Authors: Graven, Mellony , Westaway, Lise
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/69700 , vital:29568 , https://DOI: 10.1007/s13394-018-0237-7
- Description: This article addresses the question: Why teachers of mathematics have yet to ‘take up’ progressive roles? Drawing on the philosophy of critical realism and its methodological equivalent, social realism, we analyse interview and observation data of four grade 3 teachers, with the view to identifying the mechanisms conditioning the expression of teachers’ identities. In so doing, we show how post-apartheid changes in systemic roles of teachers create contradictory tensions for teachers as these bring their own mathematical learning and teaching experiences into contradiction with the new post-apartheid roles they are mandated to enact. We examine how this contradiction, together with beliefs about mathematics, pedagogy and learners, is expressed in the teaching of grade 3 mathematics. We maintain that the complementarity between teachers’ beliefs and old systemic roles provides an explanation for why teachers of grade 3 mathematics have yet to ‘take-up’ progressive roles. The implications point to the need for teacher development that creates enablers that lead to changes in classroom practices that align with policy-designated, progressive roles in teaching mathematics.
- Full Text:
Exploring learning networks for homestead food gardening and smallholder farming
- Authors: Lotz-Sisitka, Heila
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/182775 , vital:43873 , xlink:href="https://hdl.handle.net/10520/EJC-f09c3866c "
- Description: The Water Research Commission (WRC) is well known for its high quality knowledge products. The Water Utilisation in Agriculture (WUA) section has, over the years, produced valuable knowledge to guide the harvesting and conservation of rainwater to improve agricultural productivity among smallholder crop farmers and household food producers. This knowledge is useful for especially the many women farmers around the country growing crops to feed their families, and whenever possible selling excess to generate some income. However, one of the problems experienced in the field is that this knowledge does not always reach the intended audience. This is the problem that the Amanzi [Water] for Food project was engaged with.
- Full Text:
- Authors: Lotz-Sisitka, Heila
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/182775 , vital:43873 , xlink:href="https://hdl.handle.net/10520/EJC-f09c3866c "
- Description: The Water Research Commission (WRC) is well known for its high quality knowledge products. The Water Utilisation in Agriculture (WUA) section has, over the years, produced valuable knowledge to guide the harvesting and conservation of rainwater to improve agricultural productivity among smallholder crop farmers and household food producers. This knowledge is useful for especially the many women farmers around the country growing crops to feed their families, and whenever possible selling excess to generate some income. However, one of the problems experienced in the field is that this knowledge does not always reach the intended audience. This is the problem that the Amanzi [Water] for Food project was engaged with.
- Full Text:
Exploring molecular insights into the interaction mechanism of cholesterol derivatives with the Mce4A: A combined spectroscopic and molecular dynamic simulation studies
- Khan, Shagufta, Khan, Faez I, Khan, Parvez, Hasan, Gulam M, Lobb, Kevin A, Islam, Asimul, Ahmad, Faizan, Hassan, M Imtaiyaz
- Authors: Khan, Shagufta , Khan, Faez I , Khan, Parvez , Hasan, Gulam M , Lobb, Kevin A , Islam, Asimul , Ahmad, Faizan , Hassan, M Imtaiyaz
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447041 , vital:74579 , xlink:href="https://doi.org/10.1016/j.ijbiomac.2017.12.160"
- Description: Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns. In silico studies were further validated by fluorescence-binding studies to calculate actual binding affinity and number of binding site(s). The non-toxicity of all ligands was confirmed on human monocytic cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism of interaction of Mce4A to cholesterol derivatives, which may be further exploited to design potential and specific inhibitors to ameliorate the Mycobacterium pathogenesis.
- Full Text:
- Authors: Khan, Shagufta , Khan, Faez I , Khan, Parvez , Hasan, Gulam M , Lobb, Kevin A , Islam, Asimul , Ahmad, Faizan , Hassan, M Imtaiyaz
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447041 , vital:74579 , xlink:href="https://doi.org/10.1016/j.ijbiomac.2017.12.160"
- Description: Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns. In silico studies were further validated by fluorescence-binding studies to calculate actual binding affinity and number of binding site(s). The non-toxicity of all ligands was confirmed on human monocytic cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism of interaction of Mce4A to cholesterol derivatives, which may be further exploited to design potential and specific inhibitors to ameliorate the Mycobacterium pathogenesis.
- Full Text:
Exploring para-thiophenols to expand the SAR of antimalarial 3-indolylethanones
- Authors: Chisango, Ruramai Lissa
- Date: 2018
- Subjects: Antimalarials , Malaria Chemotherapy , Thiols , Plasmodium falciparum , Blood-brain barrier
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63515 , vital:28428
- Description: According to the WHO, malaria is responsible for over half a million deaths annually especially in populations from disadvantaged settings. Although there has been a documented improvement in the mortality rates, malaria has proved to be a global emergency. Mostly affecting the poor population, this disease is perpetuating a vicious cycle of poverty in the developing world as current preventive measures are not adequate unless adopted in addition to effective treatment. However, there has been a worldwide increase in resistance to available treatment which presents a need for novel, affordable treatment. A study conducted in our laboratory identified two hit thiophenol containing compounds 2.24 and 2.25. These molecules provided initial insight into the SAR and potential pharmacophore of this class of compounds. We decided to further explore these compounds by making bioisosteric replacements to optimize the structure as we monitor the effect of these modifications on the anti-plasmodial activity. The synthetic pathway to form the target compounds of our study comprised of three steps which were initiated by the Friedel-Crafts acetylation of the indoles resulting in compounds 3.5 - 3.7. A bromination step followed which yielded the -bromo ketones (3.8 - 3.11). Some of the thiophenols (3.14 and 3.16) were not readily available in our laboratory and so were synthesized for the final synthetic step. This step involved the nucleophilic displacement of the -bromine to generate the -aryl substituted 3-indolylethanones (3.17 - 3.27). The thioethers displayed improved antimalarial activity from 2.24 and 2.25 against the chloroquine sensitive 3D7 Plasmodium falciparum strain. In addition, these compounds were non-toxic against HeLa cells which indicated this potential novel class of antimalarials is selective for the malaria parasite as hypothesized in the previous study conducted in our laboratory. In an attempt to predict the bioavailability of some of our compounds, in silico studies were conducted revealing that these compounds could be passively absorbed by the gastrointestinal tract, a positive result for bioavailability purposes. However, results from these studies indicate that modifications of these compounds would be necessary to allow for permeation through the blood brain barrier (BBB) for instances when the patient has cerebral malaria. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
- Authors: Chisango, Ruramai Lissa
- Date: 2018
- Subjects: Antimalarials , Malaria Chemotherapy , Thiols , Plasmodium falciparum , Blood-brain barrier
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63515 , vital:28428
- Description: According to the WHO, malaria is responsible for over half a million deaths annually especially in populations from disadvantaged settings. Although there has been a documented improvement in the mortality rates, malaria has proved to be a global emergency. Mostly affecting the poor population, this disease is perpetuating a vicious cycle of poverty in the developing world as current preventive measures are not adequate unless adopted in addition to effective treatment. However, there has been a worldwide increase in resistance to available treatment which presents a need for novel, affordable treatment. A study conducted in our laboratory identified two hit thiophenol containing compounds 2.24 and 2.25. These molecules provided initial insight into the SAR and potential pharmacophore of this class of compounds. We decided to further explore these compounds by making bioisosteric replacements to optimize the structure as we monitor the effect of these modifications on the anti-plasmodial activity. The synthetic pathway to form the target compounds of our study comprised of three steps which were initiated by the Friedel-Crafts acetylation of the indoles resulting in compounds 3.5 - 3.7. A bromination step followed which yielded the -bromo ketones (3.8 - 3.11). Some of the thiophenols (3.14 and 3.16) were not readily available in our laboratory and so were synthesized for the final synthetic step. This step involved the nucleophilic displacement of the -bromine to generate the -aryl substituted 3-indolylethanones (3.17 - 3.27). The thioethers displayed improved antimalarial activity from 2.24 and 2.25 against the chloroquine sensitive 3D7 Plasmodium falciparum strain. In addition, these compounds were non-toxic against HeLa cells which indicated this potential novel class of antimalarials is selective for the malaria parasite as hypothesized in the previous study conducted in our laboratory. In an attempt to predict the bioavailability of some of our compounds, in silico studies were conducted revealing that these compounds could be passively absorbed by the gastrointestinal tract, a positive result for bioavailability purposes. However, results from these studies indicate that modifications of these compounds would be necessary to allow for permeation through the blood brain barrier (BBB) for instances when the patient has cerebral malaria. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
Exploring the adaptability and applicability of military mental skills training for South African paramedics
- Authors: Minnie, Chantel
- Date: 2018
- Subjects: Allied health personnel -- South Africa , Allied health personnel -- Mental health -- South Africa , Post-traumatic stress disorder -- South Africa , Emergency medical services -- Psychological aspects
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/61580 , vital:28039
- Description: Paramedics in South Africa are among the best in the world (MacFarlane, van Loggerenberg, & Kloeck, 2005). However, the domain of pre-hospital emergency care is fraught with challenges and paramedics face numerous personal and professional difficulties. South Africa, with its diverse patient population and challenges, cannot afford to undermine the importance of supportive interventions for emergency medical technicians. Whilst there is a growing body of literature examining the effectiveness of mental skills training in the sporting domain (Gould, Dieffenbach, & Moffett, 2002; Landers & Boutcher, 1998), there is a lack of research on mental skills training as it pertains to paramedics. It is argued here, that the use of mental skills training derived from sporting science and adapted for the military, provides the most comparable context in relation to the paramedic industry. This study thus aims to explore the adaptability and applicability of military mental skills training techniques in the context of South African paramedics. This study made use of an exploratory, qualitative case study design, focusing on participatory research strategies. The analysis revealed that various aspects of existing military mental skills models can be adapted to be of relevance in the emergency medical services field as it related to three paramedic participants. A prominent emerging theme was that of PTSD among paramedics, and it was an area that the participants felt should receive much more attention, research and intervention.
- Full Text:
- Authors: Minnie, Chantel
- Date: 2018
- Subjects: Allied health personnel -- South Africa , Allied health personnel -- Mental health -- South Africa , Post-traumatic stress disorder -- South Africa , Emergency medical services -- Psychological aspects
- Language: English
- Type: text , Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/61580 , vital:28039
- Description: Paramedics in South Africa are among the best in the world (MacFarlane, van Loggerenberg, & Kloeck, 2005). However, the domain of pre-hospital emergency care is fraught with challenges and paramedics face numerous personal and professional difficulties. South Africa, with its diverse patient population and challenges, cannot afford to undermine the importance of supportive interventions for emergency medical technicians. Whilst there is a growing body of literature examining the effectiveness of mental skills training in the sporting domain (Gould, Dieffenbach, & Moffett, 2002; Landers & Boutcher, 1998), there is a lack of research on mental skills training as it pertains to paramedics. It is argued here, that the use of mental skills training derived from sporting science and adapted for the military, provides the most comparable context in relation to the paramedic industry. This study thus aims to explore the adaptability and applicability of military mental skills training techniques in the context of South African paramedics. This study made use of an exploratory, qualitative case study design, focusing on participatory research strategies. The analysis revealed that various aspects of existing military mental skills models can be adapted to be of relevance in the emergency medical services field as it related to three paramedic participants. A prominent emerging theme was that of PTSD among paramedics, and it was an area that the participants felt should receive much more attention, research and intervention.
- Full Text:
Exploring the potential of developmental work research and change laboratory to support sustainability transformations: a case study of organic agriculture in Zimbabwe
- Mukute, Mutizwa, Mudokwani, Kuda, McAllistair, Georgina, Nyikahadzoi, Kefasi
- Authors: Mukute, Mutizwa , Mudokwani, Kuda , McAllistair, Georgina , Nyikahadzoi, Kefasi
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/392119 , vital:68723 , xlink:href="https://doi.org/10.1080/10749039.2018.1451542"
- Description: This paper explores the emergence of transgressive learning in CHAT-informed development work research in a networked organic agriculture case study in Zimbabwe, based on intervention research involving district organic associations tackling interconnected issues of climate change, water, food security and solidarity. The study established that We change laboratories can be used to support transgressive learning through: confronting unproductive local norms; collective reframing of problematic issues; stimulating expansive learning and sustainability transformations in minds, relationships and landscapes across time. The study also confirms the need for fourth generation CHAT to address the complex social-ecological problems of today.
- Full Text:
- Authors: Mukute, Mutizwa , Mudokwani, Kuda , McAllistair, Georgina , Nyikahadzoi, Kefasi
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/392119 , vital:68723 , xlink:href="https://doi.org/10.1080/10749039.2018.1451542"
- Description: This paper explores the emergence of transgressive learning in CHAT-informed development work research in a networked organic agriculture case study in Zimbabwe, based on intervention research involving district organic associations tackling interconnected issues of climate change, water, food security and solidarity. The study established that We change laboratories can be used to support transgressive learning through: confronting unproductive local norms; collective reframing of problematic issues; stimulating expansive learning and sustainability transformations in minds, relationships and landscapes across time. The study also confirms the need for fourth generation CHAT to address the complex social-ecological problems of today.
- Full Text:
Exploring the potential of imines as antiprotozoan agents with focus on t. Brucei and p. Falciparum
- Authors: Oluwafemi, Kola Augustus
- Date: 2018
- Subjects: Protozoa , Parasites , Imines , Nuclear magnetic resonance , HeLa cells , Plasmodium falciparum , Trypanosoma brucei , Isomerism
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/62235 , vital:28145 , DOI 10.21504/10962/62235
- Description: This work focuses on the design, synthesis and evaluation of imine-containing heterocyclic and acyclic compounds with special focus on their bioactivity against parasitic protozoans (P. falciparum and T. brucei) - given the context of drug resistance in the treatment of malaria and Human African sleeping sickness and the fact that several bioactive organic compounds have been reported to possess the imino group. Starting from 2-aminopyridine, novel #-alkylated-5-bromo-7-azabenzimidazoles and substituted 5-bromo-1-(carbamoylmethy)-7-azabenzimidazole derivatives were prepared, and their bioactivity against parasitic protozoans was assessed. NMR spectra of the substituted 5- bromo-1-(carbamoylmethy)-7-azabenzimidazole derivatives exhibited rotational isomerism, and a dynamic NMR study was used in the estimation of the rate constants and the free- energies of activation for rotation. The free-energy differences between the two rotamers were determined and the more stable conformations were predicted. Novel 2-phenyl-7-azabenzimidazoles were also synthesised from 2-aminopyridine. A convenient method for the regioselective formylation of 2,3-diaminopyridines into 2-amino- 7-(benzylimino)pyridine analogues of 2-phenyl-7-azabenzimidazole was developed, and some of the resulting imino derivatives were hydrogenated to verify the importance of the imino moiety for bioactivity. The 2-phenyl-7-azabenzimidazoles and the 2-amino-7- (benzylimino)pyridine analogues were screened for their anti-protozoal activity and their cytotoxicity level was determined against the HeLa cell line. In order to validate the importance of the pyridine moiety, novel #-(phenyl)-2- hydroxybenzylimines, #-(benzyl)-2-hydroxybenzylimines and (±)-trans-1,2-bis[2- hydroxybenzylimino]cyclohexanes were also synthesized and screened for activity against the parasitic protozoans and for cytotoxicity against the HeLa cell line. The biological assay results indicated that these compounds are not significantly cytotoxic and a good number of them show potential as lead compounds for the development of new malaria and trypanosomiasis drugs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2018
- Full Text:
- Authors: Oluwafemi, Kola Augustus
- Date: 2018
- Subjects: Protozoa , Parasites , Imines , Nuclear magnetic resonance , HeLa cells , Plasmodium falciparum , Trypanosoma brucei , Isomerism
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/62235 , vital:28145 , DOI 10.21504/10962/62235
- Description: This work focuses on the design, synthesis and evaluation of imine-containing heterocyclic and acyclic compounds with special focus on their bioactivity against parasitic protozoans (P. falciparum and T. brucei) - given the context of drug resistance in the treatment of malaria and Human African sleeping sickness and the fact that several bioactive organic compounds have been reported to possess the imino group. Starting from 2-aminopyridine, novel #-alkylated-5-bromo-7-azabenzimidazoles and substituted 5-bromo-1-(carbamoylmethy)-7-azabenzimidazole derivatives were prepared, and their bioactivity against parasitic protozoans was assessed. NMR spectra of the substituted 5- bromo-1-(carbamoylmethy)-7-azabenzimidazole derivatives exhibited rotational isomerism, and a dynamic NMR study was used in the estimation of the rate constants and the free- energies of activation for rotation. The free-energy differences between the two rotamers were determined and the more stable conformations were predicted. Novel 2-phenyl-7-azabenzimidazoles were also synthesised from 2-aminopyridine. A convenient method for the regioselective formylation of 2,3-diaminopyridines into 2-amino- 7-(benzylimino)pyridine analogues of 2-phenyl-7-azabenzimidazole was developed, and some of the resulting imino derivatives were hydrogenated to verify the importance of the imino moiety for bioactivity. The 2-phenyl-7-azabenzimidazoles and the 2-amino-7- (benzylimino)pyridine analogues were screened for their anti-protozoal activity and their cytotoxicity level was determined against the HeLa cell line. In order to validate the importance of the pyridine moiety, novel #-(phenyl)-2- hydroxybenzylimines, #-(benzyl)-2-hydroxybenzylimines and (±)-trans-1,2-bis[2- hydroxybenzylimino]cyclohexanes were also synthesized and screened for activity against the parasitic protozoans and for cytotoxicity against the HeLa cell line. The biological assay results indicated that these compounds are not significantly cytotoxic and a good number of them show potential as lead compounds for the development of new malaria and trypanosomiasis drugs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2018
- Full Text:
Extended and Continuous Decline in Effective Population Size Results in Low Genomic Diversity in the World’s Rarest Hyena Species, the Brown Hyena
- Westbury, Michael V, Hartmann, Stefanie, Barlow, Axel, Wiesel, Ingrid, Leo, Viyanna, Welch, Rebecca J, Parker, Daniel M, Sicks, Florian, Ludwig, Arne, Dalén, Love, Hofreiter, Michael
- Authors: Westbury, Michael V , Hartmann, Stefanie , Barlow, Axel , Wiesel, Ingrid , Leo, Viyanna , Welch, Rebecca J , Parker, Daniel M , Sicks, Florian , Ludwig, Arne , Dalén, Love , Hofreiter, Michael
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124482 , vital:35616 , https://doi.org/10.1093/molbev/msy037
- Description: Hyenas (family Hyaenidae), as the sister group to cats (family Felidae), represent a deeply diverging branch within the cat-like carnivores (Feliformia). With an estimated population size of < 10,000 individuals worldwide, the brown hyena (Parahyaena brunnea) represents the rarest of the four extant hyena species and has been listed as Near Threatened by the IUCN. Here, we report a high-coverage genome from a captive bred brown hyena and both mitochondrial and low coverage nuclear genomes of 14 wild-caught brown hyena individuals from across southern Africa.We find that brown hyena harbor extremely low genetic diversity on both the mitochondrial and nuclear level, most likely resulting from a continuous and ongoing decline in effective population size that started_1Ma and dramatically accelerated towards the end of the Pleistocene. Despite the strikingly low genetic diversity, we find no evidence of inbreeding within the captive bred individual and reveal phylogeographic structure, suggesting the existence of several potential subpopulations within the species.
- Full Text:
- Authors: Westbury, Michael V , Hartmann, Stefanie , Barlow, Axel , Wiesel, Ingrid , Leo, Viyanna , Welch, Rebecca J , Parker, Daniel M , Sicks, Florian , Ludwig, Arne , Dalén, Love , Hofreiter, Michael
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124482 , vital:35616 , https://doi.org/10.1093/molbev/msy037
- Description: Hyenas (family Hyaenidae), as the sister group to cats (family Felidae), represent a deeply diverging branch within the cat-like carnivores (Feliformia). With an estimated population size of < 10,000 individuals worldwide, the brown hyena (Parahyaena brunnea) represents the rarest of the four extant hyena species and has been listed as Near Threatened by the IUCN. Here, we report a high-coverage genome from a captive bred brown hyena and both mitochondrial and low coverage nuclear genomes of 14 wild-caught brown hyena individuals from across southern Africa.We find that brown hyena harbor extremely low genetic diversity on both the mitochondrial and nuclear level, most likely resulting from a continuous and ongoing decline in effective population size that started_1Ma and dramatically accelerated towards the end of the Pleistocene. Despite the strikingly low genetic diversity, we find no evidence of inbreeding within the captive bred individual and reveal phylogeographic structure, suggesting the existence of several potential subpopulations within the species.
- Full Text:
Extending functionality and knowledge transfer of the Water Quality Systems Assessment Model
- Slaughter, Andrew R, Gwapedza, David, Mantel, Sukhmani K, Hughes, Denis A, Griffin, Neil J
- Authors: Slaughter, Andrew R , Gwapedza, David , Mantel, Sukhmani K , Hughes, Denis A , Griffin, Neil J
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , report
- Identifier: http://hdl.handle.net/10962/438115 , vital:73436 , ISBN 978-0-6392-0059-0 , https://wrcwebsite.azurewebsites.net/wp-content/uploads/mdocs/2448_final.pdf
- Description: This report has been generated by the Water Research Commission (WRC) funded project Developing Climate Change Adaptation Measures and Decision-Support System for Selected South African Water Boards (Project No. K5/2018).
- Full Text:
- Authors: Slaughter, Andrew R , Gwapedza, David , Mantel, Sukhmani K , Hughes, Denis A , Griffin, Neil J
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , report
- Identifier: http://hdl.handle.net/10962/438115 , vital:73436 , ISBN 978-0-6392-0059-0 , https://wrcwebsite.azurewebsites.net/wp-content/uploads/mdocs/2448_final.pdf
- Description: This report has been generated by the Water Research Commission (WRC) funded project Developing Climate Change Adaptation Measures and Decision-Support System for Selected South African Water Boards (Project No. K5/2018).
- Full Text: