Mechanistic analysis of two cytotoxic thiazolidinones as novel inhibitors of Triple-Negative Breast Cancer
- Authors: Vukea, Nyeleti
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365734 , vital:65780
- Description: Thesis embargoes. Expected release date early 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Vukea, Nyeleti
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365734 , vital:65780
- Description: Thesis embargoes. Expected release date early 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-10-14
Regulation of Oct4 expression during cell stress
- Authors: Samson, William John
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365712 , vital:65778
- Description: Thesis embargoed. Expected release date early 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Samson, William John
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365712 , vital:65778
- Description: Thesis embargoed. Expected release date early 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-10-14
Socio-historical analysis of organisational change: a case study of Zimbabwe Posts (Zimpost), 2010–2020
- Kambarami-Zengeni, Faith Chipo
- Authors: Kambarami-Zengeni, Faith Chipo
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422518 , vital:71954 , DOI 10.21504/10962/422518
- Description: Postal organisations play an important role in the provision of basic communication services. In Zimbabwe, post offices have a large physical distribution network of over 240 post offices country-wide to make communication services accessible to the populace. However, e-substitution has threatened mail business significantly. Postal operators globally are experiencing declining mail volumes in the face of advanced information and communication technologies. The overall goal of this thesis was to undertake a socio-historical analysis of organisational change at ZimPost using Taylorism, Fordism and post-Fordism as broad ideal types to explain how industry evolves in different phases of capitalism. National politics and economics play an integral role in how Taylorism, Fordism and post-Fordism assumed at ZimPost. Studies on these broad organising types have mainly focused on private sector organisations. However, this thesis argues that these analytical paradigms are also valid in public sector organisations, but they will unfold differently given the context in which change is experienced. Using a qualitative approach, the study established that the 1980s and 1990s can best be described as the ‘golden years’ of postal services in Zimbabwe, characterised by mass production and mass consumption of postal products and services. At that time the Posts and Telecommunications Corporation enjoyed a monopoly of postal services in the country. The stable market share, competitive salaries for postal workers, increased unionisation and a fairly stable economy enabled a Fordist regime of accumulation to develop. The cycle broke down when the mode of regulation was weakened by national economic and political changes towards the late 1990s. PTC started to experience a decline in the consumption of postal products. The decline was also attributed to increased competition from smaller private courier operators that could provide specialised services to a market with changing needs. With increased competition, the advancement of information, and communication technologies, mail volumes dwindled. This period can best be described as the crisis of Fordism at ZimPost. In the year 2000, the government unbundled the posts and telecommunications corporation to create four companies including Zimbabwe Posts. This was perceived as one of the most radical organisational changes in the history of postal services in Zimbabwe. More organisational changes took place at ZimPost that can best be described as characteristics of post-Fordism. These changes were attempts by ZimPost to remain relevant in light of the economic, political and technological changes taking place in the country. The postal operator introduced customised products in the form of agency services, supported by increased use of information and communication technologies in the post office. Organisational changes at ZimPost were shaped mainly by the economic and political environment in which they took place. Organisational change is complex, changes do not follow a linear pattern, they are processual. , Thesis (PhD) -- Faculty of Humanities, Sociology, 2023
- Full Text:
- Date Issued: 2022-10-14
- Authors: Kambarami-Zengeni, Faith Chipo
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422518 , vital:71954 , DOI 10.21504/10962/422518
- Description: Postal organisations play an important role in the provision of basic communication services. In Zimbabwe, post offices have a large physical distribution network of over 240 post offices country-wide to make communication services accessible to the populace. However, e-substitution has threatened mail business significantly. Postal operators globally are experiencing declining mail volumes in the face of advanced information and communication technologies. The overall goal of this thesis was to undertake a socio-historical analysis of organisational change at ZimPost using Taylorism, Fordism and post-Fordism as broad ideal types to explain how industry evolves in different phases of capitalism. National politics and economics play an integral role in how Taylorism, Fordism and post-Fordism assumed at ZimPost. Studies on these broad organising types have mainly focused on private sector organisations. However, this thesis argues that these analytical paradigms are also valid in public sector organisations, but they will unfold differently given the context in which change is experienced. Using a qualitative approach, the study established that the 1980s and 1990s can best be described as the ‘golden years’ of postal services in Zimbabwe, characterised by mass production and mass consumption of postal products and services. At that time the Posts and Telecommunications Corporation enjoyed a monopoly of postal services in the country. The stable market share, competitive salaries for postal workers, increased unionisation and a fairly stable economy enabled a Fordist regime of accumulation to develop. The cycle broke down when the mode of regulation was weakened by national economic and political changes towards the late 1990s. PTC started to experience a decline in the consumption of postal products. The decline was also attributed to increased competition from smaller private courier operators that could provide specialised services to a market with changing needs. With increased competition, the advancement of information, and communication technologies, mail volumes dwindled. This period can best be described as the crisis of Fordism at ZimPost. In the year 2000, the government unbundled the posts and telecommunications corporation to create four companies including Zimbabwe Posts. This was perceived as one of the most radical organisational changes in the history of postal services in Zimbabwe. More organisational changes took place at ZimPost that can best be described as characteristics of post-Fordism. These changes were attempts by ZimPost to remain relevant in light of the economic, political and technological changes taking place in the country. The postal operator introduced customised products in the form of agency services, supported by increased use of information and communication technologies in the post office. Organisational changes at ZimPost were shaped mainly by the economic and political environment in which they took place. Organisational change is complex, changes do not follow a linear pattern, they are processual. , Thesis (PhD) -- Faculty of Humanities, Sociology, 2023
- Full Text:
- Date Issued: 2022-10-14
Computational analysis of known drug resistant mutants of Plasmodium falciparum Dihydrofolate Reductase (PfDHFR) and screening for novel antifolates against the enzyme
- Authors: Tata, Rolland Bantar
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234184 , vital:50170
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: Tata, Rolland Bantar
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234184 , vital:50170
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08
Diversified computational approaches for the identification of orthosteric drugs, allosteric modulators and unveiling drug resistance mechanisms: application to infectious diseases
- Authors: Boateng, Rita Afriyie
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234173 , vital:50169
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: Boateng, Rita Afriyie
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/234173 , vital:50169
- Description: Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Date Issued: 2022-04-08
Synthesis and evaluation of the medicinal potential of novel 4-hydroxycoumarin derivatives
- Authors: Manyeruke, Meloddy Hlatini
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164458 , vital:41120 , doi:10.21504/10962/164458
- Description: This research has focused on the synthesis and biological evaluation of a broad range of compounds characterised by the presence of the pharmacologically significant 4-hydroxycoumalin scaffold. The compounds were designed to contain additional pharmachophoric centres to enhance bioactivity and generate lead compounds with dualaction potential. The use of 4-hydroxycoumarin as the primary synthon enabled access to various series of 4-hydroxycoumarin conjugates, the reactive 3-position on the 4-hydroxycoumarin moiety being exploited for regioselective construction of the targeted compounds in several steps. Some of the reactants required in the construction of these compounds were specially synthesised and included propargyloxy benzaldehydes, benzyloxy benzaldehydes and 2,3-dihydroxysuccino-dihydride. Overall, eight different families of novel compounds were accessed, comprising conjugates of 4-hydroxycoumarin with bisethylidenesuccinohyrazide, trifluoroacetamide, amino, benzyloxyphenyl-iminoethyl, benzylidenehyrazinyl-thiazoyl, benzylidenehydrazonoethyl, propargyloxybenzylidenehydrazonoethyl and phenylacryloyl moieties using protocols that required minimal work-up and purification. The eighty novel compounds synthesised in the study were fully characterised using HMRS and advanced NMR techniques. Cytotoxicity, HIV-1 IN and PR inhibitory, and antitrypanosomal, antimalarial and anti-Mtb assays were conducted on the synthesised coumarin derivatives. Several compounds exhibited activity against HIV-1 IN, the most potent being a bis-ethylidenesuccinohyrazide with an IC50 value of 3.5 μM. Various compounds exhibited anti-malarial activity (% pLDH viability in the range 62-77%), anti-trypanosomal activity (the most potent with an IC50 = 0.9 μM against T.b. brucei) and a measure of anti-Mtb activity. Apart from two chalconyl derivatives, none of the synthesised compounds exhibited significant cytotoxicity. Conflicting results were obtained from the in silico docking studies; in some cases supporting the observed in vitro assay data while, in others, exhibiting no correlation. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2022-04-08
- Authors: Manyeruke, Meloddy Hlatini
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164458 , vital:41120 , doi:10.21504/10962/164458
- Description: This research has focused on the synthesis and biological evaluation of a broad range of compounds characterised by the presence of the pharmacologically significant 4-hydroxycoumalin scaffold. The compounds were designed to contain additional pharmachophoric centres to enhance bioactivity and generate lead compounds with dualaction potential. The use of 4-hydroxycoumarin as the primary synthon enabled access to various series of 4-hydroxycoumarin conjugates, the reactive 3-position on the 4-hydroxycoumarin moiety being exploited for regioselective construction of the targeted compounds in several steps. Some of the reactants required in the construction of these compounds were specially synthesised and included propargyloxy benzaldehydes, benzyloxy benzaldehydes and 2,3-dihydroxysuccino-dihydride. Overall, eight different families of novel compounds were accessed, comprising conjugates of 4-hydroxycoumarin with bisethylidenesuccinohyrazide, trifluoroacetamide, amino, benzyloxyphenyl-iminoethyl, benzylidenehyrazinyl-thiazoyl, benzylidenehydrazonoethyl, propargyloxybenzylidenehydrazonoethyl and phenylacryloyl moieties using protocols that required minimal work-up and purification. The eighty novel compounds synthesised in the study were fully characterised using HMRS and advanced NMR techniques. Cytotoxicity, HIV-1 IN and PR inhibitory, and antitrypanosomal, antimalarial and anti-Mtb assays were conducted on the synthesised coumarin derivatives. Several compounds exhibited activity against HIV-1 IN, the most potent being a bis-ethylidenesuccinohyrazide with an IC50 value of 3.5 μM. Various compounds exhibited anti-malarial activity (% pLDH viability in the range 62-77%), anti-trypanosomal activity (the most potent with an IC50 = 0.9 μM against T.b. brucei) and a measure of anti-Mtb activity. Apart from two chalconyl derivatives, none of the synthesised compounds exhibited significant cytotoxicity. Conflicting results were obtained from the in silico docking studies; in some cases supporting the observed in vitro assay data while, in others, exhibiting no correlation. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2022-04-08
An ethnographic exploration of black lesbians rape survivors’ access to support services in Cape Town South Africa
- Wilson, Kaythrine Esther Jacqueline
- Authors: Wilson, Kaythrine Esther Jacqueline
- Date: 2022-04
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/232646 , vital:50010
- Description: Thesis (PhD) -- Faculty of Humanities, Sociology, 2022
- Full Text:
- Date Issued: 2022-04
- Authors: Wilson, Kaythrine Esther Jacqueline
- Date: 2022-04
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/232646 , vital:50010
- Description: Thesis (PhD) -- Faculty of Humanities, Sociology, 2022
- Full Text:
- Date Issued: 2022-04
A green approach for the synthesis of symmetrical and unsymmetrical 1,2,4,5-tetraoxanes as anti-protozoal agents
- Authors: Cossa, Teresa Manuel
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192786 , vital:45264
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Cossa, Teresa Manuel
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192786 , vital:45264
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Development and optimisation of a mucoadhesive chitosan-based intranasal microemulsion and nanomicelle solution for lamotrigine using artificial neural networks
- Authors: Melamane, Siyabonga
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/${Handle} , vital:45247
- Description: Thesis (PhD) -- Faculty of Science, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Melamane, Siyabonga
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/${Handle} , vital:45247
- Description: Thesis (PhD) -- Faculty of Science, Pharmacy, 2021
- Full Text:
- Date Issued: 2021-10-29
Integration of dual metallophthalocyanine catalysis and green energy for sustainable oxidative removal of endocrine disrupting compounds
- Authors: Kruid, Jan
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192820 , vital:45267
- Description: Thesis (PhD) -- Faculty of Science, Biotechnology Innovation Centre, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Kruid, Jan
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192820 , vital:45267
- Description: Thesis (PhD) -- Faculty of Science, Biotechnology Innovation Centre, 2021
- Full Text:
- Date Issued: 2021-10-29
Legal ethics and the lawyer-client relationship in South Africa: A proposal for reform using local values
- Authors: Kruuse, Helen Julia
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192765 , vital:45262
- Description: Thesis (PhD) -- Faculty of Law, Law, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Kruuse, Helen Julia
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192765 , vital:45262
- Description: Thesis (PhD) -- Faculty of Law, Law, 2021
- Full Text:
- Date Issued: 2021-10-29
Neutral Atomic Hydrogen in Gravitationally Lensed Systems
- Authors: Blecher, Tariq Dylan
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192776 , vital:45263
- Description: Thesis (PhD) -- Faculty of Law, Law, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Blecher, Tariq Dylan
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192776 , vital:45263
- Description: Thesis (PhD) -- Faculty of Law, Law, 2021
- Full Text:
- Date Issued: 2021-10-29
Shifting Norms and Practices of International Criminal Justice: Exploring African State and Non-State Agency at the International Criminal Court
- Authors: Mtero, Shingirai
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192875 , vital:45273
- Description: Thesis (PhD) -- Faculty of Humanities, Political and International Studies, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Mtero, Shingirai
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192875 , vital:45273
- Description: Thesis (PhD) -- Faculty of Humanities, Political and International Studies, 2021
- Full Text:
- Date Issued: 2021-10-29
Stable Covalent pH-Sensitive Metallophthalocyanines Thin Monolayer Films for Selective Detection of Neurotransmitters
- Idowu, Abosede Omowumi Atinuke
- Authors: Idowu, Abosede Omowumi Atinuke
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192922 , vital:45279
- Description: Thesis (PhD) -- Faculty of Humanities, Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Idowu, Abosede Omowumi Atinuke
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192922 , vital:45279
- Description: Thesis (PhD) -- Faculty of Humanities, Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Synthesis, characterization and antiparasitic evaluation of chalcone hybrids
- Authors: Zulu, Ayanda Ignatia
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192853 , vital:45271
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Zulu, Ayanda Ignatia
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192853 , vital:45271
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Systematics of the Afrotropical Chalcididae (Hymenoptera: Chalcidoidea)
- Authors: Faure, Sariana
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192808 , vital:45266
- Description: Thesis (PhD) -- Faculty of Science, Zoology and Entomology, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Faure, Sariana
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192808 , vital:45266
- Description: Thesis (PhD) -- Faculty of Science, Zoology and Entomology, 2021
- Full Text:
- Date Issued: 2021-10-29
Traversing Sonic Spaces: Expressions of Identity, Gender, and Power in the Musical Traditions of the Nupe in Northern Nigeria
- Authors: Njoku, Obianuju Akunna
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192886 , vital:45276
- Description: Thesis (PhD) -- Faculty of Humanities, Music and Musicology, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Njoku, Obianuju Akunna
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192886 , vital:45276
- Description: Thesis (PhD) -- Faculty of Humanities, Music and Musicology, 2021
- Full Text:
- Date Issued: 2021-10-29
Exploring pre-service teachers’ reflective practice in the context of video-based lesson analysis
- Authors: Chikiwa, Samukeliso
- Date: 2020-04-30
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/355357 , vital:64492
- Description: This study explored the development of reflective practice in foundation phase pre-service teachers in the context of video-based lesson analysis at a university in South Africa. The study was conducted in the field of mathematics education, responding to the urgent need to equip pre-service South African teachers with the knowledge and skills for effective mathematics teaching. The research is foregrounded by the continuing poor performance of South African learners in mathematics at all levels of education in the country, which has been linked to the inadequate knowledge and skills of mathematics teachers. Pre-service teacher education is putting considerable effort into improving the preparation of mathematics teachers and developing their ability to reflect on their teaching practice is one of the strategies being employed for this purpose. Research has demonstrated the importance of reflective practice (RP) in both developing and extending teachers’ mathematical knowledge for teaching. This study therefore contributes to current research that supports the development of RP as a professional skill for promoting the acquisition of knowledge for teaching in pre-service teacher education. The study adopted a qualitative case study approach with two phases of data collection. In Phase 1 I collected and analysed three sets of 19 pre-service teachers’ written reflections to establish the nature of the reflections that they developed when analysing video-recorded mathematics lessons of experienced teachers’ practice. Phase 2 was conducted with four PSTs who reflected on video-recorded mathematics lessons of their own practice, and similarly sought to investigate the nature of the reflections they developed when reflecting on practice. The four PSTs wrote one set of reflections on their own lessons, went through three sessions of facilitator-guided reflections, then wrote another set of reflections to establish if the support provided in small group facilitator-guided sessions improved their reflections. Iterative content analysis was employed to analyse the PSTs’ written reflections, using an analytic tool that I developed for this purpose through merging Lee’s (2007) and Muir and Beswick’s (2007) levels of reflection frameworks. My model had four levels of reflection: description, explanation, suggestion and reflectivity. The names of each of the levels connect to the key indicator for that level. PSTs’ written reflections were coded and analysed according to these levels. The study found that PSTs’ initial reflections were mostly description of general classroom events with little reflection at the levels of explanation and suggestion, and an absence of reflectivity. Most reflections focused on general events in the lesson rather than mathematical events, even though the six lens framework they were given to guide their reflections prompted them to steer their attention towards mathematical events. The second and third sets of reflections, although mostly still at level 1, showed some shifts towards explanation and suggestion, although an increased focus on mathematical events though reflectivity was still largely absent. No PST reached the fourth level of reflectivity in Phase 1. However, in Phase 2, the PSTs’ reflections after the three small group facilitator-guided sessions included some evidence of reflectivity. The findings suggest the need for pre-service teacher educators to make a concerted effort to teach PSTs what reflection is and how to reflect on their practice. The findings also showed the need for small group facilitator-guided support in the development of PSTs’ reflective practice. , Thesis (PhD) -- Faculty of Education, Education, 2020
- Full Text:
- Date Issued: 2020-04-30
- Authors: Chikiwa, Samukeliso
- Date: 2020-04-30
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/355357 , vital:64492
- Description: This study explored the development of reflective practice in foundation phase pre-service teachers in the context of video-based lesson analysis at a university in South Africa. The study was conducted in the field of mathematics education, responding to the urgent need to equip pre-service South African teachers with the knowledge and skills for effective mathematics teaching. The research is foregrounded by the continuing poor performance of South African learners in mathematics at all levels of education in the country, which has been linked to the inadequate knowledge and skills of mathematics teachers. Pre-service teacher education is putting considerable effort into improving the preparation of mathematics teachers and developing their ability to reflect on their teaching practice is one of the strategies being employed for this purpose. Research has demonstrated the importance of reflective practice (RP) in both developing and extending teachers’ mathematical knowledge for teaching. This study therefore contributes to current research that supports the development of RP as a professional skill for promoting the acquisition of knowledge for teaching in pre-service teacher education. The study adopted a qualitative case study approach with two phases of data collection. In Phase 1 I collected and analysed three sets of 19 pre-service teachers’ written reflections to establish the nature of the reflections that they developed when analysing video-recorded mathematics lessons of experienced teachers’ practice. Phase 2 was conducted with four PSTs who reflected on video-recorded mathematics lessons of their own practice, and similarly sought to investigate the nature of the reflections they developed when reflecting on practice. The four PSTs wrote one set of reflections on their own lessons, went through three sessions of facilitator-guided reflections, then wrote another set of reflections to establish if the support provided in small group facilitator-guided sessions improved their reflections. Iterative content analysis was employed to analyse the PSTs’ written reflections, using an analytic tool that I developed for this purpose through merging Lee’s (2007) and Muir and Beswick’s (2007) levels of reflection frameworks. My model had four levels of reflection: description, explanation, suggestion and reflectivity. The names of each of the levels connect to the key indicator for that level. PSTs’ written reflections were coded and analysed according to these levels. The study found that PSTs’ initial reflections were mostly description of general classroom events with little reflection at the levels of explanation and suggestion, and an absence of reflectivity. Most reflections focused on general events in the lesson rather than mathematical events, even though the six lens framework they were given to guide their reflections prompted them to steer their attention towards mathematical events. The second and third sets of reflections, although mostly still at level 1, showed some shifts towards explanation and suggestion, although an increased focus on mathematical events though reflectivity was still largely absent. No PST reached the fourth level of reflectivity in Phase 1. However, in Phase 2, the PSTs’ reflections after the three small group facilitator-guided sessions included some evidence of reflectivity. The findings suggest the need for pre-service teacher educators to make a concerted effort to teach PSTs what reflection is and how to reflect on their practice. The findings also showed the need for small group facilitator-guided support in the development of PSTs’ reflective practice. , Thesis (PhD) -- Faculty of Education, Education, 2020
- Full Text:
- Date Issued: 2020-04-30
Repurposing a polymer precursor scaffold for medicinal application: Synthesis, characterization and biological evaluation of ferrocenyl 1,3-benzoxazine derivatives as potential antiprotozoal and anticancer agents
- Authors: Mbaba, Mziyanda
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164502 , vital:41124 , DOI 10.21504/10962/164502
- Description: The benzoxazines are a prominent class of heterocyclic compounds that possess a multitude of properties. To this end, benzoxazine derivatives have been used as versatile compounds for various utilities ranging from biological applications to the fabrication of polymers. Particularly, the 1,3-benzoxazine scaffold has featured in several bioactive compounds showing antimalarial, anticancer and antibacterial activities. Traditionally, it has been employed as a substrate in the synthesis of polymers with appealing physical and chemical properties. Due to the increasing interest in the polymer application of 1,3-benzoxazines, research of the 1,3-benzoxazine motif for polymer synthesis has been prioritized over other applications including its medicinal potential. The continuous development of resistance to clinical anticancer and antimalarial drugs has necessitated the need for the search of innovative bioactive compounds as potential alternative medicinal agents. To address this, the field of medicinal chemistry is adapting new approaches to counter resistance by incorporating nonconventional chemical moieties such as organometallic complexes, like ferrocene, into bioactive chemical motifs to serve as novel compounds with medicinal benefits. Incorporation of ferrocene into known bioactive chemical moieties has been shown to impart beneficial biological effects into the resultant compounds, which include the introduction of novel, and sometimes varied, mechanistic modalities and enhanced potency. Presented with the benefits of this strategy, the current work aims to design and evaluate the pharmaceutical capacity of novel derivatives containing 1,3-benzoxazine scaffold (traditionally applied in polymer synthesis) hybridized with the organometallic ferrocene unit as bioactive agents. Using a combination of expedient synthetic procedures such as the Burke three-component Mannich-type condensation, Vilsmeier-Haack formylation and reductive amination, four series of ferrocenyl 1,3-benzoxazine derivatives were synthesized and their structures confirmed by common spectroscopic techniques: nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). The target compounds were evaluated in vitro for potential antimalarial and anticancer activities against strains of the malaria parasite (Plasmodium falciparum 3D7 and Dd2) and the triple-negative breast cancer cell line HCC70. Compounds exhibited higher potency towards the Plasmodium falciparum strains with IC50 values in the low and sub-micromolar range in comparison to the breast cancer cell line against for which mid-molar activities were observed. To gain insight into the possible mode of action of ferrocenyl 1,3-benzoxazines, representative compounds showing most efficacy from each series were assessed for DNA binding affinity by employing UV-Vis and fluorescence DNA titration experiments. The selected compounds were found to interact with the DNA by binding to the minor groove, and these findings were confirmed by in silico ligand docking studies using a B-DNA structure as the receptor. Compound 3.16c (IC50: 0.261 μM [3D7], 0.599 μM [Dd2], 11.0 μM [HCC70]), which emerged as the most promising compound, was found to induce DNA damage in HCC70 cancer cells when investigated for effects of DNA interaction. Additionally, compound 3.16c displayed a higher binding constant (Kb) against DNA isolated from 3D7 Plasmodium falciparum trophozoites (Kb = 1.88×106 M-1) than the mammalian DNA (Kb = 6.33×104 M-1) from calf thymus, thus explaining the preferred selectivity of the compounds for the malaria parasite. Moreover, the investigated compounds demonstrated binding affinity for synthetic hemozoin, β-hematin. Collectively, these data suggest that the compounds possess a dual mode of action for antimalarial activity involving DNA interaction and hemozoin inhibition. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mbaba, Mziyanda
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164502 , vital:41124 , DOI 10.21504/10962/164502
- Description: The benzoxazines are a prominent class of heterocyclic compounds that possess a multitude of properties. To this end, benzoxazine derivatives have been used as versatile compounds for various utilities ranging from biological applications to the fabrication of polymers. Particularly, the 1,3-benzoxazine scaffold has featured in several bioactive compounds showing antimalarial, anticancer and antibacterial activities. Traditionally, it has been employed as a substrate in the synthesis of polymers with appealing physical and chemical properties. Due to the increasing interest in the polymer application of 1,3-benzoxazines, research of the 1,3-benzoxazine motif for polymer synthesis has been prioritized over other applications including its medicinal potential. The continuous development of resistance to clinical anticancer and antimalarial drugs has necessitated the need for the search of innovative bioactive compounds as potential alternative medicinal agents. To address this, the field of medicinal chemistry is adapting new approaches to counter resistance by incorporating nonconventional chemical moieties such as organometallic complexes, like ferrocene, into bioactive chemical motifs to serve as novel compounds with medicinal benefits. Incorporation of ferrocene into known bioactive chemical moieties has been shown to impart beneficial biological effects into the resultant compounds, which include the introduction of novel, and sometimes varied, mechanistic modalities and enhanced potency. Presented with the benefits of this strategy, the current work aims to design and evaluate the pharmaceutical capacity of novel derivatives containing 1,3-benzoxazine scaffold (traditionally applied in polymer synthesis) hybridized with the organometallic ferrocene unit as bioactive agents. Using a combination of expedient synthetic procedures such as the Burke three-component Mannich-type condensation, Vilsmeier-Haack formylation and reductive amination, four series of ferrocenyl 1,3-benzoxazine derivatives were synthesized and their structures confirmed by common spectroscopic techniques: nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). The target compounds were evaluated in vitro for potential antimalarial and anticancer activities against strains of the malaria parasite (Plasmodium falciparum 3D7 and Dd2) and the triple-negative breast cancer cell line HCC70. Compounds exhibited higher potency towards the Plasmodium falciparum strains with IC50 values in the low and sub-micromolar range in comparison to the breast cancer cell line against for which mid-molar activities were observed. To gain insight into the possible mode of action of ferrocenyl 1,3-benzoxazines, representative compounds showing most efficacy from each series were assessed for DNA binding affinity by employing UV-Vis and fluorescence DNA titration experiments. The selected compounds were found to interact with the DNA by binding to the minor groove, and these findings were confirmed by in silico ligand docking studies using a B-DNA structure as the receptor. Compound 3.16c (IC50: 0.261 μM [3D7], 0.599 μM [Dd2], 11.0 μM [HCC70]), which emerged as the most promising compound, was found to induce DNA damage in HCC70 cancer cells when investigated for effects of DNA interaction. Additionally, compound 3.16c displayed a higher binding constant (Kb) against DNA isolated from 3D7 Plasmodium falciparum trophozoites (Kb = 1.88×106 M-1) than the mammalian DNA (Kb = 6.33×104 M-1) from calf thymus, thus explaining the preferred selectivity of the compounds for the malaria parasite. Moreover, the investigated compounds demonstrated binding affinity for synthetic hemozoin, β-hematin. Collectively, these data suggest that the compounds possess a dual mode of action for antimalarial activity involving DNA interaction and hemozoin inhibition. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
The Role of HSP70/HSP90 Organizing Protein (Hop) in the Heat Shock Factor 1 (HSF1)-mediated Stress Response
- Authors: Chakraborty, Abantika
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/163204 , vital:41018 , doi:10.21504/10962/163204
- Description: Molecular chaperones regulate cellular proteostasis. They control protein conformation and prevent misfolding and aggregation under both normal and stressful environments, ultimately resulting in cell survival. The project aimed to understand the role of the HSP70 – HSP90 Organizing Protein (Hop/STIP1) in the survival of stressed cells and the function of the stress-responsive transcription factor, Heat Shock Factor 1 (HSF1). HSF1 protein levels were significantly reduced in Hop-depleted HEK293T cells compared to controls by ELISA, western blot, and mass spectrometry. HSF1 transcriptional activity at the HSP70 promoter, and binding of a biotinylated HSE oligonucleotide under basal conditions were significantly reduced, consistent with the reduced levels of HSF1. In response to heat shock, HSF1 levels in Hop-depleted cells increased to that of controls, but there was still significantly lowerHSF1 transcriptional activity and HSE binding. Hop-depleted HEK293T cells were more sensitive than controls to the HSF1 inhibitor KRIBB11 and showed reduced short-term and long-term proliferation. Unlike the HSP90 inhibitor 17-DMAG, which had no effect, the HSP70 inhibitor JG98, further decreased the levels of HSF1 in Hop-depleted cells, suggesting a role for HSP70 in the Hop-mediated effects. There was punctate nuclear staining for HSF1 in Hop-depleted cells under both basal and heat shock conditions, as well as reduced nuclear localization and increased cytoplasmic accumulation of HSF1 in response to heat shock. Hop and HSF1 colocalized in cells, and HSF1 could be isolated in complex with Hop and HSP70. Loss of Hop reduced HSF1 in HSP70complexes but did not affect HSF1 abundance in HSP90 complexes. Hop-depleted cells showed reduced short-term and long-term survival compared to controls, an effect that was potentiated by the JG98 HSP70 inhibitor. Taken together, these data suggest that Hop regulation of HSF1activity is via a mechanism involving reductions in HSP70 interaction, as well as reduced nuclear localization, and DNA binding, and is consistent with reduced cellular fitness under basal and stress conditions. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Chakraborty, Abantika
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/163204 , vital:41018 , doi:10.21504/10962/163204
- Description: Molecular chaperones regulate cellular proteostasis. They control protein conformation and prevent misfolding and aggregation under both normal and stressful environments, ultimately resulting in cell survival. The project aimed to understand the role of the HSP70 – HSP90 Organizing Protein (Hop/STIP1) in the survival of stressed cells and the function of the stress-responsive transcription factor, Heat Shock Factor 1 (HSF1). HSF1 protein levels were significantly reduced in Hop-depleted HEK293T cells compared to controls by ELISA, western blot, and mass spectrometry. HSF1 transcriptional activity at the HSP70 promoter, and binding of a biotinylated HSE oligonucleotide under basal conditions were significantly reduced, consistent with the reduced levels of HSF1. In response to heat shock, HSF1 levels in Hop-depleted cells increased to that of controls, but there was still significantly lowerHSF1 transcriptional activity and HSE binding. Hop-depleted HEK293T cells were more sensitive than controls to the HSF1 inhibitor KRIBB11 and showed reduced short-term and long-term proliferation. Unlike the HSP90 inhibitor 17-DMAG, which had no effect, the HSP70 inhibitor JG98, further decreased the levels of HSF1 in Hop-depleted cells, suggesting a role for HSP70 in the Hop-mediated effects. There was punctate nuclear staining for HSF1 in Hop-depleted cells under both basal and heat shock conditions, as well as reduced nuclear localization and increased cytoplasmic accumulation of HSF1 in response to heat shock. Hop and HSF1 colocalized in cells, and HSF1 could be isolated in complex with Hop and HSP70. Loss of Hop reduced HSF1 in HSP70complexes but did not affect HSF1 abundance in HSP90 complexes. Hop-depleted cells showed reduced short-term and long-term survival compared to controls, an effect that was potentiated by the JG98 HSP70 inhibitor. Taken together, these data suggest that Hop regulation of HSF1activity is via a mechanism involving reductions in HSP70 interaction, as well as reduced nuclear localization, and DNA binding, and is consistent with reduced cellular fitness under basal and stress conditions. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020