PhD / Doctoral

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    Open Access
    Hybrid governance in the global south: A case study of collusion within the South African construction industry
    (2020) Kasipo, Mafaro; Julie Berg, Annette Hübschle, Clifford D. Shearing and Dee Smythe
    What is the nature of hybrid governance in the Global South? In the African context, a state- centric conceptualisation of governance fails to capture the nuances and realities of governance where non-state actors often fulfil duties that are traditionally the responsibility of the Weberian state. It is against this background that this dissertation seeks to contribute to hybridity literature by exploring the relationships between the state and the construction industry through a case study of collusion in the South African construction industry to build the 2010 FIFA World Cup stadiums. The research goes beyond arguing for a plurality of governance actors and draws on the concept of hybridity to highlight the contestations that characterise the relationship between the different governance actors. The original contribution to hybridity literature made by this research lies in examining how the state and the construction industry enact authority in a setting of hybrid governance. To analyse the process of hybridisation I draw on the concepts of corruption, authority and governmentality as lenses through which to analyse the rationalities, strategies and practices used in the enactment of authority. The research findings reveal that the process of hybridisation as the state and construction industry articulate authority is characterised by contradictions, blurring and boundary-making. The findings suggest that the manifestations of these characteristics during hybridisation is context specific and should be empirically determined
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    Open Access
    Exotic (QQ)n-Mesons in perturbative cavity QCD using a modified boundary condition
    (1999) Fetea, Remus Florian
    [Cannot OCR properly, page 1 watermark not created in Acrobat]
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    The control of melanogenesis in early avian embryos
    (1993) Hulley, Philippa Anne; Dr Sue Kidson
    The developing neural crest in avian embryos presents a unique system for the investigation of cell migration and differentiation. A variety of histological, cellular and molecular techniques have been used in this study to explore and clarify the exact sequence of events occurring during the determination and differentiation of neural crest cells into melanocytes, to discover where in the developing embryo these events take place and to investigate the mechanisms whereby these processes are controlled. Homo- and heterotypic combinations of white (Yhite Plymouth Rock x Cornish Game) and black (Black Australorp x New Hampshire Red) chick epidermis and dermis have been used to demonstrate that premelanocytes migrate first through the sub-epidermal mesenchyme and then begin to cross into the epidermis from day 4. Results from these grafts and from tritium-labelling studies strongly suggest that there is little or no reverse migration from epidermis to dermis. This resolves the conflict of whether premelanocytes migrate immediately into the epidermis from the neural crest or spread out laterally around the body in the dermis before crossing into the epidermis. Since the microenvironment is thought to play a key role in the control of neural crest cell diversification, the timing and route of migration may be critical factors in melanocyte differentiation. Pigmented melanocytes first become visible in the dermis at day 5 and tyrosinase activity (the key enzyme in melanin production) was detected in 5 day chick skin using a radiometric assay. In sicu vi hybridization of sections through 5 day embryos using Digoxygenin-labelled riboprobe revealed the presence of numerous tyrosinase mRNA-positive cells in the dermis and crossing into the epidermis. It is therefore likely that the dermis provides the first appropriate environment for melanocyte differentiation and not the epidermis as previously thought. However the role of the dermis may be permissive rather than active because when the dermis was replaced with gut mesenchyme, melanocytes still differentiated. The presence of epidermis was shown to be critical for melanocyte differentiation. When 4 day dermis (prior to the appearance of melanin) was 1 cultured in isolation from epidermis, melanocytes did not difrerentiate. Similarly, when epidermis was replaced with gut or chorionic epithelium, melanocytes largely failed to differentiate. Therefore the epidermis seems to be inducing terminal melanocyte differentiation, albeit at a distance from the migrating cells. Although the dermis does not seem to be essential for melanocyte differentiation, it appears to inhibit melanocyte differentiation in white pattern feathers. When the epidermis on the dorsal surface of quail wing buds was replaced with epidermis from a white chick, normally pigmented feathers formed but when the ventral wing epidermis was replaced, most of the resulting feathers were unpigmented. This is the normal colour pattern of quail wing feathers and the result therefore indicates that the ventral wing dermis is responsible for inhibiting melanocyte differentiation in the white pattern feathers of an otherwise pigmented bird. The question of how melanocytes locate and physically migrate into the epidermis was addressed by developing a variety of novel organ culture procedures. When whole 4 day skin or heterotypic combinations of pigmented dermis with white epidermis were cultured on rafts floating in medium containing GRGDS, the cellbinding site peptide sequence of fibronectin, epidermal pigmentation was severely inhibited. When the laminin cell-binding site peptide, YIGSR, was similarly vii used, normally pigmented epidermis and feathers developed. Therefore it is likely that melanocytes use fibronectin and not laminin when migrating through the dermis and into the epidermis . Melanocytes may also need to produce proteases in order to invade the epidermis since raft culture of skin in TLCK, a serine protease inhibitor, prevented epidermal melanisation. Finally, the ability of the epidermis to chemotactically attract melanocytes was investigated by assessing the change in distribution of melanocytes in dermis cultured on a filter above a well containing pieces of epidermis. The epidermis appears to be producing a diffusible factor which attracts melanocytes and is not mimicked by NGF, EGF, bFGF or retinoic acid. This is the first evidence that the epidermis may play a role in the homing of melanocytes.The developing neural crest in avian embryos presents a unique system for the investigation of cell migration and differentiation. A variety of histological, cellular and molecular techniques have been used in this study to explore and clarify the exact sequence of events occurring during the determination and differentiation of neural crest cells into melanocytes, to discover where in the developing embryo these events take place and to investigate the mechanisms whereby these processes are controlled. Homo- and heterotypic combinations of white (Yhite Plymouth Rock x Cornish Game) and black (Black Australorp x New Hampshire Red) chick epidermis and dermis have been used to demonstrate that premelanocytes migrate first through the sub-epidermal mesenchyme and then begin to cross into the epidermis from day 4. Results from these grafts and from tritium-labelling studies strongly suggest that there is little or no reverse migration from epidermis to dermis. This resolves the conflict of whether premelanocytes migrate immediately into the epidermis from the neural crest or spread out laterally around the body in the dermis before crossing into the epidermis. Since the microenvironment is thought to play a key role in the control of neural crest cell diversification, the timing and route of migration may be critical factors in melanocyte differentiation. Pigmented melanocytes first become visible in the dermis at day 5 and tyrosinase activity (the key enzyme in melanin production) was detected in 5 day chick skin using a radiometric assay. In sicu vi hybridization of sections through 5 day embryos using Digoxygenin-labelled riboprobe revealed the presence of numerous tyrosinase mRNA-positive cells in the dermis and crossing into the epidermis. It is therefore likely that the dermis provides the first appropriate environment for melanocyte differentiation and not the epidermis as previously thought. However the role of the dermis may be permissive rather than active because when the dermis was replaced with gut mesenchyme, melanocytes still differentiated. The presence of epidermis was shown to be critical for melanocyte differentiation. When 4 day dermis (prior to the appearance of melanin) was 1 cultured in isolation from epidermis, melanocytes did not difrerentiate. Similarly, when epidermis was replaced with gut or chorionic epithelium, melanocytes largely failed to differentiate. Therefore the epidermis seems to be inducing terminal melanocyte differentiation, albeit at a distance from the migrating cells. Although the dermis does not seem to be essential for melanocyte differentiation, it appears to inhibit melanocyte differentiation in white pattern feathers. When the epidermis on the dorsal surface of quail wing buds was replaced with epidermis from a white chick, normally pigmented feathers formed but when the ventral wing epidermis was replaced, most of the resulting feathers were unpigmented. This is the normal colour pattern of quail wing feathers and the result therefore indicates that the ventral wing dermis is responsible for inhibiting melanocyte differentiation in the white pattern feathers of an otherwise pigmented bird. The question of how melanocytes locate and physically migrate into the epidermis was addressed by developing a variety of novel organ culture procedures. When whole 4 day skin or heterotypic combinations of pigmented dermis with white epidermis were cultured on rafts floating in medium containing GRGDS, the cellbinding site peptide sequence of fibronectin, epidermal pigmentation was severely inhibited. When the laminin cell-binding site peptide, YIGSR, was similarly vii used, normally pigmented epidermis and feathers developed. Therefore it is likely that melanocytes use fibronectin and not laminin when migrating through the dermis and into the epidermis . Melanocytes may also need to produce proteases in order to invade the epidermis since raft culture of skin in TLCK, a serine protease inhibitor, prevented epidermal melanisation. Finally, the ability of the epidermis to chemotactically attract melanocytes was investigated by assessing the change in distribution of melanocytes in dermis cultured on a filter above a well containing pieces of epidermis. The epidermis appears to be producing a diffusible factor which attracts melanocytes and is not mimicked by NGF, EGF, bFGF or retinoic acid. This is the first evidence that the epidermis may play a role in the homing of melanocytes.
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    Open Access
    Evolution of viral populations in individuals infected with single and multiple HIV subtypes : a study of HIV-1 dual infection in a high risk cohort of female bar workers from Tanzania
    (2007) Malaza, Abraham Lucky; Prof. Carolyn Williamson and Dr. Darren Martin
    The Human Immunodeficiency virus (HIV) is characterized by high replication rate and high levels of diversity resulting in numerous quasispecies that form a 'swarm' in the infected individual. HIV diversification is driven by selection pressure exerted by the host. The role of high viral diversity in disease progression in context of infection with more than one subtype (dual infection) is not elucidated. Delineating of the evolving viral diversity in dual infection will contribute to our understMding of HIV pathogenesis and thus enable for better strategies for effective therapy and vaccine development strategies. This study forms part of the HIV Superinfection Study (HISIS, www.mmrp.org) which aimed to identify the frequency of dual and superinfection in a high risk cohort of women in Mbeya, Tanzania. The Mbeya region is characterized by a highly diverse HIV epidemic where multiple HIV-1 subtypes co-circulate including A, C, and D, as well as recombinant forms. The aims of this thesis were: firstly, to investigate the distribution of HIV subtypes and recombinant forms in a cohort from Mbeya, and to determine the prevalence of HIV dual infection using the multi region hybridization assay (MHA); secondly to investigate the dynamics of viral evolution among dually infected individuals using a gel based screening assay (heteroduplex mobility assay, HMA) and sequencing, lastly the study aimed to investigate the role of point mutations and recombination on viral diversity and immune escape in a dually infected individual. The MHA was used to screen for different subtypes present in the study population (n=57). Subtypes A, C, D and their recombinants forms were detected. Subtype A accounted for 5%, C 33%, D 7% and recombinants 44%. Dual infection was detected in 11 % of individuals. AC recombinants accounted for 60% of all recombinant viral strains, ACD and CD strains accounted for approximately 12% each and AD recombinants accounted for 16%. This study provides additional information on the virus strains circulating in Tanzania. Overall these studies confirm that Tanzania harbours a complex diversity of viruses with a large proportion of the viruses being recombinant forms. The high prevalence of dual infections is clearly fuelling the generation of these recombinant viruses and it would be of interest to monitor the molecular epidemiology of the epidemic to determine if new circulating recombinant forms emerge. In a selected subset of chronically infected participants monitored over 21 months, we identified dual infection in four out of the twelve individuals. The presence of dual infections was screened for using the HMA based on the vpu and env C2C3 regions of the genome. Sequencing was employed to cpnfirm subtypes. Abstract 111 Four of the twelve women were dually infected with two distinct subtypes (A and C). The majority of single infections were by subtype C (n= 4), two were infected with subtype A, while subtype D was responsible for one infection. One individual was infected by a CD recombinant virus. Analysis of 20 randomly selected clones from different timepoints was used to determine diversity at selected timepoints. Env C2C3 region was more diverse than the vpu region with the mean DNA distances of vpu ranging from 0.9% to 8.5% compared to 0.3% and 19.5% in the env C2C3 region. Tz14 was found to harbour the most diverse viral strains with a maximum DNA distance of 12% (median 7%) in the vpu region and 14% (median 11 %) in the env C2C3 region. This individual was selected for an indepth analysis of the role of point mutations and recombination on viral evolution in dual infection. Analysis of clones from different timepoints demonstrated that dual infections were detectable in a minority of follow-up visits with only one individual having detectable dual infection at most timepoints. This emphasizes the importance of analyzing multiple time-points and that cross-sectional studies will likely underestimate the prevalence of dual infections. An analysis of the contribution of different viral variants in dual infection to overall viral burden illustrated large fluctuations of viral populations over time. However, generally the viral populations were relatively homogeneous at single time point suggesting that, while there is very high potential diversity, this diversity is largely constrained. Lastly, through full-length gene (gag and nef) sequencing we investigated positive selection, recombination patterns and screened for evidence of CTL escape in a dually infected individual (Tz14) over time (21 months). No evidence of positive selection was detected in both genes during the study period. Recombination analysis revealed that gag sequences had similar break points at time point F0 and F7. Furthermore, it was shown that none of the sequences obtained from both genes were 'pure' subtypes. Limited evidence of predicted CTL escape was observed in the nef and gag. Based on these results we postulate that viral diversity observed in these individuals is mostly a result of recombination and to a very limited extent through point mutations. This study confirms that multiple HIV -1 subtypes and recombinant viruses co-circulate in the population of Mbeya, and that there is a high prevalence of dual infections. While dually infected individuals harbour highly divergent viruses with high fluctuation of diversity over time, the diversity at a single timepoint is usually constrained. An investigation of full-length gag and nef suggests that the major mechanism of viral evolution is through recombination.
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    Pseudoxanthoma elasticum in Southern Africa ; by Denis Lowe Viljoen
    (1991) Viljoen, Denis Lowe; Professor Peter Beighton
    Pseudoxanthoma elasticum (PXE) is a rare heritable disorder of elastin with major manifestations in the cardiovascular system, skin and eyes. The disorder is heterogeneous, but the underlying genetic defects remain unresolved. The study was undertaken to evaluate the frequency, clinical presentation, natural history, medical complications and therapeutic options for individuals with PXE in Southern Africa. During the investigation, in which 86 patients in 58 families were studied, it became apparent that in addition to the 4 previously delineated forms of the disorder, there was an autonomous entity confined to individuals of Afrikaner stock in which serious ophthalmological sequelae occurred. Detailed genealogical studies were performed in this group, common ancestors were identified and a high prevalence of the condition was discovered. The dermatological, cardiovascular and ophthalmological manifestations of PXE were investigated at a clinical, biochemical and ultrastructural level. Restriction fragment length polymorphisms related to type I collagen and to the human elastin gene were used in linkage studies in an attempt to resolve the question of possible heterogeneity. · Therapeutic options for the oph thalmological and cosmetic complications were evaluated. As a result of this investigation and subsequent publications, information regarding the clinical consequences of a new form of PXE within the Afrikaner community has been disseminated to colleagues in the dermatological, genetic, medical, cardiac and ophthalmological fields in South Africa and abroad. In the light of my observations, antenatal diagnosis and carrier detection are likely to be feasible in the foreseeable future.