Browsing by Author "Du Toit, Francois"
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- ItemControl analysis of the action potential and its propagation in the Hodgkin-Huxley model(Stellenbosch : University of Stellenbosch, 2010-12) Du Toit, Francois; Snoep, Jacky L.; University of Stellenbosch. Faculty of Science. Dept. of Biochemistry.ENGLISH ABSTRACT: The Hodgkin-Huxley model, created in 1952, was one of the first models in computational neuroscience and remains the best studied neuronal model to date. Although many other models have a more detailed system description than the Hodgkin-Huxley model, it nonetheless gives an accurate account of various high-level neuronal behaviours. The fields of computational neuroscience and Systems Biology have developed as separate disciplines for a long time and only fairly recently has the neurosciences started to incorporate methods from Systems Biology. Metabolic Control Analysis (MCA), a Systems Biology tool, has not been used in the neurosciences. This study aims to further bring these two fields together, by testing the feasibility of an MCA approach to analyse the Hodgkin-Huxley model. In MCA it is not the parameters of the system that are perturbed, as in the more traditional sensitivity analysis, but the system processes, allowing the formulation of summation and connectivity theorems. In order to determine if MCA can be performed on the Hodgkin-Huxley model, we identified all the discernable model processes of the neuronal system. We performed MCA and quantified the control of the model processes on various high-level time invariant system observables, e.g. the action potential (AP) peak, firing threshold, propagation speed and firing frequency. From this analysis we identified patterns in process control, e.g. the processes that would cause an increase in sodium current, would also cause the AP threshold to lower (decrease its negative value) and the AP peak, propagation speed and firing frequency to increase. Using experimental inhibitor titrations from literature we calculated the control of the sodium channel on AP characteristics and compared it with control coefficients derived from our model simulation. Additionally, we performed MCA on the model’s time-dependent state variables during an AP. This revealed an intricate linking of the system variables via the membrane potential. We developed a method to quantify the contribution of the individual feedback loops in the system. We could thus calculate the percentage contribution of the sodium, potassium and leak currents leading to the observed global change after a system perturbation. Lastly, we compared ion channel mutations to our model simulations and showed how MCA can be useful in identifying targets to counter the effect of these mutations. In this thesis we extended the framework of MCA to neuronal systems and have successfully applied the analysis framework to quantify the contribution of the system processes to the model behaviour.
- ItemThe Influence of pile batter angle, soil unit weight and soil moisture content on the ultimate axial tensile load capacity of micropiles(Stellenbosch : Stellenbosch University, 2020-03) Du Toit, Francois; Fouche, Nanine; Stellenbosch University. Faculty of Engineering. Dept. of Civil Engineering.ENGLISH ABSTRACT: Battered piles are commonly adopted to resist overturning moments acting on the foundations of high-rise buildings and tower structures. Urbanization at an exponential rate is leading to an increase in the construction of high-rise buildings coupled with confined operating spaces and challenges regarding site accessibility. Micropiles are 300 mm or less in diameter, have various applications, require compact installation rigs and ancillary equipment and are thereby ideal for foundation engineering solutions in confined spaces. Battered micropiles are often utilized to act under tension, however several theories exist regarding the effect of batter angle on ultimate axial tensile load capacity, while literature addressing the effect of soil unit weight and moisture content is seldom. The aim of this study was to gain insight into the effects of batter angle, soil unit weight and soil moisture content on the ultimate axial tensile load capacity of a micropile. The aim was achieved through in situ tests, laboratory tests and scale model simulations. A variation in ultimate axial tensile load capacity of 28.87% was observed over a 30° change in batter angle during in situ testing conducted on micropiles. Soil-soil and soil-grout direct shear test results suggested that soil unit weight does not have a significant impact on the development of the soil-grout interface of a pile shaft and scale model simulation results revealed that soil unit weight affects the magnitude of variation in ultimate axial tensile load capacity associated with a change in batter angle, while soil moisture content greatly influences ultimate axial tensile load capacity through soil suction.
- Itemn Beginselmatige ontleding van onreelmatighede in die strafproses : met besondere verwysing na die ondervragingsprosedure by pleitverrigtinge(Stellenbosch : Stellenbosch University, 1994) Du Toit, Francois; Stellenbosch University. Faculty of . Dept. of .
- ItemTargeting pathogen metabolism without collateral damage to the host(Nature Research, 2017-01-13) Haanstra, Jurgen R.; Gerding, Albert; Dolga, Amalia M.; Sorgdrager, Freek J. H.; Buist-Homan, Manon; Du Toit, Francois; Faber, Klaas Nico; Holzhutter, Hermann-Georg; Szoor, Balazs; Matthews, Keith R.; Snoep, Jacky L.; Westerhoff, Hans V.; Bakker, Barbara M.The development of drugs that can inactivate disease-causing cells (e.g. cancer cells or parasites) without causing collateral damage to healthy or to host cells is complicated by the fact that many proteins are very similar between organisms. Nevertheless, due to subtle, quantitative differences between the biochemical reaction networks of target cell and host, a drug can limit the flux of the same essential process in one organism more than in another. We identified precise criteria for this ‘network-based’ drug selectivity, which can serve as an alternative or additive to structural differences. We combined computational and experimental approaches to compare energy metabolism in the causative agent of sleeping sickness, Trypanosoma brucei, with that of human erythrocytes, and identified glucose transport and glyceraldehyde-3-phosphate dehydrogenase as the most selective antiparasitic targets. Computational predictions were validated experimentally in a novel parasite-erythrocytes co-culture system. Glucose-transport inhibitors killed trypanosomes without killing erythrocytes, neurons or liver cells.
- ItemTesteervryheid in die Suid-Afrikaanse reg in die lig van 'n handves van regte(Stellenbosch : Stellenbosch University, 2000-12) Du Toit, Francois; De Waal, M. J.; Stellenbosch University. Faculty of Law. Dept. of Public Law.ENGLISH ABSTRACT: Freedom of testation is one of the underlying principles of the South African law of testate succession. South African testators may therefore dispose of their assets by way of will in any manner they deem fit. This freedom is however not absolute and is indeed restricted in accordance with certain social and economic considerations - some of the restrictions on free testamentary disposition originated at common law while others are couched in the form of statute. The boni mores or legal convictions of the community is one of the socially founded mechanisms which operate to limit freedom of testation in South African law. The South African legislature as well as the South African courts have however been somewhat remiss in attending to (and rejuvinating) the legal position regarding the restriction of freedom of testation in terms of the boni mores. The need for legal development in this area is all the more acute in view of South Africa's new constitutional dispensation - the interpretation and application of South Africa's final Constitution has rendered the influence of constitutional rights and principles on private law (and therefore also on freedom of testation) a pertinent legal issue. In view of the above-mentioned considerations, this work entails a general study of freedom of testation with specific reference to the application of a constitutionally founded boni morescriterion on the restriction of free testamentary disposition. This study proceeds with due cognisance of relevant juridical, social and economic considerations which provide a basis for both freedom of testation and its limitation. In this regard a historical perspective is obtained at the outset through an analysis of the approach to freedom of testation in Roman and Roman-Dutch law. The position with regard to South African law is thereafter investigated. The "traditional" approach to freedom of testation (and its restriction) is examined first, whereafter the possible impact of relevant provisions of the South African Bill of Rights on free testamentary disposition is considered from a theoretical perspective. A comparative study then follows. In this regard the approach to freedom of testation in both common law and continental or civil law legal systems is investigated. English and Australian law are considered as examples of the former while Dutch, Belgian and German law are considered as examples of the latter. The investigation into all the legal systems mentioned above has a dual focus. On the one hand the support which is rendered to freedom of testation in each legal system is considered. This support is readily founded on the acknowledgement in each system of private ownership and hence private succession, the latter which in turn acknowledges testamentary freedom. Other elements of the law of testate succession which render support to freedom of testation in each system are also examined. The restriction of free testamentary disposition in each legal system is investigated on the other hand. This investigation is principally focused on the impact of the boni mores, legal convictions of the community, public interest, public policy (the last-mentioned consideration is of particular importance in common law legal systems) and the good morals (particularly relevant in civil law legal systems) on the restriction of freedom of testation. Proposals for a future approach to the restriction of freedom of testation in South African law in accordance with a constitutionally founded boni mores-criterion are advanced in the closing chapter. The principal proposal in this regard is couched in the form of a new statutory provision which would best address the legal problem under discussion. This proposal is then illustrated with reference to practical examples.