Thesis (MScEng (Civil Engineering))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The primary aim of this study was to evaluate, calibrate and verify the SDF run-off coefficients at a quaternary catchment level in the C5 secondary drainage region (SDF basin 9) and other selected SDF basins in South Africa by establishing the catchment parameters and SDF/probability distribution-ratios. The probability distribution-ratios were based on the comparison between the flood peaks estimated by the SDF method and statistical analyses of observed flow data. These quaternary run-off coefficients were then compared with the existing regional SDF run-off coefficients, whilst the run-off coefficient adjustment factors as proposed by Van Bladeren (2005) were also evaluated. It was evident from this study that the calibrated run-off coefficients obtained are spread around those of Alexander (2003), but were generally lower in magnitude. The adjusted run-off coefficients (Van Bladeren, 2005) had a tendency to decrease in magnitude with increasing recurrence interval, whilst some of the adjusted run-off coefficients exceeded unity. The extent to which the original SDF method overestimated the magnitude and frequency of flood peaks varied form basin to basin, with the SDF/probability distribution-ratios the highest in the Highveld and southern coastal regions with summer convective precipitation. In these regions the flood peak-ratios were occasionally different by up to a factor of 3 or even more. The southern coastal regions with winter orographic/frontal precipitation demonstrated the best flood peak-ratios, varying from 0.78 to 1.63. The adjusted SDF method results (Van Bladeren, 2005) were only better in 26% of all the basins under consideration when compared to those estimated by the original SDF method. On average, the adjusted SDF/probability distribution-ratios varied between 0.30 and 6.58, which is unacceptable. The calibrated version of the SDF method proved to be the most accurate in all the basins under consideration. On average, the calibrated SDF/probability distribution-ratios varied between 0.85 and 1.15, whilst at some basins and individual return periods, less accurate results were evident. Verification tests were conducted in catchments not considered during the calibration process with a view to establish whether the calibrated run-off coefficients are predictable and to confirm that the method is reliable. The verification results showed that the calibrated/verified SDF method is the most accurate and similar trends were evident in all the basins under consideration. On average, the verified SDF/probability distribution-ratios varied between 0.82 and 1.19, except in SDF basins 6 and 21 where the 5 to 20-year return period flood peaks were overestimated by 41% and 56% respectively, which is still conservative. The secondary aim of this study was to develop a customised, user-friendly Design Flood Estimation Tool (DFET) in a Microsoft Office Excel/Visual Basic for Applications environment in order to assess the use and applicability of the various design flood estimation methods. The developed DFET will provide designers with a software tool for the rapid investigation and evaluation of alternative design flood estimation methods either at a regional or site specific scale. The focus user group of the application will comprises of engineering technicians, engineering technologist and engineers employed at civil engineering consultants, not necessarily specialists in the field of flood hydrology. The DFET processed all the catchment, meteorological (precipitation) and hydrological (observed flows) data used as input for the various design flood estimation methods. / AFRIKAANSE OPSOMMING: Die primêre doelwit van die studie was om die SDF-afloopkoëffisiënte op ‘n kwartinêre opvangsgebiedvlak in die C5-sekondêre dreineringsgebied (SDFopvangsgebied 9) en ander gekose SDF-opvangsgebiede in Suid-Afrika te evalueer, te kalibreer en te verifieer deur die opvangsgebiedparameters en SDF/waarskynlikheidsverspreiding-verhoudings vas te stel. Dié waarskynlikheidsverspreiding-verhoudings was gebaseer op die vergelyking tussen die vloedpieke soos beraam deur die SDF-metode en statistiese analises van waargenome vloeidata. Dié kwartinêre afloopkoëffisiënte is met die bestaande streeksgebonde SDF-afloopkoëffisiënte vergelyk, terwyl die afloopkoëffisiënt-aanpassingsfaktore soos voorgestel deur Van Bladeren (2005) ook geëvalueer is. Dit het duidelik uit die studie geblyk dat die gekalibreerde afloopkoëffisiënte verspreid rondom die van Alexander (2003) is, maar in die algemeen laer in omvang. Die aangepaste afloopkoëffisiënte (Van Bladeren, 2005) was geneig om af te neem in grootte met ‘n toename in die herhalingsperiode, terwyl sommige afloopkoëffisiënte ‘n waarde van 1 oorskry het. Die omvang waartoe die oorspronklike SDF metode die grootte en herhaalperiode van vloedpieke oorskat het, wissel van opvangsgebied tot opvangsgebied, met die SDF/waarskynlikheidsverspreiding-verhoudings die hoogste in die Hoëveld en suidelike kusstreke gekenmerk deur konveksie-somerreënval. In hierdie streke het die vloedpiekverhoudings gereeld verskil tot en met ‘n faktor van 3 of selfs meer. Die suidelike kusstreke met kenmerkende ortografiese/frontale winterreënval het oor die beste vloedpiekverhoudings beskik wat gewissel het tussen 0.78 en 1.63. Die resultate van die aangepaste SDF-metode (Van Bladeren, 2005) was slegs in 26% van al die opvangsgebiede beter as die beramings van die oorspronklike SDF-metode. Die aangepaste SDF/waarskynlikheidsverspreiding-verhoudings het, met verwysing na gemiddeldes, tussen 0.30 en 6.58 gewissel, wat onaanvaarbaar is. Die gekalibreerde weergawe van die SDF-metode was die mees akkurate metode in al die opvangsgebiede van belang. Die gekalibreerde SDF/waarskynlikheidsverspreiding-verhoudings het, met verwysing na gemiddeldes, tussen 0.85 en 1.15 gewissel, terwyl die resultate van sommige opvangsgebiede en individuele herhalingsperiodes minder akkuraat was. Verifikasietoetse is uitgevoer in die opvangsgebiede wat nie tydens die kalibrasieproses gebruik was nie om vas te stel of die gekalibreerde afloopkoëffisiënte voorspelbaar is en om te bevestig dat die metode betroubaar is. Die verifikasieresultate het getoon dat die gekalibreerde/geverifieerde SDFmetode die mees akkurate metode is en dat soortgelyke tendense duidelik was in al die relevante opvangsgebiede. Die geverifieerde SDF/waarskynlikheidsverspreiding-verhoudings het, met verwysing na gemiddeldes, tussen 0.82 en 1.19 gewissel, behalwe in SDF-opvangsgebiede 6 en 21 waar die 5- en 20-jaar herhalingsperiode-vloedpieke onderskeidelik met 41% en 56% oorskat is, wat steeds konserwatief is. Die sekondêre doelwit van die studie was om ‘n gebruikersvriendelike “Design Flood Estimation Tool” (DFET) in ‘n Microsoft Office Excel/Visual Basic for Applications omgewing te ontwikkel om die gebruik en toepaslikheid van die verskeie ontwerpvloedberamingsmetodes te bepaal. Die DFET sal ontwerpers voorsien van ‘n sagtewareprogram om alternatiewe ontwerpvloedberamingsmetodes op streek- of plaaslike skaal te ondersoek en te evalueer. Die fokus-gebruikersgroep vir die toepassing van die program sal bestaan uit ingenieurstegnici, ingenieurstegnoloë en ingenieurs werksaam by raadgewende siviele ingenieurs, nie noodwendig vakkundiges in die veld van hidrologie nie. Die DFET was gebruik om al die opvangsgebied-, meteorologiese (reënval) en hidrologiese (waargenome vloeie) data vir die verskeie ontwerpvloedberamingsmetodes te verwerk.

Le cancer épithélial de l'ovaire (CEO) est une cause majeure de mortalité parcancer gynécologique. Il est associé à un mauvais pronostic car il est souventdécouvert à un stade tardif. Mieux comprendre les causes et les mécanismesmoléculaires et cellulaires associés à la progression de ce cancer représente unenjeu majeur.Les deux chimiokines CXCL12/SDF-1 et fractalkine (FKN)/CX3CL1 ont étéimpliquées dans diverses tumeurs. La chimiokine SDF-1, a un effetimmunosuppresseur dans le CEO. Elle est aussi impliquée dans l'angiogenèsetumorale. L'effet de SDF-1 médié par CXCR4 est également impliqué dans larégulation de la prolifération, la survie, la migration et l'invasion des cellulescancéreuses. La FKN, a largement été mise en évidence dans les tissusépithéliaux et dans divers cancers où elle peut avoir soit un rôle anti-tumoral soitun rôle pro-tumoral. Jusqu'à présent la FKN n'a pas été étudié dans le CEO.Dans notre étude, nous avons démontré l'expression de SDF-1 et de la FKNdans l'épithélium de surface de l'ovaire sain et dans les tumeurs bénignes etmalignes. Ces résultats montrent que l'expression de SDF-1 et de la FKNpréexiste à la tumorigenèse. Nous avons démontré une expression hétérogènedes deux chimiokines dans les cellules du CEO. Les niveaux d'expression deSDF-1 dans les cellules tumorales sur une cohorte de 183 patientes n'ont aucunevaleur pronostique sur la survie globale et sur la survie sans progressiontumorale des patientes atteintes par le CEO. L'étude de la corrélation del'expression de la FKN avec les deux marqueurs de prolifération, Ki-67 etGILZ, sur une autre cohorte de 54 patientes, complétée par des expériences invitro, a montré que GILZ augmente l'expression de la FKN et d'autre part que laFKN elle-même augmente la prolifération. Cette étude contribue à élucider lerôle de SDF-1 et de la FKN dans le CEO.

Le traitement du cancer à l’aide d’une exposition aux radiations ionisantes (RI) peut mener au développement de plusieurs effets secondaires importants, dont un retard de réparation et de régénération des tissus. Les mécanismes responsables de ces effets demeurent largement inconnus encore aujourd’hui, ce qui a pour effet de limiter le développement d’approches thérapeutiques. À l’aide d’un modèle de guérison de plaie cutanée chez la souris, nous avons cherché à déterminer les mécanismes par lesquels l’exposition aux RI limite la régénération de la peau. Nos résultats démontrent que l’induction de la "stromal-derived growth factor 1α" (SDF-1α), une cytokine normalement surexprimée dans les tissus hypoxiques, est sévèrement diminuée dans les plaies de souris irradiées versus non-irradiées. Ce défaut corrèle avec un retard de guérison des plaies et est encore évident plusieurs mois suivant l’exposition aux RI, suggérant qu’il y a une altération permanente de la capacité de la peau à se réparer. Parce que SDF-1α est secrété principalement par les fibroblastes du derme, nous avons évalué le potentiel des cellules stromales multipotentes (MSCs), qui sont reconnues pour secréter des niveaux élevés de SDF-1α, à accélérer la régénération de la peau chez les souris irradiées. L’injection de MSCs en périphéries des plaies a mené à une accélération remarquable de la guérison de la peau chez les souris exposées aux RI. Les actions des MSCs étaient principalement paracrines, dû au fait que les cellules n’ont pas migré à l’extérieur de leur site d’injection et ne se sont pas différentiées en kératinocytes. L’inhibition spécifique de l’expression de SDF-1α a mené à une réduction drastique de l’efficacité des MSCs à accélérer la fermeture de plaie indiquant que la sécrétion de SDF-1α par les MSCs est largement responsable de leur effet bénéfique. Nous avons découvert aussi qu’un des mécanismes par lequel SDF-1α accélère la guérison de plaie implique l’augmentation de la vascularisation au niveau de la peau blessée. Les résultats présentés dans ce mémoire démontrent collectivement que SDF-1α est une importante cytokine dérégulée au niveau des plaies cutanées irradiées, et que le déclin du potentiel de régénération des tissus qui est observé suivant une exposition au RI peut être renversé, s’il est possible de restaurer le microenvironnement de la blessure avec un support stromal adéquat. / Cancer treatment using ionizing radiation (IR) may lead to significant side effects, like delayed tissue repair and regeneration. The mechanisms mediating these defects remain largely unknown at present, thus limiting the development of therapeutic approaches. Using a wound healing model, we investigate the mechanisms by which IR exposure limits skin regeneration. Our results show that induction of the stromal-derived growth factor 1α (SDF-1α), a cytokine normally overexpressed in hypoxic tissues, is severely impaired in the wounded skin of irradiated, compared to non-irradiated, mice. This defect is correlated with delayed healing, and is evident for several months following exposure to IR, suggesting permanent impairment of skin repair. Because SDF-1α is secreted mainly by dermal fibroblasts, we evaluated the potential of multipotent stromal cells (MSCs), which secrete high levels of SDF-1α, to improve skin regeneration in irradiated mice. Injection of MSCs into the wound margin led to remarkable enhancement of skin healing in mice exposed to IR. The MSC actions were mainly paracrine, as the cells did not migrate away from the injection site or differentiate into keratinocytes. Specific knockdown of SDF-1α expression led to drastically reduced efficiency of MSCs in improving wound closure, indicating that SDF-1α secretion by MSCs is largely responsible for their beneficial action. We also found that one mechanism by which SDF-1α enhances wound closure likely involves increased skin vascularization. Findings presented in this thesis collectively indicate that SDF-1α is an important deregulated cytokine in irradiated wounded skin, and that the decline in tissue regeneration potential following IR can be reversed, given adequate microenvironmental support.

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability among young adults and has been a significant field in medical research over the past decades. Intensive studies focusing on how to repair tissue damage resulting from head injuries have discovered that the central nervous system (CNS) retains a regenerative capacity throughout life due to the persistent presence of neural stem/progenitor cells (NS/NPCs) in the neurogenic regions. In the normal brain, cells generated in the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to the olfactory bulb and cells in the subgranular zone (SGZ) migrate laterally into the granule cell layer of the dentate gyrus. Directed movement of these NS/NPCs is controlled by a variety of factors, and among them the chemoattractant SDF-1 is of particular importance. Studies have identified that the chemokine SDF-1α and its receptor CXCR4 play an important role in guiding cell migration in many types of cells including NS/NPCs. The current study tested if SDF-1 could be delivered through alginate to attract and guide migration of NS/NPCs and its progeny both in vitro and in vivo. Using a Boyden chamber migration assay, we found SDF-1α either added directly in the medium or incorporated into alginate threads was capable of influencing migration of cultured NS/NPCs in a dose-dependent manner. In the in vivo study, when injected directly into the cerebral cortex, SDF-1  showed limited capability in inducing neuroblasts migration off the normal tract to the site of SDF-1 injection. When SDF-1 was delivered via alginate thread to the focal injury site at 2 days post TBI, significantly increased number of migrating neuroblasts derived from the SVZ was observed around the injury site. Increased expression of SDF-1 receptor CXCR4 was observed in the NS/NPCs in the SVZ and around the injury site following TBI. These data suggest that bioactive SDF-1α can be delivered via alginate thread and exogenous delivery of SDF-1α and its interaction with receptor CXCR4 mediates migration of newly generated neurons from the SVZ to the site of injury following TBI. Collectively, our study indicates that SDF-1α could be utilized as a guidance cue for tissue repair following brain injury.

No description available.

Many digital signal processing and real-time streaming systems are modeled using dataflow graphs, such as Synchronous Dataflow (SDF) and Cyclo-static Dataflow (CSDF) graphs that allow static analysis and optimization techniques. However, mapping of such descriptions into tightly constrained real-time implementations requires optimization of resource sharing, buffering and scheduling across a multi-dimensional latency-throughput-area objective space. This requires techniques that can find the Pareto-optimal set of implementations for the designer to choose from. In this work, we address the problem of multi-objective mapping and scheduling of SDF and CSDF graphs onto heterogeneous multi-processor platforms. Building on previous work, this thesis extends existing two-stage hybrid heuristics that combine an evolutionary algorithm with an integer linear programming (ILP) model to jointly optimize throughput, area and latency for SDF graphs. The primary contributions of this work include: (1) extension of the ILP model to support CSDFGs with additional buffer size optimizations; (2) a further optimization in the ILP-based scheduling model to achieve a runtime speedup of almost a factor of 10 compared to the existing SDFG formulation; (3) a list scheduling heuristic that replaces the ILP model in the hybrid heuristic to generate Pareto-optimal solutions at significantly decreased runtime while maintaining near-optimality of the solutions within an acceptable gap of 10% when compared to its ILP counterparts. The list scheduling heuristic presented in this work is based on existing modulo scheduling approaches for software pipelining in the compiler domain, but has been extended by introducing a new concept of mobility-based rescheduling before resorting to backtracking. It has been proved in this work that if mobility-based rescheduling is performed, the number of required backtrackings and hence overall complexity and runtime is less. / text

The development of a bioartificial pancreas (BAP) has the potential to substantially improve the treatment of insulin-dependent diabetes. Composed of insulin-secreting cells encapsulated in a hydrogel material, a BAP may provide superior glycemic regulation compared with conventional exogenous insulin-delivery therapies. Towards this goal, β- cells or islets encapsulated in alginate microcapsules remain a promising approach. Due to the limited supply of human islets, alternative cell sources are under investigation for incorporation into a BAP, including porcine islets and β- cell lines. Several challenges remain to clinical implementation, including loss of islet or β- cell function and viability following transplantation and host response to the transplanted microcapsules. The objective of this work was to evaluate strategies to improve a BAP by supporting the function and survival of encapsulated islets and β -cells. Towards this goal, two areas were explored: 1) the provision of pro-survival and insulinotropic factors, namely, CXCL12 and GLP-1 (or a GLP-1 analog, Exendin-4), to encapsulated islets and β-cells and 2) modification of the alginate microcapsule to confer long-term resistance to host cell adhesion. To achieve the first objective, methods to deliver both pro-survival and insulinotropic factors to a BAP were developed and their effects on encapsulated β-cells and porcine islets were studied, both in vitro and in vivo. Results demonstrate that delivery of pro-survival and insulinotropic factors is a promising strategy to prolong the survival and function of a BAP. To reduce host cell adhesion to the microcapsule, we employed covalent conjugation of PEG to the surface of alginate-PLL capsules to replace the un-crosslinked layer of alginate used in traditional alginate-PLL-alginate (APA) microcapsules. Results demonstrate that while PEGylation of alginate-PLL microcapsules initially reduced host cell adhesion over 2 weeks in vivo compared with APA capsules, the PEG coating did not provide long-term protection over 3 months. Taken together, these studies represent a multipronged approach towards improving the duration of BAP function, with the ultimate goal of advancing this technology to the clinic.

No description available.

Le traitement du cancer à l’aide d’une exposition aux radiations ionisantes (RI) peut mener au développement de plusieurs effets secondaires importants, dont un retard de réparation et de régénération des tissus. Les mécanismes responsables de ces effets demeurent largement inconnus encore aujourd’hui, ce qui a pour effet de limiter le développement d’approches thérapeutiques. À l’aide d’un modèle de guérison de plaie cutanée chez la souris, nous avons cherché à déterminer les mécanismes par lesquels l’exposition aux RI limite la régénération de la peau. Nos résultats démontrent que l’induction de la "stromal-derived growth factor 1α" (SDF-1α), une cytokine normalement surexprimée dans les tissus hypoxiques, est sévèrement diminuée dans les plaies de souris irradiées versus non-irradiées. Ce défaut corrèle avec un retard de guérison des plaies et est encore évident plusieurs mois suivant l’exposition aux RI, suggérant qu’il y a une altération permanente de la capacité de la peau à se réparer. Parce que SDF-1α est secrété principalement par les fibroblastes du derme, nous avons évalué le potentiel des cellules stromales multipotentes (MSCs), qui sont reconnues pour secréter des niveaux élevés de SDF-1α, à accélérer la régénération de la peau chez les souris irradiées. L’injection de MSCs en périphéries des plaies a mené à une accélération remarquable de la guérison de la peau chez les souris exposées aux RI. Les actions des MSCs étaient principalement paracrines, dû au fait que les cellules n’ont pas migré à l’extérieur de leur site d’injection et ne se sont pas différentiées en kératinocytes. L’inhibition spécifique de l’expression de SDF-1α a mené à une réduction drastique de l’efficacité des MSCs à accélérer la fermeture de plaie indiquant que la sécrétion de SDF-1α par les MSCs est largement responsable de leur effet bénéfique. Nous avons découvert aussi qu’un des mécanismes par lequel SDF-1α accélère la guérison de plaie implique l’augmentation de la vascularisation au niveau de la peau blessée. Les résultats présentés dans ce mémoire démontrent collectivement que SDF-1α est une importante cytokine dérégulée au niveau des plaies cutanées irradiées, et que le déclin du potentiel de régénération des tissus qui est observé suivant une exposition au RI peut être renversé, s’il est possible de restaurer le microenvironnement de la blessure avec un support stromal adéquat. / Cancer treatment using ionizing radiation (IR) may lead to significant side effects, like delayed tissue repair and regeneration. The mechanisms mediating these defects remain largely unknown at present, thus limiting the development of therapeutic approaches. Using a wound healing model, we investigate the mechanisms by which IR exposure limits skin regeneration. Our results show that induction of the stromal-derived growth factor 1α (SDF-1α), a cytokine normally overexpressed in hypoxic tissues, is severely impaired in the wounded skin of irradiated, compared to non-irradiated, mice. This defect is correlated with delayed healing, and is evident for several months following exposure to IR, suggesting permanent impairment of skin repair. Because SDF-1α is secreted mainly by dermal fibroblasts, we evaluated the potential of multipotent stromal cells (MSCs), which secrete high levels of SDF-1α, to improve skin regeneration in irradiated mice. Injection of MSCs into the wound margin led to remarkable enhancement of skin healing in mice exposed to IR. The MSC actions were mainly paracrine, as the cells did not migrate away from the injection site or differentiate into keratinocytes. Specific knockdown of SDF-1α expression led to drastically reduced efficiency of MSCs in improving wound closure, indicating that SDF-1α secretion by MSCs is largely responsible for their beneficial action. We also found that one mechanism by which SDF-1α enhances wound closure likely involves increased skin vascularization. Findings presented in this thesis collectively indicate that SDF-1α is an important deregulated cytokine in irradiated wounded skin, and that the decline in tissue regeneration potential following IR can be reversed, given adequate microenvironmental support.

Environmental assessments and authorisations surrounding project level developments are often made in isolation, without consideration of the regional or strategic context within which individual developments are done. This research investigates the quality of Environmental Management Frameworks (EMF) as strategic environmental instrument. EMF is a unique South African instrument that was first conceptualised in 1989, enacted in 2006 and updated in 2010. EMFs were developed to map environmental sensitivity to aid the screening out of undesired developments in sensitive environments and to minimise unnecessary project level assessments in preferred development areas. EMFs form an important link between environmental assessment (EA) processes and planning strategies such as Spatial Development Frameworks (SDFs) and Integrated Development Plans (IDPs), due to their spatial output of environmental sensitivity maps and their ability to feed strategic assessment processes required by SDFs. They have a legal mandate which ensures their assimilation and use. This research uses a multiple case study approach to review seven EMF documents for their quality. The quality aspects identified are the process, methodology and documentation components, using the printed EMF documentation as primary information source. Quality review criteria were subsequently developed to investigate these inputs, using the legal mandate of EMF as basis. Each case was rated for compliance with the quality criteria using a six–level rating schedule. Further analyses were made by comparing the performance of cases against one another. Public participation emerged as the weakest component of EMF practice, while aspects of sensitivity analysis also performed weaker than other aspects. More focus is required on aligning scales and resolutions of map inputs, mapping methods and general integration of spatial data, especially those of adjoining districts. The need to substantiate a rationale for buffer determination also requires further refinement. The practice of conducting EMF is well established and it can be valuable in sustainable development planning and decisionmaking. Recommendations to enhance the sustainability outcomes and hence effectiveness of this instrument are made, as well as future research objectives for increasing its utility. / Thesis (M. Environmental Management)--North-West University, Potchefstroom Campus, 2011.