Text in Afrikaans / In hierdie studie het die navorser die probleem van kurrikulumdifferensiasie vir Wiskunde Graad R aangespreek, sodat leerders met erge intellektuele gestremdheid ook sukses in Wiskunde Graad R kan ervaar. Die primêre vraag wat aangespreek is, is hoe die vereiste begrippe en vaardighede van die Kurrikulum- en Assesseringsbeleidsverklaring (KABV), vir Wiskunde Graad R aangepas kan word vir leerders met erge intellektuele gestremdheid. Die belangrikheid van die studie lê in die verskil wat differensiasie kan maak aan 'n leerder se geleentheid om sukses te ervaar volgens sy vermoë. Die doel hiervan is om leerkragte wat leerders met erge intellektuele gestremdheid onderrig, te bemagtig. Dit word gedoen deur aanpassings en aktiwiteite voor te stel wat tot voordeel van hierdie leerders in hul onderrigprogram geïmplementeer kan word. Dit sal daartoe bydra dat hierdie leerders die vereistes wat in die kurrikulum gestel word, in ’n beperkte mate kan bereik. Die navorsing is onderneem vanuit 'n inklusiewe perspektief aan die hand van 'n literatuurstudie en kwalitatiewe navorsing (gevalle-studie) wat semi-gestruktureerde onderhoude ingesluit het. Die resultate toon dat differensiasie wel moontlik is en dat daar verskeie aanpassings en aktiwiteite is wat leerkragte kan gebruik om hierdie leerders die geleentheid te bied om sukses te kan ervaar. / In this study the researcher addressed the challenges of curriculum differentiation for Mathematics Grade R to ensure that learners with severe intellectual disability may experience success. The primary question addressed was the manner in which the concepts and skills requirements of the Curriculum and Assessment Policy Statement (CAPS), for Mathematics Grade R can be adjusted to suit the needs of learners with severe intellectual impairment. The importance of this study lies in the significant impact that differentiation can make in providing the opportunity for a learner to experience success according to his abilities. The purpose of this study was to empower teachers of learners with severe intellectual disability with the necessary knowledge, enabling them to successfully implement adaptations. This would allow the learners to achieve the requirements of the proposed curriculum, to a limited extent. Qualitative (case study) research was conducted from an inclusive perspective using a literature review and semi-structured interviews. The results showed that differentiation is possible and that there are several adaptations and activities that could be used by teachers to offer these learners the opportunity to experience success. / Inclusive Education / M. Ed. (Inklusiewe Onderwys)

Since the 1950s modernization theory predicted within the Third World a trajectory for social evolution and development mirroring perceived social and developmental evolution in Western societies since the 17th Century. Despite this theory being much discredited in both Western societies and the developing world; this theory still forms the basis for much analysis and policy formulation within post-1990 South Africa. This thesis looks at various aspects of urban black South Africans' existence and concludes that African tradition has found a place within an urban existence due to it's flexibility in dealing with peoples' daily challenges. An urban existence can thus no-longer be thought of as supplanting tradition in favour of western influences, but rather as bringing about a mixture of western and traditional influences - with positive and negative theoretical and practical developmental consequences / Development Studies / M.A.

The traditional health care system as it prevails in South Africa is part of African culture and intricately linked with the African world view. It embraces traditional norms and values that have survived to this day. In this sense it is more than a constituent part of medical pluralism which has become a global phenomenon. The role of the traditional healer is far more extensive than that of the modern medical doctor. He advises on all aspects of life, including physical, psychological, spiritual, moral and legal matters. He shares the client's world view. He understands the significance of ancestral spirits, the belief in supernatural forces and the reality of witches. It is in this context that modern scientific medicine has not been able to replace traditional medicine, and arguably never will. Traditional medicine is faced with enormous challenges at present. Firstly, the traditional social order is fast disappearing, making way for the state and the individual whose rights as contained in the Bill of Rights of the 1996 Constitution of the Republic of South Africa may seriously clash with traditional norms. Secondly, especially in an urban environment, the healer may encounter stiff competition from more progressive colleagues and modern physicians. Thirdly, scientific medicine basically regards traditional activities as unscientific, unregulated, often harmful and sometimes fatal. Fourthly, anti-witchcraft legislation hinders the traditional practitioner to deal with witches in the culturally appropriate manner. Traditional medicine will not go away. It is therefore necessary to find ways and means to see it practised in a safe and competent manner. As healers agitate for official recognition, it will be regarded as their corresponding duty to professionalise the traditional sector, create a traditional medical council and establish a register of bona fide healers who possess stipulated qualifications and are subject to rules of conduct and discipline. The modern and traditional sectors are essentially complementary and should be accommodated within a legal framework of official health care that protects healers and healed alike. The legal implications of this strategy are discussed in a global as well as regional African context. / Jurisprudence / LL.D.

Summary in English / Romanticism as a broad movement of thought developed as a reaction against rationalism and empiricism in the period of Enlightenment. In his critical evaluation of Getman literature Eichendorff as a historian exammes the excessiveness of esoteric theories in the work of the young intellectuals of the early romantic period in Getmany. The romanticists' idealist celebration of the self, and their tendency to overestimate the power of the imagination and the supreme value of art led to self-adulation and subjectivism which was unacceptable to Eichendorff s understanding of art and religion. The "romantic" attempt at creating a new mythology usmg art as a new kind of religion and thereby making the poet an omnipotent creator could only be rejected by Eichendorff whose moral convictions were strongly based on Christian Catholic beliefs. The young romanticists replaced ethics with aesthetics. Eichendorffs judgement of this development is devastating. He describes the early romantic movement as a "premature abortion". / Classics and Modern European Languages / M.A. (German)

attitudes amongst the members of different races towards the implementation of affirmative action in the Correctional Services Department of South Africa. A literature study on affirmative action was completed and thereafter a questionnaire was developed. An emperical study was done by questionnaire on the determination of perceptions and attitudes of members of the South African Correctional Services Department towards the application of Affirmative Action policies. serious problems if not correctly managed. It was established that the success in any affirmative action strategy rests on the understanding and acceptance of cultural diversity as manifested in perceptions and attitudes. Management information systems needs to be effective and efficient at all times. Changing perceptions and attitudes increased passion and job satisfaction. Recommendations are made for further research on aspects highlighted by the findings. / Penology / M.A. (Penology)

This dissertation focuses on utopian versus dystopian perceptions of rural indigenous African societies with regard to the modern metropolis. Since the evolution of the modern metropolis, rural African societies have undergone significant and complex cultural changes that have dislodged rural cultures from being perceived in terms of the traditional notion of fixity. This has lead to the modern city being seen as either utopian or dystopian by rural African societies. The dissertation questions the “utopianess” of the modern metropolis with a special focus on its central idea of “progress”. Special attention is given to artists who explore this cultural phenomenon in the utopian–dystopian paradigm. The dissertation goes further to address the cultural impact of recent technological developments on rural and urban societies, the researcher’s perceptions of this impact and how this has contributed to the dynamics that characterise the cultures of contemporary rural and urban migrants / Art History, Visual Arts & Musicology / M.A. (Visual Arts)

Durch den Transfer der Gene des heterodimeren T-Zellrezeptors (TZR) mithilfe viraler Vektoren können T-Zellen programmiert werden, ein ausgewähltes Antigen spezifisch zu erkennen. In klinischen Studien wurden solche T-Zellen bereits mit Erfolg zur Immuntherapie von Krebs und viralen Infektionen eingesetzt. Genmodifizierte T-Zellen unterscheiden sich jedoch von normalen T-Zellen, weil sie neben den beiden zelleigenen auch die zwei übertragenen TZR-Gene exprimieren. Diese Situation erlaubt die Bildung vier verschiedener TZR-Heterodimere: der zelleigene TZR, der übertragene TZR und zwei gemischte TZR, bestehend aus je einer übertragenen und einer zelleigenen TZR-Kette. Gemischte TZR bergen das Risiko von Nebenwirkungen, weil sie durch Zufall gesundes Körpergewebe erkennen und so Autoimmunität auslösen könnten. In dieser Arbeit wurden deshalb virale Vektoren entwickelt, die gleichzeitig mit der Übertragung von neuen TZR-Genen den zelleigenen TZR durch RNA Interferenz (RNAi) unterdrücken. Mikro-RNA (miRNA), die in den Vektor MP71 eingefügt wurden, reduzierten den zelleigenen TZR in Maus-T-Zellen um mehr als 85%. Dies hatte zur Folge, dass beide Ketten des übertragenen P14-TZR in gleicher Menge auf der Zelloberfläche exprimiert wurden und die Bildung von gemischten TZR reduziert wurde. In einem Mausmodell der adoptiven T-Zelltherapie verhinderte die Unterdrückung des zelleigenen TZR die Entstehung von Autoimmunität, die andernfalls durch gemischte TZR verursacht wurde. Im Gegensatz dazu führte die Anwendung von gentechnisch optimierten P14-TZR-Genen weder zur angeglichenen Oberflächenexpression der P14-TZR Ketten noch zu weniger Autoimmunität im Mausmodell. Ein anderes Tierexperiment zeigte, dass die miRNA die Funktion der genmodifizierten T-Zellen nicht beeinträchtigte. Schließlich wurde ein viraler Vektor entwickelt und getestet, der die Expression des zelleigenen TZR in menschlichen T-Zellen effektiv unterdrückte und die Bildung von gemischten TZR reduzieren konnte. / T cells can be genetically modified using viral vectors. The transfer of genes encoding both chains of the heterodimeric T cell receptor (TCR) programs T cells to specifically react towards an antigen of choice. Such TCR gene-modified T cells were already successfully applied in clinical studies to treat cancer and viral infections. However, in contrast to nonmanipulated T cells these cells express the transferred TCR in addition to the endogenous TCR and this situation allows the assembly of four different TCR heterodimers: the endogenous TCR, the transferred TCR, and two mixed TCR dimers, composed of one endogenous and one transferred TCR chain. The formation of mixed TCR dimers represents a safety issue because they may by chance recognize self-antigens and thereby cause autoimmune side effects. To overcome this problem, an RNAi-TCR replacement vector was developed that simultaneously silences the endogenous TCR and expresses an RNAi-resistant therapeutic TCR. The expression of miRNA encoded by a retroviral MP71 vector in transduced mouse T cells reduced the surface levels of the endogenous TCR by more than 85%. The knockdown of the endogenous TCR in turn resulted in equal surface expression levels of both transferred P14 TCR chains and prevented the formation of mixed TCR dimers. Accordingly, the development of lethal mixed TCR dimer-dependent autoimmunity (TI-GVHD) in a mouse model of adoptive T cell therapy was dramatically reduced by the knockdown of the endogenous TCR. In contrast, the usage of genetically optimized TCR genes neither resulted in equal surface levels of both P14 TCR chains nor in reduced autoimmunity. A second mouse model demonstrated that the in vivo functionality of the transduced T cells was not negatively influenced by the expression of the miRNA. Finally, an RNAi-TCR replacement vector for human T cells was developed that effectively reduced the expression of the endogenous TCR and prevented the formation of mixed TCR dimers.

La sclérodermie systémique (ScS) est une maladie auto-immune caractérisée par une fibrose cutanée et viscérale ainsi que par des anomalies microcirculatoires. Son origine multifactorielle et ses manifestations cliniques variées en font une maladie à la physiopathologie complexe. Cette maladie rare demeure une affection dont l’étiologie est encore inconnue et pour laquelle il n’existe aucun traitement curatif. Notre laboratoire a mis en évidence le rôle des formes réactives de l’oxygène en mettant au point un modèle animal induit par l’acide hypochloreux. Ce modèle nous a permis d’explorer différentes voies de signalisation intracellulaire, impliquées dans la formation de FRO, favorisant la fibrose. Dans ce travail, nous avons choisi d’explorer dans la sclérodermie systémique différentes voies de signalisation impliquées dans l’inflammation à l’aide d’un modèle de réaction du greffon contre l’hôte sclérodermiforme (GVH-Scl) et d’un modèle de sclérodermie induit par les formes réactives de l’oxygène. De plus, nous avons étudié l’impact de molécules ciblant ces voies afin de fournir de nouvelles données permettent d’enrichir l’arsenal thérapeutique de cette maladie, actuellement pauvre. Les souris obtenues à partir du premier modèle présentent une fibrose cutanée et pulmonaire, une alopécie, une diarrhée et une inflammation hépatique. Une quantité importante d’auto-anticorps ainsi qu’une activation du système immunitaire sont retrouvées. Nous avons observés une activation de la voie de l’EGFR, de STAT3, de Wnt/β-caténine, d’AKT, d’ERK1/2 et de Notch dans la GVH-Scl. L’inhibition de la voie de l’EGFR par l’erlotinib a montré une amélioration clinique associée à une réduction de la fibrose cutanée et de l’inflammation cutanée et hépatique. De plus, l’erlotinib agit sur le système immunitaire et restaure la proportion de LT CD4+ naïfs chez les souris malades ainsi que le taux d’auto-anticorps anti-topoisomérase 1. La co-inhibition des voies de signalisation STAT3, Wnt/β-caténine, AKT, ERK1/2 et Notch par le niclosamide améliore les symptômes de la GVH-Scl chez la souris. Nous avons noté une diminution de la fibrose cutanée et pulmonaire, une diminution de l’inflammation cutanée, hépatique et gastro-intestinale et une diminution de la production d’auto-anticorps. La proportion de cellules naïves parmi les LT CD4+ et CD8+ est plus élevée chez les souris malades traitées que chez les malades non traitées. Les souris du second modèle présentent une fibrose cutanée et pulmonaire et une activation du système immunitaire accompagnée d’une production d’autoanticorps anti-topoisomérase. Nous avons retrouvé une activation des voies de signalisation de STAT3, de Wnt/β-caténine et d’AKT chez les souris sclérodermiques. Nous avons également observés une activation de la voie de signalisation de STAT6 et une surexpression de KLF4 chez ces souris malades. La co-inhibition des voies de signalisation STAT3, Wnt/β-caténine et AKT par le niclosamide améliore la fibrose cutanée et pulmonaire chez les souris sclérodermiques. Cette molécule diminue le nombre et l’activation des LB et des LT CD4+ et CD8+ ainsi que la production des auto-anticorps chez les souris malades. Le traitement de souris sclérodermique par le léflunomide, inhibiteur de STAT6, a aussi montré une amélioration de la fibrose cutanée et pulmonaire et des anomalies immunitaires présentées par les souris sclérodermiques. De plus l’inhibition de STAT6 et de KLF4 par le léflunomide inhibe la polarisation des macrophages en macrophages M2. Ainsi nous avons mis en évidence le rôle des voies de signalisation de l’EGFR, de STAT3, de Wnt/β-caténine, d’AKT, de STAT6 et de KLF4 dans la physiopathologie de la sclérodermie systémique. (...) / Systemic sclerosis (SSc) is a connective tissue disorder that results in skin and inner organs fibrosis, microvascular injuries and auto-immunity. This rare disease has a complex physiopathology which is due to its multifactorial origin and its various clinical manifestations. Its etiology remains unknown and no curative treatment exists at present. Our team highlighted the role of reactive oxygen species (ROS) by developing a hypochlorous acid (HOCl)-induced mouse model of SSc. This model allowed the exploration of several intracellular signalizing pathways which were involved in ROS production and promote fibrosis. In this work, we choose to investigate inflammatory signalizing pathways in SSc with a sclerodermatous graft versus host disease (Scl-GVHD) mouse model and a ROS-induced mouse model. Moreover, we studied the effects of drugs targeting these pathways in order to reinforce data providing new therapeutics. Mice from Scl-GVHD model developed a diffuse cutaneous SSc with pulmonary fibrosis, alopecia, diarrhea and liver inflammation. Production of anti-DNA topoisomerase 1 auto-antibodies and immunological activation was also found. We observed an activation of EGFR, STAT3, Wnt/β-catenin, AKT, ERK1/2 and Notch signaling pathways in Scl-GVHD. Inhibition of EGFR by Erlotinib showed clinical amelioration with a decreased skin fibrosis and decreased skin and liver inflammation. Moreover, Erlotinib decreased production of activated/memory CD4+ T cells and of auto-antibody anti-topoisomerase1. Co-inhibition of STAT3, Wnt/β-catenin, AKT, ERK1/2 and Notch pathways by Niclosamide reversed clinical symptoms of Scl-GVHD in mice. We observed an improvement of skin and lung fibrosis, of cutaneous, hepatic and intestinal inflammation, and a reduced production of auto-antibodies. The ratio of CD4 and CD8 naive T cells was higher in Niclosamide-treated GVHD mice than in untreated GVHD mice. Mice from HOCl-model present skin and lung fibrosis and an immune activation along with the production of auto-antibodies anti-topoisomerase. We found an activation of STAT3, Wnt/β-catenin and AKT signaling pathways in HOCl-mice. We also observed an activation of STAT6 signaling pathway and an overexpression of KLF4 in these sicked mice. Co-inhibition of STAT3, Wnt/β-catenin and AKT pathways by Niclosamide improves skin and lung fibrosis in HOCl-mice. This drug decreased number and activation of B cells and CD4+ and CD8+ T cells and auto-antibodies production in mice. Treatment of HOCl-mice with Leflunomide, STAT6 inhibitor, also showed an improvement of skin and lung fibrosis and of immunological abnormalities in HOCl-mice. Moreover, inhibition of STAT6 and KLF4 by Leflunomide inhibits M2 polarization of macrophages. Thus, we highlighted the role of EGFR, STAT3, Wnt/β-catenin, AKT, STAT6 and KLF4 signaling pathways in physiopathology of SSc. Use of inhibitors of these pathways such as Etrlotinib, Niclosamide and Leflunomide, indicate a clinical and biological efficacity in mouse. These drugs allow the control of the 3 characteristic features of SSc reproduced in these animal models: fibrosis, inflammation and autoimmunity and could thus be effective in fighting the development of clinical-biological abnormalities of SSc.

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogenic blood stem cell transplantation

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