Die verhandeling ondersoek die wyse waarop Deon Opperman die versetmotief in sy Afrikanerdramas uitbeeld en vernuwe om die veranderende sosiale omgewing te weerspieël. Hoofstuk 1 verskaf ‘n oorsig oor verset as leefwyse en motief in die Afrikaanse drama. Hoofstuk 2 bied ‘n teoretiese ondersoek van The theatre of revolt (Brustein 1991), ’n bespreking van begrippe soos herskrywing, multikulturalisme, moderne diaspora en globalisasie sowel as ‘n kontekstuele studie van Deon Opperman se Afrikaanse oeuvre. Hoofstuk 3 (Donkerland) fokus op verset binne ‘n postkoloniale herskrywing van die Afrikanergeskiedenis. Hoofstuk 4 (Kruispad en Ons vir jou) sentreer rondom sosiale verset binne ‘n multikulturele omgewing, terwyl hoofstuk 5 Kaburu as weerkaatsende teks en die aktuele kwessie van die moderne diaspora as versetreaksie aanspreek. Die verhandeling kom tot die slotsom dat Opperman versetteater gebruik om kommentaar op aktuele probleme te lewer en om terselfdertyd‘n boodskap van transformasie oor te dra. / The dissertation examines how Deon Opperman portrays and regenerates the revolt motif in his Afrikaner dramas, in order to reflect the changing social environment. Chapter 1 provides an overview of revolt as lifestyle and as motif in Afrikaans drama. Chapter 2 offers a theoretical examination of The theatre of revolt (Brustein 1991), a discussion of concepts such as rewriting, multiculturalism, modern diaspora and globalization, as well as a contextual study of Deon Opperman’s Afrikaans oeuvre. Chapter 3 (Donkerland) focuses on revolt within the postcolonial rewriting of Afrikaner history. Chapter 4 (Kruispad and Ons vir jou) deals with social revolt within a multicultural milieu, whereas chapter 5 discusses Kaburu as a reflecting text and addresses the issue of the modern diaspora as a reaction to political transition. The dissertation reaches the conclusion that Opperman is using South African theatre as a platform for revolt as well as for transformation. / Afrikaans & theory of Literature / MA (Afrikaans en Algemene Literatuurwetenskap)

Die verhandeling ondersoek die wyse waarop Deon Opperman die versetmotief in sy Afrikanerdramas uitbeeld en vernuwe om die veranderende sosiale omgewing te weerspieël. Hoofstuk 1 verskaf ‘n oorsig oor verset as leefwyse en motief in die Afrikaanse drama. Hoofstuk 2 bied ‘n teoretiese ondersoek van The theatre of revolt (Brustein 1991), ’n bespreking van begrippe soos herskrywing, multikulturalisme, moderne diaspora en globalisasie sowel as ‘n kontekstuele studie van Deon Opperman se Afrikaanse oeuvre. Hoofstuk 3 (Donkerland) fokus op verset binne ‘n postkoloniale herskrywing van die Afrikanergeskiedenis. Hoofstuk 4 (Kruispad en Ons vir jou) sentreer rondom sosiale verset binne ‘n multikulturele omgewing, terwyl hoofstuk 5 Kaburu as weerkaatsende teks en die aktuele kwessie van die moderne diaspora as versetreaksie aanspreek. Die verhandeling kom tot die slotsom dat Opperman versetteater gebruik om kommentaar op aktuele probleme te lewer en om terselfdertyd‘n boodskap van transformasie oor te dra. / The dissertation examines how Deon Opperman portrays and regenerates the revolt motif in his Afrikaner dramas, in order to reflect the changing social environment. Chapter 1 provides an overview of revolt as lifestyle and as motif in Afrikaans drama. Chapter 2 offers a theoretical examination of The theatre of revolt (Brustein 1991), a discussion of concepts such as rewriting, multiculturalism, modern diaspora and globalization, as well as a contextual study of Deon Opperman’s Afrikaans oeuvre. Chapter 3 (Donkerland) focuses on revolt within the postcolonial rewriting of Afrikaner history. Chapter 4 (Kruispad and Ons vir jou) deals with social revolt within a multicultural milieu, whereas chapter 5 discusses Kaburu as a reflecting text and addresses the issue of the modern diaspora as a reaction to political transition. The dissertation reaches the conclusion that Opperman is using South African theatre as a platform for revolt as well as for transformation. / Afrikaans and theory of Literature / M. A. (Afrikaans en Algemene Literatuurwetenskap)

Die Therapie der HIV Infektion besteht aus Kombination mehrerer antiretroviraler Substanzen und birgt ein erhöhtes Risiko an Arzneimittelwechselwirkungen. Das bekannte Problem der Virusresistenz kann zudem durch Enzyminduktion begünstigt werden. Das Ziel der vorliegenden Arbeit lag in Untersuchungen zu Einflüssen der Virustatika auf die Expression von Cytochrom P450 Enzymen: 1A1, 1B1, 3A4 sowie der P-Glykoproteins (MDR1) an immortalisierten Zellsystemen. Die Protease Inhibitoren Indinavir, Nelfinavir, Ritonavir und Saquinavir induzierten die Regulation der mRNA Expression über den Aryl-Kohlenwasserstoff-Rezeptor (AhR) und den Pregnan-X-Rezeptor (PXR) dosisabhängig und signifikant. Die Nukleosidischen Reverse Transkriptase Inhibitoren Zalcitabin, Zidovudin und Lamivudin sowie der Nicht-Nukleosidische Inhibitor Nevirapin zeigten induktive Eigenschaften nur für die AhR Zielgene CYP1A1 und CYP1B1. Amprenavir und Efavirenz aktivierten die PXR-Regulation. Die möglichen Auswirkungen der Induktion der untersuchten Gene wurden ausführlich diskutiert. Die molekularen Grundlagen der interindividuell variierenden Aktivität von CYP3A wurden in einer Probandenstudie untersucht. Es wurden die mRNA Expression in den Leukozyten, die Aktivität des Enzyms und einige bekannte Polymorphismen unter Einwirkung von Rifampicin untersucht und diskutiert. / The therapy of HIV infection requires a combination of several antiretroviral substances accompanying risk factors for drug-drug interactions. Moreover, virus resistance can be promoted by enzyme induction caused by antiretroviral drugs. The aim of the study was to investigate the influences of antiretroviral substances on the expression of cytochrome P450 enzymes: 1A1, 1B1, 3A4 and p-glycoprotein (MDR1) using immortalized cell systems. The protease inhibitors indinavir, nelfinavir, ritonavir and saquinavir induced significantly the regulation of mRNA expression through the aryl hydrocarbon receptor (AhR) and the pregnane-x-receptor (PXR) in a concentration-dependent manner. The nucleoside reverse transcriptase inhibitors zalcitabine, zidovudine and lamivudine and the non-nucleoside reverse transcriptase inhibitor nevirapine showed inductive properties only for the AhR target genes CYP1A1 and CYP1B1.Amprenavir and efavirenz activated the PXR target genes. Potentially effects of the described induction are discussed. In a second part of the work, the molecular mechanisms of the individual varying activity of the CYP3A enzyme were investigated applying an in vivo study. CYP3A4 mRNA expression and rifampicin mediated induction in leucocytes were correlated with systemic enzyme activity under induction and known polymorphisms.

Die invasiven und metastatischen Eigenschaften vieler Tumore werden mit einer Veränderung im physiologischen Gleichgewicht der Matrix Metalloproteinasen (MMP) und ihrer spezifischen und unspezifischen Inhibitoren in Zusammenhang gebracht. Das Ziel dieser Dissertation war es, die Wirkung von Batimastat, einem synthetischen Inhibitor der MMP, auf hormonabhängige und hormonunabhängige Prostatakarzinomzellinien sowie auf das Tumorwachstum im orthotopen Tumormodell des Dunning Tumor (R3327) zu untersuchen. Methoden: Im Zellkulturversuch wurde die Wirkung verschiedener Konzentrationen von Batimastat untersucht und die Proliferation mit dem MTT Test gemessen. Die Induktion des orthotopen Tumors erfolgte durch Inokulation von MATLyLu Zellen in die Rattenprostata (Dunning Tumor der Copenhagen Ratte). 10 Tiere wurden nach Tumorinduktion täglich mit 30 mg/kg Batimastat durch intraperitoneale Gabe behandelt, 10 weitere Ratten erhielten nur das Vehikel. Zehn Kontrolltiere blieben unbehandelt. Der Effekt auf des lokale Tumorwachstum wurden durch Bestimmung des Tumorgewichtes nach 20 Tagen definiert. Results:Batimastat zeigte eine dosisabhänige Hemmung des Wachstums der Prostatakarzinomzellinien in vitro. Bei 4000 ng/ml kam es zu einer eindeutigen Hemmung des Zellwachstums. Im Tierversuch fand sich nach 20 Tagen in der Kontrollgruppe ein mittleres Tumorgewicht von 18.9 ± 5,4 g, in der Vehikelgruppe von 22.3 ± 4,3 g und in der mit Batimastat behandelten Gruppe von 11.1 ± 2,6 g. Im Vergleich zur Kontroll- und Vehikelgruppe, zeigte sich in der Batimastatgruppe ein signifikant geringeres Tumorgewicht. Zusammenfassung: Batimastat kann das Tumorwachstum in einem Standardtiermodell des Prostatakarzinoms vermindern. Der Dunning Tumor der Copenhagen Ratte ist ein zuverlässiges Tiermodell zur weiteren Untersuchung von synthetischen Inhibitoren der MMP. / Background: Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of this dissertation was to determine the potential of a synthetic metallproteinase inhibitor, batimastat, to show its in vitro effect on hormonedependent and hormoneindependent prostate cancer cell lines and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats. Methods: In vitro, a dose response curve of batimastat was generated over 5 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MATLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg / kg / body weight) or vehicle once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation. Results: Significant inhibiton of tumor cell proliferation in vitro occurred at 4000 ng / ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 ± 5,4 g in the control group without treatment, to 22.3 ± 4,3 g in the vehicle group, an to 11.1 ± 2,6 g in the treated group. In comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat. Conclusions: Batimastat is able to reduce tumor growth in the standard prostate cancer model. Using this model, activity against cancer progression of future inhibitory agents can be reliably assessed.

This thesis analyzes the major theme of ‘postcolonial genealogy’ in portraying the African bending under the weight of colonial history in Le vieux nègre et la médaille, Une vie de boy of Ferdinand Oyono and Le Chercheur d’Afriques of Henri Lopes. Being a product of a colonial Genesis, the African character runs behind the colonizer’s mirror through his Civilizing Mission. René Girard’s ‘double bind’ theory explains how this cultural assimilation is, in Le vieux nègre et la médaille and Une vie de boy, a dead end because the colonizer needs a subordinate and not an equal. The cohabitation of a black housewife with the French Commander in Le Chercheur d’Afriques should be seen as simply an allegory of postcolonial Africa’s dependency on the West. The consequences of the feminization of the African continent are enormous in the post-colonial imaginary. While the colonizer had conquered Africa with his Herculean body, in Oyono’s novels, his Fall is obtained through the aesthetics of Bakhtinian ‘rabaissement’ which degrades his ‘grotesque body’ to that of the colonized. The colonizer and the colonized are neutralized and leveled in their perishable bodies, thus, making futile the Civilizing Mission that operated by ranking races. Power is never total. It is always imperfect, and can never destroy a subjectivity that resists it. In Oyono’s novels, the Fall of the colonial Father is also obtained through the inquisitive gaze that the colonized return back to the colonizer, and through their ‘subversive mimicry’ that parodies his codes. In Une vie de boy and Le Chercheur d’Afriques, the ‘son-Father’ relationship between the hero and the colonial Father, is also symbolic of the ‘Africa-West’ rapports. Living under the specter of the Father, the son has to negotiate his survival between weaning and parricide. The biological miscegenation in Le Chercheur d’Afriques is a metaphor of the ‘rhizome identity’ of the postcolonial African who renounces both the Fathers of Negritude and those of the Civilizing Mission. / Thesis (Ph.D, French) -- Queen's University, 2011-06-24 12:43:30.006

The central thesis of this dissertation is that by combining classical scheduling methodologies with those of inventory management and queueing theory we can better model, understand and solve complex real-world scheduling problems. In part II of this dissertation, we provide models of a realistic supply chain scheduling problem that capture both its combinatorial nature and its dependence on inventory availability. We present an extensive empirical evaluation of how well implementations of these models in commercially available software solve the problem. We are therefore able to address, within a specific problem, the need for scheduling to take into account related decision-making processes. In order to simultaneously deal with combinatorial and dynamic properties of real scheduling problems, in part III we propose to integrate queueing theory and deterministic scheduling. Firstly, by reviewing the queueing theory literature that deals with dynamic resource allocation and sequencing and outlining numerous future work directions, we build a strong foundation for the investigation of the integration of queueing theory and scheduling. Subsequently, we demonstrate that integration can take place on three levels: conceptual, theoretical and algorithmic. At the conceptual level, we combine concepts, ideas and problem settings from the two areas, showing that such combinations provide insights into the trade-off between long-run and short-run objectives. Next, we show that theoretical integration of queueing and scheduling can lead to long-run performance guarantees for scheduling algorithms that have previously been proved only for queueing policies. In particular, we are the first to prove, in two flow shop environments, the stability of a scheduling method that is based on the traditional scheduling literature and utilizes processing time information to make sequencing decisions. Finally, to address the algorithmic level of integration, we present, in an extensive future work chapter, one general approach for creating hybrid queueing/scheduling algorithms. To our knowledge, this dissertation is the first work that builds a framework for integrating queueing theory and scheduling. Motivated by characteristics of real problems, this dissertation takes a step toward extending scheduling research beyond traditional assumptions and addressing more realistic scheduling problems.

The central thesis of this dissertation is that by combining classical scheduling methodologies with those of inventory management and queueing theory we can better model, understand and solve complex real-world scheduling problems. In part II of this dissertation, we provide models of a realistic supply chain scheduling problem that capture both its combinatorial nature and its dependence on inventory availability. We present an extensive empirical evaluation of how well implementations of these models in commercially available software solve the problem. We are therefore able to address, within a specific problem, the need for scheduling to take into account related decision-making processes. In order to simultaneously deal with combinatorial and dynamic properties of real scheduling problems, in part III we propose to integrate queueing theory and deterministic scheduling. Firstly, by reviewing the queueing theory literature that deals with dynamic resource allocation and sequencing and outlining numerous future work directions, we build a strong foundation for the investigation of the integration of queueing theory and scheduling. Subsequently, we demonstrate that integration can take place on three levels: conceptual, theoretical and algorithmic. At the conceptual level, we combine concepts, ideas and problem settings from the two areas, showing that such combinations provide insights into the trade-off between long-run and short-run objectives. Next, we show that theoretical integration of queueing and scheduling can lead to long-run performance guarantees for scheduling algorithms that have previously been proved only for queueing policies. In particular, we are the first to prove, in two flow shop environments, the stability of a scheduling method that is based on the traditional scheduling literature and utilizes processing time information to make sequencing decisions. Finally, to address the algorithmic level of integration, we present, in an extensive future work chapter, one general approach for creating hybrid queueing/scheduling algorithms. To our knowledge, this dissertation is the first work that builds a framework for integrating queueing theory and scheduling. Motivated by characteristics of real problems, this dissertation takes a step toward extending scheduling research beyond traditional assumptions and addressing more realistic scheduling problems.

The study was conducted in the Brits District. Six schools were chosen of which 3 belonged to the former model C schools where the language of teaching and learning is Afrikaans, and the other 3 schools were previously disadvantaged/rural schools. A qualitative study was used to garner information in the form of interviews, document analysis and observation. The study attempt to find out the exact role that the School governing body (SGBs) play in the implementation of language policy as stipulated in the Constitution. It was revealed that of the 2 types of schools the school governing body (SGBs) for former model C schools are aware of the role they have to play in the implementation of the language policy whereas the school governing body (SGBs) for the rural schools are still grappling with their role as custodian of language policy implementation. A number of concepts emerged from the study where it became apparent that rural schools and former model C school’s play field were not equally levelled from the onset. Former model C school governing body (SGBs) seem to be aware of their role in the implementation of language policy, whereas the rural school, school governing body (SGBs) are aware of their other roles e.g. school maintenance, school fund and hiring of educators. On the other hand they are of the opinion that language policies is for the principal and the school management team. In addition it was observed that the school governing body (SGBs) for rural schools has low morale, do not have the language policy document and generally lack interest in the services they are supposed to provide critical theory underpins this study. / Educational Leadership and Management / M. Ed. (Education Management)

Serotonin gilt als Hauptangriffsstelle gängiger Antidepressiva bei schweren Depressionen, wie bspw. selektive Serotonin-Wiederaufnahmehemmer (SSRI), und -Enhancer (SSRE). Es bleibt offen, ob SSRI / E ausschließlich über die Manipulation des Serotoninspiegels wirken, oder ob alternative Signalwege daran beteiligt sind. Ansatzpunkte hierfür sind beispielsweise die neurotrophen Signalwege (spez. Brain derived neurotophic factor, BDNF) oder die Hypothalamus-Hypophysen-Nebennieren- (HPA) – Signalwege des Stressachsensystems. Ebenfalls wurde in Nagetiermodellen beobachtet, dass mit der Dysregulation des zentralen Serotoninsystems bei schweren Depressionen, ein Rückgang der Neurogenese im Gyrus dentatus des Hippocampus einhergeht. Ziel dieser Arbeit war, das Zusammenspiel von Serotonin, BDNF, adulter Neurogenese und der Stressachse zu untersuchen. Zentrum der Studien ist ein Mausmodell, mit einer genetischen Depletion des zentralen Serotonin-synthetisierenden Enzyms Tryptophanhydroxylase 2 (sog. Tph2-/- Mäuse). Es wurden die physiologische Reaktionen auf die Behandlung mit gängigen Antidepressiva abhängig von der Abwesenheit von Serotonin untersucht, um mögliche alternative Signalwege aufzeigen zu können. Die bekannte Zunahme der Neurogenese nach SSRI/SSRE-Behandlung wurde in Wildtyptieren beobachtet, während die Therapie in Tph2-/- Mäusen keine direkte kausale Wirkung zeigte. Im Gegensatz dazu waren die BDNF-Spiegel in depressionsrelevanten Hirnregionen in Tph2-/- Mäusen nach SSRI, signifikant verringert. Auch zeigen die Studien eine neurobiologische Relevanz von Serotonin im ZNS, bei den antidepressiven Mechanismen einer Elektrokonvulsiven Krampftherapie. Ebenfalls deuten erhöhte Neurogeneseraten bei lebenslanger Abwesenheit von Serotonin im ZNS, Therapiemethoden-unabhängig, möglicherweise auf eine modulierte Stressreaktion hin. Untersuchungen der Parameter des HPA-Stressachsensystems, wiesen auf einen grundlegend veränderten Stresshormonspiegel in Tph2-/- Mäusen hin. / Serotonin, the "molecule of happiness" is an important target for antidepressants. The mainly prescribed drugs in major depression are selective serotonin re-uptake inhibitors (SSRI); but recently, SSR-enhancer (SSRE) have also attracted clinical attention. However, only a quarter of patients responds to treatment. It needs to be determined, whether SSRI/E act solely via manipulating serotonin levels or whether other pathways are involved, e.g. neurotrophic signaling (brain-derived neurotrophic factor, BDNF) or the hypothalamus-pituitary-adrenal (HPA)-axis. Furthermore, in major depression, dysregulation of central serotonin signaling is accompanied with a decline in hippocampal neurogenesis, as has been observed in rodent models. At the center of this thesis is a mouse model deficient in the central serotonin-synthesizing enzyme, tryptophan hydroxylase 2 (Tph2-/- mice). I have investigated physiological responses to antidepressant treatment in the absence of brain serotonin, and the possible role of alternative pathways. I observed the typical increase in neurogenesis upon SSRI treatment in WT mice, while it had no effect in Tph2-/- mice. In contrast, BDNF levels were significantly decreased in Tph2-/- mice after treatment with no effect in WT control mice. Furthermore, my results show a critical role of brain serotonin in the neurobiological effects of electroconvulsive seizure. Surprisingly, in animals lacking central serotonin, increased neurogenesis was observed independently of the treatment. The gathered data indicated an altered stress response; therefore, parameters of the HPA-axis have been studied, indicating a downregulated HPA system in Tph2-/-animals in baseline state, but showed no difference in treatment or feedback control. This thesis gives insight into the mechanisms of antidepressant action and reveals ideas for novel pathways involved in the process that could be used as targets in therapeutic approaches and further research in major depression.

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