In The Passion According to GH, Clarice Lispector novel, published in 1964, to verify how is the disintegration mimetic narrative, occurs an everyday and trite situation - a woman, identified only as G. H, kill a cockroach - but this fact in the story takes many dimensions and results an existential quest of character. This quest unleash changes in the psychology of GH, which are reviewed in the study, in the light of Freudian theory, especially the theory of drive, the element "strange" and the pleasure principle. We also verify the process of abjection, Kristeva, and their correspondence in the narrative. The analysis is done by inserting the reading in an attempt to show as getting rid of the referential illusion and the failure of the narrative, which finds its limits in silence. / Em A paixão segundo G. H., romance de Clarice Lispector, publicado em 1964, no qual se busca verificar como se dá a desintegração mimética na narrativa, ocorre uma situação cotidiana e banal uma mulher, identificada apenas como G. H, mata uma barata , mas esse fato adquire muitas dimensões na narração e origina uma busca existencial da personagem. Essa busca desencadeia transformações na psicologia de G. H., as quais são revistas, no estudo, à luz da teoria freudiana, principalmente, da teoria das pulsões, do elemento estranho e do princípio de prazer. Também se busca verificar o processo da abjeção de Kristeva, e suas correspondências na narrativa. A análise se faz pela inserção na leitura na tentativa de mostrar como acontece o desfazer-se da ilusão referencial e o fracasso da narrativa, que encontra seus limites no silêncio.

Initiée par René Girard, la théorie mimétique suggère que l’égalité des conditions consacrée comme un droit exacerbe la rivalité entre semblables. Quand l’étiolement de la souveraineté étatique et la logique compétitive de l’économie marchande coïncident avec la prolifération de conflits aux enjeux planétaires, cette rivalité des égaux prend une valeur paradigmatique. L’ambition d’une anthropologie mimétique à traiter de l’époque contemporaine mieux que la philosophie politique idéaliste ou la science politique réaliste suppose une reformulation. Espérance de pallier une insuffisance d’être, le désir mimétique, ou désir d’être autre, aboutit à un résultat contradictoire, la déception de rester insuffisant, l’autre étant alors perçu à la fois comme modèle et obstacle. Pour les acteurs politiques, ce désir devient la revendication d’une égale puissance d’être, promesse faite autant par la citoyenneté, le droit des peuples à disposer d’eux-mêmes que la souveraineté des États sur leur territoire et leur population.En tant que modalité de la contention de la violence, le politique serait ainsi analysable par une « science des rapports humains », anthropologie englobante et non-disciplinaire adoptant un interdividualisme méthodologique. Sur fond de menaces inédites pour la pérennité de l’humanité, la réciprocité des rapports humains fait douter de la compatibilité entre projet égalitaire, quête d’identité et concorde sociale. Ces rapports questionnent également la prépondérance actuelle de la compétition dans les institutions, entre autres politiques, laquelle s’est imposée comme liant paradoxal du gouvernement représentatif et de l’économie de marché. / Conceived by René Girard, mimetic theory suggests that the equality of conditions, established as a right, exacerbates the rivalry between similar individuals or groups. When the withering away of state sovereignty and the competitive logic of the market economy overlap with the multiplication of conflicts, this rivalry of equals becomes a relevant paradigm.Mimetic anthropology’s ambition – to address contemporary issues better than either idealistic political philosophy or realistic political science –, demands nevertheless to be revisited. The hope to overcome a lack of being, mimetic desire, or one’s desire to become someone else ends up giving way to a contradictory outcome: the disappointment of remaining oneself, the other thereby being perceived as both one’s model and one’s obstacle. For political actors, this desire turns into the claim of the equal power to be, which the promise of citizenship, the right of peoples to self-determination and the state sovereignty over its people and its territory each exemplify. As a modality of the containment of violence, politics could then be analyzed by a non-disciplinary "science of human relationships", implementing a methodological interdividualism. Against the backdrop of unprecedented threats to the survival of humanity, the reciprocity of human relationships casts doubt on the compatibility between the egalitarian project, the quest for identity, and social harmony. These relationships also question the current predominance of competition in the institutions, including political institutions, which has become the paradoxical binding agent between representative governments and the market economy.

The NF-κB family of transcription factors can be activated through canonical (classical) or non-canonical (alternative) signalling pathways, which are regulated by the redundant ubiquitin ligases, cellular inhibitor of apoptosis 1 and 2 (cIAP1 and cIAP2). While the canonical NF-κB pathway is needed for myoblast proliferation, it is inactivated during myoblast differentiation. However, the non-canonical NF-κB pathway is a major factor in promoting myoblast fusion, which is crucial to the processes of myogenesis and muscle repair. Ablation of cIAP1 levels through a chemical antagonist such as a SMAC- mimetic compound (SMC) activates non-canonical signalling to enhance myogenesis. The cytokine TNF-like weak inducer of apoptosis (TWEAK) has also been shown to activate primarily the alternative NF-κB pathway when signalling through its receptor Fn14. Here I show that alternative NF-κB signalling activity, stimulated by the addition of TWEAK or loss of cIAP1, can promote myogenesis. I also demonstrate that TWEAK is an endogenous myokine produced by myoblasts to promote their own differentiation, and suggest that targeting the alternative NF-κB pathway, with SMAC-mimetics or recombinant TWEAK for example, would be of therapeutic value in the repair and regeneration of muscle for various myopathies.

Tuberous sclerosis complex (TSC) is a multisystem tumor-forming disorder caused by biallelic inactivation of TSC1 or TSC2. The primary cause of mortality arises from mesenchymal manifestations in the lung and kidney: pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipomas (RAMLs). Despite a well-described monogenic etiology, there remains an incomplete understanding of disease pathogenesis. Consequentially, tractable models which fully recapitulate disease characteristics are lacking. Here, I develop and study novel tissue-engineered models of TSC lung and kidney disease. In my first chapter, I demonstrate that lung-mimetic hydrogel culture of pluripotent stem cell-derived diseased cells more faithfully recapitulates human LAM biology compared to conventional culture on two-dimensional plastic. Leveraging this culture system, I conducted a three-dimensional drug screen using a custom 800-compound library, tracking cytotoxicity and invasion modulation phenotypes at the single cell level. I identified histone deacetylase (HDAC) inhibitors as a group of anti-invasive agents that are also selectively cytotoxic towards TSC2-/- cells. HDAC inhibitor therapeutic effects remained consistent in vivo upon xenotransplantation of LAM cellular models into zebrafish. In my second chapter, I develop a genetically-engineered human renal organoid model which recapitulates pleiotropic features of RAMLs in vitro and upon orthotopic xenotransplantation. I find that loss of TSC1/2 affects multiple developmental processes in the renal epithelial, stromal, and glial compartments. First, loss of TSC1/2 leads to an expanded stroma by favouring stromal cell fate acquisition and alters terminal stromal cell identity. Second, epithelial cells in the TSC1/2-/- organoids exhibit a rapamycin-insensitive epithelial-to-mesenchymal transition. Third, a melanocytic population forms exclusively in TSC1/2-/- organoids, branching from MITF+ Schwann cell precursors of a bona fide neural crest-to-Schwann cell differentiation trajectory. Through these two thesis chapters, I realize the power of tissue-engineered models for the study of TSC. This work offers novel insights into the pathogenesis of RAMLs and identifies a new class of therapeutics suitable for trialing in patients with pulmonary LAM.

The main subject of the presented work is the question of power within the context of sociological theory, and in relation to the mechanism of psychological mimesis and the phenomenon of the sacred. Our starting point is René Girard's mimetic theory, which systematizes the relationship between the mechanism of psychological mimesis and the sacred - in the light of the phenomenon of violence. We, firstly, present Girard's mimetic theory, explicate its main concepts, and situate all into a broader context. Further, we critically examine Girard's theoretical scheme and come to the conclusion that his theoretical and conceptual framework calls for a revision, if it is to be utilized within the context of sociology and social theory. Consequently, we try to "sociologize" Girard's thinking. First, we position his line of thought into the wider sociological context, and then examine his theory in the light of thinking of two classical sociologists, Gabriel Tarde and Émile Durkheim. We then project this examination into a theoretical and conceptual synthesis on the basis of which we formulate our own conceptual scheme, which is based on the assumption of psychological mimesis as an anthropological constant, and which overcomes the main shortcomings of Girard's theoretical framework. On the basis of this...

Proposing the concept of mimetic uncertainty, this project aims to provide a critical inquiry into the correspondence of unreliable narration and realism. Building on Springett (2013) and Olsen (2003), a distinction between narratorial unreliability and uncertainty is proposed to denote whether a narrator explicitly signals an awareness of their fallible narration. I thereafter indicate how narratorial uncertainty, on the one hand, can serve to evoke a “reality effect” (Barthes 1989) on a receptive aesthetic level; and on the other hand, can provide a form of historicity (Jameson 1985) and discursive realism (Auerbach 2003) on an expressive historical axis. Through this tripartite framework, realism is contextualised within the discourse of unreliable narration, as well as the specific debate which surrounds uncertainty and fallibility. The textual analysis focuses on three separate works—Daniel Defoe’s A Journal of the Plague year (1722), Virginia Woolf’s Mrs Dalloway (1925), and finally, Tao Lin’s Taipei (2013)—with the twofold aim of (1) providing a model for approaching uncertain narration and (2) applying a historically contingent realist reading. I argue that in all three novels, emphasis on how readers may respond to uncertain narration provides insight into socio-historical and discursive points of friction surrounding their authors. The overarching ambition of this study is to provide a more substantial and historicized understanding of the stylistic devices of contemporary authorship, while more broadly signifying the unexpected critical acuity of mimetic approaches as well as the challenges and demands which metamodernist literature approaches.

Bakgrund och problem: Bolagisering är ett växande fenomen inom svenska kommuner där övergången till ett kommunalt bolag innebär en rad förändringar inom verksamheten såsom tillämpning av aktiebolagslagen och en förändrad styrkedja. Motiven bakom bolagisering omfattas av att öka effektiviteten i verksamheten samtidigt som kostnadsreduceringar kan uppnås. Däremot presenteras även en rad risker som reformeringen kan medföra såsom en minskad insyn i det kommunala bolaget till följd av en separation av kontroll och ägande samt att bolaget driftar från kommunen. Till följd av den kritik som riktats mot bolagisering så kan lämpligheten ifrågasättas i specifika kontexter samt vilka faktorer som påverkat beslutet att genomföra reformeringen.  Syfte: Syftet med denna studie är att skapa förståelse för vilka faktorer som påverkar ett bolagiseringsbeslut i en vård- och omsorgsförvaltning samt om beslutet fastställts till följd av att andra kommuner tidigare genomfört en bolagisering.Metod:Denna studie är av kvalitativt slag där en abduktiv forskningsansats antagits. Vidare har en enfallsstudie genomförts där empirisk insamling skett dels genom semistrukturerade intervjuer men även genom dokumentgranskning.Slutsats: Bolagiseringsbeslutet i en vård- och omsorgsförvaltning baseras på ett erhållande av ekonomiska fördelar i form av gynnsammare mervärdesskatteregler. Vidare påvisas även att kommunernas samverkan påverkar beslutet att genomföra en bolagisering där en uttryckt efterliknelse präglat beslutsfattandet samt genomförandet. Bolagiseringen hade troligtvis inte uppdagats om inte en närliggande kommun genomfört reformeringen tidigare vilket påvisar betydande influenser kommunerna emellan. Metod: Denna studie är av kvalitativt slag där en abduktiv forskningsansats antagits. Vidare har en enfallsstudie genomförts där empirisk insamling skett dels genom semistrukturerade intervjuer men även genom dokumentgranskning.Slutsats: Bolagiseringsbeslutet i en vård- och omsorgsförvaltning baseras på ett erhållande av ekonomiska fördelar i form av gynnsammare mervärdesskatteregler. Vidare påvisas även att kommunernas samverkan påverkar beslutet att genomföra en bolagisering där en uttryckt efterliknelse präglat beslutsfattandet samt genomförandet. Bolagiseringen hade troligtvis inte uppdagats om inte en närliggande kommun genomfört reformeringen tidigare vilket påvisar betydande influenser kommunerna emellan. Slutsats: Bolagiseringsbeslutet i en vård- och omsorgsförvaltning baseras på ett erhållande av ekonomiska fördelar i form av gynnsammare mervärdesskatteregler. Vidare påvisas även att kommunernas samverkan påverkar beslutet att genomföra en bolagisering där en uttryckt efterliknelse präglat beslutsfattandet samt genomförandet. Bolagiseringen hade troligtvis inte uppdagats om inte en närliggande kommun genomfört reformeringen tidigare vilket påvisar betydande influenser kommunerna emellan. / Background and problem: Corporatization is a growing phenomenon in Swedish municipalities where the transition to a municipal company implicates a number of changes such as application of aktiebolagslagen and a changed control chain. The motives behind corporatization are to increase efficiency while enabling cost reduction. On the other hand, corporatization is also associated with risks such as a reduced insight in the municipal company due to separation of ownership and control and that the municipal company is being separated from the municipality. As a result of the criticism of corporatization, the adequacy has been questioned in specific industries as well as the factors that influence the decision to realize the reform.  Purpose: The purpose of this study is to create an understanding of the factors that influence a decision to corporatize a health- and social care administration and also if the decision was made as a result of other municipalities realizing the reform earlier. Method:  This study is of a qualitative nature where an abductive research approach has been adopted. Furthermore, a case study has been conducted where the empirical material is based on semi-structured interviews and document review. Conclusion: The decision to corporatize a health- and social care administration is based on beneficial VAT-regulations. Furthermore, it is also shown that a cooperation between municipalities affects the decision to realize a corporatization where an expressed imitation occurs regarding the decision-making as well as the implementation. If the nearby municipality would not have realized a corporatization the phenomenon would probably not have been discovered which demonstrates significant influences between the municipalities.  Method: This study is of a qualitative nature where an abductive research approach has been adopted. Furthermore, a case study has been conducted where the empirical material is based on semi-structured interviews and document review.  Conclusion: The decision to corporatize a health- and social care administration is based on beneficial VAT-regulations. Furthermore, it is also shown that a cooperation between municipalities affects the decision to realize a corporatization where an expressed imitation occurs regarding the decision-making as well as the implementation. If the nearby municipality would not have realized a corporatization the phenomenon would probably not have been discovered which demonstrates significant influences between the municipalities.

All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.

No description available.

Thesis (MA)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The stereotypical figure of the femme fatale as irresistible seductress, who inevitably brings about death, is well known. This figure is nevertheless strangely absent from Afrikaans literature. This is what makes the appearance of the character of Nicolette in André Brink’s novel, The Ambassador (1963), so remarkable. Not only is she a complex femme fatale, she also adds a new dimension to the cliché. The striking similarities between Nicolette and Kathe, the female protagonist in Henri-Pierre Roché’s novel Jules et Jim (1953), justify a comparative study between these two novels. Although both of them bring about death, it seems that the presence of these femme fatale characters has positive rather than negative consequences. Contrary to the stereotypical evil temptress, Nicolette and Kathe are more natural, spontaneous and unpredictable – apparently free from the constricting qualities of the bloodthirsty femme fatale. In this comparative study, the image of the femme fatale is investigated through the close examination of its role and function in Jules et Jim and The Ambassador. By examining the philosopher René Girard’s theories on mimetic desire, violence and sacrifice as well as Georges Bataille’s ideas on eroticism and death, the nature of the femme fatale in these two novels is analysed in order to determine to what extent the image of the femme fatale as negative archetype could be reconsidered. / AFRIKAANSE OPSOMMING: Die stereotipiese figuur van die femme fatale as onweerstaanbare verleidster wat noodwendig die dood teweegbring, is alombekend. Tog blyk daar 'n opvallende afwesigheid van dié gevaarlike karakter in die Afrikaanse letterkunde te wees. Dit is waarom die verskyning van die karakter van Nicolette in André P. Brink se roman, Die Ambassadeur (1963), so merkwaardig is. Nie net is Nicolette 'n komplekse femme fatale karakter nie, maar bring sy ook 'n nuwe dimensie tot die geykte stereotipe. Dit is dan veral die treffende ooreenkoms tussen Nicolette en Kathe, die vroulike protagonis in Henri-Pierre Roché se roman Jules et Jim (1953), wat 'n vergelykende studie tussen hierdie twee romans regverdig. Alhoewel albei die dood teweegbring, blyk dit dat die teenwoordigheid van hierdie femme fatale karakters eerder positiewe as negatiewe gevolge het. Anders as die stereotipiese bose verleidster, is Nicolette en Kathe meer natuurlik, spontaan en onvoorspelbaar – oënskynlik vry van die beperkende eienskappe van die bloeddorstige femme fatale. In hierdie vergelykende studie word die beeld van die femme fatale ondersoek deur die rol en funksie daarvan in Jules et Jim en Die Ambassadeur in diepte te bestudeer. Deur die filosoof René Girard se teorieë oor mimetiese begeerte, geweld en offergawe asook Georges Bataille se idees oor erotisme en die dood te ondersoek, word die aard van die femme fatale in hierdie twee romans vergelykend ontleed om sodoende te bepaal tot watter mate die beeld van die femme fatale as negatiewe argetipe heroorweeg kan word. / RESUME: La figure stéréotypée de la femme fatale comme séductrice irrésistible et malfaisante qui entraîne inévitablement la mort, est bien connue. Néanmoins, nous constatons une absence frappante de cette figure dans la littérature de langue afrikaans. Voilà ce qui rend d’autant plus remarquable et surprenante l’apparence du personnage de Nicolette dans le roman L’Ambassadeur d’André Brink (1963). Non seulement est-elle une femme fatale complexe, mais Nicolette apporte aussi une nouvelle dimension à la figure rebattue. Ce sont surtout les similarités évidentes entre Nicolette et Kathe, la protagoniste féminine du roman Jules et Jim d’Henri-Pierre Roché (1953), qui justifient une étude comparée de ces deux romans. Bien que ces deux personnages féminins provoquent la mort d’un homme, il semblerait que la présence de ces femmes fatales ait des conséquences positives plutôt que négatives. Contrairement au stéréotype de la séductrice maléfique, les personnages de Kathe et de Nicolette sont plus naturels, spontanés et imprévisibles – apparemment libres de toute étiquette restrictive attribuée à la femme fatale assoiffée de sang. Dans cette étude comparée nous nous pencherons sur l’image de la femme fatale en examinant son rôle et sa fonction dans les romans Jules et Jim d’Henri-Pierre Roché et L’Ambassadeur d’André Brink. En considérant les théories sur le désir mimétique, la violence et le sacrifice que propose René Girard ainsi que les idées de Georges Bataille sur l’érotisme, nous essayons enfin d’établir dans quelle mesure on pourrait reconsidérer la définition étriquée de la femme fatale comme archétype négatif.