One of the most interesting aspects of Le Petit Prince by Antoine de Saint-Exupéry (1999[1946]) is its dual address. The illustrated narrative is at once a charming story for children and an allegory inviting adults to consider philosophical questions. In the graphic-novel adaptation of the book by Joann Sfar (2008), this allegory is obscured:; the abstract, philosophical ideas recede to the background while the material details of the story become more prominent. But this recession of the allegory does not mean that the adaptation turns its back on adult readers completely. The graphic novel creates a web of intertextual references, which, among other things, amplify the suggestion in the source text that the protagonist is Antoine de Saint-Exupéry himself. It thus displaces the adult interest from allegory to autobiography and the mechanism of adult address from allegory to intertextuality, restricting its adult audience. For those adult readers who remain addressed by the graphic novel, however, the text identifies itself explicitly as a translation, which has consequences for we should think about the “voice” of the translator. Un des aspects les plus intéressants du livre Le Petit Prince d’Antoine de Saint-Exupéry (1999 [1946]) tient au fait que le récit illustré est une histoire charmante pour les enfants en même temps qu’il invite les adultes à réfléchir à des questions philosophiques. Dans l’adaptation du récit en bande dessinée par Joann Sfar (2008), les éléments abstraits du livre s’estompent derrière les détails concrets de l’histoire. Cet effacement de l’allégorie ne signifie pourtant pas que la bande dessinée tourne le dos aux adultes : elle crée un réseau intertextuel qui renforce l’impression donnée par le texte source que le véritable protagoniste est Antoine de Saint-Exupéry. Ainsi, l’intérêt pour les questions philosophiques se reporte sur l’autobiographie et, passant de l’allégorie à l’intertextualité, la bande dessinée sollicite alors moins les adultes. Cependant, pour les adultes auquelles la bande dessinée s’addresse toujours, le texte s’identifie explicitement comme une traduction, ce qui implique une réévaluation du concept de la “voix” du traducteur.

Matrix assisted laser desorption/ionisation mass spectrometry (MALDI-MS) for small molecule analysis has been plagued with inherent problems associated with matrix interference. The matrix plays an important role in MALDI-MS where it has the ability to absorb UV energy from the laser employed and transfer it to the analyte, acts as a proton donor and protecting the analytes from being obliterated. For decades, research has been performed to eradicate matrix interference by matrix avoidance, finding alternative matrices, suppression through sample preparation methods and via chemical modification.In this investigation a number of the above mentioned approaches have been undertaken. First, a mesoporous silica powder, SBA-16, functionalised with a phenyl group to absorb UV from the MALDI-MS laser gave unfruitful results due to inhomogeneous dispersion of the SBA-16 powder. Therefore the same material was prepared but as a thin film and a homogeneously coated surface was generated with the phenyl group incorporated into the silica and this was compared with a conventional matrix, 2,5-dihydroxybenzoic acid (DHB). This was by far the most sensitive method which was accurate, with little background noise and importantly for small molecule analysis clear of matrix interference. Other surface systems were also tested such as graphene on copper and silver on copper, but the functionalised SBA-16 thin film remained the best. Graphite and 2B pencil were also investigated for MALDI-MS but were compared with conventional matrices (DHB and α-cyano-4-hydroxycinnamic acid (CHCA)) in a functional genomics study. The ability of all methods to find subtle phenotypic differences in various yeast strains was assessed with the help of multivariate data analysis (MVDA). Although DHB came out best, 2B pencil produce notably good separations that correlated nicely with the different genotypes. Therefore in addition to conventional matrices, 2B pencil should be considered for functional genomic studies when MALDI-MS is used as it is such a rapid and inexpensive method. Finally, chemical modifications were performed on amino acids where picolinic acid was used to attach a chromophore to the compounds, therefore, allowing UV absorption from the laser. Upon attaching the picolinate UV absorbing group, the amino acid compounds were detected LC-MS at an increased intensity of 10 to 100-fold. Moreover, enhanced separation in LC-MS was also observed.This project has successfully investigated alternative approaches to matrix-free MALDI-MS analysis. Functionalised SBA-16 thin films were by far the best method and this novel surface for MALDI-MS has the potential to transform small molecule analysis.

Le problème de la communication, et pas seulement du danger des liaisons, est au cœur du roman épistolaire de manière générale et de Clarissa de Samuel Richardson en particulier. Sans cesse menacée d'interruption, la communication représentée dans la diégèse du deuxième roman de Richardson influe également sur le sens et relève à ce titre de ce que Janet Altman a appelé l'épistolarité. Cette étude se concentre sur le code de la communication représentée dans l'œuvre et saisit la lettre dans l’économie de l’information toute particulière dont elle participe, à la croisée d'une communication interne entre ses personnages et des exigences d'une communication externe qui voit le matériau épistolaire affluer vers le Lecteur. Elle s'efforce de souligner à quel point le scénario romanesque est informé par la nature des communications au travers desquelles il s’exprime ainsi qu'à travers les communications auxquelles il donne lieu (Clarissa étant l'objet d'âpres négociations entre son auteur et ses lecteurs), tout comme il informe à son tour la nature de ces communications. L'examen de la communication dans et autour du roman de Richardson met en évidence l'existence d'une poétique qui est aussi une économie. L'histoire de Clarissa n'est pas tant l'histoire de ses lettres que celle de ses communications. / The problem of communication, and not only that of the danger of the liaisons, is at the heart of the epistolary novel in general and of Samuel Richardson's Clarissa in particular. Constantly threatened with interruption, the communication represented in the diegesis of Richardson's second novel also informs meaning and thus belongs to what Janet Altman called epistolarity. This study concentrates on the code of communication represented in the work and endeavors to grasp the letter in its particular economy of communication, at the crossroads of internal communication between its characters and the demands of an external communication that requires that the epistolary material be oriented towards the reader. This study strives to underline to what extent the novelistic scenario is informed by the nature of the communications through which it expresses itself as well as by the communications it produces among its readers in the shape of letters to the author. The examination of communication in and around Richardson's novel bears witness to the existence of a poetics that is also an economy. The history of Clarissa is not so much that of its letters as that of its communications.

The primary aim of this study was to use a computational structure-based ligand design strategy in finding novel ligands that could act as inhibitors of PfGST as basis for future antimalarial drug development. Since there is only one PfGST isoenzyme present in the parasite and the architecture of the binding site differs significantly from its human counter part, PfGST is considered a highly attractive drug target. Inhibition of PfGST is expected to interfere at more than one metabolic site in synergy: it is likely to disrupt the glutathione-dependent detoxification process, which will lead to an increase in the cytotoxic peroxide concentration and most likely lead to an increase in the levels of ferriprotoporphyrin IX and hemin as well. S-hexyl glutathione was co-crystallized with PfGST (Harwaldt et al., 2004), consequently it was seen as one of the most important lead compounds in the development of PfGST inhibitors. The first step in the rational drug design strategy was to modify GTX, concentrating on its ability to bind competitively to the G site and the hydrocarbon chain protrudes into the H site as well. Considering the 3D structure of the enzyme, modifications to GTX were made by LUDI and NEWLEAD, resulting in a library of active site binding ligands ranked by AutoDock according to their ability to optimally bind to PfGST. Additionally, the ligands were ranked according to their affinity for binding to PfGST produced by AutoDock, LUDI and XScore. Once all the compounds were ranked by these in silico methods they were screened for acquisition or synthetic accessibility and those available were experimentally screened for activity against recombinantly expressed PfGST. Based on in silico predictions NDA was the best inhibitor followed by LAP and EDP. From the biological assay and Lineweaver-Burk analysis the order of inhibition was NDA as the best inhibitor tested, followed by LAP and EDP. EDP and LAP showed competitive inhibition but the inhibition constant values were signi_cantly lower than GTX. With respect to GSH and CDNB, NDA was found to be a non-competitive inhibitor. It was suggested therefore that NDA binds to a non-substrate Summary 93 binding site that may lead to conformational change of the enzyme and hence lead to a loss in enzyme activity. This data leads to the conclusion that the H site should be better exploited in order to find more potent inhibitors or non-substrate binding sites. It was concluded that the experimental results add confidence to the discriminative power of the structure-based ligand design strategy and that these inhibitors could form scaffolds for future antimalarial drug development. / Dissertation (MSc (Bioinformatics))--University of Pretoria, 2008. / Biochemistry / unrestricted

Malaria is a global health threat that causes 300 – 500 million clinical cases annually, resulting in approximately 2 million deaths. Chemotherapy and prophylaxis are becoming less effective because of increasing drug resistance by the parasite. Resurgence of malaria calls for the development of mechanistically novel drugs. The bifunctional organization of the two rate-limiting enzymes, AdoMetDC and ODC, in the P. Falciparum polyamine pathway and the presence of six parasite-specific inserts, present potential target sites for novel Plasmodia-specific drugs. The inserts are species-specific, hydrophilic, low complexity segments and form non-globular domains. The inserts are involved in intra- and interdomain interactions, which are important for stability and activity of the bifunctional construct. This study investigated properties of the parasite-specific inserts, one being the mobility of the O1 insert and the other the secondary structures present in the parasitespecific inserts. It is postulated that the mobility of the O1 insert plays a role in either heterotetrameric complex formation of the bifunctional construct or that the O1 insert acts as a “lid” to the ODC active site, which is necessary for catalytic function. Successful mutagenesis of the O1 flanking Gly residues to Ala, rendered the O1 insert immobile. The probable immobility of the O1 insert had a detrimental effect on the activity of both the AdoMetDC and ODC domains of the bifunctional protein. Molecular dynamics studies showed that movement restriction of the insert caused a conformational change in the ODC monomers. The decrease of both domain activities upon movement restriction of the O1 insert suggests that the insert is involved in protein-protein interactions, which is communicated throughout the protein. In addition, the roles of selected, predicted secondary structures in the Hinge, O1 and O2 parasite-specific inserts were investigated. á-Helices were disrupted by the introduction of a Pro residue, â-plates were removed with deletion mutagenesis. The effects of the secondary structure alterations on protein activity were monitored in the bifunctional PfAdoMetDC/ODC protein. Both domain activities were affected by the disruptions, although the ODC domain was more sensitive to the small changes. The results obtained in this study showed that the secondary structures in the parasite-specific insert are important for activity of both the AdoMetDC and ODC domains of the bifunctional protein, possibly via interdomain protein-protein interactions. The delineation of essential intra- and interdomain protein-protein interactions presents possible interaction sites for disruptive molecules in the combat against malaria. Copyright / Dissertation (MSc)--University of Pretoria, 2009. / Biochemistry / unrestricted

Uppsatsen behandlar den ordlösa grafiska novellen Home av Eric Drooker, en tecknad serienovell på 42 sidor där Drooker använder sig av specifika visuella medel för att kommunicera. Syftet med uppsatsen är att undersöka hur en berättelse kan formuleras med bildspråk där olika symboler hjälper läsaren att förstå innehållet. Med hjälp av en innehållsanalys utifrån en semiotisk metod kartläggs användandet och frekvensen av symboler. Resultatet visar att symbolerna Drooker använder är gester, ordbilder, siffror, skiljetecken, noter, emanata, grafiska och ikoniska symboler, paneler, ramar och sidlayout. Rapporten vänder sig till forskare, studenter och yrkesutövare samt till intresserade av tecknade serier, grafisk design, layout och bildspråk. / The essay investigates the wordless graphic short story Home by Eric Drooker, a comic on 42 pages where Drooker uses specific visual means to communicate. The purpose of the thesis is to investigate how a narrative can be formulated with imagery where different symbols are included. The use and frequency of symbols are documented by a content analysis and a semiotic perspective. The result shows that the symbols Drooker uses are gestures, word pictures, numbers, punctuation marks, notes, emanata, graphic as well as iconic symbols, panels, frames and page layout. The report is aimed at researchers, students and professionals, and at those who are interested in comics, graphic design, layout and visual language.

Thesis advisor: Kalpana Seshadri / The novel is generally read through a Western lens that privileges both individual subjectivity and the nation-state. My dissertation acts as an intervention into the critical tradition that sees the novel as a genre preoccupied with the individual, the nation-state, and the rights and responsibilities of citizenship through which the two relate to each other. This tradition includes seminal theorists Ian Watt, Fredric Jameson, and Benedict Anderson as well as contemporary critics such as Pascale Casanova and Joseph Slaughter. Transnational Communities challenges this accepted framework for understanding the novel genre through an examination of novels which decenter the categories of individual and nation-state and argues that in this moment of unprecedented globalization, the novel’s ability to imagine new forms of community is an increasingly relevant social function. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: English.

Philosophiae Doctor - PhD / This thesis examines how “unhomeliness” in a Zimbabwean context enjoins mobility and the diasporic particularities that manifest as subjects move back and forth in a homemaking journey between the country-side and the urban, as well as mobility to foreign countries and back to the homeland. Particularities of inclusion and exclusion, (re)emplacement, (re)identity, assimilation, rejection and (un)belonging, all loom large as mobility, paradoxically, takes root and comes to shape experience in as significant a way as being in a homeland or hostland. This thesis is also about the ways in which the “diasporic” settler, in one of the novels which destabilises the familiar paradigms of diasporic literature, can exist and be dominant in the foreign but colonised spatial setting without needing to assimilate, and how this attempt to territorialise can traumatise those marginalised by the settler community. Since the end of the twentieth century, there has been a rise in the significance of space in humanities and literary studies. Theories about diaspora, identity and belonging have featured strongly in works of scholars of space and place such as Henri Lefebvre, Yi-Fu Tuan, Doreen Massey, Edward Soja, Tim Cresswell, Nigel Thrift, Robin Cohen, John Agnew, and Kelly Baker. Space is largely regarded as a dimension within which matter is located.

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The first part of this submission is a graphic novel entitled “Diss”. The novel is set in South African in the near future, and is based on Dante’s “Inferno”. The work also draws on various ancient mythologies and works of fiction. Essentially, this graphic novel is a reflection on contemporary South African society, as the reader travels with the main character, Dirk, through the rooms of a club in the South African capital, Pretoria. The club contains the nine circles of hell, and leads Dirk to discover aspects of himself that he has suppressed, such as his mother’s brutal murder. He meets his three guardians from ancient Egyptian mythology, who are also the keepers of the hallway. He further has to confront the three aspects of the Queen of hell, based on the three archetypal aspects of woman, who tempt him into letting go of a memory. At the climax, he is confronted with the queen herself, who, craving the taste of Dirk’s pain, tries to remove the memory from him by force. Throughout “Diss” Dirk’s best friend Gugu travels with his, and acts as his moral guide in the club. The second section is entitled “The graphic novel: an international and South African exploration.” The research essay explores the definitions and background of the graphic novel, and looks at how the genre can uniquely explore aspects of time and space, myth and intertext and hybridity and cultural production. To illustrate these aspects the essay explores definitive works in the genre, namely “Maus” by Art Spiegelman, “The Sandman” series by Neil Gaiman, and “Persepolis” by Marjane Satrapi. The essay further looks at the history of African comics, and, more specifically, the graphic novel publication industry in South Africa. Lastly, the essay explores the possibilities of the graphic novel within the multimodal classroom, particularly in how the genre can be used in promoting literacy. / Dissertation (MA)--University of Pretoria, 2011. / Afrikaans / unrestricted