Dans ce mémoire, je présente mes études sur la synthèse, la caractérisation et l’évaluation biologique de différentes séries d’analogues du D-heptapeptide appelé 101.10, un modulateur négatif allostérique du récepteur de l’interleukine-1β (IL-1β). Sachant que les peptides ont généralement de faibles propriétés pharmacologiques, le but de ce projet portait sur l’examen des structures nécessaires à la bioactivité, la conformation tridimensionnelle de ces derniers afin d’améliorer la droguabilité du peptide parent. Les stratégies d’optimisation du 101.10 utilisées furent : la coupure N- et C-terminale; la substitution par la proline, α-amino-γ-lactame (Agl), β-amino-γ-lactame (Bgl) et α-amino-β-hydroxy-γ-lactame (Hgl); et la rigidification du squelette à l’aide d’un bicycle, l’indolozidin-2-one (I2aa). Afin de clarifier certaines relations de structure-activité, quelques modifications furent apportées au peptide, incluant l’échange de la thréonine pour la valine, la permutation de la stéréochimie de certains résidus clés ainsi que le remplacement de certaines chaînes latérales par un méthyle. Pour pallier aux difficultés de reproductibilité des résultats avec des échantillons provenant de différentes sources, des études sur l’identité du contre-anion et la pureté du peptide furent conduites. Afin d’évaluer l’effet des modifications sur la conformation aqueuse et l’activité biologique du peptide, des analyses de dichroïsme circulaire et des tests in vitro mesurant l’inhibition de certains effets de l’IL-1β furent effectués. Ces essais cellulaires comportaient l’inhibition de la prolifération de cellules immunes et de l’activation des voies de signalisation inflammatoires du facteur nucléaire κB (NF-κB) et de la protéine kinase activée par mitogène (MAPK), toutes deux stimulées par l’IL-1β. La compilation de ces données a permis de déceler certaines tendances entre la structure, la conformation et l’activité anti-IL-1β des peptidomimétiques. / In this thesis, I present my studies toward the synthesis, characterisation and biological evaluation of different series of analogues of the D-heptapeptide called 101.10, a negative allosteric modulator of the interleukin-1β (IL-1β) receptor. Considering that peptides generally exhibit poor pharmacological properties, the objective of this project consisted in: the examination of the peptidic structures essential to elicit bioactivity; the investigation of the three-dimensional arrangement of these moieties; and the improvement of the “drug-like” properties of the parent peptide. The optimisation strategies that were used include: N- and C-terminal truncation; positional scanning using monocycles such as proline, α-amino-γ-lactam (Agl), β-amino-γ-lactam (Bgl) and α-amino-β-hydroxy-γ-lactam (Hgl); and backbone rigidification with indolizidin-2-one (I2aa). Moreover, in order to validate certain structure-activity relationships, further modifications were performed on the peptide: substitution of threonine for valine, exchange of stereochemistry, and substitution of certain side-chain for a methyl group. Lastly, due to divergent behaviour between peptide samples obtained from different sources, studies on the identity of the counter-anion and on the sample purity were conducted. In order to evaluate the influence of these modifications on the aqueous conformation and on the biological activity of the peptide, circular dichroism analyses and in vitro tests measuring the inhibition of certain IL-1β-mediated effects were performed. These cellular assays comprised the inhibition of IL-1β-stimulated proliferation of immune cells, as well as activation of the inflammatory pathways of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Compiling these data revealed certain trends existing between the structure, conformation and anti-IL-1β activity of the peptidomimetics.

Les azapeptides sont des mimes peptidiques où le carbone alpha d’un ou de plusieurs acides aminés est remplacé par un atome d’azote. Cette modification tend à stabiliser une conformation en repliement beta en raison de la répulsion électronique entre les paires d’électrons libres des atomes d’azote adjacents et de la géométrie plane de l’urée. De plus, le résidu semicarbazide a une meilleure résistance face aux protéases en plus d’être chimiquement plus stable qu’une liaison amide. Bien que les propriétés des azapeptides en fassent des mimes peptidiques intéressants, leurs méthodes de synthèses font appel à la synthèse laborieuse d’hydrazines substituées en solution. Le peptide sécréteur d’hormone de croissance 6 (GHRP-6, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) est un hexapeptide synthétique qui possède une affinité pour deux récepteurs distincts: les récepteurs GHS-R1a et CD36. Les travaux effectués au cours de mon doctorat qui seront détaillés dans cet ouvrage visent à atteindre deux objectifs: (1) le développement d’analogues du peptide GHRP-6 sélectif à un seul récepteur et (2) la mise au point d’une nouvelle méthodologie pour la synthèse combinatoire d’azapeptides. En réponse au premier objectif, la synthèse parallèle de 49 analogues aza-GHRP-6 a été effectuée et certains candidats sélectifs au récepteur CD36 ont été identifiés. L’étude de leurs propriétés anti-angiogéniques, effectuée par nos collaborateurs, a également permis d’identifier des candidats intéressants pour le traitement potentiel de la dégénérescence maculaire liée à l’âge. Une nouvelle approche pour la synthèse combinatoire d’azapeptides, faisant appel à l’alkylation et la déprotection chimiosélective d’une sous-unité semicarbazone ancrée sur support solide, a ensuite été développée. La portée de cette méthodologie a été augmentée par la découverte de conditions permettant l’arylation régiosélective de cette sous-unité semicarbazone, donnant accès à treize nouveaux dérivés aza-GHRP-6 possédant des résidus aza-arylglycines aux positions D-Trp2 et Trp4. L’élaboration de conditions propices à l’alkylation et la déprotection chimiosélective de la semicarbazone a donné accès à une variété de chaînes latérales sur l’acide aminé « aza » préalablement inaccessibles. Nous avons, entre autres, démontré qu’une chaîne latérale propargyl pouvait être incorporée sur l’acide aminé « aza ». Tenant compte de la réactivité des alcynes, nous avons ensuite élaboré des conditions réactionnelles permettant la formation in situ d’azotures aromatiques, suivie d’une réaction de cycloaddition 1,3-dipolaire sur support solide, dans le but d’obtenir des mimes de tryptophane. Sept analogues du GHRP-6 ont été synthétisés et testés pour affinité au récepteur CD36 par nos collaborateurs. De plus, nous avons effectué une réaction de couplage en solution entre un dipeptide possédant un résidu aza-propargylglycine, du paraformaldehyde et une variété d’amines secondaires (couplage A3) afin d’accéder à des mimes rigides d’aza-lysine. Ces sous-unités ont ensuite été incorporées sur support solide afin de générer sept nouveaux azapeptides avec des dérivés aza-lysine à la position Trp4 du GHRP-6. Enfin, une réaction de cyclisation 5-exo-dig a été développée pour la synthèse de N-amino imidazolin-2-ones en tant que nouveaux mimes peptidiques. Leur fonctionnalisation par une série de groupements benzyliques à la position 4 de l’hétérocycle a été rendue possible grâce à un couplage Sonogashira précédant la réaction de cyclisation. Les propriétés conformationnelles de cette nouvelle famille de composés ont été étudiées par cristallographie aux rayons X et spectroscopie RMN d’un tétrapeptide modèle. L’activité biologique de deux mimes peptidiques, possédant un résidu N-amino-4-méthyl- et 4-benzyl-imidazolin-2-one à la position Trp4 du GHRP-6, a aussi été examinée. L’ensemble de ces travaux devrait contribuer à l’avancement des connaissances au niveau des facteurs structurels et conformationnels requis pour le développement d’azapeptides en tant que ligands du récepteur CD36. De plus, les résultats obtenus devraient encourager davantage l’utilisation d’azapeptides comme peptidomimétiques grâce à leur nouvelle facilité de synthèse et la diversité grandissante au niveau de la chaîne latérale des acides aminés « aza ». / Azapeptides are peptide mimics in which the CH alpha in one or more amino acids has been replaced with a nitirogen atom. Such a modification tends to induce beta turn conformations in peptides, because of the consequences of lone–pair lone–pair repulsion between the two adjacent nitrogens and the planar geometry of the urea in the semicarbazide moiety. Furthermore, the semicarbazide increases protease resistance and is chemically more stable than its amide counterpart. Despite the potential advantages of using azapeptides mimics, their synthesis has been hampered by the solution-phase construction of substituted hydrazines prior to their incorporation into peptide sequences. Growth Hormone Releasing Peptide 6 sequence (GHRP-6, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide that binds to two distinct receptor: the Growth Hormone Secretatgogue Receptor 1a (GHS-R1a) and the Cluster of Differentiation 36 (CD36) receptor. The body of my Ph.D thesis has been generally targeted towards two objectives: (a) the development of azapeptide analogs of GHRP-6 with enhanced receptor selectivity and (b) the elaboration of a new synthetic approach for combinatorial submonomer azapeptide synthesis. In response to the first objective, 49 aza-GHRP-6 derivatives were synthesized and evaluated for receptor binding and biological activity. From this library, certain candidates were identified which exhibited decreased affinity for the GHS-R1a receptor with maintained affinity for the CD36 receptor. Furthermore, in studying their anti-angiogenic properties, our collaborators have identified aza-GHRP-6 analogs, which caused a marked decrease in microvascular sprouting in choroid explants, as well as another displaying potential to increase angiogenesis. A new approach for the combinatorial synthesis of azapeptides was developed to better conduct SAR studies using azapeptides. This method features the chemoselective alkylation and deprotection of a resin-bound semicarbazone building block. The scope of the methodology was further expanded by the development of reaction conditions for the chemoselective N-arylation of this semicarbazone residue, yielding 13 aza-GHRP-6 derivatives with aza-arylglycines residues at the D-Trp2 and Trp4 positions. The elaboration of a methodology based on the chemoselective alkylation and deprotection of a semicarbazone has allowed for greater aza-amino acid side chain diversity, enabling for example, the efficient incorporation of aza-propargylglycine residues into peptide sequences. Considering the reactivity of alkynes, we developed reaction conditions for in situ formation of aromatic azides, followed by a 1,3-dipolar cycloaddition reaction on solid support to yield aza-1-aryl,2,3-triazole-3-alanine residues as tryptophan mimics. Seven aza-GHRP-6 analogs were synthesized and subsequently tested for binding to the CD36 receptor by our collaborators. Moreover, the coupling reaction between an aza-propargylglycine-containing dipeptide building block, paraformaldehyde and a variety of secondary amines (A3 coupling) was accomplished in solution to provide access to rigid aza-lysine mimics. These aza-dipeptides were subsequently incorporated at the Trp4 position of seven new aza-GHRP-6 analogues using a solid-phase protocol, and the resulting azaLys mimics were tested for binding towards the CD36 receptor. Finally, conditions for a 5-exo-dig cyclization of an aza-propargylglycine residue were developed to give N-amino imidazolin-2-ones as turn-inducing peptide mimics. Their modification at the 4 position was achieved using a Sonogashira coupling protocol prior to the cyclization step. The conformational properties of these new heterocyclic motifs were assessed by X-ray crystallography and NMR spectroscopy on a tetrapeptide model system. The incorporation of N-amino-4-methyl- and 4-benzyl-imidazolin-2-ones at the Trp4 position of GHRP-6 was further accomplished and the biological evaluation of the peptidomimetics was examined. Taken together, these results should lead to a better understanding of the structural and conformational factors responsible for binding and biological activity of azapeptide ligands of the CD36 receptor. Furthermore, the submonomer approach for azapeptide synthesis developed should promote the use of azapeptides as peptide mimics, given its accessibility and the increased aza-amino acid side-chain diversity available.

Les pyrrolodiazépinones ont des activités biologiques intéressantes sur différents récepteurs biologiques, ce qui en font une cible de choix pour développer de nouvelles petites molécules biologiquement actives. Une méthodologie en solution a été développée pour synthétiser des pyrrolo[3,2-e][1,4]diazépin-2-ones, qui utilise la réaction de Pictet-Spengler pour former le cycle diazépinone, comme réaction clé. Il a été démontré que le pyrrolo[3,2-e][1,4]diazépin-2-one mime un tour-γ inverse par l’analyse de cristaux par rayon X. Cette méthodologie a été transposée sur trois types de support, soit la résine de Merrifield, de Wang et un support soluble (TAP). Le système urotensinergétique joue un rôle dans certaines pathologies du système cardiovasculaire, comme l’hypertension artérielle, l’insuffisance cardiaque et l’athérosclérose. Le système urotensinergétique est exprimé dans le système circulatoire, extractoire et le système nerveux central et comprend l’UII, l’URP et le récepteur UT. L’UII et l’URP humains sont composés respectivement des séquences d’acides aminés : H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH et H-Ala-c[Cys-Phe-Trp-LysTyr-Cys]-Val-OH. L’UII est le peptide vasoconstricteur le plus puissant connu à ce jour, dont l’URP est son isoforme. Les deux peptides ont des effets biologiques différents et on peut supposer qu’ils jouent un rôle distinct dans certaines pathologies. Il a été démontré que la partie active de l’UII est composée du tripeptide : Trp-Lys-Tyr. Dans l’URP, il a été démontré que ce tripeptide forme un tour-γ inverse, ce qui fait du récepteur UT une bonne cible biologique pour tester une librairie de pyrrolo[3,2-e][1,4]diazépin-2-ones, reprenant le tripeptide Trp-Lys-Tyr. Dernièrement, l’équipe du professeur David Chatenet a mis au point un peptide, l’urocontrin en remplaçant le segment Trp par un groupement biphénylalanine, qui a démontré un comportement spécifique comme antagoniste du récepteur UT. La Librairie de pyrrolo[3,2-e][1,4]diazépin-2-ones est basée sur la séquence TrpLys-Tyr de l’UII et de l’URP et de la séquence Trp-Lys-Bip de l’urocontrin. La synthèse de la librairie est faite sur la résine de Wang. La chaîne latérale de Tyr est mimée en utilisant la tyramine, Lys et Orn sont utilisés et la chaîne latérale de Trp a été reproduite II en utilisant le biphényle (comme dans l’urocontrin), le 1-naphthyle et le 2-naphthyle, sont introduits en employant les aldéhydes respectifs dans la réaction de Pictet-Spengler, ce qui donne les pyrrolo[3,2-e][1,4]diazépin-2-ones insaturés et les saturés S- et R-. L’évaluation de l’activité biologique des pyrrolo[3,2-e][1,4]diazépin-2-ones obtenues sur le récepteur UT se fait par des tests in vitro et ex vivo. Les tests in vitro consistent en un essai de liaisons sur des cellules CHO exprimant le récepteur UT en employant hUII-125I, comme contrôle radiomarqé. Les tests ex vivo sont effectués sur des aortes de rats pour mesurer la capacité à induire des contractions ou de moduler les contractions induites par hUII et URP. Certains R-pyrrolo[3,2-e][1,4]diazépin-2-ones causent une réduction de 50% du signal radioactivité du hUII-125I. Les pyrrolo[3,2-e][1,4]diazépin-2-ones ne montrent guère d’activité ex vivo, mais ils ont la capacité de moduler les contractions induites par l’hUII et l’URP. Par exemple, l’analogue Lys R-saturé avec le biphényle inhibe toutes les contractions de l’aorte à 14 µM avec un pKb de 5,54 à 4 µM, sans influencer les contractions de l’aorte induites par l’URP. Les pyrrolo[3,2-e][1,4]diazépin-2-ones ont une sélectivité pour le système urotensinergétique et sont inactifs sur le récepteur de l’endotheline-1. Les pyrrolo[3,2-e][1,4]diazépin-2-ones sont les premières petites molécules qui peuvent moduler l’activité biologique de l’UII et URP et offrir un potentiel intéressant comme outil pour étudier le système urotensinergétique. / The pyrrolodiazepinones have interesting biological activities on various biological receptors, which makes them a prime target for developing new biologically active small molecules. A methodology in solution had been developed for synthesizing pyrrolo[3,2-e][1,4]diazepin-2-ones, which utilized the Pictet-Spengler condensation as the key reaction to form the diazepinone ring. Pyrrolo[3,2-e][1,4]diazepin-2-ones were found to mimic an inverse γ-turn conformation by X-ray crystallographic analysis. The methodology was subsequently implemented on three types of support: Merrifield resin, Wang resin and the soluble TAP support. The urotensinergic system plays a role in certain diseases of the cardiovascular system, such as hypertension, heart failure and atherosclerosis. The urotensinergic system is expressed in the circulatory system, excretory and central nervous systems and includes the endogenous ligands urotensin II (UII) and urotensin II-related peptide (URP), and the urotensin receptor UT. The ligands UII and human URP are composed of the respective amino acid sequences: H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH and H-Ala-c[Cys-Phe-Lys-Tyr-Trp-Cys]-Val-OH. The peptide UII is the most potent vasoconstrictor known to date. The two peptides have different biological effects and may exhibit distinct roles in certain diseases. Their common Trp-Lys-Tyr sequence is believed to play an important role in the activity of UII and URP, and has been suggested to adopt an inverse γ-turn conformation. Notably, the laboratory of Professor David Chatenet developed the UT receptor antagonist peptide urocontrin by replacing the Trp residue by biphenylalanine (Bip) in URP. A library of pyrrolo[3,2-e][1,4]diazepin-2-one analogs was thus designed to mimic the inverse γ-turn sequence and targeted against UT. The pyrrolo[3,2-e][1,4]diazepin-2-one library was designed based on the Trp-Lys-Tyr sequence of UII and URP, and Trp-Lys-Bip sequence of urocontrin. The synthesis of the pyrrolo[3,2-e][1,4]diazepin-2-one library was achieved on Wang resin. The side chain of Tyr was mimicked using tyramine, Lys and Orn were used as the basic amino acid component, and the side chain of Trp was replicated using biphenyl (as in urocontrin) 1-naphthyl and 2-naphthyl groups that were introduced by employing their respective aldehydes in a Pictet-Spengler reaction, which furnished unsaturated and saturated S- and R-pyrrolo[3,2-e][1,4]diazepin-2-ones. Evaluation of the biological activity of the pyrrolo[3,2-e][1,4]diazepin-2-ones on the UT receptor was performed in vitro and ex vivo. Tests in vitro measured binding in CHO-cells which expressed UT by employing hUII-125I as radiolabeled control. In rat aorta, ex vivo tests measured capacity to induce contraction, or modulate the contractions induced by hUII and URP. Certain R-pyrrolo[3,2-e][1,4]diazepin-2-ones caused an up to 50% reduction of the radioactive signal of hUII-125I. Pyrrolo[3,2-e][1,4]diazepin-2-ones exhibited little activity ex vivo; however, they modulated contractions induced by hUII and URP. For example, the saturated R-analog possessing lysine and a biphenyl side chain inhibited completely hUII-induced contractions of the aorta at 14 µM with a pKb of 5.54 at 4 µM, without influencing URP-induced contractions. Pyrrolo[3,2-e][1,4]diazepin-2-ones were selective for the urotensinergic system and inactive on the related receptor endothelin-1. Pyrrolo[3,2-e][1,4]diazepin-2-ones represent the first small molecules that can differently modulate the biological activities of UII and URP, and offer interesting potential as tools for studying the urotensinergic system.

This thesis is a cultural history of the early Fabian Society, focusing on the decades between 1884, the Society’s inaugural year, and 1914. The canonical view is that ‘Fabianism,’ which the Oxford English Dictionary defines as the ‘doctrine and principles of the Fabian Society,’ is synonymous with State socialism and bureaucratic ‘efficiency.’ By bringing the methods of cultural history to bear on the Society’s founding members and decades, this thesis reveals that ‘Fabianism’ was in fact used as a dynamic metonymy, not a fixed doctrine, which signified a range of cultural, and even literary, meanings for British commentators in the 1890s and 1900s (Part 1). Further, by expanding the scope of traditional histories of the Fabian Society, which conventionally operate within political and economic sub-fields and focus on the Society’s ‘official’ literature, to include a close examination of the broader discursive context in which ‘Fabianism’ came into being, this thesis sets out to recover the symbolic aspects of the Fabians’ efforts to negotiate what ‘Fabianism’ meant to the English reading public. The Fabians’ conspicuous leadership in the modern education debates and the liberal fight for a ‘free stage,’ and their solidarity with the international political émigrés living in London at the turn of the twentieth century all contribute to this revised perspective on who the founding Fabians were, what they saw themselves as trying to achieve, and where the Fabian Society belonged—and was perceived to belong—in relation to British politics, culture, and society (Part 2). The original contribution of this thesis is the argument that the Fabians explicitly and implicitly evoked Matthew Arnold as a precursor in their efforts to articulate a kind of Fabian—latterly social-democratic—liberalism and a public vocation that balanced English liberties and the duty of the State to provide the ‘best’ for its citizens in education and in culture, as in politics.

Based on ethnographic fieldwork conducted in Seoul from July 2012 until July 2013, this dissertation offers a novel perspective on human-animal interactions and public discourses regarding livestock versus pet moral boundaries in contemporary Korea. I aim to explore how Koreans struggle to make sense of the tension between the emergence of animal welfare and the perpetuation of traditional health behaviours that involve animal processing. The focus will be on why participants in my study, whether activists or not, defended both animal ethics and cat and dog meat consumption, while including Korean animals in fluid and instrumental conceptions of Koreanness. I have analysed a variety of discourses produced by both Korean and non-Korean, academic and non-academic stakeholders, in order to reveal the on-going tension between these powerful ubiquitous ideas and the lived experience of Koreans today. Moreover, I examine how the aesthetics of cruelty and empathy is employed in order to singularize livestock into companion animals thereby transgressing cultural taboos regarding Western ethics of species separation. I also demonstrate that converging and conflicting economic, political, social and cultural agendas are responsible for making Korea’s public discourses about animal welfare very unsettled. My research thus contributes to key anthropological debates about the cross-cultural circulation and cross-fertilisation of moral values that impact the ethics of post-industrial human-animal interactions; and about the influence of policy dialogue, at both national and international levels, on applied animal ethics, cultural stigmatization and the reinforcement of national sentiment.

The works of Erik Beckman (1935-1995) are quite unique within the Swedish literary scene. His texts convert the experimental language of the concretists of the sixties into a new form of fabulation that undermines our understanding of what literature can be, ranging from novels and poetry to theatre pieces and radio theatre. His literary style has been discussed by critics, but the depths of it are yet to be fully explored. There is a lot to gain from combining contemporary theories of materiality and corporeality with his self-proclaimed materialistic poetics. The novel Inlandsbanan (1967) is a fragmentary account of an inland train going through Sweden, with characters coming and going in a frustrating tempo. The text is filled with word games, narrative constructs and a language that brings forth the material aspects of communication that push the boundaries of literary interpretation. This thesis examines Beckman’s novel through the lens of theoretical concepts of thingliness and corporeality developed by the likes of Judith Butler, Karen Barad, and Andrew Pickering in order to elaborate an analysis that goes beyond the surface of its experimental and materialistic use of literary language. Using bodily themes, I analyze specific passages in the novel in order to find a new understanding of its semantic functions. By doing this through the concept of performativity, not only can I identify a thematized corporeality, but beyond that a literary form and a language that problematizes the very notion of the written text as a body and highlights a material agency in literature. This method enables an interpretation of the novel that can illuminates important aspects at play that previously have not been explored.

The thesis analyses selected phenomena of graphy, phonology, morfology, lexicology and words-formation of the Frederick from Donin's Czech book of travels, which was written at the turn of the 16th and 17th century. Partly, it also deals with the syntax and style of the work. Selected phenomena of individual language levels are studied using the original manuscript. The thesis intends to show in which aspects the text is close to early modern language usage, and conversely in which aspects it differs from it. The language of the manuscript is also compared with the contemporary Czech language.

Text in English / This study examines and discovers the translation strategies as employed in the Sesotho sa Leboa translation of Mandela's Long Walk to Freedom. Mandela's Long Walk to Freedom was published in 1995 and was translated into Sesotho sa Leboa by S M Serudu in 2001. The Sesotho sa Leboa translation of the life history of Mandela, Leetotelele go ya Tokologong (Long Walk to Freedom) is one of the four completed translations to date that form part of the assignment to translate the original text into the official languages of South Africa. The aim of this study is to investigate the translation strategies used to transfer linguistic and cultural items in the translation of Mandela's autobiography. The study is mainly qualitative and examines the strategies employed by Serudu. For data collection, the source and target texts of Mandela's Long Walk to Freedom as well as the semi-structured face-to-face interviews with four translators into Sesotho sa Leboa, isiZulu, isiXhosa and Afrikaans were used. The study is based on the Descriptive Translation Studies Theory, Bassnett and Lefevere's "cultural turn" as well as the domestication and foreignization strategies. In this case, it investigates if Serudu has domesticated and/or foreignized his translation. The findings revealed that Serudu domesticated his translation by using metaphors, similes, personification, euphemism, hyperbole, proverbs, idioms and the use of descriptive words. Foreignization was also found when the translator dealt with the borrowing and loaning of words where most of the concepts were transferred, Sotholised, retained and transferred, as they were, especially culture specific items. / African Languages / D. Litt. et Phil. (African Languages)

Adoptant la langue des flux et des fluides, la théorie sociologique caractérisent aujourd’hui les acteurs sociaux comme des êtres composites, prédisposés à changer et capables d’agencements feuilletés. Alors que l’importance de la mobilité pour penser et analyser le social contemporain est généralement reconnue, rare sont les travaux qui se consacre à en développer les modalités fondamentales. L’objectif de cette thèse est de développer une approche plus différenciée et gradualiste des mobilités que celle proposée par les principales options théoriques en vigueur, sans pour autant abandonner la dimension fluctuante, non linéaire et imprévisible du mouvement sur laquelle elles attirent l’attention. Qu’est-ce qu’être mobile ?Une théorie de l’expérience, en l’occurrence celle proposée par la phénoménologie, offrirait-elle des ressources critiques susceptibles d’ouvrir à l’approfondissement des mobilités comme elles sont vécues ?À titre d’hypothèse, cette thèse pose qu’un ensemble de phénomènes demeurent énigmatiques à l’intérieur de la conception généralement admise du social contemporain et qu’une articulation plus explicite du thème de la mobilité à celui de l’action humaine permet d’approfondir les processus du déplacement dans l’espace des sociétés, du passage du temps impliqué par le déplacement et du changement social. Comment émerge du nouveau dans le cours d’actions ?Qu’est-ce que pouvoir agir ?Quelle est la source du changement ?À partir d’une enquête inédite sur des voyageurs se rendant quotidiennement à Bruxelles et des personnages de romans de route étatsuniens, l’auteur explore des questions de fond portant sur l’expérience du transport, autour de l’éloignement des choses et des personnes aimées, du vide du temps d’attente, des aléas aussi insignifiants qu’irritants, de l’étrangeté des rencontres, de la décision de prendre la route et de choisir une orientation nouvelle. Ces moments de vacillation sont importants, soutient l’auteur, car ils nous ramènent aux motivations fondamentales et aux buts ultimes de nos déplacements les plus quotidiens. À une époque marquée par un idéal de mouvement fluide et sans accrocs, cette thèse éclaire ce qui se passe dans l’expérience des mobilités. Elle incite à une réflexion sur ce que nous éprouvons sur la route et aux possibles que cette expérience fait émerger. / Doctorat en Sciences politiques et sociales / info:eu-repo/semantics/nonPublished

A tese discute a transformação dos discursos político-criminais sobre a pena de prisão no Brasil, no período que compreende os debates para a elaboração da Parte Geral do Código Penal e da Lei de Execução Penal, que reformaram o sistema penal em 1984, e os dispositivos penais e processuais penais discutidos na Assembleia Nacional Constituinte e contemplados na Constituição de 1988. Utilizando conceitos da literatura político-criminal anglo-saxã, as teorias tradicionais da pena e analisando os debates legislativos dos principais marcos legais do período escolhido, pretendeu-se verificar se o processo de superencarceramento brasileiro está inserido no contexto ocidental de valorização da prisão no final do século XX, ou se as peculiaridades do caso nacional indicam tratar-se de um fenômeno com causas endógenas. O trabalho parte da hipótese de que a virada punitiva brasileira está ligada ao processo de redemocratização, que atribuiu ao sistema de justiça criminal o papel de instrumento de resolução de problemas sociais complexos. Em um curto período, partiu-se de uma concepção de pena criminal como ultima ratio, instrumento de um sistema mais amplo de ressocialização e inclusão social, para um direito penal essencialmente punitivo. Nesse processo, a pena criminal foi revalorizada tanto por setores conservadores que se aproveitaram da utilidade eleitoral da política criminal para construir a narrativa da pena como instrumento de exclusão dos indesejáveis, em detrimento dos direitos humanos dos condenados quanto por setores progressistas que viram no potencial simbólico da prisão uma forma de assegurar pautas e de buscar direitos sociais. Assim, de maneira paradoxal, a pena de prisão assumiu o papel de síntese das demandas contraditórias que se apresentaram durante as disputas políticas nos anos 1980. Ao final, conclui-se que a prática contemporânea do sistema penal brasileiro está ligada à função atribuída à pena de prisão a partir da abertura política. O recurso a penas cada vez mais altas, o perene apelo a restrições processuais penais e a indiferença quanto à situação dos cárceres (agora concebidos como meros instrumentos de exclusão) refletem a lógica de colonização do sistema de justiça pelo aparato de segurança pública, característica constitutiva do antimodernismo penal no país. / The thesis presents a discussion about the transformation of criminal policy discourses on imprisonment in Brazil, from the 1984 criminal justice reform laws to the debates on the constitutional framework of the criminal justice system during the National Constituent Assembly, in 1988. Using concepts developed in the Anglo-Saxon criminology and the traditional justifications for criminal sanctions, the work analyses the legislative debates in order to verify if Brazilian overincarceration is part of the punitive turn wave which took place in the Western world in the late 20th century, or if its peculiarities should rather be explained by endogenous causes. It goes to illustrate how, in few years, Brazilian punitive turn departed from a welfare penal agenda to one essentially based on punitive sanctions. The hypothesis investigated along the work is that this phenomenon has direct links to the democratization process which attributed to the criminal justice system the role of solving complex social problems. Both conservatives, who discovered the electoral potential of penal populism, and new social movements, who relied on the symbolic nature of criminal law to support and organize civil rights demands, reinvigorated imprisonment. Paradoxically, prison became a synthesis of contradictory political forces and demands raised at the decline of military regime. The work concludes that contemporary practices of Brazilian criminal justice system are determined by the role assigned to imprisonment since democratization. Ever-higher prison sentences, limits on procedural rights for the accused and indifference towards inhumane prisons (now merely defined as a neutralization tool) reflects colonization of the criminal justice system by crime control apparatus, which is a constitutive feature of penal late modernism in Brazil.