120589 research outputs found
Sort by
"The Play's the Thing": Underspecification in Shakespearean Drama
No full textWilliam Shakespeare, renowned for his linguistic agility, is also exceptional in his use of a word without meaning. The word ‘thing’, a semantically vacuous word, is particularly frequent in Shakespeare’s plays. Whilst ambiguity is frequently noted to be fundamental to literature, few literary scholars have engaged with explorations of this phenomenon in linguistics. Adopting a linguistic concept called ‘underspecification’, this thesis argues that Shakespeare strategically employs the word ‘thing’ to attract attention to and delay the comprehension of the ‘thing’ so designated. The utility of this technique is explored in four dramatic contexts: staging the supernatural, scenes of judgement, representations of sentential speech, and comic exchanges. Paying attention to such lapses in meaning, this thesis contends, offers new insight into the way in which Shakespeare anticipated and actively shaped the reception of his drama
News Coverage of Immigration and the Normalization of Far-Right Nativism
No full textFar-right parties advocating nativist, anti-immigration ideologies are gaining momentum across Western liberal democracies, despite their stigmatization. What was once a fringe political force is moving towards the mainstream, as evidenced by the increasing presence and influence of far-right parties in parliaments and their ability to shape the public agenda on immigration. This shift suggests a significant transformation in the political landscape, where far-right narratives on immigration are becoming central to the discourse on national identity and immigration policy. In other words, it seems that the far-right's nativist ideology is becoming increasingly normalized, winning over public support and acceptance. The reasons behind this normalization, however, remain unclear. This thesis examines the role of the valence of immigration news on the normalization of nativism, the far-right's immigration ideology. While previous research has shown that immigration news with a negative valence is linked with higher support for the far-right and its nativist ideology, it remains unclear whether this relationship is due to the valence of immigration news normalizing this ideology. Furthermore, the socio-psychological mechanisms that underlie this normalization are unclear. In this thesis, I hypothesize that immigration news with a negative valence contributes to normalizing the far-right's nativist ideology through four key mechanisms: First, more negative immigration news relates with an increase of threat perceptions that justify and legitimize the expression of anti-immigrant prejudice. Second, negative immigration news facilitates a dissociation between nativist ideology and its far-right source, which encourages focusing on the ideology, reducing identity concerns associated with endorsing a stigmatized political identity. Third, a reduction of discomfort in openly expressing nativism, illustrating a decrease in the discrepancy between the self and non-discriminatory standards. Fourth, a shift in the perceptions of social norms regarding this ideology. Through three articles, this thesis provides empirical evidence supporting the hypothesis that immigration news with a negative valence normalizes the far-right's nativist ideology via these four socio-psychological mechanisms, which, in turn, increase the overall support for this ideology. Together, these findings offer insights into why immigration news with a negative valence helps normalize far-right nativist ideology, thereby increasing support for this view
Computer-aided Drug Design in the Era of Cryptic Pockets, Allosterism and Event-driven Pharmacology
No full textMost of the current approved drugs block receptors/enzymes by competing with agonists/substrates for binding to the same pocket. While this type of drugs revolutionized health care since the advent of the modern pharmaceutical industry, the accumulating research in complex diseases such as cancer highlighted the limitations of such drugs in certain environmental context.
Novel strategies have been employed to circumvent those limitations and offer a superior pharmacological profile. In this PhD thesis, we employed computer-assisted drug discovery tools to help guiding and designing three binders that do not follow the traditional drug profile: a PROTAC to target HIF2α in the context of renal cell carcinoma, a covalent drug to offer an alternative to anti-TNFα biologics and a negative allosteric modulator to tune A2AR activation by adenosine and improve the immune system efficacy in the tumor micro-environment. </p
The PYRIDOXAL PHOSPHATE HOMEOSTASIS PROTEIN expands the role of vitamin B<sub>6</sub> metabolism in Arabidopsis
No full textVitamin B6 is a family of compounds and in its form as pyridoxal 5ʹ-phosphate (PLP) functions as a coenzyme in every form of life in hundreds of enzymatic reactions. Biosynthetic pathways yielding vitamin B6 de novo and through so-called salvage pathways have been described in plants to service provision of PLP and to maintain a balance between the various forms of vitamin B6 (vitamers) - critical for plant health. Over the past decade, an enigmatic PLP-binding protein has emerged as being vital to balance vitamin B6 levels and maintain vitamin B6-dependent metabolism. The protein named PLP HOMEOSTASIS PROTEIN (PLPHP) has been associated with vitamin B6 dependent epilepsy as well as other severe brain disorders in humans. Strikingly, at the outset of this thesis, the PLPHP protein had not been explored in plants. So, this study aimed to investigate the contribution of PLPHPs to vitamin B6 homeostasis and consequently plant fitness using the model plant Arabidopsis thaliana.
A phylogenetic analysis performed here shows that core Angiosperms exceptionally have two PLPHP homologues with residues conserved that are predicted to bind PLP. Recombinant versions of Arabidopsis PLPHP homologues (AtPLPHP1/2) harbour a Schiff-base bound PLP at a conserved lysine residue and appeared as monomeric proteins with PLP surface exposed, in stark contrast to the higher order nature of PLP-dependent proteins where the active site is shielded. Analysis of AtPLPHP1/2 mutants revealed that the two homologues contribute redundantly to vitamin B6 balance throughout the whole plant. Characteristic features are a general deficit in PLP with accumulation of pyridoxic acid (the degradation product of PLP/PL) in shoots and roots, accumulation of PNP in shoots and a deficit of PL in roots. While this imbalance appears to be dispensable under standard laboratory conditions in soil-grown plants, AtPLPHP1/2 was found to be necessary for root development on culture plates with root illumination, i.e. root photomorphogenesis. Surprisingly, the presence of AtPLPHP1/2 in the shoot was found to be sufficient to control root PLP levels and rescue root photomorphogenesis, suggesting that AtPLPHP1/2 may service PLP homeostasis distally. Further investigation revealed that in the absence of AtPLPHP1/2, Arabidopsis is probably unable to achieve auxin/ethylene homeostasis, thereby compromising root development under illumination. Although the shoot morphology of soil-grown AtPLPHP1/2 mutants is apparently unaffected, metabolic profiling of these plants revealed that the homeostasis of certain aspartate and chorismate derived amino acids is compromised in the shoot, providing a basis for future investigations into the physiological role of AtPLPHP1/2 in plants. In general, as plant foods are the main source of vitamin B6 in the human diet, a better understanding of how plants regulate levels could help us to improve not only plant health but also human health by increasing the nutritional quality of crops. This work presents PLPHP as an unexplored factor regulating vitamin B6 levels in plants and provides a basis for future investigations into the role of PLPHP in the green lineage.
</p
Paradigme de l'énaction et conception de formation hybride. Un cas de conception et d'analyse d'un dispositif de formation pour enseignants à la pratique professionnelle incluantun environnement numérique
No full textLa recherche présentée dans cet ouvrage s'intègre dans le champ de l'analyse de l'activité. Elle porte sur l'activité collective de futurs maîtres de pratique engagés dans la formation professionnelle d'apprentis en Suisse. Cette étude s'apparente à un projet de recherche technologique s'inscrivant dans une orientation scientifique qui considère les processus de formation comme étant itératifs et évolutifs. Les formateurs impliqués dans cette étude participent à un module de formation dont l'objectif est de les confronter à la notion « d'interdisciplinarité » au travers d'un dispositif de formation hybride ou blended learning créé pour l'occasion à l'Institut fédéral des hautes études en formation professionnelle (IFFP). Ces futurs formateurs passent de compétences techniques spécifiques à leur métier (maçonnerie, mécanique, etc.) à des compétences intégrant l'utilisation de nouveaux outils (projecteur vidéo, outils de bureautique, etc.) et de nouvelles pratiques (animation, gestion, etc.). Notre projet vise à mettre en évidence ces nouvelles pratiques et à comprendre comment elles émergent d'un tel dispositif. Cette étude relève pour nous d'un triple objectif qui inclut a) l'élaboration d'un dispositif de formation hybride reposant sur un environnement technologique d'apprentissage collaboratif, b) l'expérimentation d'un tel dispositif dans une situation réelle et c) l'analyse scientifique de l'activité collective des étudiants engagés dans ce processus. Plus globalement, nous souhaitons ouvrir la discussion autour des trois thématiques que sont : a) la construction d'expériences pour les apprenants, b) la conception de formations et c) le développement d'environnements numériques de formation
Bunkering Tourism in Bamako: Humanitarians Reshape Hotels in the Sahelian Conflict Zones
No full textSur la formation des "terres noires" cuprifères dans le bassin du Niari (Congo français)
No full textPas de résumé disponibl
«Изображение рая»: поэтика созерцания Леонида Аронзона
No full textL’œuvre de Leonid Aronzon (1939–1970), malgré le volume relativement faible de son héritage, est devenue une composante importante de la littérature non-officielle de Leningrad. Le poète a vécu une courte vie et est mort à l’âge de 31 ans, mais il est parvenu à créer un monde poétique intégral dans lequel les aspects formels coexistent de façon organique avec le visionnarisme mystique.
Je me suis donné pour tâche principale dans ce travail d’examiner comment l’image du paradis apparaît dans la vision du poète et/ou de son personnage lyrique, comment et dans quelles circonstances cette contemplation visionnaire peut survenir, de quoi elle s’accompagne et où elle mène celui qui contemple. L’objectif de cette analyse est de déterminer la perspective lyrique de la poésie d’Aronzon, perspective dans laquelle le paradis constitue le vecteur principal régissant l’ensemble de l’ œuvre et faisant de celle-ci un jalon important de la poésie métaphysique russe du XXe siècle.</p
