Les lymphocytes T (LT) jouent un rôle clé dans la mise en place d’une réponse immunitaire efficace. De part des besoins énergétiques et biosynthétiques distincts, leur activation, leur prolifération et leur différenciation fonctionnelle requièrent un contrôle métabolique très fin. La kinase mTOR est apparue comme un régulateur important de la biologie des LT. En effet, cette kinase contrôle le métabolisme et permet une augmentation de la synthèse d’énergie notamment par une augmentation de la glycolyse, indispensable à l’activation des LT. mTOR détecte la disponibilité des nutriments (ex. les acides aminés et le glucose) ainsi que les facteurs de croissance, puis intègre de tels signaux pour réguler le métabolisme des LT. Un rôle clé des acides aminés dans la réponse des LT a été mis en évidence. La petite protéine-G RagA joue un rôle clé dans la détection du glucose et des acides aminés ramifiés, requise pour l’activation de mTOR dans le complexe mTORC1, impliqué dans le contrôle du métabolisme. Afin d’appréhender l’influence du microenvironnement métabolique sur l’activation, la prolifération et la polarisation des LT auxiliaires, nous avons généré et analysé des souris avec des mutations de RagA dans les LT. Les souris mutantes ne présentent aucun signe macroscopique de perturbations du système immunitaire tel que des pathologies autoimmunes ou le développement de tumeurs. Le développement des LT dans le thymus est globalement normal, même si l’on peut observer une légère diminution du développement des LT régulateurs. En périphérie, l’homéostasie immunitaire ne semble pas altérée mis à part une légère diminution du pourcentage de LT mémoires. Nous avons constaté que la perte de RagA entraîne une diminution substantielle de l’activité de mTORC1 observée après activation des LT mais, de façon inattendue, pas une abolition totale. A l’inverse, nous avons observé une augmentation de l’activité de mTORC2 dans les cellules KO. De façon plus surprenante, nous avons mis en évidence que, très rapidement après la délétion de RagA dans le thymus, une faible activité basale de mTORC1 se met en place. Précocement après activation, les LT RagA KO ne présentent pas de problème de survie, cependant ils prolifèrent moins rapidement, ce qui est vraisemblablement dû à un apport d’énergie plus faible par glycolyse. Nous avons constaté que des LT RagA-KO activés in vitro dans des conditions « neutres » expriment spontanément des niveaux plus élevés de T-bet, facteur de transcription « maître » des lymphocytes T auxiliaires de type I (Th1). Aussi suite à une activation des LT en condition polarisante Th1, nous avons observé davantage de cellules RagA-KO que WT produisant de l’interféron-γ. Ces résultats montrent que l’activité de RagA, et par conséquent vraisemblablement de mTORC1, inhibe la différenciation Th1. Nous avons pu constater que les LT RagA-KO favorisent la différenciation Th1 au moins en partie par des mécanismes intrinsèques et extrinsèques. De plus, nous observons une activité tardive de mTORC1 dans les LT RagA-KO. Nous émettons l’hypothèse que RagA inhibe l’activité tardive de mTORC1 et que cette activité tardive permet une meilleure différenciation en Th1. En conclusion, nos résultats montrent que l’absence de la GTPase RagA dans les LT diminue l’activité de mTORC1 sans l’abolir totalement. De façon importante et surprenante, nous démontrons que malgré la baisse d’activité de mTORC1 en absence de RagA, la différenciation en lymphocytes Th1 est augmentée. Ainsi, la GTPase RagA semble avoir un rôle inhibiteur de la différenciation en Th1 potentiellement en inhibant une activité à long terme de mTORC1. / T lymphocytes play a key role in the development of an effective immune response. Because of their distinct energy and biosynthetic needs, their activation, proliferation and functional differentiation require very fine metabolic control. The mTOR kinase has emerged as an important regulator of the biology of helper T cells. Indeed, this kinase controls the metabolism and allows an increase in the synthesis of energy in particular by an increase in glycolysis, essential for the activation of T cells. mTOR detects the availability of nutrients, such as amino acids, glucose and growth factors, and then integrates such signals to regulate T cell metabolism. Studies have shown a key role of amino acids in the response of T cells. The small RagA-G protein plays a key role in the detection of glucose and branched amino acids required for the activation of mTOR in the mTORC1 complex involved in metabolic control. In order to understand the influence of the metabolic microenvironment on the activation, proliferation and polarization of helper T cells we generated and analyzed mice with mutations of RagA in T cells. Mutant mice show no signs of immune system disturbances such as autoimmune pathologies or tumor development. T cell development in the thymus is g normal even though a slight decrease in the development of regulatory T cells can be observed. In the periphery, immune homeostasis does not seem to be altered except for a slight decrease in the percentage of memory T cells.We found that the loss of RagA results in a substantial decrease in mTORC1 activity after T cell activation but unexpectedly not complete abolition. Conversely, we observed an increase in mTORC2 activity in KO cells. More surprisingly, we have shown that, very soon after the deletion of RagA in the thymus, a low basal activity of mTORC1 takes place. Early after activation, RagA KO T cells did not present a survival problem, however they proliferated less rapidly, which is probably due to a lower energy intake by glycolysis. We have found that RagA KO T cells activated in vitro under "neutral" conditions spontaneously express higher levels of T-bet, the "master regulator" transcription factor of type I (Th1) helper T cells. Therefore, following activation of T cells in polarizing condition Th1, we observed more RagA KO cells than wt producing interferon-γ. These results show that the activity of RagA, and therefore presumably of mTORC1, inhibits Th1 differentiation. We have seen that RagA KO cells favor Th1 differentiation by intrinsic and extrinsic mechanisms. We hypothesize that IFN-γ, more produced by RagA-KO cells, is involved. In addition, we observed a late activity of mTORC1 in RagA-KO LT. We hypothesize that RagA inhibits the late activity of mTORC1 and that this late activity allows better Th1 differentiation. In conclusion, our results show that the absence of RagA GTPase in T cells decreases the activity of mTORC1 without completely abolishing it. Significantly and surprisingly, we demonstrate that despite the decrease in mTORC1 activity, Th1 cell differentiation is increased in the absence of RagA. Thus, RagA GTPase appears to have an inhibitory role in Th1 differentiation potentially by inhibiting a long-term activity of mTORC1.

In Indian Classical Music (ICM), the Raga is a musical piece's melodic framework. It encompasses the characteristics of a scale, a mode, and a tune, with none of them fully describing it, rendering the Raga a unique concept in ICM. The Raga provides musicians with a melodic fabric, within which all compositions and improvisations must take place. Identifying and categorizing the Raga is challenging due to its dynamism and complex structure as well as the polyphonic nature of ICM. Hence, Raga recognition—identify the constituent Raga in an audio file—has become an important problem in music informatics with several known prior approaches. Advancing the state of the art in Raga recognition paves the way to improving other Music Information Retrieval tasks in ICM, including transcribing notes automatically, recommending music, and organizing large databases. This thesis presents a novel melodic pattern-based approach to recognizing Ragas by representing this task as a document classification problem, solved by applying a deep learning technique. A digital audio excerpt is hierarchically processed and split into subsequences and gamaka sequences to mimic a textual document structure, so our model can learn the resulting tonal and temporal sequence patterns using a Recurrent Neural Network. Although training and testing on these smaller sequences, we predict the Raga for the entire audio excerpt, with the accuracy of 90.3% for the Carnatic Music Dataset and 95.6% for the Hindustani Music Dataset, thus outperforming prior approaches in Raga recognition. / Master of Science / In Indian Classical Music (ICM), the Raga is a musical piece's melodic framework. The Raga is a unique concept in ICM, not fully described by any of the fundamental concepts of Western classical music. The Raga provides musicians with a melodic fabric, within which all compositions and improvisations must take place. Raga recognition refers to identifying the constituent Raga in an audio file, a challenging and important problem with several known prior approaches and applications in Music Information Retrieval. This thesis presents a novel approach to recognizing Ragas by representing this task as a document classification problem, solved by applying a deep learning technique. A digital audio excerpt is processed into a textual document structure, from which the constituent Raga is learned. Based on the evaluation with third-party datasets, our recognition approach achieves high accuracy, thus outperforming prior approaches.

In this dissertation, overviews and detailed examinations of three compositions are presented. These compositions which constitute the portfolio of the M.MUS degree, are an attempt to explore syncretism between Indian and western music. Two of these works are written for a flute quartet (flute, violin, viola and cello) accompanied in part by a mridangam (Indian percussion instrument). The third work is written for a jazz quartet (piano, saxophone, double bass and drums). Syncretism between western and Indian music can take on a variety of forms, and while this concept is not new, there exists no suitable model or framework through which these compositions can be analysed. The approach used In this dissertation IS therefore guided solely by the compositions themselves. The syncretism in these works lies in the use of melodic, rhythmic and timbral elements of Indian music within two ensembles which are essentially western. This dissertation describes each of these elements in their traditional context as well as the method of incorporating them into western ensemble playing.

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The rasa theory of Indian aesthetics is concerned with the nature of the genesis of emotions and their corresponding experiences, as well as the condition of being in and experiencing the aesthetic world. According to the Indian aesthetic theory, rasa ("juice" or "essence," something that is savored, that is tasted) is an embodied aesthetic experienced through an artistic performance. In this thesis, I have investigated how the aesthetics of rasa philosophy account for creative presence and its experiences in Karnatik vocal performances. Beyond the facets of grammar, Karnatik rāga performance signifies a deeper ontological meaning as a way to experience rasa, idiomatically termed as rāga-rasa by South Indian rāga practitioners. A vocal performance of a rāga ideally depends on a singer's embodied experience of rāga and rāga-bhāva (emotive expression of rāga), as much as it does on his/her theoretical knowledge and skillset of a rāga's svaras (scale degrees), gamakas (ornamentation), lakṣhaṇās (emblematic phrases), and so on. Reflecting on my own experience of being a Karnatik student and performer for the last two decades, participant observation, interviews, and analysis of Indian aesthetic theory of rasa, I propose a way of understanding that to sing rāga is to embody bhāva opening the space that brings rasa into being. Reflecting on the epistemology of rāga theory, particularly its smaller entities of svaras and gamakas, and through a phenomenological description of the process through which a vocalist embodies rāga (including how a guru transmits this musical embodiment to his shishya [disciple]), I argue that the notion of rāga-rasa itself has agency in determining the nature of svaras and its gamakas in a rāga performance. Additionally, focusing on the relationship between performers and rasikas (drinkers of the juice), this thesis examines how the embodiment of rāga-bhāva and the experience of rasa open the possibility for musicians and audiences to live rāga-rasa in a performance.

This thesis is an investigation into the historical evolution of Ajegunle Raga, a reggae form developed within an urban ghetto in Lagos called Ajegunle and the construction and negotiation of identities therein. The research further argues that Ajegunle Raga is a home-grown oppositional music subculture that draws inspiration from diasporic musical subcultures like Reggae and Hip Hop but retains a genuine representation of Ajegunle in its tales of survival, poverty, marginalization and expressions of creativity within the ambience of the music.