Cette thèse propose l’introduction de scénarios temporels pour guider ou composer l’improvisation musicale homme-machine. Ce travail étudie la dialectique entre planification et réactivité dans les systèmes interactifs dédiés à l’improvisation : des systèmes informatiques pouvant générer de la musique en relation directe avec le contexte produit par une situation de concert. On cherche ici à appréhender l'improvisation pulsée et dite « idiomatique ». En s’appuyant sur l’existence d’une structure formalisée antérieure à la performance dans de nombreux répertoires improvisés (une « grille d’accords » par exemple) ces travaux proposent : un modèle d’improvisation guidée par un « scénario » introduisant des mécanismes d’anticipation ; une architecture temporelle hybride combinant anticipation et réactivité et permettant la synchronisation du rendu multimédia avec une pulsation non métronomique ; et un cadre pour composer des sessions d’improvisation idiomatique ou non à l’échelle du scénario en exploitant la généricité des modèles. Ces recherches ont été menées en interaction constante avec des musiciens experts, en intégrant pleinement ces collaborations au processus itératif de conception des modèles et architectures. Ceux-ci ont été implémentés dans le système ImproteK, utilisé à de nombreuses reprises lors de performances avec des improvisateurs. Au cours de ces collaborations, les sessions d'expérimentations ont été associées à des entretiens et séances de réécoute afin de recueillir de nombreuses appréciations formulées par les musiciens pour valider et affiner les choix technologiques. / This thesis focuses on the introduction of authoring and controls in human-computer music improvisation through the use of temporal scenarios to guide or compose interactive performances, and addresses the dialectic between planning and reactivity in interactive music systems dedicated to improvisation. An interactive system dedicated to music improvisation generates music on the fly, in relation to the musical context of a live performance. We focus here on pulsed and idiomatic music relying on a formalized and temporally structured object, for example a harmonic progression in jazz improvisation. The same way, the models and architecture we developed rely on a formal temporal structure. This thesis thus presents: a music generation model guided by a ''scenario'' introducing anticipatory behaviors; an architecture combining this anticipation with reactivity using mixed static/dynamic scheduling techniques; an audio rendering module to perform live re-injection of captured material in synchrony with a non-metronomic beat; and a framework to compose improvised interactive performances at the ''scenario'' level. This work fully integrated frequent interactions with expert musicians to the iterative design of the models and architectures. These latter are implemented in the interactive music system ImproteK that was used at various occasions during live performances with improvisers. During these collaborations, work sessions were associated to listening sessions and interviews to gather numerous judgments expressed by the musicians in order to validate and refine the scientific and technological choices.

High-throughput genomics projects have resulted in a rapid accumulation of protein sequences. Therefore, computational methods that can predict protein functions and functional sites efficiently and accurately are in high demand. In addition, prediction methods utilizing only sequence information are of particular interest because for most proteins, 3-dimensional structures are not available. However, there are several key challenges in developing methods for predicting protein function and functional sites. These challenges include the following: the construction of representative datasets to train and evaluate the method, the collection of features related to the protein functions, the selection of the most useful features, and the integration of selected features into suitable computational models. In this proposed study, we tackle these challenges by developing procedures for benchmark dataset construction and protein feature extraction, implementing efficient feature selection strategies, and developing effective machine learning algorithms for protein function and functional site predictions. We investigate these challenges in three bioinformatics tasks: the discovery of transmembrane beta-barrel (TMB) proteins in gram-negative bacterial proteomes, the identification of deleterious non-synonymous single nucleotide polymorphisms (nsSNPs), and the identification of helix-turn-helix (HTH) motifs from protein sequence.

No description available.

One of the most profound open questions in biology is how the genetic code developed. The blueprints for proteins are encoded by triplets of nucleic acids, which in turn require proteins for interpretation and replication. The mere existence of this self-referencing system is a chicken-and-egg dilemma. Aminoacyl-tRNA synthetases are key players in the transfer of genetic information and reflect the earliest episode of life. These enzymes are responsible for loading tRNA molecules with the correct amino acid. Two protein superfamilies of aminoacyl-tRNA synthetases emerged, each responsible for ten amino acids. Despite sequence and structure similarity, the delicate balance between these superfamilies is manifested in two structural motifs, which were identified in the context of this thesis: the Backbone Brackets and the Arginine Tweezers. Both motifs realize constant ligand recognition and can be found in almost all protein structures of aminoacyl-tRNA synthetases. In this thesis, I thoroughly characterized Backbone Brackets and Arginine Tweezers. The specific characteristics of these motifs require high-precision methods for their detection and analysis. However, existing algorithms do not feature an adequate computational representation of structural motifs at the atom level and the support of isofunctional residue mutations. In order to address these limitations, I designed the Fit3D algorithm for template-based and template-free detection of structural motifs. I show that proper computational representation of structural motifs is crucial and improves accuracy up to 26% for a benchmark dataset. Fit3D is a general-purpose tool for structural motif detection in high-resolution protein structure data. In conjunction with the accelerating progress in experimental methods, the demand for such tools will increase rapidly over the next years. I applied Fit3D to structures of aminoacyl-tRNA synthetases to investigate whether Backbone Brackets and Arginine Tweezers are universal building blocks for ligand recognition, and to quantify structural changes upon ligand binding. While the Arginine Tweezers motif is exclusively found in aminoacyl-tRNA synthetases and paralogs, the Backbone Brackets seem to be a general pattern to recognize functional groups of certain ligands. The results show subtle differences in side chain orientation for one structural motif and a backbone shift for the other. This suggests a structural rearrangement to be a general mechanism in some aminoacyl-tRNA synthetases. The detailed level of these analyses would not have been possible without high-precision structural motif detection with Fit3D. The results emphasize the importance of structural motifs, which consist of only a few residues, for the global function of the enzyme. Furthermore, the stunning conservation of the structural motifs located in the core domains of aminoacyl-tRNA synthetases suggests their presence in the earliest predecessors of these enzymes. Both motifs might have played a fundamental role in shaping the genetic code as we know it.

Peter L. Berger's conception of agency in his earliest writings (c.1954-1960) is logically and empirically inadequate. At the root of this inadequacy is an idealism that prevents him from providing a compelling account of actual empirical agency. Chapter 1 asserts that Berger's earlier works warrant analysis. Chapter 2 discusses Berger's earliest influences, particularly Max Weber and The Swedish Lund School of motif research. Chapter 3 identifies a unique commitment to Christian Humanism at the base of Berger's conception of agency. Chapter 4 clarifies how Berger's Christian humanism interacts with his Weberian, and Parsonian-inspired functional analysis of the American religious establishment. The thesis concludes (Chapter 5) by identifying more specifically how and why Berger's Christian humanism undermines his attempt to empirically ground human agency.

Pharmaceutical solids tend to exist in different physical forms termed as polymorphs. Issues about pharmaceutical systems are mainly concerned with the active ingredient's physico-chemical stability and bioavailability. The main aim of this study is to investigate the non-bonded interactions in pharmaceutical solids that govern the physical pharmaceutics performance of such materials and through the use of structural techniques and correlation of these results with crystal structural database to establish the presence of physical motifs in selected systems. Structural motifs were identified by the use of single crystal and crystal packing analysis on diverse range of pharma-relevant materials including chalcones, cryptolepines, biguanides and xanthines. These selected systems were validated using functional group and molecular analysis and correlating them to the Cambridge Structural Database. Crystallization studies are done on these selected systems as well as exploiting those using synthetic analogues. A total of 51 crystal structures were investigated including 16 new structure determinations. Addition synthesis of new xanthines to investigate novel intermolecular patterns was also undertaken. The understanding and exploitation of intermolecular interactions involving hydrogen bonds and coordination complexation during packing can be used in the design and synthesis of solid state molecular structures with desired physical and chemical properties.

Ce mémoire est composé de deux sections, une de création et l’autre de réflexion. La première consiste d’un roman de fantaisie satirique, Incompetent Gods (écrit en anglais) et la deuxième d’un essai à propos de ce genre. Incompetent Gods - Dans une dimension parallèle, créée par les dieux écœurés de l’athéisme régnant dans la nôtre, immortels et mortels vivent ensemble en cacophonie. Leurs relations sont étroitement surveillées par la compagnie Dieux Inc. qui emploie et contrôle la plupart des divinités. Son PDG, la reine Louhi Pohjola, court un grave danger car Goblin et son souverain-fifre Japhet essaient de se débarrasser d’elle afin de conquérir le monde. Ce récit satirique, en utilisant la transvalorisation de mythes anciens, la parodie de lieux communs présents en fantaisie, la transposition de dieux dans un contexte corporatif et des jeux de langage, se veut une critique de notre société, de nos valeurs et de nos utopies. Effets de miroirs. De la satire en fantaisie - Cet essai présente une étude littéraire de l’œuvre de Terry Pratchett, un des géniteurs de la fantaisie satirique contemporaine, suivie d’une réflexion sur le processus de création. Cela dans le but de répondre à deux questions : comment se moquer d’une chose alors qu’on en évoque une autre? Et comment créer un effet de reconnaissance entre le merveilleux et le réel? Idéalement, ceci permettra d’offrir une nouvelle perspective sur ce genre si mal apprécié. / This thesis is made up of two parts. The first one, Incompetent Gods, is a short satirical fantasy novel written in English. The second part consists of an essay about the genre. Incompetent Gods - In a parallel world, created by the gods sickened with the atheism in our dimension, mortals and immortals live together in cacophony. Their relations are monitored by Gods Inc., a huge multinational that employs and controls most divinities. Its CEO, Queen Louhi Pohjola, is in grave danger, for in order to conquer the world, Goblin and his side-king Japhet are doing all they can to get rid of her. By devaluing old myths, parodying the clichés of fantasy, transposing gods into a corporate context and playing with language, this satirical fable aims to critique our society, our values and our utopias. Effets de miroirs. De la satire en fantaisie - This essay (in French) presents a literary study of the works of Terry Pratchett, one of the most famed authors of contemporary satirical fantasy, and a reflection on the creative process that answers two questions: how to ridicule one thing while evoking another? And how to create a mirror of reality through the use of fantasy? Ideally, this will give new insights into this badly perceived genre.

L'ironie se rencontre dans la réécriture du Berger extravagant de Charles Sorel comme une figure de double pensée. À la fois critique des romans ± fabuleux ¿ et promotion de la fiction romanesque, Y Anti-roman se construit selon un plan contradictoire, voire paradoxal, où la plupart des énoncés rencontrent une double signification. Conséquence des bouleversements liés à la constitution du champ littéraire parisien des années 1620-1630 (par exemple le procès de Théophile de Viau ou la montée du purisme de l'Académie), l'ironie de Y Anti-roman n'est pas uniquement orientée vers la dévalorisation ou la célébration de l'imaginaire du roman pastoral ; elle met aussi en scène plusieurs discours qui ont marqué le premier XVIIe siècle, tels que l'apologétique chrétienne du jésuite François Garasse ou l'effritement graduel de l'humanisme des commentateurs renaissants, aboutissant au finale à une critique des Fables et des conceptions gnoséologiques qui s'y rattachent. À l'aide de l'ironie et de ses définitions historiques, ce mémoire explore les avenues et les échecs d'un "roman-commentaire" qui gardera une place de choix dans l'histoire moderne du genre romanesque.

Both technological and experimental advancements in the field of biotechnology have allowed scientists to make leaps in areas such nucleic acid, antibody, and recombinant protein technologies. Here we focus on the use of recombinant proteins as molecular recognition motifs, wound healing biomaterials, and agents for cell cycle pathway elucidation are discussed. The author's primary project is described in chapters 2 and 3, and is focused on designed leucine-rich repeat proteins which offer increased stability, modularity, and surface area for binding interactions. These proteins bind at least two muramyl dipeptide ligands with picomolar to nanomolar affinity (Kd1 = 0.04 – 3.5 nM); as measured by fluorescence quenching experiments and ITC. The longest designed repeat, CLRR8, has a Kd app value of 1.0 nM which is comparable to full length native NOD2 protein. Molecular docking simulations revealed the locations of two potential binding sites and their respective interactions. The series of proteins represents a foundation for a high affinity and highly specific molecular recognition scaffold that has the potential to bind a variety of ligands. Previously the author contributed to the design of recombinant keratin proteins, and the work in Chapter 4 builds on the original design to allow for controlled degradation in wound healing systems. Site-directed mutagenesis was utilized to introduce these degradation sites, and modified keratin proteins were expressed with no differences to native recombinant keratin proteins. Success in engineering a variation of native keratin protein with no issues in expression lay the foundation for further engineering of native keratin or other relevant proteins for improved functionality. Chapter 5 describes steps towards producing human Aurora borealis (Bora) protein, an important substrate in cell cycle regulation, by in vitro transcription-translation with locked Ser–Pro analogues. This will allow for the elucidation of the active isomerization form to ensure proper cell division. Site-directed mutagenesis successfully introduced the amber codon to relevant Ser-Pro sites at positions 274 and 278. These mutated Bora genes along with modified ribosomes and aminoacyl tRNA will allow for the incorporation of locked dipeptide analogues. Expression of native Bora was carried out as a control, and appeared to express in dimeric form. The experiments carried out in Chapter 5 describe and outline all the molecular biology work completed and to be completed for this novel method of studying cis-trans isomerization in living cells. / Doctor of Philosophy / Sequencing of the human genome and the rapid development of gene editing and recombinant DNA technologies paved the way for a massive shift in the pharmaceutical industry. The first pharmaceutical companies in the 19th century started as fine chemicals businesses. The discovery of penicillin introduced antibiotics, and improved synthetic techniques led to the giants we know as big pharma today. Today, in the 21st century both computing and biotechnology has allowed for great leaps forward in precision medicine. Biotechnology refers to the manipulation of living organisms or their components to produce useful commercial products. In the pharmaceutical industry this refers to genetic engineering for novel pharmaceuticals. Here, we focus on the use of recombinant technology to create proteins for use in biomedical applications. Recombinant proteins are proteins formed by laboratory methods of molecular cloning. Through this technology, we are able to elucidate sequence-structure-function relationships of proteins, and determine their specific functions. Additionally, recombinant methods allow us to fine tune or modify the sequences of natural proteins to be more effective scaffolds or reagents. Chapter 3 focuses on the development of synthetic proteins for medical diagnostics. We designed a protein scaffold, based on natural innate immunity proteins, to detect bacteria cell wall components. Chapter 4 focuses on the engineering of keratin protein with applications in wound healing. We introduce controlled degradation of the biomaterial for use in potential drug delivery systems at the wound site. Chapter 5 focuses on the use of recombinant technologies aiding in the elucidation of a regulatory protein's function in cell division.

No description available.