In peptide-based medicinal chemistry, mimicry of turn conformations is important because of the significance of such secondary structures for molecular recognition. In this context, N-aminoimidazol-2-one (Nai) residues have demonstrated ability to mimic the central residue of turn conformers. Moreover, potential to functionalize the 4- and 5-positions of the Nai heterocycle offer opportunities to add and orient side chain functionalities with constrained c-geometry. Methods have been developed to employ Nai residues for peptide mimicry. Previously, Nai dipeptide esters with substituents at the imidazol-2-one 4-position were obtained as racemic mixtures. By employing alternative C-terminal groups, epimerization has now been minimized. Functionalization of the Nai 5-position after cyclization has also been achieved by novel chemistry. For example, (4-Me, 5-aldehyde)Nai residues were obtained by 5-position formylation. The aldehyde was then reduced and oxidized to provide alcohol and acid functionality. Reductive aminations on (4-Me, 5-aldehyde)Nai residues using different primary and secondary amines and amino methylation of (4-Me)Nai residues were also used to prepare constrained diaminobutyric acid analogs. In the interest to prepare Nai analogs that can serve as constrained phenylalanine residues, palladium-catalyzed chemistry was developed to cross-couple different aryl iodides at the 5-position. In model peptides, the (4-Me, 5-aryl)Nai residues were predicted by molecular dynamic calculations to be located at the i+1 position of type II’ β-turn conformations with the aryl side chain positioned in the gauche (–). The synthesis of biologically relevant Nai peptides was next explored using methods for accessing enantioenriched residues and conditions for their 5-position arylation. Peptide derivatives of growth hormone releasing peptide-6 (GHRP-6) were targeted using the Nai residues because the corresponding semicarbazide analogs had exhibited selective and relatively high binding affinity for the cluster of differentiation receptor (CD36) receptor and potential to mediate macrophage-driven inflammation in conditions leading to age-related macular degeneration, atherosclerosis and angiogenesis. Previous studies with GHRP-6 analogs demonstrated that replacement of Trp4 with a semicarbazide possessing an aromatic side chain favored a turn conformation and selective CD36 binding affinity. Solid-phase methodology was developed to synthesize [(4-Me, 5-Aryl)Nai4]-GHRP-6 analogs and used to prepare four different Nai peptides on Rink amide resin. All four analogs were effective at mediating nitric oxide (NO) overproduction in macrophages cells treated with a Toll-like receptor 2 (TLR2) agonist. Although biological evaluation of the [(4-Me,5-Aryl)Nai4]-GHRP-6 analogs is still being performed, their ability to modulate NO overproduction strongly indicated backbone and side chain conformational requirements for biological activity. In sum, this thesis has provided effective methods for preparing novel constrained peptide analogs for mimicry of the backbone and side chain geometry in β-turns. Enantiomerically enriched Nai residues were synthesized, introduced into peptide sequences, and functionalized at the 4- and 5-positions. Employment of the 4,5-disubstituted Nai analogs in the study of peptide medicinal chemistry offers powerful potential for exploring structure-activity relationships to identify and replicate biologically active conformers. / Le développement de mimes de tours peptidiques pose un intérêt particulier en chimie médicinale, en raison de leur importance dans la reconnaissance moléculaire. Dans ce contexte, les résidus N-aminoimidazol-2-one (Nai) ont démontré une tendance à occuper la position centrale de repliements peptidiques. De plus, la présence de l’unité imidazolone offre un potentiel de fonctionnalisation en position 4 et 5 pouvant jouer le rôle de chaînes latérales rigidifiées dans l’espace χ. Des méthodes ont été développées pour rendre possible l’utilisation de résidus Nai en chimie peptidique. Par le passé, des esters de dipeptide Nai possédant un substituant à la position 4 de l’hétérocycle ont été synthétisés de manière racémique. L’utilisation de groupement C-terminaux a permis de grandement réduire l’épimérisation due à l’utilisation de base forte utilisée durant l’étape de cyclisation. La fonctionnalisation de la position 5 du cycle après la cyclisation a aussi été rendue possible par le développement de nouvelles conditions réactionnelles. Par exemple, des conditions de formylation ont donné des résidus (4-Me, 5-Aldéhyde)Nai. La fonction aldéhyde a été réduite et oxydée, donnant accès a des fonctions alcool et acide carboxylique. L’amination réductrice du squelette (4-Me, 5-Aldéhyde)Nai en utilisant des amines primaires et secondaires ainsi que l’amino-méthylation de résidus (4-Me)Nai ont donné accès à des résidus d’acide diaminobutyrique rigidifiés. Dans le but de préparer des analogues Nai pouvant servir de mimes rigidifiés de résidus phénylalanine, la catalyse au palladium a rendu possible l’installation de groupements 5-aryle par couplage croisé avec différents iodoaryles. Dans un modèle de peptide, le résidu (4-Me, 5-aryl)Nai a été soumis à une analyse par dynamique moléculaire qui a révélé le positionnement de la portion Nai à la position i+1 d’un tour β de type II’, avec la chaine latérale aryle adoptant une conformation gauche (-). Ayant en main des conditions de synthèse énantioenrichie ainsi que de diversification de la position 5, la construction de peptides Nai possédant un intérêt biologique a été entreprise. Des dérivés du peptide Growth hormone releasing peptide-6 (GHRP-6) ont été ciblés car les analogues semicarbazide correspondant ont précédemment démontré avoir à la fois de la sélectivité et une affinité relativement grande pour le Cluster of differentiation receptor (CD36). Ils ont ainsi le potentiel de moduler l’inflammation attribuable aux macrophages dans des conditions menant à la dégénérescence maculaire liée à l’âge, l’athérosclérose et l’angiogenèse. Des études précédentes ont démontré que le remplacement du résidu Trp4 du GHRP-6 par un semicarbazide possédant une chaîne latérale aromatique favorisait l’adoption d’un repliement de la chaîne peptidique et une affinité sélective envers le récepteur CD36. Une méthode de synthèse sur phase solide d’analogues [(4-Me, 5-Aryle)Nai4]-GHRP-6 a été développée et utilisée pour synthétiser quatre différents peptides Nai en utilisant la résine Rink amide. Les quatre analogues se sont montrés efficaces à réduire la surproduction d’oxide nitrique (NO) dans les cellules macrophages traitées avec un agoniste du Toll-like receptor 2 (TLR2). Malgré le fait que l’évaluation biologique des analogues [(4-Me, 5-Aryle)Nai4]-GHRP-6 soit toujours en cours, leur habilité à moduler la surproduction d’oxide nitrique montre qu’ils possèdent la bonne géométrie quant à la chaîne principale et la chaîne latérale aromatique pour interagir avec le récepteur. En somme, la présente thèse a fourni des méthodes efficaces de synthèse de nouveaux analogues de peptides rigidifiés pour mimer les chaînes principale et latérales de tours β. Les résidus Nai énantioenrichis ont été synthétisés, introduits dans des séquences peptidiques d’intérêt sur phase solide et fonctionnalisés à la 4ième et 5ième position. L’utilisation de ces analogues Nai 4,5-disubstitués en chimie médicinale et peptidique offre un potentiel considérable dans l’exploration de la relation structure-activité de peptides d’intérêt biologique pour identifier et mimer les conformères bioactifs.

This thesis focuses on increasing the customer satisfaction of travel agency. Customer satisfaction is a key component for maintaining market position, company reputation and its growth. Client satisfaction is especially important in the area of services, including travel agencies. Based on a questionnaire survey among customers, using the NPS method and the KANO model, measures are designed for increasing it. Also the suggestions are obtained to improve company promotion with the use of customer survey.

The goal undertaken in this Bachelor´s thesis was to establish, and possibly audit, the assumed motif, provenance, dating and formal style regarding two Medieval wooden sculptures depicting Saint Martin of Tours and Saint George. Both are preserved in the art collection formerly owned by one of the great Swedish artists and art collectors of the nineteenth century: Anders Zorn (1860-1920). The purpose of the study was to account for the two sculptures using the Iconographic analysis developed by Erwin Panofsky (1892-1968), and the style critical method founded by Giovanni Morelli (1816-1891). The goal was furthermore to incorporate the sculptures into a broader art historical context and discuss in what way history has impacted the usage of and attitude towards the Medieval wooden sculptures i Sweden. The result of the study concluded that the majority of what had earlier been assumed about the sculptures in regards to their respective motif, geographical orgin, style and age had been correct. Some new contributions were however made concerning similar representations, local contextualizations and the mere act of researching an object to which no major research had yet been devoted. The study also concluded that the ever changing usage of and attitude towards the Middle Ages from the Reformation during the sixteenth and seventeenth century until the beginning of the twentieth century, has likewise affected the usage of and attitude towards the medieval wooden sculptures. The consequences for the sculptures were never unequivocally positive or negative.

<p>In recent years there has been a growing interest in data mining and graph machine learning for techniques that can obtain frequencies of <em>k</em>-node Connected Induced Subgraphs (<em>k</em>-CIS) contained in large real-world graphs. While recent work has shown that 5-CISs can be counted exactly, no exact polynomial-time algorithms are known that solve this task for <em>k </em>> 5. In the past, sampling-based algorithms that work well in moderately-sized graphs for <em>k</em> ≤ 8 have been proposed. In this thesis I push this boundary up to <em>k</em> ≤ 16 for graphs containing up to 120M edges, and to <em>k</em> ≤ 25 for smaller graphs containing between a million to 20M edges. I do so by re-imagining two older, but elegant and memory-efficient algorithms -- FANMOD and PSRW -- which have large estimation errors by modern standards. This is because FANMOD produces highly correlated k-CIS samples and the cost of sampling the PSRW Markov chain becomes prohibitively expensive for k-CIS’s larger than <em>k </em>> 8.</p> <p>In this thesis, I introduce:</p> <p>(a)  <strong>RTS:</strong> a novel regenerative Markov chain Monte Carlo (MCMC) sampling procedure on the tree, generated on-the-fly by the FANMOD algorithm. RTS is able to run on multiple cores and multiple machines (embarrassingly parallel) and compute confidence intervals of estimates, all this while preserving the memory-efficient nature of FANMOD. RTS is thus able to estimate subgraph statistics for <em>k</em> ≤ 16 for larger graphs containing up to 120M edges, and for <em>k</em> ≤ 25 for smaller graphs containing between a million to 20M edges.</p> <p>(b) <strong>R-PSRW:</strong> which scales the PSRW algorithm to larger CIS-sizes using a rejection sampling procedure to efficiently sample transitions from the PSRW Markov chain. R-PSRW matches RTS in terms of scaling to larger CIS sizes.</p> <p>(c) <strong>Ripple:</strong> which achieves unprecedented scalability by stratifying the R-PSRW Markov chain state-space into ordered strata via a new technique that I call <em>sequential stratified regeneration</em>. I show that the Ripple estimator is consistent, highly parallelizable, and scales well. Ripple is able to <em>count</em> CISs of size up to <em>k </em>≤ 12 in real world graphs containing up to 120M edges.</p> <p>My empirical results show that the proposed methods offer a considerable improvement over the state-of-the-art. Moreover my methods are able to run at a scale that has been considered unreachable until now, not only by prior MCMC-based methods but also by other sampling approaches. </p> <p><strong>Optimization of Restricted Boltzmann Machines. </strong>In addition, I also propose a regenerative transformation of MCMC samplers of Restricted Boltzmann Machines RBMs. My approach, Markov Chain Las Vegas (MCLV) gives statistical guarantees in exchange for random running times. MCLV uses a stopping set built from the training data and has a maximum number of Markov chain step-count <em>K</em> (referred as MCLV-<em>K</em>). I present a MCLV-<em>K</em> gradient estimator (LVS-<em>K</em>) for RBMs and explore the correspondence and differences between LVS-<em>K</em> and Contrastive Divergence (CD-<em>K</em>). LVS-<em>K</em> significantly outperforms CD-<em>K</em> in the task of training RBMs over the MNIST dataset, indicating MCLV to be a promising direction in learning generative models.</p>

This item contains the agenda, minutes, and attachments for the Faculty Senate meeting on this date. There may be additional materials from the meeting available at the Faculty Center.

This diploma thesis remarks on the beginning of the equality of rights and the complete social recognition of the puppetry in Czech theatres in the years 1973 - 1982. The thesis deals with the history of the East Bohemian theatre DRAK in Hradec Kralove from its foundation, it describes the arrival of the director Josef Krofta, Prague's performances of DRAK in 1977, the first tours abroad, it observes DRAK in the context of totality, it outlines Krofta's directorial principles and the perspective of the DRAK's Theatre poetics within a decade. Significant attention is dedicated to the reconstruction of the top chosen period plays from the DRAK Theatre, directed by Josef Krofta, because these plays reflect the best the emancipation of the Czech puppet theatre.

Après la Seconde Guerre mondiale, la France, affaiblie politiquement et économiquement, développe une politique culturelle extérieure qui utilise les manifestations artistiques, et en particulier les tournées théâtrales, pour assurer le rayonnement de sa culture et de sa langue. Par l’intermédiaire de l’Association française d’action artistique (AFAA), elle envoie de par le monde ses plus grandes compagnies, la Comédie-Française, le Théâtre national populaire de Jean Vilar, et la Compagnie Renaud-Barrault qui devient théâtre national en 1959. Dans un monde façonné par la Guerre Froide, les tournées les plus prestigieuses ont lieu aux États-Unis, en Union Soviétique et en Amérique latine. Le but de cette thèse est de déterminer dans quelle mesure les compagnies théâtrales, instrumentalisées par la diplomatie culturelle française, utilisent aussi ces tournées pour leur propre statut dans le champ culturel français, pour leur économie, ou pour l’affermissement de leur propre identité. La première partie explore les origines et le développement du cadre politique et institutionnel qui a permis la naissance de tournées théâtrales subventionnées et fait du théâtre français un produit d’exportation. Le deuxième mouvement se concentre sur la caractérisation de ce théâtre envoyé à l’étranger, sur son économie et son répertoire. Le troisième temps analyse les différents impacts du déplacement du théâtre à l’étranger. Quelles sont les conséquences possibles de cette situation sur la représentation elle-même et les attentes du public étranger ? Au-delà de la question de la réception, c’est la dimension politique, l’impact esthétique et le rôle symbolique des tournées qui seront mis en lumière. / After World War II, a politically and economically weakened France develops a cultural foreign policy that uses artistic manifestations, and in particular theatrical tours, in order to ensure the influence of its culture and language. Thanks to the French Association for Artistic Action (AFAA), which was directly supported by the ministry of Foreign Affairs, France sends its greatest theatre companies all over the world, the Comédie-Française and the National Popular Theatre of Jean Vilar, as well as the Renaud-Barrault Company that becomes a national theatre in 1959. In a world shaped by the Cold War, the most prestigious tours take place in the United States, the Soviet Union, and Latin America. This thesis aims at determining to what extent these theatrical companies are not only exploited by the French government for cultural diplomacy, but manage themselves to benefit from the touring system, be that for their own status within the French cultural field, for their own economic solvency, or for the strengthening of their own identity. The first part explores the origins and development of the political and institutional frame that enabled the birth of this system of subsidized, international theatrical tours that made an export out of French theatre. The second part focuses on the characterization of French theatre abroad, on its economy and its repertory. The third section analyses the different impacts of the displacement of theatre abroad. What are the possible consequences on the performance itself and on the expectations of the international audience? Beyond the question of reception, the thesis will shed light on the political consequences, the aesthetic impact and the symbolic role of the tours.

L'étude du nombre de points rationnels d'une courbe définie sur un corps fini se divise naturellement en deux cas : lorsque le genre est petit (typiquement g<=50), et lorsqu'il tend vers l'infini. Nous consacrons une partie de cette thèse à chacun de ces cas. Dans la première partie de notre étude nous expliquons comment calculer l'équation de n'importe quel revêtement abélien d'une courbe définie sur un corps fini. Nous utilisons pour cela la théorie explicite du corps de classe fournie par les extensions de Kummer et d'Artin-Schreier-Witt. Nous détaillons également un algorithme pour la recherche de bonnes courbes, dont l'implémentation fournit de nouveaux records de nombre de points sur les corps finis d'ordres 2 et 3. Nous étudions dans la seconde partie une formule de trace d'opérateurs de Hecke sur des formes modulaires quaternioniques, et montrons que les courbes de Shimura associées forment naturellement des suites récursives de courbes asymptotiquement optimales sur une extension quadratique du corps de base. Nous prouvons également qu'alors la contribution essentielle en points rationnels est fournie par les points supersinguliers. / The study of the number of rational points of a curve defined over a finite field naturally falls into two cases: when the genus is small (typically g<=50), and when it tends to infinity. We devote one part of this thesis to each of these cases. In the first part of our study, we explain how to compute the equation of any abelian covering of a curve defined over a finite field. For this we use explicit class field theory provided by Kummer and Artin-Schreier-Witt extensions. We also detail an algorithm for the search of good curves, whose implementation provides new records of number of points over the finite fields of order 2 and 3. In the second part, we study a trace formula of Hecke operators on quaternionic modular forms, and we show that the associated Shimura curves of the form naturally form recursive sequences of asymptotically optimal curves over a quadratic extension of the base field. Moreover, we then prove that the essential contribution to the rational points is provided by supersingular points.

Les espaces fortifiés médiévaux du Velay (diocèse médiéval du Puy-en-Velay), sont analysés dans leur constitution et leur utilisation. L’enquête concerne un corpus de sites castraux, bourgs fortifiés, maisons fortes, prieurés et églises fortifiées de 145 communes situées en majorité dans le département de la Haute-Loire (France- Auvergne). Les changements que ces espaces fortifiés opèrent sur la période XIIIe-XVe s. sont mis en avant : morphologie spatiale et choix d’occupation des espaces, évolution de l’habitat individuel seigneurial et des enceintes en contexte rural et urbain. L’ensemble est documenté par des textes qui indique la nature des relations entre les différents groupes sociaux, acteurs de la construction du territoire fortifié : relations entre les seigneurs et l’évêque du Puy ou le roi, relations entre les seigneurs et les communautés urbaines ou rurales, émergence de nouveaux groupes sociaux (la petite noblesse). L’accent est mis sur l’articulation de ces espaces et le rapport social et symbolique que chacun des groupes sociaux entretient avec la fortification. Les intentions de dominations et les résistances de chacun des groupes sociaux sont ainsi mis en évidence par l’analyse du parcellaire, des édifices et de la forme de la fortification. / The fortified medieval areas of the Velay (medieval diocese of Puy-en-Velay) are analysed in their constitution and their use. The survey concerns a corpus of castle sites, fortified towns, fortified houses, priories and fortified churches in 145 communes, mostly in the department of Haute-Loire (France-Auvergne). The changes that these fortified spaces operate during the 13th-15th centuries are highlighted: spatial morphology and choices of occupancy of these areas, evolution of individual seigneurial habitats and enclosures in rural and urban context. The nature of the relations between the different social groups building this fortified territory is mainly documented by texts : relationships between the lords and the bishop of Le Puy or the king, relationships between the lords and the urban or rural communities, emergence of new social groups (the small gentry). The purpose focuses on the articulation of these areas and the social and symbolic relationships that each of the social groups has with fortifications. Thus, the intentions of domination and the resistance of each of the medieval social groups are revealed by analysing the plots, the buildings and the form of the fortification

The topic of this thesis is marketing of gastronomic travel agency. Gastronomic tourism is currently among the tourism trends. Based on the growing potential, in this paper will be presented fictitious gastronomic travel agency selling gastronomic tours. The main objective is to propose a marketing campaign of specific gastronomic tours. The marketing campaign will be set up to address, engage and make customers to purchase offered services. The campaign is therefore able to offer to potential customers exactly what they desire. The marketing approach is not the same to everyone, it reflects the consumer and media behavior of different target groups. Thanks to the proposed campaign the competitiveness of the company will be increased, profit will be gained, it means voluminous sales of offered tours and strong position in the market will be obtained.