This dissertation will examine the relationship between the narrative styles of the art cinema and those of mainstream contemporary American cinema. In particular: it will focus on a unique style of narration used in the art cinema since the early decades of the 20th century, contending that “multiform narrative”—a concept adopted from the work of Janet Murray—offers a useful framework for analyzing this style. The key structural features of the “multiform narrative” are its multiple narrative strands and multiple ontologies, and it is the latter feature that sets it apart from other narrative styles. It will argue that “multiform narratives” differ from the unified narratives of classical Hollywood cinema in their use of multiple narrative strands. However, they also differ from multi-strand narratives of American independent cinema in their use of multiple realities. The usefulness of the “multiform” as a category will be demonstrated through a consideration of a diverse group of films ranging from The Cabinet of Dr. Caligari (Robert Weine, 1919) to Rashomon (Akira Kurosawa, 1951), as well as through contemporary multiple-ontology films such as Mulholland Drive (David Lynch, 2001), Memento (Christopher Nolan, 2000), and Eternal Sunshine of the Spotless Mind (Michel Gondry, 2004). These contemporary films share many narrative and aesthetic characteristics of the earlier multiform films that have become exemplars of “modernist” and/or “art cinema,” even though they have emerged from very different social and institutional contexts. In this respect, the category of the “multiform” will be shown to offer both a flexibility and specificity that is not provided by earlier concepts. Consequently, it provides a framework for analyzing films from different movements and time periods with similar narrative structures that have yet to be considered together on this basis. As a result, the multiform will be shown to close a research gap in the field of complex narrative in the cinema and to provide a helpful refinement to the evolving taxonomy of narrative forms. In addition, it will be argued that a further distinction can be made within the category of the multiform itself through the identification of a style of multiform film that uses subjective realist narration to create its alternate ontological levels. Subjective realism presents the internal world of a character as if it were as real as other levels of narration and, in the films that will be considered, subjective realist strands are used to represent the dreams, hallucinations, and/or lying flashbacks of key characters within the films. A historical overview of subjective realist multiform cinema from 1919 to the present will be offered, and it will be argued that the innovative and challenging contemporary films which employ this narrative structure are aesthetically and narratively indebted to their precursors in the art cinema, but are also informed by recent technological developments as well as contemporary production and reception contexts. They will be shown to be part of a cycle of films emerging in the mid-1990s that has offered multiplex audiences narrative pleasures of the type formerly reserved for the denizens of art house cinema.

Imaging instruments are required for accurate tumor resection during neurosurgery, especially in the case of glioblastoma multiforme (GBM) - the most common and aggressive malignant glioma. However, current intraoperative imaging techniques for detection of glioma either suffer low sensitivity and low specificity or require a significant capital cost. Advances in diffuse reflectance spectroscopy and fluorescence spectroscopy have offered high sensitivity and high specificity in differentiating tumors from normal tissues with much lower capital cost. Whereas diffuse reflectance spectroscopy alone and fluorescence spectroscopy alone has been used in limited studies to differentiate normal brain tissues from brain tumors with moderate sensitivity and specificity, low specificity and sensitivity were usually observed when studying high grade glioma (HGG) such as GBM. Furthermore, optical properties and diffuse reflectance signal of HGG and low grade glioma (LGG) have not been observed separately, and thus a relation between optical properties and glioma progression has not been established. Intraoperative differentiation of GBM and LGG can be helpful in making treatment plan at the first surgery. This thesis focuses on characterizing a previous integrated system of diffuse reflectance spectroscopy and fluorescence spectroscopy to extract optical properties and fluorescence properties of LGG and GBM. First, tissue-simulating phantom models were developed to calibrate the integrated system. The direct method and Mie theory were used to calculate optical scattering of the phantoms while Beer-Lambert’s law was used to calculate optical absorption. Second, an experimental method was introduced to recover intrinsic fluorescence because the measured fluorescence signal is likely distorted by the presence of scatterers and absorbers in tissue (i.e. hemoglobin). Third, an experimental method was developed to recover optical properties of both GBM and LGG. In addition, the sensitivity and specificity of the integrated system was optimized. / Thesis / Doctor of Philosophy (PhD)

Les phosphinosucres appelés aussi « phostines » sont des analogues phosphorés des sucres pyranoses et des C-arylglycosides. L'évaluation biologique de ses composés a révélé une activité anticancéreuse des phosphinosucres sur les cellules de glioblastome multiforme, un cancer particulièrement malin et invasif qui ne possède pas de solution thérapeutique. Dans le but de comprendre les mécanismes d'action des phosphinosucres et la stéréo-dépendance de leur activité biologique, la caractérisation des diastéréomères de « phostines » a été menée. Suite à cette détermination structurale, le développement de synthèses diastéréosélectives a permis d'obtenir un mélange fortement enrichi en diastéréomère le plus actif par une séquence réactionnelle qui a mis en jeu une réaction d'oxydation de phosphinosucres -hydroxylés en α-cétophosphinosucres, suivie d'une réduction diastéréosélective. Afin d'améliorer l'activité antiproliférative des phosphinosucres, une diversification chimique a été réalisée. Les variations du groupement aryle lié à l'atome de phosphore nous ont amené à développer une synthèse des aryl-hydrogénophosphinates qui a permis d'obtenir une large variété de ces composés. Par la suite, les aryl-hydrogénophosphinates obtenus ont été engagés dans la synthèse des « phostines ». De plus, des variations chimiques sur le carbone en position α de l'atome de phosphore ont été entreprises et ont permis l'élaboration de plusieurs composés (triflate, azido, amino, déoxy et triazolyles), puis finalement à l'analogue phosphinosucre du N-acétylglucosamine qui a présenté une importante activité anticancéreuse in vitro. / Phosphinosugars also called « phostines » are new cyclic phosphinates, analogs of carbohydrates and C-aryglycosides, with phosphorus atom mimicking the anomeric carbon. Biological screening tests of these compounds revealed an anticancer activity against glioblastoma multiform, a highly invasive and malignant tumor without curative therapy.With the aim of understanding the phosphinosugars mode of action and their stereo-dependent biological activity, characterization of four phosphinosugars diastereomers formed during the chemical process has been performed. After their structural determination, diastereoselective synthesis enabled us to obtain an enriched mixture of the most active diastereomer based on an oxidation of -hydroxyled phosphinosugars in corresponding -keto phosphinosugars followed by a diastereoselective reduction. Thereafter, antiproliferative activity of phoshinosugars was performed by chemical diversification. Modification of the aryl group linked to phosphorus atom led us to develop aryl-hydrogenophosphinate synthesis to create a broad variety of these structures. Then, the expected aryl-hydrogenophosphinates were used for phostines preparation. Furthermore, chemical modifications on the carbon in α position of phosphorus atom were led and furnished several new compounds (triflate, azido, amino, deoxy and triazolyl), as well as the phosphinosugar analog of N-acetylglucosamine which presented in vitro a high anticancer activity.

L'œuvre de Shakespeare - et plus particulièrement les histoires et les tragédies - dont les proportions sont si vastes mais qui est si humaine, semble confirmer la conception pythagoricienne que « tout est nombre ». l'histoire du nombre, en effet, qui comprend l'innombrable, s'absorbe dans l'oeuvre théâtrale de Shakespeare. Elle tend à faire du nombre, du multiple, du multiforme et de leur présence tantôt discrète, tantôt ostentatoire, une histoire. L'histoire synchrone du nombre et de l'innombrable et inversement, celle du nombre et de l'innombrable en tant qu'histoire dans l'oeuvre de Shakespeare sont deux faits coïncidents. Dans le théâtre de Shakespeare, le nombre pullule : nombre de vers, nombre de corrections, d'augmentations, nombre d'auteurs, succession des règnes, des rois et des reines, foule innombrable…... La profusion de mots, de procédés qui se rapportent au nombre est imposante. Vertige de la liste. Le nombre est innombrable. Le nombre crée un modèle mais il existe une tension entre ce modèle et les irrégularités qui en sont l'avatar. Le vers de Shakespeare révèle l'existence de forces qui travaillent à la reproduction d'un schéma tout en valorisant et en intégrant l'irrégularité. Les mouvements désordonnés d'une foule, de la multitude qui s'émeut, qui s'enthousiasme ou qui se soulève sont canalisés par le pouvoir. le versant sombre de cette étude concerne l'appareil répressif et les relations qu'il entretient avec le spectacle. Il montre que le nombre et l'innombrable sont aussi le paradigme de l'inhumain. Hors du nombre, sans nombre, prémisses de l'innombrable, se situe l'oeuvre de Shakespeare, celle de « l'homme innombrable ». Les sciences ont pénétré l'univers de Shakespeare, qui subit, semble-t-il, l'influence des « mondes innombrables » de la cosmologie brunienne. L'innombrable est l'essence même du nombre, au confluent du démotique et de l'ésotérique. la conception d'une mystique du nombre, toutefois, ne peut être aisément raccordée à celle du génie populaire au caractère universel de Shakespeare. En raison de la coïncidence des contraires, de l'extraordinaire saisie du passé, du présent et de l'avenir, l'oeuvre se prête admirablement au jeu du dessaisissement, du désoeuvrement. / With its vast but so human proportions, Shakespeare’s theatre seems to confirm the Pythagorean conception that “all is number”. Indeed, the history of number, which combines with the multiple, the multiform and the innumerable, has been absorbed into Shakespeare’s theatre. It is apt to transform the presence of numbers, which are sometimes unobtrusive sometimes ostentatious, into a story. The synchronous history of number and the innumerable, and conversely number and the innumerable as story meet in Shakespeare’s works. Numbers abound, namely the number of lines, the number of authors, the succession of reigns, of kings and queens and infinite numbers of people… The profusion of words and devices that are related to number is imposing. Lists are dizzying. Numbers are innumerable. Number shapes patterns but there may be tension between this pattern and the irregularities that are their final manifestation. The unruly movements of the crowd, of the multitude, that is easily moved, that is enthusiastic or may rebel, are channeled by the established power. The dark side of this study concerns the repressive state apparatus and the relationship with the theatre. This study shows that the inhuman is also no doubt inherent in the very notion of number and the innumerable. It is in the space of the numberless, without number, in the premise of the innumerable, that the works of “myriad-minded” Shakespeare reside. The sciences have penetrated Shakespeare’s works, which have been thought to undergo the influence of the innumerable worlds of Brunian cosmology. The innumerable lies somewhere between the demotic and the esoteric. The conception of a mystique of numbers, however, cannot be linked to the conception of Shakespeare’s universal popular genius. On account of the coincidentia oppositorum, of the extraordinary capture of the essence of the past, of the present and of the future, Shakespeare’s works admirably lend themselves to a process that entails a sense of loss.

Les Phostines représentent une nouvelle classe de glycomimétiques contenant un atome de phosphore à la place du carbone anomérique. Leur synthèse a été réalisée par la condensation de furanoses protégés et de différents H-phosphinates en milieu basique. Ces phostines se sont révélées être très efficaces in vitro et in vivo contre des cellules cancéreuses de glioblastome de rat et humaines. Dans ce projet, nous avons eu pour premier but d’obtenir, majoritairement, le diastéréoisomère le plus actif. Différentes réactions ont été réalisées, en changeant la nature de la base ou le contre-ion de cette dernière. Une très légère amélioration a été notée avec le méthylate de césium au profit du dérivé de type glucose. Dans un deuxième temps, et dans le but d’améliorer l’activité anticancéreuse et de pouvoir étudier la biodistribution des phostines, différentes modifications chimiques ont été réalisées. Des dihydroxy-2,3- et 2,6-oxaphosphinanes, des thiophostines et des phostines de la série L ont été synthétisées. Par la suite, des variations, en alpha de l’atome de phosphore, nous ont permis d’obtenir des phostines halogénées, ainsi que deux nouveaux produits: un acide furanosylphosphinique et l’oxaphosphine-3-ène. La réactivité chimique de la fonction éther d’énol de ce dernier a été examinée, en synthétisant un beta-cétophosphinate et des beta-énaminophosphinates. Finalement des pseudo-disaccharides ont été synthétisés afin d’améliorer la biodisponibilité des phostines. Les phostines testées ont manifesté des propriétés anticancéreuses à une concentration de l’ordre du nanomolaire envers différentes lignées cellulaires, montrant la capacité de cette famille de composés de lutter contre certains types de cancers. / The Phostines represent a new class of glycomimetics, containing a phosphinolactone function instead of the anomeric carbon. Their synthesis was achieved by the reaction of protected furanose with various H-phosphinates, in the presence of a base. These compounds have been found to be very effective in vitro and in vivo against rat and human glioblastoma cells.In this project, our first goal was to obtain the most active phostine with higher diastereoselectivity. Different reactions were tested, changing the base or its counter ion. A very slight improvement was noted with cesium methoxide, favoring the glucose-like derivative.In the context of improving the anticancer activity and to study the biodistribution of the phostines, different chemical modifications were carried out. Dihydroxy-2,3- and 2,6-oxaphosphinanes, thiophostines and phostines of the L series were synthesized. Therefore, variations in alpha position of the phosphorus atom have produced halogenated phostines and two new products: furanosylphosphinic acid and the oxaphosphine-3-ene.The chemical reactivity of the enol ether of this latter has been examined by synthesizing beta-ketophosphinate and beta-enaminophosphinates. Finally, pseudo-disaccharides were synthesized to improve the bioavailability of phostines.The tested phostines have exhibited anticancer properties at nanomolar concentration against different cell lines, showing the ability of this family of compounds to fight some types of cancers.

The diploma program summarized in this paper was to evaluate the habitats of Gentianella Praecox, subsp. Bohemica, in the Chvalšiny and Český Krumlov areas where the taxon can be encountered on eight sites. The narrative section, summarizing the biological and ecological aspects of the species, provides also information on why the taxon is endangered and how it can be protected. A special chapter is dedicated to the program of its recovery. The methodological section, characterizing the area of interest and its different sites, describes also the procedure applied to create and evaluate phytocoenological relevés. The chapter is complemented with information on the numbers of plants in bloom, a figure representing the communities of Gentianella praecox, subsp. bohemica, as found at the individual habitats. Statistical evaluations of the phytocoenological relevés revealed, inter alia, a certain change in the species composition and coverage, primarily on all sites at Svatý Kříž (Chvalšiny). The change observed in these habitats manifested itself also through the increase in coverage of the more mesic species of Plantago lanceolata, Achillea millefolium, and Lotus corniculatus. The numbers of individual plants of Gentianella praecox, subsp. bohemica, encountered in bloom showed substantial year-on-year fluctuation.

This dissertation is a study of appetite in Plato’s Timaeus, Republic and Phaedrus. In recent research is it often suggested that Plato considers appetite (i) to pertain to the essential needs of the body, (ii) to relate to a distinct set of objects, e.g. food or drink, and (iii) to cause behaviour aiming at sensory pleasure. Exploring how the notion of appetite, directly and indirectly, connects with Plato’s other purposes in these dialogues, this dissertation sets out to evaluate these ideas. By asking, and answering, three philosophically and interpretatively crucial questions, individually linked to the arguments of the dialogues, this thesis aims to show (i) that the relationship between appetite and the body is not a matter of survival, and that appetite is better understood in terms of excess; (ii) that appetite is multiform and cannot be defined in terms of a distinct set of objects; and (iii) that appetite, in Plato, can also pertain to non-sensory objects, such as articulated discourse. Chapter one asks what the universe can teach us about embodied life. It argues that Plato, in the Timaeus, works with an important link between the universe and the soul, and that the account of disorder, irrationality and multiformity identifying a pre-cosmic condition of the universe provides a key to understanding the excessive behaviour and condition of a soul dominated by appetite. Chapter two asks why the philosophers of the Republic’s Kallipolis return to the cave, and suggests that Plato’s notion of the noble lie provides a reasonable account of this. By exploring the Republic’s ideas of education, poetry and tradition, it argues that appetite – a multiform and appearance oriented source of motivation – is an essential part of this account. Chapter three asks why Socrates characterizes the speeches of the Phaedrus as deceptive games. It proposes that this question should be understood in the light of two distinctions: one between playful and serious discourse and one between simple and multiform. It argues that the speeches of the Phaedrus are multiform games, and suggests that appetite is the primary source of motivation of the soul addressed, personified by Phaedrus.