It is the contention of this paper that, contrary to his own belief, John Stuart Mill did not, after his "mental crisis" of 1826, succeed in his attempt to achieve a meaningful integration of the analytical and the affective, through his cultivation of the feelings by poetry. On the contrary, through his subsequent detemination to place these two attributes (the analytic and the affective) in a clearly proscribed xelation to each other (by virtue of his postulation of the exclusive presence of the former in science or logic and the latter in poetry), Mill only succeeded in creating, in this codification, what we can describe as an image of his {to use T. S. Eliot's somewhat unfashionable phrase) "dissociated sensibility." / Thesis / Master of Arts (MA)

Le guidage axonal est un processus très important dans le développement du cerveau, permettant de lui donner sa structure et son organisation. La communauté scientifique des neurosciences lui porte un intérêt grandissant ces dernières années. Plusieurs outils appartenant au domaine des microtechnologies, que sont la microfluidique et le micropatterning, sont d’une aide importante pour étudier le guidage axonal in vitro. Ils permettent de confiner les neurones et leurs axones et de leur appliquer des gradients de molécules de guidage. Lors de ce travail de thèse, j’ai voulu développer un système pour étudier l’effet de gradients de molécules de guidage sur le guidage axonal. J’ai pour cela testé plusieurs configurations de dispositifs microfluidiques, de micromotifs (micropatterns) et de combinaisons de ces derniers.Nous avons d’abord utilisé deux approches pour isoler les axones de neurones dissociés de leurs somas afin de pouvoir étudier, à haut débit, l’effet de l’environnement moléculaire sur les cônes de croissance des neurones. La première approche consistait à faire pousser des neurones sur des motifs (patterns) de différentes protéines. Elle a permis de montrer leur capacité d’adhésion spécifique sur ces motifs. La seconde consistait à ensemencer des neurones dans un dispositif microfluidique dans lequel, lors de leur pousse, les axones sont séparés des somas par des microcanaux. Nous avons ensuite étudié l’effet, sur les axones, de gradients de molécules de guidage. Pour commencer, nous avons mesuré l’effet de deux molécules de guidage : l’éphrine et la sémaphorine, en cultivant des neurones en présence de gradients patternés de ces deux molécules. Par la suite, nous avons étudié un autre modèle où les neurones sont plus proches de leur environnement in vivo, des explants poussant sur des motifs de laminine contenant un gradient. Pour aider au positionnement de l’explant, nous avons polymérisé des hydrogels. Ensuite, nous avons mis des explants à côté de gradients patternés d’éphrine. Enfin, nous avons cherché à obtenir un gradient soluble de molécules de guidage entretenu sur des temps longs, plus proche des gradients existant in vivo. Dans ce but, nous avons voulu fabriquer un dispositif microfluidique permettant d’appliquer un gradient soluble de molécules de guidage sur des neurones. Pour obtenir un gradient stable dans le temps, nous avons aussi cultivé des neurones à côté de cellules exprimant la nétrine, une autre molécule de guidage. Pour finir, nous avons cultivé des neurones et des glies dissociés pour étudier leurs interactions.L’ensemble de ces recherches n’a pas permis d’obtenir un dispositif fiable pour étudier l’effet de molécules sur la pousse et le guidage des axones. Néanmoins, la configuration consistant en une coculture de neurones à proximité de cellules relargant de la nétrine nous a permis d’obtenir des premiers résultats encourageants. Nous avons ainsi mis au point un ensemble de méthodes qui pourront nous permettre de finaliser le développement d’un système pour étudier le guidage axonal, fonctionnel et efficace. / Axonal guidance is a very important process during brain development, allowing to give it its structure and organization. The neuroscience scientific community has a growing interest in it during the last years. Several tools belonging to the field of microtechnologies, microfluidics and micropatterning are of important help to study axonal guidance in vitro. They allow to confine neurons and their axons and to apply gradients of guidance molecules. During this thesis, my goal was to develop a system to study the effect of guidance molecules gradients on axonal guidance. For that, I tested several configurations of microfluidic devices, micropatterns and combinations of both.First, we used two approaches to isolate dissociated neurons axons from their somas. Our goal was to study the effect of the molecular environment on neurons growth cones, with a high throughput. The first approach consisted in growing neurons on different proteins patterns. It also allowed to show their capacity to adhere on these patterns. The second one consisted in seeding neurons in a microfluidic device in which, during their growth, axons are separated from somas by microchannels. Then we studied the effect, on the axons, of guidance molecules gradients. To begin, we measured the effect of two guidance molecules: ephrin and semaphorin, by culturing neurons in the presence of patterned gradients of these two molecules. After that, we studied another model where neurons are closer from their environment in vivo, explants growing on laminin patterns containing a gradient. To help the explant positioning, we polymerized hydrogels. Then, we put explants next to patterned gradients of ephrin. Finally, we tried to obtain a soluble gradient of guidance molecules, over a long period of time (days), closer to existing gradients in vivo. In that goal, we wanted to build a microfluidic device enabling the application of a soluble gradient of guidance molecules on neurons. To obtain a constant gradient, we also cultured neurons next to cells expressing netrin, another guidance molecule. Finally, we cultured dissociated neurons and glial cells to study their interactions.All these experiments did not allow to obtain a reliable device to study the effect of molecules on axons growth and guidance. Nevertheless, the configuration consisting in a coculture of neurons next to cells releasing netrin allows us to obtain promising preliminary results. We thus drew up a group of methods that will enable us to finalize the development of a system to study axonal guidance, functional and efficient.

For almost a century, the electrical properties of the brain and the nervous system have been investigated to gain a better understanding of their mechanisms and to find cures for pathological conditions. Despite the fact that today's advancements in surgical techniques, research, and medical imaging have improved our ability to treat brain disorders, our knowledge of the brain and its functions is still limited. Culturing dissociated cortical neurons on Micro-Electrode Array dishes is a powerful experimental tool for investigating functional and structural characteristics of in-vitro neuronal networks, such as the cellular basis of brain learning, memory and synaptic developmental plasticity. This dissertation focuses on combining MEAs with novel electrophysiology experimental paradigms and statistical data analysis to investigate the mechanisms that regulate brain development at the level of synaptic formation and growth cones. The goal is to use a mathematical approach and specifically designed experiments to investigate whether dissociated neuronal networks can dependably display long and short-term plasticity, which are thought to be the building blocks of memory formation in the brain. Quantifying the functional evolution of dissociated neuronal networks during in- vitro development, using a statistical analysis tool was the first aim of this work. The results of the False Discovery Rate analysis show an evolution in network activity with changes in both the number of statistically significant stimulus/recording pairs as well as the average length of connections and the number of connections per active node. It is therefore proposed that the FDR analysis combined with two metrics, the average connection length and the number of highly connected "supernodes" is a valuable technique for describing neuronal connectivity in MEA dishes. Furthermore, the statistical analysis indicates that cultures dissociated from the same brain tissue display trends in their temporal evolution that are more similar than those obtained with respect to different batches. The second aim of this dissertation was to investigate long and short-term plasticity responsible for memory formation in dissociated neuronal networks. In order to address this issue, a set of experiments was designed and implemented in which the MEA electrode grid was divided into four quadrants, two of which were chronically stimulated, every two days for one hour with a stimulation paradigm that varied over time. Overall network and quadrant responses were then analyzed to quantify what level of plasticity took place in the network and how this was due to the stimulation interruption. The results demonstrate that here were no spatial differences in the stimulus-evoked activity within quadrants. Furthermore, the implemented stimulation protocol induced depression effects in the neuronal networks as demonstrated by the consistently lower network activity following stimulation sessions. Finally, the analysis demonstrated that the inhibitory effects of the stimulation decreased over time, thus suggesting a habituation phenomenon. These findings are sufficient to conclude that electrical stimulation is an important tool to interact with dissociated neuronal cultures, but localized stimuli are not enough to drive spatial synaptic potentiation or depression. On the contrary, the ability to modulate synaptic temporal plasticity was a feasible task to achieve by chronic network stimulation. / Electrical and Computer Engineering

La thèse étudie les dénominations du procès de combattre en latin et montre que l’évolution des signes linguistiques est corrélative des realia historiques et politiques. Cette étude sémantique articule différentes approches et propose un éclairage linguistique et anthropologique sur les verbes signifiant « combattre » dans la poésie épique latine. Au vu des problématiques liées à tout sujet onomasiologique, une partie préliminaire se concentre sur l’établissement du corpus de verbes. Les première et seconde parties confrontent l’approche sémantique aux approches morphologique et syntaxique. Les lexèmes retenus sont décrits plus précisément afin de déterminer s’ils adoptent des tendances morphologiques et rectionnelles particulières, rattachables à leur signifié. La première partie permet, à travers l’étude des radicaux, des morphèmes (temps – personne) et des préverbes, de dégager des spécificités morphosémantiques en relation avec les trois types morphologiques isolés (verbes simples, locutions et préverbés). La seconde partie étudie, dans une perspective sémantico-syntaxique, les rôles sémantiques et les types rectionnels et crée des zones d’intersection entre lexèmes, qui ne rejoignent pas toujours les trois types morphologiques. Ces nouveaux recoupements permettent d’opposer les lexèmes et de déterminer les motivations (littéraires ou anthropologiques) de leurs emplois. La thèse en arrive à l’idée que la perpétuation ou le renouvellement des signes linguistiques pour dénoter le procès « combattre » a partie liée avec des données culturelles et anthropologiques et que le genre épique est un genre littéraire vivant, qui suit la mouvance et les idéologies de son temps. / This study of Latin verbs meaning “to fight” in epic poetry shows that the evolution of linguistic signs and lexical units reflects extralinguistic phenomena. It is a semantic study which, by combining several approaches, sheds new light, both linguistic and anthropological, on the verbs meaning “to fight” in Latin epic poetry. The preliminary chapter (after the introduction) presents the selected verbs belonging to the corpus. In the first and second sections of the work, the contrast is drawn between a fundamentally semantic approach to the verbs and a more morphological and syntactical approach. The first section analyses the verbs’ synchronic radicals, their tenses, their personal morphemes, and their preverbs, in order to show their semantic specificities in the context of the three morphological types in which they may be found: simple verbs, verbal phrases and preverbed verbs. In a semantic-syntactic approach, the second section deals with the participant roles and syntactic environments and creates new intersections between lexemes. These links shed light on the oppositions that exist between the individual lexemes and determine the – literary or anthropological – motivations in the use of the selected verbs. The conclusion makes two important points. Firstly, we see that the continuation or the renewal of linguistic signs and lexical units denoting the process of fighting also depend on cultural and anthropological factors. Secondly, it is made clear that the epic literary genre in Latin is not frozen throughout the historical periods studied here, since it is continually evolving and adapting to the changes and ideologies of the times.

Les entrepreneurs n’ont pas manqué de soulever l’importance et la nécessité d’une structure européenne flexible pour répondre aux besoins des PME. En effet l'introduction d'une société à conception contractuelle dans le droit européen revêt de multiples intérêts. D'une part, elle intègre les PME dans la continuité du processus de construction du marché intérieur. D’autre part, elle offre une liberté d’action appréciée par les entrepreneurs qui évoluent dans un marché fortement concurrentiel. Enfin, le caractère contractuel permet au législateur européen de revenir sur la définition des libertés d'établissement et de circulation des capitaux.Aussi encourageant que soit ce projet, il n'en demeure pas moins source d'interrogations et d'inquiétudes. La liberté contractuelle comporte des risques si elle n'évolue pas dans un cadre juridique adapté et protecteur. Cette thèse a pour objectif d’analyser les effets de la transposition de la liberté contractuelle dans le droit européen des sociétés. Pour comprendre la portée de l’adoption du texte relatif à la SPE, cette thèse tentera de définir la liberté contractuelle au sens communautaire, de souligner ses avantages et d’analyser ses inconvénients. / Entrepreneurs consider flexible structures are important to meet European SMES needs. Indeed, the transposition of a contractual company in the European law are very valuable. On the one hand, it includes SMES in the process of construction of internal market. On the other hand, it offers to entrepreneurs a freedom to manage their companies in order to be more competitive. Finally the contractual aspect of the company allows the European parliament to reconsider the definition of freedom of establishment and free movement of capital. As encouraging as this project is, it remains a source of questions and concerns. Contractual freedom could involve risks if it doesn’t evolve in a suitable protective legal framework. This thesis aims to analyze the effects of the transposition of contractual freedom in the European company law. To understand the scope of the adoption of the text relating to the SPE, this thesis will try to define the contractual freedom in EU terms, to emphasize its advantages and disadvantages analyzed

Biomedical research relies on identification and isolation of specific cell types using molecular biomarkers and sorting methods such as fluorescence or magnetic activated cell sorting. Labelling processes potentially alter the cells’ properties and should be avoided, especially when purifying cells for clinical applications. A promising alternative is the label-free identification of cells based on physical properties. Sorting real-time deformability cytometry (soRT-DC) is a microfluidic technique for label-free analysis and sorting of single cells. In soRT-FDC, bright-field images of cells are analyzed by a deep neural net (DNN) to obtain a sorting decision, but sorting was so far only demonstrated for blood cells which show clear morphological differences and are naturally in suspension. Most cells, however, grow in tissues, requiring dissociation before cell sorting which is associated with challenges including changes in morphology, or presence of aggregates. Here, we introduce methods to improve robustness of analysis and sorting of single cells from nervous tissue and provide DNNs which can distinguish visually similar cells. We employ the DNN for image-based sorting to enrich photoreceptor cells from dissociated retina for transplantation into the mouse eye.

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