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This dissertation tests the theories put forth by Mr. E.P. Thompson (The Making of the English Working Class) where he points to 18th century hunger riots as examples of incipient class formation. Using untapped local source documents, the dissertation examines the hunger riots of 1766 one by one and also in regional contexts. The dissertation concludes that issues of class have very little to do with explaining the origins of the hunger riots. Instead, what was involved was an unexpected European-wide failure of the wheat crop following an unusual weather pattern which interrupted the westerly movement of weather masses. The sudden demand for wheat was picked up by English corn merchants and they quickly acted to export large amounts of wheat to reap windfall profits. The English river and canal system, the turnpike roads and the English coastline made rapid export both possible and expedient. Large populations of rural textile workers in East Anglia, the Upper Thames Valley and the West Country were faced with vanishing supplies of bread which they relied upon. The crowds made use of common law concepts and Tudor statutes restricting sale and resale of wheat and establishing the “assize of bread”. The functioning of the central government is closely examined. The episode caught the establishment entirely off guard. Troops were sent, the riots were quashed, the rioters were quickly tried and either hung, deported to North America or merely chastised. The riots show how the industrialization of Britain led to wholly unexpected events and social situations. E.P. Thompson’s thesis was not directly supported by the evidence adduced in this study. In 1776 Adam Smith used the hunger riots of 1766 to show how the private act of hoarding grain for profitable resale could serve the public purpose of avoiding dearth and starvation. The hunger riots of 1766 are therefore what might justly be deemed the “proximate cause” of the free market economy

Cette étude portant sur 17 journaux et 236 tracts conçus par des résistants allemands et autrichiens actifs en France pendant la Seconde Guerre mondiale a permis d’en révéler les enjeux théoriques et de mieux connaître leurs auteurs, en réévaluant notamment le rôle des ressortissants autrichiens et des groupes de gauche non alignés sur la politique de la IIIe Internationale. Les messages transmis se classent en trois catégories chacune liée à l’objectif poursuivi, à savoir le recrutement, la visibilité et la définition du positionnement du groupe. On constate que quatre principaux types de lecteurs sont visés : en premier lieu les sympathisants potentiels parmi les soldats de la Wehrmacht, mais également les services de répression, les autres groupes de résistants et, enfin, les Alliés, à la fin du conflit. Une première partie analyse les productions de groupes initiés par les partis communistes. De 1941 à 1943, le Travail Allemand (TA) vise à restructurer les réseaux démantelés en 1939. À partir de 1943, les militants sont regroupés en fonction de leur nationalité dans de nouvelles organisations, le CALPO et l’ÖFF, dont les objectifs consistent non pas à réaliser des projets nationaux mais plutôt à étendre l’influence soviétique dans les nouveaux États après la guerre. La deuxième partie est dédiée aux Revolutionäre Kommunisten (RK) qui sont des communistes conseillistes autrichiens dénonçant toutes les autres forces en présence pour construire une société radicalement différente. Ce travail dresse un portrait précis et inédit de ce groupe et de ses évolutions théoriques de 1935 à 1944. Une troisième partie est consacrée à l’étude de groupes trotskystes qui souhaitent concurrencer les organisations des communistes mais qui manquent de moyens logistiques et matériels pour y parvenir. Ce groupe est actif de 1943 à 1944 et sa production s’arrête brutalement suite à une vague d’arrestations. Notre étude démontre que deux philosophies politiques coexistent et sont concurrentes. Les communistes cherchent à renverser le régime nazi pour rétablir les structures étatiques traditionnelles et accroître l’influence soviétique. Les RK et les trotskystes étendent les enjeux à la lutte contre le « capitalisme », et, ce faisant, dépassent par leurs actions ce que l’on entend habituellement par « résistance ». / This study of 17 newspapers and 236 flyers conceived by German and Austrian resistance fighters in France during World War II have revealed the theoretical issues and to provide better knowledge of the authors, by re-evaluating the role of Austrians and Left groups which were not aligned with the politics of the Third Communist International. The messages are classified in three groups each linked to the objective pursued; recruitment, visibility and the definition of the group’s position. We can see that there are four main types of readers targeted: the first group are the potential sympathizers among the Wehrmacht soldiers, but also the repression services, the other resistance groups and finally the Allies, at the end of the conflict. The first part analyses the production of organisations initiated by the German and Austrian communist parties. From 1941 to 1943, the Travail Allemand (TA) aimed to restructure the networks which had been dismantled in 1939. From 1943, the militants were regrouped into new organizations like the CALPO and ÖFF depending on their nationality. Their objectives did not consist of carrying out national projects but rather to extend Soviet influence in the new states after war. The second part is dedicated to the Revolutionäre Kommunisten (RK) who were Austrian revolutionary communists denouncing all the other forces involved to build a radically different society. This piece of work draws an original and precise portrait of this group and its theoretical evolutions from 1935 to 1944. The third part is devoted to the study of Trotskyist groups which would like to have competed with communist organizations but who lacked the logistic and material means necessary. This group was active from 1943 to 1944 and its production brutally stopped with a wave of arrests. Our study shows that two political philosophies coexist and compete. The communists want to overthrow the National Socialist government to reestablish the traditional administrative and political structures and increase Soviet influence. The RKs and Trotskyists widen the stakes to fight against capitalism and by doing so, exceed the actions that we usually call “resistance”.

Cultural and historical accounts of self-help literature typically describe its development and focus in terms of the autonomous, public male subject of the nineteenth century. This literary study recognizes that as masculine self-help discourse became widely accessible in the mid nineteenth century, mid-Victorian feminist novels, periodicals, and tracts developed versions of self-help that disrupted the dominant cultural view that the single female was helpless and “redundant” if she did not become a wife and mother. I argue that the dual focus of Victorian self-help discourse on the ability to help oneself and others was attractive for Victorian feminist writers who needed to manipulate the terms of the domestic ideal of woman as influential helpmeet, if women’s independence and civic duty were to be made culturally palatable. Chapter One focuses on how Dinah Mulock Craik drew on self-help values popularized in mid-century articles and collective biographies by Samuel Smiles, while rejecting the genre of biography for its invasiveness into female lives. By imagining a deformed single artist heroine in the context of her 1851 bildungsroman, Olive, Craik highlighted and contested the objectification of women within Victorian culture while reproducing other forms of female difference based on dominant constructions of class, sexuality, and race. Chapter Two extends formal and thematic considerations of self-help discourse to a comparison of masculine colonial accounts of class-climbing and the projection of a self-reliant, yet deeply unstable, domestic female by Maria Rye and the Female Middle-Class Emigration Society. Chapter Three exerts critical pressure on the tension between individual and mutual help by charting the debate that raged between liberal individualism and collectivism in the labour movement, particularly in The Women’s Union Journal. Returning to a focus on the binary of female aberrance and normalcy within Victorian culture, Chapter Four analyzes late-century case studies of nervous illnesses alongside Ella Hepworth Dixon’s 1894 New Woman novel that promoted self-help for women as desirable yet unattainable in a society still largely structured around the domestic ideal. At its broadest, this dissertation explores points of convergence and departure between Victorian masculine and feminine self-help texts, and touches on reverberations of this Victorian discourse in today’s self-help works directed at women in Western culture.

Parkinson’s disease patients present with the highest risk of dementia development. The thalamus, integral to several functions and behaviours is involved in the pathophysiology of Parkinson’s disease. The aim of this thesis was to determine if anatomical abnormalities in the thalamus are associated with the development of dementia in Parkinson’s disease. We examined the thalamus using macro and microstructural techniques and the white matter pathways that connect the thalamus with areas of the surrounding cortex using diffusion tensor imaging (DTI) based tractography. T1-weighted magnetic resonance and DT images were collected in 56 Parkinson’s disease patients with no cognitive impairment, 19 patients with mild cognitive impairment, 17 patients with dementia and 25 healthy individuals who acted as control subjects. An established automated segmentation procedure (FIRST FSL) was used to delineate the thalamus and a modified k-means clustering algorithm applied to segment the thalamus into clusters assumed to represent thalamic nuclei. Fibre tracts were determined using DTI probabilistic tracking methods available in FIRST. Microstructural integrity was quantified by fractional anisotropy and mean diffusivity (MD) DTI measures. Results show that microstructural measures of thalamic integrity are more sensitive to cognitive dysfunction in PD than macrostructural measures. For the first time we showed a progressive worsening of cellular integrity (MD) in the groups who had greater levels of cognitive dysfunction. Thalamic degeneration was regionally specific and most advanced in the limbic thalamic nuclei which influenced executive function and attention, areas of cognition that are known to be affected in the earliest stages of PD. The integrity of the fibre tracts corresponding to these thalamic regions was also compromised. Degeneration of fibre tracts was most evident in the dementia group, indicating that they may be more protected against Lewy pathology than the nuclei of the thalamus. Our findings confirm previous histological, animal and lesion studies and provide a reliable estimate of cortical degeneration in PD that can be applied non-invasively and in vivo. A longitudinal study is needed to monitor the progression of cognitive decline in PD but we have provided the basis for further investigation into the predictive validity of thalamic degeneration for cognitive dysfunction. In the future, the microstructural changes of the thalamus could be used as biomarkers for the identification of individuals with a higher risk for dementia development and for the longitudinal monitoring of any interventions into cognitive decline.

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Propionibacterium freudenreichii CIRM-BIA 129 (Pf) est une bactérie bénéfique utilisée comme levain fromager. Elle présente en outre de nombreuses potentialités probiotiques souche-dépendantes, dont la modulation de l’inflammation. Cette propriété résulte de la production de divers métabolites. Les protéines de surface S-layer (Slps), dont la protéine majoritaire SlpB, y jouent également un rôle immunomodulateur. Les propriétés « 2-en-1 », c’est-à-dire à la fois fermentaires et probiotiques, font de Pf un bon candidat pour développer des fromages fonctionnels, afin de prévenir les maladies inflammatoires intestinales. L’objectif de cette thèse était d’étudier l’impact de la matrice fromagère sur les propriétés immunomodulatrices de Pf, via ses protéines Slps, par comparaison à une culture sur ultrafiltrat de lait (UF). Les études conduites in vitro suggèrent que les bactéries provenant du fromage auraient une meilleure capacité de tolérance aux stress gastriques et duodénaux, mais elleauraient une moindre capacité de survie dans le côlon, par comparaison à des bactéries provenant d’une culture sur UF. De plus, la protéolyse digestive des protéines de surface améliore la survie de Pf dans le côlon. Parallèlement, l’étude de digestion in vitro a montré que la protéolyse des protéines de surface a seulement été réduite par la matrice fromagère. Cette protéolyse conduit à l’abolition des effets anti-inflammatoires des protéines Slps, qui ne sont pas exprimées de novo dans l’environnement colique. Ces résultats obtenus in vitro étaient cohérents avec l’étude in vivo qui a mont / Propionibacterium freudenreichii CIRM-BIA 129 (Pf) is a beneficial bacterium used as a cheese starter. It moreover displays versatile strain-dependent probiotic properties, including the modulation of inflammation. This property results from the production of various metabolites. S-layer surface proteins (Slps), including the major SlpB protein, also play an immunomodulatory role. The "2-in-1" properties, i.e. both fermentative and probiotic properties, make Pf a suitable candidate to develop functional cheeses, in order to prevent inflammatory bowel diseases. The aim of this thesis was to study the impact of the cheese matrix on the immunomodulatory properties of Pf, mediated by its Slps proteins, compared to a culture on milk ultrafiltrate (MUF). In vitro studies suggest that the bacteria from the cheese would have a better ability to tolerate gastric and duodenal stresses, but would have less ability to survive in the colon, compared to bacteria from a MUF culture. In addition, thethe digestive proteolysis of surface proteins improves survival of Pf in the colon. In parallel, the in vitro digestion study showed that proteolysis of surface proteins was only limited by the cheese matrix. This proteolysis leads to the abolition of the anti-inflammatory effects of Slps proteins, which are not de novo expressed in the colonic environment. These results, obtained in vitro, were consistent with the in vivo study, which showed that MUF culture and cheese delivered similar amounts of metabolically active bacteria to the piglets’ colon. This in vivo study showed, however, that t

La structure et l'organisation de la substance blanche du cerveau humain ne sont pas encore complètement connues. L'Imagerie par Résonance Magnétique de diffusion (IRMd) offre une approche unique pour étudier in vivo la structure des tissus cérébraux, permettant la reconstruction non invasive des trajectoires des faisceaux de fibres du cerveau en utilisant la tractographie. Aujourd'hui, les techniques récentes d'IRMd avec haute résolution angulaire (HARDI) ont largement amélioré la qualité de la tractographie par rapport à l'imagerie du tenseur de diffusion standard (DTI). Toutefois, les jeux de données de tractographie résultant sont très complexes et comprennent des millions de fibres, ce qui nécessite une nouvelle génération de méthodes d'analyse. Au-delà de la cartographie des principales voies de la substance blanche, cette nouvelle technologie ouvre la voie à l'étude des faisceaux d'association courts, qui ont rarement été étudiés avant et qui sont au centre de cette thèse. L'objectif est d'inférer un atlas des faisceaux de fibres du cerveau humain et une méthode qui permet le mappage de cet atlas à tout nouveau cerveau.Afin de surmonter la limitation induite par la taille et la complexité des jeux de données de tractographie, nous proposons une stratégie à deux niveaux, qui enchaîne des regroupements de fibres intra- et inter-sujet. Le premier niveau, un regroupement intra-sujet, est composé par plusieurs étapes qui effectuent un regroupement hiérarchique et robuste des fibres issues de la tractographie, pouvant traiter des jeux de données contenant des millions de fibres. Le résultat final est un ensemble de quelques milliers de faisceaux de fibres homogènes représentant la structure du jeu de données de tractographie dans sa totalité. Cette représentation simplifiée de la substance blanche peut être utilisée par plusieurs études sur la structure des faisceaux individuels ou des analyses de groupe. La robustesse et le coût de l'extensibilité de la méthode sont vérifiés à l'aide de jeux de fibres simulés. Le deuxième niveau, un regroupement inter-sujet, rassemble les faisceaux obtenus dans le premier niveau pour une population de sujets et effectue un regroupement après normalisation spatiale. Il produit en sortie un modèle composé d'une liste de faisceaux de fibres génériques qui peuvent être détectés dans la plupart de la population. Une validation avec des jeux de données simulées est appliqué afin d'étudier le comportement du regroupement inter-sujet sur une population de sujets alignés avec une transformation affine. La méthode a été appliquée aux jeux de fibres calculés à partir des données HARDI de douze cerveaux adultes. Un nouveau atlas des faisceaux HARDI multi-sujet, qui représente la variabilité de la forme et la position des faisceaux à travers les sujets, a été ainsi inféré. L'atlas comprend 36 faisceaux de la substance blanche profonde, dont certains représentent quelques subdivisions des faisceaux connus, et 94 faisceaux d'association courts de la substance blanche superficielle. Enfin, nous proposons une méthode de segmentation automatique de mappage de cet atlas à tout nouveau sujet. / Human brain white matter (WM) structure and organisation are not yet completely known. Diffusion-Weighted Magnetic Resonance Imaging (dMRI) offers a unique approach to study in vivo the structure of brain tissues, allowing the non invasive reconstruction of brain fiber bundle trajectories using tractography. Nowadays, the recent dMRI techniques with high angular resolution (HARDI) have largely improve the quality of tractography relative to standard diffusion tensor imaging. However, the resulting tractography datasets are highly complex and include millions of fibers which requires a new generation of analysis methods. Beyond the mapping of the main white matter pathways, this new technology opens the road to the study of short association bundles, which have been rarely studied before and is in the focus of this thesis. The goal is to infer an atlas of the fiber bundles of the human brain and a method mapping this atlas to any new brain.In order to overcome the limitation induced by the size and complexity of the tractography datasets, we propose a two-level strategy, chaining intra- and inter-subject fiber clustering. The first level, an intra-subject clustering, is composed by several steps performing a robust hierarchical clustering of a fiber tractography dataset that can deal with millions of diffusion-based tracts. The end result is a set of a few thousand homogeneous bundles representing the whole structure of the tractography dataset. This simplified representation of white matter can be used further for several studies of individual bundle structure or group analyses. The robustness and the cost of the scalability of the method are checked using simulated tract datasets. The second level, an inter-subject clustering, gathers the bundles obtained in the first level for a population of subjects and performs a clustering after spatial normalization. It produces as output a model composed by a list of generic fiber bundles that can be detected in most of the population. A validation with simulated datasets is applied in order to study the behavior of the inter-subject clustering over a population of subjects aligned with affine registration. The whole method was applied to the tracts computed from HARDI data obtained for twelve adult brains. A novel HARDI multi-subject bundle atlas, representing the variability of the bundle shape and position across subjects was thus inferred. The atlas includes 36 deep WM bundles, some of these representing a few subdivisions of known WM tracts, and 94 short association bundles of superficial WM. Finally, we propose an automatic segmentation method mapping this atlas to any new subject.

Edward Bouverie Pusey once towered over nineteenth-century British theology, but he has now fallen into almost entire insignificance. However, analysis of this decline (Chapter 1) leads to a reassessment. His development—especially his complicated relationship with pre-Tractarian High Church Anglicanism—shows a deep criticism of post-Enlightenment intellectual trends, from his early years through his association with the Oxford Movement and the Tracts for the Times, to the end of his life (Chapter 2). This criticism led him to the patristic use of allegory, both as a biblical hermeneutic and as a creative, complex, image-based approach to theology (Chapter 3). His development of High Church theology (seen especially through comparison with Waterland) and his use of allegory can be traced throughout his theology. His understanding of union with Christ and theosis reveals both: the sacraments have a strong symbolic dimension, while his positions on baptismal regeneration and the real presence of Christ in the Eucharist show a development rather than a rejection of earlier High Church theology (Chapters 4 and 5). His understanding of the atonement blends High Church reliance on sacrificial types with his unitive theology to reconfigure traditional satisfaction theory as restoration of love for God, rather than redemption from punishment—a position which marks Pusey as an important transitional figure in 19th c. theology (Chapter 6). The flexibility of Pusey's allegorical approach also allows him to blend a High Church tradition of spiritual sacrifice with sacramental participation in Christ's self-offering, so that sacrifice becomes an aspect of union with Christ (Chapter 7). Pusey's use of allegory shows similarities to postmodern theology, while his development of High Church theology shows his originality (Chapter 8).

Les carcinomes épidermoïdes de la tête et du cou sont souvent de mauvais pronostic, en raison de leur résistance aux traitements suivie de récidives loco-régionales, voire de métastases. Ce travail s'est focalisé sur le rôle des cellules souches cancéreuses (CSC) dans la radiorésistance d'un modèle cellulaire de cancer du larynx, SQ20B, ainsi que sur leur ciblage thérapeutique en association avec la radiothérapie photonique ou par ions carbone. Une sous-population a été isolée à partir de la lignée SQ20B par tris cellulaires successifs selon 3 critères spécifiques des CSC de tumeurs ORL : exclusion du Hoechst 33342, expression de CD44 et activité élevée de l'aldéhyde déshydrogénase (ALDH). Les cellules SQ20B/SP/CD44 high/ALDHhigh présentent bien les caractéristiques de CSC (tumorisphères, tumorigénèse, radiorésistance). La résistance des CSC aux 2 types d'irradiation, par rapport aux cellules « non souche » SQ20B/SP/CD44low/ALDHlow, implique une diminution de la mort par apoptose, une augmentation des capacités prolifératives ainsi qu'une surexpression de la voie de l'autorenouvellement Bmi1. L'effet radiosensibilisant de 3 molécules ciblant les CSC a été démontré : la mort apoptotique induite par l'UCN-01 en inhibant l'arrêt en phase G2/M ; les capacités prolifératives ciblées par l'acide trans-rétinoïque (ATRA) induisant la différenciation ; et la voie de l'autorenouvellement Bmi-1 inhibée par l'artésunate. Seule ou associées (UCN-01 + ATRA), elles agissent en synergie avec une irradiation par photons ou ions carbone. Des études pré-clinique, puis clinique, devraient confirmer l'intérêt du ciblage des CSC dans le contrôle de l'échappement de ces cancers radiorésistants / Head and neck squamous cell carcinomas (HNSCC) have a poor prognosis, due to their resistance to standard treatments. In most cases, locoregional recurrence or metastases occur. This study has focused on the role of cancer stem cells (CSC) in the radioresistance of the SQ20B HNSCC cell line and their therapeutic targeting in association with photon or carbon ions irradiation. A subpopulation of SQ20B-CSC has been isolated by cell sorting based on 3 specific characteristics of HNSCC-CSC : Hoechst 33342 exclusion, CD44 expression and high aldehyde dehydrogenase activity (ALDH). SQ20B/SP/CD44high/ALDHhigh cells show the CSC characteristics (in vitro and in vivo tumorigenesis, high radioresistance). The response of CSC to both types of irradiation was compared to the non-“stem cells” SQ20B/SP/CD44low sub-population. The observed radioresistance involves a decrease in apoptotic cell death, an increase in proliferative capacities and an overexpression of the Bmi1 self-renewing signaling pathway. The radiosensitizing effects of 3 molecules targeting the CSC has been demonstrated : an induction of apoptotic cell death by the inhibition of the G2/M phase arrest after a treatment with UCN01 ; an inhibition of proliferative capacities using the all-trans-retinoic acid (ATRA) which induce their differentiation ; and an inhibition of Bmi1 by artesunate. These treatments, alone or in combination (UCN01+ATRA) have a synergistic effect with photon or carbon ion irradiation to overcome CSC radioresistance. Preclinical and clinical studies should confirm the benefit of targeting CSC and improve the control of tumor escape in patients with radioresistant HNSCC cancers