176 resultados para Network re-configuration
Resumo:
Cette thèse, qui se base sur des entretiens qualitatifs, porte sur la négociation des références identitaires de musulmans immigrés et réfugiés en provenance de Γ ex-Yougoslavie au Luxembourg et s'intéresse à la pertinence changeante de la religion dans la conception de soi. Selon une approche constructiviste et interactionniste, l'identité est conçue comme un projet constamment négocié, reconstruit dans des processus d'interaction sociale et en fonction des contextes sociaux. Nos données suggèrent l'émergence de constructions identitaires complexes et attestent de la pluridimensionalité et de l'intersectionnalité des références identitaires utilisées dans la conception de soi et témoignent de la non-réduction des individus à des catégories fixes. Différentes catégories sont rendues significatives et de multiples frontières sont établies afin de se différencier de figures d'altérité changeantes, sélectivement choisies pour construire une certaine image de soi. Les discours identitaires témoignent de l'aspiration à une identité positive, dans une situation caractérisée par la perte du statut social et des stigmatisations multiples, en tant que ex-Yougoslaves, demandeurs d'asile et musulmans. Nos interlocuteurs établissent un répertoire identitaire composé de marqueurs transposés, inventés et revalorisés, leur permettant de reconstruire une identité positive pour soi et leurs audiences. Ce travail décrit les manières dont les individus établissent leur répertoire identitaire à l'aide de marqueurs transposés, inventés et revalorisés, leur permettant de reconstruire une identité positive pour soi et leurs audiences et montre comment les processus de différenciation de 'l'autre' dans le pays d'origine et d'accueil sont reliés. - The question addressed in this project with a qualitative design, is how muslim migrants and refugees from the former Socialist Federal Republic of Yugoslavia in Luxemburg negotiate salient identity references in a new social political environment and discusses the changing significance of religion and the way it is integrated in the identity patchwork. According to a constructivist and interactionist approach, conceiving identity as a constantly negotiated project, reconstructed in interaction and with regard to social context, identities are relevant only in relation to particular other groups and in certain situations of interaction. Our data suggest the emergence of complex identity patterns using multiple references for self- description and attest of the intersectionnality of identity references and show that individuals can't be reduced to fixed categories. Different categories are made salient and multiple symbolic boundaries are established in order to differentiate from different "others", selected in order to construct a certain self-concept. The discourses of our participants attest of an aspiration towards a positive identity in a situation characterized by the loss of social status and multiple stigmata. This thesis describes the ways how individuals establish their identity repertoire with invented, transposed and negotiated identity references, that allow them to construct a favourable identity for themselves and their public and shows how différenciation processes in home and host country are related.
Resumo:
Within the framework of the Rare Cancer Network Study, we examined 30 patients suffering from small cell neuroendocrine prostate cancer, either in an early/localized or an advanced/metastatic stage. Patients were treated with cisplatin-based chemotherapy, with or without pelvic radiotherapy. Two patients with early disease achieved complete remission for a duration of 19 and 22 months. Three patients with advanced disease achieved complete remission for 6, 7, and 54 months, respectively. Twenty-five patients succumbed to massive local and/or distant failure. No patient presented with brain metastases as the initial site of relapse. Small cell neuroendocrine prostate carcinoma is a very aggressive disease with a poor prognosis, even in its localized form. Despite initial response, the common cisplatin-based chemotherapy plus radiotherapy failed to improve outcome markedly. Improvement will come from understanding the biology of the disease and integrating new targeted therapies into the treatment of this rare and aggressive tumor.
Resumo:
PURPOSE: The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE). MATERIALS AND METHODS: Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6). RESULTS: The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose (>or=50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size >or=25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04). CONCLUSIONS: The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.
Resumo:
Modern urban lifestyle encourages the prolongation of wakefulness, leaving less and less time for sleep. Although the exact functions of sleep remain one of the biggest mysteries in neuroscience, the society is well aware of the negative consequences of sleep loss on human physical and mental health and performance. Enhancing sleep's recuperative functions might allow shortening sleep duration while preserving the beneficial effects of sleep. During sleep, brain activity oscillates across a continuum of frequencies. Individual oscillations have been suggested to underlie distinct functions for sleep and cognition. Gaining control about individual oscillations might allow boosting their specific functions. Sleep spindles are 11 - 15 Hz oscillations characteristic for light non-rapid-eye-movement sleep (NREMS) and have been proposed to play a role in memory consolidation and sleep protection against environmental stimuli. The reticular thalamic nucleus (nRt) has been identified as the major pacemaker of spindles. Intrinsic oscillatory burst discharge in nRt neurons, arising from the interplay of low-threshold (T-type) Ca2+ channels (T channels) and small conductance type 2 (SK2) K+ channels (SK2 channels), underlies this pacemaking function. In the present work we investigated the impact of altered nRt bursting on spindle generation during sleep by studying mutant mice for SK2 channels and for CaV3.3 channels, a subtype of T channels. Using in vitro electrophysiology I showed that nRt bursting was abolished in CaV3.3 knock out (CaV3.3 KO) mice. In contrast, in SK2 channel over-expressing (SK2-OE) nRt cells, intrinsic repetitive bursting was prolonged. Compared to wildtype (WT) littermates, altered nRt burst discharge lead to weakened thalamic network oscillations in vitro in CaV3.3 KO mice, while oscillatory activity was prolonged in SK2-OE mice. Sleep electroencephalographic recordings in CaV3.3 KO and SK2-OE mice revealed that reduced or potentiated nRt bursting respectively weakened or prolonged sleep spindle activity at the NREMS - REMS transition. Furthermore, SK2-OE mice showed more consolidated NREMS and increased arousal thresholds, two correlates of good sleep quality. This thesis work suggests that CaV3.3 and SK2 channels may be targeted in order to modulate sleep spindle activity. Furthermore, it proposes a novel function for spindles in NREMS consolidation. Finally, it provides evidence that sleep quality may be improved by promoting spindle activity, thereby supporting the hypothesis that sleep quality can be enhanced by modulating oscillatory activity in the brain. Le style de vie moderne favorise la prolongation de l'éveil, laissant de moins en moins de temps pour le sommeil. Même si le rôle exact du sommeil reste un des plus grands mystères des neurosciences, la société est bien consciente des conséquences négatives que provoque un manque de sommeil, à la fois sur le plan de la santé physique et mentale ainsi qu'au niveau des performances cognitives. Augmenter les fonctions récupératrices du sommeil pourrait permettre de raccourcir la durée du sommeil tout en en conservant les effets bénéfiques. Durant le sommeil, on observe des oscillations à travers un continuum de fréquences. Il a été proposé que chaque oscillation pourrait être à l'origine de fonctions spécifiques pour le sommeil et la cognition. Pouvoir de contrôler les oscillations individuelles permettrait d'augmenter leurs fonctions respectives. Les fuseaux sont des oscillations de 11 à 15 Hz caractéristiques du sommeil à ondes lentes léger et il a été suggéré qu'elles jouent un rôle majeur pour la consolidation de la mémoire ainsi que dans la protection du sommeil contre les stimuli environnementaux. Le nucleus réticulaire du thalamus (nRt) a été identifié en tant que générateur de rythme des fuseaux. Les bouffées oscillatoires intrinsèques des neurones du nRt, provenant de l'interaction de canaux calciques à bas seuil de type T (canaux T) et de canaux potassiques à faible conductance de type 2 (canaux SK2), sont à l'origine de la fonction de générateur de rythme. Dans ce travail, j'ai étudié l'impact de la modulation de bouffées de nRT sur la génération des fuseaux pendant le sommeil en investiguant des souris génétiquement modifiées pour les canaux SK2 et les canaux CaV3.3, un sous-type de canaux T. En utilisant l'électrophysiologie in vitro j'ai démontré que les bouffées du nRT étaient abolies dans les souris knock-out du type CaV3.3 (CaV3.3 KO). D'autre part, dans les cellules nRT sur-exprimant les canaux SK2 (SK2-OE), les bouffées oscillatoires intrinsèques étaient prolongées. Par rapport aux souris wild type, les souris CaV3.3 KO ont montré un affaiblissement des oscillations thalamiques en réponse à un changement des bouffées de nRT, alors que l'activité oscillatoire était prolongée dans les souris SK2-OE. Des enregistrements EEG du sommeil dans des souris de type CaV3.3 KO et SK2-OE ont révélé qu'une réduction ou augmentation des bouffées nRT ont respectivement affaibli ou prolongé l'activité des fuseaux durant les transitions du sommeil à ondes lentes au sommeil paradoxal. De plus, les souris SK2-OE ont montré des signes de consolidation du sommeil à ondes lentes et un seuil augmenté pour le réveil, deux mesures qui corrèlent avec une bonne qualité du sommeil. Le travail de cette thèse propose que les canaux CaV3.3 et SK2 pourrait être ciblés pour moduler l'activité des fuseaux. De plus, je propose une fonction nouvelle pour les fuseaux dans la consolidation du sommeil à ondes lentes. Finalement je suggère que la qualité du sommeil peut être améliorée en promouvant l'activité des fuseaux, soutenant ainsi l'idée que la qualité du sommeil peut être améliorée en modulant l'activité oscillatoire dans le cerveau.
Resumo:
Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression ('SCNA-genes') in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer.
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In rodents and nonhuman primates subjected to spinal cord lesion, neutralizing the neurite growth inhibitor Nogo-A has been shown to promote regenerative axonal sprouting and functional recovery. The goal of the present report was to re-examine the data on the recovery of the primate manual dexterity using refined behavioral analyses and further statistical assessments, representing secondary outcome measures from the same manual dexterity test. Thirteen adult monkeys were studied; seven received an anti-Nogo-A antibody whereas a control antibody was infused into the other monkeys. Monkeys were trained to perform the modified Brinkman board task requiring opposition of index finger and thumb to grasp food pellets placed in vertically and horizontally oriented slots. Two parameters were quantified before and following spinal cord injury: (i) the standard 'score' as defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contact time' as defined by the duration of digit contact with the food pellet before successful retrieval. After lesion the hand was severely impaired in all monkeys; this was followed by progressive functional recovery. Remarkably, anti-Nogo-A antibody-treated monkeys recovered faster and significantly better than control antibody-treated monkeys, considering both the score for vertical and horizontal slots (Mann-Whitney test: P = 0.05 and 0.035, respectively) and the contact time (P = 0.008 and 0.005, respectively). Detailed analysis of the lesions excluded the possibility that this conclusion may have been caused by differences in lesion properties between the two groups of monkeys.
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For self-pollinating plants to reproduce, male and female organ development must be coordinated as flowers mature. The Arabidopsis transcription factors AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8 regulate this complex process by promoting petal expansion, stamen filament elongation, anther dehiscence, and gynoecium maturation, thereby ensuring that pollen released from the anthers is deposited on the stigma of a receptive gynoecium. ARF6 and ARF8 induce jasmonate production, which in turn triggers expression of MYB21 and MYB24, encoding R2R3 MYB transcription factors that promote petal and stamen growth. To understand the dynamics of this flower maturation regulatory network, we have characterized morphological, chemical, and global gene expression phenotypes of arf, myb, and jasmonate pathway mutant flowers. We found that MYB21 and MYB24 promoted not only petal and stamen development but also gynoecium growth. As well as regulating reproductive competence, both the ARF and MYB factors promoted nectary development or function and volatile sesquiterpene production, which may attract insect pollinators and/or repel pathogens. Mutants lacking jasmonate synthesis or response had decreased MYB21 expression and stamen and petal growth at the stage when flowers normally open, but had increased MYB21 expression in petals of older flowers, resulting in renewed and persistent petal expansion at later stages. Both auxin response and jasmonate synthesis promoted positive feedbacks that may ensure rapid petal and stamen growth as flowers open. MYB21 also fed back negatively on expression of jasmonate biosynthesis pathway genes to decrease flower jasmonate level, which correlated with termination of growth after flowers have opened. These dynamic feedbacks may promote timely, coordinated, and transient growth of flower organs.
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This paper deals with the problem of spatial data mapping. A new method based on wavelet interpolation and geostatistical prediction (kriging) is proposed. The method - wavelet analysis residual kriging (WARK) - is developed in order to assess the problems rising for highly variable data in presence of spatial trends. In these cases stationary prediction models have very limited application. Wavelet analysis is used to model large-scale structures and kriging of the remaining residuals focuses on small-scale peculiarities. WARK is able to model spatial pattern which features multiscale structure. In the present work WARK is applied to the rainfall data and the results of validation are compared with the ones obtained from neural network residual kriging (NNRK). NNRK is also a residual-based method, which uses artificial neural network to model large-scale non-linear trends. The comparison of the results demonstrates the high quality performance of WARK in predicting hot spots, reproducing global statistical characteristics of the distribution and spatial correlation structure.
Resumo:
A character network represents relations between characters from a text; the relations are based on text proximity, shared scenes/events, quoted speech, etc. Our project sketches a theoretical framework for character network analysis, bringing together narratology, both close and distant reading approaches, and social network analysis. It is in line with recent attempts to automatise the extraction of literary social networks (Elson, 2012; Sack, 2013) and other studies stressing the importance of character- systems (Woloch, 2003; Moretti, 2011). The method we use to build the network is direct and simple. First, we extract co-occurrences from a book index, without the need for text analysis. We then describe the narrative roles of the characters, which we deduce from their respective positions in the network, i.e. the discourse. As a case study, we use the autobiographical novel Les Confessions by Jean-Jacques Rousseau. We start by identifying co-occurrences of characters in the book index of our edition (Slatkine, 2012). Subsequently, we compute four types of centrality: degree, closeness, betweenness, eigenvector. We then use these measures to propose a typology of narrative roles for the characters. We show that the two parts of Les Confessions, written years apart, are structured around mirroring central figures that bear similar centrality scores. The first part revolves around the mentor of Rousseau; a figure of openness. The second part centres on a group of schemers, depicting a period of deep paranoia. We also highlight characters with intermediary roles: they provide narrative links between the societies in the life of the author. The method we detail in this complete case study of character network analysis can be applied to any work documented by an index. Un réseau de personnages modélise les relations entre les personnages d'un récit : les relations sont basées sur une forme de proximité dans le texte, l'apparition commune dans des événements, des citations dans des dialogues, etc. Notre travail propose un cadre théorique pour l'analyse des réseaux de personnages, rassemblant narratologie, close et distant reading, et analyse des réseaux sociaux. Ce travail prolonge les tentatives récentes d'automatisation de l'extraction de réseaux sociaux tirés de la littérature (Elson, 2012; Sack, 2013), ainsi que les études portant sur l'importance des systèmes de personnages (Woloch, 2003; Moretti, 2011). La méthode que nous utilisons pour construire le réseau est directe et simple. Nous extrayons les co-occurrences d'un index sans avoir recours à l'analyse textuelle. Nous décrivons les rôles narratifs des personnages en les déduisant de leurs positions relatives dans le réseau, donc du discours. Comme étude de cas, nous avons choisi le roman autobiographique Les Confessions, de Jean- Jacques Rousseau. Nous déduisons les co-occurrences entre personnages de l'index présent dans l'édition Slatkine (Rousseau et al., 2012). Sur le réseau obtenu, nous calculons quatre types de centralité : le degré, la proximité, l'intermédiarité et la centralité par vecteur propre. Nous utilisons ces mesures pour proposer une typologie des rôles narratifs des personnages. Nous montrons que les deux parties des Confessions, écrites à deux époques différentes, sont structurées autour de deux figures centrales, qui obtiennent des mesures de centralité similaires. La première partie est construite autour du mentor de Rousseau, qui a symbolisé une grande ouverture. La seconde partie se focalise sur un groupe de comploteurs, et retrace une période marquée par la paranoïa chez l'auteur. Nous mettons également en évidence des personnages jouant des rôles intermédiaires, et de fait procurant un lien narratif entre les différentes sociétés couvrant la vie de l'auteur. La méthode d'analyse des réseaux de personnages que nous décrivons peut être appliquée à tout texte de fiction comportant un index.