Vários estudos têm apontado que falhas nas habilidades do processamento fonológico (consciência fonológica, memória fonológica e acesso ao léxico) estão relacionadas com distúrbios de leitura e escrita. Programas terapêuticos baseados na estimulação da consciência fonológica têm sido propostos, porém poucos se propõem a estimular as três habilidades do processamento fonológico. A efetividade dos programas terapêuticos é evidenciada por testes comportamentais e, na busca por biomarcadores da evolução terapêutica, o potencial evocado auditivo de longa latência (P300) tem sido estudado. O P300 é um potencial endógeno que avalia a resposta do sujeito a estímulos acústicos, envolvidos nas regiões cerebrais corticais e subcorticais relacionados com atenção, discriminação auditiva e memória. O presente estudo teve por objetivo investigar a eficácia de um programa de estimulação do processamento fonológico em escolares com Distúrbios de Leitura e Escrita por meio da análise dos testes comportamentais e P300 pré e pós-estimulação. Participaram deste estudo 10 escolares, que frequentavam regularmente o 4º, 5º, 6º ou 7º ano do Ensino Fundamental, com Distúrbio de Leitura e Escrita. Os escolares foram submetidos às avaliações de aritmética, consciência fonológica, memória fonológica, nomeação automática rápida, leitura e escrita, e submetidos ao exame P300, em seguida iniciaram uma intervenção baseada na estimulação das habilidades do processamento fonológico. A intervenção foi realizada em 20 sessões (semanais de 45 minutos). A proposta de intervenção foi baseada em exercícios de estimulação dos três componentes do processamento fonológico. Após a intervenção, foram novamente submetidos às mesmas avaliações comportamentais e avaliação do P300. Os resultados pré e pós-estimulação foram comparados por meio do Wilcoxon-test para amostras pareadas com o nível de significância de 0,05. Observou-se melhora no desempenho em todas as tarefas do Processamento Fonológico (p<0,05). A melhora também foi observada na leitura de palavras e pseudopalavras e compreensão de texto (p<0,05), além de diminuição de erros ortográficos no ditado e escrita espontânea (p<0,05). O P300 não apresentou diferença no período pós-estimulação, mostrando que o programa foi efetivo e que o P300 não foi um biomarcador eficiente de evolução terapêutica. / Several studies have pointed out that failures in phonological processing skills (phonological awareness, phonological memory and lexical retrieval) are related to reading and writing disorders. Therapeutic programs based on phonological awareness have been proposed, but few are meant to stimulate the three phonological processing skills. The effectiveness of therapeutic programs is evidenced by behavioral tests, however, in the search for biomarkers of therapeutic evolution, the long-latency auditory evoked potential (P300) has been studied. The P300 is an endogenous potential that evaluates the response of the subject to acoustic stimuli involved in cortical and subcortical brain regions related to attention, auditory discrimination and memory. This study aimed to investigate the effectiveness of a stimulation program of phonological processing in children with reading and writing disorders by analyzing the behavioral tests and the P300 pre and post-stimulation. The participants of this study were 10 students who regularly attended the 4th, 5th, 6th or 7th year of elementary school and have reading and writing disorder. The students were submitted to arithmetic reviews, phonological awareness, phonological memory, rapid automatized naming, reading and writing, and submitted to the P300 examination, then began an intervention based on the stimulation of phonological processing skills. This intervention was performed in 20 sessions (45 minutes weekly). The proposed intervention was based on the stimulation exercises of the three components of phonological processing. After the intervention, they were again subjected to the same behavioral assessments and evaluation of P300. The pre and post-stimulation were compared using the Wilcoxon-test for paired samples with the 0.05 significance level. There was an improved performance in all tasks of Phonological Processing (p <0.05). The improvement was also observed in reading words and pseudo words and reading comprehension (p <0.05), and a reduction of spelling errors in dictation and spontaneous writing (p <0.05). The P300 showed no difference in post-stimulation period, showing that the program was effective and P300 cannot be considered a biomarker of therapeutic evolution.

Le sommeil est défini comme un état comportemental de repos où nous perdons conscience de notre environnement et notre réactivité aux stimuli extérieurs est drastiquement réduite. Pourtant, lorsque nous dormons, l’appel par notre prénom ou à la sonnerie du réveil peuvent encore nous réveiller, suggérant qu’un certain degré de traitement des stimuli reste possible. Dans ce travail, nous soulevons la question de la profondeur du traitement de l’information extérieure pendant le sommeil. Nous avons enregistré simultanément l’activité cérébrale de sujets sains adultes en électro- et magnéto-encéphalographie (EEG et MEG) en réponse à des stimulations auditives, avant, pendant, et après une courte période de sommeil. Afin de tester la profondeur du traitement de l’information à travers la hiérarchie corticale, nous nous sommes concentrés sur les capacités de codage prédictif hiérarchique, qui permettent au cerveau d’anticiper les évènements futurs à partir d’une connaissance passée. Les prédictions sont faites à de nombreuses si ce n’est toutes les étapes de la hiérarchie corticale. Tester les différents niveaux de prédiction nous permet donc d’évaluer précisément à quel niveau l’intégration de l’information est interrompue. Nous avons d’abord testé les capacités du cerveau à détecter la nouveauté auditive. Nous avons présenté aux sujets des séquences de sons comprenant des régularités temporelles à courte (locale) ou à longue (globale) échelle de temps, et analysé les réponses cérébrales à des sons violant ces régularités. Les réponses cérébrales à ces violations locales ou globales se traduisent respectivement en EEG à l’éveil par l’émergence de deux signaux d’erreur de prédiction : la négativité de mismatch (MMN) et la P300. Notre analyse révèle que la MMN et la P300 disparaissent toutes deux dans le sommeil avec la perte des activations des aires associatives préfrontales et pariétales. Au cours de l’endormissement, la MMN diminue progressivement, tandis que la P300 disparait brutalement avec la perte de conscience des stimuli. Ce comportement tout-ou-rien renforce l’hypothèse que la P300 est un marqueur de la conscience. Malgré tout, nous avons montré que le cerveau détecte toujours les nouveaux sons et peut s’y habituer, mais seulement dans un contexte limité d’adaptation sensorielle de bas niveau. Après avoir démontré la perte des capacités de codage prédictif dans le sommeil dans le cadre de régularités statistiques arbitraires et nouvellement acquises, dans une deuxième série d’expériences nous avons testé la capacité du cerveau endormi à établir des prédictions sur les sons à venir dans le cadre de connaissances sémantiques connues déjà stockées en mémoire à long terme. Nous avons présenté à des sujets endormis des opérations arithmétiques simples, comme “deux plus deux égal neuf”, et nous avons enregistré les réponses cérébrales aux résultats corrects et aux résultats faux. Nous avons découvert que le cerveau était toujours capable de détecter les violations arithmétiques dans le sommeil, avec des activations en partie similaires à celles de l’éveil. Nous suggérons que, bien que le sommeil prévienne tout calcul explicite, il y a conservation des signaux d’erreur de prédiction pour les opérations arithmétiques simple déjà mémorisées. Ce travail clarifie à quel niveau l’intégration de l’information auditive est interrompue pendant le sommeil, et quelles fonctions cognitives persistent ou s’altèrent. La persistance de l’adaptation sensorielle et des capacités de prédiction à partir de connaissances déjà mémorisées sont probablement responsables de la réactivité résiduelle qui peut être observée pendant le sommeil alors que les sujets sont inconscients. Finalement, ces résultats aident aussi à mieux comprendre pourquoi un stimulus donné sera traité ou non dans le sommeil. (...) / Sleep can be defined as a behavioral state of rest in which consciousness of external stimuli vanishes and responsiveness to the environment is drastically reduced. When we sleep, however, we may still react and wake up to our name or to the alarm clock, suggesting that some processing of external stimuli remains. We address in the present work the question of how deeply external information is processed during sleep. We recorded brain activity in adult human subjects simultaneously in electro and magnetoencephalography (EEG and MEG) in response to auditory stimulation, before, during and after a short period of sleep. In order to test information integration through the brain hierarchy, we focused on hierarchical predictive coding capabilities, which enable the brain to anticipate the future from previous knowledge. Predictions occur at many if not all steps of the cortical hierarchy. Testing different levels of predictions enables us to assess the steps at which information integration is disrupted during sleep. We first tested the capacity of the sleeping brain to detect auditory novelty. We analyzed brain responses to violations of local and global temporal regularities, which are respectively reflected in EEG during wakefulness by two successive prediction error signals, the mismatch negativity (MMN) and the P300. Our analysis revealed that both the MMN and the P300 vanish during sleep, along with the loss of activations in prefrontal and parietal associative areas. The MMN gradually decreased in the descent to sleep, whereas the P300 vanished abruptly with the loss of awareness during N1 sleep. This all-or-none behavior strongly reinforces the hypothesis that the P300 is a marker of consciousness. Even so, we showed that sounds still activate sensory cortices, and that the brain remains able to detect new sounds and to habituate to them, but only in the limited context of sensory adaptation. Having demonstrated the disruption of predictive coding for arbitrary and newly acquired statistical regularities, in a second set of experiments we tested the capacity of the sleeping brain to develop predictions of future auditory stimuli for over-learned semantic knowledge stored in long-term memory. We presented sleeping subjects with simple arithmetic facts such as “two plus two is nine” and recorded brain responses to correct or incorrect results. We discovered that the sleeping brain was still able to detect arithmetic violations, with activations in part similar to wakefulness. We suggest that, although sleep disrupts explicit arithmetic computations, there is a preservation of prediction error signals for arithmetic facts stored in long-term memory. The present work clarifies the steps at which auditory information integration is disrupted during sleep, and which cognitive functions remain or vanish. The preservation of low-level sensory adaptation and of predictions from long term memory may account for the residual responsiveness that can be observed during sleep, while subjects are unconscious. Finally, these results also help to better understand why a given stimulus may or may not be processed during sleep. The depth of information integration is function of the ongoing spontaneous oscillations of the sleeping brain, but also of the nature of the stimulus, i.e. its salience, its knowledge, and its relevance.

La myélofibrose primitive (MFP) est un néoplasme myéloprolifératif (NMP) classique BCR-ABL négatif associé à une forte altération de la qualité de vie et à une augmentation de la mortalité. Les traitements conventionnels réduisent les symptômes mais ont peu d’effet sur l’histoire naturelle de la maladie. La MFP résulte d’interactions complexes entre le développement du clone hématopoïétique malin, l’installation d’un contexte inflammatoire et le remodelage du microenvironnement médullaire. Chacun de ces axes est une cible thérapeutique potentielle. Dans ce travail, nous avons évalué le potentiel thérapeutique de l’activation de PPARγ dans trois modèles murins de myélofibrose et nous montrons que les ligands de PPARγ permettent d’améliorer les paramètres hématologiques et histologiques en rapport avec l’installation du phénotype de myélofibrose. Chacun des axes de la physiopathologie a ensuite été exploré. Les ligands de PPARγ ont une action anti-proliférative sur le clone malin, tant dans les modèles murins de NMPs que dans les cellules JAK2V617F de lignée et dans les progéniteurs hématopoïétiques issus de patients atteints de NMPs. Le traitement atténue également l’hyperleucocytose associée au phénotype inflammatoire des NMPs et modifie la transcription de gènes de l’inflammation. Enfin, les ligands de PPARγ ont un effet protecteur sur le stroma médullaire, dépendant de la capacité de PPARγ à contrecarrer la voie de signalisation du TGF-β1, cytokine majeure du développement de la fibrose médullaire, par déplacement du cofacteur de transcription p300 de la voie du TGF-β1 vers la voie PPARγ. Par son action sur les trois composantes de la physiopathologie, l’activation de PPARγ constitue une cible thérapeutique pertinente dans la prise en charge de la MFP. / Primary myelofibrosis (PMF) is a non BCR-ABL myeloproliferative neoplasm (MPN) associated with poor quality of life and reduced survival. Current treatments are mainly symptomatic and have little effect on the natural history of the disease. PMF results from complex interactions between the emergence of a hematopoietic malignant clone, an inflammatory context and the remodeling of the bone marrow (BM) microenvironment. Each of these axes is a potential therapeutic target. Here, we evaluated the therapeutic potential of PPARγ ligands in three murine models of myelofibrosis and we showed that PPARγ ligands improve hematological and histological changes related to myelofibrosis phenotype. Then, we explored each axis of the pathophysiology. We showed that PPARγ ligands have an anti-proliferative effect and limit the proliferation of the malignant clone in murine models of MPNs, in JAK2V617F cell lines and in hematopoietic progenitors from MPNs patients. PPARγ ligands also decrease leukocytosis related to the inflammatory phenotype of MPNs and modify the transcription of inflammatory genes. Finally, we demonstrated that PPARγ ligands have a protective effect on BM stroma. They counteract the signaling pathway of TGF-β1, a major cytokine in BM fibrosis development, by moving the p300 cofactor of transcription from the TGF-β1 pathway to the PPARγ pathway. By its action on the three components of the pathophysiology, activation of PPARγ pathway is a relevant therapeutic target in PMF.

African swine fever virus (ASFV) is a large double-stranded DNA virus which causes a lethal haemorrhagic fever in domestic pigs. This virus primarily infects cells from the monocyte/macrophage lineage and its ability to manipulate the function of these cells is key to the pathogenesis of this disease. ASFV encodes several proteins involved in immune evasion. One of these proteins, A238L, has been shown to inhibit host macrophage gene transcription. This protein has been shown to interact with several cellular proteins involved in signal transduction: a serine/threonine protein phosphatase, calcinerurin (CaN), the transcription factor NF-кB, and most recently the transcriptional co-activator CREB binding protein (CBP/P300). However its exact mechanism of action is not fully understood. Previous work has been limited to the investigation of individual signaling pathways and/or the expression of individual host genes. The aim of this study was to investigate the global effect of A238L on host macrophage gene transcription and also to carry out further investigation into the mechanism by which this protein functions. To determine the global effect of A238L on host macrophage gene transcription differential gene expression between porcine cells expressing A238L and control cells was examined using a porcine oligonucleotide microarray. These results demonstrated that A238L was a potent inhibitor of host macrophage gene expression. Functional characterisation of the annotated genes showed that a large proportion of A238L down-regulated genes are typically induced in response to cell stress. Significantly, genes regulated by the I kappa B kinase (IKK), mitogen-activated protein kinase (MAPK) and janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways were all shown to be down regulated by A238L. Genes associated with the MAPK pathways were particularly enriched. The transcription of A238L-regulated genes is controlled by numerous different transcription factors, including NF-кB. All of the transcription factors identified interact with the transcription co-activator CBP/P300. This provides a common link between these factors, and indicates that A238L may target CBP/P300 to inhibit gene transcription. This observation supports recent work demonstrating that A238L interacts with and inhibits CBP/P300 function. To explore the potential mechanisms involved in the nuclear localisation of A238L, ASFV-infected Vero cells, expressing A238L under the control of its own promoter, were examined under a range of conditions using confocal microscopy. The results demonstrated that A238L was actively imported into the nucleus and exported by a CRM 1 mediated pathway, although a pool of A238L protein remained in the cytoplasm. Sequence analysis of A238L identified the presence of two putative nuclear localisation signals (NLS-1 and NLS-2). NLS-2 was located within A238L’s CaN docking motif. Mutation of these motifs indicated that both NLS-1 and NLS-2 are active and exhibit functional redundancy. Mutation of the CaN docking motif alone, in the presence of intact NLS-2, resulted in a dramatic increase in the nuclear localisation of A238L. These results are consistent with a model in which A238L functions within both the nucleus and the cytoplasm and suggest that binding of CaN to A238L masks NLS-2, contributing to the cytoplasmic retention of A238L.

Television in Thailand, as in many nations, can be regarded as an essential form of popular media. Although television plays an important role within and across all levels of society, the relationship between television and Thai cultural identity is a problematic and ambiguous one; it is also a subject of study often neglected or not taken seriously enough in Thailand. This research project, "Popular Television and the Construction of Contemporary Thai Cultural Identity', is an exploration into the relationship between television and the formation of contemporary Thai cultural identity. It draws together media and cultural studies and the study of television in contemporary Thailand. Through interviews with key media practitioners and an analysis of popular television programmes (such as the controversial game show 'The Weakest Link', popular dramas, youth programmes, and broadcasts of national rituals), the research has found that television plays a prominent role in Thai cultural identity formation. One existing line of argument is that Thai cultural identity in the era of globalisation has been inevitably influenced by western homogenisation, as is suggested by the thesis of Cultural Imperialism. Yet on the other hand, globalisation has played a multi-faceted role in creating the sense of Nationalism which has led to the strengthening of Thai traditional identity, evidence of which can be seen in the Thai government's use of television to support Thai tradition and values. In this way, television has played a unifying role in the formation of Thai cultural identity. Moreover, globalisation, as a new global-local articulation, has also created a new kind of cultural hybridity which is apparent in the styles, forms, and language usage in certain youth programmes. In addition to the theoretical analyses, focus-group discussions and in-depth interviews have been conducted in order to examine the 'cultural hybridity' of 'mixed-race' youngsters in Thailand, and the roles television has played in the formation of their identity. The research has further found that 'mixed-race' youngsters (`third-culture kids' or TCKs) in Thailand have learnt to 'translate' themselves within the different cultures. And television, in some way, has helped them make sense of, and negotiate between, the different cultures they are living in.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

The aim of this research study is to analyse the nature of undergraduate media studies in England, necessarily from the inside, and document the social practices that constitute the subject in the light of its historic and contemporary challenges and the influence of changing public higher education discourses over the period of the fieldwork, 2012-2013. Conceptually, media studies is regarded as socially constructed and enacted through discursive practices that reveal the nature of the power relationships that are the basis of the ways ‘things get done’. This approach is based on Foucault’s (1984, 2002a, 2002b, 2002c) conception of power and discourse and dovetails with a substantial part of the sociology of higher education. The fieldwork consisted of a series of semi-structured face-to-face interviews with a range of participants drawn from media studies lecturers, other university professionals, media studies graduates and a secondary school headteacher with experience of advising university applicants. This provided examples of discursive practices from both ‘inside’ and ‘outside’ media. The thematic analyses of the data show a complex set of interacting oppositional discourses that are skilfully managed by these professional practitioners to maintain a balance of Foucauldian power. This ensures that public policy changes are assimilated and ‘delivered’ whilst sometimes also mitigating their impact and maintaining a prevailing rationale for media studies. The study concludes by contrasting the findings with the emerging discourses of Critical University Studies (CUS). With a declared position (Williams, 2012a) in opposition to higher education public policy reforms, CUS is considered as a set of academic discursive practices that are distinct from the more nuanced balance of oppositional discourses evidenced through the participant responses here.

The study takes ideological domination in the field of the media as a point of departure, concentrating on current affairs as one of the most keenly debated issues in the field of mass media since the emergence of news agencies and up to the present age of satellite television channels. The study deals in particular with monopolies of news coverage by the major news agencies, including Reuters, Associated Press (AP), United Press International (UP), and Agence France Press (AFP). The study focuses on the cultural dimensions of news stories and the controversies over their content which have spurred regional and international efforts to establish alternatives to the one-way flow of news and information from core countries to the rest of the world. The study also focuses on American domination in the field of news and the establishment of CNN, which has itself become a symbol of American influence as well as a significant influence on the live news coverage of events. The impact of CNN has also triggered many reactions, including efforts in various countries to compete with it in order to cover the news from perspectives within these countries. The study goes on to focus on the Arab region, which has its own characteristics but also shares many features with other peripheral countries, particularly in the field of the mass media and the reliance of Arab audiences on news sources in core countries. This study deals with various issues concerning the mass media and news coverage in the Arab region, providing a historical framework for the development of its mass media; the political atmosphere and other factors which have affected their performance. The study also examines attempts by Arab countries to work collectively in order to establish alternatives to the core countries’ news outlets. By focusing on the Arab region this study aims to examine in particular the significance of the Arab satellite news channels and their success in competing with the news outlets of core countries. The competitiveness of the Arab satellite channels is evaluated, considering Al-Jazeera as a particularly important example. The study finally focuses on Libya as an example both of an Arab county and as a representative of peripheral countries. This section of the work involves an empirical study into perception and evaluation of regional and international news. This provides ideal opportunities to assess the theoretical framework of the study with references to the features and difficulties of peripheral countries. Libya’s efforts in the field of mass media, and particularly its news outlets, are also evaluated. In addition the study examines the attitudes of the Libyan people towards domestic, regional and international news outlets and their significance in terms of news coverage. This provides a thorough understanding of the perceived weaknesses and strengths of these news outlets, and such information may help in the development of a new strategy for the Libyan mass media in order to make them more competitive.

Postfeminism is not an ideological position or coherent theoretical framework that can be applied externally to the analysis of texts. Indeed popular postfeminism – as distinguished in this thesis from academic postfeminism – is knowable only through its workings in culture, specifically in the representation of gender in “postfeminist” media texts. Therefore, this thesis does not adopt a postfeminist position or approach to analyse the source texts, but rather seeks to identify and deconstruct a postfeminist sensibility within them. This sensibility became apparent in 1990s depictions of characters such as Bridget Jones (Renée Zellweger) and Ally McBeal (Calista Flockhart); however, it prevails in texts created in the current moment and inflects their representation of women. This thesis seeks to identify the themes and characteristics of this sensibility at the site of their creation – media texts representing women – expose the reasons why they are problematic, and show that the same traits exist in the texts considered here. In so doing it seeks to demonstrate that postfeminist ideals are still informing representations of women in the media. Furthermore, it seeks to demonstrate that this postfeminist sensibility, despite being a product of 1990s postfeminism and the current post/post-post-feminist moment, inflects representations of women from different time-periods, specifically from the Second World War and immediate post-war period. Because of the media’s (and specifically television’s) central role in the formation of cultural memory, this creates a lens through which women’s history and women’s historical identities are viewed in the present day. This postfeminist lens, or sensibility (Gill 2007), is thereby dehistoricised as an aspect of essential femininity. In this way the politics of the present are cast onto the past. Through this process, the events of the past are drained of any independent meaning and repurposed/redeployed to meet the needs of the present. The centrality and ubiquity of such postfeminist visions of the past is such that postfeminist discourse has become a central component of what this thesis terms, the Historical Sensibility which informs and structures historical drama on television.

Orientador: Francisco José Praga da Silva / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Engenharia da Informação, 2012.