INTRODUÇÃO: Os Potenciais Evocados Auditivos, associados à avaliação comportamental, podem ser uma ferramenta útil no diagnóstico e no monitoramento das mudanças ocorridas no Sistema Nervoso Auditivo Central em indivíduos com Transtorno de Processamento Auditivo (Central) submetidos a Treinamento Auditivo. OBJETIVOS: Os objetivos deste estudo foram caracterizar o P300 em crianças com Transtorno de Processamento Auditivo (Central) e verificar a evolução dos achados deste potencial frente ao Treinamento Auditivo. MÉTODOS: Participaram do estudo 29 indivíduos com Transtorno de Processamento Auditivo (Central) (Grupo Estudo) e 29 indivíduos sem Transtorno de Processamento Auditivo (Central) (Grupo Controle) com idades entre oito e 16 anos. Todos os indivíduos foram submetidos à avaliação inicial do processamento auditivo (central) e a uma primeira gravação do P300. O Grupo Estudo foi submetido a um programa de Treinamento Auditivo em cabina acústica durante oito sessões e, um mês após o término deste período, foi realizada nova avaliação do processamento auditivo (central) e nova gravação do P300. O Grupo Controle foi submetido a uma nova avaliação do P300 após três meses da avaliação inicial. RESULTADOS: Para os testes comportamentais, houve diferença estatisticamente significante em todos os testes quando comparados o Grupo Estudo ao Grupo Controle e nas situações pré e pós Treinamento Auditivo do Grupo Estudo. Quando comparados os dados eletrofisiológicos do Grupo Estudo antes e após o Treinamento Auditivo, houve diferença estatisticamente significante para a latência da onda P300. No Grupo Controle, não foram encontradas diferenças estatisticamente significantes nos dados eletrofisiológicos entre a avaliação inicial e a final. Na comparação entre o Grupo Estudo e o Grupo Controle antes do Treinamento Auditivo, houve diferença estatisticamente significante nas medidas de latência e de amplitude e, após o Grupo Estudo ser submetido ao Treinamento Auditivo, houve diferença estatisticamente significante apenas na amplitude entre os dois grupos. CONCLUSÕES: O P300 mostrou-se um instrumento útil no diagnóstico e no monitoramento da reabilitação de crianças com Transtorno de Processamento Auditivo (Central). / INTRODUCTION: Auditory Evoked Potentials associated to behavioral assessment may be a useful tool for the diagnosis and monitoring of changes in the Auditory Central Nervous System of individuals with (Central) Auditory Processing Disorder submitted to Auditory Training. AIM: The aims of this study were to characterize the P300 of children with (Central) Auditory Processing Disorder and to verify the improvement of this potentials findings after the Auditory Training. METHOD: 29 individuals with (Central) Auditory Processing Disorder (Study Group) and 29 individuals without (Central) Auditory Processing Disorder (Control Group), ranging in age from eight to 16 years old took part in this study. All of them underwent the initial assessment of (Central) Auditory Processing and a first recording of P300. The Study Group underwent an Auditory Training program in acoustic booth during eight sessions, and a month after the end of this period, a new (Central) Auditory Processing assessment and a new recording of P300 were performed. The Control Group underwent a new recording of P300 three months after the initial assessment. RESULTS: Significant statistical differences were found in all behavioral tests when the Study Group was compared to the Control Group, and in the pre and post Auditory Training situations of the Study Group. When the electrophysiological data of the Study Group was compared before and after the Auditory Training, there was a significant statistical difference for the latency of wave P300. In the Control Group, no significant statistical differences were found between the initial and the final assessments. Comparing the Study Group and the Control Group before the Auditory Training, it was observed a significant statistical difference concerning measures of latency and amplitude, and after the Auditory Training of the Study Group, it was observed a significant statistical difference between the two groups only regarding the amplitude. CONCLUSIONS: P300 showed to be a useful instrument for the diagnosis and monitoring the rehabilitation of children with (Central) Auditory Processing Disorder

OBJETIVO: verificar a inter-relação entre a recuperação postural e o bom ou baixo desempenho de indivíduos usuários de implante coclear (IC). MÉTODO: Foram avaliados 21 indivíduos divididos em três grupos: nove usuários de IC com bom desempenho, cinco de IC com baixo desempenho e sete controles. Todos os sujeitos foram submetidos a dois testes: Teste de Integração Sensorial (TIS) da Posturografia Dinâmica Computadorizada (PDC), com intervalo de 40 a 60 minutos entre eles, com a finalidade de observar o aprendizado de estratégias posturais no segundo teste. Os resultados obtidos foram submetidos à avaliação estatística. RESULTADOS: Os indivíduos com baixo desempenho apresentaram níveis significativamente mais baixos de aprendizado que os outros dois Grupos em C4, C5, C6 e IE. CONCLUSÂO: Os usuários de IC com bom desempenho mostraram melhor índice de recuperação postural quando comparados àqueles de IC com baixo desempenho / OBJECTIVE: To test the inter-relationship between postural recovery and good or poor performance of individuals using cochlear implant (CI). METHODS: We studied 21 subjects divided into three groups: nine cochlear implant users with good performance, 5 CI users with poor performance and 7 controls. All subjects underwent two tests in Sensory Integration Test (SOT) of computerized dynamic posturography (CDP) with an interval of 40 to 60 minutes between them, in order to observe the learning of postural strategies in the second test. The results were submitted to statistical evaluation. RESULTS: Individuals with poor performance had significantly lower difference between the results of the second and the first test than the other two groups at C4, C5, C6 and composite. CONCLUSION: CI users with good performance had better postural recovery rate when compared to the cochlear implant users with poor performance

Les interfaces cerveau-machine (ICM) permettent de contrôler une machine directement à partir de l'activité cérébrale. Le P300-Speller, en particulier, pourrait offrir à des patients complètement paralysés, la possibilité de communiquer sans l'aide de la parole ou du geste. Nous avons cherché à améliorer cette communication en étudiant la coadaptation entre cerveau et machine. Nous avons d'abord montré que l'adaptation d'un utilisateur peut être partiellement perçue, en temps-réel, à travers les modulations de sa réponse électrophysiologique aux feedbacks de la machine. Nous avons ensuite proposé, testé et évalué les effets sur l'utilisateur de plusieurs approches permettant d'améliorer l'interaction, notamment : la correction automatique des erreurs, grâce à la reconnaissance en temps-réel des réponses aux feedbacks ; une stimulation dynamique permettant de diminuer le risque d'erreur tout en réduisant l'inconfort lié aux stimulations ; un processus automatique de décision adaptative, en fonction de l'état de vigilance du sujet. Nos résultats montrent la présence de réponses aux feedbacks spécifiques des erreurs et modulées par l'attention ainsi que par la surprise du sujet face au résultat de l'interaction. Par ailleurs, si l'efficacité de la correction automatique est variable d'un sujet à l'autre, le nouveau mode de stimulation comme la décision adaptative apparaissent comme très avantageux et leur utilisation a un effet positif sur la motivation. Dans la perspective d'études cliniques pour évaluer l'utilité des ICM pour la communication, ces travaux soulignent et quantifient l'intérêt de développer des interfaces capables de s'adapter à chaque utilisateur / Brain-computer interfaces (BCI) aim at enabling the brain to directly control an artificial device. In particular, the P300-Speller could offer patients who cannot speak and neither move, to communicate again. This work consisted in improving this communication by implementing and studying a coadaptation between the brain and the machine. First, on the user side, we showed that adaptation is reflected in real-time by modulations of the electrophysiological responses to the feedbacks from the machine. Then, on the computer side, we proposed, tested and evaluated the effect on the user, of several approaches that endow the machine with adaptive behavior, namely: Automatic correction of errors, based on real-time recognition of feedback responses; Dynamic stimulation to increase spelling accuracy as well as to reduce the discomfort associated with the traditional row/column stimulation paradigm; Adaptive decision making for optimal stopping, depending on the attentional state of the user. Our results show the presence of feedback responses which are error specific and modulated by attention as well as user's surprise with respect to the outcome of the interaction. Besides, while the interest of automatic correction is highly subject-dependant, the new stimulation mode and the adaptive decision method proved clearly beneficial and their use had a significant positive impact on subject's motivation. In the perspective of clinical studies to assess the usefulness of ICM for communication, this work highlights and quantifies the importance of developing adaptive interfaces that are tailored to each every individual

Introdução: O P300 é um potencial evocado auditivo que ocorre aproximadamente 300 milissegundos (ms) após a apresentação do estímulo. Geralmente, é evocado ao se utilizar o paradigma tradicional, no qual são apresentados dois estímulos perceptivelmente diferentes: um estímulo frequente (85%) e um estímulo raro (15%). Os indivíduos são orientados a indicar, de alguma maneira, a quantidade de estímulos raros que perceberam durante a realização do exame. O P300 é considerado um potencial endógeno, pois ocorre devido a um evento cognitivo (decisão da ocorrência do estímulo raro). Contudo, alguns estudos mostraram que as características acústicas do estímulo podem interferir no potencial, evidenciando uma contribuição exógena ou sensorial para evocar a resposta. Essas implicações endógenas e exógenas para evocar o P300 ainda não foram totalmente definidas. A avaliação desses aspectos específicos pode ajudar a identificar os geradores desse potencial. Objetivo: verificar o efeito da contribuição endógena e exógena para obtenção do P300, utilizando paradigma tradicional e o paradigma de omissão. Métodos: participaram desse estudo 30 indivíduos jovens adultos, normo-ouvintes sem alteração neurológica ou psiquiátrica aparente. Os indivíduos foram avaliados com o paradigma tradicional (estímulo frequente: 800 Hz; estímulo raro 1200 Hz) e com o paradigma de omissão (estímulo frequente: 800 Hz; estímulo raro: ausência de som). Cada orelha foi avaliada separadamente por ambos os paradigmas na intensidade de 80 dBNPS. Foram apresentados 300 estímulos (45 raros) em cada estimulação. Para a obtenção do P300, foi utilizado o equipamento \"Neuroscan Stim2\" com 12 eletrodos ativos no escalpo, colocados nas seguintes posições: FPz, F4, Fz, F3, C4, Cz, C3, CP6, CP5, P4, Pz e P3. O maior pico após o complexo N1-P2-N2 foi considerado como P300. A amplitude foi medida considerando a linha de base do intervalo pré-estímulo, enquanto a latência foi medida no maior pico positivo. Nesse estudo, foi utilizada a Análise de Variância (ANOVA) com medidas repetidas. Foram realizados mapas topográficos do escalpo para ambas as estimulações. Resultados: para todos os 12 eletrodos analisados nesse estudo, a média da latência em milissegundos foi significantemente menor, e a média da amplitude foi significantemente maior para o paradigma tradicional quando comparado ao paradigma de omissão. Além disso, a morfologia da onda foi mais bem definida para o paradigma tradicional. Os mapas topográficos para ambos os paradigmas mostraram uma ativação mais generalizada e mais positiva na região centro-parietal, indicando que as mesmas áreas foram ativadas em ambos os paradigmas. Conclusão: o presente estudo demonstrou que o estímulo acústico, ausente no paradigma de omissão, influencia a latência, amplitude e morfologia da onda, evidenciando uma contribuição exógena/sensorial para obtenção do potencial / Introduction: The P300 is an auditory evoked potential that occurs approximately 300 ms after the stimulus presentation. It is usually elicited by a traditional paradigm in which two perceptually different stimuli are randomly presented with different proportions - one is frequent (85%) and the other is rare (15%). The tested individual is instructed to somehow indicate the amount of rare stimuli heard. According to the literature, P300 is considered an endogenous potential since it occurs in response to a cognitive event (i.e. decision of the occurrence or not of the rare stimulus). However, few studies have shown that the acoustic characteristics of the stimuli might influence the potential, evidencing some exogenous or sensorial contribution to the response formation. The implications that endogenous and exogenous contributions have to eliciting the P300 are not fully understood yet. The assessment of their specific roles would help to identify the P300 generators. Objective: To verify the effects of the endogenous and exogenous contribution to obtain/elicit the P300 using both the traditional and the omission paradigms. Methods: Thirty normal hearing young adults, without known neurological or psychiatric disorders, participated in this study. The individuals were assessed using P300 elicited by the traditional paradigm (frequent stimulus: 800 Hz; rare stimulus: 1200Hz) and by the omission paradigm (frequent stimulus: 800 Hz; rare stimulus: absence of sound). Both paradigms were presented to one ear at a time, at 80dBSPL, and 300 stimuli (45 rare) were presented in each stimulation. The \"Neuroscan Stim2\" was used to obtain the P300 with 12 active electrodes fixed at the following positions: FPz, F4, Fz, F3, C4, Cz, C3, CP6, CP5, P4, Pz e P3. The largest peak after the N1-P2-N2 complex was considered the P300. Its amplitude was measured considering the pre-stimulation response baseline, while its latency was measured at the most positive peak. The Analysis of Variance (ANOVA) with repeated measures was used in this study. Topographic maps from the scalp to both paradigms were also analyzed. Results: To all 12 electrodes positions analyzed in this study, the mean latency (ms) was significantly earlier and the mean amplitude (?V) was significantly larger for the traditional paradigm compared to the omission paradigm. Also, better wave morphology was obtained for the traditional paradigm. The topographic maps to both paradigms has shown more generalized and positive activation at the centro-parietal region, indicating that the same brain areas were involved in both paradigms. Conclusion: The current study has demonstrated that the acoustic stimulus, absent on the omission paradigm, have an impact on the wave formation in respect to its latency, amplitude and morphology, evidencing the influence of sensorial information to the P300

Malgré des développements récents dans la conception des casques électroencéphalographiques (EEG) et dans l'analyse du signal cérébrale, les interfaces cerveau-machine (ICM) sont toujours restreintes au contexte de la recherche scientifique. Toutefois, les ICM gagneraient à intégrer la réalité virtuelle (VR) car elles diminuent la distance entre l'utilisateur et son avatar en remplaçant les commandes mécaniques, et donc améliorent le sentiment d'immersion. De plus, les ICM fournissent également des informations sur l'état mental de l'utilisateur comme sa concentration, son attention ou ses points d'intérêts dans l'environnement virtuel. Dans cette thèse, nous étudions l'interaction entre ICM et VR, qui constituent une interface homme-machine dont les applications nous semblent prometteuses pour le grand public, particulièrement dans le domaine du divertissement. Nous nous concentrons sur l'utilisation d’une ICM basée sur l'EEG et sur une stimulation visuelle occasionnelle, autrement-dit une ICM basée sur la détection du P300, un potentiel évoqué positif apparaissant dans l’EEG 250 à 600 ms après l’apparition d’un stimulus. Nous étudions l’usage de cette ICM pour interagir avec un environnement simulé grâce à un casque de VR mobile utilisant un smartphone ordinaire, c’est-à-dire un matériel de VR approprié pour une utilisation grand public.Toutefois, l’intégration des ICM dans la VR pour le grand public rencontre aujourd’hui des défis d’ordre technique, expérimental et conceptuel. En effet, l’utilisation d’un matériel mobile pose des contraintes techniques considérables, et une telle technologie n’a pas encore fait l’objet d’une validation. Les facteurs influençant la performance des ICM en VR par rapport à une utilisation sur PC restent flous. Également, les caractéristiques physiologiques de la réponse du cerveau à des stimuli en VR par rapport aux mêmes stimuli présentés sous PC sont inconnues. Finalement, les ICM et la VR admettent des limites considérables, parfois incompatibles. Par exemple, l’utilisateur interagit avec la VR en bougeant, ce qui perturbe le signal EEG et diminue la performance de l’ICM. Il y a donc une nécessité d’adapter le design de l’application pour une technologie mixte ICM+VR.Dans ce travail, nous présentons une contribution dans chacun de ces domaines : une réalisation technique vers une ICM grand public en VR ; une analyse expérimentale de sa performance et une analyse des différences physiologies produites par des stimuli présentés dans un casque de VR par rapport aux mêmes stimuli sous PC - analyses menées à bien grâce à deux campagnes expérimentales portant sur 33 sujets ; une synthèse des recommandations pour un design adapté à la fois aux ICM et à la VR. / In spite of ongoing developments in the conception of electroencephalographic (EEG) headsets and brain signal analysis, the actual use of an EEG-based brain-computer interfaces (BCI) is still restricted to research settings. On the other hand, BCI technology candidates as a good complement to virtual reality as it may diminish the distance between the user and his/her avatar. A BCI can accomplish this by circumventing the usual muscular pathway between the brain and the machine, thus enhancing the immersion feeling in VR applications. Moreover, a BCI provides valuable information on the mental state of the user, such as concentration and attention for the task at hand and for the virtual objects of interest. In this thesis, we study the coupling of BCI and VR technology, a human-machine interface that is potentially ubiquitous, in particular for gaming. We focus on the use of EEG-based BCI with occasional visual stimulation, i.e., BCIs based on the detection of the P300, a positive evoked potential appearing in the EEG 250 to 600 ms after the presentation of a stimulus. We investigate the use of such a BCI to interact with VR environments obtained using a mobile head-mounted display based on an ordinary smartphone, material suiting well the general public.The fusion of BCI technology with VR faces technical, experimental and conceptual limitations. Indeed, the integration of BCI with a mobile head-mounted display is technically burdensome and has not been fully validated. The factors impacting the performance of the BCI in VR remains still unknown. Also, unknown are the physiological characteristics of the brain responses to VR stimuli as compared to the same stimuli displayed on a PC screen. Finally, both BCI and VR technologies are limited, and these limitations sometimes appears contradictory. For example, the EEG is perturbed by the user’s movements while s/he is interacting with the virtual environment, but this movement may be an essential aspect of the VR experience. Thus, it is necessary to operate a synthesis of the existing design recommendations for BCI and VR technologies from the perspective of a mixed BCI+VR application.In this work, we presents three contributions: a technical implementation of a BCI+VR system, paving the way for a general public use; an analysis of its performance and an analysis of the physiological differences produced by VR stimuli as compared to the same stimuli on a PC by means of two experimental campaigns carried out on 33 subjects; a synthesis of the recommendations to adapt the application design to BCI and VR.

This thesis examines the widespread use of bestial imagery in satirical verse, prose and prints published between 1789 – 1820, through a study of Shelley, Spence, Gillray, Gifford, Robinson, Catherine Ann Dorset, Thelwall, Eaton, and Wolcot. The thesis asks why these writers and printers used animal metaphors so frequently, but moreover, what impact the use of this imagery had on the political landscape of satire in the period. Recent criticism has focussed on the historical and political contexts of Romantic-era satire, and this thesis follows that criticism with an historicist methodology, combining literary, historical and political approaches. Furthermore, the thesis analyses verse, prose and pictorial satires as contributing to the same political discourse and as doing so in closely related cultural arenas. This thesis claims originality on the basis that not only the use of animal imagery has a significant impact on how both contemporary and modern readers interpret its political meanings and contexts, but also that this is an argument that has not yet been posited by other critics. In addition, this thesis argues that through bestial metaphors, satirical writers and artists create a community wherein imagery is exchanged, developed and manipulated, and that this practice of cultural exchange significantly shapes those satires’ historical contexts. Each of the thesis’ five chapters focuses on a major satiric animal metaphor, whereby close readings of satires are offered alongside wider political and historical contexts. Consequently, this thesis provides a map of the most common satiric animal metaphors and their concomitant politics, and in doing so creates a new critical framework in which the growing interest in Romantic- period satire can be further developed.

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

Following the terrorist attacks on America on 11 September 2001, the New Labour government enacted an unprecedented amount of terrorism legislation in the form of the Anti-Terrorism, Crime and Security Act 2001, the Prevention of Terrorism Act 2005, the Terrorism Act 2006, and finally the Counter-Terrorism Act 2008. Whilst the government viewed these terrorism laws as vital to national security, many of the measures contained in these acts, such as control orders and increased detentions, provoked intense debates over civil liberties. Much research on media-state relations in the context of responses to 9/11 have found evidence to support the elite-driven paradigm, whereby the media have been shown to fail in their adversarial ‘watchdog’ role by acting as ‘faithful servants’ (Wolfsfeld, 1997) to the political agenda. This research tested these assumptions by examining the media framing of the UK government’s legislative responses to terrorism post-9/11. In so doing, it analyses the relationship between the media and the New Labour government in the context of the policymaking process. To date, longitudinal studies that map the UK media-state nexus within the context of terrorism policymaking are lacking. This thesis therefore, addresses the lacunae in the scholarship. In terms of its theoretical framework, this thesis tests three competing models of media performance (elite-driven, oppositional and independent) on British press reporting of the parliamentary debates (Robinson et al., 2010). Methodologically, it takes an inductive approach to analysing the framing of the debates, and draws on material gleaned from interviews with four former home secretaries. The findings reveal that of the three meta-frames (national security, civil liberties and party politics), the politics frame dominated across all four case studies. Although government sources dominated the debates, the evidence suggests that they had limited influence over the news agenda, which runs contra to the elite-driven (redefined here as government-driven) hypothesis. Instead, at an aggregate level, the evidence lends greater support for the independent model. There is also evidence that some sections of the press did subject the legislation to more robust scrutiny, and thus, to some degree, fulfilled their role as political watchdogs, which supports the oppositional thesis.

Although skeletal myogenesis is largely controlled by myogenic regulatory factors, epigenetic modifications have recently emerged as an essential regulatory mechanism of gene expression. Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic factors over distal enhancer regions. Understanding the mechanistic action of active or poised enhancers is therefore, imperative for the control of stem cell differentiation. Based on the genome-wide co-occurrence of different epigenetic marks in proliferating myoblasts, we have generated a chromatin state model to profile differentiation- and rexinoid-responsive histone acetylation in early myoblast differentiation. Here, we delineate the functional mode of transcription regulators during early myogenic differentiation using genome-wide chromatin state association. We define a role of transcriptional coactivator p300, when recruited by muscle master regulator MyoD, in the establishment and regulation of myogenic loci at the onset of myoblast differentiation. In addition, we reveal an enrichment of loci-specific histone acetylation at p300 associated active or poised enhancers, mainly when enlisted by MyoD. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor (RXR), promotes the specification and differentiation of skeletal muscle lineage. Hence, we investigated the genome-wide impact of rexinoids on myogenic differentiation and uncovered a new mechanism of rexinoid action, which is mediated by the nuclear receptor and largely reconciled through direct regulation of MyoD gene expression. In addition, we determined rexinoid-responsive residue-specific histone acetylation at a distinct chromatin state associated with MyoD and myogenin. Finally, through ChIP-seq and RNA-seq analyses, we have identified dystroglycan (Dag1) as a differentiation-dependent and a rexinoid-responsive model target, and we revealed a possible co-regulation of Dag1 by p300 and MyoD accompanied by enrichment of loci-specific histone acetylation. Taken together, we provide novel molecular insights into the regulation of myogenic enhancers by p300 in concert with MyoD. Furthermore, we provide novel mechanistic perceptions into the interplay between RXR signaling and chromatin states pertinent to myogenic programs in early myoblast differentiation. Our studies present a valuable insight for driving condition-specific chromatin state or enhancers pharmacologically to treat muscle-related diseases and for the identification of additional myogenic targets and molecular interactions for therapeutic development.

Objective: P300/CBP Associated Factor (PCAF) is a histone acetyltransferase, and has been reported to interact with nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and to stimulate cyclooxygenase-2 (COX-2) transcriptional activation. The aim of this study was to determine the role of PCAF in chronic pain modulation. / Method: In an in vitro experiment, PCAF small-interfering RNA (siRNA) was used to knock down PCAF. Interleukin-1 β (IL1β) was applied as COX-2 inducer in SK-N-SH neuroblastoma cells. Luciferase assay and chromatin immunoprecipitation (ChIP) were performed regarding COX-2 promoter region. / In an in vivo experiment, PCAF was examined for its distribution in dorsal horn of Spraque-Dawley rats. COX-2 level in the spinal cord was determined after inhibition of PCAF in rats with Complete Freund's Adjuvant (CFA)-induced pain. ChIP was also performed. / Finally, we tested whether genetic variations in the PCAF gene affected the risk of chronic pain in a gene association study of 267 surgical patients. The associations of pain with genotypes (58 single nucleotide polymorphisms, SNPs)/haplotypes were analyzed by χ² and Fisher exact tests. / Results: Knock-down of PCAF reduced COX-2 level and NF-κB activity. PCAF and acetylated histone 3 lysine 14 (H3K14) were enriched at COX-2 promoter when IL1β was applied. / PCAF was expressed in neurons at superficial layers of rat dorsal horn. In the in vivo experiment, COX-2 was reduced with the inhibition of PCAF in CFA rats. PCAF was enhanced at COX-2 promoter when CFA was injected. Anacardic acid and PCAF siRNA significantly alleviated thermal nociception and mechanical allodynia. / In the gene association study, 6 SNPs and 5 haplotypes were significantly associated with higher risk of severe chronic postsurgical pain. Multivariable analysis showed that patients with a SNP rs6763504 had a higher risk of developing severe chronic postsurgical pain (p = 0.001). / Conclusion: PCAF regulated COX-2 transcription and reduction or inhibition in PCAF resulted in a decrease in COX-2 and less chronic inflammatory pain. Genetic variations in the PCAF gene increased risk of severe chronic post-surgical pain in patients. / 實驗目的：P300/CBP相關蛋白（PCAF）是一種組蛋白乙酰化轉移酶。這種蛋白已被報道可以和核因子活化B細胞κ輕鏈增強子(NF-κB)相互作用，以及增進環氧合酶-2（COX-2）的轉錄激活。本實驗的目的在於研究PCAF在疼痛調節中的作用。 / 實驗方法：在細胞實驗中，我們使用了小干擾RNA（siRNA）來降低PCAF的含量。同時我們使用了白細胞介素-1β（IL1β）來作為SK-N-SH神經母細胞瘤細胞中COX-2的誘導劑。我們使用了熒光素酶試劑和染色質免疫沉澱來研究COX-2啟動子區域。 / 在體內實驗中，我們檢測了PCAF在大鼠脊椎背角部位的分佈。在弗氏完全佐劑（CFA）致痛的大鼠模型中，我們在PCAF抑制的情況下檢測脊髓中COX-2的水平。我們還進行了染色質免疫沉澱。 / 最後，在招募了267位手術患者的基因關聯試驗中，我們對PCAF基因中的基因變異對慢性疼痛風險的影響進行了分析。我們運用卡方檢驗和費雪精確性檢驗對疼痛與基因型（58個單核苷酸多態性）和單倍型的關係進行分析。 / 實驗結果：減少的PCAF降低了COX-2的水平以及NF-κB的活性。當添加了IL1β時PCAF和乙酰化第三組蛋白14號賴胺酸（H3K14）在COX-2啟動子處富集。 / PCAF在大鼠脊椎背角部位的淺表層（第一層和第二層）的神經細胞里表達。在動物實驗中，注射了CFA的大鼠顯示COX-2會隨著PCAF的抑制而下降。大鼠注射了CFA后PCAF在COX-2啟動子處有所增加。漆樹酸和PCAF siRNA顯著地減輕了熱痛和機械痛提高了機械痛閾值。 / 在該基因關聯試驗中，我們鑒定出六個單核苷酸多態性和五種單倍型與較高風險的嚴重術後慢性痛有顯著的相關性。多元回歸分析表明在PCAF基因上具有rs6763504遺傳變異的病人在術後發展嚴重慢性痛的幾率會較高(p = 0.001)。 / 結論：PCAF調節COX-2的轉錄，而且PCAF的減少或者抑制導致了COX-2的降低同時慢性炎症痛的減少。PCAF基因上的遺傳變異提高了術後病人嚴重慢性痛的風險。 / Meng, Zhaoyu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 117-134). / Abstracts also in Chinese. / Title from PDF title page (viewed on 30, December, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.