Tesis sobre el tema "Pain mapping"

INTRODUÇÃO: Sabe-se que a doença periodontal é a doença infecciosa crônica mais prevalente na população adulta, acometendo 1/5 da população em fase ativa de trabalho e causadora de dor. As citocinas e demais substâncias moduladoras da inflamação que promovem e perpetuam a doença periodontal interagem e agravam outras doenças como o diabetes mellitus, aterosclerose e doenças autoimunes. O periodonto, com suas aferências proprioceptivas especializadas, desempenha importante papel de regulação dos movimentos da mastigação. Apesar da região orofacial ter uma ampla área de representação no córtex cerebral não se sabem os efeitos de uma inflamação crônica periodontal nesta representação. Ansiedade e estresse são conhecidos fatores correlacionados à doença periodontal e moduladores de condições dolorosas. Assim, são objetivos deste estudo a avaliação da sensibilidade mecânica em vibrissas, avaliação da ansiedade e o mapeamento do córtex motor de ratos com doença periodontal de 14 e 28 dias de evolução. MÉTODOS: Foram utilizados ratos Wistar machos pesando inicialmente entre 140 e 180 gramas, divididos em 3 grupos principais: grupo controle, grupo sham e grupo de estudo, em que a doença periodontal foi induzida por amarria no primeiro molar inferior direito. Os animais foram avaliados com 14 e 28 dias de doença, sendo a sensibilidade mecânica aferida por filamentos de Von Frey e a ansiedade avaliada por meio do labirinto em cruz elevado. O mapeamento do córtex motor foi realizado por estimulação elétrica epidural de um a dez volts. RESULTADOS: Ambos os períodos de evolução da doença causaram alterações condizentes com doença periodontal. Não houve diferenças no ganho de peso dos animais independente do grupo ao longo do estudo. Nos animais com 28 dias de doença houve maior nocicepção no lado doente com diferença estatística (p=0,042). Os animais do grupo de estudo 14 dias demonstraram mais comportamentos sugestivos de ansiedade nos parâmetros de congelamento (p=0,031), entradas nas extremidades dos braços abertos (p=0,048) e esticamento nos braços abertos (p=0,047) do labirinto em cruz elevado do que os grupos sham e controle. Os animais do grupo de estudo de 28 dias apresentaram maior comportamento de dor e medo observado através da presença do congelamento (p=0,016). O mapeamento do córtex motor evidenciou áreas representativas da mandíbula sobrepostas à área das vibrissas. Foi observada uma expansão da área da mandíbula no grupo da doença periodontal de 14 dias (p=0,038). CONCLUSÃO: A doença periodontal com 14 dias de evolução causou um aumento da resposta motora ipsilateral da mandíbula-mais-vibrissas e alterações de comportamento sugestivas de ansiedade
BACKGROUND: Periodontal disease is the most prevalent chronical infectious disease in adults, affecting 1/5 of people in active phase of labor and causing pain. Cytokines and substances that modulate inflammation promotes and perpetuate de periodontal disease, interacting and worsening other conditions such as diabetes mellitus, aterosclerosis and autoimmune diseases. The periodontium has specialized proprioceptive afferents and plays a role in the regulation of masticatory movements. Despite the wide brain cortical representation area of the orofacial structures, the periodontium has not been described in the literature and the effects of a chronical inflammation in its representation has not been clarified. Anxiety and stress are factors correlated to periodontal disease and modulators of pain. The aim of this study was evaluate vibrissae nociception through mechanical response, anxiety and the motor cortex mapping in rats with periodontal disease after 14 or 28 days of evolution. METHODS: Male Wistar rats (initial weight 140-180 grams) divided into 3 main groups: controls, sham and periodontal disease induced by placement of a cotton ligature in the mandibular right first molar tooth. The evaluations took place after 14 or 28 days of disease. Mechanical response was evaluated by von Frey filaments and anxiety was evaluated through the elevated plus maze. Epidural electrical stimulation (1 to 10 volts) was the method used for the cortical motor mapping. RESULTS: Both evolution periods caused clinical outcomes consistent to periodontal disease. There was no difference in the weight gain of the animals, whatever the group during the study. The animals with 28 days appeared to have a higher nociception in the side affected, with statistical difference (p=0.042). Animals with the disease evolution through 14 days showed more anxious behavior seen by freezing (p=0.031), entries in the extremities of open arms (p=0.048) and stretching in open arms (p=0.047) than the sham and control groups, in the elevated plus maze test. The 28 day disease evolution group showed more pain and fear behavior, seen by freezing (p=0.016). The cortical motor mapping showed an overlapping of jaw and vibrissae areas. There was an expansion of the mandibular area in the 14-day disease group (p=0.038). CONCLUSION: at 14-days, PD led to an expansion of the mandibular-plus-vibrissae motor cortical representation ipsilateral to the disease and behaviors suggestive of anxiety

La richesse des réponses aux requêtes posées aux systèmes pair-à-pair de gestion de données (PDMS) dépend du nombre de mappings entre les ontologies des différents pairs. Augmenter ce nombre permet d'améliorer les réponses aux requêtes. C'est à ce problème que nous nous intéressons dans cette thèse. Il s'agit de découvrir des liens sémantiques entre les ontologies des différents pairs du système. Ce problème, connu sous le nom d'alignement d'ontologies, est spécifique dans les systèmes pair-à-pair, au sein desquels les ontologies ne sont pas a priori complètement connues, le nombre d'ontologies à aligner est très important et l'alignement doit s'opérer en l'absence de contrôle centralisé. Nous proposons des techniques semi-automatiques pour identifier : (1) des raccourcis de mappings correspondant à une composition de mappings existants et (2) des mappings nouveaux ne pouvant être inférés en l'état actuel du système. Ces techniques sont basées sur l'exploitation des mécanismes de raisonnement des PDMS et sur des critères de filtrage restreignant le nombre de couples d'éléments à aligner. Les raccourcis de mappings sont identifiés à partir de l'analyse de la trace des requêtes posées par les utilisateurs, mais également après application de critères estimant leur utilité. La découverte de nouveaux mappings consiste à identifier les éléments de l'ontologie d'un pair donné qui permettent d'identifier des mises en correspondance jugées intéressantes puis à sélectionner les éléments de pairs distants avec lesquels il est pertinent de les aligner. Les techniques d'alignement proposées sont soit des adaptations de techniques existantes soit des techniques innovantes tirant parti des spécificités de notre cadre de travail

La richesse des réponses aux requêtes posées aux systèmes pair-à-pair de gestion de données (PDMS) dépend du nombre de mappings entre les ontologies des différents pairs. Augmenter ce nombre permet d'améliorer les réponses aux requêtes. C'est à ce problème que nous nous intéressons dans cette thèse. Il s'agit de découvrir des liens sémantiques entre les ontologies des différents pairs du système. Ce problème, connu sous le nom d'alignement d'ontologies, est spécifique dans les systèmes pair-à-pair, au sein desquels les ontologies ne sont pas a priori complètement connues, le nombre d'ontologies à aligner est très important et l'alignement doit s'opérer en l'absence de contrôle centralisé. Nous proposons des techniques semi-automatiques pour identifier : (1) des raccourcis de mappings correspondant à une composition de mappings existants et (2) des mappings nouveaux ne pouvant être inférés en l'état actuel du système. Ces techniques sont basées sur l'exploitation des mécanismes de raisonnement des PDMS et sur des critères de filtrage restreignant le nombre de couples d'éléments à aligner. Les raccourcis de mappings sont identifiés à partir de l'analyse de la trace des requêtes posées par les utilisateurs, mais également après application de critères estimant leur utilité. La découverte de nouveaux mappings consiste à identifier les éléments de l'ontologie d'un pair donné jugés intéressants puis à sélectionner les éléments de pairs distants avec lesquels il est pertinent de les aligner. Les techniques d'alignement proposées sont soit des adaptations de techniques existantes soit des techniques innovantes tirant parti des spécificités de notre cadre de travail
The richness of answers to queries asked to peer to peer data management systems (PDMS) depends on the number of mappings between ontologies of different peers. Increasing this number can improve responses to queries. This is the problem considered in this thesis. We aims at discovering semantic links between ontologies of different peers. This problem, known as ontology alignment, is specific in peer-to-peer systems in which ontologies are not completely known a priori, the number of ontologies to align is very large and alignment should be done without any centralized control. We propose semi-automatic techniques for identifying: (1) mapping shortcut corresponding to a composition of existing mappings and (2) new mappings which can not be inferred in the current state of the system. These techniques are based on the use of reasoning mechanisms of PDMS and filtering criteria restricting the number of pairs of elements to align. Mapping shortcuts are identified from the analysis of trace of queries asked by users, but also after application of criteria considering their usefulness. The discovery of new mappings consists in identifying the elements of the ontology of a given peer that are judged interesting and then in selecting the elements from distant peer with which it is relevant to align them. The proposed alignment techniques are either adaptations of existing technology or innovative techniques exploiting the specificities of our framework

La stimulation du cortex moteur (SCM) est une technique neurochirurgicale utilisée chez l'Homme comme traitement de dernier recours pour les douleurs neuropathiques rebelles. Elle a été développée sur des bases empiriques. Ce travail vise à une meilleure compréhension des mécanismes d'action de la SCM qui restent incomplètement élucidés à ce jour. L'objectif de cette thèse est d'étudier les effets électrophysiologiques de la SCM au niveau thalamique, chez un modèle de chat. La première partie de cette étude a consisté à établir une cartographie stéréotaxique du cortex moteur (CM) de cet animal, inexistante dans la littérature. À partir de cette cartographie, nous avons pu établir et valider un modèle de SCM chez cet animal, implanté de façon mini-invasive. La deuxième partie de ce travail a consisté à recueillir et analyser les changements électrophysiologiques de l'activité extracellulaire unitaire des cellules du noyau ventro-postéro-latéral (VPL) du thalamus, induits par différents protocoles de SCM. Nos résultats montrent une modulation de l'activité des cellules du VPL par la SCM, qui varie en fonction de la nature nociceptive ou non de la cellule thalamique. La SCM augmente l'activité des cellules non nociceptives et diminue celle des cellules nociceptives. Pour une cellule donnée, l'effet observé est indépendant de la correspondance somatotopique entre la région du CM stimulée et la localisation sur le corps du champ récepteur de la cellule enregistrée. Ce travail a ainsi permis de montrer l'existence d'une neuro-modulation différentielle du VPL par la SCM en fonction de la nature de la cellule thalamique
Motor cortex stimulation (MCS) is a neurosurgical technique developed on empirical basis and currently used as last solution for patients suffering from refractory neuropathic pain. The present work is a new attempt among other contemporary studies aiming to understand the mechanisms of action of MCS, which remain incompletely elucidated at that time. The main objective of this thesis is to study the electrophysiological effect of MCS at the thalamic level, in a cat model. The first part of this work aims to establish the stereotactic somatotopic map of the cat motor cortex (MC), not available so far in the literature. Based on this mapping, we created and validated a cat model of MCS, using a mini-invasive electrode implantation. The second part of this study included a recording and analysis of the potential changes of the unitary extracellular activity of cells located in the thalamic ventro-postero-lateral (VPL) nucleus, induced by different MCS protocols. Our results indicate a modulation of the VPL cells activity after MCS, depending on the nociceptive or non-nociceptive nature of the recorded thalamic cell. MCS increases the activity of non-nociceptive cells and decreases that of nociceptive cells. For a given cell the matching between the somatotopy of the MC stimulated region and the receptive field localization of the recorded thalamic cell is not a prerequisite for obtaining such a modulation. In conclusion, the present work has proven a neuro-modulatory differential effect of MCS on nociceptive and non-nociceptive cells in the thalamic VPL nucleus

Thesis (Ph. D.)--University of Oregon, 2002.
Typescript. Includes vita and abstract. Includes bibliographical references (leaves 221-234). Also available for download via the World Wide Web; free to University of Oregon users.

L'analyse des propriétés statistiques de la distribution de la matière dans le cosmos (Grandes Structures, LSS or Large Scale Structure) est l'une des principales sondes cosmologiques qui permettent l'étude du modèle standard cosmologique, en particulier les paramètres caractérisant la matière noire et l'énergie noire. Les Oscillations Acoustiques Baryoniques (BAO's) sont l'une des mesures qui peuvent être extraites de l'étude de la distribution de matière à grande échelle (LSS).L'observation de la distribution cosmique de la matière à partir de l'émission à 21 cm de l'hydrogène atomique neutre (HI) est une nouvelle méthode, complémentaire des relevés optiques pour cartographier la distribution de la matière dans le cosmos. La méthode de cartographie d'intensité (Intensity Mapping) a été proposée depuis moins d'une dizaine d'années comme une méthode efficace pour cartographier en trois dimensions l'émission radio à 21 cm. Elle n'implique en particulier pas la détection des objets individuels (galaxies), et peut donc être effectué avec des instruments plus modestes en taille que ceux comme SKA ou FAST qui sont conçus pour détecter les galaxies à 21 cm à des distances cosmologiques. Des interféromètres radio utilisant un ensemble de réflecteurs cylindriques ou paraboliques fixes, observant le ciel en mode transit sont adaptés à la cartographie d'intensité. Le mode d'observation spécifique de ce type de radio télescope en cartographie d'intensité est étudié dans le cadre de ce travail de thèse. On montre en particulier qu'une méthode spécifique de reconstruction des cartes du ciel à partir des visibilités peut être appliquée aux observations de ces interféromètres fonctionnant en mode transit. Cette méthode correspond à la décomposition en modes m des harmoniques sphériques et est très performante pour la reconstruction de grandes zones du ciel observées en mode transit. Un code de reconstruction fondé sur ce principe a été développé, ainsi que différents critères de comparaison des performances instrumentales, comme le lobe d'antenne synthétisé, le spectre de bruit sur les cartes reconstruites et la réponse globale de l'instrument dans le plan (l,m) des harmoniques sphériques. La méthode a été appliquée à différentes configurations des interféromètres composés de réflecteurs paraboliques ou cylindriques dans le cadre des projets PAON-4 et Tianlai. Outre l'optimisation des configurations des interféromètres Tianlai et PAON-4, le travail présenté inclut une première application de la méthode aux données PAON-4
The analysis of the statistical properties of the distribution of matter in the cosmos (LSS or Large Scale Structure) is one of the main cosmological probes that allow the study of the cosmological standard model, in particular the parameters characterizing dark matter and dark energy. Baryonic Acoustic Oscillations (BAO's) are one of the measurements that can be extracted from the study of matter distribution in large-scale structure (LSS).The observation of the cosmic distribution of the matter from neutral atomic hydrogen (HI) 21 cm emission is a new method, complementary to the optical observation to map the distribution of matter in the cosmos. In the last decade, the Intensity Mapping method has been proposed as an effective method for mapping the 21cm radio emission in three dimensions. In particular, it does not require the detection of individual objects (galaxies), and can therefore be performed with instruments smaller in size than those such as SKA or FAST, which are designed to detect 21 cm galaxies at cosmological distances. A radio interferometer using a set of fixed cylindrical or parabolic reflectors observing the sky in transit mode are suitable instruments for intensity mapping surveys. The specific observational mode from this type of radio telescope by intensity mapping is studied in the context of this thesis. We show in particular that a specific sky maps reconstruction method from the visibilities can be applied to the observations of these interferometers operating in transit mode. This method corresponds to the m-modes decomposition of the spherical harmonics and is very efficient for the reconstruction of large sky areas observed in transit mode. A reconstruction code based on this principle has been developed, as well as different criteria for the comparison of instrumental performances, such as the synthesized antenna lobe, the noise spectrum of the reconstructed maps and the overall instrument response in the spherical harmonics (l,m) plane. The method has then been applied to different configurations of interferometers composed of parabolic or cylindrical reflectors in the PAON-4 and Tianlai projects. In addition to optimizing the Tianlai and PAON-4 interferometer configurations, the work presented here includes a first application of the method to the PAON-4 data

Thesis (Ph.D. in Human Medical Genetics) -- University of Colorado Denver, 2008.
Typescript. Includes bibliographical references (leaves 112-128). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Metoden Kundresekartläggning har använts i årtionden för att kartlägga målgruppers upplevelser, exempelvis kunders upplevelse av en organisations tjänster. I vetenskaplig litteratur saknas beskrivning av hur datainsamling och analys går till i kundresekartläggnings-projekt. För att öka förståelsen för hur metoden går till har kunskap samlats in, främst genom intervjuer med praktiker (user experience designers och tjänstedesigners) erfarna av metoden. Resultatet blev en guide fylld av tips som kan vara bra för praktiker att tänka på inför och under den här typen av projekt, samt hur man kan engagera organisationen (beställaren av kundresekartan) i projektet så att insikterna används vidare även efter leveransen av kundresekartan. I slutet av guiden finns dessutom fem exempel på kundresekartor som praktiker delat med sig av och berättar om.

This thesis is prompted by a curiosity about the popularity of the image of Peter Pan. Realising that the familiar and ubiquitous image is as much a product of consumer culture as it is the result of multimodal adaptations and reinterpretations of J. M. Barrie?s Peter Pan, this study attempts to shovel aside present-day conceptions of Peter Pan stories, so as to unearth the bedrock, to see Peter Pan as it was when it was new, back in its own time. To do so, this study goes back to the original Peter Pan texts. Picking out elements that signal the presence of certain literary modes, this thesis explores how the Peter Pan narratives engage with these modes, genres and traditions. One of the motives of the thesis is to rescue Peter Pan from ghettoization in the cosy category of “children?s literature”, and through critical attention to take it seriously as an important work in the literature of the early twentieth century. Chapter I situates Peter Pan in the pastoral tradition. Adducing William Empson?s concept of the pastoral as the process of “putting the complex into the simple”, this thesis argues that Peter Pan portrays two competing pastoral spaces and lays claim to the tradition by challenging its parameters of innocence. The chapter also invokes Bakhtin?s idea of carnival, asserting that the Peter Pan texts are “carnivalesque” in both their self-referential play with narrative and generic conventions, and with various more or less satirical and transgressive themes. Chapter II traces elements of Pan myths in the texts, and argues that the texts engage with the late-Victorian and Edwardian interest in myth by re-envisioning an avatar of Pan that would take its place amongst other literary Pans of the era, such as those of E. M. Forster, Kenneth Grahame, Elizabeth Browning, and Arthur Machen. The final chapter sets Peter Pan in the midst of a battle of modes of representation and vision, with R. L. Stevenson championing romance and Henry James politely standing for realism. The chapter argues that while the Peter Pan texts belong more to romance, they play with the boundaries of each by critiquing both modes, all the time showing up and relishing the artificiality of narration. The chapter then picks up on the sense of play, pervading Peter Pan’s engagement with every literary mode that has been discussed, and examines the social meanings and aesthetic instances of play against the backdrop of Edwardian England. Throughout the chapters, by dint of its spirit of play, Peter Pan problematizes the modern family and deconstructs the hierarchy of generations, along with the fundamental anthropological categories of childhood and adulthood, categories which were coming under scrutiny and pressure from the modernizing forces at work at the beginning of the twentieth century. With its sustained exploration of the structure of generations, Peter Pan addresses a problem of modernity in spite of its fantasy setting, and there is a case therefore for considering it under the rubric, elaborated by Nicholas Daly, of “popular modernism”.
published_or_final_version
English
Master
Master of Philosophy

Thesis (Ph. D.)--Ohio State University, 2005.
Title from first page of PDF file. Document formatted into pages; contains xv, 122 p.; also includes graphics. Includes bibliographical references (p. 117-122). Available online via OhioLINK's ETD Center

Le mélanome cutané est un cancer des cellules de la peau (mélanocytes) qui se situe, en France, au 11e rang des cancers les plus fréquents. Sa mortalité reste élevée lorsqu’il est diagnostiqué à un stade tardif. Ce cancer résulte de nombreux facteurs génétiques, environnementaux et des interactions entre ces facteurs. La susceptibilité génétique à ce cancer recouvre un large spectre de variabilité génétique, depuis des mutations rares conférant un risque élevé jusqu’à des variants fréquents conférant un risque modeste. C’est dans le cadre de l’identification de variants fréquents liés à l’apparition du mélanome et à son pronostic que se situe mon travail de thèse. À ce jour, les études d’associations pangénomiques du mélanome ont identifié des variants fréquents à effets relativement modestes qui expliquent seulement une part de la composante génétique. Les variants fonctionnels au sein des régions identifiées sont le plus souvent inconnus. Les études pangénomiques ont eu principalement recours à des analyses simple-marqueur qui peuvent manquer de puissance pour détecter des variants ayant un effet individuel faible ou interagissant avec d’autres variants. L’objectif principal de ce travail de thèse a été de proposer des stratégies d’analyse multi-marqueurs pour identifier de nouveaux gènes impliqués dans le mélanome et pour caractériser des variants potentiellement fonctionnels au sein des régions du génome associées au mélanome.Pour identifier de nouveaux gènes associés au risque de mélanome et à un facteur pronostique de ce cancer (l’indice de Breslow), nous avons proposé une stratégie d’analyse multi-marqueurs qui intègre une analyse de pathways biologiques basée sur la méthode GSEA (Gene Set Enrichment Analysis) et une analyse d’interactions entre gènes au sein des pathways associés au mélanome. Ces analyses ont été menées dans deux études : l’étude française MELARISK et l’étude américaine du MD Anderson Cancer Center (MDACC), totalisant 2 980 cas et 3 823 témoins. Nous avons identifié une interaction entre les gènes, TERF1 et AFAP1L2, pour le risque de mélanome et une interaction entre les gènes, CDC42 et SCIN, pour l’indice de Breslow. Ces gènes sont particulièrement pertinents sur le plan biologique du fait de leur rôle dans la biologie des télomères pour la première paire de gènes et dans la dynamique des filaments d’actine pour la seconde paire. Afin d’identifier les variants potentiellement fonctionnels au sein des régions du génome mises en évidence par études pangénomiques, nous avons proposé une stratégie de cartographie fine qui repose principalement sur une méthode de régression pénalisée (méthode HyperLasso) appliquée à tous les variants de la région étudiée. Par l’analyse de la région 16q24 qui contient le gène MC1R dont les variants fonctionnels sont connus, nous avons montré que cette stratégie était capable d’identifier ces variants parmi de nombreux variants associés au mélanome dans cette région. Nous avons contribué à identifier cinq nouvelles régions du génome associées au mélanome par méta-analyse d’études pangénomiques réalisées au niveau mondial (43 000 sujets) puis mené une étude de cartographie fine de toutes les régions associées au mélanome, en se basant sur la stratégie proposée et validée dans la région 16q24. Les stratégies d’analyses multi-marqueurs proposées dans le cadre de ce travail de thèse ont permis d’identifier de nouveaux gènes associés au risque de mélanome et à un facteur pronostique de ce cancer et de caractériser les variants génétiques potentiellement fonctionnels au sein des régions du génome identifiées par études pangénomiques
Cutaneous melanoma is a skin cancer developed from melanocytes. It is the 11th most common cancers in France. Mortality due to melanoma remains high when diagnosed at a late stage. This cancer results from many genetic, environmental factors and interactions between these factors. The genetic susceptibility to melanoma covers a broad spectrum of genetic variation, from rare mutations conferring high risk to common variants conferring low risk. My thesis was conducted in the framework of low-risk variants associated with melanoma occurrence and prognosis. To date, genome-wide association studies (GWAS) of melanoma have identified common variants with relatively modest effects which only explain a part of the genetic component of this cancer. Functional variants at the identified loci are mostly unknown. GWASs have been mainly conducted using single-marker analysis which may be underpowered to detect variants with small effect or interacting with each other. The main objective of this thesis was to propose multi-marker analysis strategies to identify novel genes involved in melanoma and to characterize potentially functional variants in chromosomal regions found associated with melanoma. To identify new genes associated with melanoma risk and a prognostic factor for this cancer (Breslow thickness), we proposed a multi-marker analysis strategy which integrates pathway analysis based on the GSEA (Gene Set Enrichment Analysis) method and gene-gene interaction analysis within melanoma-associated pathways. These analyses were conducted in two studies: the French MELARISK study and the North-American MD Anderson Cancer Center (MDACC) study, with a total of 2,980 cases and 3,823 controls. We identified gene-gene interactions between TERF1 and AFAP1L2 genes for melanoma risk and between CDC42 and SCIN genes for Breslow thickness. These genes are biologically relevant because of their role in telomere biology for the former gene pair and in actin dynamics for the latter pair. To identify potentially functional variants at loci identified by GWAS, we proposed a fine mapping strategy which is mainly based on a penalized regression approach (HyperLasso method) that can be applied to all variants of the region under study. By studying the 16q24 region which harbors the MC1R gene whose functional variants are known, we showed this strategy was able to identify those variants among many variants associated with melanoma in this region. We contributed to the identification of five novel regions associated with melanoma through a worldwide meta-analysis of melanoma GWASs (43,000 subjects) and conducted fine mapping of all melanoma-associated loci using the strategy we proposed and validated in the 16q24 region. The multi-marker strategies proposed in this work have allowed identifying new biologically relevant genes associated with risk of melanoma and a major melanoma prognostic factor and characterizing potentially functional genetic variants within regions identified by GWAS

Respect for autonomy is the foundation of modern bioethics, even (or especially) where bioethics is attentive to the problem of suffering caused by the practice of medicine itself. It provides guidance in the midst of therapeutic and moral uncertainty, justification for morally problematic enterprises, and the promise of protection against self-serving or predatory medical personnel. Yet bioethical arguments that appeal to the injustice or the horror of suffering depend on an instinctual and uncomplicated association of suffering, especially imposed suffering, with evil. This uncomplicated association, this flattening of the complexities of the moral landscape, must lead to a diminished capacity to navigate the very difficulties that define the field of bioethics. This dissertation explores the relationship, particularly, of autonomy, suffering, and happiness in modern bioethics, as represented by three key theorists (James Childress, Tom Beauchamp, and H. Tristram Engelhardt). It then contrasts these findings with resources from the Christian tradition: Luke-Acts, the letters of Paul, and the theologians Thomas Aquinas, Catherine of Genoa, and Margaret Ebner. Their accounts of the meaning and experience of suffering within well-lived lives makes for a more robust account of the moral life, one in which suffering plays a formative part.

Dissertation

博士
國立臺灣大學
生命科學系
105
Pain is an unpleasant sensory and emotional experiences associated with actual or potential tissue damage, excessive and chronic pain harmful to the quality of life. Chronic pain is a major health problem which affects up to 20% of the general population. Although acute pain patients can be properly managed, most of the chronic pain patients fail to achieve adequate pain relief. Among the most difficult ones are the neuropathic pain patients. Neuropathic pain is initiated by a primary lesion or dysfunction in the nervous system, and often causes chronic pain. It had been known that peripheral nerve damage induced early onset of ectopic discharge in injured nerve fibers. We hypothesized that peripheral nerve injury also induces sustained activation in the forebrain, and these brain areas eventually develop plasticity changes involved in chronic neuropathic pain. In this dissertation, we aimed to identify the sustained activation and the plasticity changes of forebrain during the development of Spared Nerve Injury (SNI) induced neuropathic pain via multiple magnetic resonance imaging (MRI) and electrophysiological recording approaches. First, we aim to longitudinally monitor the synaptic connectivity of the specific thalamocortical pathway via dexmedetomidine-based blood oxygen level dependent functional MRI (BOLD-fMRI) protocol. In this study, a pairs of tungsten electrodes, which caused acceptable susceptibility artifact limited around the electrodes, were used to target the ventroposterior thalamus – primary somatosensory (VP-S1) pathway. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral S1. The S1 BOLD responses during the 2 sessions (one week apart) were conserved in response amplitude, area size, and location. In the second part, we combined the BOLD-fMRI and manganese-enhanced MRI (MEMRI) to monitor the brain activation during three different neuropathic pain development stages, including the brain activation at the moment of nerve injury detected using BOLD-fMRI, and the brain activity during the 1st and the 8th day using MEMRI. We observed tonic activation in bilateral insular cortices and contralateral S1 immediately after the SNI, and these areas established long-term abnormal functional connectivities. By using the electrophysiological and DBS-fMRI approach, we found the primary injured VP-S1 pathway and surrounding VP-S1 pathway established different thalamocortical plasticity after the SNI, whereas the rostral anterior insular and the anterior cingulate cortex, which have large and diffusive receptive field, showed consistent enhanced thalamocortical connection after the SNI. By combination of multiple approaches, we not only provided an integrated result of functional brain changes after peripheral neuropathy, but also demonstrated an example framework to study the brain plasticity by combining multiple fMRI methods that complement each other.

碩士
國立中央大學
土木工程學系在職專班
105
Coastal digital elevation model (DEM) is important to map the spatial distribution of marine organisms, monitor changes of seafloor morphology, and produce accurate orthorectified images. There are different approaches for bathymetry mapping. For example, sonar and airborne bathymetric Lidar have high accuracy, but both face difficulties on monitoring inaccessible and controversial area. On the other hand, satellite imagery does not have this limitation. The spectral information in satellite imagery can be helpful for retrieving coastal DEM. However, this approach requires a good quality of training data. Therefore, digital photogrammetry approaches are more preferable as they can measure accurate bathymetry without the training data requirement. This research first uses an initial DEM to generate two orthorectified images for image matching. If the DEM is accurate, these two orthorectified images should be very similar. However, if parallaxes happen between the orthorectified images, we assume they are caused by the incorrectness of the DEM. As the traditional approaches often use the exterior orientation parameters (EOPs) of images to estimate elevation corrections, EOPs may not be available for every satellite images nowadays. Hence, this research estimates the elevation corrections from parallaxes by using the convergence angle, bisector angle, and asymmetry angle of the stereo-pair. In general, the proposed method comprises four main steps: (1)pre-processing, (2) elevation correction, (3) DEM reconstruction, and (4) refraction correction. First of all, an initial DEM is applied to produce orthorectified images. In order to increase the performance for image matching, we only match the features extracted from the master image. After calculating parallaxes, we can estimate the elevation corrections and iterate the process using image pyramids. Finally, because of the refraction effect, the refraction correction is necessary to produce the final bathymetry DEM. We have examined the proposed solution on the Dongsha Atoll in the South China Sea. By comparing with a DEM derived from Lidar, we have the following observations: (1) For the accuracy of matched points, pan-sharpened image has better performance on the shallow water region, which is about 0.52 meters. (2) For the accuracy of DEM, green bend images can achieve more match points on the deeper water region, which result in a more accurate (i.e., 1.15 meters) DEM. (3) Since underwater features are less obvious, small target window size (i.e., less than 31 × 31) would result in wrong matches. (4) In terms of the correlation coefficient threshold, as the Green band has good water penetration performance, there were no significant difference when using different thresholds (i.e., 0.6, 0.7, 0.8).

Leung Chin-lung.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2003.
Includes bibliographical references (leaves 133-164).
Abstracts in English and Chinese.
Abstract --- p.iv
摘要 --- p.vi
List of abbreviation --- p.viii
Chapter Chapter 1 --- Hepatocellular Carcinoma --- p.1
Chapter 1.1 --- A Health Burden --- p.1
Chapter 1.2 --- Pathology --- p.3
Chapter 1.3 --- Epidemiology --- p.7
Chapter 1.3.1 --- Global HCC distribution --- p.7
Chapter 1.3.2 --- Age and Gender --- p.10
Chapter 1.4 --- Risk Factors of HCC --- p.12
Chapter 1.4.1 --- Hepatitis B virus (HBV) --- p.13
Chapter 1.4.1.1 --- Chronic HBV infection --- p.13
Chapter 1.4.1.2 --- Role of HBV in hepatocarcinogenesis --- p.16
Chapter 1.4.1.2 a) --- Direct Oncogenesis --- p.16
Chapter 1.4.1.2 b) --- Indirect Oncogenesis --- p.17
Chapter 1.4.2 --- Hepatitis C virus (HCV) --- p.23
Chapter 1.4.2.1 --- Chronic HCV infection --- p.23
Chapter 1.4.2.2 --- Role of HCV in hepatocarcinogenesis --- p.23
Chapter 1.4.3 --- Chemicals as liver carcinogens --- p.27
Chapter 1.4.3.1 --- Aflatoxin Bi (AFB1) --- p.28
Chapter 1.4.3.2 --- Vinyl chloride --- p.29
Chapter 1.4.3.3 --- Alcoholic beverages --- p.29
Chapter 1.4.4 --- Inborn Errors in Metabolisms --- p.30
Chapter 1.4.4.1 --- Hereditary tyrosinemia --- p.30
Chapter 1.4.4.2 --- Hereditary haemochromatosis --- p.30
Chapter 1.4.4.3 --- α1-antitrypsin deficiency --- p.31
Chapter 1.4.5 --- Liver lesions --- p.32
Chapter 1.5 --- Genetic alterations in HCC --- p.33
Chapter Chapter 2 --- Rationale of the study --- p.39
Chapter Chapter 3 --- LOH study on 8p in HCC --- p.48
Chapter 3.1 --- Introduction --- p.48
Chapter 3.1.1 --- "Knudson's ""two-hit"" model and LOH" --- p.48
Chapter 3.1.2 --- Microsatellite DNA and LOH study --- p.49
Chapter 3.2 --- Materials and Methods --- p.51
Chapter 3.2.1 --- Patients and Specimens --- p.51
Chapter 3.2.1.1 --- Genomic DNA extraction from liver tissues --- p.53
Chapter 3.2.1.2 --- Genomic DNA extraction from buffy coat --- p.55
Chapter 3.3 --- LOH study on 8p in HCC --- p.57
Chapter 3.3.1 --- Microsatellite markers --- p.57
Chapter 3.3.2 --- 5-end labeling --- p.60
Chapter 3.3.3 --- Amplification of microsatellite DNA --- p.60
Chapter 3.3.4 --- Denaturing polyacrylamide gel electrophoresis --- p.61
Chapter 3.3.5 --- Detection of LOH --- p.62
Chapter 3.4 --- Results --- p.63
Chapter 3.4.1 --- LOH status of 52 HCC cases --- p.63
Chapter 3.4.2 --- Clinicopathological correlation --- p.67
Chapter 3.4.3 --- Delineation of common deletion region (CDR) --- p.67
Chapter 3.4.4 --- Common deletion region of interest --- p.77
Chapter Chapter 4 --- Study on LZTS1 --- p.83
Chapter 4.1 --- Introduction 一 LZTS1 --- p.83
Chapter 4.2 --- Mutation analysis of LZTS1 in HCC --- p.87
Chapter 4.2.1 --- Materials and Methods --- p.87
Chapter 4.2.1.1 --- Patients and HCC cell lines --- p.87
Chapter 4.2.1.2 --- Genomic DNA extraction from HCC cell lines --- p.87
Chapter 4.2.1.3 --- Amplification of exons of LZTS1 --- p.89
Chapter 4.2.1.3a) --- Primer pairs --- p.89
Chapter 4.2.1.3b) --- PCR conditions --- p.90
Chapter 4.2.1.4 --- Purification of PCR products --- p.93
Chapter 4.2.1.5 --- Cycle sequencing reaction --- p.94
Chapter 4.2.1.6 --- Purification of cycle sequencing reaction product --- p.94
Chapter 4.2.1.7 --- Sequence analysis by automated sequencer --- p.95
Chapter 4.2.1.8 --- Search for sequence variants of LZTS1 --- p.96
Chapter 4.2.2 --- Results --- p.97
Chapter 4.3 --- Expression analysis of LZTS1 in HCC with preliminary results --- p.103
Chapter 4.3.1 --- Materials and Methods --- p.103
Chapter 4.3.1.1 --- Patients and Specimens --- p.103
Chapter 4.3.1.2 --- Total RNA extraction --- p.103
Chapter 4.3.1.3 --- Reverse transcription --- p.104
Chapter 4.3.1.4 --- Semi-quantitative PCR --- p.105
Chapter 4.3.1.4a) --- Primer pairs --- p.105
Chapter 4.3.1.4b) --- PCR conditions --- p.106
Chapter 4.3.2 --- Results --- p.109
Chapter Chapter 5 --- Discussion --- p.111
Chapter 5.1 --- LOH study on 8p in HCC --- p.111
Chapter 5.2 --- Study on LZTS1 in HCC --- p.125
Chapter 5.2.1 --- Mutation analysis of LZTS1 --- p.125
Chapter 5.2.2 --- Expression analysis of LZTS1 --- p.129
Chapter 5.3 --- Future Study --- p.132
References --- p.133

碩士
國立臺灣大學
流行病學研究所
90
The study of quantitative trait locus (QTL) is a difficult area in genetic analysis. A quantitative trait is usually affected by both the environments and multiple loci. Moreover, it may be also influenced by the interaction between QTLs and by the interaction between genes and environments. Recently, various methods are conducted for different data structure in genomewide scan for mapping QTLs. Since it is difficult to collect pedigree data, an alternative method is to collect sib-pair data for inference of the locations of QTLs on chromosomes. In this thesis, we first introduce the relevant knowledge about genetics in chapter 1, including relevant terminology, the definition of recombination frequency and the meaning of genes identity by descent (IBD). Next, we review the crucial development of linkage analysis methods (parametric and nonparametric approach) for different data structures for mapping QTLs in chapter 2. Some fundamental topics, such as limitations and problems in linkage analysis methods, are discussed. The motivation of this study is specified in chapter 2. The primary objective of this study is to develop a two-stage approach of linkage analysis inferring the location of QTLs on chromosome. In chapter 3, we propose a model-free method extending the canonical correlation to find the influential interval. The major contribution of this research is to provide a more robust approach to locate QTL in the coarse mapping. Moreover, we also conduct a development of multivariate linkage approach for fine mapping. Next, we further investigate the performance of this method by simulations, in chapter 4. The results of simulations are discussed in chapter 5. In last chapter, chapter 6, we briefly discuss the results and discoveries from this research.

碩士
國立高雄師範大學
數學系
105
Abstract Let A and B be nonempty subsets of a metric space (X,d) and F : A → B and G : B → A be two nonlinear non-self mappings. In this paper, we establish some new convergence theorems for mappings F and G satisfying the following condition: there exists an MT-funtion φ: [0,1) → [0,1) such that d(Fx,Gy) ≤ 1/3φ(d(x,y))max{d(x,y) + d(Fx,y) ; d(x,Fx) + d(y,Gy)+ d(Fx,Gy)} + (1-φ(d(x,y)))dist(A,B) for all x ∈ A and y ∈ B.