397 resultados para ASL R1459
Resumo:
An automated system for detection of head movements is described. The goal is to label relevant head gestures in video of American Sign Language (ASL) communication. In the system, a 3D head tracker recovers head rotation and translation parameters from monocular video. Relevant head gestures are then detected by analyzing the length and frequency of the motion signal's peaks and valleys. Each parameter is analyzed independently, due to the fact that a number of relevant head movements in ASL are associated with major changes around one rotational axis. No explicit training of the system is necessary. Currently, the system can detect "head shakes." In experimental evaluation, classification performance is compared against ground-truth labels obtained from ASL linguists. Initial results are promising, as the system matches the linguists' labels in a significant number of cases.
Resumo:
Facial features play an important role in expressing grammatical information in signed languages, including American Sign Language(ASL). Gestures such as raising or furrowing the eyebrows are key indicators of constructions such as yes-no questions. Periodic head movements (nods and shakes) are also an essential part of the expression of syntactic information, such as negation (associated with a side-to-side headshake). Therefore, identification of these facial gestures is essential to sign language recognition. One problem with detection of such grammatical indicators is occlusion recovery. If the signer's hand blocks his/her eyebrows during production of a sign, it becomes difficult to track the eyebrows. We have developed a system to detect such grammatical markers in ASL that recovers promptly from occlusion. Our system detects and tracks evolving templates of facial features, which are based on an anthropometric face model, and interprets the geometric relationships of these templates to identify grammatical markers. It was tested on a variety of ASL sentences signed by various Deaf native signers and detected facial gestures used to express grammatical information, such as raised and furrowed eyebrows as well as headshakes.
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Spotting patterns of interest in an input signal is a very useful task in many different fields including medicine, bioinformatics, economics, speech recognition and computer vision. Example instances of this problem include spotting an object of interest in an image (e.g., a tumor), a pattern of interest in a time-varying signal (e.g., audio analysis), or an object of interest moving in a specific way (e.g., a human's body gesture). Traditional spotting methods, which are based on Dynamic Time Warping or hidden Markov models, use some variant of dynamic programming to register the pattern and the input while accounting for temporal variation between them. At the same time, those methods often suffer from several shortcomings: they may give meaningless solutions when input observations are unreliable or ambiguous, they require a high complexity search across the whole input signal, and they may give incorrect solutions if some patterns appear as smaller parts within other patterns. In this thesis, we develop a framework that addresses these three problems, and evaluate the framework's performance in spotting and recognizing hand gestures in video. The first contribution is a spatiotemporal matching algorithm that extends the dynamic programming formulation to accommodate multiple candidate hand detections in every video frame. The algorithm finds the best alignment between the gesture model and the input, and simultaneously locates the best candidate hand detection in every frame. This allows for a gesture to be recognized even when the hand location is highly ambiguous. The second contribution is a pruning method that uses model-specific classifiers to reject dynamic programming hypotheses with a poor match between the input and model. Pruning improves the efficiency of the spatiotemporal matching algorithm, and in some cases may improve the recognition accuracy. The pruning classifiers are learned from training data, and cross-validation is used to reduce the chance of overpruning. The third contribution is a subgesture reasoning process that models the fact that some gesture models can falsely match parts of other, longer gestures. By integrating subgesture reasoning the spotting algorithm can avoid the premature detection of a subgesture when the longer gesture is actually being performed. Subgesture relations between pairs of gestures are automatically learned from training data. The performance of the approach is evaluated on two challenging video datasets: hand-signed digits gestured by users wearing short sleeved shirts, in front of a cluttered background, and American Sign Language (ASL) utterances gestured by ASL native signers. The experiments demonstrate that the proposed method is more accurate and efficient than competing approaches. The proposed approach can be generally applied to alignment or search problems with multiple input observations, that use dynamic programming to find a solution.
Resumo:
Dehydration of the airway surface liquid (ASL) and the resultant decline in function of the mucociliary escalator in cystic fibrosis airways is largely underpinned by the excessive flux of Na+ and water though ENaC. Proteolysis of the endogenous and subunits of epithelial sodium channels (ENaC) by channel activating proteases (CAPS) is the key regulatory mechanism for channel activation. Recent reports highlight that (1) CFTR (cystic fibrosis transmembrane conductance regulator) normally protects ENaC from the action of proteases and (2) a stark imbalance in proteases/protease inhibitor levels in CF airway cultures favour activation of normally inactive ENaC. The current study examines the potential therapeutic benefit of CAPS/ENaC inhibition in CF airways.
Our group has developed a panel of active-site directed affinity-based probes which target and inhibit trypsin-like proteases (potential CAPS); including the broad-spectrum inhibitor QUB-TL1. We have utilised this compound to interrogate the impact of trypsin-like protease inhibition on ENaC activity in differentiated primary airway epithelial cell cultures.
Electrophysiological data demonstrate QUB-TL1 selectively and irreversibly binds to extracellularly located trypsin-like proteases resulting in impaired ENaC-mediated Na+ transport. Visualisation of ENaC at the apical surface compartment of primary airway epithelial cells shows a large reduction in a low molecular weight (processed and active) form of ENaC, which was found to be abundant in untreated CF cultures. Consistent with the reduction in ENaC activity observed, QUB-TL1 treatment was subsequently shown to increase ASL height (performed in collaboration with Royal College of Surgeons in Ireland).
Our results are consistent with the hypothesis that targeting the CAPS-ENaC signalling axis may restore the depleted ASL seen in CF airways.
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Studies of marine sediments, cave speleothemes, annually laminated corals, and tree rings from Asian monsoon regions have added knowledge to our understanding of the factors that control inter-annual to millennial monsoon variability in the past and have provided important constraints for climate modeling scenarios. In contrast, the spatial and temporal pattern of sub-millennial scale monsoon variability and its impact on land cover in SE Asia are still unresolved. This shortcoming stems from the fact that temporally well-resolved paleo-environmental studies are missing from large parts of SE Asia, especially from Thailand. Given that global and regional climate models are increasingly using terrestrial paleo- data to test their performance, past changes in land cover are therefore important variables to better understand feedbacks between different Earth systems. We obtained sediments from Lake Nong Thale Pron, in southern Thailand (8º 10`N, 99 º23`E; 380 m.asl). The aim of our study is to reconstruct lake status changes and to evaluate whether the extent of these changes are linked to known shifts in monsoon intensity and variability. Preliminary results show that lake infilling started more than 15,000 years ago and that the sediments cover the last deglaciation and the Holocene. Current analyses include Itrax XRF core scanning, loss-on-ignition (LOI at 950 and 550ºC), CN elemental and isotopic composition. We expect that our results will be able to give a picture of how the lake's status has changed over time and whether the extent of these changes is linked to known shifts in monsoon intensity and variability.
Resumo:
Background: Excessive activation of epithelial sodium channels (ENaC) contributes to CF lung pathophysiology due to the resultant dehydration of the airway surface liquid (ASL) and impaired mucociliary clearance. Regulated proteolysis of the endogenous α and γ subunits of ENaC by apical membrane-bound Channel Activating Proteases (CAPs) is a fundamental regulatory mechanism for channel activity. In the CF lung a stark imbalance between the levels of CAPs and their natural inhibitors drives the activation of normally inactive ENaC. On this basis inhibition of CAPs-ENaC signalling represents a potential therapeutic intervention. To this end we have developed a novel cell impermeable active-site directed compound (QUB-TL1) designed to inactivate key trypsin-like CAPs highly relevant in this regard. Objectives & Methods: Utilize differentiated non-CF and CF human airway epithelial cells to assess the impact of QUB-TL1 on a range of parameters including surface CAP activities, ENaC subunit processing/channel activity, ASL height and mucociliary clearance. Results: Treatment of airway epithelial cells with QUB-TL1 results in the significant downregulation of key endogenous CAP activities found to be excessively active at the surface of CF cultures. QUB-TL1-mediated CAP inhibition subsequently causes the internalisation of a pool of processed (active) ENaCγ prominent at the apical surface of CF cultures which correlates with a decline in channel activity. This downregulation of ENaC activity results in an increase in ASL height and improved mucociliary clearance in CF cells. We further find QUB-TL1 uniquely inhibits the ENaC activating enzyme furin, which is in contrast to the alternate trypsin-like CAP inhibitors camostat mesylate and aprotinin. QUB-TL1-mediated furin inhibition correlates with a reduction in neutrophil elastase-induced ENaC activation. Moreover we find QUB-TL1 treatment protects CF cultures from Pseudomonas aeruginosa exotoxin A-induced cytotoxicity. Pseudomonas aeruginosa exotoxin A is a major toxic product activated by furin and positively associated with mortality. Conclusion: The novel inhibitor (QUB-TL1) dampens CAPs-ENaC signalling which improves hydration status mucociliary clearance in CF airway epithelial cell cultures. Moreover this compound provides additional benefit by preventing Pseudomonas aeruginosa exotoxin A-induced cytotoxicity.
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Rationale: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height
compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of ENaC have therapeutic potential in CF airways to reduce the hyperstimulated sodium and fluid absorption to levels which can restore airways hydration.
Objectives: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function.
Methods: Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy) and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured by LDH assay.
Measurements and Results: QUB-TL1 inhibits extracellularly-located CAPs, including prostasin, matriptase and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells (AECs). QUB-TL1-mediated CAPs inhibition results in diminished ENaC-mediated Na+ absorption in CF AECs due to internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A induced cell death.
Conclusions: QUB-TL1 corrects aberrant CAP activities providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CFTR mutation.
Resumo:
Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful for management of oxidative stress-related diseases.
Resumo:
O presente relatório incluído na Unidade Curricular de Dissertação/Projeto/Estágio do Mestrado (DIPRE) em Engenharia Civil do Instituto Superior de Engenharia do Porto (ISEP) e desenvolvido no âmbito do estágio curricular realizado na empresa Asl & Associados, tem como principais objetivos a minha integração no mercado de trabalho e obtenção de experiência profissional. Neste trabalho, serão abordados temas como as introduções teóricas ao Comportamento Térmico e Acústico de Edifícios de Habitação, estudos de casos práticos como o Projeto de Comportamento Térmico de uma grande intervenção, Certificação Energética de edifícios existentes com base no Regulamento de Desempenho Energético dos Edifícios de Habitação e Ensaios Acústicos de Edifícios de acordo com o Regulamento dos Requisitos Acústicos dos Edifícios. O projeto realizado consistiu no estudo do comportamento térmico do edifício na Avenida Marechal Gomes da Costa nº802, no Porto. Nesse estudo realizou-se a verificação das soluções construtivas, por vezes foram propostas alterações das mesmas de modo a verificar os requisitos impostos pelo REH e foi realizada a emissão do seu pré-certificado. A maior parte do período em que decorreu o estágio na empresa foi preenchida com a realização de certificados energéticos de frações autónomas e de moradias. Para a recolha da informação necessária à sua elaboração, foram efetuadas várias vistorias aos imóveis referidos. Foram também efetuados durante o estágio, ensaios acústicos a edifícios de habitação e comércio e elaborado o respetivo relatório de ensaio.
Resumo:
O presente relatório desenvolvido no âmbito do estágio curricular realizado na empresa – ASL & Associados, com duração de seis meses, tem como objetivo a elaboração e desenvolvimento de estudos acústicos de edifícios e elaboração de certificados energéticos de edifícios existentes. Inicialmente, será feita uma descrição da empresa acolhedora expondo a sua missão, valores e o portfólio abarcando projetos e revisão de projetos, certificação energética, ensaios acústicos, gestão e fiscalização de empreendimentos. As atividades desenvolvidas no estágio englobam a certificação energética de edifícios existentes aplicando a nova regulamentação térmica (REH), apresentando as simplificações de cálculo aplicadas a edifícios existentes e dois exemplos específicos de uma fração autónoma e um edifício unifamiliar. No campo da acústica foram estudados três edifícios, um habitacional, um misto e um de serviços. Para o condicionamento acústico dos casos de estudo serão aplicados métodos de cálculo utilizados na empresa e um método de cálculo para avaliação e classificação da qualidade acústica, o qual foi desenvolvido pelo Laboratório Nacional de Engenharia Civil – LNEC. Por fim, foram elaborados as ponderações sobre a experiência vivida, como considerações sobre os resultados obtidos tendo em conta os objetivos propostos para o desenvolvimento do estágio.
Resumo:
No contexto editorial internacional existem, atualmente, materiais de alguma qualidade destinados à aprendizagem de segundas línguas (L2), mas que, no entanto, poderiam beneficiar muito mais de uma efetiva integração dos resultados recentes da investigação desenvolvida na área da Aquisição de Segundas Línguas (ASL). No contexto nacional, a situação não parece ser muito diferente, sendo também a experiência de docência dos autores que parece orientar a conceção dos materiais, para além de ser habitual o recurso a metodologias que se centram, essencialmente, na apresentação, prática e produção, embora exista outro tipo de lacunas que se traduz na falta de materiais dirigidos a públicos mais específicos, como estudantes que aprendem português em contexto universitário, ao contrário do que se verifica, internacionalmente, para o ensino de outras línguas. Em termos de abordagens pedagógicas, embora os investigadores na área da ASL não estejam de acordo em relação ao modo como a instrução pode contribuir para o desenvolvimento de L2, tem sido proposto que o Ensino de Línguas Baseado em Tarefas e a instrução com foco na forma podem promover o tipo de processo de aprendizagem que se considera facilitar a aquisição de um novo idioma. Contudo, apesar de existir uma base psicolinguística e um conjunto de evidências que sustentam a escolha de “tarefas” como base para o ensino e aprendizagem de L2, têm havido ainda poucas tentativas para elaborar manuais ou outros materiais que reflitam, de facto, a adoção de um ensino baseado em tarefas, nomeadamente, em Portugal, onde não parece haver, ainda, uma tradição de uso de tarefas no ensino da língua. Perante a existência de várias lacunas subjacentes ao processo de elaboração de materiais didáticos dirigidos à aprendizagem de L2, em particular no contexto nacional, o presente trabalho tem como finalidade contribuir para o enriquecimento e atualização da área, mediante a planificação de um curso de línguas baseado em tarefas, dirigido a estudantes de nível inicial que aprendem Português como Língua Estrangeira em universidades europeias, o qual será acompanhado por materiais didáticos e sugestões para implementação em sala de aula.
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Studies in cystic fibrosis patients and mice overexpressing the epithelial Na(+) channel beta-subunit (betaENaC-Tg) suggest that raised airway Na(+) transport and airway surface liquid (ASL) depletion are central to the pathogenesis of cystic fibrosis lung disease. However, patients or mice with Liddle gain-of-function betaENaC mutations exhibit hypertension but no lung disease. To investigate this apparent paradox, we compared the airway phenotype (nasal versus tracheal) of Liddle with CFTR-null, betaENaC-Tg, and double mutant mice. In mouse nasal epithelium, the region that functionally mimics human airways, high levels of CFTR expression inhibited Liddle epithelial Nat channel (ENaC) hyperfunction. Conversely, in mouse trachea, low levels of CFTR failed to suppress Liddle ENaC hyperfunction. Indeed, Na(+) transport measured in Ussing chambers ("flooded" conditions) was raised in both Liddle and betaENaC-Tg mice. Because enhanced Na(+) transport did not correlate with lung disease in these mutant mice, measurements in tracheal cultures under physiologic "thin film" conditions and in vivo were performed. Regulation of ASL volume and ENaC-mediated Na(+) absorption were intact in Liddle but defective in betaENaC-Tg mice. We conclude that the capacity to regulate Na(+) transport and ASL volume, not absolute Na(+) transport rates in Ussing chambers, is the key physiologic function protecting airways from dehydration-induced lung disease.
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La Fibrose Kystique (FK) est une maladie dégénérative qui entraine une dégénération des poumons dû au problème de clairance mucociliaire (CMC). Le volume de surface liquide (SL) couvrant les cellules pulmonaires est essentiel à la clairance de mucus et au combat contre les infections. Les nucléotides extracellulaires jouent un rôle important dans la CMC des voies aériennes, en modifiant le volume de la SL pulmonaire. Cependant, les mécanismes du relâchement de l’ATP et de leurs déplacements à travers la SL, restent inconnus. Des études ultérieures démontrent que l’exocytose d’ATP mécano-sensible et Ca2+-dépendant, dans les cellules A549, est amplifié par les actions synergétiques autocrine/paracrine des cellules avoisinantes. Nous avions comme but de confirmer la présence de la boucle purinergique dans plusieurs modèles de cellules épithéliales et de développer un système nous permettant d’observer directement la SL. Nous avons démontrés que la boucle purinergique est fonctionnelle dans les modèles de cellules épithéliales examinés, mis appart les cellules Calu-3. L’utilisation de modulateur de la signalisation purinergique nous a permis d’observer que le relâchement d’ATP ainsi que l’augmentation du [Ca2+]i suivant un stress hypotonique, sont modulés par le biais de cette boucle purinergique et des récepteurs P2Y. De plus, nous avons développé un système de microscopie qui permet d’observer les changements de volume de SL en temps réel. Notre système permet de contrôler la température et l’humidité de l’environnement où se trouvent les cellules, reproduisant l’environnement pulmonaire humain. Nous avons démontré que notre système peut identifier même les petits changements de volume de SL.
Resumo:
Le dioxyde de carbone (CO2) est un résidu naturel du métabolisme cellulaire, la troisième substance la plus abondante du sang, et un important agent vasoactif. À la moindre variation de la teneur en CO2 du sang, la résistance du système vasculaire cérébral et la perfusion tissulaire cérébrale subissent des changements globaux. Bien que les mécanismes exacts qui sous-tendent cet effet restent à être élucidés, le phénomène a été largement exploité dans les études de réactivité vasculaire cérébrale (RVC). Une voie prometteuse pour l’évaluation de la fonction vasculaire cérébrale est la cartographie de la RVC de manière non-invasive grâce à l’utilisation de l’Imagerie par Résonance Magnétique fonctionnelle (IRMf). Des mesures quantitatives et non-invasives de de la RVC peuvent être obtenus avec l’utilisation de différentes techniques telles que la manipu- lation du contenu artériel en CO2 (PaCO2) combinée à la technique de marquage de spin artériel (Arterial Spin Labeling, ASL), qui permet de mesurer les changements de la perfusion cérébrale provoqués par les stimuli vasculaires. Toutefois, les préoccupations liées à la sensibilité et la fiabilité des mesures de la RVC limitent de nos jours l’adoption plus large de ces méthodes modernes de IRMf. J’ai considéré qu’une analyse approfondie ainsi que l’amélioration des méthodes disponibles pourraient apporter une contribution précieuse dans le domaine du génie biomédical, de même qu’aider à faire progresser le développement de nouveaux outils d’imagerie de diagnostique. Dans cette thèse je présente une série d’études où j’examine l’impact des méthodes alternatives de stimulation/imagerie vasculaire sur les mesures de la RVC et les moyens d’améliorer la sensibilité et la fiabilité de telles méthodes. J’ai aussi inclus dans cette thèse un manuscrit théorique où j’examine la possible contribution d’un facteur méconnu dans le phénomène de la RVC : les variations de la pression osmotique du sang induites par les produits de la dissolution du CO2. Outre l’introduction générale (Chapitre 1) et les conclusions (Chapitre 6), cette thèse comporte 4 autres chapitres, au long des quels cinq différentes études sont présentées sous forme d’articles scientifiques qui ont été acceptés à des fins de publication dans différentes revues scientifiques. Chaque chapitre débute par sa propre introduction, qui consiste en une description plus détaillée du contexte motivant le(s) manuscrit(s) associé(s) et un bref résumé des résultats transmis. Un compte rendu détaillé des méthodes et des résultats peut être trouvé dans le(s) dit(s) manuscrit(s). Dans l’étude qui compose le Chapitre 2, je compare la sensibilité des deux techniques ASL de pointe et je démontre que la dernière implémentation de l’ASL continue, la pCASL, offre des mesures plus robustes de la RVC en comparaison à d’autres méthodes pulsés plus âgées. Dans le Chapitre 3, je compare les mesures de la RVC obtenues par pCASL avec l’utilisation de quatre méthodes respiratoires différentes pour manipuler le CO2 artérielle (PaCO2) et je démontre que les résultats peuvent varier de manière significative lorsque les manipulations ne sont pas conçues pour fonctionner dans l’intervalle linéaire de la courbe dose-réponse du CO2. Le Chapitre 4 comprend deux études complémentaires visant à déterminer le niveau de reproductibilité qui peut être obtenu en utilisant des méthodes plus récentes pour la mesure de la RVC. La première étude a abouti à la mise au point technique d’un appareil qui permet des manipulations respiratoires du CO2 de manière simple, sécuritaire et robuste. La méthode respiratoire améliorée a été utilisée dans la seconde étude – de neuro-imagerie – où la sensibilité et la reproductibilité de la RVC, mesurée par pCASL, ont été examinées. La technique d’imagerie pCASL a pu détecter des réponses de perfusion induites par la variation du CO2 dans environ 90% du cortex cérébral humain et la reproductibilité de ces mesures était comparable à celle d’autres mesures hémodynamiques déjà adoptées dans la pratique clinique. Enfin, dans le Chapitre 5, je présente un modèle mathématique qui décrit la RVC en termes de changements du PaCO2 liés à l’osmolarité du sang. Les réponses prédites par ce modèle correspondent étroitement aux changements hémodynamiques mesurés avec pCASL ; suggérant une contribution supplémentaire à la réactivité du système vasculaire cérébral en lien avec le CO2.
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Die erste Ausgabe des Magazins Monu hat das Thema Paid Urbanism und untersucht urbane Veränderungen, verursacht durch Staatssubventionen. Es werden Projekte und Artikel von amerikanischen und europäischen Autoren präsentiert, die den Einfluss von Paid Urbanism auf die Form unterschiedlichster Orte wie Chicago, Coney Island (New York City) und Thüringen untersuchen und reflektieren.