No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 103-117).

Les systèmes intégrés sont aujourd’hui de plus en plus fréquemment confrontés à des contraintes de faible consommation ou d’efficacité énergétique. Ces problématiques se doivent d’être intégrées le plus en amont possible dans le flot de conception afin de réduire les temps de design et d’éviter de nombreuses itérations dans le flot. Dans ce contexte, le projet collaboratif HiCool, partenariat entre les laboratoires LIRMM et TIMA, les sociétés Defacto, Docea et ST Microelectronics, a mis en place une stratégie et un flot de conception pour concevoir des systèmes intégrés faible consommation tout en facilitant la réutilisation de blocks matériels (IPs) existants. L’approche proposée dans cette thèse s’intègre dans cette stratégie en apportant une petite dose d’asynchronisme dans des systèmes complètement synchrones. En effet, la réduction de la consommation est basée sur le constat que l’activation permanente de la totalité du circuit est inutile dans bien des cas. Néanmoins, contrôler l’activité avec des techniques de « clock gating » ou de « power gating » nécessitent usuellement d’effectuer un re-design du système et d’ajouter un organe de commande pour contrôler l’activation des zones effectuant un traitement. Le travail présenté dans ce manuscrit définit une stratégie basée sur des contrôleurs d’horloge et de domaine d’alimentation, asynchrones, distribués et facilement insérables dans un circuit avec un coût de re-design des plus réduit. / Today integrated systems are increasingly faced with the constraints of low consumption or energy efficiency. These issues need to be integrated as far upstream as possible in the design flow to reduce design time and avoid much iteration in the flow. In this context, the collaborative project HiCool, between LIRMM and TIMA laboratories, Defacto, Docea and ST Microelectronics companies, has set up a strategy and design flow to design integrated low power systems while facilitating the reuse of existing hardware blocks (IPs). The approach proposed in this thesis fits into this strategy by bringing a small dose of asynchrony in completely synchronous systems. Indeed, the reduction in consumption is based on the observation that permanent activation of the entire circuit is unnecessary in many cases. However, controlling the activity with techniques of "clock gating" or "power gating" usually need to perform a re-design of the system and to add a control device for controlling activation of areas effecting treatment. The work presented in this manuscript provides a strategy based clock controllers and power domain, asynchronous, distributed and easily insertable into a circuit with a low cost design.

abstract: Sensory gating is a process by which the nervous system preferentially admits stimuli that are important for the organism while filtering out those that may be meaningless. An optimal sensory gate cannot be static or inflexible, but rather plastic and informed by past experiences. Learning enables sensory gates to recognize stimuli that are emotionally salient and potentially predictive of positive or negative outcomes essential to survival. Olfaction is the only sensory modality in mammals where sensory inputs bypass conventional thalamic gating before entering higher emotional or cognitive brain regions. Thus, olfactory bulb circuits may have a heavier burden of sensory gating compared to other primary sensory circuits. How do the primary synapses in an olfactory system "learn"' in order to optimally gate or filter sensory stimuli? I hypothesize that centrifugal neuromodulator serotonin serves as a signaling mechanism by which primary olfactory circuits can experience learning informed sensory gating. To test my hypothesis, I conditioned genetically-modified mice using reward or fear olfactory-cued learning paradigms and used pharmacological, electrophysiological, immunohistochemical, and optical imaging approaches to assay changes in serotonin signaling or functional changes in primary olfactory circuits. My results indicate serotonin is a key mediator in the acquisition of olfactory fear memories through the activation of its type 2A receptors in the olfactory bulb. Functionally within the first synaptic relay of olfactory glomeruli, serotonin type 2A receptor activation decreases excitatory glutamatergic drive of olfactory sensory neurons through both presynaptic and postsynaptic mechanisms. I propose that serotonergic signaling decreases excitatory drive, thereby disconnecting olfactory sensory neurons from odor responses once information is learned and its behavioral significance is consolidated. I found that learning induced chronic changes in the density of serotonin fibers and receptors, which persisted in glomeruli encoding the conditioning odor. Such persistent changes could represent a sensory gate stabilized by memory. I hypothesize this ensures that the glomerulus encoding meaningful odors are much more sensitive to future serotonin signaling as such arousal cues arrive from centrifugal pathways originating in the dorsal raphe nucleus. The results advocate that a simple associative memory trace can be formed at primary sensory synapses to facilitate optimal sensory gating in mammalian olfaction. / Dissertation/Thesis / Ph.D. Biology 2012

Ingeniero Civil Electricista / Los circuitos digitales, que juegan un papel crucial en la vida cotidiana, consumen grandes cantidades de potencia lo que es considerado como una situación no deseada, lo que es particularmente cierto para equipos que dependen de baterías como celulares, es por esto que los diseñadores de circuitos así como las herramientas de síntesis utilizan diferentes técnicas con el fin de reducir su consumo de potencia. Una de las técnicas de reducción de potencia mas exitosas es clock-gating cuyo objetivo es reducir el consumo de potencia generado por las transiciones debidas a la señal de clk. La reducción de potencia se logra mediante la inserción de clock-gating cells (celdas de clock-gating) que impiden que la señal de clk llegue a los Flip-Flop cuando el valor de la salida de estos no se espera que cambie. Los diseños basados en Latch, que si bien no son tan utilizados como los diseños basados en Flip-Flop debido a sus complejidades adicionales, todavía son utilizados gracias a ciertos beneficios que presentan las restricciones de timing (timing o sincronización) de los Latch, sin embargo ninguna de las herramientas de síntesis existentes permite la inserción automática de clock-gates para diseños basados en Latches, por lo que los diseñadores de circuitos se ven forzados a insertar las clock-gates de forma manual lo que es ineficiente. El presente trabajo se enfoca en los mecanismos de clock-gating y los requisitos que se deben cumplir para permitir su uso en diseños basados en Latches desde la perspectiva de una herramienta de síntesis, al tiempo que provee de una discusión teórica sobre las diferencias entre Latches y Flip-Flops y como estas diferencias fuerzan los requerimientos de una herramienta de inserción de clock-gates Considerando las restricciones que debieran aplicar para una herramienta de inserción de clock-gates automática enfocada en Latches y utilizando el entorno de desarrollo provisto por Synopsys así como el código existente en la herramienta de síntesis desarrollada por ellos, se desarrolla un prototipo de inserción de clock-gates para Latches como parte de Design-Compiler El prototipo una vez embebido en Design-Compiler es probado en diversos diseños creados con este propósito y un diseño de mayor envergadura provisto por uno de los clientes de Synopsys y que es utilizado durante el desarrollo de circuitos reales, lo cual permite verificar la robustez de la herramienta desarrollada en diseños grandes.

Growth suppression mediated by connexin 37 (Cx37; also known as GJA4) requires interaction between its C-terminus and functional pore-forming domain. Using rat insulinoma cells, we show that Cx37 induces cell death and cell cycle arrest, and slowed cell cycling. Whether differential phosphorylation might regulate intramolecular interactions, and consequently the growth-suppressive phenotype, is unknown. Protein kinase C inhibition increased the open state probability of low-conductance gap junction channels (GJChs) and reduced GJCh closed state probability. Substituting alanine at serine residues 275, 302 and 328 eliminated Cx37-induced cell death, supported proliferation and reduced the GJCh closed state probability. With additional alanine for serine substitutions at residues 285, 319, 321 and 325, Cx37-induced cell death was eliminated and the growth arrest period prolonged, and GJCh closed state probability was restored. With aspartate substitution at these seven sites, apoptosis was induced and the open state probability of large conductance GJChs (and hemichannels) was increased. These data suggest that differential phosphorylation of the C-terminus regulates channel conformation and, thereby, cell cycle progression and cell survival.

Respiratory gating in lung PET imaging to compensate for respiratory motion artifacts is a current research issue with broad potential impact on quantitation, diagnosis and clinical management of lung tumors. However, PET images collected at discrete bins can be significantly affected by noise as there are lower activity counts in each gated bin unless the total PET acquisition time is prolonged, so that gating methods should be combined with imaging-based motion correction and registration methods. The aim of this study was to develop and validate a fast and practical solution to the problem of respiratory motion for the detection and accurate quantitation of lung tumors in PET images. This included: (1) developing a computer-assisted algorithm for PET/CT images that automatically segments lung regions in CT images, identifies and localizes lung tumors of PET images; (2) developing and comparing different registration algorithms which processes all the information within the entire respiratory cycle and integrate all the tumor in different gated bins into a single reference bin. Four registration/integration algorithms: Centroid Based, Intensity Based, Rigid Body and Optical Flow registration were compared as well as two registration schemes: Direct Scheme and Successive Scheme. Validation was demonstrated by conducting experiments with the computerized 4D NCAT phantom and with a dynamic lung-chest phantom imaged using a GE PET/CT System. Iterations were conducted on different size simulated tumors and different noise levels. Static tumors without respiratory motion were used as gold standard; quantitative results were compared with respect to tumor activity concentration, cross-correlation coefficient, relative noise level and computation time. Comparing the results of the tumors before and after correction, the tumor activity values and tumor volumes were closer to the static tumors (gold standard). Higher correlation values and lower noise were also achieved after applying the correction algorithms. With this method the compromise between short PET scan time and reduced image noise can be achieved, while quantification and clinical analysis become fast and precise.

The goal of the work is to find suitable soulition for a small water plant in kontinuity of a projekt of damaged dam repair.

Yes / X-ray crystallography has provided tremendous insight into the different structural states of membrane proteins and, in particular, of ion channels. However, the molecular forces that determine the thermodynamic stability of a particular state are poorly understood. Here we analyze the different X-ray structures of an inwardly rectifying potassium channel (Kir1.1) in relation to functional data we obtained for over 190 mutants in Kir1.1. This mutagenic perturbation analysis uncovered an extensive, state-dependent network of physically interacting residues that stabilizes the pre-open and open states of the channel, but fragments upon channel closure. We demonstrate that this gating network is an important structural determinant of the thermodynamic stability of these different gating states and determines the impact of individual mutations on channel function. These results have important implications for our understanding of not only K+ channel gating but also the more general nature of conformational transitions that occur in other allosteric proteins. / Wellcome Trust