Real-Time Dynamic PGD Calculation of Non-Linear Soil Behavior

El estudio sísmico en los últimos 50 años y el análisis del comportamiento dinámico del suelo revelan que el comportamiento del suelo es altamente no lineal e histéretico incluso para pequeñas deformaciones. El comportamiento no lineal del suelo durante un evento sísmico tiene un papel predominante en el análisis de la respuesta de sitio. Los análisis unidimensionales de la respuesta sísmica del suelo son a menudo realizados utilizando procedimientos lineales equivalentes, que requieren generalmente pocos parámetros conocidos. Los análisis de respuesta de sitio no lineal tienen el potencial para simular con mayor precisión el comportamiento del suelo, pero su aplicación en la práctica se ha visto limitada debido a la selección de parámetros poco documentadas y poco claras, así como una inadecuada documentación de los beneficios del modelado no lineal en relación al modelado lineal equivalente. En el análisis del suelo, el comportamiento del suelo es aproximado como un sólido Kelvin-Voigt con un módulo de corte elástico y amortiguamiento viscoso. En el análisis lineal y no lineal del suelo se están considerando geometrías y modelos reológicos más complejos. El primero está siendo dirigido por considerar parametrizaciones más ricas del comportamiento linealizado y el segundo mediante el uso de multi-modo de los elementos de resorte-amortiguador con un eventual amortiguador fraccional. El uso del cálculo fraccional está motivado en gran parte por el hecho de que se requieren menos parámetros para lograr la aproximación exacta a los datos experimentales. Basándose en el modelo de Kelvin-Voigt, la viscoelasticidad es revisada desde su formulación más estándar a algunas descripciones más avanzada que implica la amortiguación dependiente de la frecuencia (o viscosidad), analizando los efectos de considerar derivados fraccionarios para representar esas contribuciones viscosas. Vamos a demostrar que tal elección se traduce en modelos más ricos que pueden adaptarse a diferentes limitaciones relacionadas con la potencia disipada, amplitud de la respuesta y el ángulo de fase. Por otra parte, el uso de derivados fraccionarios permite acomodar en paralelo, dentro de un análogo de Kelvin-Voigt generalizado, muchos amortiguadores que contribuyen a aumentar la flexibilidad del modelado para la descripción de los resultados experimentales. Obviamente estos modelos ricos implican muchos parámetros, los asociados con el comportamiento y los relacionados con los derivados fraccionarios. El análisis paramétrico de estos modelos requiere técnicas numéricas eficientemente capaces de simular comportamientos complejos. El método de la Descomposición Propia Generalizada (PGD) es el candidato perfecto para la construcción de este tipo de soluciones paramétricas. Podemos calcular off-line la solución paramétrica para el depósito de suelo, para todos los parámetros del modelo, tan pronto como tales soluciones paramétricas están disponibles, el problema puede ser resuelto en tiempo real, porque no se necesita ningún nuevo cálculo, el solucionador sólo necesita particularizar on-line la solución paramétrica calculada off-line, que aliviará significativamente el procedimiento de solución. En el marco de la PGD, parámetros de los materiales y los diferentes poderes de derivación podrían introducirse como extra-coordenadas en el procedimiento de solución. El cálculo fraccional y el nuevo método de reducción modelo llamado Descomposición Propia Generalizada han sido aplicado en esta tesis tanto al análisis lineal como al análisis no lineal de la respuesta del suelo utilizando un método lineal equivalente. ABSTRACT Studies of earthquakes over the last 50 years and the examination of dynamic soil behavior reveal that soil behavior is highly nonlinear and hysteretic even at small strains. Nonlinear behavior of soils during a seismic event has a predominant role in current site response analysis. One-dimensional seismic ground response analysis are often performed using equivalent-linear procedures, which require few, generally well-known parameters. Nonlinear analyses have the potential to more accurately simulate soil behavior, but their implementation in practice has been limited because of poorly documented and unclear parameter selection, as well as inadequate documentation of the benefits of nonlinear modeling relative to equivalent linear modeling. In soil analysis, soil behaviour is approximated as a Kelvin-Voigt solid with a elastic shear modulus and viscous damping. In linear and nonlinear analysis more complex geometries and more complex rheological models are being considered. The first is being addressed by considering richer parametrizations of the linearized behavior and the second by using multi-mode spring-dashpot elements with eventual fractional damping. The use of fractional calculus is motivated in large part by the fact that fewer parameters are required to achieve accurate approximation of experimental data. Based in Kelvin-Voigt model the viscoelastodynamics is revisited from its most standard formulation to some more advanced description involving frequency-dependent damping (or viscosity), analyzing the effects of considering fractional derivatives for representing such viscous contributions. We will prove that such a choice results in richer models that can accommodate different constraints related to the dissipated power, response amplitude and phase angle. Moreover, the use of fractional derivatives allows to accommodate in parallel, within a generalized Kelvin-Voigt analog, many dashpots that contribute to increase the modeling flexibility for describing experimental findings. Obviously these rich models involve many parameters, the ones associated with the behavior and the ones related to the fractional derivatives. The parametric analysis of all these models require efficient numerical techniques able to simulate complex behaviors. The Proper Generalized Decomposition (PGD) is the perfect candidate for producing such kind of parametric solutions. We can compute off-line the parametric solution for the soil deposit, for all parameter of the model, as soon as such parametric solutions are available, the problem can be solved in real time because no new calculation is needed, the solver only needs particularize on-line the parametric solution calculated off-line, which will alleviate significantly the solution procedure. Within the PGD framework material parameters and the different derivation powers could be introduced as extra-coordinates in the solution procedure. Fractional calculus and the new model reduction method called Proper Generalized Decomposition has been applied in this thesis to the linear analysis and nonlinear soil response analysis using a equivalent linear method.

Estimación del consumo de potencia en un terminal portátil multimedia basada en la PMU del procesador

Este proyecto se incluye en una línea de trabajo que tiene como objetivo final la optimización de la energía consumida por un dispositivo portátil multimedia mediante la aplicación de técnicas de control realimentado, a partir de una modificación dinámica de la frecuencia de trabajo del procesador y de su tensión de alimentación. La modificación de frecuencia y tensión se realiza a partir de la información de realimentación acerca de la potencia consumida por el dispositivo, lo que supone un problema ya que no suele ser posible la monitorización del consumo de potencia en dispositivos de estas características. Este es el motivo por el que se recurre a la estimación del consumo de potencia, utilizando para ello un modelo de predicción. A partir del número de veces que se producen ciertos eventos en el procesador del dispositivo, el modelo de predicción es capaz de obtener una estimación de la potencia consumida por dicho dispositivo. El trabajo llevado a cabo en este proyecto se centra en la implementación de un modelo de estimación de potencia en el kernel de Linux. La razón por la que la estimación se implementa en el sistema operativo es, en primer lugar para lograr un acceso directo a los contadores del procesador. En segundo lugar, para facilitar la modificación de frecuencia y tensión, una vez obtenida la estimación de potencia, ya que esta también se realiza desde el sistema operativo. Otro motivo para implementar la estimación en el sistema operativo, es que la estimación debe ser independiente de las aplicaciones de usuario. Además, el proceso de estimación se realiza de forma periódica, lo que sería difícil de lograr si no se trabajase desde el sistema operativo. Es imprescindible que la estimación se haga de forma periódica ya que al ser dinámica la modificación de frecuencia y tensión que se pretende implementar, se necesita conocer el consumo de potencia del dispositivo en todo momento. Cabe destacar también, que los algoritmos de control se tienen que diseñar sobre un patrón periódico de actuación. El modelo de estimación de potencia funciona de manera específica para el perfil de consumo generado por una única aplicación determinada, que en este caso es un decodificador de vídeo. Sin embargo, es necesario que funcione de la forma más precisa posible para cada una de las frecuencias de trabajo del procesador, y para el mayor número posible de secuencias de vídeo. Esto es debido a que las sucesivas estimaciones de potencia se pretenden utilizar para llevar a cabo la modificación dinámica de frecuencia, por lo que el modelo debe ser capaz de continuar realizando las estimaciones independientemente de la frecuencia con la que esté trabajando el dispositivo. Para valorar la precisión del modelo de estimación se toman medidas de la potencia consumida por el dispositivo a las distintas frecuencias de trabajo durante la ejecución del decodificador de vídeo. Estas medidas se comparan con las estimaciones de potencia obtenidas durante esas mismas ejecuciones, obteniendo de esta forma el error de predicción cometido por el modelo y realizando las modificaciones y ajustes oportunos en el mismo. ABSTRACT. This project is included in a work line which tries to optimize consumption of handheld multimedia devices by the application of feedback control techniques, from a dynamic modification of the processor work frequency and its voltage. The frequency and voltage modification is performed depending on the feedback information about the device power consumption. This is a problem because normally it is not possible to monitor the power consumption on this kind of devices. This is the reason why a power consumption estimation is used instead, which is obtained from a prediction model. Using the number of times some events occur on the device processor, the prediction model is able to obtain a power consumption estimation of this device. The work done in this project focuses on the implementation of a power estimation model in the Linux kernel. The main reason to implement the estimation in the operating system is to achieve a direct access to the processor counters. The second reason is to facilitate the frequency and voltage modification, because this modification is also done from the operating system. Another reason to implement the estimation in the operating system is because the estimation must be done apart of the user applications. Moreover, the estimation process is done periodically, what is difficult to obtain outside the operating system. It is necessary to make the estimation in a periodic way because the frequency and voltage modification is going to be dynamic, so it needs to know the device power consumption at every time. Also, it is important to say that the control algorithms have to be designed over a periodic pattern of action. The power estimation model works specifically for the consumption profile generated by a single application, which in this case is a video decoder. Nevertheless, it is necessary that the model works as accurate as possible for each frequency available on the processor, and for the greatest number of video sequences. This is because the power estimations are going to be used to modify dynamically the frequency, so the model must be able to work independently of the device frequency. To value the estimation model precision, some measurements of the device power consumption are taken at different frequencies during the video decoder execution. These measurements are compared with the power estimations obtained during that execution, getting the prediction error committed by the model, and if it is necessary, making modifications and settings on this model.

Methodology for Dynamic Stability and Robustness Analysis of Commercial-Power-Module-Based DC-Distributed Systems

El propósito de esta tesis es presentar una metodología para realizar análisis de la dinámica en pequeña señal y el comportamiento de sistemas de alimentación distribuidos de corriente continua (CC), formados por módulos comerciales. Para ello se hace uso de un método sencillo que indica los márgenes de estabilidad menos conservadores posibles mediante un solo número. Este índice es calculado en cada una de las interfaces que componen el sistema y puede usarse para obtener un índice global que indica la estabilidad del sistema global. De esta manera se posibilita la comparación de sistemas de alimentación distribuidos en términos de robustez. La interconexión de convertidores CC-CC entre ellos y con los filtros EMI necesarios puede originar interacciones no deseadas que dan lugar a la degradación del comportamiento de los convertidores, haciendo el sistema más propenso a inestabilidades. Esta diferencia en el comportamiento se debe a interacciones entre las impedancias de los diversos elementos del sistema. En la mayoría de los casos, los sistemas de alimentación distribuida están formados por módulos comerciales cuya estructura interna es desconocida. Por ello los análisis presentados en esta tesis se basan en medidas de la respuesta en frecuencia del convertidor que pueden realizarse desde los terminales de entrada y salida del mismo. Utilizando las medidas de las impedancias de entrada y salida de los elementos del sistema, se puede construir una función de sensibilidad que proporciona los márgenes de estabilidad de las diferentes interfaces. En esta tesis se utiliza el concepto del valor máximo de la función de sensibilidad (MPC por sus siglas en inglés) para indicar los márgenes de estabilidad como un único número. Una vez que la estabilidad de todas las interfaces del sistema se han evaluado individualmente, los índices obtenidos pueden combinarse para obtener un único número con el que comparar la estabilidad de diferentes sistemas. Igualmente se han analizado las posibles interacciones en la entrada y la salida de los convertidores CC-CC, obteniéndose expresiones analíticas con las que describir en detalle los acoplamientos generados en el sistema. Los estudios analíticos realizados se han validado experimentalmente a lo largo de la tesis. El análisis presentado en esta tesis se culmina con la obtención de un índice que condensa los márgenes de estabilidad menos conservativos. También se demuestra que la robustez del sistema está asegurada si las impedancias utilizadas en la función de sensibilidad se obtienen justamente en la entrada o la salida del subsistema que está siendo analizado. Por otra parte, la tesis presenta un conjunto de parámetros internos asimilados a impedancias, junto con sus expresiones analíticas, que permiten una explicación detallada de las interacciones en el sistema. Dichas expresiones analíticas pueden obtenerse bien mediante las funciones de transferencia analíticas si se conoce la estructura interna, o utilizando medidas en frecuencia o identificación de las mismas a través de la respuesta temporal del convertidor. De acuerdo a las metodologías presentadas en esta tesis se puede predecir la estabilidad y el comportamiento de sistemas compuestos básicamente por convertidores CC-CC y filtros, cuya estructura interna es desconocida. La predicción se basa en un índice que condensa la información de los márgenes de estabilidad y que permite la obtención de un indicador de la estabilidad global de todo el sistema, permitiendo la comparación de la estabilidad de diferentes arquitecturas de sistemas de alimentación distribuidos. ABSTRACT The purpose of this thesis is to present dynamic small-signal stability and performance analysis methodology for dc-distributed systems consisting of commercial power modules. Furthermore, the objective is to introduce simple method to state the least conservative margins for robust stability as a single number. In addition, an index characterizing the overall system stability is obtained, based on which different dc-distributed systems can be compared in terms of robustness. The interconnected systems are prone to impedance-based interactions which might lead to transient-performance degradation or even instability. These systems typically are constructed using commercial converters with unknown internal structure. Therefore, the analysis presented throughout this thesis is based on frequency responses measurable from the input and output terminals. The stability margins are stated utilizing a concept of maximum peak criteria, derived from the behavior of impedance-based sensitivity function that provides a single number to state robust stability. Using this concept, the stability information at every system interface is combined to a meaningful number to state the average robustness of the system. In addition, theoretical formulas are extracted to assess source and load side interactions in order to describe detailed couplings within the system. The presented theoretical analysis methodologies are experimentally validated throughout the thesis. In this thesis, according to the presented analysis, the least conservative stability margins are provided as a single number guaranteeing robustness. It is also shown that within the interconnected system the robust stability is ensured only if the impedance-based minor-loop gain is determined at the very input or output of each subsystem. Moreover, a complete set of impedance-type internal parameters as well as the formulas according to which the interaction sensitivity can be fully explained and analyzed, is provided. The given formulation can be utilized equally either based on measured frequency responses, time-domain identified internal parameters or extracted analytic transfer functions. Based on the analysis methodologies presented in this thesis, the stability and performance of interconnected systems consisting of converters with unknown internal structure, can be predicted. Moreover, the provided concept to assess the least conservative stability margins enables to obtain an index to state the overall robust stability of distributed power architecture and thus to compare different systems in terms of stability.

γ-Aminobutyric acid type B receptor-dependent burst-firing in thalamic neurons: A dynamic clamp study

Synchronized network responses in thalamus depend on phasic inhibition originating in the thalamic reticular nucleus (nRt) and are mediated by the neurotransmitter γ-aminobutyric acid (GABA). A suggested role for intra-nRt connectivity in inhibitory phasing remains controversial. Recently, functional GABA type B (GABAB) receptors were demonstrated on nRt cells, and the slow time course of the GABAB synaptic response seems ideally suited to deinactivate low-threshold calcium channels. This promotes burst firing, a characteristic feature of synchronized responses. Here we investigate GABAB-mediated rebound burst firing in thalamic cells. Whole-cell current-clamp recordings were obtained from nRt cells and somatosensory thalamocortical relay cells in rat brain slices. Synthetic GABAB inhibitory postsynaptic potentials, generated by a hybrid computer–neuron synapse (dynamic clamp), triggered rebound low-threshold calcium spikes in both cell types when peak inhibitory postsynaptic potential hyperpolarization was greater than −92 mV. The threshold inhibitory postsynaptic potential conductance for rebound burst generation was comparable in nRt (7 nS) and thalamocortical (5 nS) cells. However, burst onset in nRt (1 s) was considerably delayed compared with thalamocortical (0.6 s) cells. Thus, GABAB inhibitory postsynaptic potentials can elicit low-threshold calcium spikes in both relay and nRt neurons, but the resultant oscillation frequency would be faster for thalamocortical–nRt networks (3 Hz) than for nRt–nRt networks (1–2 Hz). We conclude, therefore, that fast (>2 Hz) GABAB-dependent thalamic oscillations are maintained primarily by reciprocal connections between excitatory and inhibitory cells. These findings further indicate that when oscillatory neural networks contain both recurrent and reciprocal inhibition, then distinct population frequencies may result when one or the other type of inhibition is favored.

Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials

Action potentials in juvenile and adult rat layer-5 neocortical pyramidal neurons can be initiated at both axonal and distal sites of the apical dendrite. However, little is known about the interaction between these two initiation sites. Here, we report that layer 5 pyramidal neurons are very sensitive to a critical frequency of back-propagating action potentials varying between 60 and 200 Hz in different neurons. Bursts of four to five back-propagating action potentials above the critical frequency elicited large regenerative potentials in the distal dendritic initiation zone. The critical frequency had a very narrow range (10–20 Hz), and the dendritic regenerative activity led to further depolarization at the soma. The dendritic frequency sensitivity was suppressed by blockers of voltage-gated calcium channels, and also by synaptically mediated inhibition. Calcium-fluorescence imaging revealed that the site of largest transient increase in intracellular calcium above the critical frequency was located 400–700 μm from the soma at the site for initiation of calcium action potentials. Thus, the distal dendritic initiation zone can interact with the axonal initiation zone, even when inputs to the neuron are restricted to regions close to the soma, if the output of the neuron exceeds a critical frequency.

The Dynamic Behavior of Individual Microtubules Associated with Chromosomes In Vitro

Mitotic movements of chromosomes are usually coupled to the elongation and shortening of the microtubules to which they are bound. The lengths of kinetochore-associated microtubules change by incorporation or loss of tubulin subunits, principally at their chromosome-bound ends. We have reproduced aspects of this phenomenon in vitro, using a real-time assay that displays directly the movements of individual chromosome-associated microtubules as they elongate and shorten. Chromosomes isolated from cultured Chinese hamster ovary cells were adhered to coverslips and then allowed to bind labeled microtubules. In the presence of tubulin and GTP, these microtubules could grow at their chromosome-bound ends, causing the labeled segments to move away from the chromosomes, even in the absence of ATP. Sometimes a microtubule would switch to shortening, causing the direction of movement to change abruptly. The link between a microtubule and a chromosome was mechanically strong; 15 pN of tension was generally insufficient to detach a microtubule, even though it could add subunits at the kinetochore–microtubule junction. The behavior of the microtubules in vitro was regulated by the chromosomes to which they were bound; the frequency of transitions from polymerization to depolymerization was decreased, and the speed of depolymerization-coupled movement toward chromosomes was only one-fifth the rate of shortening for microtubules free in solution. Our results are consistent with a model in which each microtubule interacts with an increasing number of chromosome-associated binding sites as it approaches the kinetochore.

Dynamic regulation of neuronal NO synthase transcription by calcium influx through a CREB family transcription factor-dependent mechanism

Neuronal nitric oxide (NO) synthase (nNOS) is dynamically regulated in response to a variety of physiologic and pathologic stimuli. Although the dynamic regulation of nNOS is well established, the molecular mechanisms by which such diverse stimuli regulate nNOS expression have not yet been identified. We describe experiments demonstrating that Ca2+ entry through voltage-sensitive Ca2+ channels regulates nNOS expression through alternate promoter usage in cortical neurons and that nNOS exon 2 contains the regulatory sequences that respond to Ca2+. Deletion and mutational analysis of the nNOS exon 2 promoter reveals two critical cAMP/Ca2+ response elements (CREs) that are immediately upstream of the transcription start site. CREB binds to the CREs within the nNOS gene. Mutation of the nNOS CREs as well as blockade of CREB function results in a dramatic loss of nNOS transcription. These findings suggest that nNOS is a Ca2+-regulated gene through the interactions of CREB on the CREs within the nNOS exon 2 promoter and that these interactions are likely to be centrally involved in the regulation of nNOS in response to neuronal injury and activity-dependent plasticity.

Two-dimensional confocal images of organization, density, and gating of focal Ca2+ release sites in rat cardiac myocytes

In cardiac myocytes Ca2+ cross-signaling between Ca2+ channels and ryanodine receptors takes place by exchange of Ca2+ signals in microdomains surrounding dyadic junctions, allowing first the activation and then the inactivation of the two Ca2+-transporting proteins. To explore the details of Ca2+ signaling between the two sets of receptors we measured the two-dimensional cellular distribution of Ca2+ at 240 Hz by using a novel confocal imaging technique. Ca2+ channel-triggered Ca2+ transients could be resolved into dynamic “Ca2+ stripes” composed of hundreds of discrete focal Ca2+ releases, appearing as bright fluorescence spots (radius ≅ 0.5 μm) at reproducible sites, which often coincided with t-tubules as visualized with fluorescent staining of the cell membrane. Focal Ca2+ releases triggered stochastically by Ca2+ current (ICa) changed little in duration (≅7 ms) and size (≅100,000 Ca ions) between −40 and +60 mV, but their frequency of activation and first latency mirrored the kinetics and voltage dependence of ICa. The resolution of 0.95 ± 0.13 reproducible focal Ca2+ release sites per μm3 in highly Ca2+-buffered cells, where diffusion of Ca2+ is limited to 50 nm, suggests the presence of about one independent, functional Ca2+ release site per half sarcomere. The density and distribution of Ca2+ release sites suggest they correspond to dyadic junctions. The abrupt onset and termination of focal Ca2+ releases indicate that the cluster of ryanodine receptors in individual dyadic junctions may operate in a coordinated fashion.

Reciprocal electromechanical properties of rat prestin: The motor molecule from rat outer hair cells

Cochlear outer hair cells (OHCs) are responsible for the exquisite sensitivity, dynamic range, and frequency-resolving capacity of the mammalian hearing organ. These unique cells respond to an electrical stimulus with a cycle-by-cycle change in cell length that is mediated by molecular motors in the cells' basolateral membrane. Recent work identified prestin, a protein with similarity to pendrin-related anion transporters, as the OHC motor molecule. Here we show that heterologously expressed prestin from rat OHCs (rprestin) exhibits reciprocal electromechanical properties as known for the OHC motor protein. Upon electrical stimulation in the microchamber configuration, rprestin generates mechanical force with constant amplitude and phase up to a stimulus frequency of at least 20 kHz. Mechanical stimulation of rprestin in excised outside-out patches shifts the voltage dependence of the nonlinear capacitance characterizing the electrical properties of the molecule. The results indicate that rprestin is a molecular motor that displays reciprocal electromechanical properties over the entire frequency range relevant for mammalian hearing.

Characterization of a high-voltage-activated IA current with a role in spike timing and locomotor pattern generation

Transient A-type K+ channels (IA) in neurons have been implicated in the delay of the spike onset and the decrease in the firing frequency. Here we have characterized biophysically and pharmacologically an IA current in lamprey locomotor network neurons that is activated by suprathreshold depolarization and is specifically blocked by catechol at 100 μM. The biophysical properties of this current are similar to the mammalian Kv3.4 channel. The role of the IA current both in single neuron firing and in locomotor pattern generation was analyzed. The IA current facilitates Na+ channel recovery from inactivation and thus sustains repetitive firing. The role of the IA current in motor pattern generation was examined by applying catechol during fictive locomotion induced by N-methyl-d-aspartate. Blockade of this current increased the locomotor burst frequency and decreased the firing of motoneurons. Although an alternating motor pattern could still be generated, the cycle duration was less regular, with ventral roots bursts failing on some cycles. Our results thus provide insights into the contribution of a high-voltage-activated IA current to the regulation of firing properties and motor coordination in the lamprey spinal cord.

Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.

Voltage-gated Na+ channels are the molecular targets of local anesthetics, class I antiarrhythmic drugs, and some anticonvulsants. These chemically diverse drugs inhibit Na+ channels with complex voltage- and frequency-dependent properties that reflect preferential drug binding to open and inactivated channel states. The site-directed mutations F1764A and Y1771A in transmembrane segment IVS6 of type IIA Na+ channel alpha subunits dramatically reduce the affinity of inactivated channels for the local anesthetic etidocaine. In this study, we show that these mutations also greatly reduce the sensitivity of Na+ channels to state-dependent block by the class Ib antiarrhythmic drug lidocaine and the anticonvulsant phenytoin and, to a lesser extent, reduce the sensitivity to block by the class Ia and Ic antiarrhythmic drugs quinidine and flecainide. For lidocaine and phenytoin, which bind preferentially to inactivated Na+ channels, the mutation F1764A reduced the affinity for binding to the inactivated state 24.5-fold and 8.3-fold, respectively, while Y1771A had smaller effects. For quinidine and flecainide, which bind preferentially to the open Na+ channels, the mutations F1764A and Y1771A reduced the affinity for binding to the open state 2- to 3-fold. Thus, F1764 and Y1771 are common molecular determinants of state-dependent binding of diverse drugs including lidocaine, phenytoin, flecainide, and quinidine, suggesting that these drugs interact with a common receptor site. However, the different magnitude of the effects of these mutations on binding of the individual drugs indicates that they interact in an overlapping, but nonidentical, manner with a common receptor site. These results further define the contributions of F1764 and Y1771 to a complex drug receptor site in the pore of Na+ channels.

Nonuniformity of the constitutive law parameters for shear rupture and quasistatic nucleation to dynamic rupture: a physical model of earthquake generation processes.

Based on the recent high-resolution laboratory experiments on propagating shear rupture, the constitutive law that governs shear rupture processes is discussed in view of the physical principles and constraints, and a specific constitutive law is proposed for shear rupture. It is demonstrated that nonuniform distributions of the constitutive law parameters on the fault are necessary for creating the nucleation process, which consists of two phases: (i) a stable, quasistatic phase, and (ii) the subsequent accelerating phase. Physical models of the breakdown zone and the nucleation zone are presented for shear rupture in the brittle regime. The constitutive law for shear rupture explicitly includes a scaling parameter Dc that enables one to give a common interpretation to both small scale rupture in the laboratory and large scale rupture as earthquake source in the Earth. Both the breakdown zone size Xc and the nucleation zone size L are prescribed and scaled by Dc, which in turn is prescribed by a characteristic length lambda c representing geometrical irregularities of the fault. The models presented here make it possible to understand the earthquake generation process from nucleation to unstable, dynamic rupture propagation in terms of physics. Since the nucleation process itself is an immediate earthquake precursor, deep understanding of the nucleation process in terms of physics is crucial for the short-term (or immediate) earthquake prediction.

Membrane transport mechanisms probed by capacitance measurements with megahertz voltage clamp.

We have used capacitance measurements with a 1-microsecond voltage clamp technique to probe electrogenic ion-transporter interactions in giant excised membrane patches. The hydrophobic ion dipicrylamine was used to test model predictions for a simple charge-moving reaction. The voltage and frequency dependencies of the apparent dipicrylamine-induced capacitance, monitored by 1-mV sinusoidal perturbations, correspond to single charges moving across 76% of the membrane field at a rate of 9500 s-1 at 0 mV. For the cardiac Na,K pump, the combined presence of cytoplasmic ATP and sodium induces an increase of apparent membrane capacitance which requires the presence of extracellular sodium. The dependencies of capacitance changes on frequency, voltage, ATP, and sodium verify that phosphorylation enables a slow, 300- to 900-s-1, pump transition (the E1-E2 conformational change), which in turn enables fast, electrogenic, extracellular sodium binding reactions. For the GAT1 (gamma-aminobutyric acid,Na,Cl) cotransporter, expressed in Xenopus oocyte membrane, we find that chloride binding from the cytoplasmic side, and probably sodium binding from the extracellular side, results in a decrease of membrane capacitance monitored with 1- to 50-kHz perturbation frequencies. Evidently, ion binding by the GAT1 transporter suppresses an intrinsic fast charge movement which may originate from a mobility of charged residues of the transporter binding sites. The results demonstrate that fast capacitance measurements can provide new insight into electrogenic processes closely associated with ion binding by membrane transporters.

Static versus dynamic heterogeneities in the D=3 Edwards-Anderson-ising spin glass

We numerically study the aging properties of the dynamical heterogeneities in the Ising spin glass. We find that a phase transition takes place during the aging process. Statics-dynamics correspondence implies that systems of finite size in equilibrium have static heterogeneities that obey finite-size scaling, thus signaling an analogous phase transition in the thermodynamical limit. We compute the critical exponents and the transition point in the equilibrium setting, and use them to show that aging in dynamic heterogeneities can be described by a finite-time scaling ansatz, with potential implications for experimental work.

Analysis of a metallic pedestrian bridge under dynamic human loads in pre and post reinforcement phases

The purpose of this work is to study the dynamic behavior of a pedestrian bridge in Alicante, Spain. It is a very slender footbridge with vertical and horizontal vibration problems during the passage of pedestrians. Accelerations have been recorded by accelerometers installed at various locations of the bridge. Two scenarios, in free vibration (after the passage of a certain number of pedestrians on the bridge) and forced vibration produced by a fixed number of pedestrians walking on the bridge at a certain speed and frequency. In each test, the effect on the comfort of the pedestrians, the natural frequencies of vibration, the mode shapes and damping factors have been estimated. It has been found that the acceleration levels are much higher than the allowable by the Spanish standards and this should be considered in the restoration of the footbridge.