890 resultados para Discrete-time sliding mode control


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A set of software development tools for building real-time control systems on a simple robotics platform is described in the paper. The tools are being used in a real-time systems course as a basis for student projects. The development platform is a low-cost PC running GNU/Linux, and the target system is LEGO MINDSTORMS NXT, thus keeping the cost of the laboratory low. Real-time control software is developed using a mixed paradigm. Functional code for control algorithms is automatically generated in C from Simulink models. This code is then integrated into a concurrent, real-time software architecture based on a set of components written in Ada. This approach enables the students to take advantage of the high-level, model-oriented features that Simulink oers for designing control algorithms, and the comprehensive support for concurrency and real-time constructs provided by Ada.

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The combination of minimum time control and multiphase converter is a favorable option for dc-dc converters in applications where output voltage variation is required, such as RF amplifiers and dynamic voltage scaling in microprocessors, due to their advantage of fast dynamic response. In this paper, an improved minimum time control approach for multiphase buck converter that is based on charge balance technique, aiming at fast output voltage transition is presented. Compared with the traditional method, the proposed control takes into account the phase delay and current ripple in each phase. Therefore, by investigating the behavior of multiphase converter during voltage transition, it resolves the problem of current unbalance after the transient, which can lead to long settling time of the output voltage. The restriction of this control is that the output voltage that the converter can provide is related to the number of the phases, because only the duty cycles at which the multiphase converter has total ripple cancellation are used in this approach. The model of the proposed control is introduced, and the design constraints of the buck converters filter for this control are discussed. In order to prove the concept, a four-phase buck converter is implemented and the experimental results that validate the proposed control method are presented. The application of this control to RF envelope tracking is also presented in this paper.

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DNA binding with One Finger (DOF) transcription factors are involved in multiple aspects of plant growth and development but their precise roles in abiotic stress tolerance are largely unknown. Here we report a group of five tomato DOF genes, homologous to Arabidopsis Cycling DOF Factors (CDFs), that function as transcriptional regulators involved in responses to drought and salt stress and flowering-time control in a gene-specific manner. SlCDF1?5 are nuclear proteins that display specific binding with different affinities to canonical DNA target sequences and present diverse transcriptional activation capacities in vivo. SlCDF1?5 genes exhibited distinct diurnal expression patterns and were differentially induced in response to osmotic, salt, heat, and low-temperature stresses. Arabidopsis plants overexpressing SlCDF1 or SlCDF3 showed increased drought and salt tolerance. In addition, the expression of various stress-responsive genes, such as COR15, RD29A, and RD10, were differentially activated in the overexpressing lines. Interestingly, overexpression in Arabidopsis of SlCDF3 but not SlCDF1 promotes late flowering through modulation of the expression of flowering control genes such as CO and FT. Overall, our data connect SlCDFs to undescribed functions related to abiotic stress tolerance and flowering time through the regulation of specific target genes and an increase in particular metabolites

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This article describes a knowledge-based application in the domain of road traffic management that we have developed following a knowledge modeling approach and the notion of problem-solving method. The article presents first a domain-independent model for real-time decision support as a structured collection of problem solving methods. Then, it is described how this general model is used to develop an operational version for the domain of traffic management. For this purpose, a particular knowledge modeling tool, called KSM (Knowledge Structure Manager), was applied. Finally, the article shows an application developed for a traffic network of the city of Madrid and it is compared with a second application developed for a different traffic area of the city of Barcelona.

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El estudio del comportamiento de la atmósfera ha resultado de especial importancia tanto en el programa SESAR como en NextGen, en los que la gestión actual del tránsito aéreo (ATM) está experimentando una profunda transformación hacia nuevos paradigmas tanto en Europa como en los EE.UU., respectivamente, para el guiado y seguimiento de las aeronaves en la realización de rutas más eficientes y con mayor precisión. La incertidumbre es una característica fundamental de los fenómenos meteorológicos que se transfiere a la separación de las aeronaves, las trayectorias de vuelo libres de conflictos y a la planificación de vuelos. En este sentido, el viento es un factor clave en cuanto a la predicción de la futura posición de la aeronave, por lo que tener un conocimiento más profundo y preciso de campo de viento reducirá las incertidumbres del ATC. El objetivo de esta tesis es el desarrollo de una nueva técnica operativa y útil destinada a proporcionar de forma adecuada y directa el campo de viento atmosférico en tiempo real, basada en datos de a bordo de la aeronave, con el fin de mejorar la predicción de las trayectorias de las aeronaves. Para lograr este objetivo se ha realizado el siguiente trabajo. Se han descrito y analizado los diferentes sistemas de la aeronave que proporcionan las variables necesarias para obtener la velocidad del viento, así como de las capacidades que permiten la presentación de esta información para sus aplicaciones en la gestión del tráfico aéreo. Se ha explorado el uso de aeronaves como los sensores de viento en un área terminal para la estimación del viento en tiempo real con el fin de mejorar la predicción de las trayectorias de aeronaves. Se han desarrollado métodos computacionalmente eficientes para estimar las componentes horizontales de la velocidad del viento a partir de las velocidades de las aeronaves (VGS, VCAS/VTAS), la presión y datos de temperatura. Estos datos de viento se han utilizado para estimar el campo de viento en tiempo real utilizando un sistema de procesamiento de datos a través de un método de mínima varianza. Por último, se ha evaluado la exactitud de este procedimiento para que esta información sea útil para el control del tráfico aéreo. La información inicial proviene de una muestra de datos de Registradores de Datos de Vuelo (FDR) de aviones que aterrizaron en el aeropuerto Madrid-Barajas. Se dispuso de datos de ciertas aeronaves durante un periodo de más de tres meses que se emplearon para calcular el vector viento en cada punto del espacio aéreo. Se utilizó un modelo matemático basado en diferentes métodos de interpolación para obtener los vectores de viento en áreas sin datos disponibles. Se han utilizado tres escenarios concretos para validar dos métodos de interpolación: uno de dos dimensiones que trabaja con ambas componentes horizontales de forma independiente, y otro basado en el uso de una variable compleja que relaciona ambas componentes. Esos métodos se han probado en diferentes escenarios con resultados dispares. Esta metodología se ha aplicado en un prototipo de herramienta en MATLAB © para analizar automáticamente los datos de FDR y determinar el campo vectorial del viento que encuentra la aeronave al volar en el espacio aéreo en estudio. Finalmente se han obtenido las condiciones requeridas y la precisión de los resultados para este modelo. El método desarrollado podría utilizar los datos de los aviones comerciales como inputs utilizando los datos actualmente disponibles y la capacidad computacional, para proporcionárselos a los sistemas ATM donde se podría ejecutar el método propuesto. Estas velocidades del viento calculadas, o bien la velocidad respecto al suelo y la velocidad verdadera, se podrían difundir, por ejemplo, a través del sistema de direccionamiento e informe para comunicaciones de aeronaves (ACARS), mensajes de ADS-B o Modo S. Esta nueva fuente ayudaría a actualizar la información del viento suministrada en los productos aeronáuticos meteorológicos (PAM), informes meteorológicos de aeródromos (AIRMET), e información meteorológica significativa (SIGMET). ABSTRACT The study of the atmosphere behaviour is been of particular importance both in SESAR and NextGen programs, where the current air traffic management (ATM) system is undergoing a profound transformation to the new paradigms both in Europe and the USA, respectively, to guide and track aircraft more precisely on more efficient routes. Uncertainty is a fundamental characteristic of weather phenomena which is transferred to separation assurance, flight path de-confliction and flight planning applications. In this respect, the wind is a key factor regarding the prediction of the future position of the aircraft, so that having a deeper and accurate knowledge of wind field will reduce ATC uncertainties. The purpose of this thesis is to develop a new and operationally useful technique intended to provide adequate and direct real-time atmospheric winds fields based on on-board aircraft data, in order to improve aircraft trajectory prediction. In order to achieve this objective the following work has been accomplished. The different sources in the aircraft systems that provide the variables needed to derivate the wind velocity have been described and analysed, as well as the capabilities which allow presenting this information for air traffic management applications. The use of aircraft as wind sensors in a terminal area for real-time wind estimation in order to improve aircraft trajectory prediction has been explored. Computationally efficient methods have been developed to estimate horizontal wind components from aircraft velocities (VGS, VCAS/VTAS), pressure, and temperature data. These wind data were utilized to estimate a real-time wind field using a data processing approach through a minimum variance method. Finally, the accuracy of this procedure has been evaluated for this information to be useful to air traffic control. The initial information comes from a Flight Data Recorder (FDR) sample of aircraft landing in Madrid-Barajas Airport. Data available for more than three months were exploited in order to derive the wind vector field in each point of the airspace. Mathematical model based on different interpolation methods were used in order to obtain wind vectors in void areas. Three particular scenarios were employed to test two interpolation methods: a two-dimensional one that works with both horizontal components in an independent way, and also a complex variable formulation that links both components. Those methods were tested using various scenarios with dissimilar results. This methodology has been implemented in a prototype tool in MATLAB © in order to automatically analyse FDR and determine the wind vector field that aircraft encounter when flying in the studied airspace. Required conditions and accuracy of the results were derived for this model. The method developed could be fed by commercial aircraft utilizing their currently available data sources and computational capabilities, and providing them to ATM system where the proposed method could be run. Computed wind velocities, or ground and true airspeeds, would then be broadcasted, for example, via the Aircraft Communication Addressing and Reporting System (ACARS), ADS-B out messages, or Mode S. This new source would help updating the wind information furnished in meteorological aeronautical products (PAM), meteorological aerodrome reports (AIRMET), and significant meteorological information (SIGMET).

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Hybrid Stepper Motors are widely used in open-loop position applications. They are the choice of actuation for the collimators in the Large Hadron Collider, the largest particle accelerator at CERN. In this case the positioning requirements and the highly radioactive operating environment are unique. The latter forces both the use of long cables to connect the motors to the drives which act as transmission lines and also prevents the use of standard position sensors. However, reliable and precise operation of the collimators is critical for the machine, requiring the prevention of step loss in the motors and maintenance to be foreseen in case of mechanical degradation. In order to make the above possible, an approach is proposed for the application of an Extended Kalman Filter to a sensorless stepper motor drive, when the motor is separated from its drive by long cables. When the long cables and high frequency pulse width modulated control voltage signals are used together, the electrical signals difer greatly between the motor and drive-side of the cable. Since in the considered case only drive-side data is available, it is therefore necessary to estimate the motor-side signals. Modelling the entire cable and motor system in an Extended Kalman Filter is too computationally intensive for standard embedded real-time platforms. It is, in consequence, proposed to divide the problem into an Extended Kalman Filter, based only on the motor model, and separated motor-side signal estimators, the combination of which is less demanding computationally. The efectiveness of this approach is shown in simulation. Then its validity is experimentally demonstrated via implementation in a DSP based drive. A testbench to test its performance when driving an axis of a Large Hadron Collider collimator is presented along with the results achieved. It is shown that the proposed method is capable of achieving position and load torque estimates which allow step loss to be detected and mechanical degradation to be evaluated without the need for physical sensors. These estimation algorithms often require a precise model of the motor, but the standard electrical model used for hybrid stepper motors is limited when currents, which are high enough to produce saturation of the magnetic circuit, are present. New model extensions are proposed in order to have a more precise model of the motor independently of the current level, whilst maintaining a low computational cost. It is shown that a significant improvement in the model It is achieved with these extensions, and their computational performance is compared to study the cost of model improvement versus computation cost. The applicability of the proposed model extensions is demonstrated via their use in an Extended Kalman Filter running in real-time for closed-loop current control and mechanical state estimation. An additional problem arises from the use of stepper motors. The mechanics of the collimators can wear due to the abrupt motion and torque profiles that are applied by them when used in the standard way, i.e. stepping in open-loop. Closed-loop position control, more specifically Field Oriented Control, would allow smoother profiles, more respectful to the mechanics, to be applied but requires position feedback. As mentioned already, the use of sensors in radioactive environments is very limited for reliability reasons. Sensorless control is a known option but when the speed is very low or zero, as is the case most of the time for the motors used in the LHC collimator, the loss of observability prevents its use. In order to allow the use of position sensors without reducing the long term reliability of the whole system, the possibility to switch from closed to open loop is proposed and validated, allowing the use of closed-loop control when the position sensors function correctly and open-loop when there is a sensor failure. A different approach to deal with the switched drive working with long cables is also presented. Switched mode stepper motor drives tend to have poor performance or even fail completely when the motor is fed through a long cable due to the high oscillations in the drive-side current. The design of a stepper motor output fillter which solves this problem is thus proposed. A two stage filter, one devoted to dealing with the diferential mode and the other with the common mode, is designed and validated experimentally. With this ?lter the drive performance is greatly improved, achieving a positioning repeatability even better than with the drive working without a long cable, the radiated emissions are reduced and the overvoltages at the motor terminals are eliminated.

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In this work, we study the bilateral control of a nonlinear teleoperator system with constant delay, proposes a control strategy by state convergence, which directly connect the local and remote manipulator through feedback signals of position and speed. The control signal allows the remote manipulator follow the local manipulator through the state convergence even if it has a delay in the communication channel. The bilateral control of the teleoperator system considers the case when the human operator applies a constant force on the local manipulator and when the interaction of the remote manipulator with the environment is considered passive. The stability analysis is performed using functional of Lyapunov-Krasovskii, it showed that using a control algorithm by state convergence for the case with constant delay, the nonlinear local and remote teleoperation system is asymptotically stable, also speeds converge to zero and position tracking is achieved.

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In this paper, we propose a novel control scheme for bilateral teleoperation of n degree-of-freedom (DOF) nonlinear robotic systems with time-varying communication delay. We consider that the human operator contains a constant force on the local manipulator. The local and remote manipulators are coupled using state convergence control scheme. By choosing a Lyapunov-Krasovskii functional, we show that the local-remote teleoperation system is asymptotically stable. It is also shown that, in the case of reliable communication protocols, the proposed scheme guarantees that the remote manipulator tracks the delayed trajectory of the local manipulator. The time delay of communication channel is assumed to be unknown and randomly time varying, but the upper bounds of the delay interval and the derivative of the delay are assumed to be known.

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A medida que se incrementa la energía de los aceleradores de partículas o iones pesados como el CERN o GSI, de los reactores de fusión como JET o ITER, u otros experimentos científicos, se va haciendo cada vez más imprescindible el uso de técnicas de manipulación remota para la interacción con el entorno sujeto a la radiación. Hasta ahora la tasa de dosis radioactiva en el CERN podía tomar valores cercanos a algunos mSv para tiempos de enfriamiento de horas, que permitían la intervención humana para tareas de mantenimiento. Durante los primeros ensayos con plasma en JET, se alcanzaban valores cercanos a los 200 μSv después de un tiempo de enfriamiento de 4 meses y ya se hacía extensivo el uso de técnicas de manipulación remota. Hay una clara tendencia al incremento de los niveles de radioactividad en el futuro en este tipo de instalaciones. Un claro ejemplo es ITER, donde se esperan valores de 450 Sv/h en el centro del toroide a los 11 días de enfriamiento o los nuevos niveles energéticos del CERN que harán necesario una apuesta por niveles de mantenimiento remotos. En estas circunstancias se enmarca esta tesis, que estudia un sistema de control bilateral basado en fuerza-posición, tratando de evitar el uso de sensores de fuerza/par, cuyo contenido electrónico los hace especialmente sensitivos en estos ambientes. El contenido de este trabajo se centra en la teleoperación de robots industriales, que debido a su reconocida solvencia y facilidad para ser adaptados a estos entornos, unido al bajo coste y alta disponibilidad, les convierte en una alternativa interesante para tareas de manipulación remota frente a costosas soluciones a medida. En primer lugar se considera el problema cinemático de teleoperación maestro-esclavo de cinemática disimilar y se desarrolla un método general para la solución del problema en el que se incluye el uso de fuerzas asistivas para guiar al operador. A continuación se explican con detalle los experimentos realizados con un robot ABB y que muestran las dificultades encontradas y recomendaciones para solventarlas. Se concluye el estudio cinemático con un método para el encaje de espacios de trabajo entre maestro y esclavo disimilares. Posteriormente se mira hacia la dinámica, estudiándose el modelado de robots con vistas a obtener un método que permita estimar las fuerzas externas que actúan sobre los mismos. Durante la caracterización del modelo dinámico, se realizan varios ensayos para tratar de encontrar un compromiso entre complejidad de cálculo y error de estimación. También se dan las claves para modelar y caracterizar robots con estructura en forma de paralelogramo y se presenta la arquitectura de control deseada. Una vez obtenido el modelo completo del esclavo, se investigan diferentes alternativas que permitan una estimación de fuerzas externas en tiempo real, minimizando las derivadas de la posición para minimizar el ruido. Se comienza utilizando observadores clásicos del estado para ir evolucionando hasta llegar al desarrollo de un observador de tipo Luenberger-Sliding cuya implementación es relativamente sencilla y sus resultados contundentes. También se analiza el uso del observador propuesto durante un control bilateral simulado en el que se compara la realimentación de fuerzas obtenida con las técnicas clásicas basadas en error de posición frente a un control basado en fuerza-posición donde la fuerza es estimada y no medida. Se comprueba como la solución propuesta da resultados comparables con las arquitecturas clásicas y sin embargo introduce una alternativa para la teleoperación de robots industriales cuya teleoperación en entornos radioactivos sería imposible de otra manera. Finalmente se analizan los problemas derivados de la aplicación práctica de la teleoperación en los escenarios mencionados anteriormente. Debido a las condiciones prohibitivas para todo equipo electrónico, los sistemas de control se deben colocar a gran distancia de los manipuladores, dando lugar a longitudes de cable de centenares de metros. En estas condiciones se crean sobretensiones en controladores basados en PWM que pueden ser destructivas para el sistema formado por control, cableado y actuador, y por tanto, han de ser eliminadas. En este trabajo se propone una solución basada en un filtro LC comercial y se prueba de forma extensiva que su inclusión no produce efectos negativos sobre el control del actuador. ABSTRACT As the energy on the particle accelerators or heavy ion accelerators such as CERN or GSI, fusion reactors such as JET or ITER, or other scientific experiments is increased, it is becoming increasingly necessary to use remote handling techniques to interact with the remote and radioactive environment. So far, the dose rate at CERN could present values near several mSv for cooling times on the range of hours, which allowed human intervention for maintenance tasks. At JET, they measured values close to 200 μSv after a cooling time of 4 months and since then, the remote handling techniques became usual. There is a clear tendency to increase the radiation levels in the future. A clear example is ITER, where values of 450 Sv/h are expected in the centre of the torus after 11 days of cooling. Also, the new energetic levels of CERN are expected to lead to a more advanced remote handling means. In these circumstances this thesis is framed, studying a bilateral control system based on force-position, trying to avoid the use of force/torque sensors, whose electronic content makes them very sensitive in these environments. The contents of this work are focused on teleoperating industrial robots, which due its well-known reliability, easiness to be adapted to these environments, cost-effectiveness and high availability, are considered as an interesting alternative to expensive custom-made solutions for remote handling tasks. Firstly, the kinematic problem of teloperating master and slave with dissimilar kinematics is analysed and a new general approach for solving this issue is presented. The solution includes using assistive forces in order to guide the human operator. Coming up next, I explain with detail the experiments accomplished with an ABB robot that show the difficulties encountered and the proposed solutions. This section is concluded with a method to match the master’s and slave’s workspaces when they present dissimilar kinematics. Later on, the research studies the dynamics, with special focus on robot modelling with the purpose of obtaining a method that allows to estimate external forces acting on them. During the characterisation of the model’s parameters, a set of tests are performed in order to get to a compromise between computational complexity and estimation error. Key points for modelling and characterising robots with a parallelogram structure are also given, and the desired control architecture is presented. Once a complete model of the slave is obtained, different alternatives for external force estimation are review to be able to predict forces in real time, minimizing the position differentiation to minimize the estimation noise. The research starts by implementing classic state observers and then it evolves towards the use of Luenberger- Sliding observers whose implementation is relatively easy and the results are convincing. I also analyse the use of proposed observer during a simulated bilateral control on which the force feedback obtained with the classic techniques based on the position error is compared versus a control architecture based on force-position, where the force is estimated instead of measured. I t is checked how the proposed solution gives results comparable with the classical techniques and however introduces an alternative method for teleoperating industrial robots whose teleoperation in radioactive environments would have been impossible in a different way. Finally, the problems originated by the practical application of teleoperation in the before mentioned scenarios are analysed. Due the prohibitive conditions for every electronic equipment, the control systems should be placed far from the manipulators. This provokes that the power cables that fed the slaves devices can present lengths of hundreds of meters. In these circumstances, overvoltage waves are developed when implementing drives based on PWM technique. The occurrence of overvoltage is very dangerous for the system composed by drive, wiring and actuator, and has to be eliminated. During this work, a solution based on commercial LC filters is proposed and it is extensively proved that its inclusion does not introduce adverse effects into the actuator’s control.

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The three-dimensional wall-bounded open cavity may be considered as a simplified geometry found in industrial applications such as leading gear or slotted flats on the airplane. Understanding the three-dimensional complex flow structure that surrounds this particular geometry is therefore of major industrial interest. At the light of the remarkable former investigations in this kind of flows, enough evidences suggest that the lateral walls have a great influence on the flow features and hence on their instability modes. Nevertheless, even though there is a large body of literature on cavity flows, most of them are based on the assumption that the flow is two-dimensional and spanwise-periodic. The flow over realistic open cavity should be considered. This thesis presents an investigation of three-dimensional wall-bounded open cavity with geometric ratio 6:2:1. To this aim, three-dimensional Direct Numerical Simulation (DNS) and global linear instability have been performed. Linear instability analysis reveals that the onset of the first instability in this open cavity is around Recr 1080. The three-dimensional shear layer mode with a complex structure is shown to be the most unstable mode. I t is noteworthy that the flow pattern of this high-frequency shear layer mode is similar to the observed unstable oscillations in supercritical unstable case. DNS of the cavity flow carried out at different Reynolds number from steady state until a nonlinear saturated state is obtained. The comparison of time histories of kinetic energy presents a clearly dominant energetic mode which shifts between low-frequency and highfrequency oscillation. A complete flow patterns from subcritical cases to supercritical case has been put in evidence. The flow structure at the supercritical case Re=1100 resembles typical wake-shedding instability oscillations with a lateral motion existed in the subcritical cases. Also, This flow pattern is similar to the observations in experiments. In order to validate the linear instability analysis results, the topology of the composite flow fields reconstructed by linear superposition of a three-dimensional base flow and its leading three-dimensional global eigenmodes has been studied. The instantaneous wall streamlines of those composited flows display distinguish influence region of each eigenmode. Attention has been focused on the leading high-frequency shear layer mode; the composite flow fields have been fully recognized with respect to the downstream wave shedding. The three-dimensional shear layer mode is shown to give rise to a typical wake-shedding instability with a lateral motions occurring downstream which is in good agreement with the experiment results. Moreover, the spanwise-periodic, open cavity with the same length to depth ratio has been also studied. The most unstable linear mode is different from the real three-dimensional cavity flow, because of the existence of the side walls. Structure sensitivity of the unstable global mode is analyzed in the flow control context. The adjoint-based sensitivity analysis has been employed to localized the receptivity region, where the flow is more sensible to momentum forcing and mass injection. Because of the non-normality of the linearized Navier-Stokes equations, the direct and adjoint field has a large spatial separation. The strongest sensitivity region is locate in the upstream lip of the three-dimensional cavity. This numerical finding is in agreement with experimental observations. Finally, a prototype of passive flow control strategy is applied.

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A procedure for measuring the overheating temperature (ΔT ) of a p-n junction area in the structure of photovoltaic (PV) cells converting laser or solar radiations relative to the ambient temperature has been proposed for the conditions of connecting to an electric load. The basis of the procedure is the measurement of the open-circuit voltage (VO C ) during the initial time period after the fast disconnection of the external resistive load. The simultaneous temperature control on an external heated part of a PV module gives the means for determining the value of VO C at ambient temperature. Comparing it with that measured after switching OFF the load makes the calculation of ΔT possible. Calibration data on the VO C = f(T ) dependences for single-junction AlGaAs/GaAs and triple-junction InGaP/GaAs/Ge PV cells are presented. The temperature dynamics in the PV cells has been determined under flash illumination and during fast commutation of the load. Temperature measurements were taken in two cases: converting continuous laser power by single-junction cells and converting solar power by triple-junction cells operating in the concentrator modules.

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Temporal patterning of biological variables, in the form of oscillations and rhythms on many time scales, is ubiquitous. Altering the temporal pattern of an input variable greatly affects the output of many biological processes. We develop here a conceptual framework for a quantitative understanding of such pattern dependence, focusing particularly on nonlinear, saturable, time-dependent processes that abound in biophysics, biochemistry, and physiology. We show theoretically that pattern dependence is governed by the nonlinearity of the input–output transformation as well as its time constant. As a result, only patterns on certain time scales permit the expression of pattern dependence, and processes with different time constants can respond preferentially to different patterns. This has implications for temporal coding and decoding, and allows differential control of processes through pattern. We show how pattern dependence can be quantitatively predicted using only information from steady, unpatterned input. To apply our ideas, we analyze, in an experimental example, how muscle contraction depends on the pattern of motorneuron firing.

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The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells. In addition, VEGF/VPF is a potent angiogenic factor. Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a human colon adenocarcinoma (LS174T), and a human melanoma (P-MEL) into two locations in immunodeficient mice: the cranial window and the dorsal skinfold chamber. The mice bearing vascularized tumors were treated with a bolus (0.2 ml) of either a neutralizing antibody (A4.6.1) (492 μg/ml) against VEGF/VPF or PBS (control). We found that tumor vascular permeability to albumin in antibody-treated groups was lower than in the matched controls and that the effect of the antibody was time-dependent and influenced by the mode of injection. Tumor vascular permeability did not respond to i.p. injection of the antibody until 4 days posttreatment. However, the permeability was reduced within 6 h after i.v. injection of the same amount of antibody. In addition to the reduction in vascular permeability, the tumor vessels became smaller in diameter and less tortuous after antibody injections and eventually disappeared from the surface after four consecutive treatments in U87 tumors. These results demonstrate that tumor vascular permeability can be reduced by neutralization of endogenous VEGF/VPF and suggest that angiogenesis and the maintenance of integrity of tumor vessels require the presence of VEGF/VPF in the tissue microenvironment. The latter finding reveals a new mechanism of tumor vessel regression—i.e., blocking the interactions between VEGF/VPF and endothelial cells or inhibiting VEGF/VPF synthesis in solid tumors causes dramatic reduction in vessel diameter, which may block the passage of blood elements and thus lead to vascular regression.

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N-type Ca2+ channels can be inhibited by neurotransmitter-induced release of G protein βγ subunits. Two isoforms of Cav2.2 α1 subunits of N-type calcium channels from rat brain (Cav2.2a and Cav2.2b; initially termed rbB-I and rbB-II) have different functional properties. Unmodulated Cav2.2b channels are in an easily activated “willing” (W) state with fast activation kinetics and no prepulse facilitation. Activating G proteins shifts Cav2.2b channels to a difficult to activate “reluctant” (R) state with slow activation kinetics; they can be returned to the W state by strong depolarization resulting in prepulse facilitation. This contrasts with Cav2.2a channels, which are tonically in the R state and exhibit strong prepulse facilitation. Activating or inhibiting G proteins has no effect. Thus, the R state of Cav2.2a and its reversal by prepulse facilitation are intrinsic to the channel and independent of G protein modulation. Mutating G177 in segment IS3 of Cav2.2b to E as in Cav2.2a converts Cav2.2b tonically to the R state, insensitive to further G protein modulation. The converse substitution in Cav2.2a, E177G, converts it to the W state and restores G protein modulation. We propose that negatively charged E177 in IS3 interacts with a positive charge in the IS4 voltage sensor when the channel is closed and produces the R state of Cav2.2a by a voltage sensor-trapping mechanism. G protein βγ subunits may produce reluctant channels by a similar molecular mechanism.