911 resultados para Escape From Vehicle.


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This paper deals with the prediction of velocity fields on the 2415-3S airfoil which will be used for an unmanned aerial vehicle with internal propulsion system and in this way analyze the air flow through an internal duct of the airfoil using computational fluid dynamics. The main objective is to evaluate the effect of the internal air flow past the airfoil and how this affects the aerodynamic performance by means of lift and drag forces. For this purpose, three different designs of the internal duct were studied; starting from the base 2415-3S airfoil developed in previous investigation, basing on the hypothesis of decreasing the flow separation produced when the propulsive airflow merges the external flow, and in this way obtaining the best configuration. For that purpose, an exhaustive study of the mesh sensitivity was performed. It was used a non-structured mesh since the computational domain is three-dimensional and complex. The selected mesh contains approximately 12.5 million elements. Both the computational domain and the numerical solution were made with commercial CAD and CFD software, respectively. Air, incompressible and steady was analyzed. The boundary conditions are in concordance with experimental setup in the AF 6109 wind tunnel. The k-e model is utilized to describe the turbulent flow process as followed in references. Results allowed obtaining velocity contours as well as lift and drag coefficients and also the location of separation and reattachment regions in some cases for zero degrees of angle of attack on the internal and external surfaces of the airfoil. Finally, the selection of the configuration with the best aerodynamic performance was made, selecting the option without curved baffles.

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This paper deals with the prediction of pressure and velocity fields on the 2415-3S airfoil which will be used for and unmanned aerial vehicle with internal propulsion system and in this way analyze the air flow through an internal duct of the airfoil using computational fluid dynamics. The main objective is to evaluate the effect of the internal air flow past the airfoil and how this affects the aerodynamic performance by means of lift and drag forces. For this purpose, three different designs of the internal duct were studied; starting from the base 2415-3S airfoil developed in previous investigation, basing on the hypothesis of decreasing the flow separation produced when the propulsive airflow merges the external flow, and in this way obtaining the best configuration. For that purpose, an exhaustive study of the mesh sensitivity was performed. It was used a non-structured mesh since the computational domain is tridimensional and complex. The selected mesh contains approximately 12.5 million elements. Both the computational domain and the numerical solution were made with commercial CAD and CFD software respectively. Air, incompressible and steady was analyzed. The boundary conditions are in concordance with experimental setup in the AF 6109 wind tunnel. The k-ε model is utilized to describe the turbulent flow process as followed in references. Results allowed obtaining pressure and velocity contours as well as lift and drag coefficients and also the location of separation and reattachment regions in some cases for zero degrees of angle of attack on the internal and external surfaces of the airfoil. Finally, the selection of the configuration with the best aerodynamic performance was made, selecting the option without curved baffles.

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In recent decades, full electric and hybrid electric vehicles have emerged as an alternative to conventional cars due to a range of factors, including environmental and economic aspects. These vehicles are the result of considerable efforts to seek ways of reducing the use of fossil fuel for vehicle propulsion. Sophisticated technologies such as hybrid and electric powertrains require careful study and optimization. Mathematical models play a key role at this point. Currently, many advanced mathematical analysis tools, as well as computer applications have been built for vehicle simulation purposes. Given the great interest of hybrid and electric powertrains, along with the increasing importance of reliable computer-based models, the author decided to integrate both aspects in the research purpose of this work. Furthermore, this is one of the first final degree projects held at the ETSII (Higher Technical School of Industrial Engineers) that covers the study of hybrid and electric propulsion systems. The present project is based on MBS3D 2.0, a specialized software for the dynamic simulation of multibody systems developed at the UPM Institute of Automobile Research (INSIA). Automobiles are a clear example of complex multibody systems, which are present in nearly every field of engineering. The work presented here benefits from the availability of MBS3D software. This program has proven to be a very efficient tool, with a highly developed underlying mathematical formulation. On this basis, the focus of this project is the extension of MBS3D features in order to be able to perform dynamic simulations of hybrid and electric vehicle models. This requires the joint simulation of the mechanical model of the vehicle, together with the model of the hybrid or electric powertrain. These sub-models belong to completely different physical domains. In fact the powertrain consists of energy storage systems, electrical machines and power electronics, connected to purely mechanical components (wheels, suspension, transmission, clutch…). The challenge today is to create a global vehicle model that is valid for computer simulation. Therefore, the main goal of this project is to apply co-simulation methodologies to a comprehensive model of an electric vehicle, where sub-models from different areas of engineering are coupled. The created electric vehicle (EV) model consists of a separately excited DC electric motor, a Li-ion battery pack, a DC/DC chopper converter and a multibody vehicle model. Co-simulation techniques allow car designers to simulate complex vehicle architectures and behaviors, which are usually difficult to implement in a real environment due to safety and/or economic reasons. In addition, multi-domain computational models help to detect the effects of different driving patterns and parameters and improve the models in a fast and effective way. Automotive designers can greatly benefit from a multidisciplinary approach of new hybrid and electric vehicles. In this case, the global electric vehicle model includes an electrical subsystem and a mechanical subsystem. The electrical subsystem consists of three basic components: electric motor, battery pack and power converter. A modular representation is used for building the dynamic model of the vehicle drivetrain. This means that every component of the drivetrain (submodule) is modeled separately and has its own general dynamic model, with clearly defined inputs and outputs. Then, all the particular submodules are assembled according to the drivetrain configuration and, in this way, the power flow across the components is completely determined. Dynamic models of electrical components are often based on equivalent circuits, where Kirchhoff’s voltage and current laws are applied to draw the algebraic and differential equations. Here, Randles circuit is used for dynamic modeling of the battery and the electric motor is modeled through the analysis of the equivalent circuit of a separately excited DC motor, where the power converter is included. The mechanical subsystem is defined by MBS3D equations. These equations consider the position, velocity and acceleration of all the bodies comprising the vehicle multibody system. MBS3D 2.0 is entirely written in MATLAB and the structure of the program has been thoroughly studied and understood by the author. MBS3D software is adapted according to the requirements of the applied co-simulation method. Some of the core functions are modified, such as integrator and graphics, and several auxiliary functions are added in order to compute the mathematical model of the electrical components. By coupling and co-simulating both subsystems, it is possible to evaluate the dynamic interaction among all the components of the drivetrain. ‘Tight-coupling’ method is used to cosimulate the sub-models. This approach integrates all subsystems simultaneously and the results of the integration are exchanged by function-call. This means that the integration is done jointly for the mechanical and the electrical subsystem, under a single integrator and then, the speed of integration is determined by the slower subsystem. Simulations are then used to show the performance of the developed EV model. However, this project focuses more on the validation of the computational and mathematical tool for electric and hybrid vehicle simulation. For this purpose, a detailed study and comparison of different integrators within the MATLAB environment is done. Consequently, the main efforts are directed towards the implementation of co-simulation techniques in MBS3D software. In this regard, it is not intended to create an extremely precise EV model in terms of real vehicle performance, although an acceptable level of accuracy is achieved. The gap between the EV model and the real system is filled, in a way, by introducing the gas and brake pedals input, which reflects the actual driver behavior. This input is included directly in the differential equations of the model, and determines the amount of current provided to the electric motor. For a separately excited DC motor, the rotor current is proportional to the traction torque delivered to the car wheels. Therefore, as it occurs in the case of real vehicle models, the propulsion torque in the mathematical model is controlled through acceleration and brake pedal commands. The designed transmission system also includes a reduction gear that adapts the torque coming for the motor drive and transfers it. The main contribution of this project is, therefore, the implementation of a new calculation path for the wheel torques, based on performance characteristics and outputs of the electric powertrain model. Originally, the wheel traction and braking torques were input to MBS3D through a vector directly computed by the user in a MATLAB script. Now, they are calculated as a function of the motor current which, in turn, depends on the current provided by the battery pack across the DC/DC chopper converter. The motor and battery currents and voltages are the solutions of the electrical ODE (Ordinary Differential Equation) system coupled to the multibody system. Simultaneously, the outputs of MBS3D model are the position, velocity and acceleration of the vehicle at all times. The motor shaft speed is computed from the output vehicle speed considering the wheel radius, the gear reduction ratio and the transmission efficiency. This motor shaft speed, somehow available from MBS3D model, is then introduced in the differential equations corresponding to the electrical subsystem. In this way, MBS3D and the electrical powertrain model are interconnected and both subsystems exchange values resulting as expected with tight-coupling approach.When programming mathematical models of complex systems, code optimization is a key step in the process. A way to improve the overall performance of the integration, making use of C/C++ as an alternative programming language, is described and implemented. Although this entails a higher computational burden, it leads to important advantages regarding cosimulation speed and stability. In order to do this, it is necessary to integrate MATLAB with another integrated development environment (IDE), where C/C++ code can be generated and executed. In this project, C/C++ files are programmed in Microsoft Visual Studio and the interface between both IDEs is created by building C/C++ MEX file functions. These programs contain functions or subroutines that can be dynamically linked and executed from MATLAB. This process achieves reductions in simulation time up to two orders of magnitude. The tests performed with different integrators, also reveal the stiff character of the differential equations corresponding to the electrical subsystem, and allow the improvement of the cosimulation process. When varying the parameters of the integration and/or the initial conditions of the problem, the solutions of the system of equations show better dynamic response and stability, depending on the integrator used. Several integrators, with variable and non-variable step-size, and for stiff and non-stiff problems are applied to the coupled ODE system. Then, the results are analyzed, compared and discussed. From all the above, the project can be divided into four main parts: 1. Creation of the equation-based electric vehicle model; 2. Programming, simulation and adjustment of the electric vehicle model; 3. Application of co-simulation methodologies to MBS3D and the electric powertrain subsystem; and 4. Code optimization and study of different integrators. Additionally, in order to deeply understand the context of the project, the first chapters include an introduction to basic vehicle dynamics, current classification of hybrid and electric vehicles and an explanation of the involved technologies such as brake energy regeneration, electric and non-electric propulsion systems for EVs and HEVs (hybrid electric vehicles) and their control strategies. Later, the problem of dynamic modeling of hybrid and electric vehicles is discussed. The integrated development environment and the simulation tool are also briefly described. The core chapters include an explanation of the major co-simulation methodologies and how they have been programmed and applied to the electric powertrain model together with the multibody system dynamic model. Finally, the last chapters summarize the main results and conclusions of the project and propose further research topics. In conclusion, co-simulation methodologies are applicable within the integrated development environments MATLAB and Visual Studio, and the simulation tool MBS3D 2.0, where equation-based models of multidisciplinary subsystems, consisting of mechanical and electrical components, are coupled and integrated in a very efficient way.

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Here, a simple theoretical model of the vehicle induced flow and its effects on traffic sign panels is presented. The model is a continuation of a previous one by Sanz-Andrés and coworkers, now including the flexibility of the panel (and, therefore, the flow effects associated to the motion of the panel). Through the paper an aeroelastic one-degree-of-freedom model is developed and the flow effects are computed from unsteady potential theory. The influence of panel's mechanical properties (mass, damping ratio, and stiffness) in the motion induced forces are numerically analyzed.

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The determination of the loads on traffic sign panels in the current standards does not, in general, take into account the vehicle-induced loads, as explained by Quinn, Baker and Wright (QBW in what follows) (J. Wind Eng. Ind. Aerodyn. 89 (2001) 831). On the other hand, a report from Cali and Covert (CC) (J. Wind Eng. Ind. Aerodyn. 84 (2000) 87) indicates that in highway sign support structures, vehicle-induced loads have led to premature failures in some cases. The aim of this paper is to present a mathematical model for the vehicle-induced load on a flat sign panel, simple enough to give analytical results, but able to explain the main characteristics of the phenomenon. The results of the theoretical model help to explain the behaviour observed in the experiments performed in previous studies.

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En las últimas tres décadas, las dinámicas de restructuración económica a nivel global han redefinido radicalmente el papel de las ciudades. La transición del keynesianismo al neoliberalismo ha provocado un cambio en las políticas urbanas de los gobiernos municipales, que han abandonado progresivamente las tareas de regulación y redistribución para centrarse en la promoción del crecimiento económico y la competitividad. En este contexto, muchas voces críticas han señalado que la regeneración urbana se ha convertido en un vehículo de extracción de valor de la ciudad y está provocando la expulsión de los ciudadanos más vulnerables. Sin embargo, la regeneración de áreas consolidadas supone también una oportunidad de mejora de las condiciones de vida de la población residente, y es una política necesaria para controlar la expansión de la ciudad y reducir las necesidades de desplazamiento, promoviendo así ciudades más sostenibles. Partiendo de la hipótesis de que la gobernanza de los procesos de regeneración urbana es clave en el resultado final de las operaciones y determina el modelo de ciudad resultante, el objetivo de esta investigación es verificar si la regeneración urbana es necesariamente un mecanismo de extracción de valor o si puede mejorar la calidad de vida en las ciudades a través de la participación de los ciudadanos. Para ello, propone un marco de análisis del proceso de toma de decisiones en los planes de regeneración urbana y su impacto en los resultados de los planes, tomando como caso de estudio la ciudad de Boston, que desde los años 1990 trata de convertirse en una “ciudad de los barrios”, fomentando la participación ciudadana al tiempo que se posiciona en la escena económica global. El análisis se centra en dos operaciones de regeneración iniciadas a finales de los años 1990. Por un lado, el caso de Jackson Square nos permite comprender el papel de la sociedad civil y el tercer sector en la regeneración de los barrios más desfavorecidos, en un claro ejemplo de urbanismo “desde abajo” (bottom-up planning). Por otro, la reconversión del frente marítimo de South Boston para la construcción del Distrito de Innovación nos acerca a las grandes operaciones de regeneración urbana con fines de estímulo económico, tradicionalmente vinculadas a los centros financieros (downtown) y dirigidas por las élites gubernamentales y económicas (la growth machine) a través de procesos más tecnocráticos (top-down planning). La metodología utilizada consiste en el análisis cualitativo de los procesos de toma de decisiones y la relación entre los agentes implicados, así como de la evaluación de la implementación de dichas decisiones y su influencia en el modelo urbano resultante. El análisis de los casos permite afirmar que la gobernanza de los procesos de regeneración urbana influye decisivamente en el resultado final de las intervenciones; sin embargo, la participación de la comunidad local en la toma de decisiones no es suficiente para que el resultado de la regeneración urbana contrarreste los efectos de la neoliberalización, especialmente si se limita a la fase de planeamiento y no se extiende a la fase de ejecución, y si no está apoyada por una movilización política de mayor alcance que asegure una acción pública redistributiva. Asimismo, puede afirmarse que los procesos de regeneración urbana suponen una redefinición del modelo de ciudad, dado que la elección de los espacios de intervención tiene consecuencias sobre el equilibrio territorial de la ciudad. Los resultados de esta investigación tienen implicaciones para la disciplina del planeamiento urbano. Por una parte, se confirma la vigencia del paradigma del “urbanismo negociado”, si bien bajo discursos de liderazgo público y sin apelación al protagonismo del sector privado. Por otra parte, la planificación colaborativa en un contexto de “responsabilización” de las organizaciones comunitarias puede desactivar la potencia política de la participación ciudadana y servir como “amortiguador” hacia el gobierno local. Asimismo, la sustitución del planeamiento general como instrumento de definición de la ciudad futura por una planificación oportunista basada en la actuación en áreas estratégicas que tiren del resto de la ciudad, no permite definir un modelo coherente y consensuado de la ciudad que se desea colectivamente, ni permite utilizar el planeamiento como mecanismo de redistribución. ABSTRACT In the past three decades, the dynamics of global economic restructuring have radically redefined the role of cities. The transition from keynesianism to neoliberalism has caused a shift in local governments’ urban policies, which have progressively abandoned the tasks of regulation and redistribution to focus on promoting economic growth and competitiveness. In this context, many critics have pointed out that urban regeneration has become a vehicle for extracting value from the city and is causing the expulsion of the most vulnerable citizens. However, regeneration of consolidated areas is also an opportunity to improve the living conditions of the resident population, and is a necessary policy to control the expansion of the city and reduce the need for transportation, thus promoting more sustainable cities. Assuming that the governance of urban regeneration processes is key to the final outcome of the plans and determines the resulting city model, the goal of this research is to verify whether urban regeneration is necessarily a value extraction mechanism or if it can improve the quality of life in cities through citizens’ participation. It proposes a framework for analysis of decision-making in urban regeneration processes and their impact on the results of the plans, taking as a case study the city of Boston, which since the 1990s is trying to become a "city of neighborhoods", encouraging citizen participation, while seeking to position itself in the global economic scene. The analysis focuses on two redevelopment plans initiated in the late 1990s. The Jackson Square case allows us to understand the role of civil society and the third sector in the regeneration of disadvantaged neighborhoods, in a clear example of bottom-up planning. On the contrary, the conversion of the South Boston waterfront to build the Innovation District takes us to the big redevelopment efforts with economic stimulus’ goals, traditionally linked to downtowns and led by government and economic elites (the local “growth machine”) through more technocratic processes (top-down planning). The research is based on a qualitative analysis of the processes of decision making and the relationship between those involved, as well as the evaluation of the implementation of those decisions and their influence on the resulting urban model. The analysis suggests that the governance of urban regeneration processes decisively influences the outcome of interventions; however, community engagement in the decision-making process is not enough for the result of the urban regeneration to counteract the effects of neoliberalization, especially if it is limited to the planning phase and does not extend to the implementation of the projects, and if it is not supported by a broader political mobilization to ensure a redistributive public action. Moreover, urban regeneration processes redefine the urban model, since the choice of intervention areas has important consequences for the territorial balance of the city. The results of this study have implications for the discipline of urban planning. On the one hand, it confirms the validity of the "negotiated planning" paradigm, albeit under public leadership discourse and without a direct appeal to the leadership role of the private sector. On the other hand, collaborative planning in a context of "responsibilization" of community based organizations can deactivate the political power of citizen participation and serve as a "buffer" towards the local government. Furthermore, the replacement of comprehensive planning, as a tool for defining the city's future, by an opportunistic planning based on intervention in strategic areas that are supposed to induce change in the rest of the city, does not allow a coherent and consensual urban model that is collectively desired, nor it allows to use planning as a redistribution mechanism.

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In electric vehicles, passengers sit very close to an electric system of significant power. The high currents achieved in these vehicles mean that the passengers could be exposed to significant magnetic fields. One of the electric devices present in the power train are the batteries. In this paper, a methodology to evaluate the magnetic field created by these batteries is presented. First, the magnetic field generated by a single battery is analyzed using finite elements simulations. Results are compared to laboratory measurements, taken from a real battery, in order to validate the model. After this, the magnetic field created by a complete battery pack is estimated and results are discussed.

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En esta tesis se analiza el sistema de tracción de un vehículo eléctrico de batería desde el punto de vista de la eficiencia energética y de la exposición a campos magnéticos por parte de los pasajeros (radiación electromagnética). Este estudio incluye tanto el sistema de almacenamiento de energía como la máquina eléctrica, junto con la electrónica de potencia y los sistemas de control asociados a ambos. Los análisis y los resultados presentados en este texto están basados en modelos matemáticos, simulaciones por ordenador y ensayos experimentales a escala de laboratorio. La investigación llevada a cabo durante esta tesis tuvo siempre un marcado enfoque industrial, a pesar de estar desarrollada en un entorno de considerable carácter universitario. Las líneas de investigación acometidas tuvieron como destinatario final al diseñador y al fabricante del vehículo, a pesar de lo cual algunos de los resultados obtenidos son preliminares y/o excesivamente académicos para resultar de interés industrial. En el ámbito de la eficiencia energética, esta tesis estudia sistemas híbridos de almacenamiento de energía basados en una combinación de baterías de litio y supercondensadores. Este tipo de sistemas son analizados desde el punto de vista de la eficiencia mediante modelos matemáticos y simulaciones, cuantificando el impacto de ésta en otros parámetros tales como el envejecimiento de las baterías. Respecto a la máquina eléctrica, el estudio se ha centrado en máquinas síncronas de imanes permanentes. El análisis de la eficiencia considera tanto el diseño de la máquina como la estrategia de control, dejando parcialmente de lado el inversor y la técnica de modulación (que son incluidos en el estudio como fuentes adicionales de pérdidas, pero no como potenciales fuentes de optimización de la eficiencia). En este sentido, tanto la topología del inversor (trifásico, basado en IGBTs) como la técnica de modulación (control de corriente en banda de histéresis) se establecen desde el principio. El segundo aspecto estudiado en esta tesis es la exposición a campos magnéticos por parte de los pasajeros. Este tema se enfoca desde un punto de vista predictivo, y no desde un punto de vista de diagnóstico, puesto que se ha desarrollado una metodología para estimar el campo magnético generado por los dispositivos de potencia de un vehículo eléctrico. Esta metodología ha sido validada mediante ensayos de laboratorio. Otros aspectos importantes de esta contribución, además de la metodología en sí misma, son las consecuencias que se derivan de ella (por ejemplo, recomendaciones de diseño) y la comprensión del problema proporcionada por esta. Las principales contribuciones de esta tesis se listan a continuación: una recopilación de modelos de pérdidas correspondientes a la mayoría de dispositivos de potencia presentes en un vehículo eléctrico de batería, una metodología para analizar el funcionamiento de un sistema híbrido de almacenamiento de energía para aplicaciones de tracción, una explicación de cómo ponderar energéticamente los puntos de operación par-velocidad de un vehículo eléctrico (de utilidad para evaluar el rendimiento de una máquina eléctrica, por ejemplo), una propuesta de incluir un convertidor DC-DC en el sistema de tracción para minimizar las pérdidas globales del accionamiento (a pesar de las nuevas pérdidas introducidas por el propio DC-DC), una breve comparación entre dos tipos distintos de algoritmos de minimización de pérdidas para máquinas síncronas de imanes permanentes, una metodología predictiva para estimar la exposición a campos magnéticos por parte de los pasajeros de un vehículo eléctrico (debida a los equipos de potencia), y finalmente algunas conclusiones y recomendaciones de diseño respecto a dicha exposición a campos magnéticos. ABSTRACT This dissertation analyzes the powertrain of a battery electric vehicle, focusing on energy efficiency and passenger exposure to electromagnetic fields (electromagnetic radiation). This study comprises the energy storage system as well as the electric machine, along with their associated power electronics and control systems. The analysis and conclusions presented in this dissertation are based on mathematical models, computer simulations and laboratory scale tests. The research performed during this thesis was intended to be of industrial nature, despite being developed in a university. In this sense, the work described in this document was carried out thinking of both the designer and the manufacturer of the vehicle. However, some of the results obtained lack industrial readiness, and therefore they remain utterly academic. Regarding energy efficiency, hybrid energy storage systems consisting in lithium batteries, supercapacitors and up to two DC-DC power converters are considered. These kind of systems are analyzed by means of mathematical models and simulations from the energy efficiency point of view, quantifying its impact on other relevant aspects such as battery aging. Concerning the electric machine, permanent magnet synchronous machines are studied in this work. The energy efficiency analysis comprises the machine design and the control strategy, while the inverter and its modulation technique are taken into account but only as sources of further power losses, and not as potential sources for further efficiency optimization. In this sense, both the inverter topology (3-phase IGBT-based inverter) and the switching technique (hysteresis current control) are fixed from the beginning. The second aspect studied in this work is passenger exposure to magnetic fields. This topic is approached from the prediction point of view, rather than from the diagnosis point of view. In other words, a methodology to estimate the magnetic field generated by the power devices of an electric vehicle is proposed and analyzed in this dissertation. This methodology has been validated by laboratory tests. The most important aspects of this contribution, apart from the methodology itself, are the consequences (for instance, design guidelines) and the understanding of the magnetic radiation issue provided by it. The main contributions of this dissertation are listed next: a compilation of loss models for most of the power devices found in a battery electric vehicle powertrain, a simulation-based methodology to analyze hybrid energy storage performance in traction applications, an explanation of how to assign energy-based weights to different operating points in traction drives (useful when assessing electrical machine performance, for instance), a proposal to include one DC-DC converter in electric powertrains to minimize overall power losses in the system (despite the new losses added by the DC-DC), a brief comparison between two kinds of loss-minimization algorithms for permanent magnet synchronous machines in terms of adaptability and energy efficiency, a predictive methodology to estimate passenger magnetic field exposure due to power devices in an electric vehicle, and finally some useful conclusions and design guidelines concerning magnetic field exposure.

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Multidrug resistance mediated by the drug efflux protein, P-glycoprotein (P-gp), is one mechanism that tumor cells use to escape death induced by chemotherapeutic agents. However, the mechanism by which P-gp confers resistance to a large variety of structurally diverse molecules has remained elusive. In this study, classical multidrug resistant human CEM and K562 tumor cell lines expressing high levels of P-gp were less sensitive to multiple forms of caspase-dependent cell death, including that mediated by cytotoxic drugs and ligation of Fas. The DNA fragmentation and membrane damage inflicted by these stimuli were defined as caspase dependent by various soluble peptide fluoromethylketone caspase inhibitors. Inhibition of P-gp function by the anti-P-gp mAb MRK-16 or verapamil could reverse resistance to these forms of cell death. Inhibition of P-gp function also enhanced drug or Fas-mediated activation of caspase-3 in drug-resistant CEM cells. By contrast, caspase-independent cell death events in the same cells, including those mediated by pore-forming proteins or intact NK cells, were not affected by P-gp expression. These observations suggest that, in addition to effluxing drugs, P-gp may play a specific role in regulating some caspase-dependent apoptotic pathways.

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A model system for the in vivo control of tumor cell proliferation by the immune system has been used to assay for the possible immunosuppressive activity of retroviral proteins. Expression vectors for the entire or the transmembrane subunit of the Moloney murine leukemia virus envelope protein were constructed, as well as control vectors for irrelevant transmembrane proteins—or no protein. They were introduced either into MCA205 murine tumor cells, which do not proliferate upon s.c. injection into an allogeneic host, or into CL8.1 murine tumor cells, which overexpress class I antigens and are rejected in a syngeneic host. In both cases, expression of the complete envelope protein or of the transmembrane subunit resulted in tumor growth in vivo, with no effect of control vectors. Tumor cell growth results from inhibition of the host immune response, as the envelope-dependent effect was no more observed for MCA205 cells in syngeneic mice or for CL8.1 cells in x-irradiated mice. This inhibition is local because it is not observed at the level of control tumor cells injected contralaterally. These results suggest a noncanonical function of retroviral envelopes in the “penetrance” of viral infections, as well as a possible involvement of the envelope proteins of endogenous retroviruses in tumoral processes.

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The genetic variability at six polymorphic loci was examined within a global collection of 502 isolates of subgroup III, serogroup A Neisseria meningitidis. Nine “genoclouds” were identified, consisting of genotypes that were isolated repeatedly plus 48 descendent genotypes that were isolated rarely. These genoclouds have caused three pandemic waves of disease since the mid-1960s, the most recent of which was imported from East Asia to Europe and Africa in the mid-1990s. Many of the genotypes are escape variants, resulting from positive selection that we attribute to herd immunity. Despite positive selection, most escape variants are less fit than their parents and are lost because of competition and bottlenecks during spread from country to country. Competition between fit genotypes results in dramatic changes in population composition over short time periods.