Acceleration of the PanIN Development in Mice Expressing Oncogenic K-Ras Due to a High Fat Diet

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response triggering increased K-Ras activity and that Cox-2 is essential for this inflammatory reaction. To determine this, LSL-K-Ras mice were crossed with Ela-CreER (Acinar-specific) or Pdx-1-Cre (Pancreas-specific) to “knock-in” oncogenic K-Ras. Additionally, these animals were crossed with Cox-2 conditional knockout mice to access the importance of Cox-2 in the inflammatory loop present. The mice were fed isocaloric diets containing 60% energy or 10% energy from fat. We found that a high fat diet increased K-Ras activity, PanIN formation, and fibrotic stroma significantly compared to a control diet. Genetic deletion of Cox-2 prevented high fat diet induced fibrosis and PanIN formation in oncogenic K-Ras expressing mice. Additionally, long term consumption of high fat diet, increased the progression of PanIN lesions leading to invasive cancer and decreased overall survival rate. These findings indicate that a high fat diet can stimulate the activation of oncogenic K-Ras and initiate an inflammatory feed forward loop requiring Cox-2 leading to inflammation, fibrosis, and PanINs. This mechanism could explain the relationship between a high fat diet and elevated risk for pancreatic cancer.

Anticorrelation between Ion Acceleration and Nonlinear Coherent Structures from Laser-Underdense Plasma Interaction

In laser-plasma experiments, we observed that ion acceleration from the Coulomb explosion of the plasma channel bored by the laser, is prevented when multiple plasma instabilities such as filamentation and hosing, and nonlinear coherent structures (vortices/post-solitons) appear in the wake of an ultrashort laser pulse. The tailoring of the longitudinal plasma density ramp allows us to control the onset of these insabilities. We deduced that the laser pulse is depleted into these structures in our conditions, when a plasma at about 10% of the critical density exhibits a gradient on the order of 250 {\mu}m (gaussian fit), thus hindering the acceleration. A promising experimental setup with a long pulse is demonstrated enabling the excitation of an isolated coherent structure for polarimetric measurements and, in further perspectives, parametric studies of ion plasma acceleration efficiency.

Caracterización de los sistemas de protección basados en materiales naturales destinados al control de la socavación en obras marítimas presentes en instalaciones eólicas marinas

El fenómeno de la socavación puede poner en peligro la operatividad o la seguridad de estructuras offshore comprometiendo su estabilidad global. Hasta el momento, la gran mayoría de las investigaciones destinadas a estudiar el origen y el desarrollo de este fenómeno han estado centradas en entornos fluviales, bajo condiciones de corriente continua. En la última década, debido al crecimiento del mercado de la eólica marina, han surgido numerosos estudios para la caracterización de este fenómeno en el entorno marino, teniendo en cuenta que estas estructuras se encuentran sometidas de forma simultánea a los efectos de la corriente y el oleaje, y las corrientes provocadas por las mareas. Ante la observada carencia de criterios existentes para el diseño de protecciones frente a la socavación, la presente Tesis Doctoral surge con el objetivo principal de desarrollar una serie de recomendaciones que permitan mejorar y optimizar el diseño de estas estructuras, teniendo en cuenta no sólo los parámetros geométricos de las cimentaciones de los aerogeneradores, o la propia erosión, sino también, variables características del oleaje como la altura de ola, el periodo o la longitud de onda, así como la profundidad o la batimétrica de la cimentación. La caracterización de los sistemas de protección basados en materiales naturales destinados al control de la socavación en obras marítimas presentes en instalaciones eólicas marinas no es el único objetivo alcanzado en la presente Tesis Doctoral. A través de la calibración del parámetro de altura de ola adimensional (H0) en diferentes parques eólicos europeos, y de acuerdo al criterio propuesto por Van der Meer (1988), se propone la clasificación de este tipo de estructuras de protección, basadas en material granular o escollera. La información recopilada sobre la socavación registrada en numerosos parques eólicos con protección también ha permitido estudiar la funcionalidad de este tipo de protecciones instaladas hasta la fecha. Asímismo, gracias al conocimiento adquirido sobre el fenómeno de la socavación, se plantea una propuesta para la mejora de la caracterización de este fenómeno en ambiente marino basada en el estudio de la influencia del campo de aceleraciones. La presente Tesis Doctoral permite mejorar el diseño de las protecciones frente a la socavación que se utilizan en parques eólicos marinos teniendo en cuenta las acciones del clima marítimo, supliendo de este modo las carencias que hasta el momento presentan las formulaciones existentes, las cuales únicamente toman en consideración la geometría de las cimentaciones, el ángulo de rozamiento interno del terreno y la estimación de la máxima socavación que puede llegar a producirse. Scour phenomenon jeopardizes the stability and functionality of offshore structures compromising its overall stability. So far, most studies about the origin and the development of this phenomenon have been focused on river environments (under steady current conditions). In the last decade a lot of research projects about the characterization of this phenomenon have been carried out due to the growth of offshore wind industry. These projects take into account that these structures are subjected simultaneously to current, waves and tidal effects. This PhD Thesis arises due to the current lack of criteria for the design of scour protections. Its main objective is to develop some recommendations to improve and to optimize the design of scour protection structures. For that it is necessary to take into account not only the geometrical parameters of foundations or the erosion forecasted, but also wave variables such as wave height, wave period or wavelength. Characterization of protection systems based on natural materials for the control of the scour in offshore wind farms was not the only goal achieved in this PhD Thesis. Through the calibration of the dimensionless wave height parameter (H0) in different European offshore wind farms, and according to the criteria proposed by Van der Meer (1988), a classification of these protection structures based on natural elements (rocks or riprap) has been proposed. Scour data registered in numerous offshore wind farms with scour protection systems also allowed to study the functionality of this type of protection installed up to now. Thanks to the knowledge acquired about the scour development, a proposal for the improvement of the characterization of this phenomenon in marine environment is proposed. This has been based on the study of the influence of the acceleration parameters. This PhD Thesis improves the design of scour protections used in offshore wind facilities taking into account maritime climate actions. To solve the current formulae deficiencies only considering the foundation geometry, the internal friction angle of the seabed and the maximum scour depth forecasted.

Sistema de control de tracción y salida para un monoplaza de la Fórmula SAE

En este proyecto de final de carrera se detalla el proceso de diseño, fabricación, montaje y ajuste de un dispositivo electrónico que sirva como sistema de control de tracción de un vehículo y que acoplaremos sobre un monoplaza de carreras que participa en la competición Formula SAE. La Formula SAE (Society of Automotive Engineers - Sociedad de Ingenieros de Automoción), es una competición de coches de carreras monoplaza a nivel universitario que promueve el desarrollo de la ingeniera aplicada a la automoción. Se pretende que este libro sirva de guía para el correcto manejo y desempeño del sistema fabricado. Además se ha pretendido que su lectura resulte fácil y comprensible para que la persona que lea este libro sea capaz de entender el sistema realizado para así poderlo mejorar. Gracias a la colaboración entre la Escuela Técnica Superior de Ingeniería y Sistemas de Telecomunicación (ETSIST) de la Universidad Politécnica de Madrid (UPM), la Escuela de Ingenieros Industriales de esta misma Universidad (ETSII) y el Instituto Universitario de Investigación del Automóvil (INSIA), se sientan las bases de una plataforma docente en la cual se posibilita la formación y desarrollo de un vehículo tipo formula que participa en la ya mencionada competición Formula SAE. Para ello, se formo en el 2003 el equipo UPMRacing, primer representante español en el evento. El equipo se compone de más de 50 alumnos de la UPM y del Máster de Ingeniería en Automoción del INSIA. Es por tanto, en el vehículo fabricado por el equipo UPMRacing, en el que se pretende instalar este sistema de control de tracción. El control de tracción es un sistema de seguridad del automóvil diseñado para prevenir la perdida de adherencia cuando alguna rueda presenta deslizamiento, bien porque el conductor se excede en la aceleración o bien porque el firme este resbaladizo. La unidad de procesamiento del sistema de control de tracción fabricado lee la velocidad de cada rueda del vehículo mediante unos sensores y determina si existe deslizamiento, en tal caso, manda una señal a la centralita para disminuir la potencia hasta que el deslizamiento disminuya a unos valores controlados. El sistema cuenta con un control remoto que sirve como interfaz para que el piloto pueda manejarlo. Por ultimo, el dispositivo es capaz de conectarse a un bus de comunicaciones CAN para configurar ciertos parámetros. El objetivo del sistema es, básicamente, hacer que el coche no derrape en aceleraciones fuertes; concretamente en las salidas desde parado y al tomar una curva, aumentando así la velocidad en circuito y la seguridad del piloto. ABSTRACT. The purpose of this project is to describe the design, manufacture, assembly and adjustment processes of an electronic device acting as the traction control system (TCS) of a vehicle, that we will attach to a single-seater competition formula SAE car. The Formula SAE (Society of Automotive Engineers) is a graduate-level singleseater racing car competition promoting the development of automotive applied engineering. We also intend this work to serve as a technical user guide of the manufactured system. It is drafted clearly and concisely so that it will be easy for all those to whom it is addressed to understand and subject to further improvements. The close partnership among the Escuela Técnica Superior de Ingeniería y Sistemas de Telecomunicación (ETSIST), Escuela de Ingenieros Industriales (ETSII) of Universidad Politécnica de Madrid (UPM), and the Instituto Universitario de Investigación del Automóvil (INSIA), lays the foundation of a teaching platform enabling the training and development of a single-seater racing car taking part in the already mentioned Formula SAE competition. In this respect, UPMRacing team was created back in 2003, first spanish representative in this event. The team consists of more than 50 students of the UPM and of INSIA Master in Automotive Engineering. It is precisely the vehicle manufactured by UPMRacing team where we intend to install our TCS. TCS is an automotive safety system designed to prevent loss of traction when one wheel has slip, either because the driver exceeds the acceleration or because the firm is slippery. The device’s central processing unit is able to detect the speed of each wheel of the vehicle via special sensors and to determine wheel slip. If this is the case, the system sends a signal to the ECU of the vehicle to reduce the power until the slip is also diminished to controlled values. The device has a remote control that serves as an interface for the pilot to handle it. Lastly, the device is able to connect to a communication bus system CAN to set up certain parameters. The system objective is to prevent skidding under strong acceleration conditions: standing-start from the starting grid or driving into a curve, increasing the speed in circuit and pilot’s safety.

Optimization of the Integrated Guidance and Control for a Dual Aerodynamic Control Missile

Las futuras misiones para misiles aire-aire operando dentro de la atmósfera requieren la interceptación de blancos a mayores velocidades y más maniobrables, incluyendo los esperados vehículos aéreos de combate no tripulados. La intercepción tiene que lograrse desde cualquier ángulo de lanzamiento. Una de las principales discusiones en la tecnología de misiles en la actualidad es cómo satisfacer estos nuevos requisitos incrementando la capacidad de maniobra del misil y en paralelo, a través de mejoras en los métodos de guiado y control modernos. Esta Tesis aborda estos dos objetivos simultáneamente, al proponer un diseño integrando el guiado y el control de vuelo (autopiloto) y aplicarlo a misiles con control aerodinámico simultáneo en canard y cola. Un primer avance de los resultados obtenidos ha sido publicado recientemente en el Journal of Aerospace Engineering, en Abril de 2015, [Ibarrondo y Sanz-Aranguez, 2015]. El valor del diseño integrado obtenido es que permite al misil cumplir con los requisitos operacionales mencionados empleando únicamente control aerodinámico. El diseño propuesto se compara favorablemente con esquemas más tradicionales, consiguiendo menores distancias de paso al blanco y necesitando de menores esfuerzos de control incluso en presencia de ruidos. En esta Tesis se demostrará cómo la introducción del doble mando, donde tanto el canard como las aletas de cola son móviles, puede mejorar las actuaciones de un misil existente. Comparado con un misil con control en cola, el doble control requiere sólo introducir dos servos adicionales para accionar los canards también en guiñada y cabeceo. La sección de cola será responsable de controlar el misil en balanceo mediante deflexiones diferenciales de los controles. En el caso del doble mando, la complicación añadida es que los vórtices desprendidos de los canards se propagan corriente abajo y pueden incidir sobre las superficies de cola, alterando sus características de control. Como un primer aporte, se ha desarrollado un modelo analítico completo para la aerodinámica no lineal de un misil con doble control, incluyendo la caracterización de este efecto de acoplamiento aerodinámico. Hay dos modos de funcionamiento en picado y guiñada para un misil de doble mando: ”desviación” y ”opuesto”. En modo ”desviación”, los controles actúan en la misma dirección, generando un cambio inmediato en la sustentación y produciendo un movimiento de translación en el misil. La respuesta es rápida, pero en el modo ”desviación” los misiles con doble control pueden tener dificultades para alcanzar grandes ángulos de ataque y altas aceleraciones laterales. Cuando los controles actúan en direcciones opuestas, el misil rota y el ángulo de ataque del fuselaje se incrementa para generar mayores aceleraciones en estado estacionario, aunque el tiempo de respuesta es mayor. Con el modelo aerodinámico completo, es posible obtener una parametrización dependiente de los estados de la dinámica de corto periodo del misil. Debido al efecto de acoplamiento entre los controles, la respuesta en bucle abierto no depende linealmente de los controles. El autopiloto se optimiza para obtener la maniobra requerida por la ley de guiado sin exceder ninguno de los límites aerodinámicos o mecánicos del misil. Una segunda contribución de la tesis es el desarrollo de un autopiloto con múltiples entradas de control y que integra la aerodinámica no lineal, controlando los tres canales de picado, guiñada y cabeceo de forma simultánea. Las ganancias del autopiloto dependen de los estados del misil y se calculan a cada paso de integración mediante la resolución de una ecuación de Riccati de orden 21x21. Las ganancias obtenidas son sub-óptimas, debido a que una solución completa de la ecuación de Hamilton-Jacobi-Bellman no puede obtenerse de manera práctica, y se asumen ciertas simplificaciones. Se incorpora asimismo un mecanismo que permite acelerar la respuesta en caso necesario. Como parte del autopiloto, se define una estrategia para repartir el esfuerzo de control entre el canard y la cola. Esto se consigue mediante un controlador aumentado situado antes del bucle de optimización, que minimiza el esfuerzo total de control para maniobrar. Esta ley de alimentación directa mantiene al misil cerca de sus condiciones de equilibrio, garantizando una respuesta transitoria adecuada. El controlador no lineal elimina la respuesta de fase no-mínima característica de la cola. En esta Tesis se consideran dos diseños para el guiado y control, el control en Doble-Lazo y el control Integrado. En la aproximación de Doble-Lazo, el autopiloto se sitúa dentro de un bucle interior y se diseña independientemente del guiado, que conforma el bucle más exterior del control. Esta estructura asume que existe separación espectral entre los dos, esto es, que los tiempos de respuesta del autopiloto son mucho mayores que los tiempos característicos del guiado. En el estudio se combina el autopiloto desarrollado con una ley de guiado óptimo. Los resultados obtenidos demuestran que se consiguen aumentos muy importantes en las actuaciones frente a misiles con control canard o control en cola, y que la interceptación, cuando se lanza cerca del curso de colisión, se consigue desde cualquier ángulo alrededor del blanco. Para el misil de doble mando, la estrategia óptima resulta en utilizar el modo de control opuesto en la aproximación al blanco y utilizar el modo de desviación justo antes del impacto. Sin embargo la lógica de doble bucle no consigue el impacto cuando hay desviaciones importantes con respecto al curso de colisión. Una de las razones es que parte de la demanda de guiado se pierde, ya que el misil solo es capaz de modificar su aceleración lateral, y no tiene control sobre su aceleración axial, a no ser que incorpore un motor de empuje regulable. La hipótesis de separación mencionada, y que constituye la base del Doble-Bucle, puede no ser aplicable cuando la dinámica del misil es muy alta en las proximidades del blanco. Si se combinan el guiado y el autopiloto en un único bucle, la información de los estados del misil está disponible para el cálculo de la ley de guiado, y puede calcularse la estrategia optima de guiado considerando las capacidades y la actitud del misil. Una tercera contribución de la Tesis es la resolución de este segundo diseño, la integración no lineal del guiado y del autopiloto (IGA) para el misil de doble control. Aproximaciones anteriores en la literatura han planteado este sistema en ejes cuerpo, resultando en un sistema muy inestable debido al bajo amortiguamiento del misil en cabeceo y guiñada. Las simplificaciones que se tomaron también causan que el misil se deslice alrededor del blanco y no consiga la intercepción. En nuestra aproximación el problema se plantea en ejes inerciales y se recurre a la dinámica de los cuaterniones, eliminado estos inconvenientes. No se limita a la dinámica de corto periodo del misil, porque se construye incluyendo de modo explícito la velocidad dentro del bucle de optimización. La formulación resultante en el IGA es independiente de la maniobra del blanco, que sin embargo se ha de incluir en el cálculo del modelo en Doble-bucle. Un típico inconveniente de los sistemas integrados con controlador proporcional, es el problema de las escalas. Los errores de guiado dominan sobre los errores de posición del misil y saturan el controlador, provocando la pérdida del misil. Este problema se ha tratado aquí con un controlador aumentado previo al bucle de optimización, que define un estado de equilibrio local para el sistema integrado, que pasa a actuar como un regulador. Los criterios de actuaciones para el IGA son los mismos que para el sistema de Doble-Bucle. Sin embargo el problema matemático resultante es muy complejo. El problema óptimo para tiempo finito resulta en una ecuación diferencial de Riccati con condiciones terminales, que no puede resolverse. Mediante un cambio de variable y la introducción de una matriz de transición, este problema se transforma en una ecuación diferencial de Lyapunov que puede resolverse mediante métodos numéricos. La solución resultante solo es aplicable en un entorno cercano del blanco. Cuando la distancia entre misil y blanco es mayor, se desarrolla una solución aproximada basada en la solución de una ecuación algebraica de Riccati para cada paso de integración. Los resultados que se han obtenido demuestran, a través de análisis numéricos en distintos escenarios, que la solución integrada es mejor que el sistema de Doble-Bucle. Las trayectorias resultantes son muy distintas. El IGA preserva el guiado del misil y consigue maximizar el uso de la propulsión, consiguiendo la interceptación del blanco en menores tiempos de vuelo. El sistema es capaz de lograr el impacto donde el Doble-Bucle falla, y además requiere un orden menos de magnitud en la cantidad de cálculos necesarios. El efecto de los ruidos radar, datos discretos y errores del radomo se investigan. El IGA es más robusto, resultando menos afectado por perturbaciones que el Doble- Bucle, especialmente porque el núcleo de optimización en el IGA es independiente de la maniobra del blanco. La estimación de la maniobra del blanco es siempre imprecisa y contaminada por ruido, y degrada la precisión de la solución de Doble-Bucle. Finalmente, como una cuarta contribución, se demuestra que el misil con guiado IGA es capaz de realizar una maniobra de defensa contra un blanco que ataque por su cola, sólo con control aerodinámico. Las trayectorias estudiadas consideran una fase pre-programada de alta velocidad de giro, manteniendo siempre el misil dentro de su envuelta de vuelo. Este procedimiento no necesita recurrir a soluciones técnicamente más complejas como el control vectorial del empuje o control por chorro para ejecutar esta maniobra. En todas las demostraciones matemáticas se utiliza el producto de Kronecker como una herramienta practica para manejar las parametrizaciones dependientes de variables, que resultan en matrices de grandes dimensiones. ABSTRACT Future missions for air to air endo-atmospheric missiles require the interception of targets with higher speeds and more maneuverable, including forthcoming unmanned supersonic combat vehicles. The interception will need to be achieved from any angle and off-boresight launch conditions. One of the most significant discussions in missile technology today is how to satisfy these new operational requirements by increasing missile maneuvering capabilities and in parallel, through the development of more advanced guidance and control methods. This Thesis addresses these two objectives by proposing a novel optimal integrated guidance and autopilot design scheme, applicable to more maneuverable missiles with forward and rearward aerodynamic controls. A first insight of these results have been recently published in the Journal of Aerospace Engineering in April 2015, [Ibarrondo and Sanz-Aránguez, 2015]. The value of this integrated solution is that it allows the missile to comply with the aforementioned requirements only by applying aerodynamic control. The proposed design is compared against more traditional guidance and control approaches with positive results, achieving reduced control efforts and lower miss distances with the integrated logic even in the presence of noises. In this Thesis it will be demonstrated how the dual control missile, where canard and tail fins are both movable, can enhance the capabilities of an existing missile airframe. Compared to a tail missile, dual control only requires two additional servos to actuate the canards in pitch and yaw. The tail section will be responsible to maintain the missile stabilized in roll, like in a classic tail missile. The additional complexity is that the vortices shed from the canard propagate downstream where they interact with the tail surfaces, altering the tail expected control characteristics. These aerodynamic phenomena must be properly described, as a preliminary step, with high enough precision for advanced guidance and control studies. As a first contribution we have developed a full analytical model of the nonlinear aerodynamics of a missile with dual control, including the characterization of this cross-control coupling effect. This development has been produced from a theoretical model validated with reliable practical data obtained from wind tunnel experiments available in the scientific literature, complement with computer fluid dynamics and semi-experimental methods. There are two modes of operating a missile with forward and rear controls, ”divert” and ”opposite” modes. In divert mode, controls are deflected in the same direction, generating an increment in direct lift and missile translation. Response is fast, but in this mode, dual control missiles may have difficulties in achieving large angles of attack and high level of lateral accelerations. When controls are deflected in opposite directions (opposite mode) the missile airframe rotates and the body angle of attack is increased to generate greater accelerations in steady-state, although the response time is larger. With the aero-model, a state dependent parametrization of the dual control missile short term dynamics can be obtained. Due to the cross-coupling effect, the open loop dynamics for the dual control missile is not linearly dependent of the fin positions. The short term missile dynamics are blended with the servo system to obtain an extended autopilot model, where the response is linear with the control fins turning rates, that will be the control variables. The flight control loop is optimized to achieve the maneuver required by the guidance law without exceeding any of the missile aerodynamic or mechanical limitations. The specific aero-limitations and relevant performance indicators for the dual control are set as part of the analysis. A second contribution of this Thesis is the development of a step-tracking multi-input autopilot that integrates non-linear aerodynamics. The designed dual control missile autopilot is a full three dimensional autopilot, where roll, pitch and yaw are integrated, calculating command inputs simultaneously. The autopilot control gains are state dependent, and calculated at each integration step solving a matrix Riccati equation of order 21x21. The resulting gains are sub-optimal as a full solution for the Hamilton-Jacobi-Bellman equation cannot be resolved in practical terms and some simplifications are taken. Acceleration mechanisms with an λ-shift is incorporated in the design. As part of the autopilot, a strategy is defined for proper allocation of control effort between canard and tail channels. This is achieved with an augmented feed forward controller that minimizes the total control effort of the missile to maneuver. The feedforward law also maintains the missile near trim conditions, obtaining a well manner response of the missile. The nonlinear controller proves to eliminate the non-minimum phase effect of the tail. Two guidance and control designs have been considered in this Thesis: the Two- Loop and the Integrated approaches. In the Two-Loop approach, the autopilot is placed in an inner loop and designed separately from an outer guidance loop. This structure assumes that spectral separation holds, meaning that the autopilot response times are much higher than the guidance command updates. The developed nonlinear autopilot is linked in the study to an optimal guidance law. Simulations are carried on launching close to collision course against supersonic and highly maneuver targets. Results demonstrate a large boost in performance provided by the dual control versus more traditional canard and tail missiles, where interception with the dual control close to collision course is achieved form 365deg all around the target. It is shown that for the dual control missile the optimal flight strategy results in using opposite control in its approach to target and quick corrections with divert just before impact. However the Two-Loop logic fails to achieve target interception when there are large deviations initially from collision course. One of the reasons is that part of the guidance command is not followed, because the missile is not able to control its axial acceleration without a throttleable engine. Also the separation hypothesis may not be applicable for a high dynamic vehicle like a dual control missile approaching a maneuvering target. If the guidance and autopilot are combined into a single loop, the guidance law will have information of the missile states and could calculate the most optimal approach to the target considering the actual capabilities and attitude of the missile. A third contribution of this Thesis is the resolution of the mentioned second design, the non-linear integrated guidance and autopilot (IGA) problem for the dual control missile. Previous approaches in the literature have posed the problem in body axes, resulting in high unstable behavior due to the low damping of the missile, and have also caused the missile to slide around the target and not actually hitting it. The IGA system is posed here in inertial axes and quaternion dynamics, eliminating these inconveniences. It is not restricted to the missile short term dynamic, and we have explicitly included the missile speed as a state variable. The IGA formulation is also independent of the target maneuver model that is explicitly included in the Two-loop optimal guidance law model. A typical problem of the integrated systems with a proportional control law is the problem of scales. The guidance errors are larger than missile state errors during most of the flight and result in high gains, control saturation and loss of control. It has been addressed here with an integrated feedforward controller that defines a local equilibrium state at each flight point and the controller acts as a regulator to minimize the IGA states excursions versus the defined feedforward state. The performance criteria for the IGA are the same as in the Two-Loop case. However the resulting optimization problem is mathematically very complex. The optimal problem in a finite-time horizon results in an irresoluble state dependent differential Riccati equation with terminal conditions. With a change of variable and the introduction of a transition matrix, the equation is transformed into a time differential Lyapunov equation that can be solved with known numerical methods in real time. This solution results range limited, and applicable when the missile is in a close neighborhood of the target. For larger ranges, an approximate solution is used, obtained from solution of an algebraic matrix Riccati equation at each integration step. The results obtained show, by mean of several comparative numerical tests in diverse homing scenarios, than the integrated approach is a better solution that the Two- Loop scheme. Trajectories obtained are very different in the two cases. The IGA fully preserves the guidance command and it is able to maximize the utilization of the missile propulsion system, achieving interception with lower miss distances and in lower flight times. The IGA can achieve interception against off-boresight targets where the Two- Loop was not able to success. As an additional advantage, the IGA also requires one order of magnitude less calculations than the Two-Loop solution. The effects of radar noises, discrete radar data and radome errors are investigated. IGA solution is robust, and less affected by radar than the Two-Loop, especially because the target maneuvers are not part of the IGA core optimization loop. Estimation of target acceleration is always imprecise and noisy and degrade the performance of the two-Loop solution. The IGA trajectories are such that minimize the impact of radome errors in the guidance loop. Finally, as a fourth contribution, it is demonstrated that the missile with IGA guidance is capable of performing a defense against attacks from its rear hemisphere, as a tail attack, only with aerodynamic control. The studied trajectories have a preprogrammed high rate turn maneuver, maintaining the missile within its controllable envelope. This solution does not recur to more complex features in service today, like vector control of the missile thrust or side thrusters. In all the mathematical treatments and demonstrations, the Kronecker product has been introduced as a practical tool to handle the state dependent parametrizations that have resulted in very high order matrix equations.

On the Velocity and Acceleration Estimation from Discrete Time-Position Sensors

In this work is addressed the topic of estimation of velocity and acceleration from digital position data. It is presented a review of several classic methods and implemented with real position data from a low cost digital sensor of a hydraulic linear actuator. The results are analyzed and compared. It is shown that static methods have a limited bandwidth application, and that the performance of some methods may be enhanced by adapting its parameters according to the current state.

Integrated control of appetite and fat metabolism by the leptin-proopiomelanocortin pathway

Leptin deficiency results in a complex obesity phenotype comprising both hyperphagia and lowered metabolism. The hyperphagia results, at least in part, from the absence of induction by leptin of melanocyte stimulating hormone (MSH) secretion in the hypothalamus; the MSH normally then binds to melanocortin-4 receptor expressing neurons and inhibits food intake. The basis for the reduced metabolic rate has been unknown. Here we show that leptin administered to leptin-deficient (ob/ob) mice results in a large increase in peripheral MSH levels; further, peripheral administration of an MSH analogue results in a reversal of their abnormally low metabolic rate, in an acceleration of weight loss during a fast, in partial restoration of thermoregulation in a cold challenge, and in inducing serum free fatty acid levels. These results support an important peripheral role for MSH in the integration of metabolism with appetite in response to perceived fat stores indicated by leptin levels.

Dynamic Visual Servoing With Chaos Control for Redundant Robots

This paper presents a new dynamic visual control system for redundant robots with chaos compensation. In order to implement the visual servoing system, a new architecture is proposed that improves the system maintainability and traceability. Furthermore, high performance is obtained as a result of parallel execution of the different tasks that compose the architecture. The control component of the architecture implements a new visual servoing technique for resolving the redundancy at the acceleration level in order to guarantee the correct motion of both end-effector and joints. The controller generates the required torques for the tracking of image trajectories. However, in order to guarantee the applicability of this technique, a repetitive path tracked by the robot-end must produce a periodic joint motion. A chaos controller is integrated in the visual servoing system and the correct performance is observed in low and high velocities. Furthermore, a method to adjust the chaos controller is proposed and validated using a real three-link robot.

An examination of sudden acceleration. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Simulation of robot manipulator control strategies

The high capital cost of robots prohibit their economic application. One method of making their application more economic is to increase their operating speed. This can be done in a number of ways e.g. redesign of robot geometry, improving actuators and improving control system design. In this thesis the control system design is considered. It is identified in the literature review that two aspects in relation to robot control system design have not been addressed in any great detail by previous researchers. These are: how significant are the coupling terms in the dynamic equations of the robot and what is the effect of the coupling terms on the performance of a number of typical independent axis control schemes?. The work in this thesis addresses these two questions in detail. A program was designed to automatically calculate the path and trajectory and to calculate the significance of the coupling terms in an example application of a robot manipulator tracking a part on a moving conveyor. The inertial and velocity coupling terms have been shown to be of significance when the manipulator was considered to be directly driven. A simulation of the robot manipulator following the planned trajectory has been established in order to assess the performance of the independent axis control strategies. The inertial coupling was shown to reinforce the control torque at the corner points of the trajectory, where there was an abrupt demand in acceleration in each axis but of opposite sign. This reduced the tracking error however, this effect was not controllable. A second effect was due to the velocity coupling terms. At high trajectory speeds it was shown, by means of a root locus analysis, that the velocity coupling terms caused the system to become unstable.

The effect of the advanced placement examination for credit policy by the Florida State universities on the acceleration of a student's postsecondary education

The purpose of this research study was to determine if the Advanced Placement program as it is recognized by the universities in the Florida State University System (SUS) truly serves as an acceleration mechanism for those students who enter an SUS institution with passing AP scores. Despite mandates which attempt to control uniformity of policy, each public university in Florida determines which courses will be exempted and the number of credits they will grant for passing Advanced Placement courses.^ This is a descriptive study in which the AP policies of each of the SUS institutions were compared. Additionally, the college attendance and graduation data on members of a cohort of 593 Broward County high school graduates of the class of June, 1992 were compared. Approximately 28% of the cohort members entered university with passing Advanced Placement scores.^ The rate of early and on time graduation was significantly dependent on the Advanced Placement standing of the students in the cohort. Given the financial and human cost involved, it is recommended that all state universities bring their Advanced Placement policies into line with each other and implement a uniform Advanced Placement policy. It is also recommended that a follow-up study be conducted with a new cohort bound under the current 120 credit limitation for graduation. ^

Design, development and control of a new generation high performance linear actuator for parallel robots and other applications

The main focus of this research is to design and develop a high performance linear actuator based on a four bar mechanism. The present work includes the detailed analysis (kinematics and dynamics), design, implementation and experimental validation of the newly designed actuator. High performance is characterized by the acceleration of the actuator end effector. The principle of the newly designed actuator is to network the four bar rhombus configuration (where some bars are extended to form an X shape) to attain high acceleration. Firstly, a detailed kinematic analysis of the actuator is presented and kinematic performance is evaluated through MATLAB simulations. A dynamic equation of the actuator is achieved by using the Lagrangian dynamic formulation. A SIMULINK control model of the actuator is developed using the dynamic equation. In addition, Bond Graph methodology is presented for the dynamic simulation. The Bond Graph model comprises individual component modeling of the actuator along with control. Required torque was simulated using the Bond Graph model. Results indicate that, high acceleration (around 20g) can be achieved with modest (3 N-m or less) torque input. A practical prototype of the actuator is designed using SOLIDWORKS and then produced to verify the proof of concept. The design goal was to achieve the peak acceleration of more than 10g at the middle point of the travel length, when the end effector travels the stroke length (around 1 m). The actuator is primarily designed to operate in standalone condition and later to use it in the 3RPR parallel robot. A DC motor is used to operate the actuator. A quadrature encoder is attached with the DC motor to control the end effector. The associated control scheme of the actuator is analyzed and integrated with the physical prototype. From standalone experimentation of the actuator, around 17g acceleration was achieved by the end effector (stroke length was 0.2m to 0.78m). Results indicate that the developed dynamic model results are in good agreement. Finally, a Design of Experiment (DOE) based statistical approach is also introduced to identify the parametric combination that yields the greatest performance. Data are collected by using the Bond Graph model. This approach is helpful in designing the actuator without much complexity.

A transport beamline solution to control optically accelerated proton beams

Laser-target interaction represents a very promising field for several potential applications,
from the nuclear physics to the radiobiology. However optically accelerated particle beams are
characterized by some extreme features, not suitable for many applications. Therefore, beyond
the improvements at the laser-target interaction level, many researchers are spending their efforts
for the development of specific beam transport devices in order to obtain controlled and
reproducible output beams.In this background, the ELIMED (ELI-Beamlines MEDical applications)
project was born. Within 2017, a dedicated transport beam-line coupled with dosimetric
systems, named ELIMED, will be installed at the Extreme Light Infrastructure Beamlines
(ELI-Beamlines) facility in Prague (CZ),as a part of the ELIMAIA (ELI Multidisciplinary Applications
of laserâA ¸SIon Acceleration) beamline

Geometric Hamiltonian formulation of a variational problem depending on the covariant acceleration

We consider a second-order variational problem depending on the covariant acceleration, which is related to the notion of Riemannian cubic polynomials. This problem and the corresponding optimal control problem are described in the context of higher order tangent bundles using geometric tools. The main tool, a presymplectic variant of Pontryagin’s maximum principle, allows us to study the dynamics of the control problem.

A Mapping-Scheduling Algorithm for Hardware Acceleration on Reconfigurable Platforms

Reconfigurable platforms are a promising technology that offers an interesting trade-off between flexibility and performance, which many recent embedded system applications demand, especially in fields such as multimedia processing. These applications typically involve multiple ad-hoc tasks for hardware acceleration, which are usually represented using formalisms such as Data Flow Diagrams (DFDs), Data Flow Graphs (DFGs), Control and Data Flow Graphs (CDFGs) or Petri Nets. However, none of these models is able to capture at the same time the pipeline behavior between tasks (that therefore can coexist in order to minimize the application execution time), their communication patterns, and their data dependencies. This paper proves that the knowledge of all this information can be effectively exploited to reduce the resource requirements and the timing performance of modern reconfigurable systems, where a set of hardware accelerators is used to support the computation. For this purpose, this paper proposes a novel task representation model, named Temporal Constrained Data Flow Diagram (TCDFD), which includes all this information. This paper also presents a mapping-scheduling algorithm that is able to take advantage of the new TCDFD model. It aims at minimizing the dynamic reconfiguration overhead while meeting the communication requirements among the tasks. Experimental results show that the presented approach achieves up to 75% of resources saving and up to 89% of reconfiguration overhead reduction with respect to other state-of-the-art techniques for reconfigurable platforms.