Model-based Self-awareness Patterns for Autonomy

Los sistemas técnicos son cada vez más complejos, incorporan funciones más avanzadas, están más integrados con otros sistemas y trabajan en entornos menos controlados. Todo esto supone unas condiciones más exigentes y con mayor incertidumbre para los sistemas de control, a los que además se demanda un comportamiento más autónomo y fiable. La adaptabilidad de manera autónoma es un reto para tecnologías de control actualmente. El proyecto de investigación ASys propone abordarlo trasladando la responsabilidad de la capacidad de adaptación del sistema de los ingenieros en tiempo de diseño al propio sistema en operación. Esta tesis pretende avanzar en la formulación y materialización técnica de los principios de ASys de cognición y auto-consciencia basadas en modelos y autogestión de los sistemas en tiempo de operación para una autonomía robusta. Para ello el trabajo se ha centrado en la capacidad de auto-conciencia, inspirada en los sistemas biológicos, y se ha explorado la posibilidad de integrarla en la arquitectura de los sistemas de control. Además de la auto-consciencia, se han explorado otros temas relevantes: modelado funcional, modelado de software, tecnología de los patrones, tecnología de componentes, tolerancia a fallos. Se ha analizado el estado de la técnica en los ámbitos pertinentes para las cuestiones de la auto-consciencia y la adaptabilidad en sistemas técnicos: arquitecturas cognitivas, control tolerante a fallos, y arquitecturas software dinámicas y computación autonómica. El marco teórico de ASys existente de sistemas autónomos cognitivos ha sido adaptado para servir de base para este análisis de autoconsciencia y adaptación y para dar sustento conceptual al posterior desarrollo de la solución. La tesis propone una solución general de diseño para la construcción de sistemas autónomos auto-conscientes. La idea central es la integración de un meta-controlador en la arquitectura de control del sistema autónomo, capaz de percibir la estado funcional del sistema de control y, si es necesario, reconfigurarlo en tiempo de operación. Esta solución de metacontrol se ha formalizado en cuatro patrones de diseño: i) el Patrón Metacontrol, que define la integración de un subsistema de metacontrol, responsable de controlar al propio sistema de control a través de la interfaz proporcionada por su plataforma de componentes, ii) el patrón Bucle de Control Epistémico, que define un bucle de control cognitivo basado en el modelos y que se puede aplicar al diseño del metacontrol, iii) el patrón de Reflexión basada en Modelo Profundo propone una solución para construir el modelo ejecutable utilizado por el meta-controlador mediante una transformación de modelo a modelo a partir del modelo de ingeniería del sistema, y, finalmente, iv) el Patrón Metacontrol Funcional, que estructura el meta-controlador en dos bucles, uno para el control de la configuración de los componentes del sistema de control, y otro sobre éste, controlando las funciones que realiza dicha configuración de componentes; de esta manera las consideraciones funcionales y estructurales se desacoplan. La Arquitectura OM y el metamodelo TOMASys son las piezas centrales del marco arquitectónico desarrollado para materializar la solución compuesta de los patrones anteriores. El metamodelo TOMASys ha sido desarrollado para la representación de la estructura y su relación con los requisitos funcionales de cualquier sistema autónomo. La Arquitectura OM es un patrón de referencia para la construcción de una metacontrolador integrando los patrones de diseño propuestos. Este meta-controlador se puede integrar en la arquitectura de cualquier sistema control basado en componentes. El elemento clave de su funcionamiento es un modelo TOMASys del sistema decontrol, que el meta-controlador usa para monitorizarlo y calcular las acciones de reconfiguración necesarias para adaptarlo a las circunstancias en cada momento. Un proceso de ingeniería, complementado con otros recursos, ha sido elaborado para guiar la aplicación del marco arquitectónico OM. Dicho Proceso de Ingeniería OM define la metodología a seguir para construir el subsistema de metacontrol para un sistema autónomo a partir del modelo funcional del mismo. La librería OMJava proporciona una implementación del meta-controlador OM que se puede integrar en el control de cualquier sistema autónomo, independientemente del dominio de la aplicación o de su tecnología de implementación. Para concluir, la solución completa ha sido validada con el desarrollo de un robot móvil autónomo que incorpora un meta-controlador con la Arquitectura OM. Las propiedades de auto-consciencia y adaptación proporcionadas por el meta-controlador han sido validadas en diferentes escenarios de operación del robot, en los que el sistema era capaz de sobreponerse a fallos en el sistema de control mediante reconfiguraciones orquestadas por el metacontrolador. ABSTRACT Technical systems are becoming more complex, they incorporate more advanced functionalities, they are more integrated with other systems and they are deployed in less controlled environments. All this supposes a more demanding and uncertain scenario for control systems, which are also required to be more autonomous and dependable. Autonomous adaptivity is a current challenge for extant control technologies. The ASys research project proposes to address it by moving the responsibility for adaptivity from the engineers at design time to the system at run-time. This thesis has intended to advance in the formulation and technical reification of ASys principles of model-based self-cognition and having systems self-handle at runtime for robust autonomy. For that it has focused on the biologically inspired capability of self-awareness, and explored the possibilities to embed it into the very architecture of control systems. Besides self-awareness, other themes related to the envisioned solution have been explored: functional modeling, software modeling, patterns technology, components technology, fault tolerance. The state of the art in fields relevant for the issues of self-awareness and adaptivity has been analysed: cognitive architectures, fault-tolerant control, and software architectural reflection and autonomic computing. The extant and evolving ASys Theoretical Framework for cognitive autonomous systems has been adapted to provide a basement for this selfhood-centred analysis and to conceptually support the subsequent development of our solution. The thesis proposes a general design solution for building self-aware autonomous systems. Its central idea is the integration of a metacontroller in the control architecture of the autonomous system, capable of perceiving the functional state of the control system and reconfiguring it if necessary at run-time. This metacontrol solution has been formalised into four design patterns: i) the Metacontrol Pattern, which defines the integration of a metacontrol subsystem, controlling the domain control system through an interface provided by its implementation component platform, ii) the Epistemic Control Loop pattern, which defines a modelbased cognitive control loop that can be applied to the design of such a metacontroller, iii) the Deep Model Reflection pattern proposes a solution to produce the online executable model used by the metacontroller by model-to-model transformation from the engineering model, and, finally, iv) the Functional Metacontrol pattern, which proposes to structure the metacontroller in two loops, one for controlling the configuration of components of the controller, and another one on top of the former, controlling the functions being realised by that configuration; this way the functional and structural concerns become decoupled. The OM Architecture and the TOMASys metamodel are the core pieces of the architectural framework developed to reify this patterned solution. The TOMASys metamodel has been developed for representing the structure and its relation to the functional requirements of any autonomous system. The OM architecture is a blueprint for building a metacontroller according to the patterns. This metacontroller can be integrated on top of any component-based control architecture. At the core of its operation lies a TOMASys model of the control system. An engineering process and accompanying assets have been constructed to complete and exploit the architectural framework. The OM Engineering Process defines the process to follow to develop the metacontrol subsystem from the functional model of the controller of the autonomous system. The OMJava library provides a domain and application-independent implementation of an OM Metacontroller than can be used in the implementation phase of OMEP. Finally, the complete solution has been validated in the development of an autonomous mobile robot that incorporates an OM metacontroller. The functional selfawareness and adaptivity properties achieved thanks to the metacontrol system have been validated in different scenarios. In these scenarios the robot was able to overcome failures in the control system thanks to reconfigurations performed by the metacontroller.

InfIuence of wave induced second-order forces in semisubmersible fowt mooring design

The main focus of this paper is on hydrodynamic modelling of a semisubmersible platform (which can support a 1.5MW wind turbine and is composed by three buoyant columns connected by bracings) with especial emphasis on the estimation of the wave drift components and their effects on the design of the mooring system. Indeed, with natural periods of drift around 60 seconds, accurate computation of the low-frequency second-order components is not a straightforward task. As methods usually adopted when dealing with the slow-drifts of deep-water moored systems, such as Newman?s approximation, have their errors increased by the relatively low resonant periods, and as the effects of depth cannot be ignored, the wave diffraction analysis must be based on full Quadratic Transfer Functions (QTF) computations. A discussion on the numerical aspects of performing such computations is presented, making use of the second-order module available with the seakeeping software WAMIT®. Finally, the paper also provides a preliminary verification of the accuracy of the numerical predictions based on the results obtained in a series of model tests with the structure fixed in bichromatic waves.

Diseño e implementación de un sistema WDM mediante equipamiento de Fibernet

El objetivo que persigue el presente trabajo es el diseño de un sistema de interconexión basado en la tecnología WDM. Se presenta la comunicación entre dos Centros de Procesamiento de Datos (CPDs), localizados geográficamente distantes dentro de un entorno metropolitano. El punto de partida se establece sobre la base de una serie de requerimientos previos solicitados por un operador de telecomunicaciones, el cual pretende dotar de servicio mediante fibra óptica a varios centros de negocio dentro de la misma ciudad y, para ello, se solicita el diseño y la implementación de la solución lo que, en esencia, se tratará de un proyecto llave en mano. En este documento se expondrá el análisis del caso de estudio, la solución técnica desarrollada para satisfacer los requisitos requeridos por el cliente y la estimación económica del equipamiento e instalación del mismo. Del mismo modo, se establecerán líneas de trabajo futuras de cara a mejorar el sistema de comunicación implementado de acuerdo a las necesidades actuales y futuras, ya sea traducido en una mejora de las prestaciones o ahorro de costes. Para poder realizar el diseño de la solución, se establecen las bases teóricas de la tecnología WDM con el fin de disponer de los conocimientos necesarios para el estudio, diseño e implementación de la solución propuesta. ABSTRACT. The aim of this paper is to study the design of an interconnection system based on WDM technology. Communication will be means of two Data Center (DC) located at different geographical points within a metropolitan area. The starting point is based on a serie of demands requested by a telecommunications service provider, which claims to provide a communication service using fibre optics to several business centers within the same city and, to do this, it requires the design and deploy the solution that, will basically be a turnkey project. The paper analyzes the case of study, the technical solution which needs to be developed to fulfil the requirements required by the client and an estimate budget as regards the equipment and installation needed. In the same way, it describes the possible lines of work so as to improve implemented communication system taking into account the future needs, either related to improved performance or cost savings. To carry out the design of the solution, a theoretical basis of WDM technology is established in order to obtain the knowledge needed for the study, design and implementation of the proposed solution.

Sistema Integrado de Gestión Académica

El Sistema Integrado de Gestión Académica consiste en una plataforma software modular orientada a apoyar la labor del profesorado en la gestión docente de las asignaturas impartidas por el Departamento de Mecánica de la Escuela Técnica Superior de Ingeniería y Diseño Industrial de la Universidad Politécnica de Madrid. Durante los últimos 5 años se ha trabajado en la creación de esta plataforma que se encuentra ahora en su recta final. Es necesario aclarar que toda la plataforma desde su inicio ha sido creada por el mismo autor y que debido al tiempo disponible para la realización del TFG, éste se ha centrado en realizar mejoras sobre lo ya desarrollado y en implementar uno de los módulos. El trabajo desarrollado comienza con un estudio de plataformas educativas online. Se han valorado las alternativas de Moodle y ATutor como posibles soluciones a los requisitos planteados llegando a la conclusión de que era necesario realizar un desarrollo a medida. La plataforma consta de 3 módulos principales:  Plataforma de Gestión Docente en Internet (PGDNet)  Aplicación de Notas (AdN)  Plataforma de Entrega de Prácticas Académicas (PEPA) PGDNet está orientado a la realización de pruebas de evaluación online. El profesor tiene a su alcance un conjunto de opciones que le permiten la creación de actividades y ejercicios de diferente índole, gestionar alumnos y establecer periodos de evaluación. El sistema recoge los resultados y corrige automáticamente permitiendo además exportar los resultados, manteniendo de esta manera la compatibilidad con otros sistemas informáticos de la UPM. PGDNet ofrece además un servicio de correo electrónico para realizar comunicaciones con grupos predefinidos de alumnos, un gestor documental enlazado con las diferentes actividades y un gestor de encuestas programable a medida. AdN se integra en la plataforma como un sistema para la gestión de calificaciones y permite mantener un historial del alumno. Las materias pueden dividirse en diferentes evaluaciones con un determinado peso sobre la calificación final. La nota total se calcula en tiempo real y de forma automática. El alumno puede entrar a consultar sus calificaciones en cualquier momento. El módulo ofrece a los profesores acceso simultáneo a introducir las calificaciones e importar notas guardadas de convocatorias pasadas. PEPA es el nuevo módulo que se añade a la plataforma y el que concentra los esfuerzos de desarrollo de este TFG. Se trata de un sistema de entrega de prácticas online que permite al profesor centralizar la recogida de documentación para su posterior corrección. PEPA dispone de un sistema de plantillas de respuestas fijas utilizadas en los laboratorios que son corregidas de forma automática en la entrega. Los 3 módulos se complementan entre sí compartiendo datos y permitiendo realizar importaciones y exportaciones de información con las aplicaciones actuales de Secretaría de alumnos como puede ser la introducción de listas de alumnos.---ABSTRACT---Academic Management Framework (Sistema Integrado de Gestión Académica) is a module‐oriented software application that aims to help teachers from ETSIDI Department from UPM to manage all information related to graduate courses. The software, which has been in continuous developing during the last 5 years, is now about to be finished. It must be pointed out the fact that the entire application has been designed and implemented by the same author. However, due to time schedule restrictions in this TFG (spanish acronym for “Graduation Project”), it has been focused on developing a few improvements in the software already implemented and creating a specific new module. In the beginning, this TFG includes an educational software comparative study. Moodle and ATutor have been selected as plausible assembled solutions that would fit the requirements given. Nonetheless, the conclusion ends up with rejecting both possibilities and moving the project towards a custom‐developed software. The application is divided in 3 modules:  Network Based Academic Management Platform (Plataforma de Gestión Docente en Internet ‐ PGDNet)  Evaluation Aid Tool (Aplicación de Notas ‐ AdN)  Academic Lab‐Work Delivery Platform (Plataforma de Entrega de Prácticas Académicas ‐ PEPA) PGDNet main purpose is handling online tests for students. There are a bunch of tools available for teachers that allow them to create activities and different types of exercises, manage students and set examination schedules. The system gathers the results and marks exercises automatically. Moreover, the teacher is able to export this information which is compatible with other UPM systems. PGDNet offers a mail service, a document management system and a survey application among others. AdN adds new features to the system. It helps teachers to manage student marks by keeping a history over the years. Subjects can be divided into little parts with a different weight in the final mark. Eventually, the mark is automatically calculated and published. The application can be accessed by both students and teachers simultaneously. This module is also ready to import old marks into the current course and allow all teachers to fill in the results at the same time. PEPA, which is a new module added from scratch, concentrate this TFG efforts. It consists of a practice delivery system that gathers all student documentation in a single site for easy correction. Besides, PEPA deploys an answer template repository for laboratory training. Students fill the templates and PEPA corrects them automatically on sending. These 3 modules are integrated in a single system that allows them to share data and import information such as student lists from the Administration Department.

Mobile assisted language learning : prototipo de la aplicación UP2B2

La forma de consumir contenidos en Internet ha cambiado durante los últimos años. Inicialmente se empleaban webs estáticas y con contenidos pobres visualmente. Con la evolución de las redes de comunicación, esta tendencia ha variado. A día de hoy, deseamos páginas agradables, accesibles y que nos presenten temas variados. Todo esto ha cambiado la forma de crear páginas web y en todos los casos se persigue el objetivo de atraer a los usuarios. El gran auge de los smartphones y las aplicaciones móviles que invaden el mercado actual han revolucionado el mundo del estudio de los idiomas permitiendo compatibilizar los recursos punteros con el aprendizaje tradicional. La popularidad de los dispositivos móviles y de las aplicaciones ha sido el principal motivo de la realización de este proyecto. En él se realizará un análisis de las diferentes tecnologías existentes y se elegirá la mejor opción que se ajuste a nuestras necesidades para poder desarrollar un sistema que implemente el enfoque llamado Mobile Assisted Language Learning (MALL) que supone una aproximación innovadora al aprendizaje de idiomas con la ayuda de un dispositivo móvil. En este documento se va a ofrecer una panorámica general acerca del desarrollo de aplicaciones para dispositivos móviles en el entorno del e-learning. Se estudiarán características técnicas de diferentes plataformas seleccionando la mejor opción para la implementación de un sistema que proporcione los contenidos básicos para el aprendizaje de un idioma, en este caso del inglés, de forma intuitiva y divertida. Dicho sistema permitirá al usuario mejorar su nivel de inglés mediante una interfaz web de forma dinámica y cercana empleando los recursos que ofrecen los dispositivos móviles y haciendo uso del diseño adaptativo. Este proyecto está pensado para los usuarios que dispongan de poco tiempo libre para realizar un curso de forma presencial o, mejor aún, para reforzar o repasar contenidos ya aprendidos por otros medios más tradicionales o no. La aplicación ofrece la posibilidad de que se haga uso del sistema de forma fácil y sencilla desde cualquier dispositivo móvil del que se disponga como es un smartphone, tablet o un ordenador personal, compitiendo con otros usuarios o contra uno mismo y mejorando así el nivel de partida a través de las actividades propuestas. Durante el proyecto se han comparado diversas soluciones, la mayoría de código abierto y de libre distribución que permiten desplegar servicios de almacenamiento accesibles mediante Internet. Se concluirá con un caso práctico analizando los requisitos técnicos y llevando a cabo las fases de análisis, diseño, creación de la base de datos, implementación y pruebas dentro del ciclo de vida del software. Finalmente, se migrará la aplicación con toda la información a un servidor en la nube. ABSTRACT. The way of consuming content on the Internet has changed over the past years. Initially, static websites were used with poor visual contents. Nevertheless, with the evolution of communication networks this trend has changed. Nowadays, we expect pleasant, accessible and varied topic pages and such expectations have changed the way to create web pages generally aiming at appealing and therefore, attracting users. The great boom of smartphones and mobile applications in the current market, have revolutionized the world of language learning as they make it possible to combine computing with traditional learning resources. The popularity of mobile devices and applications has been the main reason for the development of this project. Here, the different existing technologies will be examined and we will try to select the best option that adapts to our needs in order to develop a system that implements Mobile Assisted Language Learning (MALL) that in broad terms implies an approach to language learning with the help of a mobile device. This report provides an overview of the development of applications for mobile devices in the e-learning environment. We will study the technical characteristics of different platforms and we will select the best option for the implementation of a system that provide the basic content for learning a language, in this case English, by means of an intuitive and fun method. This system will allow the user to improve their level of English with a web interface in a dynamic and close way employing the resources offered by mobile devices using the adaptive design. This project is intended for users who do not have enough free time to make a classroom course or to review contents from more traditional courses as it offers the possibility to make use of the system quickly and easily from any mobile device available such as a smartphone, a tablet or a personal computer, competing with other users or against oneself and thus improving their departing level through different activities. During the project, different solutions have been compared. Most of them, open source and free distribution that allow to deploy storage services accessible via the Internet. It will conclude with a case study analyzing the technical requirements and conducting phases of analysis, design and creation of a database, implementation and testing in the software lifecycle. Finally, the application will be migrated with all the information to a server in the cloud.

Arquitectura de supercomputación en la nube para la resolución de problemas de optimización combinatoria

La tesis está focalizada en la resolución de problemas de optimización combinatoria, haciendo uso de las opciones tecnológicas actuales que ofrecen las tecnologías de la información y las comunicaciones, y la investigación operativa. Los problemas de optimización combinatoria se resuelven en general mediante programación lineal y metaheurísticas. La aplicación de las técnicas de resolución de los problemas de optimización combinatoria requiere de una elevada carga computacional, y los algoritmos deben diseñarse, por un lado pensando en la efectividad para encontrar buenas soluciones del problema, y por otro lado, pensando en un uso adecuado de los recursos informáticos disponibles. La programación lineal y las metaheurísticas son técnicas de resolución genéricas, que se pueden aplicar a diferentes problemas, partiendo de una base común que se particulariza para cada problema concreto. En el campo del desarrollo de software, los frameworks cumplen esa función de comenzar un proyecto con el trabajo general ya disponible, con la opción de cambiar o extender ese comportamiento base o genérico, para construir el sistema concreto, lo que permite reducir el tiempo de desarrollo, y amplía las posibilidades de éxito del proyecto. En esta tesis se han desarrollado dos frameworks de desarrollo. El framework ILP permite modelar y resolver problemas de programación lineal, de forma independiente al software de resolución de programación lineal que se utilice. El framework LME permite resolver problemas de optimización combinatoria mediante metaheurísticas. Tradicionalmente, las aplicaciones de resolución de problemas de optimización combinatoria son aplicaciones de escritorio que permiten gestionar toda la información de entrada del problema y resuelven el problema en local, con los recursos hardware disponibles. Recientemente ha aparecido un nuevo paradigma de despliegue y uso de aplicaciones que permite compartir recursos informáticos especializados por Internet. Esta nueva forma de uso de recursos informáticos es la computación en la nube, que presenta el modelo de software como servicio (SaaS). En esta tesis se ha construido una plataforma SaaS, para la resolución de problemas de optimización combinatoria, que se despliega sobre arquitecturas compuestas por procesadores multi-núcleo y tarjetas gráficas, y dispone de algoritmos de resolución basados en frameworks de programación lineal y metaheurísticas. Toda la infraestructura es independiente del problema de optimización combinatoria a resolver, y se han desarrollado tres problemas que están totalmente integrados en la plataforma SaaS. Estos problemas se han seleccionado por su importancia práctica. Uno de los problemas tratados en la tesis, es el problema de rutas de vehículos (VRP), que consiste en calcular las rutas de menor coste de una flota de vehículos, que reparte mercancías a todos los clientes. Se ha partido de la versión más clásica del problema y se han hecho estudios en dos direcciones. Por un lado se ha cuantificado el aumento en la velocidad de ejecución de la resolución del problema en tarjetas gráficas. Por otro lado, se ha estudiado el impacto en la velocidad de ejecución y en la calidad de soluciones, en la resolución por la metaheurística de colonias de hormigas (ACO), cuando se introduce la programación lineal para optimizar las rutas individuales de cada vehículo. Este problema se ha desarrollado con los frameworks ILP y LME, y está disponible en la plataforma SaaS. Otro de los problemas tratados en la tesis, es el problema de asignación de flotas (FAP), que consiste en crear las rutas de menor coste para la flota de vehículos de una empresa de transporte de viajeros. Se ha definido un nuevo modelo de problema, que engloba características de problemas presentados en la literatura, y añade nuevas características, lo que permite modelar los requerimientos de las empresas de transporte de viajeros actuales. Este nuevo modelo resuelve de forma integrada el problema de definir los horarios de los trayectos, el problema de asignación del tipo de vehículo, y el problema de crear las rotaciones de los vehículos. Se ha creado un modelo de programación lineal para el problema, y se ha resuelto por programación lineal y por colonias de hormigas (ACO). Este problema se ha desarrollado con los frameworks ILP y LME, y está disponible en la plataforma SaaS. El último problema tratado en la tesis es el problema de planificación táctica de personal (TWFP), que consiste en definir la configuración de una plantilla de trabajadores de menor coste, para cubrir una demanda de carga de trabajo variable. Se ha definido un modelo de problema muy flexible en la definición de contratos, que permite el uso del modelo en diversos sectores productivos. Se ha definido un modelo matemático de programación lineal para representar el problema. Se han definido una serie de casos de uso, que muestran la versatilidad del modelo de problema, y permiten simular el proceso de toma de decisiones de la configuración de una plantilla de trabajadores, cuantificando económicamente cada decisión que se toma. Este problema se ha desarrollado con el framework ILP, y está disponible en la plataforma SaaS. ABSTRACT The thesis is focused on solving combinatorial optimization problems, using current technology options offered by information technology and communications, and operations research. Combinatorial optimization problems are solved in general by linear programming and metaheuristics. The application of these techniques for solving combinatorial optimization problems requires a high computational load, and algorithms are designed, on the one hand thinking to find good solutions to the problem, and on the other hand, thinking about proper use of the available computing resources. Linear programming and metaheuristic are generic resolution techniques, which can be applied to different problems, beginning with a common base that is particularized for each specific problem. In the field of software development, frameworks fulfill this function that allows you to start a project with the overall work already available, with the option to change or extend the behavior or generic basis, to build the concrete system, thus reducing the time development, and expanding the possibilities of success of the project. In this thesis, two development frameworks have been designed and developed. The ILP framework allows to modeling and solving linear programming problems, regardless of the linear programming solver used. The LME framework is designed for solving combinatorial optimization problems using metaheuristics. Traditionally, applications for solving combinatorial optimization problems are desktop applications that allow the user to manage all the information input of the problem and solve the problem locally, using the available hardware resources. Recently, a new deployment paradigm has appeared, that lets to share hardware and software resources by the Internet. This new use of computer resources is cloud computing, which presents the model of software as a service (SaaS). In this thesis, a SaaS platform has been built for solving combinatorial optimization problems, which is deployed on architectures, composed of multi-core processors and graphics cards, and has algorithms based on metaheuristics and linear programming frameworks. The SaaS infrastructure is independent of the combinatorial optimization problem to solve, and three problems are fully integrated into the SaaS platform. These problems have been selected for their practical importance. One of the problems discussed in the thesis, is the vehicle routing problem (VRP), which goal is to calculate the least cost of a fleet of vehicles, which distributes goods to all customers. The VRP has been studied in two directions. On one hand, it has been quantified the increase in execution speed when the problem is solved on graphics cards. On the other hand, it has been studied the impact on execution speed and quality of solutions, when the problem is solved by ant colony optimization (ACO) metaheuristic, and linear programming is introduced to optimize the individual routes of each vehicle. This problem has been developed with the ILP and LME frameworks, and is available in the SaaS platform. Another problem addressed in the thesis, is the fleet assignment problem (FAP), which goal is to create lower cost routes for a fleet of a passenger transport company. It has been defined a new model of problem, which includes features of problems presented in the literature, and adds new features, allowing modeling the business requirements of today's transport companies. This new integrated model solves the problem of defining the flights timetable, the problem of assigning the type of vehicle, and the problem of creating aircraft rotations. The problem has been solved by linear programming and ACO. This problem has been developed with the ILP and LME frameworks, and is available in the SaaS platform. The last problem discussed in the thesis is the tactical planning staff problem (TWFP), which is to define the staff of lower cost, to cover a given work load. It has been defined a very rich problem model in the definition of contracts, allowing the use of the model in various productive sectors. It has been defined a linear programming mathematical model to represent the problem. Some use cases has been defined, to show the versatility of the model problem, and to simulate the decision making process of setting up a staff, economically quantifying every decision that is made. This problem has been developed with the ILP framework, and is available in the SaaS platform.

Anthrax toxin-mediated delivery of a cytotoxic T-cell epitope in vivo.

The protective antigen (PA) component of anthrax toxin mediates entry of the toxin's lethal factor (LF) and edema factor into the cytosolic compartment of mammalian cells. The amino-terminal domain of LF (LFn; 255 amino acids) binds LF to PA, and when fused to heterologous proteins, the LFn domain delivers such proteins to the cytoplasm in the presence of PA. In the current study, we fused a 9-amino acid cytotoxic T-lymphocyte (CTL) epitope (LLO91-99) from an intracellular pathogen, Listeria monocytogenes, to LFn and measured the ability of the resulting LFn-LLO91-99 fusion protein to stimulate a CTL response against the epitope in BALB/c mice. As little as 300 fmol of fusion could stimulate a response. The stimulation was PA-dependent and occurred with the peptide fused to either the amino terminus or the carboxyl terminus of LFn. Upon challenge with L. monocytogenes, mice previously injected with LFn-LLO91-99 and PA showed a reduction of colony-forming units in spleen and liver, relative to nonimmunized control mice. These results indicate that anthrax toxin may be useful as a CTL-peptide delivery system for research and medical applications.

Vector-mediated delivery of 125I-labeled beta-amyloid peptide A beta 1-40 through the blood-brain barrier and binding to Alzheimer disease amyloid of the A beta 1-40/vector complex.

The brain amyloid of Alzheimer disease (AD) may potentially be imaged in patients with AD by using neuroimaging technology and a radiolabeled form of the 40-residue beta-amyloid peptide A beta 1-40 that is enabled to undergo transport through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo. Transport of 125I-labeled A beta 1-40 (125I-A beta 1-40) through the BBB was found to be negligible by experiments with both an intravenous injection technique and an internal carotid artery perfusion method in anesthetized rats. In addition, 125I-A beta 1-40 was rapidly metabolized after either intravenous injection or internal carotid artery perfusion. BBB transport was increased and peripheral metabolism was decreased by conjugation of monobiotinylated 125I-A beta 1-40 to a vector-mediated drug delivery system, which consisted of a conjugate of streptavidin (SA) and the OX26 monoclonal antibody to the rat transferrin receptor, which undergoes receptor-mediated transcytosis through the BBB. The brain uptake, expressed as percent of injected dose delivered per gram of brain, of the 125I,bio-A beta 1-40/SA-OX26 conjugate was 0.15 +/- 0.01, a level that is 2-fold greater than the brain uptake of morphine. The binding of the 125I,bio-A beta 1-40/SA-OX26 conjugate to the amyloid of AD brain was demonstrated by both film and emulsion autoradiography performed on frozen sections of AD brain. Binding of the 125I,bio-A beta 1-40/SA-OX26 conjugate to the amyloid of AD brain was completely inhibited by high concentrations of unlabeled A beta 1-40. In conclusion, these studies show that BBB transport and access to amyloid within brain may be achieved by conjugation of A beta 1-40 to a vector-mediated BBB drug delivery system.

Integration of different models in the design of chemical processes: Application to the design of a power plant

With advances in the synthesis and design of chemical processes there is an increasing need for more complex mathematical models with which to screen the alternatives that constitute accurate and reliable process models. Despite the wide availability of sophisticated tools for simulation, optimization and synthesis of chemical processes, the user is frequently interested in using the ‘best available model’. However, in practice, these models are usually little more than a black box with a rigid input–output structure. In this paper we propose to tackle all these models using generalized disjunctive programming to capture the numerical characteristics of each model (in equation form, modular, noisy, etc.) and to deal with each of them according to their individual characteristics. The result is a hybrid modular–equation based approach that allows synthesizing complex processes using different models in a robust and reliable way. The capabilities of the proposed approach are discussed with a case study: the design of a utility system power plant that has been decomposed into its constitutive elements, each treated differently numerically. And finally, numerical results and conclusions are presented.

Previ: la tipología entre la fluidez de la vida y el rigor de la edificación

Hace diez años que el Proyecto Experimental de Vivienda (Previ), de Lima, a propósito de la convocatoria de investigación de la Bienal Iberoamericana de Arquitectura y Urbanismo celebrada en 2004 en esta ciudad, despertó un renovado interés en arquitectos jóvenes y comprometidos que se aproximaban a esta experiencia con la mirada atenta de quien desea aprender para construir vivienda social de irrenunciable vocación urbana. Asimismo, la asignatura pendiente de la industrialización en la vivienda de bajo coste ha propiciado el estudio de este caso. Después de plantear los aspectos básicos de Previ que nos permiten entenderlo y proyectarlo en su contexto, este artículo se acerca de nuevo a esa experiencia para leerla desde las claves proyectuales tipológicas que, a nuestro parecer, tienden un puente entre la vida que fluye (la utilitas) y el rigor que reclama la re edificatoria (la firmitas).

Aging and the governance of the healthcare system in Japan. Bruegel Working Paper 2014/14, December 2014

Japan is the most rapidly aging country in the world. This is evidence that the social security system, which consists of the pension system, healthcare system and other programmes, has been working well. The population is shrinking because of a falling birth rate. It is expected that the population will fall from 128 million in 2010 to 87 million in 2060. During this period, the ratio of people aged 65 or over will rise from 23 percent to 39.9 percent. Japan’s age dependency ratio was 62 in 2013, the highest among advanced nations. It is expected to rise sharply to 94 in 2050 (see Figure 1 on page 4). A total reform of the Japanese social security system, therefore, is inevitable. From the point of view of fiscal reconstruction, reform of the healthcare system is the most important issue. The biggest problem in the healthcare system is that both the funding system and the care-delivery system are extremely fragmented. The government is planning its reform of the healthcare system based on the principle of integration. Other advanced economies could learn from the Japanese experience.

Wyoming CVISN program plan.

Wyoming Highway Patrol, Commercial Carrier Section, Cheyenne

Polymerizable Peptide Monomers for the Targeted and Intracellular Delivery of Cancer Therapeutics

Thesis (Ph.D.)--University of Washington, 2016-06

Targeted delivery of heparin and LMWH using a fibrin antibody prevents restenosis

This study investigates a stent-less local delivery system for anti-restenotic agents utilizing antibodies to cross-linked fibrin (XLF). Heparin and low molecular weight heparin (LMWH) were conjugated to an antibody to cross-linked fibrin D-dinner (1D2). Rabbit right carotid arteries were injured with a balloon catheter, then the animals were given a bolus injection of 40 mug/k,g 1D2-heparin (26-70 mug/kg heparin) or 1D2-LMWH (29-80 mug/kg LMWH) conjugates or controls of saline (0.5 ml/kg), heparin (150 U/kg), LMWH (2 mg), or 1D2 (40 mug/kg), with or without a heparin bolus and sacrificed after 2 weeks (8 groups, n = 6/group). The injured artery of rabbits given 1D2-heparin or 1D2-LMWH conjugates had reduced neointimal development, with decreased luminal narrowing and positive remodelling compared with animals given control drugs. Animals given 1D2-heparin conjugate (with a heparin bolus) had three to five times more endothelial cells than the rabbits given saline or unconjugated heparin, while rabbits given 1D2-LMWH conjugate had up to 59% fewer neointimal cells than those given unconjugated drugs. There was little difference in extracellular matrix organization or composition. Thus cross-linked fibrin-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall where they influence wall remodelling and endothelial and neointimal cell number, reducing neointimal formation without systemic complications. Local delivery of anti-restenotic agents should minimise systemic effects, bleeding complications and potentially the cost of treatment due to a single, lower dose. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Group A streptococcal vaccine delivery by immunization with a self-adjuvanting M protein-based lipid core peptide construct

Background & objectives: To develop a broad strain coverage GAS vaccine, several strategies have been investigated which included multi-epitope approaches as well as targeting the M protein conserved C-region. These approaches, however, have relied on the use of adjuvants that are toxic for human application. The development of safe and effective adjuvants for human use is a key issue in the development of effective vaccines. In this study, we investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting GAS vaccine delivery approach. Methods: An LCP-GAS construct was synthesised incorporating multiple copies of a protective peptide epitope (J8) from the conserved carboxy terminal C-repeat region of the M protein. B10.BR mice were immunized parenterally with the LCP-J8 construct, with or without conventional adjuvant, prior to the assessment of immunogenicity and the induction of serum opsonic antibodies. Results: Our data demonstrated immunogenicity of LCP-J8 when coadministered in complete Freund's adjuvant (CFA), or administered in the absence of conventional adjuvant. In both cases, immunization led to the induction of high-titre J8 peptide-specific serum IgG antibody responses, and the induction of heterologous opsonic antibodies that did not cross-react with human heart tissue proteins. Interpretation & conclusion: These data indicated the potential of a novel self-adjuvanting LCP vaccine delivery system incorporating a synthetic GAS M protein C-region peptide immunogen in the induction of broadly protective immune responses, and pointed to the potential application of this system in human vaccine development against infectious diseases.