Smart aeronautical structures: development and experimental validation of a structural health monitoring system for damage detection

En muchas áreas de la ingeniería, la integridad y confiabilidad de las estructuras son aspectos de extrema importancia. Estos son controlados mediante el adecuado conocimiento de danos existentes. Típicamente, alcanzar el nivel de conocimiento necesario que permita caracterizar la integridad estructural implica el uso de técnicas de ensayos no destructivos. Estas técnicas son a menudo costosas y consumen mucho tiempo. En la actualidad, muchas industrias buscan incrementar la confiabilidad de las estructuras que emplean. Mediante el uso de técnicas de última tecnología es posible monitorizar las estructuras y en algunos casos, es factible detectar daños incipientes que pueden desencadenar en fallos catastróficos. Desafortunadamente, a medida que la complejidad de las estructuras, los componentes y sistemas incrementa, el riesgo de la aparición de daños y fallas también incrementa. Al mismo tiempo, la detección de dichas fallas y defectos se torna más compleja. En años recientes, la industria aeroespacial ha realizado grandes esfuerzos para integrar los sensores dentro de las estructuras, además de desarrollar algoritmos que permitan determinar la integridad estructural en tiempo real. Esta filosofía ha sido llamada “Structural Health Monitoring” (o “Monitorización de Salud Estructural” en español) y este tipo de estructuras han recibido el nombre de “Smart Structures” (o “Estructuras Inteligentes” en español). Este nuevo tipo de estructuras integran materiales, sensores, actuadores y algoritmos para detectar, cuantificar y localizar daños dentro de ellas mismas. Una novedosa metodología para detección de daños en estructuras se propone en este trabajo. La metodología está basada en mediciones de deformación y consiste en desarrollar técnicas de reconocimiento de patrones en el campo de deformaciones. Estas últimas, basadas en PCA (Análisis de Componentes Principales) y otras técnicas de reducción dimensional. Se propone el uso de Redes de difracción de Bragg y medidas distribuidas como sensores de deformación. La metodología se validó mediante pruebas a escala de laboratorio y pruebas a escala real con estructuras complejas. Los efectos de las condiciones de carga variables fueron estudiados y diversos experimentos fueron realizados para condiciones de carga estáticas y dinámicas, demostrando que la metodología es robusta ante condiciones de carga desconocidas. ABSTRACT In many engineering fields, the integrity and reliability of the structures are extremely important aspects. They are controlled by the adequate knowledge of existing damages. Typically, achieving the level of knowledge necessary to characterize the structural integrity involves the usage of nondestructive testing techniques. These are often expensive and time consuming. Nowadays, many industries look to increase the reliability of the structures used. By using leading edge techniques it is possible to monitoring these structures and in some cases, detect incipient damage that could trigger catastrophic failures. Unfortunately, as the complexity of the structures, components and systems increases, the risk of damages and failures also increases. At the same time, the detection of such failures and defects becomes more difficult. In recent years, the aerospace industry has done great efforts to integrate the sensors within the structures and, to develop algorithms for determining the structural integrity in real time. The ‘philosophy’ has being called “Structural Health Monitoring” and these structures have been called “smart structures”. These new types of structures integrate materials, sensors, actuators and algorithms to detect, quantify and locate damage within itself. A novel methodology for damage detection in structures is proposed. The methodology is based on strain measurements and consists in the development of strain field pattern recognition techniques. The aforementioned are based on PCA (Principal Component Analysis) and other dimensional reduction techniques. The use of fiber Bragg gratings and distributed sensing as strain sensors is proposed. The methodology have been validated by using laboratory scale tests and real scale tests with complex structures. The effects of the variable load conditions were studied and several experiments were performed for static and dynamic load conditions, demonstrating that the methodology is robust under unknown load conditions.

Efficiency analysis of information technology and online social networks management : an integrated DEA-Model assessment

This paper analyses the relationship between productive efficiency and online-social-networks (OSN) in Spanish telecommunications firms. A data-envelopment-analysis (DEA) is used and several indicators of business ?social Media? activities are incorporated. A super-efficiency analysis and bootstrapping techniques are performed to increase the model?s robustness and accuracy. Then, a logistic regression model is applied to characterise factors and drivers of good performance in OSN. Results reveal the company?s ability to absorb and utilise OSNs as a key factor in improving the productive efficiency. This paper presents a model for assessing the strategic performance of the presence and activity in OSN.

Impact of Impurities on the Mechanical Strength of Multicrystalline Silicon

The usage of more inexpensive silicon feedstock for crystallizing mc-Si blocks promises cost reduction for the photovoltaic market. For example, less expensive substrates of upgraded metallurgical silicon (UMG-Si) are used as a mechanical support for the epitaxial solar cell. This feedstock has higher content of impurities which influences cell performance and mechanical strength of the wafers. Thus, it is of importance to know these effects in order to know which impurities should be preferentially removed or prevented during the crystallization process. Metals like aluminum (Al) can decrease the mechanical strength due to micro-cracking of the silicon matrix and introduction of high values of thermal residual stress. Additionally, silicon oxide (SiOx) lowers the mechanical strength of mc-Si due to thermal residual stresses and stress intensification when an external load is applied in the surrounding of the particle. Silicon carbide (SiC) introduces thermal residual stresses and intensifies slightly the stress in the surrounding of the particle but can have a toughening effect on the silicon matrix. Finally, silicon nitride (Si3N4) does not influence significantly the mechanical strength of mc- Si and can have a toughening effect on the silicon matrix.

Testing of Android testing tools: development of a benchmark for the evaluation

With the ever growing trend of smart phones and tablets, Android is becoming more and more popular everyday. With more than one billion active users i to date, Android is the leading technology in smart phone arena. In addition to that, Android also runs on Android TV, Android smart watches and cars. Therefore, in recent years, Android applications have become one of the major development sectors in software industry. As of mid 2013, the number of published applications on Google Play had exceeded one million and the cumulative number of downloads was more than 50 billionii. A 2013 survey also revealed that 71% of the mobile application developers work on developing Android applicationsiii. Considering this size of Android applications, it is quite evident that people rely on these applications on a daily basis for the completion of simple tasks like keeping track of weather to rather complex tasks like managing one’s bank accounts. Hence, like every other kind of code, Android code also needs to be verified in order to work properly and achieve a certain confidence level. Because of the gigantic size of the number of applications, it becomes really hard to manually test Android applications specially when it has to be verified for various versions of the OS and also, various device configurations such as different screen sizes and different hardware availability. Hence, recently there has been a lot of work on developing different testing methods for Android applications in Computer Science fraternity. The model of Android attracts researchers because of its open source nature. It makes the whole research model more streamlined when the code for both, application and the platform are readily available to analyze. And hence, there has been a great deal of research in testing and static analysis of Android applications. A great deal of this research has been focused on the input test generation for Android applications. Hence, there are a several testing tools available now, which focus on automatic generation of test cases for Android applications. These tools differ with one another on the basis of their strategies and heuristics used for this generation of test cases. But there is still very little work done on the comparison of these testing tools and the strategies they use. Recently, some research work has been carried outiv in this regard that compared the performance of various available tools with respect to their respective code coverage, fault detection, ability to work on multiple platforms and their ease of use. It was done, by running these tools on a total of 60 real world Android applications. The results of this research showed that although effective, these strategies being used by the tools, also face limitations and hence, have room for improvement. The purpose of this thesis is to extend this research into a more specific and attribute-­‐ oriented way. Attributes refer to the tasks that can be completed using the Android platform. It can be anything ranging from a basic system call for receiving an SMS to more complex tasks like sending the user to another application from the current one. The idea is to develop a benchmark for Android testing tools, which is based on the performance related to these attributes. This will allow the comparison of these tools with respect to these attributes. For example, if there is an application that plays some audio file, will the testing tool be able to generate a test input that will warrant the execution of this audio file? Using multiple applications using different attributes, it can be visualized that which testing tool is more useful for which kinds of attributes. In this thesis, it was decided that 9 attributes covering the basic nature of tasks, will be targeted for the assessment of three testing tools. Later this can be done for much more attributes to compare even more testing tools. The aim of this work is to show that this approach is effective and can be used on a much larger scale. One of the flagship features of this work, which also differentiates it with the previous work, is that the applications used, are all specially made for this research. The reason for doing that is to analyze just that specific attribute in isolation, which the application is focused on, and not allow the tool to get bottlenecked by something trivial, which is not the main attribute under testing. This means 9 applications, each focused on one specific attribute. The main contributions of this thesis are: A summary of the three existing testing tools and their respective techniques for automatic test input generation of Android Applications. • A detailed study of the usage of these testing tools using the 9 applications specially designed and developed for this study. • The analysis of the obtained results of the study carried out. And a comparison of the performance of the selected tools.

Design and implementation of a modular interface to integrate CLP and tabled execution

Logic programming (LP) is a family of high-level programming languages which provides high expressive power. With LP, the programmer writes the properties of the result and / or executable specifications instead of detailed computation steps. Logic programming systems which feature tabled execution and constraint logic programming have been shown to increase the declarativeness and efficiency of Prolog, while at the same time making it possible to write very expressive programs. Tabled execution avoids infinite failure in some cases, while improving efficiency in programs which repeat computations. CLP reduces the search tree and brings the power of solving (in)equations over arbitrary domains. Similarly to the LP case, CLP systems can also benefit from the power of tabling. Previous implementations which take ful advantage of the ideas behind tabling (e.g., forcing suspension, answer subsumption, etc. wherever it is necessary to avoid recomputation and terminate whenever possible) did not offer a simple, well-documented, easy-to-understand interface. This would be necessary to make the integratation of arbitrary CLP solvers into existing tabling systems possible. This clearly hinders a more widespread usage of the combination of both facilities. In this thesis we examine the requirements that a constraint solver must fulfill in order to be interfaced with a tabling system. We propose and implement a framework, which we have called Mod TCLP, with a minimal set of operations (e.g., entailment checking and projection) which the constraint solver has to provide to the tabling engine. We validate the design of Mod TCLP by a series of use cases: we re-engineer a previously existing tabled constrain domain (difference constraints) which was connected in an ad-hoc manner with the tabling engine in Ciao Prolog; we integrateHolzbauer’s CLP(Q) implementationwith Ciao Prolog’s tabling engine; and we implement a constraint solver over (finite) lattices. We evaluate its performance with several benchmarks that implement a simple abstract interpreter whose fixpoint is reached by means of tabled execution, and whose domain operations are handled by the constraint over (finite) lattices, where TCLP avoids recomputing subsumed abstractions.---ABSTRACT---La programación lógica con restricciones (CLP) y la tabulación son extensiones de la programación lógica que incrementan la declaratividad y eficiencia de Prolog, al mismo tiempo que hacen posible escribir programasmás expresivos. Las implementaciones anteriores que integran completamente ambas extensiones, incluyendo la suspensión de la ejecución de objetivos siempre que sea necesario, la implementación de inclusión (subsumption) de respuestas, etc., en todos los puntos en los que sea necesario para evitar recomputaciones y garantizar la terminación cuando sea posible, no han proporcionan una interfaz simple, bien documentada y fácil de entender. Esta interfaz es necesaria para permitir integrar resolutores de CLP arbitrarios en el sistema de tabulación. Esto claramente dificulta un uso más generalizado de la integración de ambas extensiones. En esta tesis examinamos los requisitos que un resolutor de restricciones debe cumplir para ser integrado con un sistema de tabulación. Proponemos un esquema (y su implementación), que hemos llamadoMod TCLP, que requiere un reducido conjunto de operaciones (en particular, y entre otras, entailment y proyección de almacenes de restricciones) que el resolutor de restricciones debe ofrecer al sistema de tabulación. Hemos validado el diseño de Mod TCLP con una serie de casos de uso: la refactorización de un sistema de restricciones (difference constraints) previamente conectado de un modo ad-hoc con la tabulación de Ciao Prolog; la integración del sistema de restricciones CLP(Q) de Holzbauer; y la implementación de un resolutor de restricciones sobre retículos finitos. Hemos evaluado su rendimiento con varios programas de prueba, incluyendo la implementación de un intérprete abstracto que alcanza su punto fijo mediante el sistema de tabulación y en el que las operaciones en el dominio son realizadas por el resolutor de restricciones sobre retículos (finitos) donde TCLP evita la recomputación de valores abstractos de las variables ya contenidos en llamadas anteriores.

Improved static analysis and verification of energy consumption and other resources via abstract interpretation

Resource analysis aims at inferring the cost of executing programs for any possible input, in terms of a given resource, such as the traditional execution steps, time ormemory, and, more recently energy consumption or user defined resources (e.g., number of bits sent over a socket, number of database accesses, number of calls to particular procedures, etc.). This is performed statically, i.e., without actually running the programs. Resource usage information is useful for a variety of optimization and verification applications, as well as for guiding software design. For example, programmers can use such information to choose different algorithmic solutions to a problem; program transformation systems can use cost information to choose between alternative transformations; parallelizing compilers can use cost estimates for granularity control, which tries to balance the overheads of task creation and manipulation against the benefits of parallelization. In this thesis we have significatively improved an existing prototype implementation for resource usage analysis based on abstract interpretation, addressing a number of relevant challenges and overcoming many limitations it presented. The goal of that prototype was to show the viability of casting the resource analysis as an abstract domain, and howit could overcome important limitations of the state-of-the-art resource usage analysis tools. For this purpose, it was implemented as an abstract domain in the abstract interpretation framework of the CiaoPP system, PLAI.We have improved both the design and implementation of the prototype, for eventually allowing an evolution of the tool to the industrial application level. The abstract operations of such tool heavily depend on the setting up and finding closed-form solutions of recurrence relations representing the resource usage behavior of program components and the whole program as well. While there exist many tools, such as Computer Algebra Systems (CAS) and libraries able to find closed-form solutions for some types of recurrences, none of them alone is able to handle all the types of recurrences arising during program analysis. In addition, there are some types of recurrences that cannot be solved by any existing tool. This clearly constitutes a bottleneck for this kind of resource usage analysis. Thus, one of the major challenges we have addressed in this thesis is the design and development of a novel modular framework for solving recurrence relations, able to combine and take advantage of the results of existing solvers. Additionally, we have developed and integrated into our novel solver a technique for finding upper-bound closed-form solutions of a special class of recurrence relations that arise during the analysis of programs with accumulating parameters. Finally, we have integrated the improved resource analysis into the CiaoPP general framework for resource usage verification, and specialized the framework for verifying energy consumption specifications of embedded imperative programs in a real application, showing the usefulness and practicality of the resulting tool.---ABSTRACT---El Análisis de recursos tiene como objetivo inferir el coste de la ejecución de programas para cualquier entrada posible, en términos de algún recurso determinado, como pasos de ejecución, tiempo o memoria, y, más recientemente, el consumo de energía o recursos definidos por el usuario (por ejemplo, número de bits enviados a través de un socket, el número de accesos a una base de datos, cantidad de llamadas a determinados procedimientos, etc.). Ello se realiza estáticamente, es decir, sin necesidad de ejecutar los programas. La información sobre el uso de recursos resulta muy útil para una gran variedad de aplicaciones de optimización y verificación de programas, así como para asistir en el diseño de los mismos. Por ejemplo, los programadores pueden utilizar dicha información para elegir diferentes soluciones algorítmicas a un problema; los sistemas de transformación de programas pueden utilizar la información de coste para elegir entre transformaciones alternativas; los compiladores paralelizantes pueden utilizar las estimaciones de coste para realizar control de granularidad, el cual trata de equilibrar el coste debido a la creación y gestión de tareas, con los beneficios de la paralelización. En esta tesis hemos mejorado de manera significativa la implementación de un prototipo existente para el análisis del uso de recursos basado en interpretación abstracta, abordando diversos desafíos relevantes y superando numerosas limitaciones que éste presentaba. El objetivo de dicho prototipo era mostrar la viabilidad de definir el análisis de recursos como un dominio abstracto, y cómo se podían superar las limitaciones de otras herramientas similares que constituyen el estado del arte. Para ello, se implementó como un dominio abstracto en el marco de interpretación abstracta presente en el sistema CiaoPP, PLAI. Hemos mejorado tanto el diseño como la implementación del mencionado prototipo para posibilitar su evolución hacia una herramienta utilizable en el ámbito industrial. Las operaciones abstractas de dicha herramienta dependen en gran medida de la generación, y posterior búsqueda de soluciones en forma cerrada, de relaciones recurrentes, las cuales modelizan el comportamiento, respecto al consumo de recursos, de los componentes del programa y del programa completo. Si bien existen actualmente muchas herramientas capaces de encontrar soluciones en forma cerrada para ciertos tipos de recurrencias, tales como Sistemas de Computación Algebraicos (CAS) y librerías de programación, ninguna de dichas herramientas es capaz de tratar, por sí sola, todos los tipos de recurrencias que surgen durante el análisis de recursos. Existen incluso recurrencias que no las puede resolver ninguna herramienta actual. Esto constituye claramente un cuello de botella para este tipo de análisis del uso de recursos. Por lo tanto, uno de los principales desafíos que hemos abordado en esta tesis es el diseño y desarrollo de un novedoso marco modular para la resolución de relaciones recurrentes, combinando y aprovechando los resultados de resolutores existentes. Además de ello, hemos desarrollado e integrado en nuestro nuevo resolutor una técnica para la obtención de cotas superiores en forma cerrada de una clase característica de relaciones recurrentes que surgen durante el análisis de programas lógicos con parámetros de acumulación. Finalmente, hemos integrado el nuevo análisis de recursos con el marco general para verificación de recursos de CiaoPP, y hemos instanciado dicho marco para la verificación de especificaciones sobre el consumo de energía de programas imperativas embarcados, mostrando la viabilidad y utilidad de la herramienta resultante en una aplicación real.

Extending the expressiveness of fuzzy logic languages

En el trabajo que aquí presentamos se incluye la base teórica (sintaxis y semántica) y una implementación de un framework para codificar el razonamiento de la representación difusa o borrosa del mundo (tal y como nosotros, seres humanos, entendemos éste). El interés en la realización de éste trabajo parte de dos fuentes: eliminar la complejidad existente cuando se realiza una implementación con un lenguaje de programación de los llamados de propósito general y proporcionar una herramienta lo suficientemente inteligente para dar respuestas de forma constructiva a consultas difusas o borrosas. El framework, RFuzzy, permite codificar reglas y consultas en una sintaxis muy cercana al lenguaje natural usado por los seres humanos para expresar sus pensamientos, pero es bastante más que eso. Permite representar conceptos muy interesantes, como fuzzificaciones (funciones usadas para convertir conceptos no difusos en difusos), valores por defecto (que se usan para devolver resultados un poco menos válidos que los que devolveríamos si tuviésemos la información necesaria para calcular los más válidos), similaridad entre atributos (característica que utilizamos para buscar aquellos individuos en la base de datos con una característica similar a la buscada), sinónimos o antónimos y, además, nos permite extender el numero de conectivas y modificadores (incluyendo modificadores de negación) que podemos usar en las reglas y consultas. La personalización de la definición de conceptos difusos (muy útil para lidiar con el carácter subjetivo de los conceptos borrosos, donde nos encontramos con que cualificar a alguien de “alto” depende de la altura de la persona que cualifica) es otra de las facilidades incluida. Además, RFuzzy implementa la semántica multi-adjunta. El interés en esta reside en que introduce la posibilidad de obtener la credibilidad de una regla a partir de un conjunto de datos y una regla dada y no solo el grado de satisfacción de una regla a partir de el universo modelado en nuestro programa. De esa forma podemos obtener automáticamente la credibilidad de una regla para una determinada situación. Aún cuando la contribución teórica de la tesis es interesante en si misma, especialmente la inclusión del modificador de negacion, sus multiples usos practicos lo son también. Entre los diferentes usos que se han dado al framework destacamos el reconocimiento de emociones, el control de robots, el control granular en computacion paralela/distribuída y las busquedas difusas o borrosas en bases de datos. ABSTRACT In this work we provide a theoretical basis (syntax and semantics) and a practical implementation of a framework for encoding the reasoning and the fuzzy representation of the world (as human beings understand it). The interest for this work comes from two sources: removing the existing complexity when doing it with a general purpose programming language (one developed without focusing in providing special constructions for representing fuzzy information) and providing a tool intelligent enough to answer, in a constructive way, expressive queries over conventional data. The framework, RFuzzy, allows to encode rules and queries in a syntax very close to the natural language used by human beings to express their thoughts, but it is more than that. It allows to encode very interesting concepts, as fuzzifications (functions to easily fuzzify crisp concepts), default values (used for providing results less adequate but still valid when the information needed to provide results is missing), similarity between attributes (used to search for individuals with a characteristic similar to the one we are looking for), synonyms or antonyms and it allows to extend the number of connectives and modifiers (even negation) we can use in the rules. The personalization of the definition of fuzzy concepts (very useful for dealing with the subjective character of fuzziness, in which a concept like tall depends on the height of the person performing the query) is another of the facilities included. Besides, RFuzzy implements the multi-adjoint semantics. The interest in them is that in addition to obtaining the grade of satisfaction of a consequent from a rule, its credibility and the grade of satisfaction of the antecedents we can determine from a set of data how much credibility we must assign to a rule to model the behaviour of the set of data. So, we can determine automatically the credibility of a rule for a particular situation. Although the theoretical contribution is interesting by itself, specially the inclusion of the negation modifier, the practical usage of it is equally important. Between the different uses given to the framework we highlight emotion recognition, robocup control, granularity control in parallel/distributed computing and flexible searches in databases.

Distribution of microservices for hardware interoperability in the Smart Grid

Due to the significant increase of population and their natural desire of improving their standard of living, usage of energy extracted from world commodities, especially shaped as electricity, has increased in an intense manner during the last decades. This fact brings up a challenge with a complicated solution, which is how to guarantee that there will be enough energy so as to satisfy the energy demand of the world population. Among all the possible solutions that can be adopted to mitigate this problem one of them is almost of mandatory adoption, which consists of rationalizing energy utilization, in a way that its wasteful usage is minimized and it can be leveraged during a longer period of time. One of the ways to achieve it is by means of the improvement of the power distribution grid, so that it will be able to react in a more efficient manner against common issues, such as energy demand peaks or inaccurate electricity consumption forecasts. However, in order to be able to implement this improvement it is necessary to use technologies from the ICT (Information and Communication Technologies) sphere that often present challenges in some key areas: advanced metering infrastructure integration, interoperability and interconnectivity of the devices, interfaces to offer the applications, security measures design, etc. All these challenges may imply slowing down the adoption of the smart grid as a system to prolong the lifespan and utilization of the available energy. A proposal for an intermediation architecture that will make possible solving these challenges is put forward in this Master Thesis. Besides, one implementation and the tests that have been carried out to know the performance of the presented concepts have been included as well, in a way that it can be proved that the challenges set out by the smart grid can be resolved. RESUMEN. Debido al incremento significativo de la población y su deseo natural de mejorar su nivel de vida, la utilización de la energía extraída de las materias primas mundiales, especialmente en forma de electricidad, ha aumentado de manera intensa durante las últimas décadas. Este hecho plantea un reto de solución complicada, el cual es cómo garantizar que se dispondrá de la energía suficiente como para satisfacer la demanda energética de la población mundial. De entre todas las soluciones posibles que se pueden adoptar para mitigar este problema una de ellas es de casi obligatoria adopción, la cual consiste en racionalizar la utilización de la energía, de tal forma que se minimice su malgasto y pueda aprovecharse durante más tiempo. Una de las maneras de conseguirlo es mediante la mejora de la red de distribución de electricidad para que ésta pueda reaccionar de manera más eficaz contra problemas comunes, tales como los picos de demanda de energía o previsiones imprecisas acerca del consumo de electricidad. Sin embargo, para poder implementar esta mejora es necesario utilizar tecnologías del ámbito de las TIC (Tecnologías de la Información y la Comunicación) que a menudo presentan problemas en algunas áreas clave: integración de infraestructura de medición avanzada, interoperabilidad e interconectividad de los dispositivos, interfaces que ofrecer a las aplicaciones, diseño de medidas de seguridad, etc. Todos estos retos pueden implicar una ralentización en la adopción de la red eléctrica inteligente como un sistema para alargar la vida y la utilización de la energía disponible. En este Trabajo Fin de Máster se sugiere una propuesta para una arquitectura de intermediación que posibilite la resolución de estos retos. Además, una implementación y las pruebas que se han llevado a cabo para conocer el rendimiento de los conceptos presentados también han sido incluidas, de tal forma que se demuestre que los retos que plantea la red eléctrica inteligente pueden ser solventados.

Youth participation in development planning: case study of Sayausí (Rural Parish) Cuenca-Ecuador

Young people now represent the highest percentage of the world population. Soon, they will be seniors and they will take decisions for a more orderly and equitable world. For this reason, the participation of young people in development planning is very important and many countries are trying to promote it through various measures. This article analyzes the trajectory of youth participation in the Latin American region and specifically the profile of youth participation in Ecuador, country in which the Constitution recognizes the strategic role of youth in development. The case study of Sayausí rural parish in canton Cuenca is analyzed, through surveys, interviews and an Empowerment Evaluation workshop to young people and decentralized government. The results obtained allow to propose strategies to help improve the participation of youth in the community.

A technological framework based on automatic messaging for improving adherence of diabetic patients

En todo el mundo se ha observado un crecimiento exponencial en la incidencia de enfermedades crónicas como la hipertensión y enfermedades cardiovasculares y respiratorias, así como la diabetes mellitus, que causa un número de muertes cada vez mayor en todo el mundo (Beaglehole et al., 2008). En concreto, la prevalencia de diabetes mellitus (DM) está aumentando de manera considerable en todas las edades y representa un serio problema de salud mundial. La diabetes fue la responsable directa de 1,5 millones de muertes en 2012 y 89 millones de años de vida ajustados por discapacidad (AVAD) (OMS, 2014). Uno de los principales dilemas que suelen asociarse a la gestión de EC es la adherencia de los pacientes a los tratamientos, que representa un aspecto multifactorial que necesita asistencia en lo relativo a: educación, autogestión, interacción entre los pacientes y cuidadores y compromiso de los pacientes. Medir la adherencia del tratamiento es complicado y, aunque se ha hablado ampliamente de ello, aún no hay soluciones “de oro” (Reviews, 2002). El compromiso de los pacientes, a través de la participación, colaboración, negociación y a veces del compromiso firme, aumentan las oportunidades para una terapia óptima en la que los pacientes se responsabilizan de su parte en la ecuación de adherencia. Comprometer e involucrar a los pacientes diabéticos en las decisiones de su tratamiento, junto con expertos profesionales, puede ayudar a favorecer un enfoque centrado en el paciente hacia la atención a la diabetes (Martin et al., 2005). La motivación y atribución de poder de los pacientes son quizás los dos factores interventores más relevantes que afectan directamente a la autogestión de la atención a la diabetes. Se ha demostrado que estos dos factores desempeñan un papel fundamental en la adherencia a la prescripción, así como en el fomento exitoso de un estilo de vida sana y otros cambios de conducta (Heneghan et al., 2013). Un plan de educación personalizada es indispensable para proporcionarle al paciente las herramientas adecuadas que necesita para la autogestión efectiva de la enfermedad (El-Gayar et al. 2013). La comunicación efectiva es fundamental para proporcionar una atención centrada en el paciente puesto que influye en las conductas y actitudes hacia un problema de salud ((Frampton et al. 2008). En este sentido, la interactividad, la frecuencia, la temporalización y la adaptación de los mensajes de texto pueden promover la adherencia a un régimen de medicación. Como consecuencia, adaptar los mensajes de texto a los pacientes puede resultar ser una manera de hacer que las sugerencias y la información sean más relevantes y efectivas (Nundy et al. 2013). En este contexto, las tecnologías móviles en el ámbito de la salud (mHealth) están desempeñando un papel importante al conectar con pacientes para mejorar la adherencia a medicamentos recetados (Krishna et al., 2009). La adaptación de los mensajes de texto específicos de diabetes sigue siendo un área de oportunidad para mejorar la adherencia a la medicación y ofrecer motivación a adultos con diabetes. Sin embargo, se necesita más investigación para entender totalmente su eficacia. Los consejos de texto personalizados han demostrado causar un impacto positivo en la atribución de poder a los pacientes, su autogestión y su adherencia a la prescripción (Gatwood et al., 2014). mHealth se puede utilizar para ofrecer programas de asistencia de autogestión a los pacientes con diabetes y, al mismo tiempo, superar las dificultades técnicas y financieras que supone el tratamiento de la diabetes (Free at al., 2013). El objetivo principal de este trabajo de investigación es demostrar que un marco tecnológico basado en las teorías de cambios de conducta, aplicado al campo de la mHealth, permite una mejora de la adherencia al tratamiento en pacientes diabéticos. Como método de definición de una solución tecnológica, se han adoptado un conjunto de diferentes técnicas de conducta validadas denominado marco de compromiso de retroacción conductual (EBF, por sus siglas en inglés) para formular los mensajes, guiar el contenido y evaluar los resultados. Los estudios incorporan elementos del modelo transteórico (TTM, por sus siglas en inglés), la teoría de la fijación de objetivos (GST, por sus siglas en inglés) y los principios de comunicación sanitaria persuasiva y eficaz. Como concepto general, el modelo TTM ayuda a los pacientes a progresar a su próxima fase de conducta a través de mensajes de texto motivados específicos y permite que el médico identifique la fase actual y adapte sus estrategias individualmente. Además, se adoptan las directrices del TTM para fijar objetivos personalizados a un nivel apropiado a la fase de cambio del paciente. La GST encierra normas que van a ponerse en práctica para promover la intervención educativa y objetivos de pérdida de peso. Finalmente, los principios de comunicación sanitaria persuasiva y eficaz aplicados a la aparición de los mensajes se han puesto en marcha para aumentar la efectividad. El EBF tiene como objetivo ayudar a los pacientes a mejorar su adherencia a la prescripción y encaminarlos a una mejora general en la autogestión de la diabetes mediante mensajes de texto personalizados denominados mensajes de retroacción automáticos (AFM, por sus siglas en inglés). Después de una primera revisión del perfil, consistente en identificar características significativas del paciente basadas en las necesidades de tratamiento, actitudes y conductas de atención sanitaria, el sistema elige los AFM personalizados, los aprueba el médico y al final se transfieren a la interfaz del paciente. Durante el tratamiento, el usuario recopila los datos en dispositivos de monitorización de pacientes (PMD, por sus siglas en inglés) de una serie de dispositivos médicos y registros manuales. Los registros consisten en la toma de medicación, dieta y actividad física y tareas de aprendizaje y control de la medida del metabolismo. El compromiso general del paciente se comprueba al estimar el uso del sistema y la adherencia del tratamiento y el estado de los objetivos del paciente a corto y largo plazo. El módulo de análisis conductual, que consiste en una serie de reglas y ecuaciones, calcula la conducta del paciente. Tras lograr el análisis conductual, el módulo de gestión de AFM actualiza la lista de AFM y la configuración de los envíos. Las actualizaciones incluyen el número, el tipo y la frecuencia de mensajes. Los AFM los revisa periódicamente el médico que también participa en el perfeccionamiento del tratamiento, adaptado a la fase transteórica actual. Los AFM se segmentan en distintas categorías y niveles y los pacientes pueden ajustar la entrega del mensaje de acuerdo con sus necesidades personales. El EBF se ha puesto en marcha integrado dentro del sistema METABO, diseñado para facilitar al paciente diabético que controle sus condiciones relevantes de una manera menos intrusiva. El dispositivo del paciente se vincula en una plataforma móvil, mientras que una interfaz de panel médico permite que los profesionales controlen la evolución del tratamiento. Herramientas específicas posibilitan que los profesionales comprueben la adherencia del paciente y actualicen la gestión de envíos de AFM. El EBF fue probado en un proyecto piloto controlado de manera aleatoria. El principal objetivo era examinar la viabilidad y aceptación del sistema. Los objetivos secundarios eran también la evaluación de la eficacia del sistema en lo referente a la mejora de la adherencia, el control glucémico y la calidad de vida. Se reclutaron participantes de cuatro centros clínicos distintos en Europa. La evaluación del punto de referencia incluía datos demográficos, estado de la diabetes, información del perfil, conocimiento de la diabetes en general, uso de las plataformas TIC, opinión y experiencia con dispositivos electrónicos y adopción de buenas prácticas con la diabetes. La aceptación y eficacia de los criterios de evaluación se aplicaron para valorar el funcionamiento del marco tecnológico. El principal objetivo era la valoración de la eficacia del sistema en lo referente a la mejora de la adherencia. En las pruebas participaron 54 pacientes. 26 fueron asignados al grupo de intervención y equipados con tecnología móvil donde estaba instalado el EBF: 14 pacientes tenían T1DM y 12 tenían T2DM. El grupo de control estaba compuesto por 25 pa cientes que fueron tratados con atención estándar, sin el empleo del EBF. La intervención profesional tanto de los grupos de control como de intervención corrió a cargo de 24 cuidadores, entre los que incluían diabetólogos, nutricionistas y enfermeras. Para evaluar la aceptabilidad del sistema y analizar la satisfacción de los usuarios, a través de LimeSurvey, se creó una encuesta multilingüe tanto para los pacientes como para los profesionales. Los resultados también se recopilaron de los archivos de registro generados en los PMD, el panel médico profesional y las entradas de la base de datos. Los mensajes enviados hacia y desde el EBF y los archivos de registro del sistema y los servicios de comunicación se grabaron durante las cinco semanas del estudio. Se entregaron un total de 2795 mensajes, lo que supuso una media de 107,50 mensajes por paciente. Como se muestra, los mensajes disminuyen con el tiempo, indicando una mejora global de la adherencia al plan de tratamiento. Como se esperaba, los pacientes con T1DM recibieron más consejos a corto plazo, en relación a su estado. Del mismo modo, al ser el centro de T2DM en cambios de estilo de vida sostenible a largo plazo, los pacientes con T2DM recibieron más consejos de recomendación, en cuanto a dietas y actividad física. También se ha llevado a cabo una comparación de la adherencia e índices de uso para pacientes con T1DM y T2DM, entre la primera y la segunda mitad de la prueba. Se han observado resultados favorables para el uso. En lo relativo a la adherencia, los resultados denotaron una mejora general en cada dimensión del plan de tratamiento, como la nutrición y las mediciones de inserción de glucosa en la sangre. Se han llevado a cabo más estudios acerca del cambio a nivel educativo antes y después de la prueba, medidos tanto para grupos de control como de intervención. Los resultados indicaron que el grupo de intervención había mejorado su nivel de conocimientos mientras que el grupo de control mostró una leve disminución. El análisis de correlación entre el nivel de adherencia y las AFM ha mostrado una mejora en la adherencia de uso para los pacientes que recibieron los mensajes de tipo alertas, y unos resultados no significativos aunque positivos relacionados con la adherencia tanto al tratamiento que al uso correlacionado con los recordatorios. Por otra parte, los AFM parecían ayudar a los pacientes que no tomaban suficientemente en serio su tratamiento en el principio y que sí estaban dispuestos a responder a los mensajes recibidos. Aun así, los pacientes que recibieron demasiadas advertencias, comenzaron a considerar el envío de mensajes un poco estresante. El trabajo de investigación llevado a cabo al desarrollar este proyecto ofrece respuestas a las cuatro hipótesis de investigación que fueron la motivación para el trabajo. • Hipótesis 1 : es posible definir una serie de criterios para medir la adherencia en pacientes diabéticos. • Hipótesis 2: es posible diseñar un marco tecnológico basado en los criterios y teorías de cambio de conducta mencionados con anterioridad para hacer que los pacientes diabéticos se comprometan a controlar su enfermedad y adherirse a planes de atención. • Hipótesis 3: es posible poner en marcha el marco tecnológico en el sector de la salud móvil. • Hipótesis 4: es posible utilizar el marco tecnológico como solución de salud móvil en un contexto real y tener efectos positivos en lo referente a indicadores de control de diabetes. La verificación de cada hipótesis permite ofrecer respuesta a la hipótesis principal: La hipótesis principal es: es posible mejorar la adherencia diabética a través de un marco tecnológico mHealth basado en teorías de cambio de conducta. El trabajo llevado a cabo para responder estas preguntas se explica en este trabajo de investigación. El marco fue desarrollado y puesto en práctica en el Proyecto METABO. METABO es un Proyecto I+D, cofinanciado por la Comisión Europea (METABO 2008) que integra infraestructura móvil para ayudar al control, gestión y tratamiento de los pacientes con diabetes mellitus de tipo 1 (T1DM) y los que padecen diabetes mellitus de tipo 2 (T2DM). ABSTRACT Worldwide there is an exponential growth in the incidence of Chronic Diseases (CDs), such as: hypertension, cardiovascular and respiratory diseases, as well as diabetes mellitus, leading to rising numbers of deaths worldwide (Beaglehole et al. 2008). In particular, the prevalence of diabetes mellitus (DM) is largely increasing among all ages and constitutes a major worldwide health problem. Diabetes was directly responsible for 1,5 million deaths in 2012 and 89 million Disability-adjusted life year (DALYs) (WHO 2014). One of the key dilemmas often associated to CD management is the patients’ adherence to treatments, representing a multi-factorial aspect that requires support in terms of: education, self-management, interaction between patients and caregivers, and patients’ engagement. Measuring adherence is complex and, even if widely discussed, there are still no “gold” standards ((Giardini et al. 2015), (Costa et al. 2015). Patient’s engagement, through participation, collaboration, negotiation, and sometimes compromise, enhance opportunities for optimal therapy in which patients take responsibility for their part of the adherence equation. Engaging and involving diabetic patients in treatment decisions, along with professional expertise, can help foster a patient-centered approach to diabetes care (Martin et al. 2005). Patients’ motivation and empowerment are perhaps the two most relevant intervening factors that directly affect self-management of diabetes care. It has been demonstrated that these two factors play an essential role in prescription adherence, as well as for the successful encouragement of a healthy life-style and other behavioural changes (Heneghan et al. 2013). A personalised education plan is indispensable in order to provide the patient with the appropriate tools needed for the effective self-management of the disease (El-Gayar et al. 2013). Effective communication is at the core of providing patient-centred care since it influences behaviours and attitudes towards a health problem (Frampton et al. 2008). In this regard, interactivity, frequency, timing, and tailoring of text messages may promote adherence to a medication regimen. As a consequence, tailoring text messages to patients can constitute a way of making suggestions and information more relevant and effective (Nundy et al. 2013). In this context, mobile health technologies (mHealth) are playing significant roles in improving adherence to prescribed medications (Krishna et al. 2009). The tailoring of diabetes-specific text messages remains an area of opportunity to improve medication adherence and provide motivation to adults with diabetes but further research is needed to fully understand their effectiveness. Personalized text advices have proven to produce a positive impact on patients’ empowerment, self-management, and adherence to prescriptions (Gatwood et al. 2014). mHealth can be used for offering self-management support programs to diabetes patients and at the same time surmounting the technical and financial difficulties involved in diabetes treatment (Free et al. 2013). The main objective of this research work is to demonstrate that a technological framework, based on behavioural change theories, applied to mHealth domain, allows improving adherence treatment in diabetic patients. The framework, named Engagement Behavioural Feedback Framework (EBF), is built on top of validated behavioural techniques to frame messages, guide the definition of contents and assess outcomes: elements from the Transtheoretical Model (TTM), the Goal-Setting Theory (GST), Effective Health Communication (EHC) guidelines and Principles of Persuasive Technology (PPT) were incorporated. The TTM helps patients to progress to a next behavioural stage, through specific motivated text messages, and allow clinician’s identifying the current stage and tailor its strategies individually. Moreover, TTM guidelines are adopted to set customised goals at a level appropriate to the patient’s stage of change. The GST was used to build rules to be applied for enhancing educational intervention and weight loss objectives. Finally, the EHC guidelines and the PPT were applied to increase the effectiveness of messages. The EBF aims to support patients on improving their prescription adherence and persuade them towards a general improvement in diabetes self-management, by means of personalised text messages, named Automatic Feedback Messages (AFM). After a first profile screening, consisting in identifying meaningful patient characteristics based on treatment needs, attitudes and health care behaviours, customised AFMs are selected by the system, approved by the professional, and finally transferred into the patient interface. During the treatment, the user collects the data into a Patient Monitoring Device (PMD) from a set of medical devices and from manual inputs. Inputs consist in medication intake, diet and physical activity, metabolic measurement monitoring and learning tasks. Patient general engagement is checked by estimating the usage of the system and the adherence of treatment and patient goals status in the short and the long term period. The Behavioural Analysis Module, consisting in a set of rules and equations, calculates the patient’s behaviour. After behavioural analysis is accomplished, the AFM library and the dispatch setting are updated by the AFM Manager module. Updates include the number, the type and the frequency of messages. The AFMs are periodically supervised by the professional who also participates to the refinement of the treatment, adapted to the current transtheoretical stage. The AFMs are segmented in different categories and levels and patients can adjust message delivery in accordance with their personal needs. The EBF was integrated to the METABO system, designed to facilitate diabetic patients in managing their disease in a less intrusive approach. Patient device corresponds in a mobile platform, while a medical panel interface allows professionals to monitoring the treatment evolution. Specific tools allow professional to check patient adherence and to update the AFMs dispatch management. The EBF was tested in a randomised controlled pilot. The main objective was to examine the feasibility and acceptance of the system. Secondary objectives were also the assessment of the effectiveness of system in terms of adherence improvement, glycaemic control, and quality of life. Participants were recruited from four different clinical centres in Europe. The baseline assessment included demographics, diabetes status, profile information, knowledge about diabetes in general, usage of ICT platforms, opinion and experience about electronic devices and adoption of good practices with diabetes. Acceptance and the effectiveness evaluation criteria were applied to evaluate the performance of the technological framework. The main objective was the assessment of the effectiveness of system in terms of adherence improvement. Fifty-four patients participated on the trials. Twenty-six patients were assigned in the intervention group and equipped with mobile where the EBF was installed: 14 patients were T1DM and 12 were T2DM. The control group was composed of 25 patients that were treated through a standard care, without the usage of the EBF. Professional’s intervention for both intervention and control groups was carried out by 24 care providers, including endocrinologists, nutritionists, and nurses. In order to evaluate the system acceptability and analyse the users’ satisfaction, an online multi-language survey, using LimeSurvey, was produced for both patients and professionals. Results were also collected from the log-files generated in the PMDs, the professional medical panel and the entries of the data base. The messages sent to and from the EBF and the log-files of the system and communication services were recorded over 5 weeks of the study. A total of 2795 messages were submitted, representing an average of 107,50 messages per patient. As demonstrated, messages decrease over time indicating an overall improvement of the care plan’s adherence. As expected, T1DM patients were more loaded with short-term advices, in accordance with their condition. Similarly, being the focus of T2DM on long-term sustainable lifestyle changes, T2DM received more reminders advices, as for diet and physical activity. Favourable outcomes were observed for treatment and usage adherences of the intervention group: for both the adherence indices, results denoted a general improvement on each care plan’s dimension, such as on nutrition and blood glucose input measurements. Further studies were conducted on the change on educational level before and after the trial, measured for both control and intervention groups. The outcomes indicated the intervention group has improved its level of knowledge, while the control group denoted a low decrease. The correlation analysis between the level of adherences and the AFMs showed an improvement in usage adherence for patients who received warnings message, while non-significantly yet even positive indicators related to both treatment and usage adherence correlated with the Reminders. Moreover, the AFMs seemed to help those patients who did not take their treatment seriously enough in the beginning and who were willing to respond to the messages they received. Even though, patients who received too many Warnings, started to consider the message dispatch to be a bit stressful. The research work carried out in developing this research work provides responses to the four research hypothesis that were the motivation for the work: •Hypothesis 1: It is possible to define a set of criteria to measure adherence in diabetic patients. •Hypothesis 2: It is possible to design a technological framework, based on the aforementioned criteria and behavioural change theories, to engage diabetic patients in managing their disease and adhere to care plans. •Hypothesis 3: It is possible to implement the technological framework in the mobile health domain. •Hypothesis 4: It is possible to use the technological framework as a mobile health solution in a real context and have positive effects in terms of diabetes management indicators. The verification of each hypothesis allowed us to provide a response to the main hypothesis: The Main Hypothesis is: It is possible to improve diabetic adherence through a mHealth technological framework based on behavioural change theories. The work carried out to answer these questions is explained in this research work. The framework was developed and applied in the METABO project. METABO is an R&D project, co-funded by the European Commission (METABO 2008) that integrates mobile infrastructure for supporting the monitoring, management, and treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients.

Quality of experience of adaptive video streaming: investigation in service parameters and subjective quality assessment methodology

The usage of HTTP adaptive streaming (HAS) has become widely spread in multimedia services. Because it allows the service providers to improve the network resource utilization and user׳s Quality of Experience (QoE). Using this technology, the video playback interruption is reduced since the network and server status in addition to capability of user device, all are taken into account by HAS client to adapt the quality to the current condition. Adaptation can be done using different strategies. In order to provide optimal QoE, the perceptual impact of adaptation strategies from point of view of the user should be studied. However, the time-varying video quality due to the adaptation which usually takes place in a long interval introduces a new type of impairment making the subjective evaluation of adaptive streaming system challenging. The contribution of this paper is two-fold: first, it investigates the testing methodology to evaluate HAS QoE by comparing the subjective experimental outcomes obtained from ACR standardized method and a semi-continuous method developed to evaluate the long sequences. In addition, influence of using audiovisual stimuli to evaluate the video-related impairment is inquired. Second, impact of some of the adaptation technical factors including the quality switching amplitude and chunk size in combination with high range of commercial content type is investigated. The results of this study provide a good insight toward achieving appropriate testing method to evaluate HAS QoE, in addition to designing switching strategies with optimal visual quality.

Prominence of the dopamine D2 short isoform in dopaminergic pathways

As a result of alternative splicing, the D2 gene of the dopamine receptor family exists in two isoforms. The D2 long is characterized by the insertion of 29 amino acids in the third cytoplasmic loop, which is absent in the short isoform. We have produced subtype-specific antibodies against both the D2 short and D2 long isoforms and found a unique compartmentalization between these two isoforms in the primate brain. The D2 short predominates in the cell bodies and projection axons of the dopaminergic cell groups of the mesencephalon and hypothalamus, whereas the D2 long is more strongly expressed by neurons in the striatum and nucleus accumbens, structures targeted by dopaminergic fibers. These results show that the splice variants of the dopamine D2 receptor are differentially distributed and possess distinct functions. The strategic localization of the D2 short isoform in dopaminergic cell bodies and axons strongly suggests that this isoform is the likely dopamine autoreceptor, whereas the D2 long isoform is primarily a postsynaptic receptor.

An intercalation inhibitor altering the target selectivity of DNA damaging agents: Synthesis of site-specific aflatoxin B1 adducts in a p53 mutational hotspot

Aflatoxin B1 (AFB1) is a potent human carcinogen implicated in the etiology of hepatocellular carcinoma. Upon metabolic activation to the reactive epoxide, AFB1 forms DNA adducts primarily at the N7 position of guanines. To elucidate more fully the molecular mechanism of AFB1-induced mutagenesis, an intercalation inhibitor was designed to probe the effects of intercalation by AFB1 epoxide on its reaction with DNA. DNA duplexes were prepared consisting of a target strand containing multiple potentially reactive guanines and a nontarget strand containing a cis-syn thymidine-benzofuran photoproduct. Because the covalently linked benzofuran moiety physically occupies an intercalation site, we reasoned that such a site would be rendered inaccessible to AFB1 epoxide. By strategic positioning of this intercalation inhibitor in the intercalation site 5′ to a specific guanine, the adduct yield at that site was greatly diminished, indicating that intercalation by AFB1 epoxide contributes favorably to adduct formation. Using this approach it has been possible to simplify the production of site-specifically modified oligonucleotides containing AFB1 adducts in the sequence context of a p53 mutational hotspot. Moreover, we report herein isolation of site-specifically AFB1-modified oligonucleotides in sequences containing multiple guanines. Use of intercalation inhibitors will facilitate both investigation of the ability of other carcinogens to intercalate into DNA and the synthesis of specific carcinogen-DNA adducts.

Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug

Triabin, a 142-residue protein from the saliva of the blood-sucking triatomine bug Triatoma pallidipennis, is a potent and selective thrombin inhibitor. Its stoichiometric complex with bovine α-thrombin was crystallized, and its crystal structure was solved by Patterson search methods and refined at 2.6-Å resolution to an R value of 0.184. The analysis revealed that triabin is a compact one-domain molecule essentially consisting of an eight-stranded β-barrel. The eight strands A to H are arranged in the order A-C-B-D-E-F-G-H, with the first four strands exhibiting a hitherto unobserved up-up-down-down topology. Except for the B-C inversion, the triabin fold exhibits the regular up-and-down topology of lipocalins. In contrast to the typical ligand-binding lipocalins, however, the triabin barrel encloses a hydrophobic core intersected by a unique salt-bridge cluster. Triabin interacts with thrombin exclusively via its fibrinogen-recognition exosite. Surprisingly, most of the interface interactions are hydrophobic. A prominent exception represents thrombin’s Arg-77A side chain, which extends into a hydrophobic triabin pocket forming partially buried salt bridges with Glu-128 and Asp-135 of the inhibitor. The fully accessible active site of thrombin in this complex is in agreement with its retained hydrolytic activity toward small chromogenic substrates. Impairment of thrombin’s fibrinogen converting activity or of its thrombomodulin-mediated protein C activation capacity upon triabin binding is explained by usage of overlapping interaction sites of fibrinogen, thrombomodulin, and triabin on thrombin. These data demonstrate that triabin inhibits thrombin via a novel and unique mechanism that might be of interest in the context of potential therapeutic applications.

Carbohydrate-deficient glycoprotein syndrome type V: Deficiency of dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase

Deficiency of dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase is the cause of an additional type of carbohydrate-deficient glycoprotein syndrome (CDGS type V). Clinically this type resembles the classical type Ia of CDGS caused by the deficiency of phosphomannomutase. As a result of the glucosyltransferase deficiency in CDGS type V nonglucosylated lipid-linked oligosaccharides accumulate. The defect is leaky and glucosylated oligosaccharides are found on nascent glycoproteins. The limited availability of glucosylated lipid-linked oligosaccharides explains the incomplete usage of N-glycosylation sites in glycoproteins. This finding is reflected in the presence of transferrin forms in serum that lack one or both of the two N-linked oligosaccharides and the reduction of mannose incorporation to about one-third of control in glycoproteins of fibroblasts.