Decision making in beach volleyball defense: Crucial factors derived from interviews with top-level experts

Objectives: In fast ball sports like beach volleyball, decision-making skills are a determining factor for excellent performance. The current investigation aimed to identify factors that influence the decisionmaking process in top-level beach volleyball defense in order to find relevant aspects for further research. For this reason, focused interviews with top players in international beach volleyball were conducted and analyzed with respect to decision-making characteristics. Design: Nineteen world-tour beach volleyball defense players, including seven Olympic or world champions, were interviewed, focusing on decision-making factors, gaze behavior, and interactions between the two. Methods: Verbal data were analyzed by inductive content analysis according to Mayring (2008). This approach allows categories to emerge from the interview material itself instead of forcing data into preset classifications and theoretical concepts. Results: The data analysis showed that, for top-level beach volleyball defense, decision making depends on opponent specifics, external context, situational context, opponent's movements, and intuition. Information on gaze patterns and visual cues revealed general tendencies indicating optimal gaze strategies that support excellent decision making. Furthermore, the analysis highlighted interactions between gaze behavior, visual information, and domain-specific knowledge. Conclusions: The present findings provide information on visual perception, domain-specific knowledge, and interactions between the two that are relevant for decision making in top-level beach volleyball defense. The results can be used to inform sports practice and to further untangle relevant mechanisms underlying decision making in complex game situations.

Climate sensitivity across marine domains of life: limits to evolutionary adaptation shape species interactions, supplementary material

Organisms in all domains, Archaea, Bacteria, and Eukarya will respond to climate change with differential vulnerabilities resulting in shifts in species distribution, coexistence, and interactions. The identification of unifying principles of organism functioning across all domains would facilitate a cause and effect understanding of such changes and their implications for ecosystem shifts. For example, the functional specialization of all organisms in limited temperature ranges leads us to ask for unifying functional reasons. Organisms also specialize in either anoxic or various oxygen ranges, with animals and plants depending on high oxygen levels. Here, we identify thermal ranges, heat limits of growth, and critically low (hypoxic) oxygen concentrations as proxies of tolerance in a meta-analysis of data available for marine organisms, with special reference to domain-specific limits. For an explanation of the patterns and differences observed, we define and quantify a proxy for organismic complexity across species from all domains. Rising complexity causes heat (and hypoxia) tolerances to decrease from Archaea to Bacteria to uni- and then multicellular Eukarya. Within and across domains, taxon-specific tolerance limits likely reflect ultimate evolutionary limits of its species to acclimatization and adaptation. We hypothesize that rising taxon-specific complexities in structure and function constrain organisms to narrower environmental ranges. Low complexity as in Archaea and some Bacteria provide life options in extreme environments. In the warmest oceans, temperature maxima reach and will surpass the permanent limits to the existence of multicellular animals, plants and unicellular phytoplankter. Smaller, less complex unicellular Eukarya, Bacteria, and Archaea will thus benefit and predominate even more in a future, warmer, and hypoxic ocean.

Combined determination of sharing and freeness of program variables through abstract interpretation

In this paper, abstract interpretation algorithms are described for computing the sharmg as well as the freeness information about the run-time instantiations of program variables. An abstract domain is proposed which accurately and concisely represents combined freeness and sharing information for program variables. Abstract unification and all other domain-specific functions for an abstract interpreter working on this domain are presented. These functions are illustrated with an example. The importance of inferring freeness is stressed by showing (1) the central role it plays in non-strict goal independence, and (2) the improved accuracy it brings to the analysis of sharing information when both are computed together. Conversely, it is shown that keeping accurate track of sharing allows more precise inference of freeness, thus resulting in an overall much more powerful abstract interpreter.

Integración de Fuentes con Información de Contexto y Sistemas Interactivos

Durante el transcurso de esta Tesis Doctoral se ha realizado un estudio de la problemática asociada al desarrollo de sistemas de interacción hombre-máquina sensibles al contexto. Este problema se enmarca dentro de dos áreas de investigación: los sistemas interactivos y las fuentes de información contextual. Tradicionalmente la integración entre ambos campos se desarrollaba a través de soluciones verticales específicas, que abstraen a los sistemas interactivos de conocer los procedimientos de bajo nivel de acceso a la información contextual, pero limitan su interoperabilidad con otras aplicaciones y fuentes de información. Para solventar esta limitación se hace imprescindible potenciar soluciones interoperables que permitan acceder a la información del mundo real a través de procedimientos homogéneos. Esta problemática coincide perfectamente con los escenarios de \Computación Ubicua" e \Internet de las Cosas", donde se apunta a un futuro en el que los objetos que nos rodean serán capaces de obtener información del entorno y comunicarla a otros objetos y personas. Los sistemas interactivos, al ser capaces de obtener información de su entorno a través de la interacción con el usuario, pueden tomar un papel especial en este escenario tanto como consumidores como productores de información. En esta Tesis se ha abordado la integración de ambos campos teniendo en cuenta este escenario tecnológico. Para ello, en primer lugar se ha realizado un an álisis de las iniciativas más importantes para la definición y diseño de sistemas interactivos, y de las principales infraestructuras de suministro de información. Mediante este estudio se ha propuesto utilizar el lenguaje SCXML del W3C para el diseño de los sistemas interactivos y el procesamiento de los datos proporcionados por fuentes de contexto. Así, se ha reflejado cómo las capacidades del lenguaje SCXML para combinar información de diferentes modalidades pueden también utilizarse para procesar e integrar información contextual de diferentes fuentes heterogéneas, y por consiguiente diseñar sistemas de interacción sensibles al contexto. Del mismo modo se presenta a la iniciativa Sensor Web, y a su extensión semántica Semantic Sensor Web, como una iniciativa idónea para permitir un acceso y suministro homogéneo de la información a los sistemas interactivos sensibles al contexto. Posteriormente se han analizado los retos que plantea la integración de ambos tipos de iniciativas. Como resultado se ha conseguido establecer una serie de funcionalidades que son necesarias implementar para llevar a cabo esta integración. Utilizando tecnologías que aportan una gran flexibilidad al proceso de implementación y que se apoyan en recomendaciones y estándares actuales, se implementaron una serie de desarrollos experimentales que integraban las funcionalidades identificadas anteriormente. Finalmente, con el fin de validar nuestra propuesta, se realizaron un conjunto de experimentos sobre un entorno de experimentación que simula el escenario de la conducción. En este escenario un sistema interactivo se comunica con una extensión semántica de una plataforma basada en los estándares de la Sensor Web para poder obtener información y publicar las observaciones que el usuario realizaba al sistema. Los resultados obtenidos han demostrado la viabilidad de utilizar el lenguaje SCXML para el diseño de sistemas interactivos sensibles al contexto que requieren acceder a plataformas avanzadas de información para consumir y publicar información a la vez que interaccionan con el usuario. Del mismo modo, se ha demostrado cómo la utilización de tecnologías semánticas en los procesos de consulta y publicación de información puede facilitar la reutilización de la información publicada en infraestructuras Sensor Web por cualquier tipo de aplicación, y de este modo contribuir al futuro escenario de Internet de las Cosas. ABSTRACT In this Thesis, we have addressed the difficulties related to the development of context-aware human-machine interaction systems. This issue is part of two research fields: interactive systems and contextual information sources. Traditionally both fields have been integrated through domain-specific vertical solutions that allow interactive systems to access contextual information without having to deal with low-level procedures, but restricting their interoperability with other applications and heterogeneous data sources. Thus, it is essential to boost the research on interoperable solutions that provide access to real world information through homogeneous procedures. This issue perfectly matches with the scenarios of \Ubiquitous Computing" and \Internet of Things", which point toward a future in which many objects around us will be able to acquire meaningful information about the environment and communicate it to other objects and to people. Since interactive systems are able to get information from their environment through interaction with the user, they can play an important role in this scenario as they can both consume real-world data and produce enriched information. This Thesis deals with the integration of both fields considering this technological scenario. In order to do this, we first carried out an analysis of the most important initiatives for the definition and design of interactive systems, and the main infrastructures for providing information. Through this study the use of the W3C SCXML language is proposed for both the design of interactive systems and the processing of data provided by different context sources. Thus, this work has shown how the SCXML capabilities for combining information from different modalities can also be used to process and integrate contextual information from different heterogeneous sensor sources, and therefore to develope context-aware interaction systems. Similarly, we present the Sensor Web initiative, and its semantic extension Semantic Sensor Web, as an appropriate initiative to allow uniform access and delivery of information to the context-aware interactive systems. Subsequently we have analyzed the challenges of integrating both types of initiatives: SCXML and (Semantic) Sensor Web. As a result, we state a number of functionalities that are necessary to implement in order to perform this integration. By using technologies that provide exibility to the implementation process and are based on current recommendations and standards, we implemented a series of experimental developments that integrate the identified functionalities. Finally, in order to validate our approach, we conducted different experiments with a testing environment simulating a driving scenario. In this framework an interactive system can access a semantic extension of a Telco plataform, based on the standards of the Sensor Web, to acquire contextual information and publish observations that the user performed to the system. The results showed the feasibility of using the SCXML language for designing context-aware interactive systems that require access to advanced sensor platforms for consuming and publishing information while interacting with the user. In the same way, it was shown how the use of semantic technologies in the processes of querying and publication sensor data can assist in reusing and sharing the information published by any application in Sensor Web infrastructures, and thus contribute to realize the future scenario of \Internet of Things".

A model to develop a platform for personalised health applications

Antecedentes Europa vive una situación insostenible. Desde el 2008 se han reducido los recursos de los gobiernos a raíz de la crisis económica. El continente Europeo envejece con ritmo constante al punto que se prevé que en 2050 habrá sólo dos trabajadores por jubilado [54]. A esta situación se le añade el aumento de la incidencia de las enfermedades crónicas, relacionadas con el envejecimiento, cuyo coste puede alcanzar el 7% del PIB de un país [51]. Es necesario un cambio de paradigma. Una nueva manera de cuidar de la salud de las personas: sustentable, eficaz y preventiva más que curativa. Algunos estudios abogan por el cuidado personalizado de la salud (pHealth). En este modelo las prácticas médicas son adaptadas e individualizadas al paciente, desde la detección de los factores de riesgo hasta la personalización de los tratamientos basada en la respuesta del individuo [81]. El cuidado personalizado de la salud está asociado a menudo al uso de las tecnologías de la información y comunicación (TICs) que, con su desarrollo exponencial, ofrecen oportunidades interesantes para la mejora de la salud. El cambio de paradigma hacia el pHealth está lentamente ocurriendo, tanto en el ámbito de la investigación como en la industria, pero todavía no de manera significativa. Existen todavía muchas barreras relacionadas a la economía, a la política y la cultura. También existen barreras puramente tecnológicas, como la falta de sistemas de información interoperables [199]. A pesar de que los aspectos de interoperabilidad están evolucionando, todavía hace falta un diseño de referencia especialmente direccionado a la implementación y el despliegue en gran escala de sistemas basados en pHealth. La presente Tesis representa un intento de organizar la disciplina de la aplicación de las TICs al cuidado personalizado de la salud en un modelo de referencia, que permita la creación de plataformas de desarrollo de software para simplificar tareas comunes de desarrollo en este dominio. Preguntas de investigación RQ1 >Es posible definir un modelo, basado en técnicas de ingeniería del software, que represente el dominio del cuidado personalizado de la salud de una forma abstracta y representativa? RQ2 >Es posible construir una plataforma de desarrollo basada en este modelo? RQ3 >Esta plataforma ayuda a los desarrolladores a crear sistemas pHealth complejos e integrados? Métodos Para la descripción del modelo se adoptó el estándar ISO/IEC/IEEE 42010por ser lo suficientemente general y abstracto para el amplio enfoque de esta tesis [25]. El modelo está definido en varias partes: un modelo conceptual, expresado a través de mapas conceptuales que representan las partes interesadas (stakeholders), los artefactos y la información compartida; y escenarios y casos de uso para la descripción de sus funcionalidades. El modelo fue desarrollado de acuerdo a la información obtenida del análisis de la literatura, incluyendo 7 informes industriales y científicos, 9 estándares, 10 artículos en conferencias, 37 artículos en revistas, 25 páginas web y 5 libros. Basándose en el modelo se definieron los requisitos para la creación de la plataforma de desarrollo, enriquecidos por otros requisitos recolectados a través de una encuesta realizada a 11 ingenieros con experiencia en la rama. Para el desarrollo de la plataforma, se adoptó la metodología de integración continua [74] que permitió ejecutar tests automáticos en un servidor y también desplegar aplicaciones en una página web. En cuanto a la metodología utilizada para la validación se adoptó un marco para la formulación de teorías en la ingeniería del software [181]. Esto requiere el desarrollo de modelos y proposiciones que han de ser validados dentro de un ámbito de investigación definido, y que sirvan para guiar al investigador en la búsqueda de la evidencia necesaria para justificarla. La validación del modelo fue desarrollada mediante una encuesta online en tres rondas con un número creciente de invitados. El cuestionario fue enviado a 134 contactos y distribuido en algunos canales públicos como listas de correo y redes sociales. El objetivo era evaluar la legibilidad del modelo, su nivel de cobertura del dominio y su potencial utilidad en el diseño de sistemas derivados. El cuestionario incluía preguntas cuantitativas de tipo Likert y campos para recolección de comentarios. La plataforma de desarrollo fue validada en dos etapas. En la primera etapa se utilizó la plataforma en un experimento a pequeña escala, que consistió en una sesión de entrenamiento de 12 horas en la que 4 desarrolladores tuvieron que desarrollar algunos casos de uso y reunirse en un grupo focal para discutir su uso. La segunda etapa se realizó durante los tests de un proyecto en gran escala llamado HeartCycle [160]. En este proyecto un equipo de diseñadores y programadores desarrollaron tres aplicaciones en el campo de las enfermedades cardio-vasculares. Una de estas aplicaciones fue testeada en un ensayo clínico con pacientes reales. Al analizar el proyecto, el equipo de desarrollo se reunió en un grupo focal para identificar las ventajas y desventajas de la plataforma y su utilidad. Resultados Por lo que concierne el modelo que describe el dominio del pHealth, la parte conceptual incluye una descripción de los roles principales y las preocupaciones de los participantes, un modelo de los artefactos TIC que se usan comúnmente y un modelo para representar los datos típicos que son necesarios formalizar e intercambiar entre sistemas basados en pHealth. El modelo funcional incluye un conjunto de 18 escenarios, repartidos en: punto de vista de la persona asistida, punto de vista del cuidador, punto de vista del desarrollador, punto de vista de los proveedores de tecnologías y punto de vista de las autoridades; y un conjunto de 52 casos de uso repartidos en 6 categorías: actividades de la persona asistida, reacciones del sistema, actividades del cuidador, \engagement" del usuario, actividades del desarrollador y actividades de despliegue. Como resultado del cuestionario de validación del modelo, un total de 65 personas revisó el modelo proporcionando su nivel de acuerdo con las dimensiones evaluadas y un total de 248 comentarios sobre cómo mejorar el modelo. Los conocimientos de los participantes variaban desde la ingeniería del software (70%) hasta las especialidades médicas (15%), con declarado interés en eHealth (24%), mHealth (16%), Ambient Assisted Living (21%), medicina personalizada (5%), sistemas basados en pHealth (15%), informática médica (10%) e ingeniería biomédica (8%) con una media de 7.25_4.99 años de experiencia en estas áreas. Los resultados de la encuesta muestran que los expertos contactados consideran el modelo fácil de leer (media de 1.89_0.79 siendo 1 el valor más favorable y 5 el peor), suficientemente abstracto (1.99_0.88) y formal (2.13_0.77), con una cobertura suficiente del dominio (2.26_0.95), útil para describir el dominio (2.02_0.7) y para generar sistemas más específicos (2_0.75). Los expertos también reportan un interés parcial en utilizar el modelo en su trabajo (2.48_0.91). Gracias a sus comentarios, el modelo fue mejorado y enriquecido con conceptos que faltaban, aunque no se pudo demonstrar su mejora en las dimensiones evaluadas, dada la composición diferente de personas en las tres rondas de evaluación. Desde el modelo, se generó una plataforma de desarrollo llamada \pHealth Patient Platform (pHPP)". La plataforma desarrollada incluye librerías, herramientas de programación y desarrollo, un tutorial y una aplicación de ejemplo. Se definieron cuatro módulos principales de la arquitectura: el Data Collection Engine, que permite abstraer las fuentes de datos como sensores o servicios externos, mapeando los datos a bases de datos u ontologías, y permitiendo interacción basada en eventos; el GUI Engine, que abstrae la interfaz de usuario en un modelo de interacción basado en mensajes; y el Rule Engine, que proporciona a los desarrolladores un medio simple para programar la lógica de la aplicación en forma de reglas \if-then". Después de que la plataforma pHPP fue utilizada durante 5 años en el proyecto HeartCycle, 5 desarrolladores fueron reunidos en un grupo de discusión para analizar y evaluar la plataforma. De estas evaluaciones se concluye que la plataforma fue diseñada para encajar las necesidades de los ingenieros que trabajan en la rama, permitiendo la separación de problemas entre las distintas especialidades, y simplificando algunas tareas de desarrollo como el manejo de datos y la interacción asíncrona. A pesar de ello, se encontraron algunos defectos a causa de la inmadurez de algunas tecnologías empleadas, y la ausencia de algunas herramientas específicas para el dominio como el procesado de datos o algunos protocolos de comunicación relacionados con la salud. Dentro del proyecto HeartCycle la plataforma fue utilizada para el desarrollo de la aplicación \Guided Exercise", un sistema TIC para la rehabilitación de pacientes que han sufrido un infarto del miocardio. El sistema fue testeado en un ensayo clínico randomizado en el cual a 55 pacientes se les dio el sistema para su uso por 21 semanas. De los resultados técnicos del ensayo se puede concluir que, a pesar de algunos errores menores prontamente corregidos durante el estudio, la plataforma es estable y fiable. Conclusiones La investigación llevada a cabo en esta Tesis y los resultados obtenidos proporcionan las respuestas a las tres preguntas de investigación que motivaron este trabajo: RQ1 Se ha desarrollado un modelo para representar el dominio de los sistemas personalizados de salud. La evaluación hecha por los expertos de la rama concluye que el modelo representa el dominio con precisión y con un balance apropiado entre abstracción y detalle. RQ2 Se ha desarrollado, con éxito, una plataforma de desarrollo basada en el modelo. RQ3 Se ha demostrado que la plataforma es capaz de ayudar a los desarrolladores en la creación de software pHealth complejos. Las ventajas de la plataforma han sido demostradas en el ámbito de un proyecto de gran escala, aunque el enfoque genérico adoptado indica que la plataforma podría ofrecer beneficios también en otros contextos. Los resultados de estas evaluaciones ofrecen indicios de que, ambos, el modelo y la plataforma serán buenos candidatos para poderse convertir en una referencia para futuros desarrollos de sistemas pHealth. ABSTRACT Background Europe is living in an unsustainable situation. The economic crisis has been reducing governments' economic resources since 2008 and threatening social and health systems, while the proportion of older people in the European population continues to increase so that it is foreseen that in 2050 there will be only two workers per retiree [54]. To this situation it should be added the rise, strongly related to age, of chronic diseases the burden of which has been estimated to be up to the 7% of a country's gross domestic product [51]. There is a need for a paradigm shift, the need for a new way of caring for people's health, shifting the focus from curing conditions that have arisen to a sustainable and effective approach with the emphasis on prevention. Some advocate the adoption of personalised health care (pHealth), a model where medical practices are tailored to the patient's unique life, from the detection of risk factors to the customization of treatments based on each individual's response [81]. Personalised health is often associated to the use of Information and Communications Technology (ICT), that, with its exponential development, offers interesting opportunities for improving healthcare. The shift towards pHealth is slowly taking place, both in research and in industry, but the change is not significant yet. Many barriers still exist related to economy, politics and culture, while others are purely technological, like the lack of interoperable information systems [199]. Though interoperability aspects are evolving, there is still the need of a reference design, especially tackling implementation and large scale deployment of pHealth systems. This thesis contributes to organizing the subject of ICT systems for personalised health into a reference model that allows for the creation of software development platforms to ease common development issues in the domain. Research questions RQ1 Is it possible to define a model, based on software engineering techniques, for representing the personalised health domain in an abstract and representative way? RQ2 Is it possible to build a development platform based on this model? RQ3 Does the development platform help developers create complex integrated pHealth systems? Methods As method for describing the model, the ISO/IEC/IEEE 42010 framework [25] is adopted for its generality and high level of abstraction. The model is specified in different parts: a conceptual model, which makes use of concept maps, for representing stakeholders, artefacts and shared information, and in scenarios and use cases for the representation of the functionalities of pHealth systems. The model was derived from literature analysis, including 7 industrial and scientific reports, 9 electronic standards, 10 conference proceedings papers, 37 journal papers, 25 websites and 5 books. Based on the reference model, requirements were drawn for building the development platform enriched with a set of requirements gathered in a survey run among 11 experienced engineers. For developing the platform, the continuous integration methodology [74] was adopted which allowed to perform automatic tests on a server and also to deploy packaged releases on a web site. As a validation methodology, a theory building framework for SW engineering was adopted from [181]. The framework, chosen as a guide to find evidence for justifying the research questions, imposed the creation of theories based on models and propositions to be validated within a scope. The validation of the model was conducted as an on-line survey in three validation rounds, encompassing a growing number of participants. The survey was submitted to 134 experts of the field and on some public channels like relevant mailing lists and social networks. Its objective was to assess the model's readability, its level of coverage of the domain and its potential usefulness in the design of actual, derived systems. The questionnaires included quantitative Likert scale questions and free text inputs for comments. The development platform was validated in two scopes. As a small-scale experiment, the platform was used in a 12 hours training session where 4 developers had to perform an exercise consisting in developing a set of typical pHealth use cases At the end of the session, a focus group was held to identify benefits and drawbacks of the platform. The second validation was held as a test-case study in a large scale research project called HeartCycle the aim of which was to develop a closed-loop disease management system for heart failure and coronary heart disease patients [160]. During this project three applications were developed by a team of programmers and designers. One of these applications was tested in a clinical trial with actual patients. At the end of the project, the team was interviewed in a focus group to assess the role the platform had within the project. Results For what regards the model that describes the pHealth domain, its conceptual part includes a description of the main roles and concerns of pHealth stakeholders, a model of the ICT artefacts that are commonly adopted and a model representing the typical data that need to be formalized among pHealth systems. The functional model includes a set of 18 scenarios, divided into assisted person's view, caregiver's view, developer's view, technology and services providers' view and authority's view, and a set of 52 Use Cases grouped in 6 categories: assisted person's activities, system reactions, caregiver's activities, user engagement, developer's activities and deployer's activities. For what concerns the validation of the model, a total of 65 people participated in the online survey providing their level of agreement in all the assessed dimensions and a total of 248 comments on how to improve and complete the model. Participants' background spanned from engineering and software development (70%) to medical specialities (15%), with declared interest in the fields of eHealth (24%), mHealth (16%), Ambient Assisted Living (21%), Personalized Medicine (5%), Personal Health Systems (15%), Medical Informatics (10%) and Biomedical Engineering (8%) with an average of 7.25_4.99 years of experience in these fields. From the analysis of the answers it is possible to observe that the contacted experts considered the model easily readable (average of 1.89_0.79 being 1 the most favourable scoring and 5 the worst), sufficiently abstract (1.99_0.88) and formal (2.13_0.77) for its purpose, with a sufficient coverage of the domain (2.26_0.95), useful for describing the domain (2.02_0.7) and for generating more specific systems (2_0.75) and they reported a partial interest in using the model in their job (2.48_0.91). Thanks to their comments, the model was improved and enriched with concepts that were missing at the beginning, nonetheless it was not possible to prove an improvement among the iterations, due to the diversity of the participants in the three rounds. From the model, a development platform for the pHealth domain was generated called pHealth Patient Platform (pHPP). The platform includes a set of libraries, programming and deployment tools, a tutorial and a sample application. The main four modules of the architecture are: the Data Collection Engine, which allows abstracting sources of information like sensors or external services, mapping data to databases and ontologies, and allowing event-based interaction and filtering, the GUI Engine, which abstracts the user interface in a message-like interaction model, the Workow Engine, which allows programming the application's user interaction ows with graphical workows, and the Rule Engine, which gives developers a simple means for programming the application's logic in the form of \if-then" rules. After the 5 years experience of HeartCycle, partially programmed with pHPP, 5 developers were joined in a focus group to discuss the advantages and drawbacks of the platform. The view that emerged from the training course and the focus group was that the platform is well-suited to the needs of the engineers working in the field, it allowed the separation of concerns among the different specialities and it simplified some common development tasks like data management and asynchronous interaction. Nevertheless, some deficiencies were pointed out in terms of a lack of maturity of some technological choices, and for the absence of some domain-specific tools, e.g. for data processing or for health-related communication protocols. Within HeartCycle, the platform was used to develop part of the Guided Exercise system, a composition of ICT tools for the physical rehabilitation of patients who suffered from myocardial infarction. The system developed using the platform was tested in a randomized controlled clinical trial, in which 55 patients used the system for 21 weeks. The technical results of this trial showed that the system was stable and reliable. Some minor bugs were detected, but these were promptly corrected using the platform. This shows that the platform, as well as facilitating the development task, can be successfully used to produce reliable software. Conclusions The research work carried out in developing this thesis provides responses to the three three research questions that were the motivation for the work. RQ1 A model was developed representing the domain of personalised health systems, and the assessment of experts in the field was that it represents the domain accurately, with an appropriate balance between abstraction and detail. RQ2 A development platform based on the model was successfully developed. RQ3 The platform has been shown to assist developers create complex pHealth software. This was demonstrated within the scope of one large-scale project, but the generic approach adopted provides indications that it would offer benefits more widely. The results of these evaluations provide indications that both the model and the platform are good candidates for being a reference for future pHealth developments.

Knowledge-based spatiotemporal linear abstraction

We present a theoretical framework and a case study for reusing the same conceptual and computational methodology for both temporal abstraction and linear (unidimensional) space abstraction, in a domain (evaluation of traffic-control actions) significantly different from the one (clinical medicine) in which the method was originally used. The method, known as knowledge-based temporal abstraction, abstracts high-level concepts and patterns from time-stamped raw data using a formal theory of domain-specific temporal-abstraction knowledge. We applied this method, originally used to interpret time-oriented clinical data, to the domain of traffic control, in which the monitoring task requires linear pattern matching along both space and time. First, we reused the method for creation of unidimensional spatial abstractions over highways, given sensor measurements along each highway measured at the same time point. Second, we reused the method to create temporal abstractions of the traffic behavior, for the same space segments, but during consecutive time points. We defined the corresponding temporal-abstraction and spatial-abstraction domain-specific knowledge. Our results suggest that (1) the knowledge-based temporal-abstraction method is reusable over time and unidimensional space as well as over significantly different domains; (2) the method can be generalized into a knowledge-based linear-abstraction method, which solves tasks requiring abstraction of data along any linear distance measure; and (3) a spatiotemporal-abstraction method can be assembled from two copies of the generalized method and a spatial-decomposition mechanism, and is applicable to tasks requiring abstraction of time-oriented data into meaningful spatiotemporal patterns over a linear, decomposable space, such as traffic over a set of highways.

SMART Protocols: seMAntic represenTation for experimental protocols

Two important characteristics of science are the ?reproducibility? and ?clarity?. By rigorous practices, scientists explore aspects of the world that they can reproduce under carefully controlled experimental conditions. The clarity, complementing reproducibility, provides unambiguous descriptions of results in a mechanical or mathematical form. Both pillars depend on well-structured and accurate descriptions of scientific practices, which are normally recorded in experimental protocols, scientific workflows, etc. Here we present SMART Protocols (SP), our ontology-based approach for representing experimental protocols and our contribution to clarity and reproducibility. SP delivers an unambiguous description of processes by means of which data is produced; by doing so, we argue, it facilitates reproducibility. Moreover, SP is thought to be part of e-science infrastructures. SP results from the analysis of 175 protocols; from this dataset, we extracted common elements. From our analysis, we identified document, workflow and domain-specific aspects in the representation of experimental protocols. The ontology is available at http://purl.org/net/SMARTprotocol

Mutations in Drosophila Enabled and Rescue by Human Vasodilator-stimulated Phosphoprotein (VASP) Indicate Important Functional Roles for Ena/VASP Homology Domain 1 (EVH1) and EVH2 Domains

Drosophila Enabled (Ena) was initially identified as a dominant genetic suppressor of mutations in the Abelson tyrosine kinase and, more recently, as a member of the Ena/human vasodilator-stimulated phosphoprotein (VASP) family of proteins. We have used genetic, biochemical, and cell biological approaches to demonstrate the functional relationship between Ena and human VASP. In addition, we have defined the roles of Ena domains identified as essential for its activity in vivo. We have demonstrated that VASP rescues the embryonic lethality associated with loss of Ena function in Drosophila and have shown that Ena, like VASP, is associated with actin filaments and focal adhesions when expressed in cultured cells. To define sequences that are central to Ena function, we have characterized the molecular lesions present in two lethal ena mutant alleles that affected the Ena/VASP homology domain 1 (EVH1) and EVH2. A missense mutation that resulted in an amino acid substitution in the EVH1 domain eliminated in vitro binding of Ena to the cytoskeletal protein zyxin, a previously reported binding partner of VASP. A nonsense mutation that resulted in a C-terminally truncated Ena protein lacking the EVH2 domain failed to form multimeric complexes and exhibited reduced binding to zyxin and the Abelson Src homology 3 domain. Our analysis demonstrates that Ena and VASP are functionally homologous and defines the conserved EVH1 and EVH2 domains as central to the physiological activity of Ena.

X-ray structure of the human hyperplastic discs protein: An ortholog of the C-terminal domain of poly(A)-binding protein

The poly(A)-binding protein (PABP) recognizes the 3′ mRNA poly(A) tail and plays an essential role in eukaryotic translation initiation and mRNA stabilization/degradation. PABP is a modular protein, with four N-terminal RNA-binding domains and an extensive C terminus. The C-terminal region of PABP is essential for normal growth in yeast and has been implicated in mediating PABP homo-oligomerization and protein–protein interactions. A small, proteolytically stable, highly conserved domain has been identified within this C-terminal segment. Remarkably, this domain is also present in the hyperplastic discs protein (HYD) family of ubiquitin ligases. To better understand the function of this conserved region, an x-ray structure of the PABP-like segment of the human HYD protein has been determined at 1.04-Å resolution. The conserved domain adopts a novel fold resembling a right-handed supercoil of four α-helices. Sequence profile searches and comparative protein structure modeling identified a small ORF from the Arabidopsis thaliana genome that encodes a structurally similar but distantly related PABP/HYD domain. Phylogenetic analysis of the experimentally determined (HYD) and homology modeled (PABP) protein surfaces revealed a conserved feature that may be responsible for binding to a PABP interacting protein, Paip1, and other shared interaction partners.

The role of left prefrontal cortex in language and memory

This article reviews attempts to characterize the mental operations mediated by left inferior prefrontal cortex, especially the anterior and inferior portion of the gyrus, with the functional neuroimaging techniques of positron emission tomography and functional magnetic resonance imaging. Activations in this region occur during semantic, relative to nonsemantic, tasks for the generation of words to semantic cues or the classification of words or pictures into semantic categories. This activation appears in the right prefrontal cortex of people known to be atypically right-hemisphere dominant for language. In this region, activations are associated with meaningful encoding that leads to superior explicit memory for stimuli and deactivations with implicit semantic memory (repetition priming) for words and pictures. New findings are reported showing that patients with global amnesia show deactivations in the same region associated with repetition priming, that activation in this region reflects selection of a response from among numerous relative to few alternatives, and that activations in a portion of this region are associated specifically with semantic relative to phonological processing. It is hypothesized that activations in left inferior prefrontal cortex reflect a domain-specific semantic working memory capacity that is invoked more for semantic than nonsemantic analyses regardless of stimulus modality, more for initial than for repeated semantic analysis of a word or picture, more when a response must be selected from among many than few legitimate alternatives, and that yields superior later explicit memory for experiences.

Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development.

Neuregulins are ligands for the erbB family of receptor tyrosine kinases and mediate growth and differentiation of neural crest, muscle, breast cancer, and Schwann cells. Neuregulins contain an epidermal growth factor-like domain located C-terminally to either an Ig-like domain or a cysteine-rich domain specific to the sensory and motor neuron-derived isoform. Here it is shown that elimination of the Ig-like domain-containing neuregulins by homologous recombination results in embryonic lethality associated with a deficiency of ventricular myocardial trabeculation and impairment of cranial ganglion development. The erbB receptors are expressed in myocardial cells and presumably mediate the neuregulin signal originating from endocardial cells. The trigeminal ganglion is reduced in size and lacks projections toward the brain stem and mandible. We conclude that IgL-domain-containing neuregulins play a major role in cardiac and neuronal development.

Phage display selection of ligand residues important for Src homology 3 domain binding specificity.

The Src homology 3 (SH3) domain is a 50-aa modular unit present in many cellular proteins involved in intracellular signal transduction. It functions to direct protein-protein interactions through the recognition of proline-rich motifs on associated proteins. SH3 domains are important regulatory elements that have been demonstrated to specify distinct regulatory pathways important for cell growth, migration, differentiation, and responses to the external milieu. By the use of synthetic peptides, ligands have been shown to consist of a minimum core sequence and to bind to SH3 domains in one of two pseudosymmetrical orientations, class I and class II. The class I sites have the consensus sequence ZP(L/P)PP psi P whereas the class II consensus is PP psi PPZ (where psi is a hydrophobic residue and Z is a SH3 domain-specific residue). We previously showed by M13 phage display that the Src, Fyn, Lyn, and phosphatidylinositol 3-kinase (PI3K) SH3 domains preferred the same class I-type core binding sequence, RPLPP psi P. These results failed to explain the specificity for cellular proteins displayed by SH3 domains in cells. In the current study, class I and class II core ligand sequences were displayed on the surface of bacteriophage M13 with five random residues placed either N- or C-terminal of core ligand residues. These libraries were screened for binding to the Src, Fyn, Lyn, Yes, and PI3K SH3 domains. By this approach, additional ligand residue preferences were identified that can increase the affinity of SH3 peptide ligands at least 20-fold compared with core peptides. The amino acids selected in the flanking sequences were similar for Src, Fyn, and Yes SH3 domains; however, Lyn and PI3K SH3 domains showed distinct binding specificities. These results indicate that residues that flank the core binding sequences shared by many SH3 domains are important determinants of SH3 binding affinity and selectivity.

A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution.

In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several heterogeneous proteins of yeast and nematode. The EH domain spans about 70 amino acids and shows approximately 60% overall amino acid conservation. We demonstrated the ability of the EH domain to specifically bind cytosolic proteins in normal and malignant cells of mesenchymal, epithelial, and hematopoietic origin. These observations prompted our search for additional EH-containing proteins in mammalian cells. Using an EH domain-specific probe derived from the eps15 cDNA, we cloned and characterized a cDNA encoding an EH-containing protein with overall similarity to Eps15; we designated this protein Eps15r (for Eps15-related). Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins.

A new algorithm to accelerate harmonic analysis of time series

The Lomb periodogram has been traditionally a tool that allows us to elucidate if a frequency turns out to be important for explaining the behaviour of a given time series. Many linear and nonlinear reiterative harmonic processes that are used for studying the spectral content of a time series take into account this periodogram in order to avoid including spurious frequencies in their models due to the leakage problem of energy from one frequency to others. However, the estimation of the periodogram requires long computation time that makes the harmonic analysis slower when we deal with certain time series. Here we propose an algorithm that accelerates the extraction of the most remarkable frequencies from the periodogram, avoiding its whole estimation of the harmonic process at each iteration. This algorithm allows the user to perform a specific analysis of a given scalar time series. As a result, we obtain a functional model made of (1) a trend component, (2) a linear combination of Fourier terms, and (3) the so-called mixed secular terms by reducing the computation time of the estimation of the periodogram.

Domain Globalization: Using Languages to Support Technical and Social Coordination

When a project is realized in a globalized environment, multiple stakeholders from different organizations work on the same system. Depending on the stakeholders and their organizations, various (possibly overlapping) concerns are raised in the development of the system. In this context a Domain Specific Language (DSL) supports the work of a group of stakeholders who are responsible for addressing a specific set of concerns. This chapter identifies the open challenges arising from the coordination of globalized domain-specific languages. We identify two types of coordination: technical coordination and social coordination. After presenting an overview of the current state of the art, we discuss first the open challenges arising from the composition of multiple DSLs, and then the open challenges associated to the collaboration in a globalized environment.