Self -management behavior in patients with cystic fibrosis

Self-management is being promoted in cystic fibrosis (CF). However, it has not been well studied. Principal aims of this research were (1) to evaluate psychometric properties of a CF disease status measure, the NIH Clinical Score; (2) to develop and validate a measure of self-management behavior, the SMQ-CF scale, and (3) to examine the relation between self-management and disease status in CF patients over two years.^ In study 1, NIH Clinical Scores for 200 patients were used. The scale was examined for internal consistency, interrater reliability, and content validity using factor analysis. The Cronbach's alpha (.81) and interrater reliability (.90) for the total scale were high. General scale items were less reliable. Factor analysis indicated that most of the variance in disease status is accounted for by Factor 1 which consists of pulmonary disease items.^ The SMQ-CF measures the performance of CF self-management. Pilot testing was done with 98 CF primary caregivers. Internal consistency reliability, social desirability bias, and content validity using factor analysis were examined. Internal consistency was good (alpha =.95). Social desirability correlation was low (r =.095). Twelve factors identified were consistent with conceptual groupings of behaviors. Around two hundred caregivers from two CF centers were surveyed and multivariate analysis of variance was used to assess construct validity. Results confirmed expected relations between self-management, patient age, and disease status. Patient age accounted for 50% and disease status 18% of the variance in the SMQ-CF scale.^ It was hypothesized that self-management would positively affect future disease status. Data from 199 CF patients (control and education intervention groups) were examined. Models of hypothesized relations were tested using LISREL structural equation modeling. Results indicated that the relations between baseline self-management and Time 1 disease status were not significant. Significant relations were observed in self-management behaviors from time 1 to time 2 and patterns of significant relations differed between the two groups.^ This research has contributed to refinements in the ability to measure self-management behavior and disease status outcomes in cystic fibrosis. In addition, it provides the first steps in exploratory behavioral analysis with regard to self-management in this disease. ^

SIRGAS reference frame realization SIR11P01

To estimate the kinematics of the SIRGAS reference frame, the Deutsches Geodätisches Forschungsinstitut (DGFI) as the IGS Regional Network Associate Analysis Centre for SIRGAS (IGS RNNAC SIR), yearly computes a cumulative (multi-year) solution containing all available weekly solutions delivered by the SIRGAS analysis centres. These cumulative solutions include those models, standards, and strategies widely applied at the time in which they were computed and cover different time spans depending on the availability of the weekly solutions. This data set corresponds to the multi-year solution SIR11P01. It is based on the combination of the weekly normal equations covering the time span from 2000-01-02 (GPS week 1043) to 2011-04-16 (GPS week 1631), when the IGS08 reference frame was introduced. It refers to ITRF2008, epoch 2005.0 and contains 230 stations with 269 occupations. Its precision was estimated to be ±1.0 mm (horizontal) and ±2.4 mm (vertical) for the station positions, and ±0.7 mm/a (horizontal) and ±1.1 mm/a (vertical) for the constant velocities. Computation strategy and results are in detail described in Sánchez and Seitz (2011). The IGS RNAAC SIR computation of the SIRGAS reference frame is possible thanks to the active participation of many Latin American and Caribbean colleagues, who not only make the measurements of the stations available, but also operate SIRGAS analysis centres processing the observational data on a routine basis (more details in http://www.sirgas.org). The achievements of SIRGAS are a consequence of a successful international geodetic cooperation not only following and meeting concrete objectives, but also becoming a permanent and self-sustaining geodetic community to guarantee quality, reliability, and long-term stability of the SIRGAS reference frame. The SIRGAS activities are strongly supported by the International Association of Geodesy (IAG) and the Pan-American Institute for Geography and History (PAIGH). The IGS RNAAC SIR highly appreciates all this support.

Territorial quality and sustainable development : Indicators of performance in the context of a model for participatory rural tourism certification

El turismo rural ha sido incorporado por pequeños establecimientos agropecuarios del partido de Cnel. Suárez, provincia de Buenos Aires, Argentina, como actividad alternativa para mejorar la calidad de vida de sus miembros y superar situaciones de crisis agravadas por la marginalidad productiva del SO bonaerense, región a la que pertenecen. Bajo el programa Cambio Rural del INTA (Instituto Nacional de Tecnología Agropecuaria) conforman el Grupo 'Cortaderas II', junto a otros emprendedores interesados en valorar el medio rural. Han avanzado en el proceso de reconocimiento de su identidad y puesta en valor de recursos específicos con anclaje en el territorio. Esta identidad comienza a apreciarse internamente, a raíz de la dinámica grupal lograda y la incipiente articulación con otros actores para la construcción de un partenariado público y privado que genere sinergias y contribuya al desarrollo sustentable del territorio. Sin embargo, aún no es claramente percibida por el turista, cada vez más exigente. Por lo tanto, el presente trabajo persigue proponer indicadores para evaluar el desempeño de un Sistema de Gestión de Calidad con enfoque territorial que, adaptando el modelo europeo 'Marca de Calidad Territorial', sustente una estrategia comercial de diferenciación del servicio y simultáneamente, mida el progreso hacia una mejor calidad de vida y fortalecimiento de vínculos con la cultura local y el entorno físico-natural en el marco del desarrollo sustentable. La investigación se plantea para la micro escala, ya que se trata de un estudio de caso, relevándose información primaria mediante observación directa y entrevistas semi-estructuradas, complementada con información secundaria diagnóstica utilizada por INTA. Las características del grupo y su dinámica de funcionamiento bajo el programa Cambio Rural revelan que es posible adoptar un proceso de certificación participativa propuesto para cuatro pilares de la calidad: de Bienes y Servicios, Institucional, Social y Ambiental. El modelo se integra con indicadores de evaluación de desempeño, agrupados en áreas clave para cada una de las dimensiones de la sustentabilidad, que contemplan el paisaje y la gestión de los recursos naturales; el impacto económico de la actividad, la calidad de la oferta y satisfacción del turista; así como las relaciones sociales internas y los vínculos con otros actores del territorio. Principalmente se encontraron fortalezas en la búsqueda de partenariados y debilidades en aspectos de comunicación y promoción. Se considera que este sistema de herramientas de gestión sustentable permitiría superar las dificultades de una certificación individual, pudiendo aplicarse a emprendimientos con otra ubicación geográfica

Territorial quality and sustainable development : Indicators of performance in the context of a model for participatory rural tourism certification

El turismo rural ha sido incorporado por pequeños establecimientos agropecuarios del partido de Cnel. Suárez, provincia de Buenos Aires, Argentina, como actividad alternativa para mejorar la calidad de vida de sus miembros y superar situaciones de crisis agravadas por la marginalidad productiva del SO bonaerense, región a la que pertenecen. Bajo el programa Cambio Rural del INTA (Instituto Nacional de Tecnología Agropecuaria) conforman el Grupo 'Cortaderas II', junto a otros emprendedores interesados en valorar el medio rural. Han avanzado en el proceso de reconocimiento de su identidad y puesta en valor de recursos específicos con anclaje en el territorio. Esta identidad comienza a apreciarse internamente, a raíz de la dinámica grupal lograda y la incipiente articulación con otros actores para la construcción de un partenariado público y privado que genere sinergias y contribuya al desarrollo sustentable del territorio. Sin embargo, aún no es claramente percibida por el turista, cada vez más exigente. Por lo tanto, el presente trabajo persigue proponer indicadores para evaluar el desempeño de un Sistema de Gestión de Calidad con enfoque territorial que, adaptando el modelo europeo 'Marca de Calidad Territorial', sustente una estrategia comercial de diferenciación del servicio y simultáneamente, mida el progreso hacia una mejor calidad de vida y fortalecimiento de vínculos con la cultura local y el entorno físico-natural en el marco del desarrollo sustentable. La investigación se plantea para la micro escala, ya que se trata de un estudio de caso, relevándose información primaria mediante observación directa y entrevistas semi-estructuradas, complementada con información secundaria diagnóstica utilizada por INTA. Las características del grupo y su dinámica de funcionamiento bajo el programa Cambio Rural revelan que es posible adoptar un proceso de certificación participativa propuesto para cuatro pilares de la calidad: de Bienes y Servicios, Institucional, Social y Ambiental. El modelo se integra con indicadores de evaluación de desempeño, agrupados en áreas clave para cada una de las dimensiones de la sustentabilidad, que contemplan el paisaje y la gestión de los recursos naturales; el impacto económico de la actividad, la calidad de la oferta y satisfacción del turista; así como las relaciones sociales internas y los vínculos con otros actores del territorio. Principalmente se encontraron fortalezas en la búsqueda de partenariados y debilidades en aspectos de comunicación y promoción. Se considera que este sistema de herramientas de gestión sustentable permitiría superar las dificultades de una certificación individual, pudiendo aplicarse a emprendimientos con otra ubicación geográfica

Territorial quality and sustainable development : Indicators of performance in the context of a model for participatory rural tourism certification

El turismo rural ha sido incorporado por pequeños establecimientos agropecuarios del partido de Cnel. Suárez, provincia de Buenos Aires, Argentina, como actividad alternativa para mejorar la calidad de vida de sus miembros y superar situaciones de crisis agravadas por la marginalidad productiva del SO bonaerense, región a la que pertenecen. Bajo el programa Cambio Rural del INTA (Instituto Nacional de Tecnología Agropecuaria) conforman el Grupo 'Cortaderas II', junto a otros emprendedores interesados en valorar el medio rural. Han avanzado en el proceso de reconocimiento de su identidad y puesta en valor de recursos específicos con anclaje en el territorio. Esta identidad comienza a apreciarse internamente, a raíz de la dinámica grupal lograda y la incipiente articulación con otros actores para la construcción de un partenariado público y privado que genere sinergias y contribuya al desarrollo sustentable del territorio. Sin embargo, aún no es claramente percibida por el turista, cada vez más exigente. Por lo tanto, el presente trabajo persigue proponer indicadores para evaluar el desempeño de un Sistema de Gestión de Calidad con enfoque territorial que, adaptando el modelo europeo 'Marca de Calidad Territorial', sustente una estrategia comercial de diferenciación del servicio y simultáneamente, mida el progreso hacia una mejor calidad de vida y fortalecimiento de vínculos con la cultura local y el entorno físico-natural en el marco del desarrollo sustentable. La investigación se plantea para la micro escala, ya que se trata de un estudio de caso, relevándose información primaria mediante observación directa y entrevistas semi-estructuradas, complementada con información secundaria diagnóstica utilizada por INTA. Las características del grupo y su dinámica de funcionamiento bajo el programa Cambio Rural revelan que es posible adoptar un proceso de certificación participativa propuesto para cuatro pilares de la calidad: de Bienes y Servicios, Institucional, Social y Ambiental. El modelo se integra con indicadores de evaluación de desempeño, agrupados en áreas clave para cada una de las dimensiones de la sustentabilidad, que contemplan el paisaje y la gestión de los recursos naturales; el impacto económico de la actividad, la calidad de la oferta y satisfacción del turista; así como las relaciones sociales internas y los vínculos con otros actores del territorio. Principalmente se encontraron fortalezas en la búsqueda de partenariados y debilidades en aspectos de comunicación y promoción. Se considera que este sistema de herramientas de gestión sustentable permitiría superar las dificultades de una certificación individual, pudiendo aplicarse a emprendimientos con otra ubicación geográfica

Key Factors to Successful Community Development: The Korean Experience

The Saemaul Undong of the Republic of Korea has been world-widely recognized as a successful model of rural community development. The Saemaul Undong was a pure Korean way of community development program which was initiated by the political will of the top national leadership in order to escape from poverty. There are several key factors to the success of the Saemaul Undong. First, the national government's guidance and support for the movement played a very important role in the whole period of the movement. Second, there was a wide range of people's participation in the implementation process. Third, the Saemaul Undong could make a big success by nurturing community leadership which was selected by rural residents themselves. Finally, as a movement for the spiritual reform, the Saemaul Undong imbued the people with the spirits of diligence, the self-reliance, and cooperation.

Study of the Influence of Fines on a Self-Compacting Concrete

The paper presents the results of the tests of a self-compacting concrete made with fines which include Portland cement and three fillers: hornfels, limestone and metakaolin, in a weight proportion between 23% and 45% of the admixtures. The first mix proportions were designed with a high proportion of Portland cement (720-750kg/m3), and are compared to those having a smaller content of cement and more fillers. The results obtained show that the limestone filler percentage should be higher than the hornfels one, and both of them significantly higher than that of the metakaolin so as to facilitate the fluidity and self-compactability. AIso, the higher proportion of fillers causes a rounded porosity in the mixing which has a bearing on better compressive strength results.

Object Kinetic Monte Carlo calculations of irradiated Fe-Cr dilute alloys: The effect of the interaction radius between substitutional Cr and self-interstitial Fe

ObjectKineticMonteCarlo models allow for the study of the evolution of the damage created by irradiation to time scales that are comparable to those achieved experimentally. Therefore, the essential ObjectKineticMonteCarlo parameters can be validated through comparison with experiments. However, this validation is not trivial since a large number of parameters is necessary, including migration energies of point defects and their clusters, binding energies of point defects in clusters, as well as the interactionradii. This is particularly cumbersome when describing an alloy, such as the Fe–Cr system, which is of interest for fusion energy applications. In this work we describe an ObjectKineticMonteCarlo model for Fe–Cr alloys in the dilute limit. The parameters used in the model come either from density functional theory calculations or from empirical interatomic potentials. This model is used to reproduce isochronal resistivity recovery experiments of electron irradiateddiluteFe–Cr alloys performed by Abe and Kuramoto. The comparison between the calculated results and the experiments reveal that an important parameter is the capture radius between substitutionalCr and self-interstitialFe atoms. A parametric study is presented on the effect of the capture radius on the simulated recovery curves.

Sustainable Planning And Land Valuation, New Forms Of Suburban Growth In Areas Of The Spanish Mediterranean Coast

The present study analyzes residential models in coastal areas with large influxes of tourism, the sustainability of their planning and its repercussion on urban values. The project seeks to establish a methodology for territorial valuation through the analysis of externalities that have influenced urban growth and its impact on the formation of residential real estate values. This will make it possible to create a map for qualitative land valuation, resulting from a combination of environmental, landscape, social and productive valuations. This in turn will establish a reference value for each of the areas in question, as well as their spatial interrelations. These values become guidelines for the study of different territorial scenarios, which help improve the sustainable territorial planning process. This is a rating scale for urban planning. The results allow us to establish how the specific characteristics of the coast are valued and how they can be incorporated into sustainable development policies.

Gobernar la complejidad urbana desde la sostenibilidad. Evaluación del gobierno de la gestión visible utilizando indicadores de gobernanza (Venezuela)

Se evalúa con indicadores de gobernanza urbana la sostenibilidad de las formas de hacer ciudad hibrida compleja del gobierno de la gestión visible (GGV). Argumenta que el GGV hace ciudad para legitimarse por desempeño y fortalecer la gobernanza local, en un contexto de mutaciones múltiples y radicales que tienden a diluir y centralizar el poder local y fractalizar la ciudad, profundizando la segregación sociopolítica-territorial y la ingobernabilidad genética de la ciudad hibrida, poniendo en riesgo el Estado federal descentralizado, el derecho a la ciudad, al gobierno local y la gobernanza urbana y multinivel (hipótesis). La estrategia de evaluación de gobernanza innovadora (EEG+i) diseñada para evaluar la relación entre las formas de hacer ciudad hibrida (variables espaciales) y gobernanza (variable a-espacial) es transversal, multidimensional y se construye desde la complejidad, el análisis de escenarios, formulación de constructos, modelos e indicadores de gobernanza, entretejiendo tres campos de conocimiento, gobierno, ciudad y sostenibilidad, en cuatro fases. La Fase 1, contextualiza la gobernanza en la dramática del siglo XXI. La Fase 2, desarrolla la fundamentación teórico-práctica, nuevos conceptos y un abordaje analítico propio ‘genética territorial’, para analizar y comprehender la complejidad de la ciudad hibrida de países en desarrollo, tejiendo ontogenética territorial y el carácter autopoiético del gen informal. En la Fase 3, se caracterizan las formas de hacer ciudad desde la genética del territorio, se formulan modelos e indicadores de gobernanza con los que se evalúan, aplicando un delphi y cuestionarios, los genes tipológicos-formas de hacer ciudad y validan las conclusiones. En la Fase 4, se correlacionan los resultados de los instrumentos aplicados con la praxis urbana del GGV, durante cuatro periodos de gobierno (1996-2010). Concluyendo que, la estrategia de evaluación comprobó las hipótesis y demostró la correlación transversal y multinivel existente entre, las mutaciones en curso que contradicen el modelo de gobernanza constitucional, el paisaje de gobernanza latinoamericano y venezolano, la praxis de los regímenes híbridos ricos en recursos naturales, las perspectivas de desarrollo globales y se expresa sociopolíticamente en déficit de gobernanza, Estado de derecho y cohesión-capital social y, espaciolocalmente, en la ciudad hibrida dispersa y diluida (compleja) y en el gobierno del poder diluido centralizado. La confrontación de flujos de poder centrípetos y centrífugos en la ciudad profundiza la fragmentación socioespacial y política y el deterioro de la calidad de vida, incrementando las protestas ciudadanas e ingobernabilidad que obstaculiza la superación de la pobreza y gobernanza urbana y multinivel. La evaluación de la praxis urbana del GGV evidenció que la correlación entre gobernanza, la producción de genes formales y la ciudad por iniciativa privada tiende a ser positiva y entre gobernanza, genes y producción de ciudad informal negativa, por el carácter autopoiético-autogobernable del gen informal y de los nuevos gobiernos sublocales que dificulta gobernar en gobernanza. La praxis del GGV es contraria al modelo de gobernanza formulado y la disolución centralizada del gobierno local y de la ciudad hibrida-dispersa es socio-espacial y políticamente insostenible. Se proponen estrategias y tácticas de gobernanza multinivel para recuperar la cohesión social y de planificación de la gestión innovadora (EG [PG] +i) para orquestar, desde el Consejo Local de Gobernanza (CLG) y con la participación de los espacios y gobiernos sublocales, un proyecto de ciudad compartido y sostenible. ABSTRACT The sustainability of the forms of making the hybrid-complex city by the visible management government (VMG) is evaluated using urban governance indicators. Argues that the VMG builds city to legitimate itself by performance and to strengthen local governance in a context of multiple and radical mutations that tend to dilute and centralize local power and fractalize the city, deepening the socio-spatial and political segregation, the genetic ingovernability of the hybrid city and placing the decentralized federal State, the right to city, local government and urban governance at risk (hypothesis). The innovative governance evaluation strategy (GES+i) designed to assess the relationship between the forms of making the hybrid city (spatial variables) and governance (a-spatial variable) is transversal, multidimensional; is constructed from complexity, scenario analysis, the formulation of concepts, models and governance indicators, weaving three fields of knowledge, government, city and sustainability in four phases. Phase 1, contextualizes governance in the dramatic of the twenty-first century. Phase 2, develops the theoretical and practical foundations, new concepts and a proper analytical approach to comprehend the complexity of the hybrid city from developing countries, weaving territorial ontogenetic with the autopiethic character of the informal city gen. In Phase 3, the ways of making city are characterized from the genetics of territory; governance indicators and models are formulated to evaluate, using delphi and questionnaires, the ways of making city and validate the conclusions. In Phase 4, the results of the instruments applied are correlated with the urban praxis of the VMG during the four periods of government analyzed (1996-2010). Concluding that, the evaluation strategy proved the hypothesis and showed the transversal and multilevel correlation between, mutations that contradict the constitutional governance model, the governance landscape of Latinamerica and the country, the praxis of the hybrid regimes rich in natural resources, the perspectives of the glocal economy and expresses socio-politically the governance and rule of law and social capital-cohesion deficit and spatial-temporarily the hybrid disperse and diluted city (complex) and the diluted-centralized local government. The confrontation of flows of power centripetal and centrifugal in the city deepens the socio-spatial and political fragmentation and deterioration of the quality of life, increasing citizens' protests and ingovernability which hinders poverty eradication and, multilevel and urban governance. The evaluation of the VMG urban praxis showed the correlation between governance, the production of formal genes and city by private initiative tended to be positive and, between informal genes-city production and governance negative, due to its autopiethic-self governable character that hinders governance. The urban praxis of the VMG contradicts the formulated governance model and thecentralized dissolution of the local government and hybrid city are socio-spatial and politically unsustainable. Multiscale governance strategies are proposed to recreate social cohesion and a management planning innovative method (EG [PG] + i) to orchestrate, from the Local Governance Council (LGC) and with the participation of sublocal governments and spaces, a shared and sustainable city project.

Social attitude toward sustainable development in 2025: A case for reinforcing scenario design

This paper shows the role that some foresight tools, such as scenario design, may play in exploring the future impacts of global challenges in our contemporary Society. Additionally, it provides some clues about how to reinforce scenario design so that it displays more in-depth analysis without losing its qualitative nature and communication advantages. Since its inception in the early seventies, scenario design has become one of the most popular foresight tools used in several fields of knowledge. Nevertheless, its wide acceptance has not been seconded by the urban planning academic and professional realm. In some instances, scenario design is just perceived as a story telling technique that generates oversimplified future visions without the support of rigorous and sound analysis. As a matter of fact, the potential of scenario design for providing more in-depth analysis and for connecting with quantitative methods has been generally missed, giving arguments away to its critics. Based on these premises, this document tries to prove the capability of scenario design to anticipate the impacts of complex global challenges and to do it in a more analytical way. These assumptions are tested through a scenario design exercise which explores the future evolution of the sustainable development paradigm (SD) and its implications in the Spanish urban development model. In order to reinforce the perception of scenario design as a useful and added value instrument to urban planners, three sets of implications –functional, parametric and spatial— are displayed to provide substantial and in-depth information for policy makers. This study shows some major findings. First, it is feasible to set up a systematic approach that provides anticipatory intelligence about future disruptive events that may affect the natural environment and socioeconomic fabric of a given territory. Second, there are opportunities for innovating in the Spanish urban planning processes and city governance models. Third, as a foresight tool, scenario design can be substantially reinforced if proper efforts are made to display functional, parametric and spatial implications generated by the scenarios. Fourth, the study confirms that foresight offers interesting opportunities for urban planners, such as anticipating changes, formulating visions, fostering participation and building networks

Innovative self management system for guided cardiac rehabilitation

This paper describes the design and development of a system for cardio rehabilitation of patients that suffered a myocardial infarction. The proposed solution focuses on exercise prescriptions and the encouragement of healthy behaviors. The innovative strategy of the design takes into account health promotion models to provide safe, assistive exercise training sessions, personalized feedbacks, and educational contents.

Mathematical models for the arrangement and the cleaning of the river basin and surroundings of the river sandy grounds to its passage by the city of Salta (Argentina)

The province of Salta is located the Northwest of Argentina in the border with Bolivia, Chile and Paraguay. Its Capital is the city of Salta that concentrates half of the inhabitants of the province and has grown to 600000 hab., from a small active Spanish town well founded in 1583. The city is crossed by the Arenales River descending from close mountains at North, source of water and end of sewers. But with actual growing it has become a focus of infection and of remarkable unhealthiness. It is necessary to undertake a plan for the recovery of the river, directed to the attainment of the well-being and to improve the life?s quality of the Community. The fundamental idea of the plan is to obtain an ordering of the river basin and an integral management of the channel and its surroundings, including the cleaning out. The improvement of the water?s quality, the healthiness of the surroundings and the improvement of the environment, must go hand by hand with the development of sport activities, of relaxation, tourism, establishment of breeding grounds, kitchen gardens, micro enterprises with clean production and other actions that contribute to their benefit by the society, that being a basic factor for their care and sustainable use. The present pollution is organic, chemical, industrial, domestic, due to the disposition of sweepings and sewer effluents that affects not only the flora and small fauna, destroying the biodiversity, but also to the health of people living in their margins. Within the plan it will be necessary to consider, besides hydric and environmental cleaning and the prevention of floods, the planning of the extraction of aggregates, the infrastructure and consolidation of margins works and the arrangement of all the river basin. It will be necessary to consider the public intervention at state, provincial and local level, and the private intervention. In the model it has been necessary to include the sub-model corresponding to the election of the entity to be the optimal instrument to reach the proposed objectives, giving an answer to the social, environmental and economic requirements. For that the authors have used multi-criteria decision methods to qualify and select alternatives, and for the programming of their implementation. In the model the authors have contemplated the short, average and long term actions. They conform a Paretooptimal alternative which secures the ordering, integral and suitable management of the basin of the Arenales River, focusing on its passage by the city of Salta.

Fault Tolerance Analysis and Self-Healing Strategy of Autonomous, Evolvable Hardware Systems

This paper presents an analysis of the fault tolerance achieved by an autonomous, fully embedded evolvable hardware system, which uses a combination of partial dynamic reconfiguration and an evolutionary algorithm (EA). It demonstrates that the system may self-recover from both transient and cumulative permanent faults. This self-adaptive system, based on a 2D array of 16 (4×4) Processing Elements (PEs), is tested with an image filtering application. Results show that it may properly recover from faults in up to 3 PEs, that is, more than 18% cumulative permanent faults. Two fault models are used for testing purposes, at PE and CLB levels. Two self-healing strategies are also introduced, depending on whether fault diagnosis is available or not. They are based on scrubbing, fitness evaluation, dynamic partial reconfiguration and in-system evolutionary adaptation. Since most of these adaptability features are already available on the system for its normal operation, resource cost for self-healing is very low (only some code additions in the internal microprocessor core)

Oscillatory genetic circuits: new designs and mathematical models

Introduction and motivation: A wide variety of organisms have developed in-ternal biomolecular clocks in order to adapt to cyclic changes of the environment. Clock operation involves genetic networks. These genetic networks have to be mod¬eled in order to understand the underlying mechanism of oscillations and to design new synthetic cellular clocks. This doctoral thesis has resulted in two contributions to the fields of genetic clocks and systems and synthetic biology, generally. The first contribution is a new genetic circuit model that exhibits an oscillatory behav¬ior through catalytic RNA molecules. The second and major contribution is a new genetic circuit model demonstrating that a repressor molecule acting on the positive feedback of a self-activating gene produces reliable oscillations. First contribution: A new model of a synthetic genetic oscillator based on a typical two-gene motif with one positive and one negative feedback loop is pre¬sented. The originality is that the repressor is a catalytic RNA molecule rather than a protein or a non-catalytic RNA molecule. This catalytic RNA is a ribozyme that acts post-transcriptionally by binding to and cleaving target mRNA molecules. This genetic clock involves just two genes, a mRNA and an activator protein, apart from the ribozyme. Parameter values that produce a circadian period in both determin¬istic and stochastic simulations have been chosen as an example of clock operation. The effects of the stochastic fluctuations are quantified by a period histogram and autocorrelation function. The conclusion is that catalytic RNA molecules can act as repressor proteins and simplify the design of genetic oscillators. Second and major contribution: It is demonstrated that a self-activating gene in conjunction with a simple negative interaction can easily produce robust matically validated. This model is comprised of two clearly distinct parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the oscillator dynamics are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this study is that a simple and usual negative interaction, such as degradation, se¬questration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. At the genetic level, this means that an explicit negative feedback loop is not necessary. Unlike many genetic oscillators, this model needs neither cooperative binding reactions nor the formation of protein multimers. Applications and future research directions: Recently, RNA molecules have been found to play many new catalytic roles. The first oscillatory genetic model proposed in this thesis uses ribozymes as repressor molecules. This could provide new synthetic biology design principles and a better understanding of cel¬lular clocks regulated by RNA molecules. The second genetic model proposed here involves only a repression acting on a self-activating gene and produces robust oscil¬lations. Unlike current two-gene oscillators, this model surprisingly does not require a second repressor gene. This result could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. Possible follow-on research directions are: validate models in vivo and in vitro, research the potential of second model as a genetic memory, investigate new genetic oscillators regulated by non-coding RNAs and design a biosensor of positive feedbacks in genetic networks based on the operation of the second model Resumen Introduccion y motivacion: Una amplia variedad de organismos han desarro-llado relojes biomoleculares internos con el fin de adaptarse a los cambios ciclicos del entorno. El funcionamiento de estos relojes involucra redes geneticas. El mo delado de estas redes geneticas es esencial tanto para entender los mecanismos que producen las oscilaciones como para diseiiar nuevos circuitos sinteticos en celulas. Esta tesis doctoral ha dado lugar a dos contribuciones dentro de los campos de los circuitos geneticos en particular, y biologia de sistemas y sintetica en general. La primera contribucion es un nuevo modelo de circuito genetico que muestra un comportamiento oscilatorio usando moleculas de ARN cataliticas. La segunda y principal contribucion es un nuevo modelo de circuito genetico que demuestra que una molecula represora actuando sobre el lazo de un gen auto-activado produce oscilaciones robustas. Primera contribucion: Es un nuevo modelo de oscilador genetico sintetico basado en una tipica red genetica compuesta por dos genes con dos lazos de retroa-limentacion, uno positivo y otro negativo. La novedad de este modelo es que el represor es una molecula de ARN catalftica, en lugar de una protefna o una molecula de ARN no-catalitica. Este ARN catalitico es una ribozima que actua despues de la transcription genetica uniendose y cortando moleculas de ARN mensajero (ARNm). Este reloj genetico involucra solo dos genes, un ARNm y una proteina activadora, aparte de la ribozima. Como ejemplo de funcionamiento, se han escogido valores de los parametros que producen oscilaciones con periodo circadiano (24 horas) tanto en simulaciones deterministas como estocasticas. El efecto de las fluctuaciones es-tocasticas ha sido cuantificado mediante un histograma del periodo y la función de auto-correlacion. La conclusion es que las moleculas de ARN con propiedades cataliticas pueden jugar el misnio papel que las protemas represoras, y por lo tanto, simplificar el diseno de los osciladores geneticos. Segunda y principal contribucion: Es un nuevo modelo de oscilador genetico que demuestra que un gen auto-activado junto con una simple interaction negativa puede producir oscilaciones robustas. Este modelo ha sido estudiado y validado matematicamente. El modelo esta compuesto de dos partes bien diferenciadas. La primera parte es un lazo de retroalimentacion positiva creado por una proteina que se une al promotor de su propio gen activando la transcription. La segunda parte es una interaction negativa en la que una molecula represora evita la union de la proteina con el promotor. Un estudio estocastico muestra que el sistema es robusto al ruido. Un estudio determinista muestra que la dinamica del sistema es debida principalmente a dos tipos de biomoleculas: la proteina, y el complejo formado por el represor y esta proteina. La conclusion principal de este estudio es que una simple y usual interaction negativa, tal como una degradation, un secuestro o una inhibition, actuando sobre el lazo de retroalimentacion positiva de un solo gen es una condition suficiente para producir oscilaciones robustas. Un gen es suficiente y el lazo de retroalimentacion positiva no necesita activar a un segundo gen represor, tal y como ocurre en los relojes actuales con dos genes. Esto significa que a nivel genetico un lazo de retroalimentacion negativa no es necesario de forma explicita. Ademas, este modelo no necesita reacciones cooperativas ni la formation de multimeros proteicos, al contrario que en muchos osciladores geneticos. Aplicaciones y futuras lineas de investigacion: En los liltimos anos, se han descubierto muchas moleculas de ARN con capacidad catalitica. El primer modelo de oscilador genetico propuesto en esta tesis usa ribozimas como moleculas repre¬soras. Esto podria proporcionar nuevos principios de diseno en biologia sintetica y una mejor comprension de los relojes celulares regulados por moleculas de ARN. El segundo modelo de oscilador genetico propuesto aqui involucra solo una represion actuando sobre un gen auto-activado y produce oscilaciones robustas. Sorprendente-mente, un segundo gen represor no es necesario al contrario que en los bien conocidos osciladores con dos genes. Este resultado podria ayudar a clarificar los principios de diseno de los relojes celulares naturales y constituir una nueva y eficiente he-rramienta para crear osciladores geneticos sinteticos. Algunas de las futuras lineas de investigation abiertas tras esta tesis son: (1) la validation in vivo e in vitro de ambos modelos, (2) el estudio del potential del segundo modelo como circuito base para la construction de una memoria genetica, (3) el estudio de nuevos osciladores geneticos regulados por ARN no codificante y, por ultimo, (4) el rediseno del se¬gundo modelo de oscilador genetico para su uso como biosensor capaz de detectar genes auto-activados en redes geneticas.