871 resultados para Radical and Incremental ideas
Resumo:
Synaesthesia is a heterogeneous phenomenon, even when considering one particular sub-type. The purpose of this study was to design a reliable and valid questionnaire for grapheme-colour synaesthesia that captures this heterogeneity. By the means of a large sample of 628 synaesthetes and a factor analysis, we created the Coloured Letters and Numbers (CLaN) questionnaire with 16 items loading on 4 different factors (i.e., localisation, automaticity/attention, deliberate use, and longitudinal changes). These factors were externally validated with tests which are widely used in the field of synaesthesia research. The questionnaire showed good test–retest reliability and construct validity (i.e., internally and externally). Our findings are discussed in the light of current theories and new ideas in synaesthesia research. More generally, the questionnaire is a useful tool which can be widely used in synaesthesia research to reveal the influence of individual differences on various performance measures and will be useful in generating new hypotheses.
Resumo:
Introduction: Measuring trait mindfulness and change in mindfulness may be a crucial prerequisite for the evaluation and further development of mindfulness based interventions for the treatment of mental disorders. This endeavour is nontrivial as current measures cover varying aspects and mindfulness and may have problems regarding validity. This presentation describes the development and validation of a questionnaire for the comprehensive assessment of mindfulness: the Comprehensive Inventory of Mindfulness Experiences (CHIME). Method: The factor structure, reliability, and validity of the CHIME were established in a community sample (N = 298) and a sample of MBSR group participants (N = 161). Results: Factor-analytical procedures supported an eight-factor structure. The structure was tested in a further confirmatory sample (N = 202). The questionnaire and its subscales exhibited good reliability (internal consistency and retest-reliability). Analysis of the measurement invariance of the single items over groups differing in age, gender, meditation experience, and symptom load pointed to the absence of systematic differences in the items' semantic understanding. Parameters reflecting construct validity, criterion validity, and incremental validity as well as change sensitivity were all at least satisfactory. Conclusions: The CHIME is a self-report measure with favorable psychometric properties based on all aspects of mindfulness that are included in current mindfulness scales. This scale may be helpful in the evaluation and further development of mindfulness based interventions.
Resumo:
Transition to psychosis in at-risk individuals has markedly declined in recent years. So far it has never been discussed in detail that with the growing awareness and increasing availability of early psychosis services, a much broader diagnostic spectrum is now being seen in these services. Subsequently, subjects present with symptoms that meet psychosis risk on a purely psychometric basis but may be the phenotypical expression of another underlying mental disorder. Here we critically review four groups of symptoms and clinical features that are frequently reported by individuals with suspected psychosis risk states, yet share strong commonalities with other mental disorders and conditions: isolated hallucinations; unusual bodily perceptions, hypochondriatic fears and cenesthetic psychotic symptoms; depersonalization; obsessive–compulsive, overvalued and delusional ideas. Of the 616 individuals so far assessed in the Bruderholz Early Psychosis Outpatient Service for Adolescents and Young Adults, 218 (30.5%) met ultra-high risk (UHR) criteria, 188 (86.2%) of whom suffered from one of the four above-mentioned symptom groups. The appraisal of the diagnostic spectra and their overlapping symptoms constitute a tremendous challenge in the clinical assessment of each referred individual. The final conclusion of a clinical assessment should not end with the mere assignment – or non-assignment – to a presumed psychosis risk group, but needs to take into account the ‘Gestalt’ of these particular symptoms and clinical features and thus be based on many more facets than solely a psychometric or nosological approach. Such an approach may break down the heterogeneous psychosis risk group and enable appropriate treatment regimes.
Resumo:
Sunlight is a major driving force of atmospheric processes. A detailed knowledge of atmospheric photochemistry is therefore required in order to understand atmospheric chemistry and climate. Considerable progress has been made in this field in recent decades. This contribution will highlight a set of new and emerging ideas (and will therefore not provide a complete review of the field) mainly dealing with long wavelength photochemistry both in the gas phase and on a wide range of environmental surfaces. Besides this, some interesting bulk photochemistry processes are discussed. Altogether these processes have the potential to introduce new chemical pathways into tropospheric chemistry and may impact atmospheric radical formation.
Resumo:
Objectives. The objectives of this report were to describe current best standards in online education, class competencies, class objectives, class activities and to compare the class competencies, objectives and activities undertaken with the current best practices in online teaching and to provide a list of recommendations based on the most efficacious practices. ^ Methods. Utilizing the key words- online teaching, national standards, quality, online courses, I: (1) conducted a search on Google to find the best standard for quality online courses; the search yielded National Standards for Quality Online Teaching as the gold standard in online course quality; (2) specified class objectives and competencies as well as major activities undertaken as a part of the class. Utilizing the Southern Regional Education Board evaluation checklist for online courses, I: (1) performed an analysis comparing the class activities, objectives, and competencies with the current best standards; (2) utilized the information obtained from the analysis and class experiences to develop recommendations for the most efficacious online teaching practices. ^ Results. The class met the criteria set by the Southern Regional Education Board for evaluating online classes completely in 75%, partially in 16% and did not meet the criteria in 9% cases. The majority of the parameters in which the class did not meet the standards (4 of 5) were due to technological reasons beyond the scope of the class instructor, teaching assistant and instructional design. ^ Discussion. Successful online teaching requires awareness of technology, good communication, methods, collaboration, reflection and flexibility. Creation of an online community, engaging online learners and utilizing different learning styles and assessment methods promote learning. My report proposes that online teaching should actively engage the students and teachers with multiple interactive strategies as evidenced from current best standards of online education and my “hands-on” work experience. ^ Conclusion. The report and the ideas presented are intended to create a foundation for efficacious practice on the online teaching platform. By following many of the efficacious online practices described in the report and adding from their own experiences, online instructors and teaching assistants can contribute to effective online learning. ^
Resumo:
The intensity of care for patients at the end-of-life is increasing in recent years. Publications have focused on intensity of care for many cancers, but none on melanoma patients. Substantial gaps exist in knowledge about intensive care and its alternative, hospice care, among the advanced melanoma patients at the end of life. End-of-life care may be used in quite different patterns and induce both intended and unintended clinical and economic consequences. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases to identify patients aged 65 years or older with metastatic melanoma who died between 2000 and 2007. We evaluated trends and associations between sociodemographic and health services characteristics and the use of hospice care, chemotherapy, surgery, and radiation therapy and costs. Survival, end-of-life costs, and incremental cost-effectiveness ratio were evaluated using propensity score methods. Costs were analyzed from the perspective of Medicare in 2009 dollars. In the first journal Article we found increasing use of surgery for patients with metastatic melanoma from 13% in 2000 to 30% in 2007 (P=0.03 for trend), no significant fluctuation in use of chemotherapy (P=0.43) or radiation therapy (P=0.46). Older patients were less likely to receive radiation therapy or chemotherapy. The use of hospice care increased from 61% in 2000 to 79% in 2007 (P =0.07 for trend). Enrollment in short-term (1-3 days) hospice care use increased, while long-term hospice care (≥ 4 days) remained stable. Patients living in the SEER Northeast and South regions were less likely to undergo surgery. Patients enrolled in long-term hospice care used significantly less chemotherapy, surgery and radiation therapy. In the second journal article, of 611 patients identified for this study, 358 (59%) received no hospice care after their diagnosis, 168 (27%) received 1 to 3 days of hospice care, and 85 (14%) received 4 or more days of hospice care. The median survival time was 181 days for patients with no hospice care, 196 days for patients enrolled in hospice for 1 to 3 days, and 300 days for patients enrolled for 4 or more days (log-rank test, P < 0.001). The estimated hazard ratios (HR) between 4 or more days hospice use and survival were similar within the original cohort Cox proportional hazard model (HR, 0.62; 95% CI, 0.49-0.78, P < 0.0001) and the propensity score-matched model (HR, 0.61; 95% CI, 0.47-0.78, P = 0.0001). Patients with ≥ 4 days of hospice care incurred lower end-of-life costs than the other two groups ($14,298 versus $19,380 for the 1- to 3-days hospice care, and $24,351 for patients with no hospice care; p < 0.0001). In conclusion, Surgery and hospice care use increased over the years of this study while the use of chemotherapy and radiation therapy remained consistent for patients diagnosed with metastatic melanoma. Patients diagnosed with advanced melanoma who enrolled in ≥ 4 days of hospice care experienced longer survival than those who had 1-3 days of hospice or no hospice care, and this longer overall survival was accompanied by lower end-of-life costs.^
Resumo:
Abstract Idea Management Systems are web applications that implement the notion of open innovation though crowdsourcing. Typically, organizations use those kind of systems to connect to large communities in order to gather ideas for improvement of products or services. Originating from simple suggestion boxes, Idea Management Systems advanced beyond collecting ideas and aspire to be a knowledge management solution capable to select best ideas via collaborative as well as expert assessment methods. In practice, however, the contemporary systems still face a number of problems usually related to information overflow and recognizing questionable quality of submissions with reasonable time and effort allocation. This thesis focuses on idea assessment problem area and contributes a number of solutions that allow to filter, compare and evaluate ideas submitted into an Idea Management System. With respect to Idea Management System interoperability the thesis proposes theoretical model of Idea Life Cycle and formalizes it as the Gi2MO ontology which enables to go beyond the boundaries of a single system to compare and assess innovation in an organization wide or market wide context. Furthermore, based on the ontology, the thesis builds a number of solutions for improving idea assessment via: community opinion analysis (MARL), annotation of idea characteristics (Gi2MO Types) and study of idea relationships (Gi2MO Links). The main achievements of the thesis are: application of theoretical innovation models for practice of Idea Management to successfully recognize the differentiation between communities, opinion metrics and their recognition as a new tool for idea assessment, discovery of new relationship types between ideas and their impact on idea clustering. Finally, the thesis outcome is establishment of Gi2MO Project that serves as an incubator for Idea Management solutions and mature open-source software alternatives for the widely available commercial suites. From the academic point of view the project delivers resources to undertake experiments in the Idea Management Systems area and managed to become a forum that gathered a number of academic and industrial partners. Resumen Los Sistemas de Gestión de Ideas son aplicaciones Web que implementan el concepto de innovación abierta con técnicas de crowdsourcing. Típicamente, las organizaciones utilizan ese tipo de sistemas para conectar con comunidades grandes y así recoger ideas sobre cómo mejorar productos o servicios. Los Sistemas de Gestión de Ideas lian avanzado más allá de recoger simplemente ideas de buzones de sugerencias y ahora aspiran ser una solución de gestión de conocimiento capaz de seleccionar las mejores ideas por medio de técnicas colaborativas, así como métodos de evaluación llevados a cabo por expertos. Sin embargo, en la práctica, los sistemas contemporáneos todavía se enfrentan a una serie de problemas, que, por lo general, están relacionados con la sobrecarga de información y el reconocimiento de las ideas de dudosa calidad con la asignación de un tiempo y un esfuerzo razonables. Esta tesis se centra en el área de la evaluación de ideas y aporta una serie de soluciones que permiten filtrar, comparar y evaluar las ideas publicadas en un Sistema de Gestión de Ideas. Con respecto a la interoperabilidad de los Sistemas de Gestión de Ideas, la tesis propone un modelo teórico del Ciclo de Vida de la Idea y lo formaliza como la ontología Gi2MO que permite ir más allá de los límites de un sistema único para comparar y evaluar la innovación en un contexto amplio dentro de cualquier organización o mercado. Por otra parte, basado en la ontología, la tesis desarrolla una serie de soluciones para mejorar la evaluación de las ideas a través de: análisis de las opiniones de la comunidad (MARL), la anotación de las características de las ideas (Gi2MO Types) y el estudio de las relaciones de las ideas (Gi2MO Links). Los logros principales de la tesis son: la aplicación de los modelos teóricos de innovación para la práctica de Sistemas de Gestión de Ideas para reconocer las diferenciasentre comu¬nidades, métricas de opiniones de comunidad y su reconocimiento como una nueva herramienta para la evaluación de ideas, el descubrimiento de nuevos tipos de relaciones entre ideas y su impacto en la agrupación de estas. Por último, el resultado de tesis es el establecimiento de proyecto Gi2MO que sirve como incubadora de soluciones para Gestión de Ideas y herramientas de código abierto ya maduras como alternativas a otros sistemas comerciales. Desde el punto de vista académico, el proyecto ha provisto de recursos a ciertos experimentos en el área de Sistemas de Gestión de Ideas y logró convertirse en un foro que reunión para un número de socios tanto académicos como industriales.
Resumo:
Ciao Prolog incorporates a module system which allows sepárate compilation and sensible creation of standalone executables. We describe some of the main aspects of the Ciao modular compiler, ciaoc, which takes advantage of the characteristics of the Ciao Prolog module system to automatically perform sepárate and incremental compilation and efficiently build small, standalone executables with competitive run-time performance, ciaoc can also detect statically a larger number of programming errors. We also present a generic code processing library for handling modular programs, which provides an important part of the functionality of ciaoc. This library allows the development of program analysis and transformation tools in a way that is to some extent orthogonal to the details of module system design, and has been used in the implementation of ciaoc and other Ciao system tools. We also describe the different types of executables which can be generated by the Ciao compiler, which offer different tradeoffs between executable size, startup time, and portability, depending, among other factors, on the linking regime used (static, dynamic, lazy, etc.). Finally, we provide experimental data which illustrate these tradeoffs.
Resumo:
The overall objective of this research project is to enrich geographic data with temporal and semantic components in order to significantly improve spatio-temporal analysis of geographic phenomena. To achieve this goal, we intend to establish and incorporate three new layers (structures) into the core of the Geographic Information by using mark-up languages as well as defining a set of methods and tools for enriching the system to make it able to retrieve and exploit such layers (semantic-temporal, geosemantic, and incremental spatio-temporal). Besides these layers, we also propose a set of models (temporal and spatial) and two semantic engines that make the most of the enriched geographic data. The roots of the project and its definition have been previously presented in Siabato & Manso-Callejo 2011. In this new position paper, we extend such work by delineating clearly the methodology and the foundations on which we will base to define the main components of this research: the spatial model, the temporal model, the semantic layers, and the semantic engines. By putting together the former paper and this new work we try to present a comprehensive description of the whole process, from pinpointing the basic problem to describing and assessing the solution. In this new article we just mention the methods and the background to describe how we intend to define the components and integrate them into the GI.
Resumo:
The famous plan for Toulouse-Le Mirail, by Candilis/Josic/Woods (1961), proposed a radical and hitherto new public space, the dalle, an elevated linear ?stem? that wove the whole urban intervention and concentrated all the commercial, social and cultural activity of the neighbourhood. However, the project is today stigmatized as a total social failure. The dalle has been demolished and a traditional commercial street has been implemented. Was demolition the sole alternative for Le Mirail?s future? This paper aims at identifying certain themes around the conception of the dalle, capable of informing today?s theory and practice in the design of new shopping/public-scapes. It reflects on both the most positive values of the project and on its naiveties and mistakes, conscious of the social unrest that aggrandized them. Ultimately, it calls for a deeper reflection on the urban proposals of the Modern Movement, beyond demolition as the only possible solution.
Resumo:
En un mundo donde el cambio es constante y cada vez más vertiginoso, la innovación es el combustible que utilizan las empresas que permite su renovación constante y, como consecuencia, su supervivencia en el largo plazo. La innovación es sin dudas un elemento fundamental para determinar la capacidad de las empresas en crear valor a lo largo del tiempo, y por ello, las empresas suelen dedicar esfuerzos considerables y recursos de todo tipo para identificar nuevas alternativas de innovación que se adapten a su estrategia, cultura, objetivos y ambiciones corporativas. Una forma específica para llevar a cabo la innovación es la innovación abierta. Esta se entiende como la innovación que se realiza de manera conjunta con otras empresas o participantes del ecosistema. Cabe la aclaración que en este documento se toma la definición de ecosistema referida al conjunto de clientes, proveedores, competidores y otros participantes que interactúan en un mismo entorno donde existen posiciones de liderazgo que pueden cambiar a lo largo del tiempo (Moore 1996). El termino de innovación abierta fue acuñado por Henry Chesbrough hace algo mas de una década para referirse a esta forma particular de organizar la innovación corporativa. Como se observa en el presente trabajo la innovación abierta es un nuevo paradigma que ha capturado el interés académico y empresarial desde algo más de una década. Se verán varios casos de innovación abierta que se están llevando a cabo en diversos países y sectores de la economía. El objetivo principal de este trabajo de investigación es el de desarrollar y explicar un modelo de relación entre la innovación abierta y la creación de valor en las empresas. Para ello, y como objetivos secundarios, se ha investigado los elementos de un Programa de Innovación Abierta, los impulsores 1 de creación de valor, el proceso de creación de valor y, finalmente, la interacción entre estos tres elementos. Como producto final de la investigación se ha desarrollado un marco teórico general para establecer la conexión entre la innovación abierta y la creación de valor que facilita la explicación de la interacción entre ambos elementos. Se observa a partir de los casos de estudio que la innovación abierta puede abarcar todos los sectores de la economía, múltiples geografías y empresas de distintos tamaños (grandes empresas, pequeñas y medianas empresas, incluso empresas de reciente creación) cada una de ellas con distinta relevancia dentro del ecosistema en el que participan. Elementos de un Programa de Innovación Abierta La presente investigación comienza con la enumeración de los distintos elementos que se encuentran presentes en los Programas de Innovación Abierta. De esta manera, se describen los diversos elementos que se han identificado a través de la revisión de la literatura académica que se ha llevado a cabo. En función de una serie de características comunes, los distintos elementos se agrupan en cuatro niveles diferentes para lograr un mejor entendimiento de los Programas de Innovación Abierta. A continuación se detallan estos elementos § Organización del Programa. En primer lugar se menciona la existencia de una estructura organizativa capaz de cumplir una serie de objetivos establecidos previamente. Por su naturaleza de innovación abierta deberá existir cierto grado de interacción entre los distintos miembros que participen en el proceso de innovación. § Talento Interno. El talento interno asociado a los programas de innovación abierta juega un rol fundamental en la ejecución y éxito del programa. Bajo este nivel se asocian elementos como la cultura de innovación abierta y el liderazgo como mecanismo para entender uno de los elementos que explica el grado de adopción de innovación en una empresa. Estrechamente ligados al liderazgo se encuentran los comportamientos organizacionales como elementos diferenciadores para aumentar las posibilidades de creación de innovación abierta. § Infraestructura. En este nivel se agrupan los elementos relacionados con la infraestructura tecnológica necesaria para llevar a cabo el programa incluyendo los procesos productivos y las herramientas necesarias para la gestión cotidiana. § Instrumentos. Por último, se mencionan los instrumentos o vehículos que se utilizan en el entorno corporativo para implementar innovación abierta. Hay varios instrumentos disponibles como las incubadoras corporativas, los acuerdos de licenciamiento o las áreas de capital de riesgo corporativo. Para este último caso se hará una mención especial por el creciente y renovado interés que ha despertado tanto en el entorno académico como empresarial. Se ha identificado al capital de riesgo corporativo como un de los elementos diferenciales en el desarrollo de la estrategia de innovación abierta de las empresas ya que suele aportar credibilidad, capacidad y soporte tecnológico. Estos cuatro elementos, interactuando de manera conjunta y coordinada, tienen la capacidad de crear, potenciar e incluso desarrollar impulsores de creación de valor que impactan en la estrategia y organización de la empresa y partir de aquí en su desempeño financiero a lo largo del tiempo. Los Impulsores de Creación de Valor Luego de identificar, ordenar y describir los distintos elementos presentes en un Programa de Innovación Abierta se ha avanzado en la investigación con los impulsores de creación de valor. Estos pueden definirse como elementos que potencian o determinan la capacidad de crear valor dentro del entorno empresarial. Como se puede observar, se detallan estos impulsores como punto de interacción entre los elementos del programa y el proceso de creación de valor corporativo. A lo largo de la presente investigación se han identificado 6 impulsores de creación de valor presentes en un Programa de Innovación Abierta. § Nuevos Productos y Servicios. El impulsor de creación de valor más directo y evidente en un Programa de Innovación Abierta es la capacidad de crear nuevos productos y servicios dado que se relacionan directamente con el proceso de innovación de la empresa § Acceso a Mercados Adyacentes. El proceso de innovación también puede ser una fuente de valor al permitir que la empresa acceda a mercados cercanos a su negocio tradicional, es decir satisfaciendo nuevas necesidades de sus clientes existentes o de nuevos clientes en otro mercado. § Disponibilidad de Tecnologías. La disponibilidad de tecnologías es un impulsor en si mismo de la creación de valor. Estas pueden ser tanto complementarias como de apalancamiento de tecnologías ya existentes dentro de la empresa y que tengan la función de transformar parte de los componentes de la estrategia de la empresa. § Atracción del Talento Externo. La introducción de un Programa de Innovación Abierta en una empresa ofrece la oportunidad de interactuar con otras organizaciones del ecosistema y, por tanto, de atraer el talento externo. La movilidad del talento es una característica singular de la innovación abierta. § Participación en un Ecosistema Virtuoso. Se ha observado que las acciones realizadas en el entorno por cualquiera de los participantes también tendrán un claro impacto en la creación de valor para el resto de participantes por lo tanto la participación en un ecosistema virtuoso es un impulsor de creación de valor presente en la innovación abierta. § Tecnología “Dentro--‐Fuera”. Como último impulsor de valor es necesario comentar que la dirección que puede seguir la tecnología puede ser desde la empresa hacia el resto del ecosistema generando valor a partir de disponibilizar tecnologías que no son de utilidad interna para la empresa. Estos seis impulsores de creación de valor, presentes en los procesos de innovación corporativos, tienen la capacidad de influir en la estrategia y organización de la empresa aumentando su habilidad de crear valor. El Proceso de Creación de Valor en las Empresas Luego se ha investigado la práctica de la gestión basada en valor que sostiene la necesidad de alinear la estrategia corporativa y el diseño de la organización con el fin de obtener retornos financieros superiores al resto de los competidores de manera sostenida, y finalmente crear valor a lo largo del tiempo. Se describe como los impulsores de creación de valor influyen en la creación y fortalecimiento de las ventajas competitivas de la empresa impactando y alineando su estrategia y organización. Durante la investigación se ha identificado que las opciones reales pueden utilizarse como una herramienta para gestionar entornos de innovación abierta que, por definición, tienen altos niveles de incertidumbre. Las opciones reales aportan una capacidad para la toma de decisiones de forma modular y flexible que pueden aplicarse al entorno corporativo. Las opciones reales han sido particularmente diseñadas para entender, estructurar y gestionar entornos de múltiples incertidumbres y por ello tienen una amplia aplicación en los entornos de innovación. Se analizan los usos potenciales de las opciones reales como complemento a los distintos instrumentos identificados en los Programas de Innovación Abierta. La Interacción Entre los Programas de Innovación Abierta, los Impulsores de Creación de Valor y el Proceso de Creación de Valor A modo de conclusión del presente trabajo se puede mencionar que se ha desarrollado un marco general de creación de valor en el entorno de los Programas de Innovación Abierta. Este marco general incluye tres elementos fundamentales. En primer lugar describe los elementos que se encuentran presentes en los Programas de Innovación Abierta, en segundo lugar como estos programas colaboran en la creación de los seis impulsores de creación de valor que se han identificado y finalmente en tercer lugar como estos impulsores impactan sobre la estrategia y la organización de la empresa para dar lugar a la creación de valor de forma sostenida. A través de un Programa de Innovación Abierta, se pueden desarrollar los impulsores de valor para fortalecer la posición estratégica de la empresa y su capacidad de crear de valor. Es lo que denominamos el marco de referencia para la creación de valor en un Programa de Innovación Abierta. Se presentará la idea que los impulsores de creación de valor pueden colaborar en generar una estrategia óptima que permita alcanzar un desempeño financiero superior y lograr creación de valor de la empresa. En resumen, se ha desarrollado un modelo de relación que describe el proceso de creación de valor en la empresa a partir de los Programas de Innovación Abierta. Para ello, se han identificado los impulsores de creación de valor y se ha descripto la interacción entre los distintos elementos del modelo. ABSTRACT In a world of constant, accelerating change innovation is fuel for business. Year after year, innovation allows firms to renew and, therefore, advance their long--‐term survival. Undoubtedly, innovation is a key element for the firms’ ability to create value over time. Companies often devote considerable effort and diverse resources to identify innovation alternatives that could fit into their strategy, culture, corporate goals and ambitions. Open innovation refers to a specific approach to innovate by collaborating with other firms operating within the same business ecosystem.2 The term open innovation was pioneered by Henry Chesbrough more than a decade ago to refer to this particular mode of driving corporate innovation. Open innovation is a new paradigm that has attracted academic and business interest for over a decade. Several cases of open innovation from different countries and from different economic sectors are included and reviewed in this document. The main objective of this study is to explain and develop a relationship model between open innovation and value creation. To this end, and as secondary objectives, we have explored the elements of an Open Innovation Program, the drivers of value creation, the process of value creation and, finally, the interaction between these three elements. As a final product of the research we have developed a general theoretical framework for establishing the connection between open innovation and value creation that facilitates the explanation of the interaction between the two. From the case studies we see that open innovation can encompass all sectors of the economy, multiple geographies and varying businesses – large companies, SMEs, including (even) start--‐ups – each with a different relevance within the ecosystem in which they participate. Elements of an Open Innovation Program We begin by listing and describing below the items that can be found in an Open Innovation Program. Many of such items have been identified through the review of relevant academic literature. Furthermore, in order to achieve a better understanding of Open Innovation, we have classified those aspects into four different categories according to the features they share. § Program Organization. An organizational structure must exist with a degree of interaction between the different members involved in the innovation process. This structure must be able to meet a number of previously established objectives. § Internal Talent. Internal talent plays a key role in the implementation and success of any Open Innovation program. An open innovation culture and leadership skills are essential for adopting either radical or incremental innovation. In fact, leadership is closely linked to organizational behavior and it is essential to promote open innovation. § Infrastructure. This category groups the elements related to the technological infrastructure required to carry out the program, including production processes and daily management tools. § Instruments. Finally, we list the instruments or vehicles used in the corporate environment to implement open innovation. Several instruments are available, such as corporate incubators, licensing agreements or venture capital. There has been a growing and renewed interest in the latter, both in academia and business circles. The use of corporate venture capital to sustain the development of the open innovation strategy brings ability, credibility, and technological support to the process. The combination of elements from these four categories, interacting in a coordinated way, makes it possible to create, enhance and develop value creation drivers that may impact the company’s strategy and organization and affect its financial performance over time. The Drivers of Value Creation After identifying describing and categorizing the different elements present in an Open Innovation Program our research examines the drivers of value creation. These can be defined as elements that enhance or determine the ability to create value in the business environment. As can be seen, these drivers can act as interacting points between the elements of the program and the process of value creation. The study identifies six drivers of value creation that might be found in an Open Innovation Program. § New Products and Services. The more direct and obvious driver of value creation in any Open Innovation Program is the ability to create new products and services. This is directly related to the company’s innovation process. § Access to Adjacent Markets. The innovation process can also serve as a source of value by granting access to adjacent markets through satisfying new needs for existing customers or attracting new customers from other markets. § Availability of Technologies. The availability of technology is in itself a driver for value creation. New technologies can either be complementary and/or can leverage existing technologies within the firm. They can partly transform certain elements of the company’s strategy. § External Talent Strategy. Incorporating an Open Innovation Program offers the opportunity to interact with other organizations operating in the same ecosystem and can therefore attract external skilled resources. Talent mobility is a unique feature of open innovation. § Becoming Part of a Virtuous Circle. The actions carried out in the environment by any of its members will also have a clear impact on value creation for the other participants. Participation in a virtuous ecosystem is thus a driver for value creation in an open innovation strategy. § Inside--‐out Technology. Value creation may also evolve by allowing other firms in the ecosystem to incorporate internally developed under--‐utilized technologies into their own innovation processes. These six drivers that are present in the innovation process can influence the strategy and the organization of the company, increasing its ability to create value. The Value Creation Process Value--‐based management is the management approach that requires aligning the corporate strategy and the organizational design to create value and obtain sustained financial returns (at least, higher returns than its competitors). We describe how the drivers of value creation can enhance corporate advantages by aligning its strategy and organization. During this study, we were able to determine that real options can be used as managing tools in open innovation environments which, by definition, have high uncertainty levels. Real options provide capability for flexible and modular decision--‐making in the business environment. In particular, real options have been designed for uncertainty management and, therefore, they may be widely applied in innovation environments. We analyze potential uses of real options to supplement the various instruments identified in the Open Innovation programs. The Interaction Between Open Innovation Programs, Value Creation drivers and Value Creation Process As a result of this study, we have developed a general framework for value creation in Open Innovation Programs. This framework includes three key elements. We first described the elements that are present in Open Innovation Programs. Next, we showed how these programs can boost six drivers of value creation that have been identified. Finally, we analyzed how the drivers impact on the strategy and organization of the company in order to lead to the creation of sustainable value. Through an Open Innovation Program, value drivers can be developed to strengthen a company’s strategic position and its ability to create value. That is what we call the framework for value creation in the Open Innovation Program. Value drivers can collaborate in generating an optimal strategy that helps foster a superior financial performance and a sustained value creation process. In sum, we have developed a relationship model that describes the process of creating value in a firm with an Open Innovation Program. We have identified the drivers of value creation and described how the different elements of the model interact with each other.
Resumo:
Los nuevos comportamientos urbanos nos permiten observar cada vez con más frecuencia en nuestras calles y plazas realidades que siempre habíamos considerado domésticas. Al contrario también pasa, todos los días vivimos en nuestras casas situaciones que implican relacionarnos con personas que no son de nuestro núcleo familiar. El diseño doméstico de nuestras ciudades y el urbanismo del diseño de interiores parecen herramientas oportunas en el mundo que nos ha tocado vivir. Esto nos lleva a pensar que los espacios públicos y privados son términos simplificados, definidos en base a conceptos de propiedad para organizar la ciudad. En cambio, sus usos y vivencias, su gestión y sus comportamientos se han complejizado, distorsionando la terminología convencional hasta hacerla obsoleta. En este contexto, considerado también el marco socioeconómico actual, surgen las “acciones de abajo a arriba” como nuevo paradigma o modelo de renovación urbana, que entienden la involucración del ciudadano como parte activa en el proceso de construcción de la urbe desde la misma gestación del proyecto, frente a las acciones habituales que consideran al usuario como mero receptor de las propuestas. Un ciudadano que parece estar cada vez más radicalizado y una administración que parece asustarse ante el desconcierto que el acercamiento al ciudadano puede acarrear, han ocasionado por un lado, espacios “gueto” de carácter casi anárquico y, por el otro lado, lugares tan institucionalizados que derivan en espacios asociados a la administración y ajenos al ciudadano. Por ello, se considera imprescindible la colaboración entre ambos poderes. De acuerdo con el discurso que precede, dentro de un marco comparativo, se estudian 5 supuestos seleccionados de las ciudades Madrid y Zaragoza. Madrid porque es referencia nacional e internacional en el desarrollo urbano a través de procesos ‘abajo arriba’. Zaragoza porque es una ciudad ‘media’ que históricamente no se ha definido por estrategias urbanas claras, ya sean de carácter social o institucional. Sin embargo, en el momento actual se pueden identificar planteamientos relacionados con la recuperación de construcciones y espacios vacantes que pueden ser determinantes a la hora de alcanzar equilibrios con los intensos procesos institucionales acaecidos en las dos últimas décadas. De los procesos urbanos registrados en cada lugar, desarrollados en construcciones y espacios vacantes, he seleccionado: Construcciones Vacantes Madrid |Tabacalera de Lavapiés Zaragoza | Antiguo I.E.S. Luis Buñuel y antiguo Convento de Mínimos Espacios Vacantes Madrid | Campo de Cebada [solar] Zaragoza | Patio ‘antiguo I.E.S. Luis Buñuel [espacio libre] y plaza Eduardo Ibarra [espacio libre] El proyecto de investigación ha partido de las hipótesis de partida que siguen: UNA… Las ‘acciones de abajo arriba’ o renovación desde abajo no tienen cabida como elementos urbanos aislados sino conectados entre sí, posibilitando la producción de sinergias y la construcción de la ciudad; pudiendo ser consideradas acciones de desarrollo y enlace urbano, pues su objetivo es convertirse en motores del espacio público. Cuestión que es aplicable al resto de los procesos o acciones urbanas [‘horizontales’ o ‘institucionales’] DOS… La capacidad de adaptación manifestada por las ‘acciones de abajo arriba’ implica un marco ideológico de referencia asociado a la importancia de la construcción con mínimos recursos [Re-ocupación y/o Re- Construcción de estructuras urbanas en desuso] en los procesos urbanos descritos, como vía para comprender los concepto sostenibilidad y calidad figurativa de lo construido. Cuestión que es aplicable a la recuperación de aquellos aspectos de la arquitectura que la convierten en necesaria para la sociedad. Y tiene como objetivo: Identificar modelos de sostenibilidad urbana como una estrategia que va de lo individual a lo colectivo y que se transmite fundamentalmente con la acción, mezclando la innovación y la tecnología en múltiples ámbitos, utilizando los recursos naturales e intelectuales de una manera eficiente y entendiendo la inteligencia humana y sobre todo la inteligencia colectiva, como principio y justificación. Se han analizado los siguientes aspectos: sociales [participación ciudadana e implicación de la administración pública], urbanos [conexiones con otros colectivos o espacios urbanos / transformaciones urbanas a través de los procesos de gestión utilizados], constructivos [materiales utilizados en la re-construcción de construcciones y espacios vacantes / sistemas constructivos utilizados] y los relacionados con la sostenibilidad [sostenibilidad económica / sostenibilidad de mantenimiento / sostenibilidad funcional / inteligencia colectiva] El estudio de los aspectos considerados se ha desarrollado con las herramientas metodológicas siguientes: Entrevistas abiertas a expertos: se han obtenido respuestas de 25 personas expertas [5 por cada espacio o construcción vacante] relacionadas con las acciones urbanas sostenibles, la cultura y las relaciones sociales, y que también conocen los lugares y su entorno desde los puntos de vista urbano y construido. Son ‘tipos ideales’ asociados a uno de los cinco poderes que se manifiestan en la ciudad: el poder educativo [la universidad], el poder creativo [la cultura], el poder administrativo [la política], el poder empresarial [la empresa privada] y los usuarios [un usuario activo y representativo de cada lugar elegido que haya intervenido en la gestación del proceso]. Han sido personas que conocían el tejido social y urbano de la ciudad de Zaragoza y Madrid, ya que la herramienta ‘entrevista abierta a expertos’, recoge datos y opiniones planteadas en las construcciones y espacios vacantes ubicados en Zaragoza y Madrid. Entrevistas cerradas a usuarios: como la población de usuarios que se somete a la investigación es infinita o muy grande, resulta imposible o inconveniente realizar la obtención de los datos sobre todos aquellos elementos que la forman. Por lo tanto, he decidido estudiar sólo una parte de la población que denomino ‘tipos ideales’, obteniendo respuestas de 150 usuarios [30 personas por cada espacio o construcción vacante]. La selección de grupos de personas entrevistadas, debe permitir que los resultados sean representativos de la población total de usuarios. Además, la elección de ‘tipos ideales’ se ha identificado con los vecinos de los núcleos urbanos [o barrios] en los que se ubican las construcciones o espacios vacantes analizados. Observación estructurada: recoger información a través de la observación me ha permitido conocer las actuaciones y comportamientos de los ciudadanos en el medio urbano. Esto ha facilitado el estudio del medio a nivel práctico, valorando el uso que la sociedad da a las construcciones y a los espacios vacantes analizados. Es importante posicionar la estrategia en relación con el tema de investigación propuesto. Una estrategia que dibuje un panorama plural, desarrollado a través de herramientas sociales y constructivas que permitan que la arquitectura hable de cosas parecidas a lo que interesa a la ciudadanía. Para ello, propuse un catálogo de herramientas arquitectónicas que han permitido evaluar todas las propuestas. Un contexto de estrategias comunes que han descrito con los mismos códigos las distintas actuaciones analizadas. Estas herramientas tocan diferentes campos de interés. Desde las partes más tectónicas y constructivas, hasta las más ligadas con el desarrollo urbanístico y social. Acciones de participación colectiva: Experiencias o laboratorios urbanos participados por los alumnos del grado de arquitectura de la UNIZAR y los agentes sociales. Las acciones son una herramienta propositiva. Investigar y analizar proponiendo ha permitido que el análisis del contexto pueda llegar a capas de mucha más profundidad. No se ha trabajado estableciendo jerarquías de profesores y alumnos, sino que se ha intentado posibilitar la conexión de distintos agentes que trabajan coordinadamente durante el tiempo que han durado las acciones. Por un lado esto ha permite que cada integrante haya aportado al grupo lo que mejor sabe hacer y de la misma manera, que cada uno pueda aprender aquello de lo que tenga más ganas… y reflexionar sobre determinados aspectos objeto del análisis. Una vez interpretados los resultados, obtenidos a través de las herramientas metodológicas referenciadas, se ha concluido lo que sigue: Respecto de la Hipótesis de partida UNO LAS ACCIONES ‘ABAJO ARRIBA’ han revelado que no se puede entender ningún proceso de gestión urbana fuera de la participación ciudadana. El ‘ESPACIO LIBRE’ de una ciudad necesita lugares de autogestión, espacios de cogestión, movimientos de ‘arriba abajo’ y también modelos que todavía no sabemos ni que existen. LAS ACCIONES INSTITUCIONALES ‘ARRIBA ABAJO’ han demostrado que no han presentado permeabilidad ni relación con las circulaciones de entorno. Tampoco han tenido en cuenta a otras muchas personas, ‘usuarios productores’, a las que les interesan los procesos de búsqueda y las fórmulas de conexión más interactivas. Respecto de la hipótesis de partida DOS LAS ACCIONES ‘ABAJO ARRIBA’ han revelado que el ‘derecho a la ciudad’, paradigma defendido por Lefebvre desde el cual se piensa el urbanismo ciudadano, en estos supuestos podría entenderse como el ‘derecho a la infraestructura’. El ESPACIO LIBRE es infraestructura y se quiere para infraestructurar los derechos de cada uno. Y aunque también es verdad que estas acciones son simples destellos, han hecho visible otro paradigma de gestión y propuesta urbana que puede ser predominante en un futuro próximo. LAS ACCIONES INSTITUCIONALES ‘ARRIBA ABAJO’ han revelado que las intervenciones estuvieron enfocadas únicamente a la resolución de los procesos constructivos y a la incorporación del programa como un dato ‘problema’ que era necesario resolver para evitar la afección al diseño. ABSTRACT The new urban ways of behaviour let us watch more and more frequently in our streets and squares, realities that we had always considered as domestic. This also happens the other way round. Every day we have to go through situations at home which imply relationships with people who don’t belong to our family circle. The domestic design of our cities and the urban planning of indoor design seem to be adequate tools in the world we have to live in. This leads us to think that public and private spaces are simplified terms, defined according to concepts of property in order to organise the city. On the other hand, its uses and the experiences of people, its management and ways of behaviour is now more complex, changing the conventional terminology that has become outdated. In this context, ‘bottom-up’ actions arise as a new paradigm or model of urban renewal. These actions consider the active role of social participation in the process of building up the city from the very beginning, in comparison with the former way of acting that considered the user as mere receptor of the proposals. A citizen who seems to become more and more radical, and an administration that seems to be afraid of the unknown, have created both almost anarchic ghetto spaces and, on the other hand, spaces which have been so institutionalised that derive into areas associated to the administration but alienated from the citizen. For this reason, cowork of both forces is considered as crucial. In accordance with the above mentioned ideas and within a comparative framework, five situations chosen from the cities of Madrid and Zaragoza are studied. Madrid because is a national and international reference in urban development that uses “bottom-up” processes. Zaragoza because is a “medium-size” city that, historically, has not been defined by clear social or institutional urban strategies. Nevertheless, at the present time we can identify approaches on the recovery of constructions and empty areas that may be determining for reaching a balance with the intense institutional processes that have taken place in the two last decades. From the urban processes registered in every place and developed in vacant areas and constructions, I have chosen: Vacant constructions Madrid | Lavapiés Tobacco Factory Zaragoza | Old Secondary School Luis Buñuel and old Convent of the Minimos Vacant areas Madrid | Campo de Cebada [non-built site]. Zaragoza | Old courtyard of the secondary school and Eduardo Ibarra square [free space] The research project has been issued from the following starting hypotheses: ONE… “Bottom-up actions” or renewal from below have no place as isolated urban elements but as connected parts that can produce synergies and the construction of the city, and that can also be considered as actions producing urban development and links. This can also be applied to the rest of urban processes or actions [‘horizontal’ or ‘institutional’]. TWO… The capacity of adaptation shown by “bottom-up actions” implies an ideological framework of reference which is related to the importance of construction with minimal resources (re-occupation and/or reconstruction of urban structures in disuse) in the above mentioned urban processes, as a way for understanding the concepts of sustainability and the representational quality of what has been constructed. This can also be applied to the recovery of those architectural aspects that make architecture necessary for society. And its objective is: Identify models of urban sustainability as a strategy going from the individual to the collective, which are mainly transferred by action and that mix innovation and technology in many fields. Models that use natural and intellectual resources in an efficient way, and understand human intelligence and, above all, collective intelligence, as principle and justification. The following aspects have been analysed: social [civic participation and involvement of the public Administration], urban [connections with other collectives or urban spaces / urban transformation by the processes of administration used], constructive [materials used for the re-construction of empty spaces / construction systems used] and those focusing on sustainability [economic sustainability /maintenance sustainability /functional sustainability / collective intelligence]. For researching into the above mentioned aspects, the following methodological tools have been developed: Open interviews with experts: answers from 25 experts have been obtained [five for every vacant space or empty construction] on sustainable urban actions, culture and social relations, who also know the places and their environment from an urban and constructive point of view. These are “ideal types” linked to one of the five powers acting in the city: the educational power [University], the creative power [culture], the administration power [politics], the corporate power [private companies] and the users [an active and representative user for every place selected during the establishment of the process]. They were people who knew the social and urban fabric of Zaragoza and Madrid, since the “open interview for experts” tool collects data and points of view set out in vacant constructions and spaces of Zaragoza and Madrid. Close interviews with users: as the number of users targeted for the research is very big or infinite, it is impossible or inconvenient to get data from all its constituent parts. Therefore, I have decided to research into the part of the population that I call “ideal types”, obtaining answers from 150 users [30 people for every empty space or construction]. The selection of the groups of people interviewed must produce results which are representative of the total population of users. Furthermore, the election of “ideal types” has been identified with the inhabitants of urban areas [or city districts] in which the vacant spaces or constructions analysed are located. A structured observation: I have known the actions and ways of behaving of the citizens in the urban environment by means of collecting information after observation. Therefore, the practical research into the target environment has been easier by valuing the use that society gives to the empty constructions and spaces analysed. It is important to position the strategy with respect to the research subject proposed. It involves a strategy able to get an overview of a plural landscape, developed by social and constructive tools, allowing architecture to talk about topics which are interesting for city dwellers. Therefore, I proposed a set of architectural tools to evaluate all the proposals. A context of common strategies describing the different actions analysed by using the same codes. These tools focus on different fields of interests, from the most tectonic and constructive parts, to the most related to urban and social development. Actions on collective participation: experiences or urban laboratories shared by the students of architecture of the University of Zaragoza and social agents. The actions are a proactive tool. Researching and analysing by means of proposing, has allowed me to analyse the context and much deeper layers. This work has not been done by establishing ranks of professors and student, but trying to get an interaction between the different agents who work in close coordination during the implementation of the actions. This has allowed every agent to contribute the group what they do the best, and also every individual has had the possibility to learn what s/he prefers…, thinking about the different aspects targeted by the analysis. Once the different methodological tools have been interpreted, this is the conclusion: With regard to the initial hypothesis ONE “BOTTOM-UP” ACTIONS have proven that no process of urban management can be understood outside civic participation. The “FREE SPACE” of a city needs self-managed places, co-managed spaces, “up-bottom” movements, and also models whose existence is still ignored. “UP-BOTTOM” INSTITUTIONAL ACTIONS have proven that they have not presented neither permeability nor relation with local ideas. They have also disregarded many other people, the “usersproducers”, who are interested in the most interactive means of searching and connecting processes. With regard to the initial hypothesis TWO Under these premises, “BOTTOM-UP” ACTIONS have shown that the “right to the city”, a paradigm defended by Lefebvre and from which citizen-focused urbanism is conceived, could be considered as a “right to the infrastructures”. A FREE SPACE is an infrastructure and must be used to “infrastructure” the rights of every citizen. And, even though it is true that these actions are mere flashes, they have made visible another paradigm of management and urban proposal that can be prevailing in a near future. “UP-BOTTOM” INSTITUTIONAL ACTIONS have revealed that the interventions have only focused on resolving construction processes and the incorporation of the program as a “problem” data that was necessary to resolve in order to avoid its influence on the design.
Resumo:
“La ciudad radical” es una tentativa de catálogo de ciudades radicales, un atlas abierto de los límites imaginarios de la convivencia colectiva. Llamo al catálogo “tentativa” porque un catálogo siempre es abierto. Abierto en un doble sentido, en sentido de inacabado, siempre caben futuras revisiones, adiciones, modificaciones, alteraciones de orden… y en el sentido de permitir multitud lecturas y posibilidades abiertas de interpretación. El tema central de este trabajo es, el imaginario, lo imaginario, la fantasía, la ficción…como condición fundamental de creación en el ámbito social. En lo imaginario, y en el imaginario, reside la infinita y reiterativa capacidad de la sociedad para inventarse y re-inventarse, para crearse y re-crearse en el mundo, a través de la ciudad. Ciudad radical es una ciudad extremada, en la que una de sus rasgos ha sido llevado al extremo. Pero radical (del latín radix) también quiere decir raíz, origen, fundamento. El objeto del catálogo también es doble. Por un lado, el interés de generar un compendio de ciudades radicales, extremadas, acumuladas en la historia. Por otro lado, el objeto del catálogo es aproximarnos a la idea que nos hemos hecho, a lo largo de la historia, de nuestra gran “obra” en la tierra, el artificio esencialmente humano que es la ciudad. El análisis de las ciudades radicales sirve de método para la aproximación a la idea de ciudad y para desentrañar las metáforas urbanas que nos habitan, aquellas que nos hacen pensar la ciudad y en las que la ciudad nos piensa. En última instancia esta tesis pretender encontrar indicios que nos ayuden en la respuesta de una pregunta esencial, por qué ciudades, qué fuerzas nos empujan hacia los otros bajo la forma de la ciudad, desde los orígenes. La historia de nuestras sociedades es la historia de nuestras ciudades. La historia de la ciudad, es nuestra historia. La ciudad es la gran creación humana en la tierra, el objeto y el sujeto de la convivencia, del hábitat social. En este sentido la radicalización nos acerca a la esencia humana, desde el extremo llegamos al centro, al origen. Pensamos la ciudad, la ciudad nos piensa. Creamos la ciudad, la ciudad nos crea. La ciudad es radical en un doble sentido, está en el extremo y está en el origen, que es también el fin. ABSTRACT “The radical city” is an attempt to catalogue radical cities throughout history, it aims to be an open atlas of the imaginary limits of coexistence and the living together. I call this work an “attempt” of catalogue due to the implied open nature of catalogues. Open in the sense of unfinished, there is always space for adding, reviewing, modifying, altering…but also open in the sense of multiple readings and several possibilities for interpretation, which this work allows. The main background theme underlying this catalogue, providing context to the way of understanding human beings, is the imaginary, imagination, fantasy, and fiction as the fundamental condition for social creation. The imaginary is where the endless and reiterative capacity for societies to invent and re-invent themselves, to create and re-create themselves through the city, lies in. Radical city is an extreme city, which one of the features has been pushed to the limit. Radical, (from the Latin form, radix) also means root, origin and fundament. The object of this catalogue is double as well. On the one hand, the intention of putting together, as accumulating, a whole range of radical and extreme cities throughout history. On the other hand, the intention of the catalogue is approaching the idea, the way we, as humans, envision our own creation on Earth, the city as a purely and essentially human invention. In this sense, the analysis of radically produced cities helps as a means to understand, or at least, to get closer to the idea of the city itself; to figure out the urban metaphors envisioning “us” as living in cities, those metaphors determining the way we envision “inhabiting” as an essential need, and which set up the imaginary limits within we, as social individuals, dream of the city or the way in which the city, as the radix, “dreams of ourselves”. Ultimately, this work aims to approach the answer to a fundamental question, why cities? Which forces push us towards the others in the form of the city since forever? The history of our societies is the history of our cities. The history of our cities is our own history. Cities are our greatest invention, object and subject of coexistence, radical trigger for the living together. In this sense, radicalization helps us to get closer to human essence, is by approaching the limits that we can we reach the centre, the origin. We envision the city and¬¬¬ the city envisions us. The city is radical in a double way, is both origin and limits, origin and end.
Resumo:
Eukaryotic Cu,Zn superoxide dismutases (CuZnSODs) are antioxidant enzymes remarkable for their unusually stable β-barrel fold and dimer assembly, diffusion-limited catalysis, and electrostatic guidance of their free radical substrate. Point mutations of CuZnSOD cause the fatal human neurodegenerative disease amyotrophic lateral sclerosis. We determined and analyzed the first crystallographic structure (to our knowledge) for CuZnSOD from a prokaryote, Photobacterium leiognathi, a luminescent symbiont of Leiognathid fish. This structure, exemplifying prokaryotic CuZnSODs, shares the active-site ligand geometry and the topology of the Greek key β-barrel common to the eukaryotic CuZnSODs. However, the β-barrel elements recruited to form the dimer interface, the strategy used to forge the channel for electrostatic recognition of superoxide radical, and the connectivity of the intrasubunit disulfide bond in P. leiognathi CuZnSOD are discrete and strikingly dissimilar from those highly conserved in eukaryotic CuZnSODs. This new CuZnSOD structure broadens our understanding of structural features necessary and sufficient for CuZnSOD activity, highlights a hitherto unrecognized adaptability of the Greek key β-barrel building block in evolution, and reveals that prokaryotic and eukaryotic enzymes diverged from one primordial CuZnSOD and then converged to distinct dimeric enzymes with electrostatic substrate guidance.
Resumo:
The Escherichia coli DNA repair enzyme MutY plays an important role in the prevention of DNA mutations by removing misincorporated adenine residues from 7,8-dihydro-8-oxo-2′-deoxyguanosine:2′-deoxyadenosine (OG:A) mispairs. The N-terminal domain of MutY (Stop 225, Met1–Lys225) has a sequence and structure that is characteristic of a superfamily of base excision repair glycosylases; however, MutY and its homologs contain a unique C-terminal domain. Previous studies have shown that the C-terminal domain confers specificity for OG:A substrates over G:A substrates and exhibits homology to the d(OG)TPase MutT, suggesting a role in OG recognition. In order to provide additional information on the importance of the C-terminal domain in damage recognition, we have investigated the kinetic properties of a form lacking this domain (Stop 225) under multiple- and single-turnover conditions. In addition, the interaction of Stop 225 with a series of non-cleavable substrate and product analogs was evaluated using gel retardation assays and footprinting experiments. Under multiple-turnover conditions Stop 225 exhibits biphasic kinetic behavior with both OG:A and G:A substrates, likely due to rate-limiting DNA product release. However, the rate of turnover of Stop 225 was increased 2-fold with OG:A substrates compared to the wild-type enzyme. In contrast, the intrinsic rate for adenine removal by Stop 225 from both G:A and OG:A substrates is significantly reduced (10- to 25-fold) compared to the wild-type. The affinity of Stop 225 for substrate analogs was dramatically reduced, as was the ability to discriminate between substrate analogs paired with OG over G. Interestingly, similar hydroxyl radical and DMS footprinting patterns are observed for Stop 225 and wild-type MutY bound to DNA duplexes containing OG opposite an abasic site mimic or a non-hydrogen bonding A analog, suggesting that similar regions of the DNA are contacted by both enzyme forms. Importantly, Stop 225 has a reduced ability to prevent DNA mutations in vivo. This implies that the reduced adenine glycosylase activity translates to a reduced capacity of Stop 225 to prevent DNA mutations in vivo.