Diseño para fabricación digital: definición unívoca entre forma y fabricación en arquitectura

La presente investigación se inicia planteando el objetivo de identificar los parámetros geométricos que son exclusivos del proceso de generación de la Forma y relacionarlos con los invariantes relacionados con la Fabricación digital aplicada a la Arquitectura. Con ello se pretende recuperar la geometría como herramienta principal del proceso de Proyecto ampliando su ámbito de actuación al encontrar una relación con los procesos de fabricación digital. El primer capítulo describe los antecedentes y contexto histórico centrándose especialmente en la influencia de la capacidad de definir geometrías complejas digitalmente mediante la aplicación de algoritmos. En los primeros ejemplos la aproximación del Arquitecto a proyectos con geometrías complejas no euclídeas aún se emplea sin precisión en la comunicación de la geometría ideada para su puesta en obra. Las técnicas constructivas obligan a asumir una tolerancia de desviación entre proyecto y obra y la previsión del comportamiento de esa geometría no permite asegurar su comportamiento final. No será hasta la introducción de herramientas CAD en el proceso de ideación arquitectónica cuando el Arquitecto se capacite para generar geometrías no representables de forma analógica. Sin embargo, la imposibilidad de trasladar la geometría proyectada a la praxis constructiva impedirá la plasmación de un proceso completo, salvo en las contadas ocasiones que se recogen en este texto. “El análisis cronológico de las referencias establece como aspecto esencial para la construcción de geometrías complejas la capacidad primero para definir y comunicar de forma precisa e inequívoca la geometría y después la capacidad de analizar el desempeño prestacional de dicha propuesta geométrica”. La presente investigación se inicia planteando el objetivo de identificar los parámetros geométricos que son exclusivos del proceso de generación de la Forma y relacionarlos con los invariantes relacionados con la Fabricación digital aplicada a la Arquitectura. Con ello se pretende recuperar la geometría como herramienta principal del proceso de Proyecto ampliando su ámbito de actuación al encontrar una relación con los procesos de fabricación digital. El primer capítulo describe los antecedentes y contexto histórico centrándose especialmente en la influencia de la capacidad de definir geometrías complejas digitalmente mediante la aplicación de algoritmos. En los primeros ejemplos la aproximación del Arquitecto a proyectos con geometrías complejas no euclídeas aún se emplea sin precisión en la comunicación de la geometría ideada para su puesta en obra. Las técnicas constructivas obligan a asumir una tolerancia de desviación entre proyecto y obra y la previsión del comportamiento de esa geometría no permite asegurar su comportamiento final. No será hasta la introducción de herramientas CAD en el proceso de ideación arquitectónica cuando el Arquitecto se capacite para generar geometrías no representables de forma analógica. Sin embargo, la imposibilidad de trasladar la geometría proyectada a la praxis constructiva impedirá la plasmación de un proceso completo, salvo en las contadas ocasiones que se recogen en este texto. “El análisis cronológico de las referencias establece como aspecto esencial para la construcción de geometrías complejas la capacidad primero para definir y comunicar de forma precisa e inequívoca la geometría y después la capacidad de analizar el desempeño prestacional de dicha propuesta geométrica”. Establecida la primera conclusión, el capítulo de contexto histórico continúa enfocándose sobre la aplicación de las técnicas digitales en el Proceso de proyecto primero, y en la puesta en obra después. Los casos de estudio identifican claramente como un punto de inflexión para la generación de formas complejas mediante un software CAD el Museo Guggenheim de Bilbao en 1992. El motivo esencial para elegir este proyecto como el primer proyecto digital es el uso de la herramienta de definición digital de la geometría para su reproducción inequívoca en obra. “La revolución digital ha aportado al Arquitecto la posibilidad de abandonar las tipologías arquitectónicas basados en restricciones geométricas-constructivas. La aplicación de técnicas de fabricación digital ha permitido la capacidad de diseñar con independencia del sistema constructivo y libertad formal. En este nuevo contexto las prestaciones suponen los nuevos límites conceptuales, ya que el acceso y disposición de la información del comportamiento de las alternativas que cada geometría conlleva demanda del Arquitecto la jerarquización de los objetivos y la formulación en un conjunto coherente de parámetros”. Los proyectos que emplean herramientas digitales para la resolución de las distintas etapas del proceso proyectual se verán incrementados de forma exponencial desde 1992 hasta nuestros días. A pesar del importante auge de las técnicas de diseño asistido por ordenador el principal desafío sigue siendo la vinculación de las geometrías y materiales propuestos con las capacidades de las técnicas de manufactura y puesta en obra. El proceso de diseño para fabricación en un entorno digital es una tecnología madura en otras industrias como la aeroespacial o la automovilística, incluso la de productos de consumo y decoración, sin embargo en el sector de Construcción es un sistema inmaduro e inconexo. Las particularidades de la industria de la construcción aún no han sido abordadas en su totalidad y las propuestas de investigación realizadas en este ámbito se han centrado hasta 2015 en partes del proceso y no en el proceso total. “El principal obstáculo para la estandarización e implantación globalizada de un proceso digital desde el origen de la forma hasta la construcción es la inexistencia de un protocolo integrado que integre las limitaciones de fabricación, económicas y de puesta en obra junto a la evaluación de desempeño prestacional durante la fases iniciales de proyecto”. En el capítulo número 3 se estudian los distintos procesos de generación de la forma. Se propone una definición específica para el ámbito de la investigación de “forma” en el entendemos que se incluye la envolvente exterior y el conjunto organizativo de espacios interiores conectados. Por lo tanto no es excluyente del interior. El objetivo de este estudio es analizar y clasificar los procesos para la generación digital de formas en los distintos proyectos seleccionados como emblemáticos de cada tipología. Se concluye que la aproximación a este proceso es muy variada y compleja, con aplicación segregada y descoordinada entre los distintos agentes que han intervenir. En un proceso de generación formal analógico los parámetros que intervienen son en parte conscientes y en parte inconscientes o aprendidos. El Arquitecto sólo tiene control sobre la parte consciente de los parámetros a integrar en el diseño, de acuerdo a sus conocimientos y capacidades será capaz de manejar un número limitado de parámetros. La parte aprendida permanece en el inconsciente y dirige el proceso analógico, aportando prejuicios estéticos incorporados durante el proceso formativo y propio del entorno cultural. “El empleo de herramientas digitales basadas en la evaluación prestacional durante el proceso de selección formal permite al Arquitecto conocer “en tiempo real” el desempeño en el conjunto de prestaciones evaluadoras del conjunto de alternativas geométricas a la propuesta previamente definida por la intuición arquitectónica. El proceso definido no persigue identificar una solución óptima sino asistir al Arquitecto en el proceso de generación de la forma mediante la evaluación continua de los vectores direccionales más idóneos que el procedimiento generativo plantea”. La definición de complejidad en generación y producción de formas en relación con el proceso de diseño digital paramétrico global o integrado, es esencial para establecer un protocolo que optimice su gestión. “Se propone como definición de complejidad como factor resultante de multiplicar el número de agentes intervinientes por el número de parámetros e interacciones comunes que intervienen en el proceso de generación de la forma, dividido por la complejidad de intercambio de información digital desde el origen hasta la fase de fabricación y construcción”. Una vez analizados los procesos de generación digital de Arquitectura se propone identificar los parámetros geométricos que definen el proceso de Diseño digital, entendiendose por Diseño el proceso que engloba desde la proposición de una forma inicial basada en la intuición del Arquitecto, la generación y evaluación de variantes y posterior definición digital para producción, tanto de un objeto, un sistema o de la totalidad del Proyecto. En la actualidad el proceso de Diseño es discontinuo y lineal organizandose los parámetros por disciplinas en las que está estructurada las atribuciones profesionales en la industria de la construcción. Para simplificar la identificación y listado se han agrupado siguiendo estos grupos de conocimiento. Entendemos parametros invariables aquellos que son independientes de Tipologías arquitectónicas o que dependen del mismo proceso de generación de la Forma. “El listado de los parámetros que intervienen en un proceso de generación formal es una abstracción de una realidad compleja. La parametrización de las decisiones que intervienen en la selección de una forma determinada mediante “well defined problems” es imposible. El proceso que esta tesis describe entiende esta condición como un elemento que pone en valor el propio procedimiento generativo por la riqueza que la subjetividad que el equipo de diseño aporta”. La segunda parte esencial de esta investigación pretende extraer las restricciones propias del estado del arte de la fabricación digital para posteriormente incorporarlos en los procesos digitales de definición de la Forma arquitectónica. “La integración de las restricciones derivadas de las técnicas de fabricación y construcción digitales en el proceso de generación de formas desde el ámbito de la Arquitectura debe referirse a los condicionantes geométricos asociados a cada sistema constructivo, material y técnica de fabricación. La geometría es además el vínculo que permite asociar el conjunto de parámetros prestacionales seleccionados para un Proyecto con los sistemas de fabricación digital”. A estos condicionantes geométricos obtenidos del análisis de cada sistema de fabricación digital se les ha denominado “invariantes geométricos”. Bajo este término se engloban tanto límites dimensionales de fabricación, como materiales compatibles, tolerancias de manufactura e instalación y cualidades prestacionales asociadas. El objetivo de esta propuesta es emplear la geometría, herramienta fundamental y propia del Arquitecto, como nexo de unión entre el conjunto complejo y heterogéneo de parámetros previamente listados y analizados. Para ello se han simplificado en tablas específicas para cada parámetro prestacional los condicionantes geométricos que se derivan de los Sistemas de fabricación digital compatibles (ver apéndice 1). El estudio y evaluación de las capacidades y objetivos de las distintas plataformas de software disponibles y de las experiencias profesionales evaluadas en los proyectos presentados, permiten concluir que la propuesta de plataforma digital de diseño integral multi-paramétrico de formas arquitectónicas requiere de un protocolo de interoperatibilidad específico aún no universalmente establecido. Actualmente el enfoque de la estrategia para normalizar y universalizar el contexto normativo para regular la interoperatibilidad se centra en figura del gestor denominado “BIM manager”. Las atribuciones y roles de esta figura se enfocan a la gestión del continente y no del contenido (Definición de los formatos de intercambio, niveles de desarrollo (LOD) de los componentes o conjuntos constructivos, detección de interferencias y documentación del propio modelo). Siendo este ámbito un desarrollo necesario para la propuesta de universalización del sistema de diseño para fabricación digital integrado, la presente investigación aporta un organigrama y protocolo asociado. El protocolo: 1. Establece la responsabilidad de identificar y definir la Información que debe determinar el proceso de generación y desarrollo de la forma arquitectónica. 2. Define la forma digital apropiada para generar la geometría del Proyecto, incluyendo la precisión necesaria para cada componente y el nivel de detalle necesario para su exportación inequívoca al proceso de fabricación. 3. Define el tempo de cada etapa de diseño identificando un nivel de detalle acorde. 4. Acopla este organigrama dentro de las estructuras nuevas que se proponen en un entorno BIM para asegurar que no se producen solapes o vacíos con las atribuciones que se identifican para el BIM Manager. “El Arquitecto debe dirigir el protocolo de generación coordinada con los sistemas de producción digital para conseguir que la integración completa. El protocolo debe asistir al proceso de generación de forma mediante la evaluación del desempeño prestacional de cada variante en tiempo real. La comunicación entre herramientas digitales es esencial para permitir una ágil transmisión de información. Es necesario establecer un protocolo adaptado a los objetivos y las necesidades operativas de cada proyecto ya que la estandarización de un protocolo único no es posible”. Una decisión estratégica a la hora de planificar una plataforma de diseño digital común es establecer si vamos a optar por un Modelo digital único o diversos Modelos digitales federados. Cada uno de los modos de trabajo tiene fortalezas y debilidades, no obstante en el ámbito de investigación se ha concluido que un proceso integrado de Diseño que incorpore la evaluación prestacional y conceptual definida en el Capítulo 3, requiere necesariamente de varios modelos de software distintos que han de relacionarse entre sí mediante un protocolo de comunicación automatizado. Una plataforma basada en un modelo federado consiste en establecer un protocolo de comunicación entre los programas informáticos empleados por cada disciplina. En este modelo de operación cada equipo de diseño debe establecer las bases de comunicación en función del número y tipo de programas y procesos digitales a emplear. En esta investigación se propone un protocolo basado en los estándares de intercambio de información que estructura cualquier proceso de generación de forma paramétrico “La investigación establece el empleo de algoritmos evolutivos como el sistema actual óptimo para desarrollar un proceso de generación de formas basadas en la integración y coordinación de invariantes geométricos derivados de un conjunto de objetivos prestacionales y constructivos. No obstante, para la aplicación en el caso práctico realizado se ha podido verificar que la evaluación del desempeño aún no puede realizarse en una única herramienta y por lo tanto el proceso de selección de las variantes genéticas óptimas ha de ejecutarse de forma manual y acumulativa. El proceso debe realizarse de manera federada para la selección evolutiva de los invariantes geométricos dimensionales”. La evaluación del protocolo de integración y los condicionantes geométricos obtenidos como parámetros geométricos que controlan las posibles formas compatibles se realiza mediante su aplicación en un caso práctico. El ejercicio simula la colaboración multidisciplinar con modelos federados de plataformas distintas. La elección del tamaño y complejidad constructiva del proyecto se ha modulado para poder alcanzar un desarrollo completo de cada uno de los parámetros prestacionales seleccionados. Continuando con el mismo objetivo propuesto para los parámetros prestacionales, la tipología constructiva-estructural seleccionada para el ejercicio permite la aplicación la totalidad de invariantes geométricos asociados. El objetivo de este caso práctico es evaluar la capacidad alterar la forma inicialmente propuesta mediante la evaluación del desempeño prestacional de conjunto de variantes geométricas generadas a partir de un parámetro dimensional determinado. Para que este proceso tenga sentido, cada una de las variantes debe ser previamente validada conforme a las limitaciones geométricas propias de cada sistema de fabricación y montaje previstos. El interés de las conclusiones obtenidas es la identificación de una variante geométrica distante a la solución simétrica inicialmente como la solución óptima para el conjunto de parámetros seleccionados. Al tiempo se ha comprobado como la participación de un conjunto de parámetros multi-disciplinares que representan la realidad compleja de los objetivos arquitectónicos favorecen la aparición de variaciones genéticas con prestaciones mejoradas a la intuición inicial. “La herencias tipológicas suponen un límite para la imaginación de variantes formales al proceso de ideación arquitectónica. El ejercicio realizado demuestra que incluso en casos donde aparentemente la solución óptima aparenta ser obvia una variante aleatoria puede mejorar su desempeño global. La posibilidad de conocer las condiciones geométricas de las técnicas de fabricación digital compatibles con el conjunto de parámetros seleccionados por el Arquitecto para dirigir el proceso asegura que los resultados del algoritmo evolutivo empleado sean constructivamente viables. La mejora de imaginación humana con la aportación de geometrías realmente construibles supone el objetivo último de esta tesis”. ABSTRACT Architectural form generation process is shifting from analogical to digital. Digital technology has changed the way we design empowering Architects and Engineers to precisely define any complex geometry envisioned. At the same time, the construction industry, following aeronautical and automotive industries, is implementing digital manufacturing techniques to improve efficiency and quality. Consequently construction complexity will no longer be related to geometry complexity and it is associated to coordination with digital manufacturing capacities. Unfortunately it is agreed that non-standard geometries, even when proposed with performance optimization criteria, are only suitable for projects with non-restricted budgets. Furthemore, the lack of coordinated exportation protocol and geometry management between design and construction is avoiding the globalization of emergence process in built projects Present research first objective is to identify exclusive form-generation parameters related to digital manufacturing geometrical restraints. The intention was to use geometry as the form-generation tool and integrate the digital manufacturing capacities at first stages of the project. The first chapter of this text describes the investigation historical context focusing on the influence between accurate geometry definition at non-standard forms and its construction. At first examples of non-Euclidean geometries built the communication between design and construction were based on analogical partial and imprecise documentation. Deficient communication leads to geometry adaptation on site leaving the final form uncontrolled by the Architect. Computer Aided Design enable Architects to define univocally complex geometries that previously where impossible to communicate. “The univocally definition of the Form, and communication between design and construction is essential for complex geometry Projects”. The second chapter is focused on digital technologies application in form finding process and site construction. The case studies selected identifies a clear inflexion node at 1992 with the Guggenheim Museum in Bilbao. The singularity of this project was the use of Aeronautics software to define digitally the external envelope complex geometry to enable the contractor to build it. “The digital revolution has given the Architect the capacity to design buildings beyond the architectural archetypes driven by geometric-constructive limitations. The application of digital manufacturing techniques has enabled a free-form construction without geometrical limitations. In this new context performance shall be the responsible to set new conceptual boundaries, since the behavior of each possible geometry can be compare and analyze beforehand. The role of the Architect is to prioritize the performance and architectural objectives of each project in a complete and coherent set of parameters”. Projects using digital tools for solving various stages of the design process were increased exponentially since 1992 until today. Despite the significant rise of the techniques of computer-aided design the main challenge remains linking geometries and materials proposed at each design with the capabilities of digital manufacturing techniques. Design for manufacturing in a digital environment is a mature technology in other industries such as aerospace and automotive, including consumer products and decoration, but in the construction sector is an immature and disjointed system. The peculiarities of the construction industry have not yet been addressed in its entirety and research proposals made in this area until 2015 have focused in separate parts of the process and not the total process. “The main obstacle to global standardization and implementation of a complete digital process from the form-finding to construction site is the lack of an integrated protocol that integrates manufacturing, economic and commissioning limitations, together with the performance evaluation of each possible form”. The different form generation processes are studied at chapter number 3. At the introduction of this chapter there is a specific definition of "form" for the research field. Form is identified with the outer envelope geometry, including the organizational set of connected indoor spaces connected to it. Therefore it is not exclusive of the interior. The aim of this study is to analyze and classify the main digital form generation processes using different selected projects as emblematic of each type. The approach to this process is complex, with segregated and uncoordinated different actors have to intervene application. In an analogical form-generation process parameters involved are partly conscious and partly unconscious or learned. The architect has control only over limited part of the parameters to be integrated into the design, according to their knowledge and. There is also a learned aesthetical prejudice that leads the form generation process to a specific geometry leaving the performance and optimization criteria apart from the decision making process. “Using performance evaluation digital tools during form finding process provides real-time comparative information to the Architect enabling geometry selection based on its performance. The generative form generation process described at this document does not ambition to identify the optimum geometry for each set of parameters. The objective is to provide quick information at each generation of what direction is most favorable for the performance parameters selected”. Manufacturing complexity definition in relation to a global and integral process of digital design for manufacture is essential for establishing an efficient managing protocol. “The definition of complexity associated to design for production in Architecture is proposed as the factor between number of different agents involved in the process by the number of interactions required between them, divided by the percentage of the interchange of information that is standardized and proof of information loss”. Design in architecture is a multi-objective process by definition. Therefore, addressing generation process linked to a set of non-coherent parameters requires the selection of adequate generative algorithm and the interaction of the architect. During the second half of the twentieth century and early twenty-first century it have been developed various mathematical algorithms for multi-parametric digital design. Heuristic algorithms are the most adequate algorithms for architectural projects due to its nature. The advantage of such algorithms is the ability to efficiently handle large scale optimization cases where a large number of design objectives and variables are involved. These generative processes do not pursue the optimum solution, in fact it will be impossible to proof with such algorithm. This is not a problem in architectural design where the final goal is to guide the form finding process towards a better performance within the initial direction provided by the architect. This research has focused on genetic algorithms due to its capacity to generate geometric alternatives in multiple directions and evaluate the fitness against a set of parameters specified in a single process. "Any protocol seeks to achieve standardization. The design to manufacturing protocol aims to provide a coordinated and coherent form generation process between a set of design parameters and the geometrical requirements of manufacturing technique. The protocol also provides an information exchange environment where there is a communication path and the level of information is ensured. The research is focused on the process because it is considered that each project will have its own singularities and parameters but the process will stay the same. Again the development of a specific tool is not a goal for the research, the intention is to provide an open source protocol that is valid for any set of tools”. Once the digital generation processes are being analized and classified, the next step is to identify the geometric parameters that define the digital design process. The definition of design process is including from the initial shape proposal based on the intuition of the architect to the generation, evaluation, selection and production of alternatives, both of an object , system or of the entire project . The current design process in Architecture is discontinuous and linear, dividing the process in disciplines in which the construction industry is structured. The proposal is to unify all relevant parameters in one process. The parameters are listed in groups of knowledge for internal classification but the matrix used for parameter relationship determination are combined. “A multi-parameter determination of the form-finding process is the integration all the measurable decisions laying behind Architect intuition. It is not possible to formulate and solve with an algorithm the design in Architecture. It is not the intention to do so with the proposal of this research. The process aims to integrate in one open protocol a selection of parameters by using geometry as common language. There is no optimum solution for any step of the process, the outcome is an evaluation of performance of all the form variations to assist the Architect for the selection of the preferable solution for the project”. The research follows with the geometrical restrictions of today Digital manufacturing techniques. Once determined it has been integrated in the form-finding process. “Digital manufacturing techniques are integrated in the form-finding process using geometry as common language. Geometric restraints define the boundary for performance parametric form-finding process. Geometrical limitations are classified by material and constructive system”. Choose between one digital model or several federate models is a strategic decision at planning a digital design for manufacturing protocol. Each one of the working models have strengths and weakens, nevertheless for the research purposes federated models are required to manage the different performance evaluation software platforms. A protocol based on federated models shall establish a communication process between software platforms and consultants. The manager shall integrate each discipline requirements defining the communication basis. The proposed protocol is based on standards on information exchange with singularities of the digital manufacturing industry. “The research concludes evolutionary algorithms as current best system to develop a generative form finding process based on the integration and coordination of a set of performance and constructive objectives. However, for application in professional practice and standardize it, the performance evaluation cannot be done in only one tool and therefore the selection of optimal genetic variants must be run in several iterations with a cumulative result. Consequently, the evaluation process within the geometrical restraints shall be carried out with federated models coordinated following the information exchange protocol”. The integration protocol and geometric constraints evaluation is done by applying in a practical case study. The exercise simulates multidisciplinary collaboration across software platforms with federated models. The choice of size and construction complexity of the project has been modulated to achieve the full development of each of the parameters selected. Continuing with the same objective proposed for the performance parameters the constructive and structural type selected for the exercise allows the application all geometric invariants associated to the set of parameters selected. The main goal of the case study is to proof the capacity of the manufacturing integrated form finding process to generate geometric alternatives to initial form with performance improved and following the restrictions determined by the compatible digital manufacturing technologies. The process is to be divided in consecutive analysis each one limited by the geometrical conditions and integrated in a overall evaluation. The interest of this process is the result of a non-intuitive form that performs better than a double symmetrical form. The second conclusion is that one parameter evaluation alone will not justify the exploration of complex geometry variations, but when there is a set of parameters with multidisciplinary approach then the less obvious solution emerge as the better performing form. “Architectural typologies impose limitation for Architects capacity to imagine formal variations. The case study and the research conclusions proof that even in situations where the intuitive solution apparently is the optimum solution, random variations can perform better when integrating all parameters evaluation. The capacity of foreseing the geometrical properties linking each design parameter with compatible manufacturing technologies ensure the result of the form-finding process to be constructively viable. Finally, the propose of a complete process where the geometry alternatives are generated beyond the Architect intuition and performance evaluated by a set of parameters previously selected and coordinated with the manufacturing requirements is the final objective of the Thesis”.

Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis

Signal transducer and activator of transcription (STAT) proteins perform key roles in mediating signaling by cytokines and growth factors, including platelet-derived growth factor (PDGF). In addition, Src family kinases activate STAT signaling and are required for PDGF-induced mitogenesis in normal cells. One STAT family member, Stat3, has been shown to have an essential role in cell transformation by the Src oncoprotein. However, the mechanisms by which STAT-signaling pathways contribute to mitogenesis and transformation are not fully defined. We show here that disruption of Stat3 signaling by using dominant-negative Stat3β protein in NIH 3T3 fibroblasts suppresses c-Myc expression concomitant with inhibition of v-Src-induced transformation. Ectopic expression of c-Myc is able to partially reverse this inhibition, suggesting that c-Myc is a downstream effector of Stat3 signaling in v-Src transformation. Furthermore, c-myc gene knockout fibroblasts are refractory to transformation by v-Src, consistent with a requirement for c-Myc protein in v-Src transformation. In normal NIH 3T3 cells, disruption of Stat3 signaling with dominant-negative Stat3β protein inhibits PDGF-induced mitogenesis in a manner that is reversed by ectopic c-Myc expression. Moreover, inhibition of Src family kinases with the pharmacologic agent, SU6656, blocks Stat3 activation by PDGF. These findings, combined together, delineate the signaling pathway, PDGF → Src → Stat3 → Myc, that is important in normal PDGF-induced mitogenesis and subverted in Src transformation.

Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication.

We report the isolation and characterization of CDC45, which encodes a polypeptide of 650 amino acids that is essential for the initiation of chromosomal DNA replication in the budding yeast, Saccharomyces cerevisiae. CDC45 genetically interacts with at least two members of the MCM (minichromosome maintenance) family of replication genes, CDC46 and CDC47, which are proposed to perform a role in restricting initiation of DNA replication to once per cell cycle. Like mutants in several MCM genes, alleles of CDC45 also show a severe minichromosome maintenance defect. Together, these observations imply that Cdc45p performs a role in the control of initiation events at chromosomal replication origins. We investigated this possibility further and present evidence demonstrating that Cdc45p is assembled into complexes with one MCM family member, Cdc46p/Mcm5p. These observations point to a role for Cdc45p in controlling the early steps of chromosomal DNA replication in conjunction with MCM polypeptide complexes. Unlike the MCMs, however, the subcellular localization of Cdc45p does not vary with the cell cycle, making it likely that Cdc45p interacts with MCMs only during the nuclear phase of MCM localization in G1.

GRO J1008−57: an (almost) predictable transient X-ray binary

A study of archival RXTE, Swift, and Suzaku pointed observations of the transient high-mass X-ray binary GRO J1008−57 is presented. A new orbital ephemeris based on pulse arrival-timing shows the times of maximum luminosities during outbursts of GRO J1008−57 to be close to periastron at orbital phase − 0.03. This makes the source one of a few for which outburst dates can be predicted with very high precision. Spectra of the source in 2005, 2007, and 2011 can be well described by a simple power law with high-energy cutoff and an additional black body at lower energies. The photon index of the power law and the black-body flux only depend on the 15–50 keV source flux. No apparent hysteresis effects are seen. These correlations allow us to predict the evolution of the pulsar’s X-ray spectral shape over all outbursts as a function of just one parameter, the source’s flux. If modified by an additional soft component, this prediction even holds during GRO J1008−57’s 2012 type II outburst.

The works of Thomas Middleton, now first collected,

Imperfect: frontpiece wanting. cf. v.1, p. 4211.

Maintenance Strategies for used equipment under lease

Abstract: Purpose – The aim of this research is to determine the optimal upgrade and preventive maintenance actions that minimize the total expected cost (maintenance costs+penalty costs). Design/methodology/approach – The problem is a four-parameter optimization with two parameters being k-dimensional. The optimal solution is obtained by using a four-stage approach where at each stage a one-parameter optimization is solved. Findings – Upgrading action is an extra option before the lease of used equipment, in addition to preventive maintenance action. Upgrading action makes equipment younger and preventive maintenance action lowers the ROCOF. Practical implications – There is a growing trend towards leasing equipment rather than owning it. The lease contract contains penalties if the equipment fails often and repairs are done within reasonable time period. This implies that the lessor needs to look at optimal preventive maintenance strategies in the case of new equipment lease, and upgrade actions plus preventive maintenance in the case of used equipment lease. The paper deals with this topic and is of great significant to business involved with leasing equipment. Originality/value – Nowadays many organizations are interested in leasing equipment and outsourcing maintenance. The model in this paper addresses the preventive maintenance problem for leased equipment. It provides an approach to dealing with this problem.

Contrast discrimination and pattern masking: contrast gain control with fixed additive noise

We studied the visual mechanisms that serve to encode spatial contrast at threshold and supra-threshold levels. In a 2AFC contrast-discrimination task, observers had to detect the presence of a vertical 1 cycle deg-1 test grating (of contrast dc) that was superimposed on a similar vertical 1 cycle deg-1 pedestal grating, whereas in pattern masking the test grating was accompanied by a very different masking grating (horizontal 1 cycle deg-1, or oblique 3 cycles deg-1). When expressed as threshold contrast (dc at 75% correct) versus mask contrast (c) our results confirm previous ones in showing a characteristic 'dipper function' for contrast discrimination but a smoothly increasing threshold for pattern masking. However, fresh insight is gained by analysing and modelling performance (p; percent correct) as a joint function of (c, dc) - the performance surface. In contrast discrimination, psychometric functions (p versus logdc) are markedly less steep when c is above threshold, but in pattern masking this reduction of slope did not occur. We explored a standard gain-control model with six free parameters. Three parameters control the contrast response of the detection mechanism and one parameter weights the mask contrast in the cross-channel suppression effect. We assume that signal-detection performance (d') is limited by additive noise of constant variance. Noise level and lapse rate are also fitted parameters of the model. We show that this model accounts very accurately for the whole performance surface in both types of masking, and thus explains the threshold functions and the pattern of variation in psychometric slopes. The cross-channel weight is about 0.20. The model shows that the mechanism response to contrast increment (dc) is linearised by the presence of pedestal contrasts but remains nonlinear in pattern masking.

Edge coding in human vision: a psychophysical and computational investigation

This thesis presents a study of how edges are detected and encoded by the human visual system. The study begins with theoretical work on the development of a model of edge processing, and includes psychophysical experiments on humans, and computer simulations of these experiments, using the model. The first chapter reviews the literature on edge processing in biological and machine vision, and introduces the mathematical foundations of this area of research. The second chapter gives a formal presentation of a model of edge perception that detects edges and characterizes their blur, contrast and orientation, using Gaussian derivative templates. This model has previously been shown to accurately predict human performance in blur matching tasks with several different types of edge profile. The model provides veridical estimates of the blur and contrast of edges that have a Gaussian integral profile. Since blur and contrast are independent parameters of Gaussian edges, the model predicts that varying one parameter should not affect perception of the other. Psychophysical experiments showed that this prediction is incorrect: reducing the contrast makes an edge look sharper; increasing the blur reduces the perceived contrast. Both of these effects can be explained by introducing a smoothed threshold to one of the processing stages of the model. It is shown that, with this modification,the model can predict the perceived contrast and blur of a number of edge profiles that differ markedly from the ideal Gaussian edge profiles on which the templates are based. With only a few exceptions, the results from all the experiments on blur and contrast perception can be explained reasonably well using one set of parameters for each subject. In the few cases where the model fails, possible extensions to the model are discussed.

Ocular changes and other factors relating to two forms of contact lenses:a comparative study

The work utilising a new material for contact lenses has fallen into three parts: Physioloeical considerations: Since the cornea is devoid of blood vessels, its oxygen is derived from the atmosphere. Early hydrophilic gel contact lenses interrupted the flow of oxygen and corneal insult resulted. Three techniques of fenestration were tried to overcome this problem. High speed drilling with 0.1 mm diameter twist drills. was found to be mechanically successful, but under clinical conditions mucous blockage of the fenestrations occurred. An investigation was made into the amount of oxygen arriving at the corneal interface; related to gel lens thickness. The results indicated an improvement in corneal oxygen as lens thickness was reduced. The mechanism is thought to be a form of mechanical pump. A series of clinical studies con:firmed the experimental work; the use of thin lenses removing the symptoms of corneal hypoxia. Design: The parameters of lens back curvature. lens thickness and lens diameter have been isolated and related to three criteria of vision (a) Visual acuity. (b) Visual stability and (c) Induced astigmatism. From the results achieved a revised and basically successful design of lens has been developed. Comparative study: The developed form of lens was compared with traditional lenses in a controlled survey. Twelve factors were assessed over a twenty week period of wear using a total of eighty four patients. The results of this study indicate that whilst the expected changes were noted with the traditional lens wearers, gel lens wearers showed no discernible change in any of the factors measured. ldth the exception of' one parameter. In addition to a description of' the completed l'iork. further investigations are ·sug~ested l'lhich. it is hoped. l'iould further improve the optical performance of gel lenses.

Oxidised phospholipid regulation of toll-like receptor signalling

Toll-like receptors (TLRs) serve to initiate inflammatory signalling in response to the detection of conserved microbial molecules or products of host tissue damage. Recent evidence suggests that TLR-signalling plays a considerable role in a number of inflammatory diseases, including atherosclerosis and arthritis. Agents which modulate TLR-signalling are, therefore, receiving interest in terms of their potential to modify inflammatory disease processes. One such family of molecules, the oxidised phospholipids (OxPLs), which are formed as a result of inflammatory events and accumulate at sites of chronic inflammation, have been shown to modulate TLR-signalling in both in vitro and in vivo systems. As the interaction between OxPLs and TLRs may play a significant role in chronic inflammatory disease processes, consideration is given in this review to the potential role of OxPLs in the regulation of TLR-signalling.

Dynamic models of exchange rate dependence using option prices and historical returns

Models for the conditional joint distribution of the U.S. Dollar/Japanese Yen and Euro/Japanese Yen exchange rates, from November 2001 until June 2007, are evaluated and compared. The conditional dependency is allowed to vary across time, as a function of either historical returns or a combination of past return data and option-implied dependence estimates. Using prices of currency options that are available in the public domain, risk-neutral dependency expectations are extracted through a copula repre- sentation of the bivariate risk-neutral density. For this purpose, we employ either the one-parameter \Normal" or a two-parameter \Gumbel Mixture" specification. The latter provides forward-looking information regarding the overall degree of covariation, as well as, the level and direction of asymmetric dependence. Specifications that include option-based measures in their information set are found to outperform, in-sample and out-of-sample, models that rely solely on historical returns.

Nonlinear Normalization in Limit Theorems for Extremes

2000 Mathematics Subject Classification: 60G70, 60F05.

The Deformed Trigonometric Functions of two Variables

MSC 2010: 33B10, 33E20

Measured parental weight status and familial socio-economic status correlates with childhood overweight and obesity at age 9

Background: Parental obesity is a predominant risk factor for childhood obesity. Family factors including socio-economic status (SES) play a role in determining parent weight. It is essential to unpick how shared family factors impact on child weight. This study aims to investigate the association between measured parent weight status, familial socio-economic factors and the risk of childhood obesity at age 9. Methodology/Principal Findings: Cross sectional analysis of the first wave (2008) of the Growing Up in Ireland (GUI) study. GUI is a nationally representative study of 9-year-old children (N = 8,568). Schools were selected from the national total (response rate 82%) and age eligible children (response rate 57%) were invited to participate. Children and their parents had height and weight measurements taken using standard methods. Data were reweighted to account for the sampling design. Childhood overweight and obesity prevalence were calculated using International Obesity Taskforce definitions. Multinomial logistic regression examined the association between parent weight status, indicators of SES and child weight. Overall, 25% of children were either overweight (19.3%) or obese (6.6%). Parental obesity was a significant predictor of child obesity. Of children with normal weight parents, 14.4% were overweight or obese whereas 46.2% of children with obese parents were overweight or obese. Maternal education and household class were more consistently associated with a child being in a higher body mass index category than household income. Adjusted regression indicated that female gender, one parent family type, lower maternal education, lower household class and a heavier parent weight status significantly increased the odds of childhood obesity. Conclusions/Significance: Parental weight appears to be the most influential factor driving the childhood obesity epidemic in Ireland and is an independent predictor of child obesity across SES groups. Due to the high prevalence of obesity in parents and children, population based interventions are required.

Is Trading Behavior Stable Across Contexts? Evidence from Style and Multi-Style Investors

In this paper we study priming of identity within the context of inherent vs. contextual financial decision making. We use a sample of individual trading accounts in equity-style funds taken from one fund family to test the hypothesis that trading styles are inherent vs. contextual. Our sample contains investors who invest either in a growth fund, a value fund, or both. We document behavioral differences between growth fund investors and value fund investors. We find that their trades depend on past returns in different ways: growth fund investors tend towards momentum trading and value fund investors tend towards contrarian trading. These differences may be due to inherent clientele characteristics, including beliefs about market prices, specific personality traits and cognitive strategies that cause them to self-select into one or the other style. We use a sample of investors that trade in both types of funds to test this proposition. Consistent with the contextual hypothesis, we find that investors who hold both types of funds trade growth fund shares differently than value fund shares.