Nano Aerosol Chamber for In-Vitro Toxicity (NACIVT) studies.

Abstract Inhalation of ambient air particles or engineered nanoparticles (NP) handled as powders, dispersions or sprays in industrial processes and contained in consumer products pose a potential and largely unknown risk for incidental exposure. For efficient, economical and ethically sound evaluation of health hazards by inhaled nanomaterials, animal-free and realistic in vitro test systems are desirable. The new Nano Aerosol Chamber for in-vitro Toxicity studies (NACIVT) has been developed and fully characterized regarding its performance. NACIVT features a computer-controlled temperature and humidity conditioning, preventing cellular stress during exposure and allowing long-term exposures. Airborne NP are deposited out of a continuous air stream simultaneously on up to 24 cell cultures on Transwell® inserts, allowing high-throughput screening. In NACIVT, polystyrene as well as silver particles were deposited uniformly and efficiently on all 24 Transwell® inserts. Particle-cell interaction studies confirmed that deposited particles reach the cell surface and can be taken up by cells. As demonstrated in control experiments, there was no evidence for any adverse effects on human bronchial epithelial cells (BEAS-2B) due to the exposure treatment in NACIVT. The new, fully integrated and transportable deposition chamber NACIVT provides a promising tool for reliable, acute and sub-acute dose-response studies of (nano)particles in air-exposed tissues cultured at the air-liquid interface.

Exposure of silver-nanoparticles and silver-ions to lung cells in vitro at the air-liquid interface

BACKGROUND: Due to its antibacterial properties, silver (Ag) has been used in more consumer products than any other nanomaterial so far. Despite the promising advantages posed by using Ag-nanoparticles (NPs), their interaction with mammalian systems is currently not fully understood. An exposure route via inhalation is of primary concern for humans in an occupational setting. Aim of this study was therefore to investigate the potential adverse effects of aerosolised Ag-NPs using a human epithelial airway barrier model composed of A549, monocyte derived macrophage and dendritic cells cultured in vitro at the air-liquid interface. Cell cultures were exposed to 20 nm citrate-coated Ag-NPs with a deposition of 30 and 278 ng/cm2 respectively and incubated for 4 h and 24 h. To elucidate whether any effects of Ag-NPs are due to ionic effects, Ag-Nitrate (AgNO3) solutions were aerosolised at the same molecular mass concentrations. RESULTS: Agglomerates of Ag-NPs were detected at 24 h post exposure in vesicular structures inside cells but the cellular integrity was not impaired upon Ag-NP exposures. Minimal cytotoxicity, by measuring the release of lactate dehydrogenase, could only be detected following a higher concentrated AgNO3-solution. A release of pro-inflammatory markers TNF-alpha and IL-8 was neither observed upon Ag-NP and AgNO3 exposures as well as was not affected when cells were pre-stimulated with lipopolysaccharide (LPS). Also, an induction of mRNA expression of TNF-alpha and IL-8, could only be observed for the highest AgNO3 concentration alone or even significantly increased when pre-stimulated with LPS after 4 h. However, this effect disappeared after 24 h. Furthermore, oxidative stress markers (HMOX-1, SOD-1) were expressed after 4 h in a concentration dependent manner following AgNO3 exposures only. CONCLUSIONS: With an experimental setup reflecting physiological exposure conditions in the human lung more realistic, the present study indicates that Ag-NPs do not cause adverse effects and cells were only sensitive to high Ag-ion concentrations. Chronic exposure scenarios however, are needed to reveal further insight into the fate of Ag-NPs after deposition and cell interactions.

Polybrominated diphenyl ether (PBDE) exposure in North Americans: Cause for concern?

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants (BFRs) that have been widely produced and used as flame retardants since the 1970’s in many consumer products such as carpet and drape linings, plastics used in electronics, computer and television casings and polyurethane foam used in chairs, sofas and mattresses. PBDEs are persistent organic pollutants (POPs), which, by definition, are toxic in nature, persistent in the environment and accumulative in living organisms. Animal studies have found PBDEs to cause health defects such as fetal malformations, delayed onset of puberty, decreased sperm count, behavioral changes, permanent learning and memory impairment, endocrine disruption, as well as cancer at high doses. Recent research involving humans reported that elevated breast milk PBDEs levels in their mothers are associated with cryptorchidism (absence of one or both testes from the scrotum) in newborn boys and adverse birth outcomes as well as elevated serum PBDE levels in mothers are associated with low sperm count in young men. There are three commonly manufactured PBDE commercial mixtures: Penta-, Octa-, and Deca-BDEs. Two of them (Octa- and Penta-BDEs) have been banned by the European Union and are being voluntarily phased out in the United States. However, Deca continues to be manufactured, used, and imported in the United States. This MPH thesis consists of a literature review of peer reviewed scientific articles concerned with PBDEs in the environment and in humans, as well as a discussion concerning different routes of exposure to PBDEs and their blood, milk and tissue levels as surrogates for body burdens in North Americans and in people from other countries. Results of this literature review shows PBDE levels in human blood, milk and tissues are higher in North Americans than people from other countries worldwide. To date, the highest level of PBDEs was found in a toddler’s blood in a California study. Despite the fact that PBDEs are associated with adverse health effects, and highest levels of PBDEs in North Americans, Deca-BDE is still manufactured, used and imported in the United States. There is an urgent need of new federal regulatory policy to ban completely the production, importation and use of all commercial mixtures of PBDEs.^

AN INVESTIGATION OF VOLATILE ORGANIC AIR CONTAMINANTS IN THE INDOOR MANUFACTURED HOUSING ENVIRONMENT (TEXAS)

Manufactured housing has been found to have substantial levels of formaldehyde in the indoor air. Because mobile homes are more affordable than conventional housing, there has been a large increase in their use in the U.S. This increase in mobile home use has been substantial in the sunbelt regions such as Texas, where high temperatures and humidities may enhance out-gassing of formaldehyde and other volatile organic compounds from construction and furnishing materials and increase any potential health hazards.^ The influences of environmental, architectural and temporal factors on the presence of indoor formaldehyde and other organic compounds were investigated in conjunction with the Texas Indoor Air Quality Study of manufactured housing. A matched pair of mobile homes, one with electric heating and cooking utilities and the other with propane gas utilities, were used for a series of controlled experiments over a fourteen month period from October, 1982 through November, 1983.^ Over this fourteen month period formaldehyde levels decreased approximately 33%. Daily fluctuations of 20% to 40% were observed even with a constant indoor temperature. An increase in indoor temperature of 8(DEGREES)C doubled the measured formaldehyde concentration. Opening windows resulted in decreases of indoor formaldehyde levels of up to 50%. Studies of the impact of propane as a cooking source showed no increase in formaldehyde levels with stove use.^ The presence and concentration of selected volatile organic compounds is influenced greatest by occupancy. Occupants continually open and close windows and doors, vary the operation and settings (temperature) of air control systems, and vary in their selection of furnishings and use of consumer products, which may act as sources of indoor air contaminants. ^

The Interior City Infinity and Concavity in the No-Stop City (1970-1971)

In the late 60s it had become clear how the environment technification had allowed some typologies (supermarkets, car parks, factories) to reach potentially unlimited built depths becoming, therefore, independent from the outside. The No-Stop City is born from a very simple idea: to extend this technification to the totality of built reality encompassing, not only almost all functions, but ultimately, the whole city. This operation has paradoxical effects: as architecture grows, it loses most of the features that have traditionally defined it. A dissolution by hypertrophy that gives rise to an homogeneous, concave and potentially infinite space. But beyond the pure technical feasibility, there are two key influences, seemingly contradictory, that explain this endeavor for an interior and endless city: Marxism and Pop Art. The project is, in many senses, a built manifesto reflecting the militancy of the group members within the Italian Marxism. But it is also the embodiment of the groups declared interest in Pop Art, popular culture and mass society. The cross-influence of communism and consumerism explains this "quantitative utopia" in which the society and the factory, the production and consumption, would match. A city based on the centrality of consumer products and the subsequent loss of prominence of architecture, in which the urban phenomenon, while spreading endlessly over territory, ignoring its rural exteriority, dissolves the home as a sphere of privacy, ignoring its domestic interiority. A project, also in the wake of Marshall McLuhan, that illustrates like few others the conversion of the urbane into a virtually omnipresent "condition" and that still interrogates us with questions that are, on the other hand, eternal: What is a building? What is a city?

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”.

SILVER NANOPARTICLES AND THE PLANT-ASSOCIATING ABILITIES OF RHIZOBIACEAE BACTERIA

The use of nanoparticle technology in consumer products has been increasing due to their broad-spectrum antimicrobial properties. Specifically, silver nanoparticles (AgNPs) can demonstrate distinct physiochemical properties compared to bulk silver, including a large surface area to volume ratio that allows for higher reactivity with bacterial cell surfaces. AgNPs are being released into the environment, including soil ecosystems through various pathways such as points of production or during disposal of silver-containing products. This raises the concern about the potential impact on beneficial soil bacteria and their surrounding ecosystems. Members of the Rhizobiaceae family play important roles in nutrient cycling and contribute to overall soil fertility and the experiments in this thesis address the potential for AgNP-mediated toxicity on these plant-associating bacteria. Respiration analysis of Bradyrhizobium japonicum, Azospirillum brasilense, and Agrobacterium tumefaciens has revealed that AgNPs can negatively impact the growth and survival of these bacterial species, with B. japonicum being the most susceptible. Additionally, swimming motility assays using B. japonicum showed a significant decrease in colony diameter when treated with AgNPs (50 ppm). A significant decrease in root colonization of Triticum aestivum roots by A. brasilense was observed as AgNP treatment concentrations increased. Although some of the experiments could not be completed, taken together, these experiments and the research reported herein highlights the potential toxicological effects of AgNPs on bacterial species vital to the growth and health of agriculturally important crops.

Energy budget procedures and performance criteria for energy conserving building illumination systems /

"April 1980, issued May 1980."

Final report on the "Motion transformer".

"A cooperative project between Office of Production Research and Development, Consumer Products Branch, War Production Board; the Utah Scientific Research Foundation; and the Utah State Engineering Experiment Station of the Utah State Agricultural College."-Intro.

Fixed Site Amusement Rides: Who Regulates Safety?

There is currently no national regulation of fixed site (ex. roller coaster) amusement ride safety. The current regulatory system is highly fragmented and consists of many disparate efforts by State and local agencies, judicial intervention in the form of tort litigation and industry self regulatory compliance. The Federal government has no authority over fixed site ride safety. The authors review the state of fixed site ride regulation and the merits of both centralized and de-centralized regulation, including a proposed Federal statute conferring jurisdiction of the matter upon the Consumer Products Safety Commission. They conclude with proposals for enhancing the management of fixed site ride safety.

Development of a Lab-on-a-Chip Device for Rapid Nanotoxicity Assessment In Vitro

Increasing useof nanomaterials in consumer products and biomedical applications creates the possibilities of intentional/unintentional exposure to humans and the environment. Beyond the physiological limit, the nanomaterialexposure to humans can induce toxicity. It is difficult to define toxicity of nanoparticles on humans as it varies by nanomaterialcomposition, size, surface properties and the target organ/cell line. Traditional tests for nanomaterialtoxicity assessment are mostly based on bulk-colorimetric assays. In many studies, nanomaterials have found to interfere with assay-dye to produce false results and usually require several hours or days to collect results. Therefore, there is a clear need for alternative tools that can provide accurate, rapid, and sensitive measure of initial nanomaterialscreening. Recent advancement in single cell studies has suggested discovering cell properties not found earlier in traditional bulk assays. A complex phenomenon, like nanotoxicity, may become clearer when studied at the single cell level, including with small colonies of cells. Advances in lab-on-a-chip techniques have played a significant role in drug discoveries and biosensor applications, however, rarely explored for nanomaterialtoxicity assessment. We presented such cell-integrated chip-based approach that provided quantitative and rapid response of cellhealth, through electrochemical measurements. Moreover, the novel design of the device presented in this study was capable of capturing and analyzing the cells at a single cell and small cell-population level. We examined the change in exocytosis (i.e. neurotransmitterrelease) properties of a single PC12 cell, when exposed to CuOand TiO2 nanoparticles. We found both nanomaterials to interfere with the cell exocytosis function. We also studied the whole-cell response of a single-cell and a small cell-population simultaneously in real-time for the first time. The presented study can be a reference to the future research in the direction of nanotoxicity assessment to develop miniature, simple, and cost-effective tool for fast, quantitative measurements at high throughput level. The designed lab-on-a-chip device and measurement techniques utilized in the present work can be applied for the assessment of othernanoparticles' toxicity, as well.

The Effects of Brominated Flame Retardants on Thyroid Hormone Homeostasis in Human Placenta Tissues and Cell Culture

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) that have been heavily used in consumer products such as furniture foams, plastics, and textiles since the mid-1970’s. BFRs are added to products in order to meet state flammability standards intended to increase indoor safety in the event of a fire. The three commercial PBDE mixtures, Penta-, Octa-, and DecaBDE, have all been banned in the United States, however, limited use of DecaBDE is still permitted. PBDEs were phased out of production and added to the Stockholm Convention due to concerns over their environmental persistence and toxicity. Human exposure to PBDEs occurs primarily through the inadvertent ingestion of contaminated house dust, as well as though dietary sources. Despite the phase-out and discontinued use of PBDEs, human exposure to this class of chemicals is likely to continue for decades due to the continued use of treated products and existing environmental reservoirs of PBDEs. Extensive research over the years has shown that PBDEs disrupt thyroid hormone (TH) levels and neurodevelopmental endpoints in rodent and fish models. Additionally, there is growing epidemiological evidence linking PBDE exposure in humans to altered TH homeostasis and neurodevelopmental impairments in children. Due to the importance of THs throughout gestation, there is a great need to understand the effects of BFRs on the developing fetus. Specifically, the placenta plays a critical role in the transport, metabolism, and delivery of THs to the fetal compartment during pregnancy and is a likely target for BFR bioaccumulation and endocrine disruption. The central hypothesis of this dissertation research is that BFRs disrupt the activity of TH sulfotransferase (SULT) enzymes, thereby altering TH concentrations in the placenta.

In the first aim of this dissertation research, the concentrations of PBDEs and 2,4,6-TBP were measured in a cohort of 102 placenta tissue samples from an ongoing pregnancy cohort in Durham, NC. Methods were developed for the extraction and analysis of the BFR analytes. It was found that 2,4,6-TBP was significantly correlated with all PBDE analytes, indicating that 2,4,6-TBP may share common product applications with PBDEs or that 2,4,6-TBP is a metabolite of PBDE compounds. Additionally, this was the first study to measure 2,4,6-TBP in human placenta tissues.

In the second aim of this dissertation research, the placenta tissue concentrations of THs, as well as the endogenous activity of deiodinase (DI) and TH SULT enzymes were quantified using the same cohort of 102 placenta tissue samples. Enzyme activity was detected in all samples and this was the first study to measure TH DI and SULT activity in human placenta tissues. Enzyme activities and TH concentrations were compared with BFR concentrations measured in Aim 1. There were few statistically significant associations observed for the combined data, however, upon stratifying the data set based on infant sex, additional significant associations were observed. For example, among males, those with the highest concentrations of BDE-99 in placenta had T3 levels 0.80 times those with the lowest concentration of BDE-99 (95% confidence interval (CI): 0.59, 1.07). Whereas females with the highest concentrations of BDE-99 in placenta had T3 levels 1.50 times those with the lowest concentration of BDE-99 (95% CI: 1.10, 2.04). Additionally, all BFR analyte concentrations were higher in the placenta of males versus females and they were significantly higher for 2,4,6-TBP and BDE-209. 3,3’-T2 SULT activity was significantly higher in female placenta tissues, while type 3 DI activity was significantly higher in male placenta tissues. This research is the first to show sex-specific differences in the bioaccumulation of BFRs in human placenta tissue, as well as differences in TH concentrations and endogenous DI and SULT activity. The underlying mechanisms of these observed sex differences warrant further investigation.

In the third aim of this dissertation research, the effects of BFRs were examined in a human choriocarcinoma placenta cell line, BeWo. Michaelis-Menten parameters and inhibition curves were calculated for 2,4,6-TBP, 3-OH BDE-47, and 6-OH BDE-47. 2,4,6-TBP was shown to be the most potent inhibitor of 3,3’-T2 SULT activity with a calculated IC50 value of 11.6 nM. It was also shown that 2,4,6-TBP and 3-OH BDE-47 exhibit mixed inhibition of 3,3’-T2 sulfation in BeWo cell homogenates. Next, a series of cell culture exposure experiments were performed using 1, 6, 12, and 24 hour exposure durations. Once again, 2,4,6-TBP was shown to be the most potent inhibitor of basal 3,3’-T2 SULT activity by significantly decreasing activity at the high and medium dose (1 M and 0.5 M, respectively) at all measured time points. Interestingly, BDE-99 was also shown to inhibit basal 3,3’-T2 SULT activity in BeWo cells following the 24 hour exposure, despite exhibiting no inhibitory effects in the BeWo cell homogenate experiments. This indicates that BDE-99 must act through a pathway other than direct enzyme inhibition. Following exposures, the TH concentrations in the cell culture growth media and mRNA expression of TH-related genes were also examined. There was no observed effect of BFR treatment on these endpoints. Future work should focus on determining the downstream biological effects of TH SULT disruption in placental cells, as well as the underlying mechanisms of action responsible for reductions in basal TH SULT activity following BFR exposure.

This was one of the first studies to measure BFRs in a cohort of placenta tissue samples from the United States and the first study to measure THs, DI activity, and SULT activity in human placenta tissues. This research provides a novel contribution to our growing understanding of the effects of BFRs on TH homeostasis within the human placenta, and provides further evidence for sex-specific differences within this important organ. Future research should continue to investigate the effects of environmental contaminants on TH homeostasis within the placenta, as this represents the most critical and vulnerable stage of human development.

Organic functionalisation, doping and characterisation of semiconductor surfaces for future CMOS device applications

Organic Functionalisation, Doping and Characterisation of Semiconductor Surfaces for Future CMOS Device Applications Semiconductor materials have long been the driving force for the advancement of technology since their inception in the mid-20th century. Traditionally, micro-electronic devices based upon these materials have scaled down in size and doubled in transistor density in accordance with the well-known Moore’s law, enabling consumer products with outstanding computational power at lower costs and with smaller footprints. According to the International Technology Roadmap for Semiconductors (ITRS), the scaling of metal-oxide-semiconductor field-effect transistors (MOSFETs) is proceeding at a rapid pace and will reach sub-10 nm dimensions in the coming years. This scaling presents many challenges, not only in terms of metrology but also in terms of the material preparation especially with respect to doping, leading to the moniker “More-than-Moore”. Current transistor technologies are based on the use of semiconductor junctions formed by the introduction of dopant atoms into the material using various methodologies and at device sizes below 10 nm, high concentration gradients become a necessity. Doping, the controlled and purposeful addition of impurities to a semiconductor, is one of the most important steps in the material preparation with uniform and confined doping to form ultra-shallow junctions at source and drain extension regions being one of the key enablers for the continued scaling of devices. Monolayer doping has shown promise to satisfy the need to conformally dope at such small feature sizes. Monolayer doping (MLD) has been shown to satisfy the requirements for extended defect-free, conformal and controllable doping on many materials ranging from the traditional silicon and germanium devices to emerging replacement materials such as III-V compounds This thesis aims to investigate the potential of monolayer doping to complement or replace conventional doping technologies currently in use in CMOS fabrication facilities across the world.

SILVER NANOPARTICLES AND THE PLANT-ASSOCIATING ABILITIES OF RHIZOBIACEAE BACTERIA

The use of nanoparticle technology in consumer products has been increasing due to their broad-spectrum antimicrobial properties. Specifically, silver nanoparticles (AgNPs) can demonstrate distinct physiochemical properties compared to bulk silver, including a large surface area to volume ratio that allows for higher reactivity with bacterial cell surfaces. AgNPs are being released into the environment, including soil ecosystems through various pathways such as points of production or during disposal of silver-containing products. This raises the concern about the potential impact on beneficial soil bacteria and their surrounding ecosystems. Members of the Rhizobiaceae family play important roles in nutrient cycling and contribute to overall soil fertility and the experiments in this thesis address the potential for AgNP-mediated toxicity on these plant-associating bacteria. Respiration analysis of Bradyrhizobium japonicum, Azospirillum brasilense, and Agrobacterium tumefaciens has revealed that AgNPs can negatively impact the growth and survival of these bacterial species, with B. japonicum being the most susceptible. Additionally, swimming motility assays using B. japonicum showed a significant decrease in colony diameter when treated with AgNPs (50 ppm). A significant decrease in root colonization of Triticum aestivum roots by A. brasilense was observed as AgNP treatment concentrations increased. Although some of the experiments could not be completed, taken together, these experiments and the research reported herein highlights the potential toxicological effects of AgNPs on bacterial species vital to the growth and health of agriculturally important crops.

Nanotechnology in the food industry I: applications

Nanotechnology is a multidisciplinary science that is having a boom today, providing new products with attractive physicochemical properties for many applications. In agri/feed/food sector, nanotechnology offers great opportunities for obtaining products and innovative applications for agriculture and livestock, water treatment and the production, processing, storage and packaging of food. To this end, a wide variety of nanomaterials, ranging from metals and inorganic metal oxides to organic nanomaterials carrying bioactive ingredients are applied. This review shows an overview of current and future applications of nanotechnology in the food industry. Food additives and materials in contact with food are now the main applications, while it is expected that in the future are in the field of nano-encapsulated and nanocomposites in applications as novel foods, additives, biocides, pesticides and materials food contact.