Design, synthesis and biological evaluation of 5$\sp\prime$-mononucleotide prodrugs: Strategies to introduce nucleotides into cells

The neutral bis ((pivaloyloxy)methyl) (PIV$\sb2\rbrack$ derivatives of FdUMP, ddUMP, and AZTMP were synthesized as potential membrane-permeable prodrugs of FdUMP, ddUMP, and AZTMP. These compounds were designed to enter cells by passive diffusion and revert to the parent nucleotides after removal of the PIV groups by hydrolytic enzymes. These prodrugs were prepared by condensation of FUdR, ddU, and AZT with PIV$\sb2$ phosphate in the presence of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobo reagent). PIV$\sb2$-FdUMP, PIV$\sb2$-ddUMP, and PIV$\sb2$-AZTMP were stable in the pH range 1.0-4.0 (t$\sb{1/2} = {>}$100 h). They were also fairly stable at pH 7.4 (t$\sb{1/2} = {>}$40 h). In 0.05 M NaOH solution, however, they were rapidly degraded (t$\sb{1/2} < 2$ min). In the presence hog liver carboxylate esterase, they were converted quantitatively to the corresponding phosphodiesters, PIV$\sb1$-FdUMP, PIV$\sb1$-ddUMP, and PIV$\sb1$-AZTMP; after 24 h incubation, only trace amounts of FdUMP, ddUMP, and AZTMP (1-5%) were observed indicating that the PIV$\sb1$ compounds were poor substrates for the enzyme. In human plasma, the PIV$\sb2$ compounds were rapidly degraded with half-lives of less than 5 min. The rate of degradation of the PIV$\sb2$ compounds in the presence of phosphodiesterase I was the same as that in buffer controls, indicating that they were not substrates for this enzyme. In the presence of phosphodiesterase I, PIV$\sb1$-FdUMP, PIV$\sb1$-ddUMP, and PIV$\sb1$-AZTMP were converted quantitatively to FdUMP, ddUMP, and AZTMP.^ PIV$\sb2$-ddUMP and PIV$\sb2$-AZTMP were effective at controlling HIV type 1 infection in MT-4 and CEM tk$\sp-$ cells in culture. Mechanistic studies demonstrated that PIV$\sb2$-ddUMP and PIV$\sb2$-AZTMP were taken up by the cells and converted to ddUTP and AZTTP, both potent inhibitors of HIV reverse transcriptase. However, a potential shortcoming of PIV$\sb2$-ddUMP and PIV$\sb2$-AZTMP as clinical therapeutic agents is that they are rapidly degraded (t$\sb{1/2}$ = approx. 4 minutes) in human plasma by carboxylate esterases. To circumvent this limitation, chemically-labile nucleotide prodrugs and liposome-encapsulated nucleotide prodrugs were investigated. In the former approach, the protective groups bis(N, N-(dimethyl)carbamoyloxymethyl) (DM$\sb2$) and bis (N-(piperidino)carbamoyloxymethyl) (DP$\sb2$) were used to synthesize DM$\sb2$-ddUMP and DP$\sb2$-ddUMP, respectively. In aqueous buffers (pH range 1.0-9.0) these compounds were degraded with half-lives of 3 to 4 h. They had similar half-lives in human plasma demonstrating that they were resistant to esterase-mediated cleavage. However, neither compound gave rise to significant concentrations of ddUMP in CEM or CEM tk$\sp-$ cells. In the liposome-encapsulated nucleotide prodrug approach, three different liposomal formulations of PIV$\sb2$-ddUMP (L-PIV$\sb2$-ddUMP) were investigated. The half-lifes of these L-PIV$\sb2$-ddUMP preparations in human plasma were 2 h compared with 4 min for the free drug. The preparations were more effective at controlling HIV-1 infection than free PIV$\sb2$-ddUMP in human T cells in culture. Collectively, these data indicate that PIV$\sb2$-FdUMP, PIV$\sb2$-ddUMP, and PIV$\sb2$-AZTMP are effective membrane-permeable prodrugs of FdUMP, ddUMP, and AZTMP. ^

Epidemiology of allergic gastroenteritis in socio-culture perspective of rural Egypt

Diarrhea is a major public health problem in developing countries among infants and young children. Not all episodes of diarrhea are confirmed as infectious, suggesting alternate mechanisms. One such is immunoglobulin E (IgE) mediated or allergic diarrhea that can be seen in food allergy. In order to determine the relation between allergic gastroenteritis and feeding practice, a cohort of 152 infants were followed from birth to one year age in a rural community of Egypt between October, 1987 to April, 1988 were analyzed. In multivariate analysis of the data, statistically conclusive higher risk had been observed with presence of factors, like consumption of milk pudding (RR = 7.4, CI = 1.5-36.2 and p = 0.01), infant's age 3-6 months (RR = 7.7, CI = 1.3-45.9 and p = 0.02), infants whose mothers were vaccinated antenatally (RR = 3.1, CI = 1.3-7.0 and p = 1.3-7.0, p = 0.0) and wet-nursed infants (RR = 2.7, CI = 1.1-6.5 and p = 0.02). In contrast, infants who were completely breast-fed (RR = 0.13, CI = 0.02-0.6 and p = 0.01), and infants family owning a television set (RR = 0.29, CI = 0.1-0.6 and p = 0.0) were less likely to develop allergic gastroenteritis. The role of IgE on development of persistent diarrhea was also examined in a nested case-control design. Multivariate analysis revealed a significant association between detection of fecal IgE and development of persistent diarrhea compared to acute diarrhea (OR = 3.32, CI = 1.0-10.9 and p = 0.04) and health or non diarrhea (OR = 4.8, CI = 1.07-21.7 and p = 0.03) controls. ^

Design, Synthesis and Development of Transporter Targeting Agents for Image-guided Therapy and Drug Delivery

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with 99mTc and 68Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both 99mTc-N4amG and 99mTc-GP were stable up to 6 hours, whereas 68Ga-GP was stable up to 2 hours. Cell culture studies confirmed radiolabeled N4amG and GP could penetrate the cell membrane through nucleoside transporters and amino acid transporters, respectively. Up to 40% of intracellular 99mTc-N4amG and 99mTc-GP was found within cell nucleus following 2 hours of incubation. Flow cytometry analysis revealed 99mTc-N4amG was a cell cycle S phase-specific agent. There was a significant difference of the uptake of 99mTc-GP between pre- and post- paclitaxel-treated cells, which suggests that 99mTc-GP may be useful in chemotherapy treatment monitoring. Moreover, radiolabeled N4amG and GP were tested in vivo using tumor-bearing animal models. 99mTc-N4amG showed an increase in tumor-to-muscle count density ratios up to 5 at 4 hour imaging. Both 99mTc-labeled agents showed decreased tumor uptake after paclitaxel treatment. Immunohistochemistry analysis demonstrated that the uptake of 99mTc-N4amG was correlated with Ki-67 expression. Both 99mTc-N4amG and 99mTc-GP could differentiate between tumor and inflammation in animal studies. Furthermore, 68Ga-GP was compared to 18F-FDG in rabbit PET imaging studies. 68Ga-GP had lower tumor standardized uptake values (SUV), but similar uptake dynamics, and different biodistribution compared with 18F-FDG. Finally, to demonstrate that GP can be a potential drug carrier for cancer theranostics, several drugs, including doxorubicin, were selected to be conjugated to GP. Imaging studies demonstrated that tumor uptake of GP-drug conjugates was increased as a function of time. GP-doxorubicin (GP-DOX) showed a slow-release pattern in in vitro cytotoxicity assay and exhibited anti-cancer efficacy with reduced toxicity in in vivo tumor growth delay study. In conclusion, both N4amG and GP are transporter-based targeting agents. Radiolabeled N4amG can be used for tumor cell proliferation assessment. GP is a potential agent for image-guided therapy and drug delivery.

An Analysis of the Influence of Students´ Technological Culture on Their Technology

decade has raised the interest among the research community on the acceptance and use of these systems by both teachers and students. At first, the implementation of LMS was based on their technical design and the adaptation of the learning processes to the virtual environment, neglecting students’ characteristics when the systems were deployed, which led to expensive and failing implementations. The Unified Theory of Acceptance and Use of Technology (UTAUT) proposes a framework which allows the study of the acceptance and use of technology that takes into consideration the students’ characteristics and how they affect the acceptance and the degree of use of educational technology. This study questions the role of the user’s attitude towards use of LMS and uses the UTAUT to examine the moderating effect of technological culture in the adoption of LMS in Spain. The results from the comparison and analysis of three different models confirm the relevance of attitude towards use as an antecedent of intention to use the system, as well as the important moderating effect of gender and technological culture. The discussion of results suggests the need for a more in-depth analysis and interrelations of cultural dimensions in the adoption of educational technologies and learning management systems

Contribution to the design of waveguide-fed compound-slot arrays by means of equivalent circuit modelling

Los arrays de ranuras son sistemas de antennas conocidos desde los años 40, principalmente destinados a formar parte de sistemas rádar de navíos de combate y grandes estaciones terrenas donde el tamaño y el peso no eran altamente restrictivos. Con el paso de los años y debido sobre todo a importantes avances en materiales y métodos de fabricación, el rango de aplicaciones de este tipo de sistemas radiantes creció en gran medida. Desde nuevas tecnologías biomédicas, sistemas anticolisión en automóviles y navegación en aviones, enlaces de comunicaciones de alta tasa binaria y corta distancia e incluso sistemas embarcados en satélites para la transmisión de señal de televisión. Dentro de esta familia de antennas, existen dos grupos que destacan por ser los más utilizados: las antennas de placas paralelas con las ranuras distribuidas de forma circular o espiral y las agrupaciones de arrays lineales construidos sobre guia de onda. Continuando con las tareas de investigación desarrolladas durante los últimos años en el Instituto de Tecnología de Tokyo y en el Grupo de Radiación de la Universidad Politécnica de Madrid, la totalidad de esta tesis se centra en este último grupo, aunque como se verá se separa en gran medida de las técnicas de diseño y metodologías convencionales. Los arrays de ranuras rectas y paralelas al eje de la guía rectangular que las alimenta son, sin ninguna duda, los modelos más empleados debido a la fiabilidad que presentan a altas frecuencias, su capacidad para gestionar grandes cantidades de potencia y la sencillez de su diseño y fabricación. Sin embargo, también presentan desventajas como estrecho ancho de banda en pérdidas de retorno y rápida degradación del diagrama de radiación con la frecuencia. Éstas son debidas a la naturaleza resonante de sus elementos radiantes: al perder la resonancia, el sistema global se desajusta y sus prestaciones degeneran. En arrays bidimensionales de slots rectos, el campo eléctrico queda polarizado sobre el plano transversal a las ranuras, correspondiéndose con el plano de altos lóbulos secundarios. Esta tesis tiene como objetivo el desarrollo de un método sistemático de diseño de arrays de ranuras inclinadas y desplazadas del centro (en lo sucesivo “ranuras compuestas”), definido en 1971 como uno de los desafíos a superar dentro del mundo del diseño de antennas. La técnica empleada se basa en el Método de los Momentos, la Teoría de Circuitos y la Teoría de Conexión Aleatoria de Matrices de Dispersión. Al tratarse de un método circuital, la primera parte de la tesis se corresponde con el estudio de la aplicabilidad de las redes equivalentes fundamentales, su capacidad para recrear fenómenos físicos de la ranura, las limitaciones y ventajas que presentan para caracterizar las diferentes configuraciones de slot compuesto. Se profundiza en las diferencias entre las redes en T y en ! y se condiciona la selección de una u otra dependiendo del tipo de elemento radiante. Una vez seleccionado el tipo de red a emplear en el diseño del sistema, se ha desarrollado un algoritmo de cascadeo progresivo desde el puerto alimentador hacia el cortocircuito que termina el modelo. Este algoritmo es independiente del número de elementos, la frecuencia central de funcionamiento, del ángulo de inclinación de las ranuras y de la red equivalente seleccionada (en T o en !). Se basa en definir el diseño del array como un Problema de Satisfacción de Condiciones (en inglés, Constraint Satisfaction Problem) que se resuelve por un método de Búsqueda en Retroceso (Backtracking algorithm). Como resultado devuelve un circuito equivalente del array completo adaptado a su entrada y cuyos elementos consumen una potencia acorde a una distribución de amplitud dada para el array. En toda agrupación de antennas, el acoplo mutuo entre elementos a través del campo radiado representa uno de los principales problemas para el ingeniero y sus efectos perjudican a las prestaciones globales del sistema, tanto en adaptación como en capacidad de radiación. El empleo de circuito equivalente se descartó por la dificultad que suponía la caracterización de estos efectos y su inclusión en la etapa de diseño. En esta tesis doctoral el acoplo también se ha modelado como una red equivalente cuyos elementos son transformadores ideales y admitancias, conectada al conjunto de redes equivalentes que representa el array. Al comparar los resultados estimados en términos de pérdidas de retorno y radiación con aquellos obtenidos a partir de programas comerciales populares como CST Microwave Studio se confirma la validez del método aquí propuesto, el primer método de diseño sistemático de arrays de ranuras compuestos alimentados por guía de onda rectangular. Al tratarse de ranuras no resonantes, el ancho de banda en pérdidas de retorno es mucho mas amplio que el que presentan arrays de slots rectos. Para arrays bidimensionales, el ángulo de inclinación puede ajustarse de manera que el campo quede polarizado en los planos de bajos lóbulos secundarios. Además de simulaciones se han diseñado, construido y medido dos prototipos centrados en la frecuencia de 12GHz, de seis y diez elementos. Las medidas de pérdidas de retorno y diagrama de radiación revelan excelentes resultados, certificando la bondad del método genuino Method of Moments - Forward Matching Procedure desarrollado a lo largo de esta tésis. Abstract The slot antenna arrays are well known systems from the decade of 40s, mainly intended to be part of radar systems of large warships and terrestrial stations where size and weight were not highly restrictive. Over the years, mainly due to significant advances in materials and manufacturing methods, the range of applications of this type of radiating systems grew significantly. From new biomedical technologies, collision avoidance systems in cars and aircraft navigation, short communication links with high bit transfer rate and even embedded systems in satellites for television broadcast. Within this family of antennas, two groups stand out as being the most frequent in the literature: parallel plate antennas with slots placed in a circular or spiral distribution and clusters of waveguide linear arrays. To continue the vast research work carried out during the last decades in the Tokyo Institute of Technology and in the Radiation Group at the Universidad Politécnica de Madrid, this thesis focuses on the latter group, although it represents a technique that drastically breaks with traditional design methodologies. The arrays of slots straight and parallel to the axis of the feeding rectangular waveguide are without a doubt the most used models because of the reliability that they present at high frequencies, its ability to handle large amounts of power and their simplicity of design and manufacturing. However, there also exist disadvantages as narrow bandwidth in return loss and rapid degradation of the radiation pattern with frequency. These are due to the resonant nature of radiating elements: away from the resonance status, the overall system performance and radiation pattern diminish. For two-dimensional arrays of straight slots, the electric field is polarized transverse to the radiators, corresponding to the plane of high side-lobe level. This thesis aims to develop a systematic method of designing arrays of angled and displaced slots (hereinafter "compound slots"), defined in 1971 as one of the challenges to overcome in the world of antenna design. The used technique is based on the Method of Moments, Circuit Theory and the Theory of Scattering Matrices Connection. Being a circuitry-based method, the first part of this dissertation corresponds to the study of the applicability of the basic equivalent networks, their ability to recreate the slot physical phenomena, their limitations and advantages presented to characterize different compound slot configurations. It delves into the differences of T and ! and determines the selection of the most suitable one depending on the type of radiating element. Once the type of network to be used in the system design is selected, a progressive algorithm called Forward Matching Procedure has been developed to connect the proper equivalent networks from the feeder port to shorted ending. This algorithm is independent of the number of elements, the central operating frequency, the angle of inclination of the slots and selected equivalent network (T or ! networks). It is based on the definition of the array design as a Constraint Satisfaction Problem, solved by means of a Backtracking Algorithm. As a result, the method returns an equivalent circuit of the whole array which is matched at its input port and whose elements consume a power according to a given amplitude distribution for the array. In any group of antennas, the mutual coupling between elements through the radiated field represents one of the biggest problems that the engineer faces and its effects are detrimental to the overall performance of the system, both in radiation capabilities and return loss. The employment of an equivalent circuit for the array design was discarded by some authors because of the difficulty involved in the characterization of the coupling effects and their inclusion in the design stage. In this thesis the coupling has also been modeled as an equivalent network whose elements are ideal transformers and admittances connected to the set of equivalent networks that represent the antennas of the array. By comparing the estimated results in terms of return loss and radiation with those obtained from popular commercial software as CST Microwave Studio, the validity of the proposed method is fully confirmed, representing the first method of systematic design of compound-slot arrays fed by rectangular waveguide. Since these slots do not work under the resonant status, the bandwidth in return loss is much wider than the longitudinal-slot arrays. For the case of two-dimensional arrays, the angle of inclination can be adjusted so that the field is polarized at the low side-lobe level plane. Besides the performed full-wave simulations two prototypes of six and ten elements for the X-band have been designed, built and measured, revealing excellent results and agreement with the expected results. These facts certify that the genuine technique Method of Moments - Matching Forward Procedure developed along this thesis is valid and trustable.

Late Gothic German Vault Design Methods and Its Relationship with Spanish Ribbed Vaults

The arrival of European master masons to Burgos and Toledo during the mid-fifteenth century was essential for the promotion of the late Gothic ribbed vault design techniques in Spain. The Antigua Chapel in Seville Cathedral, designed by the Spanish master mason Simón de Colonia on 1497, provides an outstanding case study on this subject. This vault is characterized by the interlacing of the ribs near the springing, reflecting the influence of German ribbed vault designs. This paper analyses the relationship between German ribbed vaults and their design methods with those of Spanish ribbed vaults; with particular attention to the presence of ribs that cut through one another above the springing, materialized in the work of Simón de Colonia. This characteristic is reflected in some manuscripts in the German area, like the Wiener Sammlungen (15th-16th centuries) and the Codex Miniatus 3 (ca. 1560-1570), but no Spanish documents of the same period make reference to it.

Integration of Correlation Processes in Design Systems.

The integration of correlation processes in design systems has as a target measurements in 3D directly and according to the users criteria in order to generate the required database for the development of the project. In the phase of photogrammetric works, internal and external orientation parameters are calculated and stereo models are created from standard images. The aforementioned are integrated in the system where the measurement of the selected items is done by applying developed correlation algorithms. The processing period has the tools to carry out the calculations in an easy and automatic way, as well as image measurement techniques to acquire the most correct information. The proposed software development is done on Visual Studio platforms for PC, applying the most apt codes and symbols according to the terms of reference required for the design. The results of generating the data base in an interactive way with the geometric study of the structures, facilitates and improves the quality of the works in the projects.

The historical heritage of domestic architecture is a reliable model for a satisfactory design. The case of the Mediterranean region

The purpose of this paper is to expose the importance of observing cultural systems present in a territory as a reference for the design of urban infrastructures in the new cities and regions of rapid development. If we accept the idea that architecture is an instrument or cultural system developed by man to act as an intermediary to the environment, it is necessary to understand the elemental interaction between man and his environment to meet a satisfactory design. To illustrate this purpose, we present the case of the Eurasian Mediterranean region, where the architectural culture acts as a cultural system of adaptation to the environment and it is formed by an ancient process of selection. From simple observation of architectural types, construction systems and environmental mechanisms treasured in mediterranean historical heritage we can extract crucial information about this elemental interaction. Mediterranean architectural culture has environmental mechanisms responding to the needs of basics habitability, ethnics and passive conditioning. These mechanisms can be basis of an innovative design without compromising the diversity and lifestyles of human groups in the region. The main fundament of our investigation is the determination of the historical heritage of domestic architecture as holder of the formation process of these mechanisms. The result allows us to affirm that the successful introduction of new urban infrastructures in an area need a reliable reference and it must be a cultural system that entailing in essence the environmental conditioning of human existence. The urban infrastructures must be sustainable, understood and accepted by the inhabitants. The last condition is more important when the urban infrastructures are implemented in areas that are developing rapidly or when there is no architectural culture.

Trans arquitectura : imaginación, invención e individuación del objeto técnico arquitectónico : transferencia tecnológica desde la industria del transporte al proyecto arquitectónico (1900-1973)

Se presenta la tesis doctoral, titulada ‘TRANS Arquitectura. Imaginación, Invención e individuación del objeto tecnico arquitectónico. Transferencia tecnológica desde la Industria del Transporte al Proyecto de Arquitectura [1900-1973]'’, que aborda la relación entre la Arquitectura y el Objeto Técnico durante la Modernidad.1 La temática de la tesis gravita en torno a la cultura técnica, la cultura material y la historia de la Tecnología del siglo XX. Hipótesis Se sostiene aquí la existencia de unas arquitecturas que se definen como Objetos Técnicos. Para demostrarlo se estudia si éstas comparten las mismas propiedades ontológicas de los objetos técnicos. Industria y Arquitectura La historia de la Arquitectura Moderna es la historia de la Industria Moderna y sus instalaciones industriales, sus productos y artefactos o sus procedimientos y procesos productivos. Fábricas, talleres, acerías, astilleros, minas, refinerías, laboratorios, automóviles, veleros, aviones, dirigibles, transbordadores, estaciones espaciales, electrodomésticos, ordenadores personales, teléfonos móviles, motores, baterías, turbinas, aparejos, cascos, chassis, carrocerías, fuselajes, composites, materiales sintéticos, la cadena de montaje, la fabricación modular, la cadena de suministros, la ingeniería de procesos, la obsolescencia programada… Todos estos objetos técnicos evolucionan constantemente gracias al inconformismo de la imaginación humana, y como intermediarios que son, cambian nuestra manera de relacionarnos con el mundo. La Arquitectura, al igual que otros objetos técnicos, media entre el hombre y el mundo. Con el objetivo de reducir el ámbito tan vasto de la investigación, éste se ha filtrado a partir de varios parámetros y cualidades de la Industria, estableciendo un marco temporal, vinculado con un determinado modo de hacer, basado en la ciencia. El inicio del desarrollo industrial basado en el conocimiento científico se da desde la Segunda Revolución Industrial, por consenso en el último tercio del siglo XIX. Este marco centra el foco de la tesis en el proceso de industrialización experimentado por la Arquitectura desde entonces, y durante aproximadamente un siglo, recorriendo la Modernidad durante los 75 primeros años del siglo XX. Durante este tiempo, los arquitectos han realizado transferencias de imágenes, técnicas, procesos y materiales desde la Industria, que ha servido como fuente de conocimiento para la Arquitectura, y ha evolucionado como disciplina. Para poder abordar más razonablemente un periodo tan amplio, se ha elegido el sector industrial del transporte, que históricamente ha sido, no sólo fuente de inspiración para los Arquitectos, sino también fuente de transferencia tecnológica para la Arquitectura. Conjuntos técnicos como los astilleros, fábricas de automóviles o hangares de aviones, individuos técnicos como barcos, coches o aviones, y elementos técnicos como las estructuras que les dan forma y soporte, son todos ellos objetos técnicos que comparten propiedades con las arquitecturas que aquí se presentan. La puesta en marcha de la cadena móvil de montaje en 1913, se toma instrumentalmente como primer foco temporal desde el que relatar la evolución de numerosos objetos técnicos en la Primera Era de la Máquina; un segundo foco se sitúa en 19582, año de la creación de la Agencia Espacial norteamericana (NASA), que sirve de referencia para situar la Segunda Era de la Máquina. La mayoría de los objetos técnicos arquitectónicos utilizados para probar la hipótesis planteada, gravitan en torno a estas fechas, con un rango de más menos 25 años, con una clara intención de sincronizar el tiempo de la acción y el tiempo del pensamiento. Arquitectura y objeto técnico Los objetos técnicos han estado siempre relacionados con la Arquitectura. En el pasado, el mismo técnico que proyectaba y supervisaba una estructura, se ocupaba de inventar los ingenios y máquinas para llevarlas a cabo. Los maestros de obra, eran verdaderos ‘agentes de transferencia tecnológica’ de la Industria y su conocimiento relacionaba técnicas de fabricación de diferentes objetos técnicos. Brunelleschi inventó varia grúas para construir la cúpula de Santa Maria dei Fiori (ca.1461), seguramente inspirado por la reedición del tratado de Vitruvio, De Architectura (15 A.C.), cuyo último capítulo estaba dedicado a las máquinas de la arquitectura clásica romana, y citaba a inventores como Archimedes. El arquitecto florentino fue el primero en patentar un invento en 1421: una embarcación anfibia que serviría para transportar mármol de Carrara por el río Arno, para su obra en Florencia. J. Paxton. Crystal Palace. London 1851. Viga-columna. Robert McCormick. Cosechadora 1831. 2ª patente, 1845. La Segunda Revolución Industrial nos dejó un primitivo ejemplo moderno de la relación entre la Arquitectura y el objeto técnico. El mayor edificio industrializado hasta la fecha, el Crystal Palace de Londres, obra de Joseph Paxton, fue montado en Londres con motivo de la Gran Exposición sobre la Industria Mundial de 1851, y siempre estará asociado a la cosechadora McCormick, merecedora del Gran Premio del Jurado. De ambos objetos técnicos, podrían destacarse características similares, como su origen industrial, y ser el complejo resultado de un ensamblaje simple de elementos técnicos. Desde la entonces, el desarrollo tecnológico ha experimentado una aceleración continuada, dando lugar a una creciente especialización y separación del conocimiento sobre las técnicas antes naturalmente unidas. Este proceso se ha dado a expensas del conocimiento integrador y en detrimento de la promiscuidad entre la Industria y la Arquitectura. Este es, sin lugar a dudas, un signo consustancial a nuestro tiempo, que provoca un natural interés de los arquitectos y otros tecnólogos, por las transferencias, trans e inter-disciplinareidades que tratan de re-establecer los canales de relación entre los diferentes campos del conocimiento. La emergencia de objetos técnicos como los vehículos modernos a principios del siglo XX (el automóvil, el trasatlántico, el dirigible o el aeroplano) está relacionada directamente con la Arquitectura de la Primera Era de la Máquina. La fascinación de los arquitectos modernos por aquellas nuevas estructuras habitables, se ha mantenido durante más de un siglo, con diferente intensidad y prestando atención a unos objetos técnicos u otros, oscilando entre el dominio del valor simbólico de los vehículos como objetosimágenes, durante el periodo heroico de la Primera Era de la Máquina, y la mirada más inquisitiva durante la Segunda, que perseguía un conocimiento más profundo de la organización de los mismos y del sistema técnico en el que estaban incluidos. La relación homóloga que existe entre arquitecturas y vehículos, por su condición de estructuras habitables, es algo de sobra conocido desde que Le Corbusier utilizara aquellas imágenes de barcos, coches y aviones para ilustrar su manifiesto Vers une architecture, de 1923. Los vehículos modernos han sido los medios con los que transmitir los conceptos que ansiaban transformar las propiedades tradicionales de la Arquitectura, relativas a su factura, su habitabilidad, su duración, su funcionalidad o su estética. Destaca particularmente el caso del automóvil en las décadas de los años 30 y 50, y los vehículos del programa espacial en las décadas de los 60 y 70. El conocimiento y la documentación previa de estos hechos, fueron un buen indicio para identificar y confirmar que el sector industrial del transporte, era un especialmente trascendente y fértil proveedor de casos de transferencia tecnológica para la Arquitectura. La tradición Moderna inaugurada por Le Corbusier en los años 20, ha sido mantenida y defendida por una multitud de arquitectos modernos como Albert Frey, Richard Neutra, Ralph Soriano, Charles Eames o Craig Ellwood, cuyo trabajo, animado por el legado de anteriores tecnólogos como Bucky Fuller o Jean Prouvé, fue fundamental y referencia obligada para la siguiente generación de arquitectos como Cedric Price, Archigram, Norman Foster, Richard Rogers, Renzo Piano, Jean Kaplicky o Richard Horden, entre otros. Todos ellos han contribuido a engrosar el imaginario del objeto técnico, aportando sus obras arquitectónicas. Estos arquitectos que aparecen repetidamente en el discurrir de la tesis, pertenecen a un mismo linaje, y son agrupados según una estructura ‘genealógica’, que se ha denominado ‘Estirpe Técnica’. Unidos por intereses comunes y similares enfoques o actitudes ante el proyecto de arquitectura, entendida como objeto Técnico, han operado mediante la práctica de la transferencia tecnológica, sin limitarse a las técnicas compositivas propias de la disciplina arquitectónica. Durante la investigación, se ha recopilado una selección de menciones explícitas -hechas por arquitectos- sobre otros objetos técnicos para referirse a la Arquitectura, mostrando las constantes y las variaciones de sus intereses a lo largo del siglo, lo que nos ha llevado a conclusiones como por ejemplo, que los conjuntos técnicos (fábricas de zepelines, aviones, automóviles o trasatlánticos) eran tomados por los arquitectos de la primera Modernidad, como un modelo imaginario, formal y compositivo, mientras que los de la Segunda Era de la Máquina los tomaban como modelo espacial y organizativo para la arquitectura. La mencionada estirpe de tecnólogos incluye líneas de descendencia conocidas, como: EiffelSuchovBehrens GropiusMiesLeCorbusierLodsProuve, en la Europa continental, o una rama británica como: LoudonPaxtonWilliamsStirlingGowan SmithsonsPriceArchigramFosterRogersPiano KaplickyHorden. También podemos encontrar conexiones intercontinentales como Fuller EamesRudolphFosterRogers, o ramificaciones menos previsibles como: LeRicolaisKahn PianoKaplicky, o LeCorbusierFreyLacaton Vassal… Seguramente muchos más merecerían incluirse en esta lista, y de hecho, la tesis asume la imposibilidad de incluirlo todo (por motivos prácticos) aunque contempla la posibilidad de ser ampliada en un futuro. Con lo aquí incluido, se pretende mostrar la continuidad en los enfoques, planteamientos y técnicas de proyectos aplicadas, de los que podemos deducir algunas conclusiones, como por ejemplo, que en los periodos inmediatamente posteriores a las dos Guerras Mundiales, aumentó la intensidad de aportaciones de nuevas imágenes de vehículos, al imaginario del objeto técnico utilizado por los arquitectos, a través de publicaciones y exposiciones. Hoy, cien años después de que Ford pusiera en marcha la cadena móvil de montaje, aún encontramos viva esta tradición en las palabras de un arquitecto, Richard Horden, cuyo trabajo porta consigo –como la información embebida en los elementos técnicos- toda una cultura técnica de una tradición moderna. Horden representa uno de los exponentes de la que he denominado estirpe de tecnólogos. Es por ello que he querido concluir la tesis con una entrevista, realizada en Mayo de 2015, en su estudio de Berkeley Square en Londres (ver Apéndices). Guías Para el desarrollo de la presente tesis, se ha tomado, como principal obra de referencia, otra tesis, titulada El modo de existencia de los objetos técnicos, leída y publicada en 1958 por el filósofo francés Gilbert Simondon [1924-89], dedicada a la ontología del objeto técnico. Esta obra enmarca el enfoque intelectual de la tesis, que entronca con la fenomenología, para movilizar una visión particular de la Arquitectura, a la que sirve como modelo de análisis ontológico para estudiar sus procesos de génesis, invención e individuación. Para el desarrollo de éstos, se ha utilizado como complemento bibliográfico, otra obra del mismo autor, titulada Imaginación e invención 1965-66. En cuanto a las fuentes historiográficas disciplinares, se ha elegido utilizar a Reyner P. Banham [1922-1988] y a Martin E. Pawley [1938-2008] como guías a través de la arquitectura del siglo XX. Sus crónicas sobre la Primera y Segunda Era de la Máquina3 y su obra crítica, han servido como índices desde los que reconstruir el imaginario del objeto técnico moderno, y del que aprovisionarse de proyectos y obras de Arquitectura como casos de estudio para la tesis. Estas obras han servido además como índices de otra bibliografía, que ha sido complementaria a la de éstos. Objetivos de la Tesis El principal objetivo de la tesis es demostrar la hipótesis: si una obra de arquitectura puede ser considerada un objeto técnico y bajo qué condiciones, construyendo un criterio que permita reconocer cuándo una obra de Arquitectura responde a la definición de objeto técnico. Otro objetivo es demostrar la importancia y potencia de la Transferencia tecnológica en el proceso evolutivo de la Arquitectura, y para ello se presentan ejemplos de una metodología de proyecto por ensamblaje, que Martin Pawley denominaba ‘Design by Assembly’. También es un objetivo el de reconstruir un Atlas del Imaginario del objeto técnico moderno, con el fin de conocer mejor las causas, razones y finalidades que llevaron a los arquitectos modernos a perseguir una arquitectura como objeto técnico. Este Atlas permite relacionar panópticamente los distintos objetos técnicos entre sí, revelando la verdadera importancia y trascendencia de aquéllos y las arquitecturas con las que se relacionan. En él, las arquitecturas vuelven a situarse en el contexto más extenso y complejo de la industria y la historia de la tecnología, al que siempre pertenecieron. De este modo, éstas son capaces de desvelar todo el conocimiento -en forma de información- que portan en su propio código ‘genético’, desplegando capítulos completos de cultura tecnológica, tan antigua como la Humanidad y en constante y creciente evolución. Estructura de la tesis Tras una Introducción en la que se presentan algunos de los conceptos principales que se instrumentalizan en la tesis sobre la ontología Simondoniana del objeto técnico y sobre la transferencia tecnológica aplicada al proyecto de Arquitectura, el texto principal de la tesis consta de tres partes: La primera se dedica a la Imaginación, una segunda parte a la Invención y una tercera a Individuación o evolución del objeto técnico. Se termina con una Discusión de la tesis y un apartado de Conclusiones. En la Introducción al objeto técnico, éste se define ontológicamente y se distinguen sus diferentes categorías (conjuntos técnicos, individuos técnicos y elementos técnicos). Se explica el proceso de génesis del objeto técnico y sus fases de imaginación, invención e individuación. También se presentan los conceptos de transducción, tecnicidad y sistema técnico, fundamentales para entender el concepto de transferencia tecnológica que se desarrollará después. La concretización, explica el modo particular de individuación y evolución de los objetos técnicos, un proceso por el que las diferentes partes de un objeto técnico, se integran y tienden hacia la propia convergencia. Aquí se comprueba la efectividad del concepto simondoniano de Transducción, como señal o información transmitida y transformada, y se relaciona con la Transferencia Tecnológica - un proceso sinergético, por el que un sector industrial se beneficia del desarrollo de otro sector- a la que se han referido explícitamente arquitectos e historiadores para explicar sus obras, durante la Segunda Era de la Máquina, y que es determinante para el desarrollo de la Industria. La transferencia tecnológica sería la transmisión del conjunto de conocimientos sobre la técnica, que incluyen su esfera fáctica, pero también la esfera sensible de la experiencia. En su aplicación a la arquitectura, las transferencias se han clasificado según tres tipos: Eidéticas, Tectónicas, Orgánicas. En la primera parte dedicada a la Imaginación del objeto técnico arquitectónico se realiza una reconstrucción ‘arqueológica’ –y parcial- del imaginario del objeto técnico moderno, con la intención de conocer mejor su génesis y la relación con otros objetos técnicos. Las fuentes de ese imaginario se buscan en las instalaciones de la Industria de principios de siglo XX, en particular en las fábricas de vehículos, con la finalidad de comprobar hasta qué punto, esos objetos técnicos fueron importantes para imaginar la Arquitectura moderna. La reconstrucción se continúa hasta la Segunda Era de la Máquina, cuando una nueva mirada más inquisitiva y precisa, se dirige a otras fábricas, vehículos y componentes, interesándose por sus cualidades materiales y organizativas. Transferencias Eidéticas, que operan desde un conocimiento intuitivo y son útiles para transmitir información sobre la esencia de un objeto técnico que sirve de fuente. Conceptos abstractos se transmiten por medio de las imágenes—objeto, para producir una transformación en su equivalente arquitectónico. Fruto de la investigación, se han detectado un grupo de conceptos que han sido objeto de transferencias tecnológicas de naturaleza eidética, provenientes del imaginario del objeto técnico moderno: FABRICADO, HABITABLE, FUNCIONAL, EFICIENTE, OBSOLESCENTE y BELLO. En la segunda parte dedicada a la Invención del objeto técnico arquitectónico, las transferencias también pueden ser Tectónicas, cuando lo que se transmite es una técnica constructiva o estructural aplicada mediante MATERIALES artificiales (como los metales, los composites como el ferrocemento, y el plywood, o las aleaciones como el aluminio) o mediante el ensamblaje de ESTRUCTURAS o partes componentes de otro objeto técnico, (como cascos, fuselajes, carrocerías o aparejos) y tiene como resultado la invención de un nuevo objeto técnico arquitectónico. En la tercera parte dedicada a la individuación, se abordan las transferencias ORGÁNICAS, lo que se transfiere es una técnica organizativa, aplicada a través de PROCEDIMIENTOS que definen la actividad del arquitecto como tecnólogo e inventor de objetos técnicos. Estos procedimientos tienen un efecto transformador en tres instituciones tradicionales para la Arquitectura: la Escuela, el Estudio y la Obra, y sus resultados se resumen en nuevos modelos de organización de la Educación de la Arquitectura, con la aparición de los Talleres de proyectos; nuevos modelos de organización del ejercicio de arquitecto: la Oficina técnica; nuevos modelos de organización del espacio, basados en la organización espacial de la Industria, que da lugar a patrones o Matrices espaciales; un nuevo modelo de organización del proyecto, que utiliza las herramientas gráficas de la industria y el ensamblaje como metodología; y un nuevo modelo de producción arquitectónica, basado en la Industrialización. Tras explicar los conceptos y la génesis del ensamblaje y el montaje, se presenta el proyecto por ensamblaje (Design by assembly) como un método que promueve la invención arquitectónica. Se demuestra utilizando algunos casos analizados en la tesis, en los que se ha realizado alguna transferencia conceptual, constructiva u organizativa. Tras analizar las arquitecturas estudiadas en la tesis, se ha utilizado el método genético propuesto por Simondon para comprender cada evolución particular, reconstruyendo las líneas genealógicas hasta sus ancestros, e identificando una serie de linajes genéticos, que corresponderían con los conjuntos técnicos estudiados en la tesis: el astillero, la fábrica de coches, y la fábrica de aeronaves: los Ancestros de la Modernidad. Los sistemas de organización espacial de estos conjuntos técnicos, están directamente relacionados con el objeto técnico que se produce en él. A partir de ellos se definen una serie de matrices operativas (MILL, SHOP, SHED), que sirven para hacer una taxonomía del objeto técnico arquitectónico. Esto se ejemplifica con algunos proyectos de Norman Foster, Richard Rogers, Renzo Piano, Nicholas Grimshaw, Jean Kaplicky y Richard Horden. Tesis: Comprobación de la hipótesis Simondon definía ontológicamente el Objeto técnico como aquello de lo que existe génesis y que desarrolla una tendencia hacia la solidaridad y unidad. Para que una Arquitectura pueda ser reconocida como un Objeto técnico, se deben dar una serie de condiciones, en las sucesivas fases que intervienen en su modo de existencia: Imaginación. Estas arquitecturas remiten a un imaginario protagonizado por imágenes-objeto de otros objetos técnicos (conjuntos técnicos, individuos técnicos y elementos técnicos). Esas imágenes-objeto vehiculizan una transferencia eidética de los objetos técnicos que simbolizan. Invención. Estas arquitecturas son el resultado de transferencias tectónicas, que se producen durante el proceso de proyecto, mediante el ensamblaje de materiales, componentes o procedimientos, utilizados en la industria para la producción de otros objetos técnicos. Individuación. Estas arquitecturas evolucionan y se individualizan por concretización, un proceso por el que los objetos técnicos se organizan para seguir su tendencia hacia la integración de sus partes, con el fin de alcanzar la convergencia de funciones en una única estructura. Esta integración tiende hacia la naturalización del objeto técnico, mediante la inclusión simbiótica de sus medios naturales asociados. En este caso, veremos cómo se ha producido transferencias orgánicas, o lo que es lo mismo, cómo los objetos técnicos –en el nivel de los conjuntos técnicos- se han tomado como modelo de organización por la arquitectura. Tras comprobar que de ellas existe una génesis, que evoluciona por las fases de imaginación e invención y concretización, se analiza su imaginario, su materialidad, sus estructuras y su organización, con el fin de detectar patrones y principios organizativos comunes a otros objetos técnicos. Interés de la tesis Desde el comienzo del nuevo siglo, diversos autores han demostrado un renovado interés por definir qué es el proyecto, qué lo constituye para qué sirve. Las aproximaciones al tema provienen de la filosofía analítica (Galle, 2008) o de la filosofía de la tecnología (Verbeek, 2005; Vermaas, 2009) y a menudo versan sobre la relación entre diseño y la cultura material (Dorschel 2003, Boradkar 2010 o Preston 2012). Es importante indicar el reciente y también creciente interés suscitado por la obra del filósofo francés, Gilbert Simondon [1924-1989], reconocida por su importante contribución a la filosofía de la técnica y la fenomenología, y por la influencia en el pensamiento de filósofos como Gilles Deleuze, autor presente en multitud de tesis doctorales e investigaciones teóricas llevadas a cabo en las principales escuelas de Arquitectura de todo el mundo desde los años 90 hasta el presente. La reedición y traducción de la obra de Simondon (ing. 1980, esp. 2008) ha recibido la atención de filósofos actuales como Paolo Virno, Bruno Latour o Bernard Stiegler, que siguen recurriendo a su estudio y análisis para avanzar en su pensamiento, estando por tanto presente en el debate contemporáneo sobre la técnica. Tras su reciente traducción al español, el pensamiento de Simondon ha despertado un gran interés en América Latina, como demuestra la organización de varios congresos y simposios, así como la proliferación de publicaciones en torno a su obra y pensamiento. Las futuras traducciones del resto de sus principales obras, asegurarán una introducción cada vez mayor en la comunidad académica. Se ha procurado presentar una mirada alternativa de la Historia de la Arquitectura Moderna, utilizando como guía a un cronista como Reyner Banham. La Era de la Máquina se ha cruzado con la Mecanología y el “vitalismo técnico” de Simondon, obteniendo como resultado una interpretación fresca, renovada y optimista de algunas de las más importantes obras de Arquitectura del siglo XX, que seguro contribuirán al desarrollo de la del siglo XXI, inmerso ya en el cambio de paradigma hacia la sostenibilidad y la ecología. ABSTRACT 'TRANS architecture. Imagination, invention and technical individuation of the architectural technical object. Technology transfer from the Transport Industry to Architectural Design [1900- 1973]' is a thesis dealing with the relationship between Architecture and the Technical Object during Modernity5. The theme of the thesis revolves around the technical culture, material culture and the history of twentieth-century technology. Hypothesis Held here is the existence of some architectures defined as technical objects. A study has been developed to prove if those architectures share the ontological properties of a technical object. Industry and Architecture The history of Modern Architecture is also the history of modern industry and its facilities, its products and devices, its procedures and production processes. Factories, workshops, steel mills, shipyards, mines, refineries, laboratories, cars, yachts, airplanes, airships, shuttles, space stations, home appliances, personal computers, mobile phones, motors, batteries, turbines, rigs, hulls, chassis, bodies, fuselages , composites and synthetic materials, the assembly line, modular manufacturing, the supply chain, process engineering, the planned obsolescence ... All these technical objects are constantly evolving thanks to the inconsistency of the human imagination and, as our intermediates, keep changing our way of relating and being in the world. Architecture, alike other technical objects, mediates between man and the World. In order to frame the vast field of the research, it has been filtered according to various parameters and qualities of Industry, establishing also a time frame which is related to a particular science-based way of making. The start of an industrial development, based on scientific knowledge is given from the Second Industrial Revolution -by consensus on the last third of the nineteenth century. This frame puts the focus of the thesis in the process of industrialization experienced by the Architecture of at least one century, and tours through Modernity during the first 75 years of the twenieth century. During this time, architects have made transfers of images, techniques, processes and materials from Industry, serving as a source of knowledge and thus allowing Architecture to evolve as a discipline. To reasonably address the enormous scope of the thesis, the industrial sector of transportation has ben chosen. It is not only a historical source of inspiration for architects, but also a traditional source of technology transfer for Modern Architecture. Technical sets such as shipyards, automobile factories or aircraft hangars, technical individuals as boats, cars or planes, and technical elements like the structures shaping and supporting them, are all technical objects which share properties with the architectures here presented. The launch of the moving assembly line in 1913, is instrumentally taken as a first time focus, from which to describe the evolution of many technical objects in the First Machine Age; a second focus could be found in 19586, year of the creation of the North American Space Agency (NASA), serving as a reference to the Second Machine Age. Most architectural technical objects used to test the hypothesis, gravitate around this second focus, in a range of plus or minus 25 years, with a clear intention to synchronize the time for action and time of thought. Architecture and Technical Object Technical objects have always been related to Architecture. In the past, the same technician who planned and oversaw a building structure, invented the devices and machines to carry them out. The foremen were the true 'technology transfer agents' from Industry. Their knowledge naturally related different manufacturing techniques to make diverse technical objects. Brunelleschi invented various cranes to build the dome of Santa Maria dei Fiori in Florence (ca.1461). Probably inspired by the reedition of Vitruvius’ treaty De Architectura (15 BC), whose last chapter was dedicated to the machines of classical Roman architecture and quoted inventors as Archimedes, the florentine architect was the first to patent an invention in 1421: an amphibious craft serving as a means of transportation for Carrara marble along the Arno river. At the daw of the Second Industrial Revolution, whose development was based on the scientific knowledge, we find a primitive modern example of the relationship between Architecture and a Technical Object: The Crystal Palace, built in London for the Great Exhibition of 1851 World Industry and designed by Joseph Paxton, was the largest to date industrialized building, and it will be always associated with the McCormick Reaper, worthy of the Grand Jury’s Prize. Similar characteristics could be emphasized of both technical objects, such as their industrial origin and for being be the complex result of a simple assembly of technical elements. Since then, technological development has experienced a continued acceleration, resulting in an increasing specialization and separation of knowledge about techniques which were naturally attached in the past. This process has happened at the expense of an integrative knowledge and against promiscuity between Industry and Architecture. This is, undoubtedly, an inherent sign of our time, which causes the natural and interest of architects and other technicians about transfers, trans-disciplinarity and inter-disciplinarity, as a reaction to reestablish channels of relationships between these different fields of knowledge. The emergence of technical objects as modern vehicles in the early twentieth century (the car, the Ocean liner, the airship or the airplane) is directly related to the Architecture of the First Machine Age. Modern architects’ fascination for those new ‘inhabitable’ structures has been maintained for over a century, with different intensity and paying attention to one and other technical objets, ranging from the domain of the symbolic value of the vehicles as objectsimages, during heroic period of the First Machine Age, to the more inquisitive glance characterizing the Second Machine Age, which sought a deeper understanding of the organization of such objects and the technical system to which they belonged. The periods immediately following both World Wars, showed a concentrated effort to bring new images of vehicles to the imaginary of architects, by means of publications and exhibitions. The homologous relationship between architectures and vehicles, in their capacity as living structures, is something well known since Le Corbusier used the images of cars, boats and airplanes to illustrate his manifesto, Towards an architecture in 1923. Modern vehicles have been the means by which to convey the concepts eager to transform the traditional attributes of Architecture: those relating to its manufacture, habitability, duration, functionality or aesthetics. The automobile stands out during the 30s and 50s, and the new vehicles of the Space Program satnd in the 60s and 70s. The prior knowledge and documentation of these events were a good indication to identify the industrial sector of Transportation as one of especial importance and as a fertile provider of technology transfer cases for Architecture. The Modern tradition, inaugurated by Le Corbusier in the 20s, has been maintained and defended by a host of modern architects like Albert Frey, Richard Neutra, Ralph Soriano, Charles Eames and Craig Ellwood, whose work - inspired by the legacy of previous technologists as Bucky Fuller or Jean Prouvé- was fundamental and a mandatory reference for the next generation of architects like Cedric Price, Archigram, Norman Foster, Richard Rogers, Renzo Piano, Jean and Richard Horden Kaplicky, among others. They have all contributed to increase the imaginary of the technical object, adding to it their architectural works. In the passage of the thesis, we repeatedly find a number of architects, who have been grouped according to a 'genealogical' structure, which has been called 'Technical Lineage'. Gathered by common interests and similar views or attitudes to the architectural design, understood as a technical object, they have operated through the practice of technology transfer, without limiting itself to specific compositional techniques of the architectural discipline. During the investigation, a selection of explicit references made by those architects, about other technical objects referring to their Architecture, has been compiled, showing constants and variations in their interests throughout the century, which has led to conclusions such as, having technicians sets (zeppelins factories, airships factories, car factories and shipyards) been taken by the architects of the first Modernity, as their main formal, compositional and imaginary models, while the Second Machine Age had taken them as a spatial and organizational model for their architecture. The above mentioned lineage of technologists includes weel-known ‘seed lines’ as: Eiffel- Suchov-Behrens, Gropius-Mies-LeCorbusier- Lods-Prouve, in continental Europe; British branches as Loudon-Paxton-Williams-Stirling- Gowan-Smithsons-Price-Archigram-Foster- Rogers-Piano-Kaplicky-Horden. And we could also find intercontinental connections as Fuller- Eames-Rudolph-Foster-Rogers, or other less predictable ramifications as LeRicolais-Kahn Piano-Kaplicky, or LeCorbusier-Frey-Lacaton & Vassal... Many more would surely deserve to be included in this list, and indeed, the thesis assumes the impossibility of including them all (for practical reasons) and even contemplates possible future extensions. The material included herein is to demonstrate the continuity in the approaches, statements and in the applied architectural design techniques, from which we can draw some conclusions. Today, one hundred years after Ford put up the moving assembly line, we still find this tradition alive in the words of the architect Richard Horden, whose work carries with it –as with the information embedded in every technical element- the whole techncial culture of a modern tradition. Horden is represented here as one of the exponents of what I have called the lineage of technologists. That is why I wanted to conclude the thesis with an interview to Richard Horden, held in May 2015 in his studio in London's Berkeley Square (see Appendices). Guides For the development of this thesis, another thesis, entitled: The mode of existence of technical objects, is taken as the main reference work. Read and published in 1958 by the French philosopher Gilbert Simondon [1924- 1989], it was dedicated to the ontology of the technical object. This work frames the intellectual approach of the thesis, which connects with phenomenology to mobilize a particular vision of Architecture. It is used as a model of ontological analysis to study its genesis, invention and evolutionary processes. To develop these, another work by the same author, titled Imagination and Invention (1965- 1966) has been used as a bibliographical complement. As for the disciplinary historical sources, Reyner P. Banham [1922-1988] and Martin E. Pawley [1938-2008] have been chosen as guides through the modern Architecture of the twentieth century. Their cronical reports on the First and Second Machine Age and their critical works have served as an index from which to reconstruct the imaginary of the modern technical object in the Machine Age7, and to stock up on projects and works of architecture, used as case studies for the thesis. These works have also been used as triggers for other literatures, which has been complementary to the former. Objectives of the Thesis The main objective of the thesis is to prove its hypothesis: if a work of architecture can be considered a technical object and under what conditions, building then a criterion for recognizing when a work of architecture meets the definition of a technical object. Another aim is to demonstrate the importance and power of Technology Transfer in the evolutionary process of Architecture, and to do it, some examples of a methodology for architectural design that Martin Pawley called 'Design by Assembly' are presented. It is also an objective to reconstruct an Atlas of the imaginary of the modern technical object, in order to better understand the causes, reasons and purposes that led modern architects to pursue architecture as a technical object. This Atlas allows to panoptically relate the various technical objects, revealing the true importance and significance of those and the architecture with whom they interact. Architectures are again at the largest and most complex industrial context and the history of technology, which always belonged. Thus, they are able to reveal all the knowledge-in the shape of information-carried in their own 'genetic' code, displaying full chapters of technological culture as old as mankind and constantly growing and evolving. Thesis: Proving the Hypothesis Simondon ontologically defined the technical object as ‘that of which genesis exists’ and that develops ‘a tendency towards solidarity and unity’. For an architecture to be recognized as a technical object, a number of conditions should be given, in the successive phases involved in their mode of existence: Imagination. These architectures refer to an imaginary featuring images-object other technical objects (technical sets, technical individuals and technical elements). These images are the means to an eidetic transfer of the technical objects which they symbolize. Invention. These architectures are the result of tectonic transfers, which occur during the architectural design process, by assembling materials, components or procedures used in industry for the production of other technical objects. Individuation. These architectures evolve and are individualized by ‘concretization’, a process leading to the full integration of its parts and aiming the full convergence of its functions into a single structure. This integration tends towards the naturalization of the technical object, by means of a symbiotic incorporation of their associated milieus. After checking if there is a genesis of them, which evolves through the phases of imagination and invention and concretization, their imaginary, materiality, structure and organization are analyzed in order to detect patterns and common organizational principles to other technical objects counterparts. Structure The main text of the thesis consists of three parts. Before there is an Introduction to the main concepts that are exploited in the thesis on ontology Simondonian technical object, and technology transfer applied to Architecture. Then a first part covers the Imaginary of the modern technical object, a second part is dedicated to the Invention and a third part to the individuation process The thesis ends with a section for the Discussion and the Conclusions. The Introduction to the technical object, this is ontologically defined and its different categories are distinguished. The process of genesis of the technical object and the phases of imagination, invention and indivuation are explained. Concepts as Transduction, Technicality and Technical system are presented for being fundamental to understand the concept of Technology Transfer that will take place later. The concretization is explained as the particular mode of individuation and evolution of technical objects, a process by which the different parts of a technical object, are integrated and begin a tendency towards a convergence in itself. The first part, dedicated to the Imagination of the architectural technical object presents a parcial "archaeological" reconstruction the imaginary of the modern technical object, intended to better understand its genesis and the relationship with other technical objects. The imaginary sources are searched in the premises of the Industry of the early twentieth century, and particularly in the factories of modern vehicles, in order to see, to what extent these technical objects were important to imagine modern architecture. The reconstruction is continued until the Second Machine Age, when a new, more inquisitive and precise gaze turns to other factories, other vehicles and other components and materials, inquiring now about their organizational qualities. The second part is devoted to the Invention of the architectural technical object. The effectiveness of the simondonian concept of Transduction is checked: a transmitted and transformed sign or information, which relates to Technology Transfer, a synergetic process by which an industrial sector benefits from the development of another sector, to which some architects and historians have explicitly referred to explain their works during Machine Age, and which is crucial for the development of the industry. Technology transfer would be the transmission of a set of information or knowledge about technique, including the factual sphere of technique, but also the sensitive sphere of experience. In their application to Architecture, these transfers have been classified according to three types: Eidetic, Tectonic and Organic. Eidetic Transfers operate from an intuitive knowledge and are useful for transmitting information about the essence of the technical object serving as a source. Abstract concepts are transmitted through the object-images to produce an equivalent transformation in Architecture. A group of concepts that have been the subject of technology transfers of eidetic nature, and have been originated in the imaginary of the modern technical object, have been detected as a result of the research: FABRICATED, INHABITABLE, FUNCTIONAL, EFFICIENT, OBSOLESCENT, and BEAUTIFUL. The transfers can also be Tectonic when, that which is transferred is a constructive or structural technique, applied through artificial MATERIALS such as metals, composites as the ferrocement, or plywood, or alloys such as aluminum; or by means of the assembly of STRUCTURES or parts of other technical objects such as hulls, fuselages, car bodies or rigs, resulting in the invention of a new architectural technical object. In the case of ORGANIC transfers, what is transferred is an organizational technique, applied by means of a set of PROCEDURES defining the activity of the architect as a technologist and inventor of technical objects. These procedures have a transformative effect on three traditional institutions for Architecture: the School, the Atelier and the Work, and the results are summarized in new models of organization of the Education of Architecture, with the onset of the Architectural Design Studios or workshops; new models of organization of the practice of architect: the technical office; and new models of space organization, based on the spatial organization of the industry, resulting in spatial patterns or spatial matrices; a new model of organization of the project, which uses graphical tools and industrail protocols as the assembly as a methodology; a new model of architectural production based on the industrialization. After explaining the concepts and the genesis of assembly and montage, Design by assembly is presented as a method that promotes architectural invention, and is shown using some case studies analyzed in the thesis, in which there has been made some conceptual, constructive or organizational transfer. After analyzing the architectures studied in the thesis, genetic method proposed by Simondon was used to understand every particular evolution, reconstructing their genealogical lines up to their ancestors, identifying a series of genetic lineages, which correspond to the technical sets studied in the thesis : the shipyard, the car factory, and aircraft factory. The real ancestors of Modernity. The spatial organization systems of these technical sets are directly related to the technical object that is fabricated within them. From that point, a number of operational matrices are defined (MILL, SHOP, SHED) and used to make a taxonomy of the architectural technical object. This is exemplified by some projects by architects as Norman Foster, Richard Rogers, Renzo Piano, Nicholas Grimshaw, Jean and Richard Horden Kaplicky. Interest of the thesis Since the beginning of the new century, several authors have shown a renewed interest in defining what a project is, how it is constituted and what it is for. The approaches to the subject are brought from analytic philosophy (Galle, 2008) or from the philosophy of technology (Verbeek, 2005; Vermaas, 2009) and they often speak about the relationship between design and material culture (Dorschel 2003, 2010 or Preston Boradkar 2012). It is also important to note the recent and growing interest in the work of French philosopher Gilbert Simondon [1924-1989], mainly known for its important contribution to the philosophy of technology and phenomenology of the technical object, and the influence on the thinking of contemporary philosophers as Paolo Virno, Bruno Latour or Gilles Deleuze, being the latter a author present in many doctoral theses and theoretical research conducted at major architecture schools around the world since the 90s to the present. The republication and translation of the work of Simondon (eng. 1980, spn. 2008) has received the attention from current philosophers such as Bernard Stiegler who continues to use its study and analysis to advance his thinking, thus being present in the contemporary debate about the technique. After its recent translation into Spanish, the thought of Simondon has aroused great interest in Latin America, as evidenced by the organization of various conferences and symposia, as well as the proliferation of publications about his work and thought8. Future translations of the rest of his major works, will ensure increased introduction in the academic community. Efforts have been made to present an alternative view of the History of Modern Architecture, using a reporter as Reyner P.Banham as a guide. The Machine Age intersects Simondon’s mechanology and his "technical vitalism", resulting in a fresh, renewed and optimistic interpretation of some of the most important works of Architecture of the twentieth century, which will surely contribute to the development of this century’s Architecture, already immersed in the paradigm shift towards sustainability and ecology.

A general method to design dominant negatives to B-HLHZip proteins that abolish DNA binding

We describe a method to design dominant-negative proteins (D-N) to the basic helix–loop–helix–leucine zipper (B-HLHZip) family of sequence-specific DNA binding transcription factors. The D-Ns specifically heterodimerize with the B-HLHZip dimerization domain of the transcription factors and abolish DNA binding in an equimolar competition. Thermal denaturation studies indicate that a heterodimer between a Myc B-HLHZip domain and a D-N consisting of a 12-amino acid sequence appended onto the Max dimerization domain (A-Max) is −6.3 kcal⋅mol−1 more stable than the Myc:Max heterodimer. One molar equivalent of A-Max can totally abolish the DNA binding activity of a Myc:Max heterodimer. This acidic extension also has been appended onto the dimerization domain of the B-HLHZip protein Mitf, a member of the transcription factor enhancer binding subfamily, to produce A-Mitf. The heterodimer between A-Mitf and the B-HLHZip domain of Mitf is −3.7 kcal⋅mol−1 more stable than the Mitf homodimer. Cell culture studies show that A-Mitf can inhibit Mitf-dependent transactivation both in acidic extension and in a dimerization-dependent manner. A-Max can inhibit Myc-dependent foci formation twice as well as the Max dimerization domain (HLHZip). This strategy of producing D-Ns may be applicable to other B-HLHZip or B-HLH proteins because it provides a method to inhibit the DNA binding of these transcription factors in a dimerization-specific manner.

A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine.

Several polycations possessing substantial buffering capacity below physiological pH, such as lipopolyamines and polyamidoamine polymers, are efficient transfection agents per se--i.e., without the addition of cell targeting or membrane-disruption agents. This observation led us to test the cationic polymer polyethylenimine (PEI) for its gene-delivery potential. Indeed, every third atom of PEI is a protonable amino nitrogen atom, which makes the polymeric network an effective "proton sponge" at virtually any pH. Luciferase reporter gene transfer with this polycation into a variety of cell lines and primary cells gave results comparable to, or even better than, lipopolyamines. Cytotoxicity was low and seen only at concentrations well above those required for optimal transfection. Delivery of oligonucleotides into embryonic neurons was followed by using a fluorescent probe. Virtually all neurons showed nuclear labeling, with no toxic effects. The optimal PEI cation/anion balance for in vitro transfection is only slightly on the cationic side, which is advantageous for in vivo delivery. Indeed, intracerebral luciferase gene transfer into newborn mice gave results comparable (for a given amount of DNA) to the in vitro transfection of primary rat brain endothelial cells or chicken embryonic neurons. Together, these properties make PEI a promising vector for gene therapy and an outstanding core for the design of more sophisticated devices. Our hypothesis is that its efficiency relies on extensive lysosome buffering that protects DNA from nuclease degradation, and consequent lysosomal swelling and rupture that provide an escape mechanism for the PEI/DNA particles.

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.

Industry Professionals Who Attain Leadership in Energy and Environmental Design (LEED) Accreditation: An Examination of Motivations in Human Resource (HR) Training and Development

Despite the economy, the green building industry continues to grow and drive the demand for environmentally conscious, highly skilled professionals (USGBC 2009). LEED Accredited Professionals (APs) have the knowledge and skills to meet such demand; however, information is limited regarding LEED APs or their motivations and expectations toward prospective employers. The author surveyed a sample of LEED Accredited architects and found a combination of job and personal factors motivated them to attain accreditation. LEED APs value both a competitive salary and commitment to sustainability in prospective employers. To attract, retain, and utilize LEED APs, executives in this industry must reexamine corporate culture, their willingness to pay for credentialing, and the alignment of their reputation with the desires of potential applicants.

Design and Implementation of a Cloud-based Middleware for Persuasive Android Applications

Negli ultimi decenni, le tecnologie e i prodotti informatici sono diventati pervasivi e sono ora una parte essenziale delle nostre vite. Ogni giorno ci influenzano in maniera più o meno esplicita, cambiando il nostro modo di vivere e i nostri comportamenti più o meno intenzionalmente. Tuttavia, i computer non nacquero inizialmente per persuadere: essi furono costruiti per gestire, calcolare, immagazzinare e recuperare dati. Non appena i computer si sono spostati dai laboratori di ricerca alla vita di tutti i giorni, sono però diventati sempre più persuasivi. Questa area di ricerca è chiamata pesuasive technology o captology, anche definita come lo studio dei sistemi informatici interattivi progettati per cambiare le attitudini e le abitudini delle persone. Nonostante il successo crescente delle tecnologie persuasive, sembra esserci una mancanza di framework sia teorici che pratici, che possano aiutare gli sviluppatori di applicazioni mobili a costruire applicazioni in grado di persuadere effettivamente gli utenti finali. Tuttavia, il lavoro condotto dal Professor Helal e dal Professor Lee al Persuasive Laboratory all’interno dell’University of Florida tenta di colmare questa lacuna. Infatti, hanno proposto un modello di persuasione semplice ma efficace, il quale può essere usato in maniera intuitiva da ingegneri o specialisti informatici. Inoltre, il Professor Helal e il Professor Lee hanno anche sviluppato Cicero, un middleware per dispositivi Android basato sul loro precedente modello, il quale può essere usato in modo molto semplice e veloce dagli sviluppatori per creare applicazioni persuasive. Il mio lavoro al centro di questa tesi progettuale si concentra sull’analisi del middleware appena descritto e, successivamente, sui miglioramenti e ampliamenti portati ad esso. I più importanti sono una nuova architettura di sensing, una nuova struttura basata sul cloud e un nuovo protocollo che permette di creare applicazioni specifiche per smartwatch.