O 68Ga é um radionuclídeo promissor para a medicina nuclear, decaindo por emissão de pósitrons com abundância de 89%, apresentando tempo de meia vida física de 68 minutos, o que é compatível com a farmacocinética de muitas biomoléculas e substratos de baixo peso molecular. Outra característica importante é a sua disponibilidade por um sistema de gerador, onde o radionuclídeo pai, 68Ge (t1/2 = 270,95 dias) é adsorvido em uma coluna e o filho, 68Ga, é eluído na forma iônica 68Ga3+. O desenvolvimento dos geradores de 68Ge/68Ga teve início na década dos anos 60, mas o seu uso clínico começou a ser aceitável e relevante apenas recentemente. O método de separação do 68Ge do 68Ga mais utilizado é o sistema cromatográfico de troca iônica, devido sua praticidade de operação, mas outros sistemas de geradores já foram propostos, como de extração por solvente e técnica de evaporação. Atualmente, os geradores de 68Ge/68Ga são disponíveis comercialmente tanto com colunas utilizando matrizes inorgânicas preparadas com TiO2 ou SnO2 como também usando resina orgânica. A eficiência de eluição do 68Ga varia de 70 % a 80 %, apresentando uma queda ao longo do tempo. Os níveis de contaminação do 68Ge vão de 10-2 a 10-3 %, porém ocorre um aumento nos níveis de contaminação após longos períodos de uso. Mesmo com todos os avanços tecnológicos, ocorridos nas últimas décadas, no desenvolvimento dos geradores de 68Ge/68Ga, o eluato de 68Ga dos geradores comerciais ainda não é adequado para uso direto em seres humanos e algumas melhorias nos sistemas precisam ser feitas para diminuir os níveis de contaminação de 68Ge e impurezas químicas. O objetivo principal deste trabalho foi desenvolver um sistema de gerador de 68Ge/68Ga com o qual se pudesse eluir o 68Ga com qualidade necessária para uso clínico. O comportamento químico do Ge e do Ga foi avaliado em vários materiais adsorvedores inorgânicos. Foram desenvolvidos dois tipos de sistemas de geradores de 68Ge/68Ga utilizando o TiO2 como material adsorvedor: sistema de eluição com pressão manual e sistema de eluição a vácuo, controlado. As eficiências dos geradores foram similares às encontradas nos geradores comerciais, assim como os níveis de impurezas no eluato. Um novo método para o controle radionuclídico foi desenvolvido e apresentou resultados satisfatórios para determinação da contaminação do 68Ge no eluato do gerador. Foi proposto um protótipo de gerador capaz de fornecer 68Ga com a qualidade necessária para ser utilizado em aplicações médicas. / The 68Ga is a promising radionuclide for nuclear medicine, decaying by positron emission with an abundance of 89%, with physical half-life of 68 minutes, which is compatible with the pharmacokinetics of many biomolecules and low molecular weight substrates. Another important feature is its availability through a generator system, where the parent radionuclide, 68Ge (t1/2 = 270.95 days) is adsorbed on a column and the daughter, 68Ga, is eluted in an ionic form 68Ga3+. The development of 68Ge/68Ga generators began in the 60s, but its clinical use began to be acceptable and relevant only recently. The method of separation of 68Ge and 68Ga most used is the ion-exchange chromatographic system, due to its practical operation, but other generator systems have been proposed, such as solvent extraction and evaporation technique. Currently, 68Ge/68Ga generators are commercially available using inorganic matrices columns prepared with TiO2 or SnO2 as well using organic resin. The efficiency of 68Ga elution ranges from 70% to 80%, decreasing over time. The 68Ge breakthrough varies from 10-2 to10-3 % or lower in a fresh generator, but there is an increase in the levels of contamination after long periods of use. Even with all the technological advances in the development of 68Ge/68Ga generators in the past decades, the 68Ga eluted from commercial generators is not suitable for direct use in humans and some improvements in the systems need to be made to reduce the 68Ge breakthrough and chemical impurities levels. The main objective of this work was to develop a 68Ge/68Ga generator system is which 68Ga could be eluted with quality required for clinical use. The chemical behavior of Ge and Ga was evaluated on various inorganic adsorbents materials. Two types of 68Ge/68Ga generator systems were developed using TiO2 as adsorbent material: elution system with manual pressure and vacuum controlled. The efficiencies of the generators were similar to those found in commercial generators, as well as the impurity levels in the eluate. A new method for radionuclidic control was developed and showed good results for the determination of 68Ge breakthrough in 68Ga eluate. It was proposed a prototype 68Ga generator capable of providing the quality needed for use in medical applications.

En este trabajo, la técnica de control basada en datos "Virtual Reference Feedback Tuning" es tratada de diferentes maneras. Por un lado, las capacidades del método son extendidas con varias propuestas que permiten un uso más amplio del método. Una topología de control alternativa de dos grados de libertad es considerada, así como su aplicación a un controlador proporcional-integral. El caso de múltiples entradas múltiples salidas también se ha abordado mediante la adición de una selección automática de emparejamiento entre las salidas y las variables manipuladas. El método también es aplicado a la topología de Modelo de Control Interno a fin de proponer una prueba de estabilidad robusta basada exclusivamente en datos. Todas estas extensiones se aplicaron a tres casos importantes. En primer lugar, el control de plantas de tratamiento de aguas residuales es considerado. El objetivo de control, en este caso es mantener el efluente de la planta con una baja concentración de contaminantes mientras se trata de consumir la menor cantidad de energía posible. Tanto el caso de múltiples entradas múltiples salidas como el caso descentralizado son utilizados, dando buenos resultados para este sistema complejo. En segundo lugar, la selección de emparejamiento se aplica a una planta basada en celdas de combustible de óxido sólido. La tensión de salida y el exceso de oxígeno se controlan mediante la manipulación del combustible y el flujo de aire. Finalmente, los controladores de dos grados de libertad se aplican a una planta de neutralización del pH mediante el control de la velocidad de flujo de ácido. / In this work the data-driven control technique “Virtual Reference Feedback Tuning” is treated in different ways. In one hand, the capabilities of the method are extended with several proposed variations that allow a wider use of the method. An alternative two degrees of freedom control topology is considered, as well as its application to proportional-integral control. The multiple-inputs multiple-outputs case is also tackled, adding an automatic pairing selection between outputs and manipulated variables. The method is applied to the Internal Model Control topology in order to propose a robust stability test based entirely on data. All these extensions were applied to three important cases. In first place, the control of wastewater treatment plants is considered. The control objective in this case is to maintain the effluent of the plant with a low concentration of pollutants while trying to consume as less energy as possible. Both the multiple-inputs multiple-outputs and the decentralized case are used, yielding good results for this complex system. Second, the pairing selection is applied to a solid-oxide fuel cell plant. The output voltage and the oxygen excess is controlled by manipulating the fuel and the air flow rates. Finally the two degrees of freedom controllers are applied to a pH neutralization plant by controlling the acid flow rate.

Diferentes estudios realizados sobre el grado de utilización de los recursos de cómputo (CPU y memoria) en una red de PCs (cluster/NOW), han puesto de manifiesto que un elevado porcentaje de los mismos están infrautilizados. La posibilidad de utilizar esta potencia de cálculo para la ejecución de aplicaciones distribuidas con un rendimiento equivalente a un MPP, sin perturbar el trabajo del usuario local de cada workstation, ha sido objeto de estudio en este trabajo. Este doble objetivo puede ser alcanzado mediante el uso de técnicas de tiempo compartido. Un problema intrínseco de las técnicas de tiempo compartido es el modo de garantizar la coplanificación de aquellas tareas distribuidas que se comunican entre si; siendo este problema conocido como coscheduling. El principal objetivo del coscheduling es minimizar el tiempo de espera de las tareas distribuidas ante los eventos de comunicación y sincronización. El coscheduling puede ser alcanzado mediante la asignación de la CPU acorde con la ocurrencia de ciertos eventos locales, tradicionalmente de comunicación. De este modo, todas las tareas de una misma aplicación distribuida podrán progresar coordinadamente a lo largo del cluster.Este nuevo marco de trabajo impone, en nuestro modo de ver, un replanteamiento del problema clásico del coscheduling de aplicaciones distribuidas. El fin del coscheduling no solamente se debe restringir a decidir cuándo deben ser asignados los recursos de cómputo a las aplicaciones distribuidas, finalidad de las técnicas de coscheduling tradicionales, si no también cuántos recursos deben asignarse a cada aplicación. Este doble propósito nos ha llevado a desarrollar una nueva propuesta de coscheduling, denominada CoScheduling Cooperativo (CSC), orientada a la coordinación de múltiples aplicaciones paralelas en un entorno cluster no dedicado.CSC, a diferencia de las propuestas de coscheduling tradicionales, gestiona los recursos de cómputo de cada nodo, tanto en función de la ocurrencia de determinados eventos locales (de memoria, de CPU, de comunicación y de actividad del usuario local), como de la recepción de aquellos eventos ocurridos en nodos remotos y que han modificado los recursos asociados a los procesos cooperantes. El análisis de estos eventos permite a CSC adaptar los recursos de cómputo del cluster a las necesidades de ambos tipos de usuarios; el usuario local, caracterizado por unos elevados requerimientos de interactividad, y el usuario de las aplicaciones paralelas, en el cual priman los requerimientos de cómputo y de comunicación. De este modo, CSC puede gestionar la ejecución de múltiples aplicaciones paralelas simultáneamente, hecho que conlleva una mejor eficiencia en el uso de los recursos de cómputo disponibles.CSC ha sido implementado en un entorno Linux-PVM. Esta implementación ha permitido evaluar su rendimiento, con respecto a las políticas de coscheduling tradicionales, tanto en un entorno cluster controlado como en un entorno cluster productivo. La experimentación realizada ha mostrado como CSC obtiene unos resultados globales mejores que el resto de políticas evaluadas, tanto en lo que respecta al rendimiento de las aplicaciones del usuario local como de las aplicaciones distribuidas. Los resultados obtenidos por CSC demuestran que el desarrollo de políticas de planificación a corto plazo orientadas a entornos no dedicados permiten explotar, de una manera eficiente, todos aquellos recursos de cómputo disponibles, obteniendo unas métricas de speedup satisfactorias (en muchos casos superior a la mitad del número de tareas de la aplicación) y provocando un overhead inapreciable para el usuario local.

O 68Ga é um radionuclídeo promissor para a medicina nuclear, decaindo por emissão de pósitrons com abundância de 89%, apresentando tempo de meia vida física de 68 minutos, o que é compatível com a farmacocinética de muitas biomoléculas e substratos de baixo peso molecular. Outra característica importante é a sua disponibilidade por um sistema de gerador, onde o radionuclídeo pai, 68Ge (t1/2 = 270,95 dias) é adsorvido em uma coluna e o filho, 68Ga, é eluído na forma iônica 68Ga3+. O desenvolvimento dos geradores de 68Ge/68Ga teve início na década dos anos 60, mas o seu uso clínico começou a ser aceitável e relevante apenas recentemente. O método de separação do 68Ge do 68Ga mais utilizado é o sistema cromatográfico de troca iônica, devido sua praticidade de operação, mas outros sistemas de geradores já foram propostos, como de extração por solvente e técnica de evaporação. Atualmente, os geradores de 68Ge/68Ga são disponíveis comercialmente tanto com colunas utilizando matrizes inorgânicas preparadas com TiO2 ou SnO2 como também usando resina orgânica. A eficiência de eluição do 68Ga varia de 70 % a 80 %, apresentando uma queda ao longo do tempo. Os níveis de contaminação do 68Ge vão de 10-2 a 10-3 %, porém ocorre um aumento nos níveis de contaminação após longos períodos de uso. Mesmo com todos os avanços tecnológicos, ocorridos nas últimas décadas, no desenvolvimento dos geradores de 68Ge/68Ga, o eluato de 68Ga dos geradores comerciais ainda não é adequado para uso direto em seres humanos e algumas melhorias nos sistemas precisam ser feitas para diminuir os níveis de contaminação de 68Ge e impurezas químicas. O objetivo principal deste trabalho foi desenvolver um sistema de gerador de 68Ge/68Ga com o qual se pudesse eluir o 68Ga com qualidade necessária para uso clínico. O comportamento químico do Ge e do Ga foi avaliado em vários materiais adsorvedores inorgânicos. Foram desenvolvidos dois tipos de sistemas de geradores de 68Ge/68Ga utilizando o TiO2 como material adsorvedor: sistema de eluição com pressão manual e sistema de eluição a vácuo, controlado. As eficiências dos geradores foram similares às encontradas nos geradores comerciais, assim como os níveis de impurezas no eluato. Um novo método para o controle radionuclídico foi desenvolvido e apresentou resultados satisfatórios para determinação da contaminação do 68Ge no eluato do gerador. Foi proposto um protótipo de gerador capaz de fornecer 68Ga com a qualidade necessária para ser utilizado em aplicações médicas. / The 68Ga is a promising radionuclide for nuclear medicine, decaying by positron emission with an abundance of 89%, with physical half-life of 68 minutes, which is compatible with the pharmacokinetics of many biomolecules and low molecular weight substrates. Another important feature is its availability through a generator system, where the parent radionuclide, 68Ge (t1/2 = 270.95 days) is adsorbed on a column and the daughter, 68Ga, is eluted in an ionic form 68Ga3+. The development of 68Ge/68Ga generators began in the 60s, but its clinical use began to be acceptable and relevant only recently. The method of separation of 68Ge and 68Ga most used is the ion-exchange chromatographic system, due to its practical operation, but other generator systems have been proposed, such as solvent extraction and evaporation technique. Currently, 68Ge/68Ga generators are commercially available using inorganic matrices columns prepared with TiO2 or SnO2 as well using organic resin. The efficiency of 68Ga elution ranges from 70% to 80%, decreasing over time. The 68Ge breakthrough varies from 10-2 to10-3 % or lower in a fresh generator, but there is an increase in the levels of contamination after long periods of use. Even with all the technological advances in the development of 68Ge/68Ga generators in the past decades, the 68Ga eluted from commercial generators is not suitable for direct use in humans and some improvements in the systems need to be made to reduce the 68Ge breakthrough and chemical impurities levels. The main objective of this work was to develop a 68Ge/68Ga generator system is which 68Ga could be eluted with quality required for clinical use. The chemical behavior of Ge and Ga was evaluated on various inorganic adsorbents materials. Two types of 68Ge/68Ga generator systems were developed using TiO2 as adsorbent material: elution system with manual pressure and vacuum controlled. The efficiencies of the generators were similar to those found in commercial generators, as well as the impurity levels in the eluate. A new method for radionuclidic control was developed and showed good results for the determination of 68Ge breakthrough in 68Ga eluate. It was proposed a prototype 68Ga generator capable of providing the quality needed for use in medical applications.

Catullus 61 to 68 have not received the attention they deserve. Critics have either analyzed the poems in isolation or attempted superficial and selective examinations of the group as a whole. By scrutinizing the poet's use of recurrent vocabulary in poems 61 to 68, it is possible to see a definite cyclic progression throughout the poems, and a clear development of the various themes relating to love and marriage. Poem 61 presents, on the surface at least, a positive view of marriage. Certain negative elements are subtly introduced (the bride's hesitation, the potential infidelity of the groom, the role of the gods) which create some tension in the poem; but at the end, the marriage is consummated. Poem 62 brings the underlying tensions of poem 61 into the open. The boys' legalistic view of marriage overcomes the girls' emotional outcry against it; but it is the intensity and imagery of the girls' stanzas that remain in the reader's mind. Poem 63 plunges the reader into the world of mythology; but the presentation of Attis' relationship with Cybele in terms of a marriage follows logically from poems 61 and 62. The violence associated with Attis' negative "marriage" with Cybele causes the vox poetae to condemn such a relationship and wish it away from his experience. Poem 64 is a lengthy reflection on every aspect of love and marriage presented so far in the cycle. The apparently positive marriage of Peleus and Thetis is contrasted with the negative non-marriage of Theseus and Ariadne. Imagery found in the three previous poems is recalled here; the connotations associated with it eventually alter the reader's (and the poet's) perception of the outer story from positive to negative. The vox poetae returns to condemn all ages, all relationships. The vox poetae also opens poem 65, in which the poet begins to rework the material and themes from the previous poems. The death of his brother, following logically on the deaths caused by Achilles in poem 64, colours the poet's ability to write; but his devotion to his friend overcomes his inability and a glimmer of hope emerges in .the cycle. Poems 66 and 67 present the opposite extremes of love: the ideally happy marriage of Ptolemy and Berenice, and the scandal-ridden relationships mentioned by the door-bride. Poem 68 stands as a coda or summary of the entire cycle. As in poems 65 and 66, the poet is able to overcome his inability to write through the influence of his friend. He recalls the happy days of his relationship with his goddess-bride; but the allusion to the Laodamia myth is unfortunate, as it reminds the poet for the third time of his brother's death. Moreover, the details of the myth underscore how dangerous and potentially disastrous is his own relationship with his beloved. Poems 61 to 67 show that no relationship, no marriage can be truly happy. As poem 68 concludes, the poet reassesses his attempts to idealize his relationship with his beloved. He finally accepts her faults and resolves to love her on her terms. / Thesis / Doctor of Philosophy (PhD)

All mammalian cells encode microRNAs (miRNAs), which are small non-coding RNAs (~ 22 nucleotides) that control numerous physiological processes via regulation of gene expression. A number of viruses, in particular herpesviruses, also encode miRNAs. Gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi’s sarcoma associated herpesvirus (KSHV) are associated with lymphoproliferative disorders and some types of cancer in humans. Gammaherpesvirus-encoded miRNAs are predicted to contribute to pathogenesis and virus life cycle by suppressing host and viral target genes. However, the exact functions of these miRNAs during virus infection in the natural host are largely unknown. Strict species specificity has limited research on the human gammaherpesviruses mainly to in vitro studies. Murine gammaherpesvirus 68 (MHV-68) encodes at least 15 miRNAs and provides a unique tractable small animal model to investigate in vivo gammaherpesvirus pathogenic features that are difficult to assess in humans. Following intranasal infection of lab mice, the virus undergoes primary lytic infection in the lung epithelial cells and then spreads to the spleen establishing latent infection in splenic B lymphocytes, macrophages, and dendritic cells. The peak of the latent viral load occurs in the spleen at 14 dpi and then it decreases over time, but the virus is not completely eliminated and the latent viral genomes remain in the host cells for lifetime and can reactivate to produce infectious virus under certain conditions. The aims of my project were to: (1) establish and develop quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays for quantification of the MHV-68 miRNAs, (2) determine the miRNAs expression profiles during the two stages of virus infection (lytic and latent infection), (3) investigate the kinetics of the miRNAs expression during latency in vivo, (4) construct an MHV-68 miRNA mutant virus lacking 9 miRNAs (designated MHV-68.ΔmiRNAs), and (5) carry out thorough phenotypic characterisation of this mutant virus in order to determine the possible functions MHV-68 miRNAs in the context of natural host infection. It was found that the MHV-68 miRNAs expression pattern varied during different stages of infection, suggesting a differential regulation of the expression of these miRNAs depending on the phase of infection. In order to investigate the kinetics of miRNAs expression during latency in vivo, BALB/c mice were infected intranasally with MHV- 68 virus and spleens were harvested at days 10, 14, 21, and 32 post infection. The levels of miRNAs expression were determined by qRT-PCR in the splenocytes from infected mice. Interestingly, in contrast to the lytic MHV-68 protein coding genes, the expression of the miRNAs increased over time after 21 dpi, suggesting that the MHV-68-encoded miRNAs may play more fundamental roles during later stages of latent infection. In order to determine the potential roles of the MHV-68 miRNAs in virus pathogenesis, a miRNA mutant virus lacking the expression of 9 miRNAs, named MHV- 68.ΔmiRNAs, was constructed. The miRNA mutant virus replicated with the same kinetics as wild type virus in vitro and in vivo demonstrating that the deleted MHV-68 miRNAs are dispensable for virus lytic replication. To examine the roles of the miRNAs during virus latency, the MHV-68.ΔmiRNAs virus was characterised throughout a 49- day course of infection. Although the level of ex vivo reactivation of the MHV-68.ΔmiRNAs virus was comparable to that of the WT virus during the establishment of latency and as late as 28 dpi, the reactivation of the MHV-68.ΔmiRNAs virus was approximately 18-times higher than that of the WT virus at 49 dpi despite the similar levels of the genomic viral DNA loads at the same time-point. This suggests that the MHV-68 miRNAs suppress virus reactivation and promote maintenance of long-term latency. Moreover, the lytic viral gene expression levels were higher in splenocytes from the MHV-68.ΔmiRNAs-infected mice than the basal expression levels in the splenocytes from WT MHV-68-infected mice, suggesting that the MHV-68 miRNAs may suppress viral lytic gene expression during long-term latency in vivo and thus help the virus lay low.

We present a pedagogical paper on the detection of climate change and its attribution to anthropogenic influences. We attempt to separate the key thought processes and tools that are used when making qualitative statements about the level of human influence on climate. / Includes bibliographical references (p. 9). / Abstract in HTML and technical report in PDF available on the Massachusetts Institute of Technology Joint Program on the Science and Policy of Global Change website (http://mit.edu/globalchange/www/)

En la última década del siglo XX, el campo de los microsistemas para análisis total (µ-TAS) y, más concretamente, el de los DNA-chips ha adquirido una importancia preponderante en el ámbito de los microsistemas. En gran parte, el creciente interés por estos dispositivos se debe a las substanciales mejoras que prometen: análisis más rápidos, baratos y automatizados, pero también es debido a la posibilidad de implementar técnicas analíticas antes impensables (e.g. chips de hibridación). En el caso particular de los DNA-chips, se han desarrollado prototipos funcionales para PCR, LCR, electroforesis en gel, di-electroforesis, hibridación y varias combinaciones de estas técnicas, al tiempo que los chips de hibridación masiva (mayoritariamente basados en arrayers) han llegado a convertirse en un éxito comercial. Aun así, y aunque se ha llevado a cabo mucho trabajo en estos años, es necesaria todavía mucha investigación para afrontar algunos de los principales retos de los DNA-chips. En el transcurso de esta tesis doctoral, se ha llevado a cabo el desarrollo un proceso tecnológico común para la fabricación de DNA-chips multifunción (i.e. sistemas versátiles basados en PCR y electroforesis), poniendo un especial énfasis en la compatibilidad con los procesos CMOS estándar, a fin de conseguir desarrollar prototipos proto-industriales. Como demostrador de esta puesta a punto tecnológica, se han diseñado, fabricado y testado chips de PCR, y la PCR en chips ha sido optimizada con respecto a materiales de fabricación, metodologías de inserción/extracción, composición bioquímica de la mix de PCR, diferentes configuraciones de calentadores/sensores (Peltier/termopares vs. resistencias integradas) y la cinética de la reacción. / In the last decade of the twentieth century, the fields of µ-TAS and, more specifically, DNA-chips have acquired increasing importance in the microsystems arena. The main reason for this surge of interest lies in the advantages these new devices seek to bring forth: faster, cheaper and completely automated analyses, and also in the outbreak of novel analytical techniques (e.g. hybridization chips). In the particular case of DNA-chips, functional prototypes have been demonstrated for PCR, LCR, gel electrophoresis, di-electrophoresis, hybridization and various combinations of these techniques, whilst hybridization chips (mainly arrayer chips) have become a successful market application. But, even though a considerable amount of work has been carried out in these few years, much research is still required to address fundamental problems of DNA-chips. In this doctoral work, a common-ground technological setup for the production of multifunction DNA-chips (i.e. PCR plus electrophoresis systems) has been laid down, placing strong emphasis in its compatibility with standard CMOS processes in order to produce proto-industrial prototypes. As a demonstrator of this technological setup, PCR-chips have been designed, manufactured and tested, and the chip PCR reaction has been optimized with respect to surface materials, insertion and extraction methods, biochemical mix composition, heater/sensor setups (Peltier/thermocouple vs. thin-film driven systems) and reaction kinetics.

El trabajo de investigación que se describe en la presente memoria se plantea como objetivo el desarrollo de un EnFET con aplicación clínica en la medición de la concentración de urea de manera indirecta en líquido dializado para propósito de diagnóstico clínico más rápido, exacto y utilizando pequeñas cantidades de componentes químicos, específicamente en diálisis. El ENFET implementado atiende a la reacción química en donde la urea es catalizada por la enzima ureasa, utilizando una membrana enzimática con la ureasa como la enzima escogida. Para conseguir el objetivo planteado, se ha diseñado y puesto a punto la tecnología de fabricación del ISFET. Sobre la base de los resultados obtenidos por el propio autor en el desarrollo de su tesina, se ha desarrollado el tratamiento previo del transductor ISFET, su acondicionamiento y obtención de la sensibilidad adecuada para la aplicación clínica que se persigue. Se ha puesto también a punto el proceso de formación de la membrana enzimáticaconveniente, así como la técnica de inmovilización de la enzima ureasa y la "fijación" de la enzima ureasa sobre el transductor ISFET. La fijación de la membrana es uno de los puntos críticos del micro-sensor puesto que el período de vida del dispositivo depende totalmente de la "calidad" de la misma. Finalmente se han caracterizado en laboratorio los dispositivos EnFET obtenidos.El trabajo realizado ha generado un ENFET de fácil industrialización, con un tiempo de vida superior a dos meses y medio, eficiente para la medida indirecta de la concentración de urea en sangre a partir de la medida de la concentración de urea en el líquido dializado. El dispositivo se ha verificado en laboratorio realizando medidas de la concentración de urea sobre muestras ideales y comparando las medidas obtenidas con el dispositivo con medidas realizadas según procedimientos analíticos convencionales.Los parámetros del ENFET que reflejan su excelente calidad son Sensibilidad (mV/dec urea): 77.02; Límite inferior de respuesta lineal: 3.10-4 M; Rango lineal de Detección: 3.10-4 M - 2.10-3 M ;Tiempo de respuesta: 90s; Estabilidad del potencial medido: ±0.3mV; Tiempo de vida: 75 días. Los ENFETs desarrollados fueron sometidos a pruebas de reproducibilidad o repetitividad de la respuesta observándose que satisfacen ampliamente los requerimientos consistentes en que se obtienen valores de potencial eléctrico de valores similares en 10 mediciones efectuadas en dos días consecutivos. La desviación de los valores medidos respecto al valor promedio (253.61mV) aparece entre -0.34mV a 0.50mV. Estos valores del potencial eléctrico que aparece en la interfase membrana enzimática-óxido del ISFET, prácticamente constantes, y que esta relacionado en forma indirecta con la concentración de urea en la solución, permiten asegurar el buen desempeño del ENFET en pruebas reales en trabajo continuo. Posteriormente, el dispositivo se ha validado en aplicación realizando medidas de concentración de urea en muestras de liquido dializado de pacientes del Hospital Parc Tauli recogidas en distintas etapas del proceso de diálisis y procediendo a comparar y hacer las correlaciones respectivas con los valores medidos sobre las mismas muestras por un laboratorio comercial mostrándose que la diferencias en las medidas son del orden de 2.5%.

La computación grid constituye uno de los campos más prometedores de los sistemas informáticos. La próxima generación de aplicaciones científicas se beneficiará de una infraestructura de gran escala y multi organizacional que ofrece más potencia de cómputo de la que puede ofrecer cualquier institicuón de forma individual. Los sistemas grid necesitan planificadores de alto nivel que gestionen de forma adecuada los recursos distribuídos en varias organizaciones. Estos sistemas de gestión de recursos grid deben tomar decisiones de planificación sin realmente poseer los recursos y sin tener control total sobre las aplicaciones que en dichos recursos se ejecutan, introduciendo nuevos desafíos a la hora de realizar la planificación de aplicaciones. Aunque los sistemas grids consisten de muchos recursos y las aplicaciones enviados a estos sistemas pueden aprovechar estos recursos usándolos de forma coordinada, la mayoría de los sistemas de gestión de recursos se han centrado en la ejecución de aplicaciones secuenciales, convirtiendo el grid en un gran sistema multi-sitio donde las aplicaciones se ejecutan de forma batch.Sin embargo, en esta tesis nos hemos centrado en un tipo de aplicaciones que ha recibido poca atención hasta el momento: paralelas e interactivas. Las aplicaciones interactivas requieren la posibilidad de iniciar en un futuro inmediato su ejecución. Además, durante su ejecución es necesario proveer de mecanismos que establezcan un canal de comunicación entre el usuario y la aplicación. En el caso de las aplicaciones paralelas, es necesaria la co-asignación, es decir garantizar la disponibilidad simultánea de los recursos cuando la aplicación necesite usarlos. En este trabajo proponemos una nueva arquitectura para la ejecución de estos tipos de aplicaciones y una implementación de la misma: el gestor de recursos CrossBroker. Esta arquitectura incluye mecanismos que permiten la co-asignación de aplicaciones paralelos y la interacción de los usuarios con las aplicaciones en ejecución. Adicionalmente, con la introducción de un mecanismo de multiprogramación, proporcionamos un inicio de aplicaciones rápido incluso en escenarios de alta ocupación de los recursos. / Grid computing constitutes one of the most promising fields in computer systems. The next generation of scientific applications can profit from a large-scale, multi-organizational infrastructure that offers more computing power than one institution alone is able to afford. Grids need high-level schedulers that can be used to manage the resources spanning different organizations. These Grid Resource Management Systems (GRMS) have to make scheduling decisions without actually owning the grid resources, or having full control over the jobs that are running there. This introduces new challenges in the scheduling process done by the GRMSs. Although grids consist of many resources, and jobs submitted to grid may benefit from using them in a coordinated way, most of the Grid Resource Management Systems have focused on the execution of sequential jobs, with the grid being a large multi-site environment where jobs run in a batch-like way.However, in this work we concentrate on a kind of jobs that have received little attention to date: interactive and parallel jobs. Interactive jobs require the possibility of starting in the immediate future and need mechanisms to establish a communication channel with the user. Parallel applications introduce the need for co-allocation, guaranteeing the simultaneous availability of the resources when they are accessed by the applications. We address the challenges of executing such jobs with a new architecture for a GRMS and an implementation of that architecture called the CrossBroker. Our architecture includes mechanisms to allow the co-allocation of parallel jobs and the interaction of users with running applications. Additionally with the introduction of a multi-programming mechanism, a fast startup of jobs even in high occupancy scenarios is provided.