Sistemas de gestión de puentes : optimización de estrategias de mantenimiento : implementación en redes locales de carreteras

En la actualidad, y en consonancia con la tendencia de “sostenibilidad” extendida a todos los campos y parcelas de la ciencia, nos encontramos con un área de estudio basado en la problemática del inevitable deterioro de las estructuras existentes, y la gestión de las acciones a realizar para mantener las condiciones de servicio de los puentes y prolongar su vida útil. Tal y como se comienza a ver en las inversiones en los países avanzados, con una larga tradición en el desarrollo de sus infraestructuras, se muestra claramente el nuevo marco al que nos dirigimos. Las nuevas tendencias van encaminadas cada vez más a la conservación y mantenimiento, reduciéndose las partidas presupuestarias destinadas a nuevas actuaciones, debido a la completa vertebración territorial que se ha ido instaurando en estos países, entre los que España se encuentra. Este nutrido patrimonio de infraestructuras viarias, que cuentan a su vez con un importante número de estructuras, hacen necesarias las labores de gestión y mantenimiento de los puentes integrantes en las mismas. Bajo estas premisas, la tesis aborda el estado de desarrollo de la implementación de los sistemas de gestión de puentes, las tendencias actuales e identificación de campos por desarrollar, así como la aplicación específica a redes de carreteras de escasos recursos, más allá de la Red Estatal. Además de analizar las diversas metodologías de formación de inventarios, realización de inspecciones y evaluación del estado de puentes, se ha enfocado, como principal objetivo, el desarrollo de un sistema específico de predicción del deterioro y ayuda a la toma de decisiones. Este sistema, adicionalmente a la configuración tradicional de criterios de formación de bases de datos de estructuras e inspecciones, plantea, de forma justificada, la clasificación relativa al conjunto de la red gestionada, según su estado de condición. Eso permite, mediante técnicas de optimización, la correcta toma de decisiones a los técnicos encargados de la gestión de la red. Dentro de los diversos métodos de evaluación de la predicción de evolución del deterioro de cada puente, se plantea la utilización de un método bilineal simplificado envolvente del ajuste empírico realizado y de los modelos markovianos como la solución más efectiva para abordar el análisis de la predicción de la propagación del daño. Todo ello explotando la campaña experimenta realizada que, a partir de una serie de “fotografías técnicas” del estado de la red de puentes gestionados obtenidas mediante las inspecciones realizadas, es capaz de mejorar el proceso habitual de toma de decisiones. Toda la base teórica reflejada en el documento, se ve complementada mediante la implementación de un Sistema de Gestión de Puentes (SGP) específico, adaptado según las necesidades y limitaciones de la administración a la que se ha aplicado, en concreto, la Dirección General de Carreteras de la Junta de Comunidades de Castilla-La Mancha, para una muestra representativa del conjunto de puentes de la red de la provincia de Albacete, partiendo de una situación en la que no existe, actualmente, un sistema formal de gestión de puentes. Tras un meditado análisis del estado del arte dentro de los Capítulos 2 y 3, se plantea un modelo de predicción del deterioro dentro del Capítulo 4 “Modelo de Predicción del Deterioro”. De la misma manera, para la resolución del problema de optimización, se justifica la utilización de un novedoso sistema de optimización secuencial elegido dentro del Capítulo 5, los “Algoritmos Evolutivos”, en sus diferentes variantes, como la herramienta matemática más correcta para distribuir adecuadamente los recursos económicos dedicados a mantenimiento y conservación de los que esta administración pueda disponer en sus partidas de presupuesto a medio plazo. En el Capítulo 6, y en diversos Anexos al presente documento, se muestran los datos y resultados obtenidos de la aplicación específica desarrollada para la red local analizada, utilizando el modelo de deterioro y optimización secuencial, que garantiza la correcta asignación de los escasos recursos de los que disponen las redes autonómicas en España. Se plantea con especial interés la implantación de estos sistemas en la red secundaria española, debido a que reciben en los últimos tiempos una mayor responsabilidad de gestión, con recursos cada vez más limitados. Finalmente, en el Capítulo 7, se plantean una serie de conclusiones que nos hacen reflexionar de la necesidad de comenzar a pasar, en materia de gestión de infraestructuras, de los estudios teóricos y los congresos, hacia la aplicación y la práctica, con un planteamiento que nos debe llevar a cambios importantes en la forma de concebir la labor del ingeniero y las enseñanzas que se imparten en las escuelas. También se enumeran las aportaciones originales que plantea el documento frente al actual estado del arte. Se plantean, de la misma manera, las líneas de investigación en materia de Sistemas de Gestión de Puentes que pueden ayudar a refinar y mejorar los actuales sistemas utilizados. In line with the development of "sustainability" extended to all fields of science, we are faced with the inevitable and ongoing deterioration of existing structures, leading nowadays to the necessary management of maintaining the service conditions and life time extension of bridges. As per the increased amounts of money that can be observed being spent in the countries with an extensive and strong tradition in the development of their infrastructure, the trend can be clearly recognized. The new tendencies turn more and more towards conservation and maintenance, reducing programmed expenses for new construction activities, in line with the already wellestablished territorial structures, as is the case for Spain. This significant heritage of established road infrastructure, consequently containing a vast number of structures, imminently lead to necessary management and maintenance of the including bridges. Under these conditions, this thesis focusses on the status of the development of the management implementation for bridges, current trends, and identifying areas for further development. This also includes the specific application to road networks with limited resources, beyond the national highways. In addition to analyzing the various training methodologies, inventory inspections and condition assessments of bridges, the main objective has been the development of a specific methodology. This methodology, in addition to the traditional system of structure and inspection database training criteria, sustains the classification for the entire road network, according to their condition. This allows, through optimization techniques, for the correct decision making by the technical managers of the network. Among the various methods for assessing the evolution forecast of deterioration of each bridge, a simplified bilinear envelope adjustment made empirical method and Markov models as the most effective solution to address the analysis of predicting the spread of damage, arising from a "technical snapshot" obtained through inspections of the condition of the bridges included in the investigated network. All theoretical basis reflected in the document, is completed by implementing a specific Bridges Management System (BMS), adapted according to the needs and limitations of the authorities for which it has been applied, being in this case particularly the General Highways Directorate of the autonomous region of Castilla-La Mancha, for a representative sample of all bridges in the network in the province of Albacete, starting from a situation where there is currently no formal bridge management system. After an analysis of the state of the art in Chapters 2 and 3, a new deterioration prediction model is developed in Chapter 4, "Deterioration Prediction Model". In the same way, to solve the optimization problem is proposed the use of a singular system of sequential optimization elected under Chapter 5, the "Evolutionary Algorithms", the most suitable mathematical tool to adequately distribute the economic resources for maintenance and conservation for mid-term budget planning. In Chapter 6, and in the various appendices, data and results are presented of the developed application for the analyzed local network, from the optimization model, which guarantees the correct allocation of scarce resources at the disposal of authorities responsible for the regional networks in Spain. The implementation of these systems is witnessed with particular interest for the Spanish secondary network, because of the increasing management responsibility, with decreasing resources. Chapter 7 presents a series of conclusions that triggers to reconsider shifting from theoretical studies and conferences towards a practical implementation, considering how to properly conceive the engineering input and the related education. The original contributions of the document are also listed. In the same way, the research on the Bridges Management System can help evaluating and improving the used systematics.

An inhibitor of the microsomal triglyceride transfer protein inhibits apoB secretion from HepG2 cells.

The microsomal triglyceride (TG) transfer protein (MTP) is a heterodimeric lipid transfer protein that catalyzes the transport of triglyceride, cholesteryl ester, and phosphatidylcholine between membranes. Previous studies showing that the proximal cause of abetalipoproteinemia is an absence of MTP indicate that MTP function is required for the assembly of the apolipoprotein B (apoB) containing plasma lipoproteins, i.e., very low density lipoproteins and chylomicrons. However, the precise role of MTP in lipoprotein assembly is not known. In this study, the role of MTP in lipoprotein assembly is investigated using an inhibitor of MTP-mediated lipid transport, 2-[1-(3, 3-diphenylpropyl)-4-piperidinyl]-2,3-dihydro-1H-isoindol-1-o ne (BMS-200150). The similarity of the IC50 for inhibition of bovine MTP-mediated TG transfer (0.6 microM) to the Kd for binding of BMS-200150 to bovine MTP (1.3 microM) strongly supports that the inhibition of TG transfer is the result of a direct effect of the compound on MTP. BMS-200150 also inhibits the transfer of phosphatidylcholine, however to a lesser extent (30% at a concentration that almost completely inhibits TG and cholesteryl ester transfer). When BMS-200150 is added to cultured HepG2 cells, a human liver-derived cell line that secretes apoB containing lipoproteins, it inhibits apoB secretion in a concentration dependent manner. These results support the hypothesis that transport of lipid, and in particular, the transport of neutral lipid by MTP, plays a critical role in the assembly of apoB containing lipoproteins.

Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors.

The observed in vitro and in vivo benefit of combination treatment with anti-human immunodeficiency virus (HIV) agents prompted us to examine the potential of resistance development when two protease inhibitors are used concurrently. Recombinant HIV-1 (NL4-3) proteases containing combined resistance mutations associated with BMS-186318 and A-77003 (or saquinavir) were either inactive or had impaired enzyme activity. Subsequent construction of HIV-1 (NL4-3) proviral clones containing the same mutations yielded viruses that were severely impaired in growth or nonviable, confirming that combination therapy may be advantageous. However, passage of BMS-186318-resistant HIV-1 (RF) in the presence of either saquinavir or SC52151, which represented sequential drug treatment, produced viable viruses resistant to both BMS-186318 and the second compound. The predominant breakthrough virus contained the G48V/A71T/V82A protease mutations. The clone-purified RF (G48V/A71T/V82A) virus, unlike the corresponding defective NL4-3 triple mutant, grew well and displayed cross-resistance to four distinct protease inhibitors. Chimeric virus and in vitro mutagenesis studies indicated that the RF-specific protease sequence, specifically the Ile at residue 10, enabled the NL4-3 strain with the triple mutant to grow. Our results clearly indicate that viral genetic background will play a key role in determining whether cross-resistance variants will arise.

Expressão dos genes codificadores de canais de sódio Nav 1.7, Nav 1.8 e Nav 1.9 em portadores da Síndrome de Ardência Bucal

A síndrome de ardência bucal (SAB) é uma condição caracterizada pelo sintoma de ardência na mucosa oral, na ausência de qualquer sinal clínico. Sua etiologia é desconhecida e, até o momento, não dispõe de tratamento efetivo. Há entretanto características de doença neuropática que justificam investigações nesse sentido. O objetivo desse estudo foi mensurar a expressão gênica dos receptores de canais de sódio, Nav 1.7, Nav 1.8 e Nav 1.9, nos pacientes portadores de SAB. A casuística foi composta por dois grupos sendo o grupo de estudo composto por 12 pacientes portadores de SAB, selecionados através do critério estabelecido pela International Headache Society, em 2013 e o grupo controle composto por 4 pacientes não portadores de SAB. As amostras analisadas foram coletadas do dorso lingual, por meio de biópsia realizada com punch de 3 mm e profundidade de 3 mm, estas foram submetidas ao método de análise RT-PCR em tempo real. A expressividade dos genes de canais de sódio foi avaliada nos indivíduos portadores de SAB em relação aos do grupo controle, sendo esta calculada a partir da normalização dos dados da quantificação destes com os da expressão do gene constitutivo (GAPDH), pelo método de Cicle Threshold comparativo e analisados estatisticamente por meio do teste estatístico Mann-Whitnney. Observou-se o aumento da expressão gênica do Nav 1.7 (fold-change = 38.70) e diminuição da expressão gênica do Nav 1.9 (fold-change = 0.89), porém sem diferenças estatisticamente significativas entre os grupos analisados. O gene Nav 1.8 não foi expresso em nenhuma das amostras analisadas. O Nav 1.7 expressa-se tanto em neurônios nociceptivos quanto no sistema nervoso autônomo e mutações no Nav 1.9 tem sido associada a perda de percepção dolorosa. Os resultados obtidos embora não estatisticamente significativos são compatíveis com as características da doença, justificando a extensão dos estudos na linha expressão de genes codificadores dos canais de sódio em pacientes com SAB.