Genetic analysis of Pitx2 in left -right asymmetry and cardiovascular development

Pitx2, a paired-related homeobox gene that is mutated in human Rieger Syndrome, plays a key role in transferring the early asymmetric signals to individual organs. Pitx2 encodes three isoforms, Pitx2a, Pitx2b and Pitx2c. I found that Pitx2c was the Pitx2 isoform for regulating left-right asymmetry in heart, lung and the predominant isoform in guts. Previous studies suggested that the generation of left-right asymmetry within individual organs is an all or none, random event. Phenotypic analysis of various Pitx2 allelic combinations, that encode graded levels of Pitx2c, reveals an organ-intrinsic mechanism for regulating left-right asymmetric morphogenesis based on differential response to Pitx2c levels. The heart needs low Pitx2c levels, while the lungs and duodenum require higher doses of Pitx2c. In addition, the duodenal rotation is under strict control of Pitx2c activity. Left-right asymmetry development for aortic arch arteries involves complex vascular remodeling. Left-sided expression of Pitx2c in these developing vessels implied its potential function in this process. In order to determine if Pitx2c also can regulate the left-right asymmetry of the aortic arch arteries, a Pitx2c-specific loss of function mutation is generated. Although in wild type mice, the direction of the aortic arch is always oriented toward the left side, the directions of the aortic arches in the mutants were randomized, showing that Pitx2c also determined the left-right asymmetry of these vessels. I have further showed that the cardiac neural crest wasn't involved in this vascular remodeling process. In addition, all mutant embryos had Double Outlet Right Ventricle (DORV), a common congenital heart disease. This study provided insight into the mechanism of Pitx2c-mediated late stages of left-right asymmetry development and identified the roles of Pitx2c in regulation of aortic arch remodeling and heart development. ^

Analysis of the upcoming Modernisation of the Trade Pillar of the European Union-Mexico Global Agreement

Study for the EU Parliament co-authored by Rodrigo Polanco: The 1997 Global Agreement between the EC and its Member States and Mexico, together with the set of decisions taken in its framework, has been effective, and thus modifications of the agreement are mainly motivated by changes in the global landscape since it was first enacted. Therefore, broad considerations on how the European Union (EU) trade policy is shaped are extremely relevant for the upcoming negotiations with Mexico. In this context, the needs and expectations, both from the EU and Mexico, regarding any further agreements are examined, focusing in particular on areas beyond trade in goods and services such as procurement, investment, and regulatory cooperation. It is argued that the 'old' Association Agreements should be taken as models for any modifications, given their emphasis on EU-specific issues and their ability to accommodate the needs of Mexico in any deepened agreement.

Climate change technology transfer to developing countries: evidence analysis and policy recommendations

Developing countries are experiencing unprecedented levels of economic growth. As a result, they will be responsible for most of the future growth in energy demand and greenhouse gas (GHG) emissions. Curbing GHG emissions in developing countries has become one of the cornerstones of a future international agreement under the United Nations Framework Convention for Climate Change (UNFCCC). However, setting caps for developing countries’ GHG emissions has encountered strong resistance in the current round of negotiations. Continued economic growth that allows poverty eradication is still the main priority for most developing countries, and caps are perceived as a constraint to future growth prospects. The development, transfer and use of low-carbon technologies have more positive connotations, and are seen as the potential path towards low-carbon development. So far, the success of the UNFCCC process in improving the levels of technology transfer (TT) to developing countries has been limited. This thesis analyses the causes for such limited success and seeks to improve on the understanding about what constitutes TT in the field of climate change, establish the factors that enable them in developing countries and determine which policies could be implemented to reinforce these factors. Despite the wide recognition of the importance of technology and knowledge transfer to developing countries in the climate change mitigation policy agenda, this issue has not received sufficient attention in academic research. Current definitions of climate change TT barely take into account the perspective of actors involved in actual climate change TT activities, while respective measurements do not bear in mind the diversity of channels through which these happen and the outputs and effects that they convey. Furthermore, the enabling factors for TT in non-BRIC (Brazil, Russia, India, China) developing countries have been seldom investigated, and policy recommendations to improve the level and quality of TTs to developing countries have not been adapted to the specific needs of highly heterogeneous countries, commonly denominated as “developing countries”. This thesis contributes to enriching the climate change TT debate from the perspective of a smaller emerging economy (Chile) and by undertaking a quantitative analysis of enabling factors for TT in a large sample of developing countries. Two methodological approaches are used to study climate change TT: comparative case study analysis and quantitative analysis. Comparative case studies analyse TT processes in ten cases based in Chile, all of which share the same economic, technological and policy frameworks, thus enabling us to draw conclusions on the enabling factors and obstacles operating in TT processes. The quantitative analysis uses three methodologies – principal component analysis, multiple regression analysis and cluster analysis – to assess the performance of developing countries in a number of enabling factors and the relationship between these factors and indicators of TT, as well as to create groups of developing countries with similar performances. The findings of this thesis are structured to provide responses to four main research questions: What constitutes technology transfer and how does it happen? Is it possible to measure technology transfer, and what are the main challenges in doing so? Which factors enable climate change technology transfer to developing countries? And how do different developing countries perform in these enabling factors, and how can differentiated policy priorities be defined accordingly? vi Resumen Los paises en desarrollo estan experimentando niveles de crecimiento economico sin precedentes. Como consecuencia, se espera que sean responsables de la mayor parte del futuro crecimiento global en demanda energetica y emisiones de Gases de Efecto de Invernadero (GEI). Reducir las emisiones de GEI en los paises en desarrollo es por tanto uno de los pilares de un futuro acuerdo internacional en el marco de la Convencion Marco de las Naciones Unidas para el Cambio Climatico (UNFCCC). La posibilidad de compromisos vinculantes de reduccion de emisiones de GEI ha sido rechazada por los paises en desarrollo, que perciben estos limites como frenos a su desarrollo economico y a su prioridad principal de erradicacion de la pobreza. El desarrollo, transferencia y uso de tecnologias bajas en carbono tiene connotaciones mas positivas y se percibe como la via hacia un crecimiento bajo en carbono. Hasta el momento, la UNFCCC ha tenido un exito limitado en la promocion de transferencias de tecnologia (TT) a paises en desarrollo. Esta tesis analiza las causas de este resultado y busca mejorar la comprension sobre que constituye transferencia de tecnologia en el area de cambio climatico, cuales son los factores que la facilitan en paises en desarrollo y que politicas podrian implementarse para reforzar dichos factores. A pesar del extendido reconocimiento sobre la importancia de la transferencia de tecnologia a paises en desarrollo en la agenda politica de cambio climatico, esta cuestion no ha sido suficientemente atendida por la investigacion existente. Las definiciones actuales de transferencia de tecnologia relacionada con la mitigacion del cambio climatico no tienen en cuenta la diversidad de canales por las que se manifiestan o los efectos que consiguen. Los factores facilitadores de TT en paises en desarrollo no BRIC (Brasil, Rusia, India y China) apenas han sido investigados, y las recomendaciones politicas para aumentar el nivel y la calidad de la TT no se han adaptado a las necesidades especificas de paises muy heterogeneos aglutinados bajo el denominado grupo de "paises en desarrollo". Esta tesis contribuye a enriquecer el debate sobre la TT de cambio climatico con la perspectiva de una economia emergente de pequeno tamano (Chile) y el analisis cuantitativo de factores que facilitan la TT en una amplia muestra de paises en desarrollo. Se utilizan dos metodologias para el estudio de la TT a paises en desarrollo: analisis comparativo de casos de estudio y analisis cuantitativo basado en metodos multivariantes. Los casos de estudio analizan procesos de TT en diez casos basados en Chile, para derivar conclusiones sobre los factores que facilitan u obstaculizan el proceso de transferencia. El analisis cuantitativo multivariante utiliza tres metodologias: regresion multiple, analisis de componentes principales y analisis cluster. Con dichas metodologias se busca analizar el posicionamiento de diversos paises en cuanto a factores que facilitan la TT; las relaciones entre dichos factores e indicadores de transferencia tecnologica; y crear grupos de paises con caracteristicas similares que podrian beneficiarse de politicas similares para la promocion de la transferencia de tecnologia. Los resultados de la tesis se estructuran en torno a cuatro preguntas de investigacion: .Que es la transferencia de tecnologia y como ocurre?; .Es posible medir la transferencia de tecnologias de bajo carbono?; .Que factores facilitan la transferencia de tecnologias de bajo carbono a paises en desarrollo? y .Como se puede agrupar a los paises en desarrollo en funcion de sus necesidades politicas para la promocion de la transferencia de tecnologias de bajo carbono?

Analysis of Thematic Classified Aerial Images Trough Multispectral and LIDAR Data

The application of thematic maps obtained through the classification of remote images needs the obtained products with an optimal accuracy. The registered images from the airplanes display a very satisfactory spatial resolution, but the classical methods of thematic classification not always give better results than when the registered data from satellite are used. In order to improve these results of classification, in this work, the LIDAR sensor data from first return (Light Detection And Ranging) registered simultaneously with the spectral sensor data from airborne are jointly used. The final results of the thematic classification of the scene object of study have been obtained, quantified and discussed with and without LIDAR data, after applying different methods: Maximum Likehood Classification, Support Vector Machine with four different functions kernel and Isodata clustering algorithm (ML, SVM-L, SVM-P, SVM-RBF, SVM-S, Isodata). The best results are obtained for SVM with Sigmoide kernel. These allow the correlation with others different physical parameters with great interest like Manning hydraulic coefficient, for their incorporation in a GIS and their application in hydraulic modeling.

How can video analysis help laparoscopic surgeons?

Automatic analysis of minimally invasive surgical (MIS) video has the potential to drive new solutions that alleviate existing needs for safer surgeries: reproducible training programs, objective and transparent assessment systems and navigation tools to assist surgeons and improve patient safety. As an unobtrusive, always available source of information in the operating room (OR), this research proposes the use of surgical video for extracting useful information during surgical operations. Methodology proposed includes tools' tracking algorithm and 3D reconstruction of the surgical field. The motivation for these solutions is the augmentation of the laparoscopic view in order to provide orientation aids, optimal surgical path visualization, or preoperative virtual models overlay

Incremental analysis of constraint logic programs

Global analyzers traditionally read and analyze the entire program at once, in a nonincremental way. However, there are many situations which are not well suited to this simple model and which instead require reanalysis of certain parts of a program which has already been analyzed. In these cases, it appears inecient to perform the analysis of the program again from scratch, as needs to be done with current systems. We describe how the xed-point algorithms used in current generic analysis engines for (constraint) logic programming languages can be extended to support incremental analysis. The possible changes to a program are classied into three types: addition, deletion, and arbitrary change. For each one of these, we provide one or more algorithms for identifying the parts of the analysis that must be recomputed and for performing the actual recomputation. The potential benets and drawbacks of these algorithms are discussed. Finally, we present some experimental results obtained with an implementation of the algorithms in the PLAI generic abstract interpretation framework. The results show signicant benets when using the proposed incremental analysis algorithms.

Pushover analysis for the seismic response prediction of cable-stayed bridges under multi-directional excitation

Cable-stayed bridges represent nowadays key points in transport networks and their seismic behavior needs to be fully understood, even beyond the elastic range of materials. Both nonlinear dynamic (NL-RHA) and static (pushover) procedures are currently available to face this challenge, each with intrinsic advantages and disadvantages, and their applicability in the study of the nonlinear seismic behavior of cable-stayed bridges is discussed here. The seismic response of a large number of finite element models with different span lengths, tower shapes and class of foundation soil is obtained with different procedures and compared. Several features of the original Modal Pushover Analysis (MPA) are modified in light of cable-stayed bridge characteristics, furthermore, an extension of MPA and a new coupled pushover analysis (CNSP) are suggested to estimate the complex inelastic response of such outstanding structures subjected to multi-axial strong ground motions.

Incremental analysis of logic programs

Global analyzers traditionally read and analyze the entire program at once, in a non-incremental way. However, there are many situations which are not well suited to this simple model and which instead require reanalysis of certain parts of a program which has already been analyzed. In these cases, it appears inefficient to perform the analysis of the program again from scratch, as needs to be done with current systems. We describe how the fixpoint algorithms in current generic analysis engines can be extended to support incremental analysis. The possible changes to a program are classified into three types: addition, deletion, and arbitrary change. For each one of these, we provide one or more algorithms for identifying the parts of the analysis that must be recomputed and for performing the actual recomputation. The potential benefits and drawbacks of these algorithms are discussed. Finally, we present some experimental results obtained with an implementation of the algorithms in the PLAI generic abstract interpretation framework. The results show significant benefits when using the proposed incremental analysis algorithms.

3D + t Morphological Processing: Applications to Embryogenesis Image Analysis

We propose to directly process 3D + t image sequences with mathematical morphology operators, using a new classi?cation of the 3D+t structuring elements. Several methods (?ltering, tracking, segmentation) dedicated to the analysis of 3D + t datasets of zebra?sh embryogenesis are introduced and validated through a synthetic dataset. Then, we illustrate the application of these methods to the analysis of datasets of zebra?sh early development acquired with various microscopy techniques. This processing paradigm produces spatio-temporal coherent results as it bene?ts from the intrinsic redundancy of the temporal dimension, and minimizes the needs for human intervention in semi-automatic algorithms.

Automatic motion compensation of free breathing acquired myocardial perfusion data by using independent component analysis

Images acquired during free breathing using first-pass gadolinium-enhanced myocardial perfusion magnetic resonance imaging (MRI) exhibit a quasiperiodic motion pattern that needs to be compensated for if a further automatic analysis of the perfusion is to be executed. In this work, we present a method to compensate this movement by combining independent component analysis (ICA) and image registration: First, we use ICA and a time?frequency analysis to identify the motion and separate it from the intensity change induced by the contrast agent. Then, synthetic reference images are created by recombining all the independent components but the one related to the motion. Therefore, the resulting image series does not exhibit motion and its images have intensities similar to those of their original counterparts. Motion compensation is then achieved by using a multi-pass image registration procedure. We tested our method on 39 image series acquired from 13 patients, covering the basal, mid and apical areas of the left heart ventricle and consisting of 58 perfusion images each. We validated our method by comparing manually tracked intensity profiles of the myocardial sections to automatically generated ones before and after registration of 13 patient data sets (39 distinct slices). We compared linear, non-linear, and combined ICA based registration approaches and previously published motion compensation schemes. Considering run-time and accuracy, a two-step ICA based motion compensation scheme that first optimizes a translation and then for non-linear transformation performed best and achieves registration of the whole series in 32 ± 12 s on a recent workstation. The proposed scheme improves the Pearsons correlation coefficient between manually and automatically obtained time?intensity curves from .84 ± .19 before registration to .96 ± .06 after registration

Meta-analysis of strategies to control nitrate leaching in irrigated agricultural systems and their effects on crop yield.

Nitrate leaching (NL) is an important N loss process in irrigated agriculture that imposes a cost on the farmer and the environment. A meta-analysis of published experimental results from agricultural irrigated systems was conducted to identify those strategies that have proven effective at reducing NL and to quantify the scale of reduction that can be achieved. Forty-four scientific articles were identified which investigated four main strategies (water and fertilizer management, use of cover crops and fertilizer technology) creating a database with 279 observations on NL and 166 on crop yield. Management practices that adjust water application to crop needs reduced NL by a mean of 80% without a reduction in crop yield. Improved fertilizer management reduced NL by 40%, and the best relationship between yield and NL was obtained when applying the recommended fertilizer rate. Replacing a fallow with a non-legume cover crop reduced NL by 50% while using a legume did not have any effect on NL. Improved fertilizer technology also decreased NL but was the least effective of the selected strategies. The risk of nitrate leaching from irrigated systems is high, but optimum management practices may mitigate this risk and maintain crop yields while enhancing environmental sustainability.

Analysis of the impact of globalization and economic growth on food security in developing countries

A pesar de los importantes avances en la reducción del hambre, la seguridad alimentaria continúa siendo un reto de dimensión internacional. La seguridad alimentaria es un concepto amplio y multidimensional, cuyo análisis abarca distintas escalas y horizontes temporales. Dada su complejidad, la identificación de las causas de la inseguridad alimentaria y la priorización de las medias para abordarlas, son dos cuestiones que suscitan un intenso debate en la actualidad. El objetivo de esta tesis es evaluar el impacto de la globalización y el crecimiento económico en la seguridad alimentaria en los países en desarrollo, desde una perspectiva macro y un horizonte temporal a largo plazo. La influencia de la globalización se aborda de una manera secuencial. En primer lugar, se analiza la relación entre la inversión público-privada en infraestructuras y las exportaciones agrarias. A continuación, se estudia el impacto de las exportaciones agrarias en los indicadores de seguridad alimentaria. El estudio del impacto del crecimiento económico aborda los cambios paralelos en la distribución de la renta, y cómo la inequidad influye en el comportamiento de la seguridad alimentaria nacional. Además, se analiza en qué medida el crecimiento económico contribuye a acelerar el proceso de mejora de la seguridad alimentaria. Con el fin de conseguir los objetivos mencionados, se llevan a cabo varios análisis econométricos basados en datos de panel, en el que se combinan datos de corte transversal de 52 países y datos temporales comprendidos en el periodo 1991-2012. Se analizan tanto variables en niveles como variables en tasas de cambio anual. Se aplican los modelos de estimación de efectos variables y efectos fijos, ambos en niveles y en primeras diferencias. La tesis incluye cuatro tipos de modelos econométricos, cada uno de ellos con sus correspondientes pruebas de robustez y especificaciones. Los resultados matizan la importancia de la globalización y el crecimiento económico como mecanismos de mejora de la seguridad alimentaria en los países en desarrollo. Se obtienen dos conclusiones relativas a la globalización. En primer lugar, los resultados sugieren que la promoción de las inversiones privadas en infraestructuras contribuye a aumentar las exportaciones agrarias. En segundo lugar, se observa que las exportaciones agrarias pueden tener un impacto negativo en los indicadores de seguridad alimentaria. La combinación de estas dos conclusiones sugiere que la apertura comercial y financiera no contribuye por sí misma a la mejora de la seguridad alimentaria en los países en desarrollo. La apertura internacional de los países en desarrollo ha de ir acompañada de políticas e inversiones que desarrollen sectores productivos de alto valor añadido, que fortalezcan la economía nacional y reduzcan su dependencia exterior. En relación al crecimiento económico, a pesar del incuestionable hecho de que el crecimiento económico es una condición necesaria para reducir los niveles de subnutrición, no es una condición suficiente. Se han identificado tres estrategias adicionales que han de acompañar al crecimiento económico con el fin de intensificar su impacto positivo sobre la subnutrición. Primero, es necesario que el crecimiento económico sea acompañado de una distribución más equitativa de los ingresos. Segundo, el crecimiento económico ha de reflejarse en un aumento de inversiones en salud, agua y saneamiento y educación. Se observa que, incluso en ausencia de crecimiento económico, mejoras en el acceso a agua potable contribuyen a reducir los niveles de población subnutrida. Tercero, el crecimiento económico sostenible en el largo plazo parece tener un mayor impacto positivo sobre la seguridad alimentaria que el crecimiento económico más volátil o inestable en el corto plazo. La estabilidad macroeconómica se identifica como una condición necesaria para alcanzar una mayor mejora en la seguridad alimentaria, incluso habiéndose mejorado la equidad en la distribución de los ingresos. Por último, la tesis encuentra que los países en desarrollo analizados han experimentado diferentes trayectorias no lineales en su proceso de mejora de sus niveles de subnutrición. Los resultados sugieren que un mayor nivel inicial de subnutrición y el crecimiento económico son responsables de una respuesta más rápida al reto de la mejora de la seguridad alimentaria. ABSTRACT Despite the significant reductions of hunger, food security still remains a global challenge. Food security is a wide concept that embraces multiple dimensions, and has spatial-temporal scales. Because of its complexity, the identification of the drivers underpinning food insecurity and the prioritization of measures to address them are a subject of intensive debate. This thesis attempts to assess the impact of globalization and economic growth on food security in developing countries with a macro level scale (country) and using a long-term approach. The influence of globalization is addressed in a sequential way. First, the impact of public-private investment in infrastructure on agricultural exports in developing countries is analyzed. Secondly, an assessment is conducted to determine the impact of agricultural exports on food security indicators. The impact of economic growth focuses on the parallel changes in income inequality and how the income distribution influences countries' food security performance. Furthermore, the thesis analyzes to what extent economic growth helps accelerating food security improvements. To address the above mentioned goals, various econometric models are formulated. Models use panel data procedures combining cross-sectional data of 52 countries and time series data from 1991 to 2012. Yearly data are expressed both in levels and in changes. The estimation models applied are random effects estimation and fixed effects estimations, both in levels and in first differences. The thesis includes four families of econometric models, each with its own set of robustness checks and specifications. The results qualify the relevance of globalization and economic growth as enabling mechanisms for improving food security in developing countries. Concerning globalization, two main conclusions can be drawn. First, results showed that enhancing foreign private investment in infrastructures contributes to increase agricultural exports. Second, agricultural exports appear to have a negative impact on national food security indicators. These two conclusions suggest that trade and financial openness per se do not contribute directly to improve food security in development countries. Both measures should be accompanied by investments and policies to support the development of national high value productive sectors, to strengthen the domestic economy and reduce its external dependency. Referring to economic growth, despite the unquestionable fact that income growth is a pre-requisite for reducing undernourishment, results suggest that it is a necessary but not a sufficient condition. Three additional strategies should accompany economic growth to intensifying its impact on food security. Firstly, it is necessary that income growth should be accompanied by a better distribution of income. Secondly, income growth needs to be followed by investments and policies in health, sanitation and education to improve food security. Even if economic growth falters, sustained improvements in the access to drinking water may still give rise to reductions in the percentage of undernourished people. And thirdly, long-term economic growth appears to have a greater impact on reducing hunger than growth regimes that combine periods of growth peaks followed by troughs. Macroeconomic stability is a necessary condition for accelerating food security. Finally, the thesis finds that the developing countries analyzed have experienced different non-linear paths toward improving food security. Results also show that a higher initial level of undernourishment and economic growth result in a faster response for improving food security.

Asymptotic analysis of vertical geothermal boreholes in the limit of slowly varyng heat injection rates

Theoretical models for the thermal response of vertical geothermal boreholes often assume that the characteristic time of variation of the heat injection rate is much larger than the characteristic diffusion time across the borehole. In this case, heat transfer inside the borehole and in its immediate surroundings is quasi-steady in the first approximation, while unsteady effects enter only in the far field. Previous studies have exploited this disparity of time scales, incorporating approximate matching conditions to couple the near-borehole region with the outer unsteady temperatura field. In the present work matched asymptotic expansion techniques are used to analyze the heat transfer problem, delivering a rigorous derivation of the true matching condition between the two regions and of the correct definition of the network of thermal resistances that represents the quasi-steady solution near the borehole. Additionally, an apparent temperature due to the unsteady far field is identified that needs to be taken into account by the near-borehole region for the correct computation of the heat injection rate. This temperature differs from the usual mean borehole temperature employed in the literatura.

Urban transport interchanges: Importance-Performance analysis for evaluating perceived quality

As the world becomes more urbanised, public transport in cities must seek to provide viable alternatives to individual car transport. At an urban level, interchanges in public transport networks provide easy transfers between and within different transport modes and facilitate seamless travel. This study proposes a methodological framework with which to identify the factors that travellers view as key elements of an urban transport interchange. An attitudinal survey was undertaken in order to collect information about users? needs and perceptions in the Moncloa interchange in Madrid, Spain. The results obtained from an Importance-Performance Analysis (IPA) show that aspects related to the signposting of different facilities and transport services, the internal design of the interchange and the surrounding area, and safety and security are the greatest strengths of the interchange.

A linearization-based system reliability method with application to geotechnical analysis

Los análisis de fiabilidad representan una herramienta adecuada para contemplar las incertidumbres inherentes que existen en los parámetros geotécnicos. En esta Tesis Doctoral se desarrolla una metodología basada en una linealización sencilla, que emplea aproximaciones de primer o segundo orden, para evaluar eficientemente la fiabilidad del sistema en los problemas geotécnicos. En primer lugar, se emplean diferentes métodos para analizar la fiabilidad de dos aspectos propios del diseño de los túneles: la estabilidad del frente y el comportamiento del sostenimiento. Se aplican varias metodologías de fiabilidad — el Método de Fiabilidad de Primer Orden (FORM), el Método de Fiabilidad de Segundo Orden (SORM) y el Muestreo por Importancia (IS). Los resultados muestran que los tipos de distribución y las estructuras de correlación consideradas para todas las variables aleatorias tienen una influencia significativa en los resultados de fiabilidad, lo cual remarca la importancia de una adecuada caracterización de las incertidumbres geotécnicas en las aplicaciones prácticas. Los resultados también muestran que tanto el FORM como el SORM pueden emplearse para estimar la fiabilidad del sostenimiento de un túnel y que el SORM puede mejorar el FORM con un esfuerzo computacional adicional aceptable. Posteriormente, se desarrolla una metodología de linealización para evaluar la fiabilidad del sistema en los problemas geotécnicos. Esta metodología solamente necesita la información proporcionada por el FORM: el vector de índices de fiabilidad de las funciones de estado límite (LSFs) que componen el sistema y su matriz de correlación. Se analizan dos problemas geotécnicos comunes —la estabilidad de un talud en un suelo estratificado y un túnel circular excavado en roca— para demostrar la sencillez, precisión y eficiencia del procedimiento propuesto. Asimismo, se reflejan las ventajas de la metodología de linealización con respecto a las herramientas computacionales alternativas. Igualmente se muestra que, en el caso de que resulte necesario, se puede emplear el SORM —que aproxima la verdadera LSF mejor que el FORM— para calcular estimaciones más precisas de la fiabilidad del sistema. Finalmente, se presenta una nueva metodología que emplea Algoritmos Genéticos para identificar, de manera precisa, las superficies de deslizamiento representativas (RSSs) de taludes en suelos estratificados, las cuales se emplean posteriormente para estimar la fiabilidad del sistema, empleando la metodología de linealización propuesta. Se adoptan tres taludes en suelos estratificados característicos para demostrar la eficiencia, precisión y robustez del procedimiento propuesto y se discuten las ventajas del mismo con respecto a otros métodos alternativos. Los resultados muestran que la metodología propuesta da estimaciones de fiabilidad que mejoran los resultados previamente publicados, enfatizando la importancia de hallar buenas RSSs —y, especialmente, adecuadas (desde un punto de vista probabilístico) superficies de deslizamiento críticas que podrían ser no-circulares— para obtener estimaciones acertadas de la fiabilidad de taludes en suelos. Reliability analyses provide an adequate tool to consider the inherent uncertainties that exist in geotechnical parameters. This dissertation develops a simple linearization-based approach, that uses first or second order approximations, to efficiently evaluate the system reliability of geotechnical problems. First, reliability methods are employed to analyze the reliability of two tunnel design aspects: face stability and performance of support systems. Several reliability approaches —the first order reliability method (FORM), the second order reliability method (SORM), the response surface method (RSM) and importance sampling (IS)— are employed, with results showing that the assumed distribution types and correlation structures for all random variables have a significant effect on the reliability results. This emphasizes the importance of an adequate characterization of geotechnical uncertainties for practical applications. Results also show that both FORM and SORM can be used to estimate the reliability of tunnel-support systems; and that SORM can outperform FORM with an acceptable additional computational effort. A linearization approach is then developed to evaluate the system reliability of series geotechnical problems. The approach only needs information provided by FORM: the vector of reliability indices of the limit state functions (LSFs) composing the system, and their correlation matrix. Two common geotechnical problems —the stability of a slope in layered soil and a circular tunnel in rock— are employed to demonstrate the simplicity, accuracy and efficiency of the suggested procedure. Advantages of the linearization approach with respect to alternative computational tools are discussed. It is also found that, if necessary, SORM —that approximates the true LSF better than FORM— can be employed to compute better estimations of the system’s reliability. Finally, a new approach using Genetic Algorithms (GAs) is presented to identify the fully specified representative slip surfaces (RSSs) of layered soil slopes, and such RSSs are then employed to estimate the system reliability of slopes, using our proposed linearization approach. Three typical benchmark-slopes with layered soils are adopted to demonstrate the efficiency, accuracy and robustness of the suggested procedure, and advantages of the proposed method with respect to alternative methods are discussed. Results show that the proposed approach provides reliability estimates that improve previously published results, emphasizing the importance of finding good RSSs —and, especially, good (probabilistic) critical slip surfaces that might be non-circular— to obtain good estimations of the reliability of soil slope systems.