Computational methods for the analysis of protein structure and function

The vast majority of known proteins have not yet been experimentally characterized and little is known about their function. The design and implementation of computational tools can provide insight into the function of proteins based on their sequence, their structure, their evolutionary history and their association with other proteins. Knowledge of the three-dimensional (3D) structure of a protein can lead to a deep understanding of its mode of action and interaction, but currently the structures of <1% of sequences have been experimentally solved. For this reason, it became urgent to develop new methods that are able to computationally extract relevant information from protein sequence and structure. The starting point of my work has been the study of the properties of contacts between protein residues, since they constrain protein folding and characterize different protein structures. Prediction of residue contacts in proteins is an interesting problem whose solution may be useful in protein folding recognition and de novo design. The prediction of these contacts requires the study of the protein inter-residue distances related to the specific type of amino acid pair that are encoded in the so-called contact map. An interesting new way of analyzing those structures came out when network studies were introduced, with pivotal papers demonstrating that protein contact networks also exhibit small-world behavior. In order to highlight constraints for the prediction of protein contact maps and for applications in the field of protein structure prediction and/or reconstruction from experimentally determined contact maps, I studied to which extent the characteristic path length and clustering coefficient of the protein contacts network are values that reveal characteristic features of protein contact maps. Provided that residue contacts are known for a protein sequence, the major features of its 3D structure could be deduced by combining this knowledge with correctly predicted motifs of secondary structure. In the second part of my work I focused on a particular protein structural motif, the coiled-coil, known to mediate a variety of fundamental biological interactions. Coiled-coils are found in a variety of structural forms and in a wide range of proteins including, for example, small units such as leucine zippers that drive the dimerization of many transcription factors or more complex structures such as the family of viral proteins responsible for virus-host membrane fusion. The coiled-coil structural motif is estimated to account for 5-10% of the protein sequences in the various genomes. Given their biological importance, in my work I introduced a Hidden Markov Model (HMM) that exploits the evolutionary information derived from multiple sequence alignments, to predict coiled-coil regions and to discriminate coiled-coil sequences. The results indicate that the new HMM outperforms all the existing programs and can be adopted for the coiled-coil prediction and for large-scale genome annotation. Genome annotation is a key issue in modern computational biology, being the starting point towards the understanding of the complex processes involved in biological networks. The rapid growth in the number of protein sequences and structures available poses new fundamental problems that still deserve an interpretation. Nevertheless, these data are at the basis of the design of new strategies for tackling problems such as the prediction of protein structure and function. Experimental determination of the functions of all these proteins would be a hugely time-consuming and costly task and, in most instances, has not been carried out. As an example, currently, approximately only 20% of annotated proteins in the Homo sapiens genome have been experimentally characterized. A commonly adopted procedure for annotating protein sequences relies on the "inheritance through homology" based on the notion that similar sequences share similar functions and structures. This procedure consists in the assignment of sequences to a specific group of functionally related sequences which had been grouped through clustering techniques. The clustering procedure is based on suitable similarity rules, since predicting protein structure and function from sequence largely depends on the value of sequence identity. However, additional levels of complexity are due to multi-domain proteins, to proteins that share common domains but that do not necessarily share the same function, to the finding that different combinations of shared domains can lead to different biological roles. In the last part of this study I developed and validate a system that contributes to sequence annotation by taking advantage of a validated transfer through inheritance procedure of the molecular functions and of the structural templates. After a cross-genome comparison with the BLAST program, clusters were built on the basis of two stringent constraints on sequence identity and coverage of the alignment. The adopted measure explicity answers to the problem of multi-domain proteins annotation and allows a fine grain division of the whole set of proteomes used, that ensures cluster homogeneity in terms of sequence length. A high level of coverage of structure templates on the length of protein sequences within clusters ensures that multi-domain proteins when present can be templates for sequences of similar length. This annotation procedure includes the possibility of reliably transferring statistically validated functions and structures to sequences considering information available in the present data bases of molecular functions and structures.

Machine learning methods for prediction of disulphide bonding states of cysteine residues in proteins

The goal of this thesis work is to develop a computational method based on machine learning techniques for predicting disulfide-bonding states of cysteine residues in proteins, which is a sub-problem of a bigger and yet unsolved problem of protein structure prediction. Improvement in the prediction of disulfide bonding states of cysteine residues will help in putting a constraint in the three dimensional (3D) space of the respective protein structure, and thus will eventually help in the prediction of 3D structure of proteins. Results of this work will have direct implications in site-directed mutational studies of proteins, proteins engineering and the problem of protein folding. We have used a combination of Artificial Neural Network (ANN) and Hidden Markov Model (HMM), the so-called Hidden Neural Network (HNN) as a machine learning technique to develop our prediction method. By using different global and local features of proteins (specifically profiles, parity of cysteine residues, average cysteine conservation, correlated mutation, sub-cellular localization, and signal peptide) as inputs and considering Eukaryotes and Prokaryotes separately we have reached to a remarkable accuracy of 94% on cysteine basis for both Eukaryotic and Prokaryotic datasets, and an accuracy of 90% and 93% on protein basis for Eukaryotic dataset and Prokaryotic dataset respectively. These accuracies are best so far ever reached by any existing prediction methods, and thus our prediction method has outperformed all the previously developed approaches and therefore is more reliable. Most interesting part of this thesis work is the differences in the prediction performances of Eukaryotes and Prokaryotes at the basic level of input coding when ‘profile’ information was given as input to our prediction method. And one of the reasons for this we discover is the difference in the amino acid composition of the local environment of bonded and free cysteine residues in Eukaryotes and Prokaryotes. Eukaryotic bonded cysteine examples have a ‘symmetric-cysteine-rich’ environment, where as Prokaryotic bonded examples lack it.

Statistical methods for the analysis of DNA sequences: application to dinucleotide distribution in the human genome

Questa tesi si inserisce nell'ambito delle analisi statistiche e dei metodi stocastici applicati all'analisi delle sequenze di DNA. Nello specifico il nostro lavoro è incentrato sullo studio del dinucleotide CG (CpG) all'interno del genoma umano, che si trova raggruppato in zone specifiche denominate CpG islands. Queste sono legate alla metilazione del DNA, un processo che riveste un ruolo fondamentale nella regolazione genica. La prima parte dello studio è dedicata a una caratterizzazione globale del contenuto e della distribuzione dei 16 diversi dinucleotidi all'interno del genoma umano: in particolare viene studiata la distribuzione delle distanze tra occorrenze successive dello stesso dinucleotide lungo la sequenza. I risultati vengono confrontati con diversi modelli nulli: sequenze random generate con catene di Markov di ordine zero (basate sulle frequenze relative dei nucleotidi) e uno (basate sulle probabilità di transizione tra diversi nucleotidi) e la distribuzione geometrica per le distanze. Da questa analisi le proprietà caratteristiche del dinucleotide CpG emergono chiaramente, sia dal confronto con gli altri dinucleotidi che con i modelli random. A seguito di questa prima parte abbiamo scelto di concentrare le successive analisi in zone di interesse biologico, studiando l’abbondanza e la distribuzione di CpG al loro interno (CpG islands, promotori e Lamina Associated Domains). Nei primi due casi si osserva un forte arricchimento nel contenuto di CpG, e la distribuzione delle distanze è spostata verso valori inferiori, indicando che questo dinucleotide è clusterizzato. All’interno delle LADs si trovano mediamente meno CpG e questi presentano distanze maggiori. Infine abbiamo adottato una rappresentazione a random walk del DNA, costruita in base al posizionamento dei dinucleotidi: il walk ottenuto presenta caratteristiche drasticamente diverse all’interno e all’esterno di zone annotate come CpG island. Riteniamo pertanto che metodi basati su questo approccio potrebbero essere sfruttati per migliorare l’individuazione di queste aree di interesse nel genoma umano e di altri organismi.

Evolutionary forces shaping genomic islands of population differentiation in humans

Background Levels of differentiation among populations depend both on demographic and selective factors: genetic drift and local adaptation increase population differentiation, which is eroded by gene flow and balancing selection. We describe here the genomic distribution and the properties of genomic regions with unusually high and low levels of population differentiation in humans to assess the influence of selective and neutral processes on human genetic structure. Methods Individual SNPs of the Human Genome Diversity Panel (HGDP) showing significantly high or low levels of population differentiation were detected under a hierarchical-island model (HIM). A Hidden Markov Model allowed us to detect genomic regions or islands of high or low population differentiation. Results Under the HIM, only 1.5% of all SNPs are significant at the 1% level, but their genomic spatial distribution is significantly non-random. We find evidence that local adaptation shaped high-differentiation islands, as they are enriched for non-synonymous SNPs and overlap with previously identified candidate regions for positive selection. Moreover there is a negative relationship between the size of islands and recombination rate, which is stronger for islands overlapping with genes. Gene ontology analysis supports the role of diet as a major selective pressure in those highly differentiated islands. Low-differentiation islands are also enriched for non-synonymous SNPs, and contain an overly high proportion of genes belonging to the 'Oncogenesis' biological process. Conclusions Even though selection seems to be acting in shaping islands of high population differentiation, neutral demographic processes might have promoted the appearance of some genomic islands since i) as much as 20% of islands are in non-genic regions ii) these non-genic islands are on average two times shorter than genic islands, suggesting a more rapid erosion by recombination, and iii) most loci are strongly differentiated between Africans and non-Africans, a result consistent with known human demographic history.

Offline grammar-based recognition of handwritten sentences

This paper proposes a sequential coupling of a Hidden Markov Model (HMM) recognizer for offline handwritten English sentences with a probabilistic bottom-up chart parser using Stochastic Context-Free Grammars (SCFG) extracted from a text corpus. Based on extensive experiments, we conclude that syntax analysis helps to improve recognition rates significantly.

Minimal assumption derivation of a weak Clauser-Horne inequality

According to Bell's theorem a large class of hidden-variable models obeying Bell's notion of local causality (LC) conflict with the predictions of quantum mechanics. Recently, a Bell-type theorem has been proven using a weaker notion of LC, yet assuming the existence of perfectly correlated event types. Here we present a similar Bell-type theorem without this latter assumption. The derived inequality differs from the Clauser-Horne inequality by some small correction terms, which render it less constraining.

Improved cerebellar tissue classification on magnetic resonance images of brain.

PURPOSE: To develop and implement a method for improved cerebellar tissue classification on the MRI of brain by automatically isolating the cerebellum prior to segmentation. MATERIALS AND METHODS: Dual fast spin echo (FSE) and fluid attenuation inversion recovery (FLAIR) images were acquired on 18 normal volunteers on a 3 T Philips scanner. The cerebellum was isolated from the rest of the brain using a symmetric inverse consistent nonlinear registration of individual brain with the parcellated template. The cerebellum was then separated by masking the anatomical image with individual FLAIR images. Tissues in both the cerebellum and rest of the brain were separately classified using hidden Markov random field (HMRF), a parametric method, and then combined to obtain tissue classification of the whole brain. The proposed method for tissue classification on real MR brain images was evaluated subjectively by two experts. The segmentation results on Brainweb images with varying noise and intensity nonuniformity levels were quantitatively compared with the ground truth by computing the Dice similarity indices. RESULTS: The proposed method significantly improved the cerebellar tissue classification on all normal volunteers included in this study without compromising the classification in remaining part of the brain. The average similarity indices for gray matter (GM) and white matter (WM) in the cerebellum are 89.81 (+/-2.34) and 93.04 (+/-2.41), demonstrating excellent performance of the proposed methodology. CONCLUSION: The proposed method significantly improved tissue classification in the cerebellum. The GM was overestimated when segmentation was performed on the whole brain as a single object.

Genome profiling of sterol synthesis shows convergent evolution in parasites and guides chemotherapeutic attack

Sterols are an essential class of lipids in eukaryotes, where they serve as structural components of membranes and play important roles as signaling molecules. Sterols are also of high pharmacological significance: cholesterol-lowering drugs are blockbusters in human health, and inhibitors of ergosterol biosynthesis are widely used as antifungals. Inhibitors of ergosterol synthesis are also being developed for Chagas's disease, caused by Trypanosoma cruzi. Here we develop an in silico pipeline to globally evaluate sterol metabolism and perform comparative genomics. We generate a library of hidden Markov model-based profiles for 42 sterol biosynthetic enzymes, which allows expressing the genomic makeup of a given species as a numerical vector. Hierarchical clustering of these vectors functionally groups eukaryote proteomes and reveals convergent evolution, in particular metabolic reduction in obligate endoparasites. We experimentally explore sterol metabolism by testing a set of sterol biosynthesis inhibitors against trypanosomatids, Plasmodium falciparum, Giardia, and mammalian cells, and by quantifying the expression levels of sterol biosynthetic genes during the different life stages of T. cruzi and Trypanosoma brucei. The phenotypic data correlate with genomic makeup for simvastatin, which showed activity against trypanosomatids. Other findings, such as the activity of terbinafine against Giardia, are not in agreement with the genotypic profile.

Genomics of Rapid Incipient Speciation in Sympatric Threespine Stickleback

Ecological speciation is the process by which reproductively isolated populations emerge as a consequence of divergent natural or ecologically-mediated sexual selection. Most genomic studies of ecological speciation have investigated allopatric populations, making it difficult to infer reproductive isolation. The few studies on sympatric ecotypes have focused on advanced stages of the speciation process after thousands of generations of divergence. As a consequence, we still do not know what genomic signatures of the early onset of ecological speciation look like. Here, we examined genomic differentiation among migratory lake and resident stream ecotypes of threespine stickleback reproducing in sympatry in one stream, and in parapatry in another stream. Importantly, these ecotypes started diverging less than 150 years ago. We obtained 34,756 SNPs with restriction-site associated DNA sequencing and identified genomic islands of differentiation using a Hidden Markov Model approach. Consistent with incipient ecological speciation, we found significant genomic differentiation between ecotypes both in sympatry and parapatry. Of 19 islands of differentiation resisting gene flow in sympatry, all were also differentiated in parapatry and were thus likely driven by divergent selection among habitats. These islands clustered in quantitative trait loci controlling divergent traits among the ecotypes, many of them concentrated in one region with low to intermediate recombination. Our findings suggest that adaptive genomic differentiation at many genetic loci can arise and persist in sympatry at the very early stage of ecotype divergence, and that the genomic architecture of adaptation may facilitate this.

Genome-wide algorithm for detecting CNV associations with diseases

SNP genotyping arrays have been developed to characterize single-nucleotide polymorphisms (SNPs) and DNA copy number variations (CNVs). The quality of the inferences about copy number can be affected by many factors including batch effects, DNA sample preparation, signal processing, and analytical approach. Nonparametric and model-based statistical algorithms have been developed to detect CNVs from SNP genotyping data. However, these algorithms lack specificity to detect small CNVs due to the high false positive rate when calling CNVs based on the intensity values. Association tests based on detected CNVs therefore lack power even if the CNVs affecting disease risk are common. In this research, by combining an existing Hidden Markov Model (HMM) and the logistic regression model, a new genome-wide logistic regression algorithm was developed to detect CNV associations with diseases. We showed that the new algorithm is more sensitive and can be more powerful in detecting CNV associations with diseases than an existing popular algorithm, especially when the CNV association signal is weak and a limited number of SNPs are located in the CNV.^

Analysis of pattern recognition techniques for in-air signature biometrics

As a result of advances in mobile technology, new services which benefit from the ubiquity of these devices are appearing. Some of these services require the identification of the subject since they may access private user information. In this paper, we propose to identify each user by drawing his/her handwritten signature in the air (in-airsignature). In order to assess the feasibility of an in-airsignature as a biometric feature, we have analysed the performance of several well-known patternrecognitiontechniques—Hidden Markov Models, Bayes classifiers and dynamic time warping—to cope with this problem. Each technique has been tested in the identification of the signatures of 96 individuals. Furthermore, the robustness of each method against spoofing attacks has also been analysed using six impostors who attempted to emulate every signature. The best results in both experiments have been reached by using a technique based on dynamic time warping which carries out the recognition by calculating distances to an average template extracted from several training instances. Finally, a permanence analysis has been carried out in order to assess the stability of in-airsignature over time.

LiDAR simulation in modelled orchards to optimise the use of terretrial laser scanners and derived vegetative measures

Light detection and ranging (LiDAR) technology is beginning to have an impact on agriculture. Canopy volume and/or fruit tree leaf area can be estimated using terrestrial laser sensors based on this technology. However, the use of these devices may have different options depending on the resolution and scanning mode. As a consequence, data accuracy and LiDAR derived parameters are affected by sensor configuration, and may vary according to vegetative characteristics of tree crops. Given this scenario, users and suppliers of these devices need to know how to use the sensor in each case. This paper presents a computer program to determine the best configuration, allowing simulation and evaluation of different LiDAR configurations in various tree structures (or training systems). The ultimate goal is to optimise the use of laser scanners in field operations. The software presented generates a virtual orchard, and then allows the scanning simulation with a laser sensor. Trees are created using a hidden Markov tree (HMT) model. Varying the foliar structure of the orchard the LiDAR simulation was applied to twenty different artificially created orchards with or without leaves from two positions (lateral and zenith). To validate the laser sensor configuration, leaf surface of simulated trees was compared with the parameters obtained by LiDAR measurements: the impacted leaf area, the impacted total area (leaves and wood), and th impacted area in the three outer layers of leaves.

MBIS: Multivariate Bayesian Image Segmentation Tool

We present MBIS (Multivariate Bayesian Image Segmentation tool), a clustering tool based on the mixture of multivariate normal distributions model. MBIS supports multi-channel bias field correction based on a B-spline model. A second methodological novelty is the inclusion of graph-cuts optimization for the stationary anisotropic hidden Markov random field model. Along with MBIS, we release an evaluation framework that contains three different experiments on multi-site data. We first validate the accuracy of segmentation and the estimated bias field for each channel. MBIS outperforms a widely used segmentation tool in a cross-comparison evaluation. The second experiment demonstrates the robustness of results on atlas-free segmentation of two image sets from scan-rescan protocols on 21 healthy subjects. Multivariate segmentation is more replicable than the monospectral counterpart on T1-weighted images. Finally, we provide a third experiment to illustrate how MBIS can be used in a large-scale study of tissue volume change with increasing age in 584 healthy subjects. This last result is meaningful as multivariate segmentation performs robustly without the need for prior knowledge.

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.

Human activity recognition by inertial signals obtained from a smartphone

El Reconocimiento de Actividades Humanas es un área de investigación emergente, cuyo objetivo principal es identificar las acciones realizadas por un sujeto analizando las señales obtenidas a partir de unos sensores. El rápido crecimiento de este área de investigación dentro de la comunidad científica se explica, en parte, por el elevado número de aplicaciones que están surgiendo en los últimos años. Gran parte de las aplicaciones más prometedoras se encuentran en el campo de la salud, donde se puede hacer un seguimiento del nivel de movilidad de pacientes con trastornos motores, así como monitorizar el nivel de actividad física en pacientes con riesgo cardiovascular. Hasta hace unos años, mediante el uso de distintos tipos de sensores se podía hacer un seguimiento del paciente. Sin embargo, lejos de ser una solución a largo plazo y gracias a la irrupción del teléfono inteligente, este seguimiento se puede hacer de una manera menos invasiva, haciendo uso de la gran variedad de sensores integrados en este tipo de dispositivos. En este contexto nace este Trabajo de Fin de Grado, cuyo principal objetivo es evaluar nuevas técnicas de extracción de características para llevar a cabo un reconocimiento de actividades y usuarios así como una segmentación de aquellas. Este reconocimiento se hace posible mediante la integración de señales inerciales obtenidas por dos sensores presentes en la gran mayoría de teléfonos inteligentes: acelerómetro y giróscopo. Concretamente, se evalúan seis tipos de actividades realizadas por treinta usuarios: andar, subir escaleras, bajar escaleras, estar sentado, estar de pie y estar tumbado. Además y de forma paralela, se realiza una segmentación temporal de los distintos tipos de actividades realizadas por dichos usuarios. Todo ello se llevará a cabo haciendo uso de los Modelos Ocultos de Markov, así como de un conjunto de herramientas probadas satisfactoriamente en reconocimiento del habla: HTK (Hidden Markov Model Toolkit).