USING PROBABILISTIC GRAPHICAL MODELS TO DRAW INFERENCES IN SENSOR NETWORKS WITH TRACKING APPLICATIONS

Sensor networks have been an active research area in the past decade due to the variety of their applications. Many research studies have been conducted to solve the problems underlying the middleware services of sensor networks, such as self-deployment, self-localization, and synchronization. With the provided middleware services, sensor networks have grown into a mature technology to be used as a detection and surveillance paradigm for many real-world applications. The individual sensors are small in size. Thus, they can be deployed in areas with limited space to make unobstructed measurements in locations where the traditional centralized systems would have trouble to reach. However, there are a few physical limitations to sensor networks, which can prevent sensors from performing at their maximum potential. Individual sensors have limited power supply, the wireless band can get very cluttered when multiple sensors try to transmit at the same time. Furthermore, the individual sensors have limited communication range, so the network may not have a 1-hop communication topology and routing can be a problem in many cases. Carefully designed algorithms can alleviate the physical limitations of sensor networks, and allow them to be utilized to their full potential. Graphical models are an intuitive choice for designing sensor network algorithms. This thesis focuses on a classic application in sensor networks, detecting and tracking of targets. It develops feasible inference techniques for sensor networks using statistical graphical model inference, binary sensor detection, events isolation and dynamic clustering. The main strategy is to use only binary data for rough global inferences, and then dynamically form small scale clusters around the target for detailed computations. This framework is then extended to network topology manipulation, so that the framework developed can be applied to tracking in different network topology settings. Finally the system was tested in both simulation and real-world environments. The simulations were performed on various network topologies, from regularly distributed networks to randomly distributed networks. The results show that the algorithm performs well in randomly distributed networks, and hence requires minimum deployment effort. The experiments were carried out in both corridor and open space settings. A in-home falling detection system was simulated with real-world settings, it was setup with 30 bumblebee radars and 30 ultrasonic sensors driven by TI EZ430-RF2500 boards scanning a typical 800 sqft apartment. Bumblebee radars are calibrated to detect the falling of human body, and the two-tier tracking algorithm is used on the ultrasonic sensors to track the location of the elderly people.

Human TRPV5 and TRPV6: key players in cadmium and zinc toxicity

TRPV5 and TRPV6 are two major calcium transport pathways in the human body maintaining calcium homeostasis. TRPV5 is mainly expressed in the distal convoluted and connecting tubule where it is the major, regulated pathway for calcium reabsorption. TRPV6 serves as an important calcium entry pathway in the duodenum and the placenta. Previously, we showed that human TRPV6 (hTRPV6) transports several heavy metals. In this study we tested whether human TRPV5 (hTRPV5) also transports cadmium and zinc, and whether hTRPV5 together with hTRPV6 are involved in cadmium and zinc toxicity. The hTRPV5 mRNA and protein were expressed in HEK293 cells transiently transfected with pTagRFP-C1-hTRPV5. The overexpression of the hTRPV5 protein at the plasma membrane was revealed by cell surface biotinylation and immunofluorescence techniques. We observed that both cadmium and zinc permeate hTRPV5 in ion imaging experiments using Fura-2 or Newport Green DCF. Our results were further confirmed using whole-cell patch clamp technique. Transient overexpression of hTRPV5 or hTRPV6 sensitized cells to cadmium and zinc. Toxicity curves of cadmium and zinc were also shifted in hTRPV6 expressing HEK293 cells clones. Our results suggest that TRPV5 and TRPV6 are crucial gates controlling cadmium and zinc levels in the human body especially under low calcium dietary conditions, when these channels are maximally upregulated.

Bodily and Embodied: Being Human in the Tradition of the Hebrew Bible

A depiction of the ancient Hebrew understanding of the human being must take into account the fact that the Bible does not contain a systematic anthropology, but unfolds the multiplicity of human existence inductively, aspectively, and in narrative fashion. In comparison to Greek body/soul dualism, but also in the context of body-(de-)construction and gender debates, this circumstance makes it a treasure trove of interesting, often contrasting recollections and insights with liberating potential. This assertion will be illustrated concretely in terms of the nexus points of the human body (throat, heart, and womb), the relationship of humans to animals and angels, and the questions of the power and value of a human being.

Complement dependent early immunological responses during ex vivo xenoperfusion of hCD46/HLA-E double transgenic pig forelimbs with human blood.

BACKGROUND Besides α1,3-galactosyltransferase gene (GGTA1) knockout, several transgene combinations to prevent pig-to-human xenograft rejection are currently being investigated. In this study, the potential of combined overexpression of human CD46 and HLA-E to prevent complement- and NK-cell-mediated xenograft rejection was tested in an ex vivo pig-to-human xenoperfusion model. METHODS α1,3-Galactosyltransferase knockout heterozygous, hCD46/HLA-E double transgenic (transgenic) as well as wild-type pig forelimbs were ex vivo perfused with whole, heparinized human and autologous pig blood, respectively. Blood samples were analyzed for the production of porcine and/or human inflammatory cytokines as well as complement activation products. Biopsy samples were examined for deposition of human and porcine C3b/c, C4b/c, and C6 as well as CD62E (E-selectin) and CD106 (VCAM-1) expression. Apoptosis was measured in the porcine muscle tissue using TUNEL assays. Finally, the formation of thrombin-antithrombin (TAT) complexes was measured in EDTA plasma samples. RESULTS No hyperacute rejection was seen in this model. Extremity perfusions lasted for up to 12 h without increase in vascular resistance and were terminated due to continuous small blood losses. Plasma levels of porcine cytokines IL1β, IL-6, IL-8, IL-10, TNF-α, and MCP-1 as well as human complement activation markers C3a (P = 0.0002), C5a (P = 0.004), and soluble C5b-9 (P = 0.03) were lower in blood perfused through transgenic as compared to wild-type limbs. Human C3b/c, C4b/c, and C6 as well as CD62E and CD106 were deposited in tissue of wild-type limbs, but significantly lower levels (P < 0.0001) of C3b/c, C4b/c, and C6 deposition as well as CD62E and CD106 expression were detected in transgenic limbs perfused with human blood. Transgenic porcine tissue was protected from xenoperfusion-induced apoptosis (P < 0.0001). Finally, TAT levels were significantly lower (P < 0.0001) in transgenic limb as compared to wild-type limb xenoperfusions. CONCLUSION Transgenic hCD46/HLA-E expression clearly reduced humoral xenoresponses since all, the terminal pathway of complement activation, endothelial cell activation, muscle cell apoptosis, inflammatory cytokine production, as well as coagulation activation, were all downregulated. Overall, this model represents a useful tool to study early immunological responses during pig-to-human vascularized xenotransplantation in the absence of hyperacute rejection.

From Similes to Allegory: The Deconstruction of Chariot Imagery in Early Buddhist Texts, Analyzed with Cognitive Metaphor Theory

The presentation will start by unfolding the various layers of chariot imagery in early Indian sources, namely, chariots as vehicles of gods such as the sun (sūrya), i.e. as symbol of cosmic stability; chariots as symbols of royal power and social prestige e.g. of Brahmins; and, finally, chariots as metaphors for the “person”, the “mind” and the “way to liberation” (e.g., Kaṭ.-Up. III.3; Maitr.-Up. II. 6). In Buddhist and non-Buddhist sources, chariots are in certain aspects used as a metaphor for the (old) human body (e.g., Caraka-S., Vi.3.37-38; D II.100; D II.107); apart from that, there is, of course, mention of the “real” use of chariots in sports, cults, journey, and combat. The most prominent example of the Buddhist use of chariot imagery is its application as a model for the person (S I.134 f.; Milindapañha, ed. Trenckner, 26), i.e., for highlighting the “non-substantial self”. There are, however, other significant examples of the usage of chariot imagery in early Buddhist texts. Of special interest are those cases in which chariot metaphors were applied in order to explain how the ‘self’ may proceed on the way to salvation – with ‘mindfulness’ or the ‘self’ as charioteer, with ‘wisdom’ and ‘confidence’ as horses etc. (e.g. S I. 33; S V.7; Dhp 94; or the Nārada-Jātaka, No. 545, verses 181-190). One might be tempted to say that these instances reaffirm the traditional soteriology of a substantial “progressing soul”. Taking conceptual metaphor analysis as a tool, I will, in contrast, argue that there is a special Buddhist use of this metaphor. Indeed, at first sight, it seems to presuppose a non-Buddhist understanding (the “self” as charioteer; the chariot as vehicle to liberation, etc.). Yet, it will be argued that in these cases the chariot imagery is no longer fully “functional”. The Buddhist usage may, therefore, best be described as a final allegorical phase of the chariot-imagery, which results in a thorough deconstruction of the “chariot” itself.

Effect of irradiation distance on image contrast in epi-optoacoustic imaging of human volunteers

In combined clinical optoacoustic (OA) and ultrasound (US) imaging, epi-mode irradiation and detection integrated into one single probe offers flexible imaging of the human body. The imaging depth in epi-illumination is, however, strongly affected by clutter. As shown in previous phantom experiments, the location of irradiation plays an important role in clutter generation. We investigated the influence of the irradiation geometry on the local image contrast of clinical images, by varying the separation distance between the irradiated area and the acoustic imaging plane of a linear ultrasound transducer in an automated scanning setup. The results for different volunteers show that the image contrast can be enhanced on average by 25% and locally by more than a factor of two, when the irradiated area is slightly separated from the probe. Our findings have an important impact on the design of future optoacoustic probes for clinical application.

Modelling and Validation of a Mass Imbalance Oscillation Generator to Harvest Heart Motion Energy

An autonomous energy source within a human body is of key importance in the development of medical implants. This work deals with the modelling and the validation of an energy harvesting device which converts the myocardial contractions into electrical energy. The mechanism consists of a clockwork from a commercially available wrist watch. We developed a physical model which is able to predict the total amount of energy generated when applying an external excitation. For the validation of the model, a custom-made hexapod robot was used to accelerate the harvesting device along a given trajectory. We applied forward kinematics to determine the actual motion experienced by the harvesting device. The motion provides translational as well as rotational motion information for accurate simulations in three-dimensional space. The physical model could be successfully validated.

VIRTOPSY--scientific documentation, reconstruction and animation in forensic: individual and real 3D data based geo-metric approach including optical body/object surface and radiological CT/MRI scanning.

Until today, most of the documentation of forensic relevant medical findings is limited to traditional 2D photography, 2D conventional radiographs, sketches and verbal description. There are still some limitations of the classic documentation in forensic science especially if a 3D documentation is necessary. The goal of this paper is to demonstrate new 3D real data based geo-metric technology approaches. This paper present approaches to a 3D geo-metric documentation of injuries on the body surface and internal injuries in the living and deceased cases. Using modern imaging methods such as photogrammetry, optical surface and radiological CT/MRI scanning in combination it could be demonstrated that a real, full 3D data based individual documentation of the body surface and internal structures is possible in a non-invasive and non-destructive manner. Using the data merging/fusing and animation possibilities, it is possible to answer reconstructive questions of the dynamic development of patterned injuries (morphologic imprints) and to evaluate the possibility, that they are matchable or linkable to suspected injury-causing instruments. For the first time, to our knowledge, the method of optical and radiological 3D scanning was used to document the forensic relevant injuries of human body in combination with vehicle damages. By this complementary documentation approach, individual forensic real data based analysis and animation were possible linking body injuries to vehicle deformations or damages. These data allow conclusions to be drawn for automobile accident research, optimization of vehicle safety (pedestrian and passenger) and for further development of crash dummies. Real 3D data based documentation opens a new horizon for scientific reconstruction and animation by bringing added value and a real quality improvement in forensic science.

Analysis and Modelling of the Structural Components of the Elbow Joint

A recent application of computer simulation is its use for the human body, which resembles a mechanism that is complemented by torques in the joints that are caused by the action of muscles and tendons. Among others, the application can be used to provide training in surgical procedures or to learn how the body works. Some of the other applications are to make a biped walk upright, to build robots that are designed on the human body or to make prostheses or robot arms to perform specific tasks. One of the uses of simulation is to optimise the movement of the human body by examining which muscles are activated and which should or should not be activated in order to improve a person?s movements. This work presents a model of the elbow joint, and by analysing the constraint equations using classic methods we go on to model the bones, muscles and tendons as well as the logic linked to the force developed by them when faced with a specific movement. To do this, we analyse the reference bibliography and the software available to perform the validation.

Application of PZT and FBG impedance sensors for structural health monitoring of reinforced concrete beams strengthened with FRP composite materials

Esta Tesis tiene como objetivo principal el desarrollo de métodos de identificación del daño que sean robustos y fiables, enfocados a sistemas estructurales experimentales, fundamentalmente a las estructuras de hormigón armado reforzadas externamente con bandas fibras de polímeros reforzados (FRP). El modo de fallo de este tipo de sistema estructural es crítico, pues generalmente es debido a un despegue repentino y frágil de la banda del refuerzo FRP originado en grietas intermedias causadas por la flexión. La detección de este despegue en su fase inicial es fundamental para prevenir fallos futuros, que pueden ser catastróficos. Inicialmente, se lleva a cabo una revisión del método de la Impedancia Electro-Mecánica (EMI), de cara a exponer sus capacidades para la detección de daño. Una vez la tecnología apropiada es seleccionada, lo que incluye un analizador de impedancias así como novedosos sensores PZT para monitorización inteligente, se ha diseñado un procedimiento automático basado en los registros de impedancias de distintas estructuras de laboratorio. Basándonos en el hecho de que las mediciones de impedancias son posibles gracias a una colocación adecuada de una red de sensores PZT, la estimación de la presencia de daño se realiza analizando los resultados de distintos indicadores de daño obtenidos de la literatura. Para que este proceso sea automático y que no sean necesarios conocimientos previos sobre el método EMI para realizar un experimento, se ha diseñado e implementado un Interfaz Gráfico de Usuario, transformando la medición de impedancias en un proceso fácil e intuitivo. Se evalúa entonces el daño a través de los correspondientes índices de daño, intentando estimar no sólo su severidad, sino también su localización aproximada. El desarrollo de estos experimentos en cualquier estructura genera grandes cantidades de datos que han de ser procesados, y algunas veces los índices de daño no son suficientes para una evaluación completa de la integridad de una estructura. En la mayoría de los casos se pueden encontrar patrones de daño en los datos, pero no se tiene información a priori del estado de la estructura. En este punto, se ha hecho una importante investigación en técnicas de reconocimiento de patrones particularmente en aprendizaje no supervisado, encontrando aplicaciones interesantes en el campo de la medicina. De ahí surge una idea creativa e innovadora: detectar y seguir la evolución del daño en distintas estructuras como si se tratase de un cáncer propagándose por el cuerpo humano. En ese sentido, las lecturas de impedancias se emplean como información intrínseca de la salud de la propia estructura, de forma que se pueden aplicar las mismas técnicas que las empleadas en la investigación del cáncer. En este caso, se ha aplicado un algoritmo de clasificación jerárquica dado que ilustra además la clasificación de los datos de forma gráfica, incluyendo información cualitativa y cuantitativa sobre el daño. Se ha investigado la efectividad de este procedimiento a través de tres estructuras de laboratorio, como son una viga de aluminio, una unión atornillada de aluminio y un bloque de hormigón reforzado con FRP. La primera ayuda a mostrar la efectividad del método en sencillos escenarios de daño simple y múltiple, de forma que las conclusiones extraídas se aplican sobre los otros dos, diseñados para simular condiciones de despegue en distintas estructuras. Demostrada la efectividad del método de clasificación jerárquica de lecturas de impedancias, se aplica el procedimiento sobre las estructuras de hormigón armado reforzadas con bandas de FRP objeto de esta tesis, detectando y clasificando cada estado de daño. Finalmente, y como alternativa al anterior procedimiento, se propone un método para la monitorización continua de la interfase FRP-Hormigón, a través de una red de sensores FBG permanentemente instalados en dicha interfase. De esta forma, se obtienen medidas de deformación de la interfase en condiciones de carga continua, para ser implementadas en un modelo de optimización multiobjetivo, cuya solución se haya por medio de una expansión multiobjetivo del método Particle Swarm Optimization (PSO). La fiabilidad de este último método de detección se investiga a través de sendos ejemplos tanto numéricos como experimentales. ABSTRACT This thesis aims to develop robust and reliable damage identification methods focused on experimental structural systems, in particular Reinforced Concrete (RC) structures externally strengthened with Fiber Reinforced Polymers (FRP) strips. The failure mode of this type of structural system is critical, since it is usually due to sudden and brittle debonding of the FRP reinforcement originating from intermediate flexural cracks. Detection of the debonding in its initial stage is essential thus to prevent future failure, which might be catastrophic. Initially, a revision of the Electro-Mechanical Impedance (EMI) method is carried out, in order to expose its capabilities for local damage detection. Once the appropriate technology is selected, which includes impedance analyzer as well as novel PZT sensors for smart monitoring, an automated procedure has been design based on the impedance signatures of several lab-scale structures. On the basis that capturing impedance measurements is possible thanks to an adequately deployed PZT sensor network, the estimation of damage presence is done by analyzing the results of different damage indices obtained from the literature. In order to make this process automatic so that it is not necessary a priori knowledge of the EMI method to carry out an experimental test, a Graphical User Interface has been designed, turning the impedance measurements into an easy and intuitive procedure. Damage is then assessed through the analysis of the corresponding damage indices, trying to estimate not only the damage severity, but also its approximate location. The development of these tests on any kind of structure generates large amounts of data to be processed, and sometimes the information provided by damage indices is not enough to achieve a complete analysis of the structural health condition. In most of the cases, some damage patterns can be found in the data, but none a priori knowledge of the health condition is given for any structure. At this point, an important research on pattern recognition techniques has been carried out, particularly on unsupervised learning techniques, finding interesting applications in the medicine field. From this investigation, a creative and innovative idea arose: to detect and track the evolution of damage in different structures, as if it were a cancer propagating through a human body. In that sense, the impedance signatures are used to give intrinsic information of the health condition of the structure, so that the same clustering algorithms applied in the cancer research can be applied to the problem addressed in this dissertation. Hierarchical clustering is then applied since it also provides a graphical display of the clustered data, including quantitative and qualitative information about damage. The performance of this approach is firstly investigated using three lab-scale structures, such as a simple aluminium beam, a bolt-jointed aluminium beam and an FRP-strengthened concrete specimen. The first one shows the performance of the method on simple single and multiple damage scenarios, so that the first conclusions can be extracted and applied to the other two experimental tests, which are designed to simulate a debonding condition on different structures. Once the performance of the impedance-based hierarchical clustering method is proven to be successful, it is then applied to the structural system studied in this dissertation, the RC structures externally strengthened with FRP strips, where the debonding failure in the interface between the FRP and the concrete is successfully detected and classified, proving thus the feasibility of this method. Finally, as an alternative to the previous approach, a continuous monitoring procedure of the FRP-Concrete interface is proposed, based on an FBGsensors Network permanently deployed within that interface. In this way, strain measurements can be obtained under controlled loading conditions, and then they are used in order to implement a multi-objective model updating method solved by a multi-objective expansion of the Particle Swarm Optimization (PSO) method. The feasibility of this last proposal is investigated and successfully proven on both numerical and experimental RC beams strengthened with FRP.

Contribución al estudio de propiedades ópticas en medios heterogéneos

Como contribución del estudio de medios heterogéneos, esta tesis recoge el trabajo llevado a cabo sobre modelado teórico y simulación del estudio de las propiedades ópticas de la piel y del agua del mar, como ejemplos paradigmáticos de medios heterogéneos. Se ha tomado como punto de partida el estudio de la propagación de la radiación óptica, más concretamente de la radiación láser, en un tejido biológico. La importancia de la caracterización óptica de un tejido es fundamental para manejar la interacción radiación-tejido que permite tanto el diagnóstico como la terapéutica de enfermedades y/o de disfunciones en las Ciencias de la Salud. Sin olvidar el objetivo de ofrecer una metodología de estudio, con un «enfoque ingenieril», de las propiedades ópticas en un medio heterogéneo, que no tiene por qué ser exclusivamente el tejido biológico. Como consecuencia de lo anterior y de la importancia que tiene el agua dentro de los tejidos biológicos se decide estudiar en otro capítulo las propiedades ópticas del agua dentro de un entorno heterogéneo como es el agua del mar. La selección del agua del mar, como objeto de estudio adicional, es motivada, principalmente, porque se trata de un sistema heterogéneo fácilmente descriptible en cada uno de sus elementos y permite evaluar una amplia bibliografía. Además se considera que los avances que han tenido lugar en los últimos años en las tecnologías fotónicas van a permitir su uso en los métodos experimentales de análisis de las aguas. El conocimiento de sus propiedades ópticas permite caracterizar los diferentes tipos de aguas de acuerdo con sus compuestos, así como poder identificar su presencia. Todo ello abre un amplio abanico de aplicaciones. En esta tesis doctoral, se ha conseguido de manera general: • Realizar un estudio del estado del arte del conocimiento de las propiedades ópticas de la piel y la identificación de sus elementos dispersores de la luz. • Establecer una metodología de estudio que nos permita obtener datos sobre posibles efectos de la radiación en los tejidos biológicos. •Usar distintas herramientas informáticas para simular el transporte de la radiación laser en tejidos biológicos. • Realizar experimentos mediante simulación de láser, tejidos biológicos y detectores. • Comparar los resultados conocidos experimentalmente con los simulados. • Estudiar los instrumentos de medida de la respuesta a la propagación de radiación laser en tejidos anisotrópicos. • Obtener resultados originales para el diagnóstico y tratamiento de pieles, considerando diferente razas y como alteración posible en la piel, se ha estudiado la presencia del basalioma. • Aplicación de la metodología de estudio realizada en la piel a la simulación de agua de mar. • Obtener resultados originales de simulación y análisis de cantidad de fitoplancton en agua; con el objetivo de facilitar la caracterización de diferentes tipos de aguas. La tesis doctoral se articula en 6 capítulos y 3 anexos perfectamente diferenciados con su propia bibliografía en cada uno de ellos. El primer capítulo está centrado en la problemática del difícil estudio y caracterización de los medios heterogéneos debidos a su comportamiento no homogéneo y anisotrópico ante las radiaciones ópticas. Así pues, presentaremos una breve introducción al comportamiento tanto de los tejidos como del océano ante radiaciones ópticas y definiremos sus principales propiedades: la absorción, el scattering, la anisotropía y los coeficientes de reflexión. Como continuación, un segundo capítulo trata de acercarnos a la resolución del problema de cómo caracterizar las propiedades ópticas descritas en el primer capítulo. Para ello, primero se introducen los modelos teóricos, en segundo lugar los métodos de simulación más empleados y, por último, enumerar las principales técnicas de medida de la propagación de la luz en los tejidos vivos. El tercer capítulo, centrado en la piel y sus propiedades, intenta realizar una síntesis de lo que se conoce sobre el comportamiento de la piel frente a la propagación de las radiaciones ópticas. Se estudian sus elementos constituyentes y los distintos tipos de pieles. Por último se describe un ejemplo de aplicación más inmediata que se beneficia de este conocimiento. Sabemos que el porcentaje de agua en el cuerpo humano es muy elevado, en concreto en la piel se considera de aproximadamente un 70%. Es obvio, por tanto, que conocer cómo afecta el agua en la propagación de una radiación óptica facilitaría el disponer de patrones de referencia; para ello, se realiza el estudio del agua del mar. En el cuarto capítulo se estudian las propiedades del agua del mar como medio heterogéneo de partículas. En este capítulo presentamos una síntesis de los elementos más significativos de dispersores en el océano, un estudio de su comportamiento individual frente a radiaciones ópticas y su contribución al océano en su conjunto. Finalmente, en el quinto capítulo se describen los resultados obtenidos en los distintos tipos de simulaciones realizadas. Las herramientas de simulación empleadas han sido las mismas tanto para el caso del estudio de la piel como para el agua del mar, por ello ambos resultados son expuestos en el mismo capítulo. En el primer caso se analizan diferentes tipos de agua oceánica, mediante la variación de las concentraciones de fitoplancton. El método empleado permite comprobar las diferencias que pueden encontrarse en la caracterización y diagnóstico de aguas. El segundo caso analizado es el de la piel; donde se estudia el comportamiento de distintos tipos de piel, se analizan para validar el método y se comprueba cómo el resultado es compatible con aplicaciones, actualmente comerciales, como la de la depilación con láser. Como resultado significativo se muestra la posible metodología a aplicar para el diagnóstico del cáncer de piel conocido como basalioma. Finalmente presentamos un capítulo dedicado a los trabajos futuros basados en experimentación real y el coste asociado que implicaría el llevarlo a cabo. Los anexos que concluyen la tesis doctoral versan por un lado sobre el funcionamiento del vector común de toda la tesis: el láser, sus aplicaciones y su control en la seguridad y por otro presentamos los coeficientes de absorción y scattering que hemos utilizado en nuestras simulaciones. El primero condensa las principales características de una radiación láser desde el punto de vista de su generación, el segundo presenta la seguridad en su uso y el tercero son tablas propias, cuyos parámetros son los utilizados en el apartado de experimentación. Aunque por el tipo de tesis que defiendo no se ajusta a los modelos canónicos de tesis doctoral, el lector podrá encontrar en esta tesis de forma imbricada, el modelo común a todas las tesis o proyectos de investigación con una sección dedicada al estado del arte con ejemplos pedagógicos para facilitar la compresión y se plantean unos objetivos (capítulos 1-4), y un capítulo que se subdivide en materiales y métodos y resultados y discusiones (capítulo 5 con sus subsecciones), para finalizar con una vista al futuro y los trabajos futuros que se desprenden de la tesis (capítulo 6). ABSTRACT As contribution to the study of heterogeneous media, this thesis covers the work carried out on theoretical modelling and simulation study of the optical properties of the skin and seawater, as paradigmatic examples of heterogeneous media. It is taken as a starting point the study of the propagation of optical radiation, in particular laser radiation in a biological tissue. The importance of optical characterization of a tissue is critical for managing the interaction between radiation and tissues that allows both diagnosis and therapy of diseases and / or dysfunctions in Health Sciences. Without forgetting the aim of providing a methodology of study, with "engineering approach" of the optical properties in a heterogeneous environment, which does not have to be exclusively biological tissue. As a result of this and the importance of water in biological tissues, we have decided to study the optical properties of water in a heterogeneous environment such as seawater in another chapter. The selection of sea water as an object of further study is motivated mainly because it is considered that the advances that have taken place in recent years in photonic technologies will allow its use in experimental methods of water analysis. Knowledge of the optical properties to characterize the different types of waters according to their compounds, as well as to identify its presence. All of this opens a wide range of applications. In this thesis, it has been generally achieved: • Conduct a study of the state of the art knowledge of the optical properties of the skin and identifying its light scattering elements. • Establish a study methodology that allows us to obtain data on possible effects of radiation on biological tissues. • Use different computer tools to simulate the transport of laser radiation in biological tissues. • Conduct experiments by simulating: laser, detectors, and biological tissues. • Compare the known results with our experimentally simulation. • Study the measuring instruments and its response to the propagation of laser radiation in anisotropic tissues. • Get innovative results for diagnosis and treatment of skin, considering different races and a possible alteration in the skin that we studied: the presence of basal cell carcinoma. • Application of the methodology of the study conducted in the skin to simulate seawater. • Get innovative results of simulation and analysis of amount of phytoplankton in water; in order to facilitate the characterization of different types of water. The dissertation is divided into six chapters and three annexes clearly distinguished by their own literature in each of them. The first chapter is focused on the problem of difficult study and characterization of heterogeneous media due to their inhomogeneous and anisotropic behaviour of optical radiation. So we present a brief introduction to the behaviour of both tissues at the cellular level as the ocean, to optical radiation and define the main optical properties: absorption, scattering, anisotropy and reflection coefficients. Following from this, a second chapter is an approach to solving the problem of how to characterize the optical properties described in the first chapter. For this, first the theoretical models are introduced, secondly simulation methods more used and, finally, the main techniques for measuring the propagation of light in living tissue. The third chapter is focused on the skin and its properties, tries to make a synthesis of what is known about the behaviour of the skin and its constituents tackle the spread of optical radiation. Different skin types are studied and an example of immediate application of this knowledge benefits described. We know that the percentage of water in the human body is very high, particularly in the skin is considered about 70%. It is obvious, therefore, that knowing how the water is affected by the propagation of an optical radiation facilitate to get reference patterns; For this, the study of seawater is performed. In the fourth chapter the properties of seawater as a heterogeneous component particles are studied. This chapter presents a summary of the scattering elements in the ocean, its individual response to optical radiation and its contribution to the ocean as a whole. In the fifth chapter the results of the different types of simulations are described. Simulation tools used were the same for the study of skin and seawater, so both results are presented in the chapter. In the first case different types of ocean water is analysed by varying the concentrations of phytoplankton. The method allows to check the differences that can be found in the characterization and diagnosis of water. The second case analysed is the skin; where the behaviour of different skin types are studied and checked how the result is compatible with applications currently trade, such as laser hair removal. As a significant result of the possible methodology to be applied for the diagnosis of skin cancer known as basal cell carcinoma is shown. Finally we present a chapter on future work based on actual experimentation and the associated cost which it would involve carrying out. The annexes conclude the thesis deal with one hand on the functioning of the common vector of the whole thesis: laser, control applications and safety and secondly we present the absorption and scattering coefficients we used in our simulations. The first condenses the main characteristics of laser radiation from the point of view of their generation, the second presents the safety in use and the third are own tables, whose parameters are used in the experimental section. Although the kind of view which I advocate does not meet the standard models doctoral thesis, the reader will find in this thesis so interwoven, the common model to all theses or research projects with a section on the state of the art pedagogical examples to facilitate the understanding and objectives (Chapters 1-4), and a chapter is divided into materials and methods and results and discussions (Chapter 5 subsections) arise, finishing with a view to the future and work future arising from the thesis (Chapter 6).

Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.

Mutations in the recently identified presenilin 1 gene on chromosome 14 cause early onset familial Alzheimer disease (FAD). Herein we describe the expression and analysis of the protein coded by presenilin 1 (PS1) in NT2N neurons, a human neuronal model system. PS1 was expressed using recombinant Semliki Forest virions and detected by introduced antigenic tags or antisera to PS1-derived peptides. Immunoprecipitation revealed two major PS1 bands of approximately 43 and 50 kDa, neither of which were N-glycosylated or O-glycosylated. Immunoreactive PS1 was detected in cell bodies and dendrites of NT2N neurons but not in axons or on the cell surface. PS1 was also detected in BHK cells, where it was also intracellular and colocalized with calnexin, a marker for the rough endoplasmic reticulum. A mutant form of PS1 linked to FAD did not differ from the wild-type protein at the light microscopic level. The model system described here will enable studies of the function of PS1 in human neurons and the role of mutant PS1 in FAD.

Human Motion Analysis Based on Sequential Modeling of Radar Signal and Stereo Image Features

Falls are one of the greatest threats to elderly health in their daily living routines and activities. Therefore, it is very important to detect falls of an elderly in a timely and accurate manner, so that immediate response and proper care can be provided, by sending fall alarms to caregivers. Radar is an effective non-intrusive sensing modality which is well suited for this purpose, which can detect human motions in all types of environments, penetrate walls and fabrics, preserve privacy, and is insensitive to lighting conditions. Micro-Doppler features are utilized in radar signal corresponding to human body motions and gait to detect falls using a narrowband pulse-Doppler radar. Human motions cause time-varying Doppler signatures, which are analyzed using time-frequency representations and matching pursuit decomposition (MPD) for feature extraction and fall detection. The extracted features include MPD features and the principal components of the time-frequency signal representations. To analyze the sequential characteristics of typical falls, the extracted features are used for training and testing hidden Markov models (HMM) in different falling scenarios. Experimental results demonstrate that the proposed algorithm and method achieve fast and accurate fall detections. The risk of falls increases sharply when the elderly or patients try to exit beds. Thus, if a bed exit can be detected at an early stage of this motion, the related injuries can be prevented with a high probability. To detect bed exit for fall prevention, the trajectory of head movements is used for recognize such human motion. A head detector is trained using the histogram of oriented gradient (HOG) features of the head and shoulder areas from recorded bed exit images. A data association algorithm is applied on the head detection results to eliminate head detection false alarms. Then the three dimensional (3D) head trajectories are constructed by matching scale-invariant feature transform (SIFT) keypoints in the detected head areas from both the left and right stereo images. The extracted 3D head trajectories are used for training and testing an HMM based classifier for recognizing bed exit activities. The results of the classifier are presented and discussed in the thesis, which demonstrates the effectiveness of the proposed stereo vision based bed exit detection approach.

Mathematical modelling of the lower urinary tract

The lower urinary tract is one of the most complex biological systems of the human body as it involved hydrodynamic properties of urine and muscle. Moreover, its complexity is increased to be managed by voluntary and involuntary neural systems. In this paper, a mathematical model of the lower urinary tract it is proposed as a preliminary study to better understand its functioning. Furthermore, another goal of that mathematical model proposal is to provide a basis for developing artificial control systems. Lower urinary tract is comprised of two interacting systems: the mechanical system and the neural regulator. The latter has the function of controlling the mechanical system to perform the voiding process. The results of the tests reproduce experimental data with high degree of accuracy. Also, these results indicate that simulations not only with healthy patients but also of patients with dysfunctions with neurological etiology present urodynamic curves very similar to those obtained in clinical studies.

Le système endocannabinoïde dans la rétine du singe : expression, localisation et fonctions

Le cannabis produit de nombreux effets psychologiques et physiologiques sur le corps humain. Les molécules contenues dans cette plante, désignées comme « phytocannabinoïdes », activent un système endogène qu’on appelle le système endocannabinoïde (eCB). Les effets de la consommation de cannabis sur la vision ont déjà été décrits sans cependant de formulation sur les mécanismes sous-jacents. Ces résultats comportementaux suggèrent, malgré tout, la présence de ce système eCB dans le système visuel, et particulièrement dans la rétine. Cette thèse vise donc à caractériser l’expression, la localisation et le rôle du système eCB dans la rétine du singe vervet, une espèce animale ayant un système visuel semblable à celui de l’humain. Nous avons mis au point un protocole expérimental d’immunohistochimie décrit dans l’article apparaissant dans l’Annexe I que nous avons utilisé pour répondre à notre objectif principal. Dans une première série de quatre articles, nous avons ainsi caractérisé l’expression et la localisation de deux récepteurs eCBs reconnus, les récepteurs cannabinoïdes de type 1 (CB1R) et de type 2 (CB2R), et d’un 3e présumé récepteur aux cannabinoïdes, le récepteur GPR55. Dans l’article 1, nous avons démontré que CB1R et une enzyme clé de ce système, la fatty acid amide hydrolase (FAAH), sont exprimés dans les parties centrale et périphérique de la rétine, et abondamment présents dans la fovéa, une région où l’acuité visuelle est maximale. Dans l’article 2, nous avons localisé le CB2R dans des cellules gliales de la rétine : les cellules de Müller et nous avons proposé un modèle sur l’action de cette protéine dans la fonction rétinienne faisant appel à une cascade chimique impliquant les canaux potassiques. Dans l’article 3, nous avons observé le GPR55 exclusivement dans les bâtonnets qui sont responsables de la vision scotopique et nous avons soumis un deuxième modèle de fonctionnement de ce récepteur par le biais d'une modulation des canaux calciques et sodiques des bâtonnets. Vu que ces 3 récepteurs se retrouvent dans des cellules distinctes, nous avons suggéré leur rôle primordial dans l’analyse de l’information visuelle au niveau rétinien. Dans l’article 4, nous avons effectué une analyse comparative de l’expression du système eCB dans la rétine de souris, de toupayes (petits mammifères insectivores qui sont sont considérés comme l’étape intermédiaire entre les rongeurs et les primates) et de deux espèces de singe (le vervet et le rhésus). Ces résultats nous ont menés à présenter une hypothèse évolutionniste quant à l’apparition et à la fonction précise de ces récepteurs. Dans les articles subséquents, nous avons confirmé notre hypothèse sur le rôle spécifique de ces trois récepteurs par l’utilisation de l’électrorétinographie (ERG) après injection intravitréenne d’agonistes et d’antagonistes de ces récepteurs. Nous avons conclu sur leur influence indéniable dans le processus visuel rétinien chez le primate. Dans l’article 5, nous avons établi le protocole d’enregistrement ERG normalisé sur le singe vervet, et nous avons produit un atlas d’ondes ERG spécifique à cette espèce, selon les règles de l’International Society for Clinical Electrophysiology of Vision (ISCEV). Les patrons électrorétinographiques se sont avérés semblables à ceux de l’humain et ont confirmé la similarité entre ces deux espèces. Dans l’article 6, nous avons démontré que le blocage de CB1R ou CB2R entraine une modification de l’électrorétinogramme, tant au niveau photopique que scotopique, ce qui supporte l’implication de ces récepteurs dans la modulation des ondes de l’ERG. Finalement, dans l’article 7, nous avons confirmé le modèle neurochimique proposé dans l’article 3 pour expliquer le rôle fonctionnel de GPR55, en montrant que l’activation ou le blocage de ce récepteur, respectivement par un agoniste (lysophosphatidylglucoside, LPG) ou un antagoniste (CID16020046), entraine soit une augmentation ou une baisse significative de l’ERG scotopique seulement. Ces données, prises ensemble, démontrent que les récepteurs CB1R, CB2R et GPR55 sont exprimés dans des types cellulaires bien distincts de la rétine du singe et ont chacun un rôle spécifique. L’importance de notre travail se manifeste aussi par des applications cliniques en permettant le développement de cibles pharmacologiques potentielles dans le traitement des maladies de la rétine.