Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents.

OBJECTIVE To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities.

Brain-borne IL-1 adjusts glucoregulation and provides fuel support to astrocytes and neurons in an autocrine/paracrine manner.

It is still controversial which mediators regulate energy provision to activated neural cells, as insulin does in peripheral tissues. Interleukin-1β (IL-1β) may mediate this effect as it can affect glucoregulation, it is overexpressed in the 'healthy' brain during increased neuronal activity, and it supports high-energy demanding processes such as long-term potentiation, memory and learning. Furthermore, the absence of sustained neuroendocrine and behavioral counterregulation suggests that brain glucose-sensing neurons do not perceive IL-1β-induced hypoglycemia. Here, we show that IL-1β adjusts glucoregulation by inducing its own production in the brain, and that IL-1β-induced hypoglycemia is myeloid differentiation primary response 88 protein (MyD88)-dependent and only partially counteracted by Kir6.2-mediated sensing signaling. Furthermore, we found that, opposite to insulin, IL-1β stimulates brain metabolism. This effect is absent in MyD88-deficient mice, which have neurobehavioral alterations associated to disorders in glucose homeostasis, as during several psychiatric diseases. IL-1β effects on brain metabolism are most likely maintained by IL-1β auto-induction and may reflect a compensatory increase in fuel supply to neural cells. We explore this possibility by directly blocking IL-1 receptors in neural cells. The results showed that, in an activity-dependent and paracrine/autocrine manner, endogenous IL-1 produced by neurons and astrocytes facilitates glucose uptake by these cells. This effect is exacerbated following glutamatergic stimulation and can be passively transferred between cell types. We conclude that the capacity of IL-1β to provide fuel to neural cells underlies its physiological effects on glucoregulation, synaptic plasticity, learning and memory. However, deregulation of IL-1β production could contribute to the alterations in brain glucose metabolism that are detected in several neurologic and psychiatric diseases.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.174.

T- and B-cell responses and previous exposure to hepatitis B virus in 'anti-HBc alone' patients.

A serologic response to hepatitis B virus (HBV) defined as 'anti-HBc alone' is commonly observed, but its significance remains unclear. This study aimed to define the relationship between 'anti-HBc alone' serostatus and HBV infection, including HBV-specific T- and B-cell memory responses. We enrolled 31 'anti-HBc alone' patients. Total HBV DNA and cccDNA were tested by nested polymerase chain reaction (PCR) analysis in liver samples from 22 'anti-HBc alone' patients vs controls (chronic or resolved HBV infection), followed by HBsAg/HBcAg immunohistochemical (IHC) staining. IFN-γ secretion by HBV-specific T cells was compared in individuals who were 'anti-HBc alone' (n = 27), resolved HBV (n = 21), chronic HBV (n = 24) and 12 healthy controls using enzyme-linked immunospot (ELISpot) assays. An HBsAg-IgG B-cell ELISpot assay was performed in 'anti-HBc alone' patients before and after one dose of recombinant HBsAg vaccine. The majority (23/31, 74.2%) of the 'anti-HBc alone' individuals were co-infected with HCV. Infrequent intrahepatic total HBV DNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV-specific T-cell responses were similar between 'anti-HBc alone' individuals and HBV resolvers. Circulating HBV-memory B-cell responses were detected in all 'anti-HBc alone' individuals, consistent with an HBsAg-specific memory pool. After one HBV vaccine dose, increased anti-HBs antibody levels were observed, accompanied by an expansion of HBsAg-specific memory B cells (P = 0.0226). 'Anti-HBc alone' individuals showed HBV-specific T-cell and memory B-cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.

Source Memory for Mental Imagery: Influences of the Stimuli’s Ease of Imagery.

The present study investigated how ease of imagery influences source monitoring accuracy. Two experiments were conducted in order to examine how ease of imagery influences the probability of source confusions of perceived and imagined completions of natural symmetric shapes. The stimuli consisted of binary pictures of natural objects, namely symmetric pictures of birds, butterflies, insects, and leaves. The ease of imagery (indicating the similarity of the sources) and the discriminability (indicating the similarity of the items) of each stimulus were estimated in a pretest and included as predictors of the memory performance for these stimuli. It was found that confusion of the sources becomes more likely when the imagery process was relatively easy. However, if the different processes of source monitoring-item memory, source memory and guessing biases-are disentangled, both experiments support the assumption that the effect of decreased source memory for easily imagined stimuli is due to decision processes and misinformation at retrieval rather than encoding processes and memory retention. The data were modeled with a Bayesian hierarchical implementation of the one high threshold source monitoring model.

Behavioral and cellular analysis of classical conditioning of feeding behavior in Aplysia

In classical conditioning, an associative form of learning, animals learn to associate two stimuli. Cellular and molecular mechanisms for the induction and consolidation of associative learning and memory at the level of single cells and synaptic connections have been studied in both vertebrate and invertebrate animals. The majority of studies, however, relied on aversive stimuli to induce learning. This bias may limit the extent to which identified mechanisms generalize to other forms of associative learning and memory, such as appetitive forms. The goal of the present study was to develop a classical conditioning procedure for the marine mollusk Aplysia californica using appetitive reinforcement, and to analyze associative learning using behavioral and electrophysiological techniques. ^ Using tactile stimulation of the lips as the conditional stimulus (CS) and food as the unconditional stimulus (US) a training protocol was developed that reliably induced classical conditioning of feeding behavior. Memory persisted for at least 24 hours. The gross organization of reinforcement-mediating pathways was analyzed in additional behavioral experiments. Moreover, neurophysiological correlates of classical conditioning were identified and characterized in an in vitro preparation containing the circuitry for feeding behavior. In vitro stimulation of a nerve (AT4) that may mediate the CS during training, resulted in a greater number of buccal motor patterns (BMPs) in brains from conditioned animals, as compared to control animals. The majority of these BMPs were ingestion-like, consistent with the increased number of bites in response to the CS after classical conditioning. Moreover, classical conditioning correlated with increased excitatory synaptic input to BMP-initiating neuron B31/32, in response to stimulation of AT 4, as compared to controls. The expression of the correlates of classical conditioning identified in this study was specific to stimulation of AT 4, which is consistent the stimulus specificity that is characteristic for classical conditioning. ^ The identification of cellular correlates of classical conditioning documented here provides the basis for future, more detailed analyses of an appetitive form of associative learning and memory, that may extend the working knowledge of the cellular and molecular mechanisms for associative plasticity in general. ^

Polybrominated diphenyl ethers: Potential human exposure through household dust and dryer lint

This MPH thesis consists of (1) literature review of the relatively new synthetic persistent organic pollutants (POP), polybrominated diphenyl ethers (PBDEs), a type of flame retardant posing a potential public health hazard, (2) Presentation of data on PBDE levels in dryer lint from Dallas, TX and Hamburg, Germany. ^ PBDEs are used as additive fire retardants in plastics, polyurethane foam and electronic equipment to reduce flammability and thus save life and property. PBDEs have been widely used beginning in the 1970s. They resemble polychlorinated biphenyls (PCBs) in structure and toxicity. PBDEs are found in environmental sediments, sludges, and wildlife and even in human blood, milk and tissues. ^ PBDEs, due to their lipophilicity, accumulate in fat and other tissues and biomagnify up the food chain, with increasing concentrations. Animal studies have suggested potential health effects including thyroid disruption, permanent learning and memory impairment, fetal malformations, developmental neurotoxicity and, at high doses, possibly cancer. ^ PBDE levels are increasing in blood and breast milk in North America, but PBDEs intake unlike PCBs appears to be not primarily through food; food PBDE levels in the U.S. are not markedly higher than in Europe yet U.S. human blood and milk levels are much higher. For this reason various exposure pathways including PBDE contaminated dust and air have been studied to better characterize routes of PBDE intake into humans. ^ The scientific literature on PBDE levels in household dust reports higher PBDE concentration in dust than that found in dryer lint; levels in the U.S are elevated compared to other countries with congeners such as BDE 47, 99, 100 and 209 predominating. The United Kingdom has elevated BDE 209 due to high usage of Deca commercial mixture. These studies suggest that indoor PBDE contamination through household dust could be a potential source of PBDE exposure and body burden especially in young children. ^ PBDE levels in dryer lint from U.S ranged from 321 to 3073 ng/g (Mean: 1138 ng/g, Median: 803 ng/g) and from Germany were from 330 to 2069 ng/g (Median: 71ng/g, Mean: 361 ng/g). High median levels in U.S samples indicate contamination of lint with PBDEs although the source of the PBDEs in lint may be from dryer electrical components or air deposition onto clothes, lint may be one source of PBDE exposure to humans. ^

Spatial and temporal aspects of synaptic plasticity

The notion that changes in synaptic efficacy underlie learning and memory processes is now widely accepted even if definitive proof of the synaptic plasticity and memory hypothesis is still lacking. When learning occurs, patterns of neural activity representing the occurrence of events cause changes in the strength of synaptic connections within the brain. Reactivation of these altered connections constitutes the experience of memory for these events and for other events with which they may be associated. These statements summarize a long-standing theory of memory formation that we refer to as the synaptic plasticity and memory hypothesis. Since activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation, and is both necessary and sufficient for the information storage, we can speculate that a methodological study of the synapse will help us understand the mechanism of learning. Random events underlie a wide range of biological processes as diverse as genetic drift and molecular diffusion, regulation of gene expression and neural network function. Additionally spatial variability may be important especially in systems with nonlinear behavior. Since synapse is a complex biological system we expect that stochasticity as well as spatial gradients of different enzymes may be significant for induction of plasticity. ^ In that study we address the question "how important spatial and temporal aspects of synaptic plasticity may be". We developed methods to justify our basic assumptions and examined the main sources of variability of calcium dynamics. Among them, a physiological method to estimate the number of postsynaptic receptors as well as a hybrid algorithm for simulating postsynaptic calcium dynamics. Additionally we studied how synaptic geometry may enhance any possible spatial gradient of calcium dynamics and how that spatial variability affect plasticity curves. Finally, we explored the potential of structural synaptic plasticity to provide a metaplasticity mechanism specific for the synapse. ^

INDUCTION OF STRONGER AND LONG LASTING VACCINE IMMUNITY TO TUBERCULOSIS

Tuberculosis is a major cause of death due to an infection in mankind. BCG vaccine protects against childhood tuberculosis although, it fails to protect against adult tuberculosis. BCG vaccine localizes to immature phagosomes of macrophages, and avoids lysosomal fusion, which decreases peptide antigen production. Peptides are essential for macrophage-mediated priming of CD4 and CD8 T cells respectively through MHC-II and MHC-I pathways. Furthermore, BCG reduces the expression of MHC-II in macrophages of mice after infection, through Toll-like receptor-1/2 (TLR-1/2) mediated signaling. In my first aim, I hypothesized that BCG-induced reduction of MHC-II levels in macrophages can decrease CD4 T cell function, while activation of other surface Toll-like receptors (TLR) can enhance CD4 T cell function. An in vitro antigen presentation model was used where, TLR activated macrophages presented an epitope of Ag85B, a major immunogen of BCG to CD4 T cells, and T cell derived IL-2 was quantitated as a measure of antigen presentation. Macrophages with BCG were poor presenters of Ag85B while, TLR-7/9/5/4 and 1/2 activation led to an enhanced antigen presentation. Furthermore, TLR-7/9 activation was found to down-regulate the degradation of MHC-II through ubiquitin ligase MARCH1, and also stimulate MHC-II expression through activation of AP-1 and CREB transcription elements via p38 and ERK1/2 MAP kinases. I conclude from Aim-I studies that TLR-7/9 ligands can be used as more effective ‘adjuvants’ for BCG vaccine. In Aim-II, I evaluated the poor CD8 T cell function in BCG vaccinated mice thought to be due to a decreased leak of antigens into cytosol from immature phagosomes, which reduces the MHC-I mediated activation of CD8 T cells. I hypothesized that rapamycin co-treatment could boost CD8 T cell function since it was known to sort BCG vaccine into lysosomes increasing peptide generation, and it also enhanced the longevity of CD8 T cells. Since CD8 T cell function is a dynamic event better measurable in vivo, mice were given BCG vaccine with or without rapamycin injections and challenged with virulent Mycobacterium tuberculosis. Organs were analysed for tetramer or surface marker stained CD8 T cells using flow cytometry, and bacterial counts of organisms for evaluation of BCG-induced protection. Co-administration of rapamycin with BCG significantly increased the numbers of CD8 T cells in mice which developed into both short living effector- SLEC type of CD8 T cells, and memory precursor effector-MPEC type of longer-living CD8 T cells. Increased levels of tetramer specific-CD8 T cells correlated with a better protection against tuberculosis in rapamycin-BCG group compared to BCG vaccinated mice. When rapamycin-BCG mice were rested and re-challenged with M.tuberculosis, MPECs underwent stronger recall expansion and protected better against re-infection than mice vaccinated with BCG alone. Since BCG induced immunity wanes with time in humans, we made two novel observations in this study that adjuvant activation of BCG vaccine and rapamycin co-treatment both lead to a stronger and longer vaccine-mediated immunity to tuberculosis.

Calcium-dependent mechanisms and long-term potentiation: Role of NMDA receptors, voltage -dependent calcium channels and persistent protein kinase activity

Long-term potentiation (LTP) is a rapidly induced and long lasting increase in synaptic strength and is the leading cellular model for learning and memory in the mammalian brain. LTP was first identified in the hippocampus, a structure implicated in memory formation. LTP induction is dependent on postsynaptic Ca2+ increases mediated by N-methyl-D-aspartate (NMDA) receptors. Activation of other postsynaptic routes of Ca2+ entry, such as voltage-dependent Ca2+ channels (VDCCs) have subsequently been shown to induce a long-lasting increase in synaptic strength. However, it is unknown if VDCC-induced LTP utilized similar cellular mechanisms as the classical NMDA receptor-dependent LTP and if these two forms of LTP display similar properties. This dissertation determines the similarities and differences in VDCC and NMDA receptor-dependent LTP in area CA1 of hippocampal slices and demonstrates that VDCCs and NMDA receptors activate similar cellular mechanisms, such as protein kinases, to induce LTP. However, VDCC and NMDA receptor activated LTP induction mechanisms are compartmentalized in the postsynaptic neuron, such that they do not interact. Consistent with activation properties of NMDA receptors and VDCCs, NMDA receptor and VDCC-dependent LTP have different induction properties. In contrast to NMDA-dependent LTP, VDCC-induced potentiation does not require evoked presynaptic stimulation or display input specificity. These results indicate that there are two different routes of postsynaptic Ca2+ which can induce LTP and the compartmentation of VDCCs and NMDA receptors and/or their resulting Ca2+ increases may account for the distinction between these LTP induction mechanisms.^ One of the molecular targets for postsynaptic Ca2+ that is required for the induction of LTP is protein kinases. Evidence for the role of protein kinase activity in LTP expression is either correlational or controversial. We have utilized a broad range and potent inhibitors of protein kinases to systematically examine the temporal requirement for protein kinases in the induction and expression of LTP. Our results indicate that there is a critical period of persistent protein kinase activity required for LTP induction activated by tetanic stimulation and extending until 20 min after HFS. In addition, our results suggest that protein kinase activity during and immediately after HFS is not sufficient for LTP induction. These results provide evidence for persistent and/or Ca2+ independent protein kinase activity involvement in LTP induction. ^

Localization and activity detection Based on the fusion of environment And inertial sensors = Localización y detección de actividad Basadas en integración de sensores y dispositivos inerciales

Los sensores inerciales (acelerómetros y giróscopos) se han ido introduciendo poco a poco en dispositivos que usamos en nuestra vida diaria gracias a su minituarización. Hoy en día todos los smartphones contienen como mínimo un acelerómetro y un magnetómetro, siendo complementados en losmás modernos por giróscopos y barómetros. Esto, unido a la proliferación de los smartphones ha hecho viable el diseño de sistemas basados en las medidas de sensores que el usuario lleva colocados en alguna parte del cuerpo (que en un futuro estarán contenidos en tejidos inteligentes) o los integrados en su móvil. El papel de estos sensores se ha convertido en fundamental para el desarrollo de aplicaciones contextuales y de inteligencia ambiental. Algunos ejemplos son el control de los ejercicios de rehabilitación o la oferta de información referente al sitio turístico que se está visitando. El trabajo de esta tesis contribuye a explorar las posibilidades que ofrecen los sensores inerciales para el apoyo a la detección de actividad y la mejora de la precisión de servicios de localización para peatones. En lo referente al reconocimiento de la actividad que desarrolla un usuario, se ha explorado el uso de los sensores integrados en los dispositivos móviles de última generación (luz y proximidad, acelerómetro, giróscopo y magnetómetro). Las actividades objetivo son conocidas como ‘atómicas’ (andar a distintas velocidades, estar de pie, correr, estar sentado), esto es, actividades que constituyen unidades de actividades más complejas como pueden ser lavar los platos o ir al trabajo. De este modo, se usan algoritmos de clasificación sencillos que puedan ser integrados en un móvil como el Naïve Bayes, Tablas y Árboles de Decisión. Además, se pretende igualmente detectar la posición en la que el usuario lleva el móvil, no sólo con el objetivo de utilizar esa información para elegir un clasificador entrenado sólo con datos recogidos en la posición correspondiente (estrategia que mejora los resultados de estimación de la actividad), sino también para la generación de un evento que puede producir la ejecución de una acción. Finalmente, el trabajo incluye un análisis de las prestaciones de la clasificación variando el tipo de parámetros y el número de sensores usados y teniendo en cuenta no sólo la precisión de la clasificación sino también la carga computacional. Por otra parte, se ha propuesto un algoritmo basado en la cuenta de pasos utilizando informaiii ción proveniente de un acelerómetro colocado en el pie del usuario. El objetivo final es detectar la actividad que el usuario está haciendo junto con la estimación aproximada de la distancia recorrida. El algoritmo de cuenta pasos se basa en la detección de máximos y mínimos usando ventanas temporales y umbrales sin requerir información específica del usuario. El ámbito de seguimiento de peatones en interiores es interesante por la falta de un estándar de localización en este tipo de entornos. Se ha diseñado un filtro extendido de Kalman centralizado y ligeramente acoplado para fusionar la información medida por un acelerómetro colocado en el pie del usuario con medidas de posición. Se han aplicado también diferentes técnicas de corrección de errores como las de velocidad cero que se basan en la detección de los instantes en los que el pie está apoyado en el suelo. Los resultados han sido obtenidos en entornos interiores usando las posiciones estimadas por un sistema de triangulación basado en la medida de la potencia recibida (RSS) y GPS en exteriores. Finalmente, se han implementado algunas aplicaciones que prueban la utilidad del trabajo desarrollado. En primer lugar se ha considerado una aplicación de monitorización de actividad que proporciona al usuario información sobre el nivel de actividad que realiza durante un período de tiempo. El objetivo final es favorecer el cambio de comportamientos sedentarios, consiguiendo hábitos saludables. Se han desarrollado dos versiones de esta aplicación. En el primer caso se ha integrado el algoritmo de cuenta pasos en una plataforma OSGi móvil adquiriendo los datos de un acelerómetro Bluetooth colocado en el pie. En el segundo caso se ha creado la misma aplicación utilizando las implementaciones de los clasificadores en un dispositivo Android. Por otro lado, se ha planteado el diseño de una aplicación para la creación automática de un diario de viaje a partir de la detección de eventos importantes. Esta aplicación toma como entrada la información procedente de la estimación de actividad y de localización además de información almacenada en bases de datos abiertas (fotos, información sobre sitios) e información sobre sensores reales y virtuales (agenda, cámara, etc.) del móvil. Abstract Inertial sensors (accelerometers and gyroscopes) have been gradually embedded in the devices that people use in their daily lives thanks to their miniaturization. Nowadays all smartphones have at least one embedded magnetometer and accelerometer, containing the most upto- date ones gyroscopes and barometers. This issue, together with the fact that the penetration of smartphones is growing steadily, has made possible the design of systems that rely on the information gathered by wearable sensors (in the future contained in smart textiles) or inertial sensors embedded in a smartphone. The role of these sensors has become key to the development of context-aware and ambient intelligent applications. Some examples are the performance of rehabilitation exercises, the provision of information related to the place that the user is visiting or the interaction with objects by gesture recognition. The work of this thesis contributes to explore to which extent this kind of sensors can be useful to support activity recognition and pedestrian tracking, which have been proven to be essential for these applications. Regarding the recognition of the activity that a user performs, the use of sensors embedded in a smartphone (proximity and light sensors, gyroscopes, magnetometers and accelerometers) has been explored. The activities that are detected belong to the group of the ones known as ‘atomic’ activities (e.g. walking at different paces, running, standing), that is, activities or movements that are part of more complex activities such as doing the dishes or commuting. Simple, wellknown classifiers that can run embedded in a smartphone have been tested, such as Naïve Bayes, Decision Tables and Trees. In addition to this, another aim is to estimate the on-body position in which the user is carrying the mobile phone. The objective is not only to choose a classifier that has been trained with the corresponding data in order to enhance the classification but also to start actions. Finally, the performance of the different classifiers is analysed, taking into consideration different features and number of sensors. The computational and memory load of the classifiers is also measured. On the other hand, an algorithm based on step counting has been proposed. The acceleration information is provided by an accelerometer placed on the foot. The aim is to detect the activity that the user is performing together with the estimation of the distance covered. The step counting strategy is based on detecting minima and its corresponding maxima. Although the counting strategy is not innovative (it includes time windows and amplitude thresholds to prevent under or overestimation) no user-specific information is required. The field of pedestrian tracking is crucial due to the lack of a localization standard for this kind of environments. A loosely-coupled centralized Extended Kalman Filter has been proposed to perform the fusion of inertial and position measurements. Zero velocity updates have been applied whenever the foot is detected to be placed on the ground. The results have been obtained in indoor environments using a triangulation algorithm based on RSS measurements and GPS outdoors. Finally, some applications have been designed to test the usefulness of the work. The first one is called the ‘Activity Monitor’ whose aim is to prevent sedentary behaviours and to modify habits to achieve desired objectives of activity level. Two different versions of the application have been implemented. The first one uses the activity estimation based on the step counting algorithm, which has been integrated in an OSGi mobile framework acquiring the data from a Bluetooth accelerometer placed on the foot of the individual. The second one uses activity classifiers embedded in an Android smartphone. On the other hand, the design of a ‘Travel Logbook’ has been planned. The input of this application is the information provided by the activity and localization modules, external databases (e.g. pictures, points of interest, weather) and mobile embedded and virtual sensors (agenda, camera, etc.). The aim is to detect important events in the journey and gather the information necessary to store it as a journal page.

An abstract machine based execution model for computer architecture design and efficient implementation of logic programs in parallel.

The term "Logic Programming" refers to a variety of computer languages and execution models which are based on the traditional concept of Symbolic Logic. The expressive power of these languages offers promise to be of great assistance in facing the programming challenges of present and future symbolic processing applications in Artificial Intelligence, Knowledge-based systems, and many other areas of computing. The sequential execution speed of logic programs has been greatly improved since the advent of the first interpreters. However, higher inference speeds are still required in order to meet the demands of applications such as those contemplated for next generation computer systems. The execution of logic programs in parallel is currently considered a promising strategy for attaining such inference speeds. Logic Programming in turn appears as a suitable programming paradigm for parallel architectures because of the many opportunities for parallel execution present in the implementation of logic programs. This dissertation presents an efficient parallel execution model for logic programs. The model is described from the source language level down to an "Abstract Machine" level suitable for direct implementation on existing parallel systems or for the design of special purpose parallel architectures. Few assumptions are made at the source language level and therefore the techniques developed and the general Abstract Machine design are applicable to a variety of logic (and also functional) languages. These techniques offer efficient solutions to several areas of parallel Logic Programming implementation previously considered problematic or a source of considerable overhead, such as the detection and handling of variable binding conflicts in AND-Parallelism, the specification of control and management of the execution tree, the treatment of distributed backtracking, and goal scheduling and memory management issues, etc. A parallel Abstract Machine design is offered, specifying data areas, operation, and a suitable instruction set. This design is based on extending to a parallel environment the techniques introduced by the Warren Abstract Machine, which have already made very fast and space efficient sequential systems a reality. Therefore, the model herein presented is capable of retaining sequential execution speed similar to that of high performance sequential systems, while extracting additional gains in speed by efficiently implementing parallel execution. These claims are supported by simulations of the Abstract Machine on sample programs.

Vision-Based Tracking, Odometry and Control for UAV Autonomy

El principal objetivo de este trabajo es proporcionar una solución en tiempo real basada en visión estéreo o monocular precisa y robusta para que un vehículo aéreo no tripulado (UAV) sea autónomo en varios tipos de aplicaciones UAV, especialmente en entornos abarrotados sin señal GPS. Este trabajo principalmente consiste en tres temas de investigación de UAV basados en técnicas de visión por computador: (I) visual tracking, proporciona soluciones efectivas para localizar visualmente objetos de interés estáticos o en movimiento durante el tiempo que dura el vuelo del UAV mediante una aproximación adaptativa online y una estrategia de múltiple resolución, de este modo superamos los problemas generados por las diferentes situaciones desafiantes, tales como cambios significativos de aspecto, iluminación del entorno variante, fondo del tracking embarullado, oclusión parcial o total de objetos, variaciones rápidas de posición y vibraciones mecánicas a bordo. La solución ha sido utilizada en aterrizajes autónomos, inspección de plataformas mar adentro o tracking de aviones en pleno vuelo para su detección y evasión; (II) odometría visual: proporciona una solución eficiente al UAV para estimar la posición con 6 grados de libertad (6D) usando únicamente la entrada de una cámara estéreo a bordo del UAV. Un método Semi-Global Blocking Matching (SGBM) eficiente basado en una estrategia grueso-a-fino ha sido implementada para una rápida y profunda estimación del plano. Además, la solución toma provecho eficazmente de la información 2D y 3D para estimar la posición 6D, resolviendo de esta manera la limitación de un punto de referencia fijo en la cámara estéreo. Una robusta aproximación volumétrica de mapping basada en el framework Octomap ha sido utilizada para reconstruir entornos cerrados y al aire libre bastante abarrotados en 3D con memoria y errores correlacionados espacialmente o temporalmente; (III) visual control, ofrece soluciones de control prácticas para la navegación de un UAV usando Fuzzy Logic Controller (FLC) con la estimación visual. Y el framework de Cross-Entropy Optimization (CEO) ha sido usado para optimizar el factor de escala y la función de pertenencia en FLC. Todas las soluciones basadas en visión en este trabajo han sido probadas en test reales. Y los conjuntos de datos de imágenes reales grabados en estos test o disponibles para la comunidad pública han sido utilizados para evaluar el rendimiento de estas soluciones basadas en visión con ground truth. Además, las soluciones de visión presentadas han sido comparadas con algoritmos de visión del estado del arte. Los test reales y los resultados de evaluación muestran que las soluciones basadas en visión proporcionadas han obtenido rendimientos en tiempo real precisos y robustos, o han alcanzado un mejor rendimiento que aquellos algoritmos del estado del arte. La estimación basada en visión ha ganado un rol muy importante en controlar un UAV típico para alcanzar autonomía en aplicaciones UAV. ABSTRACT The main objective of this dissertation is providing real-time accurate robust monocular or stereo vision-based solution for Unmanned Aerial Vehicle (UAV) to achieve the autonomy in various types of UAV applications, especially in GPS-denied dynamic cluttered environments. This dissertation mainly consists of three UAV research topics based on computer vision technique: (I) visual tracking, it supplys effective solutions to visually locate interesting static or moving object over time during UAV flight with on-line adaptivity approach and multiple-resolution strategy, thereby overcoming the problems generated by the different challenging situations, such as significant appearance change, variant surrounding illumination, cluttered tracking background, partial or full object occlusion, rapid pose variation and onboard mechanical vibration. The solutions have been utilized in autonomous landing, offshore floating platform inspection and midair aircraft tracking for sense-and-avoid; (II) visual odometry: it provides the efficient solution for UAV to estimate the 6 Degree-of-freedom (6D) pose using only the input of stereo camera onboard UAV. An efficient Semi-Global Blocking Matching (SGBM) method based on a coarse-to-fine strategy has been implemented for fast depth map estimation. In addition, the solution effectively takes advantage of both 2D and 3D information to estimate the 6D pose, thereby solving the limitation of a fixed small baseline in the stereo camera. A robust volumetric occupancy mapping approach based on the Octomap framework has been utilized to reconstruct indoor and outdoor large-scale cluttered environments in 3D with less temporally or spatially correlated measurement errors and memory; (III) visual control, it offers practical control solutions to navigate UAV using Fuzzy Logic Controller (FLC) with the visual estimation. And the Cross-Entropy Optimization (CEO) framework has been used to optimize the scaling factor and the membership function in FLC. All the vision-based solutions in this dissertation have been tested in real tests. And the real image datasets recorded from these tests or available from public community have been utilized to evaluate the performance of these vision-based solutions with ground truth. Additionally, the presented vision solutions have compared with the state-of-art visual algorithms. Real tests and evaluation results show that the provided vision-based solutions have obtained real-time accurate robust performances, or gained better performance than those state-of-art visual algorithms. The vision-based estimation has played a critically important role for controlling a typical UAV to achieve autonomy in the UAV application.

Contribution to the improvement of communication services in nanosatellite constellations using delay and disruption tolerant networking based architectures

Esta tesis se desarrolla dentro del marco de las comunicaciones satelitales en el innovador campo de los pequeños satélites también llamados nanosatélites o cubesats, llamados así por su forma cubica. Estos nanosatélites se caracterizan por su bajo costo debido a que usan componentes comerciales llamados COTS (commercial off-the-shelf) y su pequeño tamaño como los Cubesats 1U (10cm*10 cm*10 cm) con masa aproximada a 1 kg. Este trabajo de tesis tiene como base una iniciativa propuesta por el autor de la tesis para poner en órbita el primer satélite peruano en mi país llamado chasqui I, actualmente puesto en órbita desde la Estación Espacial Internacional. La experiencia de este trabajo de investigación me llevo a proponer una constelación de pequeños satélites llamada Waposat para dar servicio de monitoreo de sensores de calidad de agua a nivel global, escenario que es usado en esta tesis. Es ente entorno y dadas las características limitadas de los pequeños satélites, tanto en potencia como en velocidad de datos, es que propongo investigar una nueva arquitectura de comunicaciones que permita resolver en forma óptima la problemática planteada por los nanosatélites en órbita LEO debido a su carácter disruptivo en sus comunicaciones poniendo énfasis en las capas de enlace y aplicación. Esta tesis presenta y evalúa una nueva arquitectura de comunicaciones para proveer servicio a una red de sensores terrestres usando una solución basada en DTN (Delay/Disruption Tolerant Networking) para comunicaciones espaciales. Adicionalmente, propongo un nuevo protocolo de acceso múltiple que usa una extensión del protocolo ALOHA no ranurado, el cual toma en cuenta la prioridad del trafico del Gateway (ALOHAGP) con un mecanismo de contienda adaptativo. Utiliza la realimentación del satélite para implementar el control de la congestión y adapta dinámicamente el rendimiento efectivo del canal de una manera óptima. Asumimos un modelo de población de sensores finito y una condición de tráfico saturado en el que cada sensor tiene siempre tramas que transmitir. El desempeño de la red se evaluó en términos de rendimiento efectivo, retardo y la equidad del sistema. Además, se ha definido una capa de convergencia DTN (ALOHAGP-CL) como un subconjunto del estándar TCP-CL (Transmission Control Protocol-Convergency Layer). Esta tesis muestra que ALOHAGP/CL soporta adecuadamente el escenario DTN propuesto, sobre todo cuando se utiliza la fragmentación reactiva. Finalmente, esta tesis investiga una transferencia óptima de mensajes DTN (Bundles) utilizando estrategias de fragmentación proactivas para dar servicio a una red de sensores terrestres utilizando un enlace de comunicaciones satelitales que utiliza el mecanismo de acceso múltiple con prioridad en el tráfico de enlace descendente (ALOHAGP). El rendimiento efectivo ha sido optimizado mediante la adaptación de los parámetros del protocolo como una función del número actual de los sensores activos recibidos desde el satélite. También, actualmente no existe un método para advertir o negociar el tamaño máximo de un “bundle” que puede ser aceptado por un agente DTN “bundle” en las comunicaciones por satélite tanto para el almacenamiento y la entrega, por lo que los “bundles” que son demasiado grandes son eliminados o demasiado pequeños son ineficientes. He caracterizado este tipo de escenario obteniendo una distribución de probabilidad de la llegada de tramas al nanosatélite así como una distribución de probabilidad del tiempo de visibilidad del nanosatélite, los cuales proveen una fragmentación proactiva óptima de los DTN “bundles”. He encontrado que el rendimiento efectivo (goodput) de la fragmentación proactiva alcanza un valor ligeramente inferior al de la fragmentación reactiva. Esta contribución permite utilizar la fragmentación activa de forma óptima con todas sus ventajas tales como permitir implantar el modelo de seguridad de DTN y la simplicidad al implementarlo en equipos con muchas limitaciones de CPU y memoria. La implementación de estas contribuciones se han contemplado inicialmente como parte de la carga útil del nanosatélite QBito, que forma parte de la constelación de 50 nanosatélites que se está llevando a cabo dentro del proyecto QB50. ABSTRACT This thesis is developed within the framework of satellite communications in the innovative field of small satellites also known as nanosatellites (<10 kg) or CubeSats, so called from their cubic form. These nanosatellites are characterized by their low cost because they use commercial components called COTS (commercial off-the-shelf), and their small size and mass, such as 1U Cubesats (10cm * 10cm * 10cm) with approximately 1 kg mass. This thesis is based on a proposal made by the author of the thesis to put into orbit the first Peruvian satellite in his country called Chasqui I, which was successfully launched into orbit from the International Space Station in 2014. The experience of this research work led me to propose a constellation of small satellites named Waposat to provide water quality monitoring sensors worldwide, scenario that is used in this thesis. In this scenario and given the limited features of nanosatellites, both power and data rate, I propose to investigate a new communications architecture that allows solving in an optimal manner the problems of nanosatellites in orbit LEO due to the disruptive nature of their communications by putting emphasis on the link and application layers. This thesis presents and evaluates a new communications architecture to provide services to terrestrial sensor networks using a space Delay/Disruption Tolerant Networking (DTN) based solution. In addition, I propose a new multiple access mechanism protocol based on extended unslotted ALOHA that takes into account the priority of gateway traffic, which we call ALOHA multiple access with gateway priority (ALOHAGP) with an adaptive contention mechanism. It uses satellite feedback to implement the congestion control, and to dynamically adapt the channel effective throughput in an optimal way. We assume a finite sensor population model and a saturated traffic condition where every sensor always has frames to transmit. The performance was evaluated in terms of effective throughput, delay and system fairness. In addition, a DTN convergence layer (ALOHAGP-CL) has been defined as a subset of the standard TCP-CL (Transmission Control Protocol-Convergence Layer). This thesis reveals that ALOHAGP/CL adequately supports the proposed DTN scenario, mainly when reactive fragmentation is used. Finally, this thesis investigates an optimal DTN message (bundles) transfer using proactive fragmentation strategies to give service to a ground sensor network using a nanosatellite communications link which uses a multi-access mechanism with priority in downlink traffic (ALOHAGP). The effective throughput has been optimized by adapting the protocol parameters as a function of the current number of active sensors received from satellite. Also, there is currently no method for advertising or negotiating the maximum size of a bundle which can be accepted by a bundle agent in satellite communications for storage and delivery, so that bundles which are too large can be dropped or which are too small are inefficient. We have characterized this kind of scenario obtaining a probability distribution for frame arrivals to nanosatellite and visibility time distribution that provide an optimal proactive fragmentation of DTN bundles. We have found that the proactive effective throughput (goodput) reaches a value slightly lower than reactive fragmentation approach. This contribution allows to use the proactive fragmentation optimally with all its advantages such as the incorporation of the security model of DTN and simplicity in protocol implementation for computers with many CPU and memory limitations. The implementation of these contributions was initially contemplated as part of the payload of the nanosatellite QBito, which is part of the constellation of 50 nanosatellites envisaged under the QB50 project.

La memoria en el proceso creativo de Juan Muñoz = Memory in the creative process of Juan Muñoz

Esta tesis integra un estudio reflexivo sobre la relación de dependencia entre la creación y la memoria a través del análisis de la última obra del escultor Juan Muñoz: Double Bind (Tate Modern, Londres, 2001). Desde esta posición es obligado replantear el análisis de la obra, lo que hace necesario su estudio cubriendo el mayor espectro posible de información accesible más allá de la obra en sí, para aproximarse a la convergencia entre memoria y creación. La perspectiva de análisis propuesta abre camino a nuevas consideraciones so¬bre la relevancia del conocimiento en el desarrollo del proceso creativo. Este análisis no debe tan sólo suponer una aportación al conocimiento del trabajo de Juan Muñoz. Debe también desprenderse de él la innegable participación y necesaria lectura del pasado en el presente. La amnesia de los tiempos pasados impide completar el atlas de imágenes en las que se apoya la creación impidiendo el conocimiento del origen de las fuentes de inspi¬ración y las bases de la creación de una determinada obra. Este hecho limita y distorsiona sus posibles interpretaciones. Pretendo un acercamiento al entendimiento de la forma de mirar y de crear a través del tiempo que es memoria. La memoria tiene un cometido de crucial importancia para la actividad mental y juega un papel fundamental en la conducta y en la creación. La obra es el resultado de la búsqueda de una idea que exprese algo que el creador no puede ex¬presar de otra manera. Es la necesidad de expresar las ideas mediante un lenguaje que se desarrolla en el tiempo y en el espacio, reflejo del ser que responde al pensamiento. Es una forma de experiencia donde subyacen las sendas del pasado y donde se plantea el futuro. Sólo el creador accede a la obra desde dentro, el observador llega a ella desde el exterior y mediante su propia subjetividad. Las obras son formas de experiencia de sus autores, comunicar el mensaje de dicha experiencia supone por tanto interpretar. Persiguiendo la necesidad de saber y entender, pretender explicar el sentido de una cosa implica una apreciación intencionada asociada al entendimiento del intérprete. Las obras son produc¬tos que portan un mensaje y que contienen en su estructura las trazas del tiempo vivido por su creador. Si se quiere adquirir un acercamiento que represente la posición de un autor, será necesario no solo mirar a través de ella, si no introducirse en el contexto de su historia. Mirar hacia atrás, hacia la profundidad del presente para tener conciencia del pensamiento presente y futuro. Recorrer de este modo la instalación Double Bind de Juan Muñoz proporciona una síntesis de sus preocupaciones e intereses a la vez que aporta un conocimiento no necesariamente inmediato, pero relevante y trascendente de la obra, su creador y la historia. ABSTRACT This thesis comprises a reflective study of the dependence relationship between creation and memory through the analysis of the latest work by the sculptor Juan Muñoz: Double Bind (Tate Modern, London, 2001). From this position, it is mandatory to rethink the analysis of the work, making it necessary to cover the widest possible range of information available beyond the work itself, in order to obtain a closer view of the convergence between memory and creation. The proposed analytical approach opens up new considerations on the relevance of knowledge during the development of the creative process. This analysis should not only make a contribution to the knowledge of the work of Juan Muñoz. It should also infer the undeniable involvement and the necessary reading of the past in the present. Amnesia regarding past makes it impossible to complete the atlas of images on which the creation is based, blocking knowledge of the origin of the sources of inspiration and the basis for the creation of a specific work. This fact limits and distorts its possible interpretations. My intention is an approach to how to understand memory as the way of looking and creating over time. Memory has a crucial role to mental activity and plays a key role in behaviour and creation. The work is the result of finding an idea that expresses something that the creator can not express otherwise. It is the need to express ideas by means of a language that develops throughout time and space, a reflection of the being that responds to the thought. It is a way of experience underlying the paths of the past and where the future is set out. Only the creator can access the work from the inside. The observer sees it from the outside and in accordance with his/her own subjectivity. The works form a part of the experience of their authors, thus implying the interpretation of the message of their experience being passed on. The pursuit of knowledge and understanding, and trying to explain the meaning of something implies a deliberate appreciation associated with the understanding of the interpreter. The works are products bearing a message and containing in their structure traces of the time lived by their creator. If one wants to come close to what the author’s posture represents, it will not only be necessary to penetrate it, but also to introduce oneself into the context of its history. Take a look back, towards the depth of the present in order to become aware of present and future thinking. To go across the installation of Double Bind by Juan Muñoz in this way offers a synthesis of his concerns and interests while also providing a not necessarily immediate knowledge, but one which is relevant and important to the work, its creator and history.

Telomere lengthening and telomerase activation during human B cell differentiation

The function of the immune system is highly dependent on cellular differentiation and clonal expansion of antigen-specific lymphocytes. However, little is known about mechanisms that may have evolved to protect replicative potential in actively dividing lymphocytes during immune differentiation and response. Here we report an analysis of telomere length and telomerase expression, factors implicated in the regulation of cellular replicative lifespan, in human B cell subsets. In contrast to previous observations, in which telomere shortening and concomitant loss of replicative potential occur in the process of somatic cell differentiation and cell division, it was found that germinal center (GC) B cells, a compartment characterized by extensive clonal expansion and selection, had significantly longer telomeric restriction fragments than those of precursor naive B cells. Furthermore, it was found that telomerase, a telomere-synthesizing enzyme, is expressed at high levels in GC B cells (at least 128-fold higher than those of naive and memory B cells), correlating with the long telomeres in this subset of B cells. Finally, both naive and memory B cells were capable of up-regulating telomerase activity in vitro in response to activation signals through the B cell antigen receptor in the presence of CD40 engagement and/or interleukin 4. These observations suggest that a novel process of telomere lengthening, possibly mediated by telomerase, functions in actively dividing GC B lymphocytes and may play a critical role in humoral immune response by maintaining the replicative potential of GC and descendant memory B cells.