Collective Organization of Complex Networks: Emergent Scales, Vulnerability, and Targeting of Desired Dynamics

Cuando una colectividad de sistemas dinámicos acoplados mediante una estructura irregular de interacciones evoluciona, se observan dinámicas de gran complejidad y fenómenos emergentes imposibles de predecir a partir de las propiedades de los sistemas individuales. El objetivo principal de esta tesis es precisamente avanzar en nuestra comprensión de la relación existente entre la topología de interacciones y las dinámicas colectivas que una red compleja es capaz de mantener. Siendo este un tema amplio que se puede abordar desde distintos puntos de vista, en esta tesis se han estudiado tres problemas importantes dentro del mismo que están relacionados entre sí. Por un lado, en numerosos sistemas naturales y artificiales que se pueden describir mediante una red compleja la topología no es estática, sino que depende de la dinámica que se desarrolla en la red: un ejemplo son las redes de neuronas del cerebro. En estas redes adaptativas la propia topología emerge como consecuencia de una autoorganización del sistema. Para conocer mejor cómo pueden emerger espontáneamente las propiedades comúnmente observadas en redes reales, hemos estudiado el comportamiento de sistemas que evolucionan según reglas adaptativas locales con base empírica. Nuestros resultados numéricos y analíticos muestran que la autoorganización del sistema da lugar a dos de las propiedades más universales de las redes complejas: a escala mesoscópica, la aparición de una estructura de comunidades, y, a escala macroscópica, la existencia de una ley de potencias en la distribución de las interacciones en la red. El hecho de que estas propiedades aparecen en dos modelos con leyes de evolución cuantitativamente distintas que siguen unos mismos principios adaptativos sugiere que estamos ante un fenómeno que puede ser muy general, y estar en el origen de estas propiedades en sistemas reales. En segundo lugar, proponemos una medida que permite clasificar los elementos de una red compleja en función de su relevancia para el mantenimiento de dinámicas colectivas. En concreto, estudiamos la vulnerabilidad de los distintos elementos de una red frente a perturbaciones o grandes fluctuaciones, entendida como una medida del impacto que estos acontecimientos externos tienen en la interrupción de una dinámica colectiva. Los resultados que se obtienen indican que la vulnerabilidad dinámica es sobre todo dependiente de propiedades locales, por tanto nuestras conclusiones abarcan diferentes topologías, y muestran la existencia de una dependencia no trivial entre la vulnerabilidad y la conectividad de los elementos de una red. Finalmente, proponemos una estrategia de imposición de una dinámica objetivo genérica en una red dada e investigamos su validez en redes con diversas topologías que mantienen regímenes dinámicos turbulentos. Se obtiene como resultado que las redes heterogéneas (y la amplia mayora de las redes reales estudiadas lo son) son las más adecuadas para nuestra estrategia de targeting de dinámicas deseadas, siendo la estrategia muy efectiva incluso en caso de disponer de un conocimiento muy imperfecto de la topología de la red. Aparte de la relevancia teórica para la comprensión de fenómenos colectivos en sistemas complejos, los métodos y resultados propuestos podrán dar lugar a aplicaciones en sistemas experimentales y tecnológicos, como por ejemplo los sistemas neuronales in vitro, el sistema nervioso central (en el estudio de actividades síncronas de carácter patológico), las redes eléctricas o los sistemas de comunicaciones. ABSTRACT The time evolution of an ensemble of dynamical systems coupled through an irregular interaction scheme gives rise to dynamics of great of complexity and emergent phenomena that cannot be predicted from the properties of the individual systems. The main objective of this thesis is precisely to increase our understanding of the interplay between the interaction topology and the collective dynamics that a complex network can support. This is a very broad subject, so in this thesis we will limit ourselves to the study of three relevant problems that have strong connections among them. First, it is a well-known fact that in many natural and manmade systems that can be represented as complex networks the topology is not static; rather, it depends on the dynamics taking place on the network (as it happens, for instance, in the neuronal networks in the brain). In these adaptive networks the topology itself emerges from the self-organization in the system. To better understand how the properties that are commonly observed in real networks spontaneously emerge, we have studied the behavior of systems that evolve according to local adaptive rules that are empirically motivated. Our numerical and analytical results show that self-organization brings about two of the most universally found properties in complex networks: at the mesoscopic scale, the appearance of a community structure, and, at the macroscopic scale, the existence of a power law in the weight distribution of the network interactions. The fact that these properties show up in two models with quantitatively different mechanisms that follow the same general adaptive principles suggests that our results may be generalized to other systems as well, and they may be behind the origin of these properties in some real systems. We also propose a new measure that provides a ranking of the elements in a network in terms of their relevance for the maintenance of collective dynamics. Specifically, we study the vulnerability of the elements under perturbations or large fluctuations, interpreted as a measure of the impact these external events have on the disruption of collective motion. Our results suggest that the dynamic vulnerability measure depends largely on local properties (our conclusions thus being valid for different topologies) and they show a non-trivial dependence of the vulnerability on the connectivity of the network elements. Finally, we propose a strategy for the imposition of generic goal dynamics on a given network, and we explore its performance in networks with different topologies that support turbulent dynamical regimes. It turns out that heterogeneous networks (and most real networks that have been studied belong in this category) are the most suitable for our strategy for the targeting of desired dynamics, the strategy being very effective even when the knowledge on the network topology is far from accurate. Aside from their theoretical relevance for the understanding of collective phenomena in complex systems, the methods and results here discussed might lead to applications in experimental and technological systems, such as in vitro neuronal systems, the central nervous system (where pathological synchronous activity sometimes occurs), communication systems or power grids.

Functional and effective connectivity in MEG. Application to the study of epilepsy

Nuestro cerebro contiene cerca de 1014 sinapsis neuronales. Esta enorme cantidad de conexiones proporciona un entorno ideal donde distintos grupos de neuronas se sincronizan transitoriamente para provocar la aparición de funciones cognitivas, como la percepción, el aprendizaje o el pensamiento. Comprender la organización de esta compleja red cerebral en base a datos neurofisiológicos, representa uno de los desafíos más importantes y emocionantes en el campo de la neurociencia. Se han propuesto recientemente varias medidas para evaluar cómo se comunican las diferentes partes del cerebro a diversas escalas (células individuales, columnas corticales, o áreas cerebrales). Podemos clasificarlos, según su simetría, en dos grupos: por una parte, la medidas simétricas, como la correlación, la coherencia o la sincronización de fase, que evalúan la conectividad funcional (FC); mientras que las medidas asimétricas, como la causalidad de Granger o transferencia de entropía, son capaces de detectar la dirección de la interacción, lo que denominamos conectividad efectiva (EC). En la neurociencia moderna ha aumentado el interés por el estudio de las redes funcionales cerebrales, en gran medida debido a la aparición de estos nuevos algoritmos que permiten analizar la interdependencia entre señales temporales, además de la emergente teoría de redes complejas y la introducción de técnicas novedosas, como la magnetoencefalografía (MEG), para registrar datos neurofisiológicos con gran resolución. Sin embargo, nos hallamos ante un campo novedoso que presenta aun varias cuestiones metodológicas sin resolver, algunas de las cuales trataran de abordarse en esta tesis. En primer lugar, el creciente número de aproximaciones para determinar la existencia de FC/EC entre dos o más señales temporales, junto con la complejidad matemática de las herramientas de análisis, hacen deseable organizarlas todas en un paquete software intuitivo y fácil de usar. Aquí presento HERMES (http://hermes.ctb.upm.es), una toolbox en MatlabR, diseñada precisamente con este fin. Creo que esta herramienta será de gran ayuda para todos aquellos investigadores que trabajen en el campo emergente del análisis de conectividad cerebral y supondrá un gran valor para la comunidad científica. La segunda cuestión practica que se aborda es el estudio de la sensibilidad a las fuentes cerebrales profundas a través de dos tipos de sensores MEG: gradiómetros planares y magnetómetros, esta aproximación además se combina con un enfoque metodológico, utilizando dos índices de sincronización de fase: phase locking value (PLV) y phase lag index (PLI), este ultimo menos sensible a efecto la conducción volumen. Por lo tanto, se compara su comportamiento al estudiar las redes cerebrales, obteniendo que magnetómetros y PLV presentan, respectivamente, redes más densamente conectadas que gradiómetros planares y PLI, por los valores artificiales que crea el problema de la conducción de volumen. Sin embargo, cuando se trata de caracterizar redes epilépticas, el PLV ofrece mejores resultados, debido a la gran dispersión de las redes obtenidas con PLI. El análisis de redes complejas ha proporcionado nuevos conceptos que mejoran caracterización de la interacción de sistemas dinámicos. Se considera que una red está compuesta por nodos, que simbolizan sistemas, cuyas interacciones se representan por enlaces, y su comportamiento y topología puede caracterizarse por un elevado número de medidas. Existe evidencia teórica y empírica de que muchas de ellas están fuertemente correlacionadas entre sí. Por lo tanto, se ha conseguido seleccionar un pequeño grupo que caracteriza eficazmente estas redes, y condensa la información redundante. Para el análisis de redes funcionales, la selección de un umbral adecuado para decidir si un determinado valor de conectividad de la matriz de FC es significativo y debe ser incluido para un análisis posterior, se convierte en un paso crucial. En esta tesis, se han obtenido resultados más precisos al utilizar un test de subrogadas, basado en los datos, para evaluar individualmente cada uno de los enlaces, que al establecer a priori un umbral fijo para la densidad de conexiones. Finalmente, todas estas cuestiones se han aplicado al estudio de la epilepsia, caso práctico en el que se analizan las redes funcionales MEG, en estado de reposo, de dos grupos de pacientes epilépticos (generalizada idiopática y focal frontal) en comparación con sujetos control sanos. La epilepsia es uno de los trastornos neurológicos más comunes, con más de 55 millones de afectados en el mundo. Esta enfermedad se caracteriza por la predisposición a generar ataques epilépticos de actividad neuronal anormal y excesiva o bien síncrona, y por tanto, es el escenario perfecto para este tipo de análisis al tiempo que presenta un gran interés tanto desde el punto de vista clínico como de investigación. Los resultados manifiestan alteraciones especificas en la conectividad y un cambio en la topología de las redes en cerebros epilépticos, desplazando la importancia del ‘foco’ a la ‘red’, enfoque que va adquiriendo relevancia en las investigaciones recientes sobre epilepsia. ABSTRACT There are about 1014 neuronal synapses in the human brain. This huge number of connections provides the substrate for neuronal ensembles to become transiently synchronized, producing the emergence of cognitive functions such as perception, learning or thinking. Understanding the complex brain network organization on the basis of neuroimaging data represents one of the most important and exciting challenges for systems neuroscience. Several measures have been recently proposed to evaluate at various scales (single cells, cortical columns, or brain areas) how the different parts of the brain communicate. We can classify them, according to their symmetry, into two groups: symmetric measures, such as correlation, coherence or phase synchronization indexes, evaluate functional connectivity (FC); and on the other hand, the asymmetric ones, such as Granger causality or transfer entropy, are able to detect effective connectivity (EC) revealing the direction of the interaction. In modern neurosciences, the interest in functional brain networks has increased strongly with the onset of new algorithms to study interdependence between time series, the advent of modern complex network theory and the introduction of powerful techniques to record neurophysiological data, such as magnetoencephalography (MEG). However, when analyzing neurophysiological data with this approach several questions arise. In this thesis, I intend to tackle some of the practical open problems in the field. First of all, the increase in the number of time series analysis algorithms to study brain FC/EC, along with their mathematical complexity, creates the necessity of arranging them into a single, unified toolbox that allow neuroscientists, neurophysiologists and researchers from related fields to easily access and make use of them. I developed such a toolbox for this aim, it is named HERMES (http://hermes.ctb.upm.es), and encompasses several of the most common indexes for the assessment of FC and EC running for MatlabR environment. I believe that this toolbox will be very helpful to all the researchers working in the emerging field of brain connectivity analysis and will entail a great value for the scientific community. The second important practical issue tackled in this thesis is the evaluation of the sensitivity to deep brain sources of two different MEG sensors: planar gradiometers and magnetometers, in combination with the related methodological approach, using two phase synchronization indexes: phase locking value (PLV) y phase lag index (PLI), the latter one being less sensitive to volume conduction effect. Thus, I compared their performance when studying brain networks, obtaining that magnetometer sensors and PLV presented higher artificial values as compared with planar gradiometers and PLI respectively. However, when it came to characterize epileptic networks it was the PLV which gives better results, as PLI FC networks where very sparse. Complex network analysis has provided new concepts which improved characterization of interacting dynamical systems. With this background, networks could be considered composed of nodes, symbolizing systems, whose interactions with each other are represented by edges. A growing number of network measures is been applied in network analysis. However, there is theoretical and empirical evidence that many of these indexes are strongly correlated with each other. Therefore, in this thesis I reduced them to a small set, which could more efficiently characterize networks. Within this framework, selecting an appropriate threshold to decide whether a certain connectivity value of the FC matrix is significant and should be included in the network analysis becomes a crucial step, in this thesis, I used the surrogate data tests to make an individual data-driven evaluation of each of the edges significance and confirmed more accurate results than when just setting to a fixed value the density of connections. All these methodologies were applied to the study of epilepsy, analysing resting state MEG functional networks, in two groups of epileptic patients (generalized and focal epilepsy) that were compared to matching control subjects. Epilepsy is one of the most common neurological disorders, with more than 55 million people affected worldwide, characterized by its predisposition to generate epileptic seizures of abnormal excessive or synchronous neuronal activity, and thus, this scenario and analysis, present a great interest from both the clinical and the research perspective. Results revealed specific disruptions in connectivity and network topology and evidenced that networks’ topology is changed in epileptic brains, supporting the shift from ‘focus’ to ‘networks’ which is gaining importance in modern epilepsy research.

High Efficiency Envelope Amplifier based on a Ripple Cancellation Buck Converter. Design, Optimization and Integration in an EER RFPA

Durante los últimos años la tendencia en el sector de las telecomunicaciones ha sido un aumento y diversificación en la transmisión de voz, video y fundamentalmente de datos. Para conseguir alcanzar las tasas de transmisión requeridas, los nuevos estándares de comunicaciones requieren un mayor ancho de banda y tienen un mayor factor de pico, lo cual influye en el bajo rendimiento del amplificador de radiofrecuencia (RFPA). Otro factor que ha influido en el bajo rendimiento es el diseño del amplificador de radiofrecuencia. Tradicionalmente se han utilizado amplificadores lineales por su buen funcionamiento. Sin embargo, debido al elevado factor de pico de las señales transmitidas, el rendimiento de este tipo de amplificadores es bajo. El bajo rendimiento del sistema conlleva desventajas adicionales como el aumento del coste y del tamaño del sistema de refrigeración, como en el caso de una estación base, o como la reducción del tiempo de uso y un mayor calentamiento del equipo para sistemas portátiles alimentados con baterías. Debido a estos factores, se han desarrollado durante las últimas décadas varias soluciones para aumentar el rendimiento del RFPA como la técnica de Outphasing, combinadores de potencia o la técnica de Doherty. Estas soluciones mejoran las prestaciones del RFPA y en algún caso han sido ampliamente utilizados comercialmente como la técnica de Doherty, que alcanza rendimientos hasta del 50% para el sistema completo para anchos de banda de hasta 20MHz. Pese a las mejoras obtenidas con estas soluciones, los mayores rendimientos del sistema se obtienen para soluciones basadas en la modulación de la tensión de alimentación del amplificador de potencia como “Envelope Tracking” o “EER”. La técnica de seguimiento de envolvente o “Envelope Tracking” está basada en la modulación de la tensión de alimentación de un amplificador lineal de potencia para obtener una mejora en el rendimiento en el sistema comparado a una solución con una tensión de alimentación constante. Para la implementación de esta técnica se necesita una etapa adicional, el amplificador de envolvente, que añade complejidad al amplificador de radiofrecuencia. En un amplificador diseñado con esta técnica, se aumentan las pérdidas debido a la etapa adicional que supone el amplificador de envolvente pero a su vez disminuyen las pérdidas en el amplificador de potencia. Si el diseño se optimiza adecuadamente, puede conseguirse un aumento global en el rendimiento del sistema superior al conseguido con las técnicas mencionadas anteriormente. Esta técnica presenta ventajas en el diseño del amplificador de envolvente, ya que el ancho de banda requerido puede ser menor que el ancho de banda de la señal de envolvente si se optimiza adecuadamente el diseño. Adicionalmente, debido a que la sincronización entre la señal de envolvente y de fase no tiene que ser perfecta, el proceso de integración conlleva ciertas ventajas respecto a otras técnicas como EER. La técnica de eliminación y restauración de envolvente, llamada EER o técnica de Kahn está basada en modulación simultánea de la envolvente y la fase de la señal usando un amplificador de potencia conmutado, no lineal y que permite obtener un elevado rendimiento. Esta solución fue propuesta en el año 1952, pero no ha sido implementada con éxito durante muchos años debido a los exigentes requerimientos en cuanto a la sincronización entre fase y envolvente, a las técnicas de control y de corrección de los errores y no linealidades de cada una de las etapas así como de los equipos para poder implementar estas técnicas, que tienen unos requerimientos exigentes en capacidad de cálculo y procesamiento. Dentro del diseño de un RFPA, el amplificador de envolvente tiene una gran importancia debido a su influencia en el rendimiento y ancho de banda del sistema completo. Adicionalmente, la linealidad y la calidad de la señal de transmitida deben ser elevados para poder cumplir con los diferentes estándares de telecomunicaciones. Esta tesis se centra en el amplificador de envolvente y el objetivo principal es el desarrollo de soluciones que permitan el aumento del rendimiento total del sistema a la vez que satisfagan los requerimientos de ancho de banda, calidad de la señal transmitida y de linealidad. Debido al elevado rendimiento que potencialmente puede alcanzarse con la técnica de EER, esta técnica ha sido objeto de análisis y en el estado del arte pueden encontrarse numerosas referencias que analizan el diseño y proponen diversas implementaciones. En una clasificación de alto nivel, podemos agrupar las soluciones propuestas del amplificador de envolvente según estén compuestas de una o múltiples etapas. Las soluciones para el amplificador de envolvente en una configuración multietapa se basan en la combinación de un convertidor conmutado, de elevado rendimiento con un regulador lineal, de alto ancho de banda, en una combinación serie o paralelo. Estas soluciones, debido a la combinación de las características de ambas etapas, proporcionan un buen compromiso entre rendimiento y buen funcionamiento del amplificador de RF. Por otro lado, la complejidad del sistema aumenta debido al mayor número de componentes y de señales de control necesarias y el aumento de rendimiento que se consigue con estas soluciones es limitado. Una configuración en una etapa tiene las ventajas de una mayor simplicidad, pero debido al elevado ancho de banda necesario, la frecuencia de conmutación debe aumentarse en gran medida. Esto implicará un bajo rendimiento y un peor funcionamiento del amplificador de envolvente. En el estado del arte pueden encontrarse diversas soluciones para un amplificador de envolvente en una etapa, como aumentar la frecuencia de conmutación y realizar la implementación en un circuito integrado, que tendrá mejor funcionamiento a altas frecuencias o utilizar técnicas topológicas y/o filtros de orden elevado, que permiten una reducción de la frecuencia de conmutación. En esta tesis se propone de manera original el uso de la técnica de cancelación de rizado, aplicado al convertidor reductor síncrono, para reducir la frecuencia de conmutación comparado con diseño equivalente del convertidor reductor convencional. Adicionalmente se han desarrollado dos variantes topológicas basadas en esta solución para aumentar la robustez y las prestaciones de la misma. Otro punto de interés en el diseño de un RFPA es la dificultad de poder estimar la influencia de los parámetros de diseño del amplificador de envolvente en el amplificador final integrado. En esta tesis se ha abordado este problema y se ha desarrollado una herramienta de diseño que permite obtener las principales figuras de mérito del amplificador integrado para la técnica de EER a partir del diseño del amplificador de envolvente. Mediante el uso de esta herramienta pueden validarse el efecto del ancho de banda, el rizado de tensión de salida o las no linealidades del diseño del amplificador de envolvente para varias modulaciones digitales. Las principales contribuciones originales de esta tesis son las siguientes: La aplicación de la técnica de cancelación de rizado a un convertidor reductor síncrono para un amplificador de envolvente de alto rendimiento para un RFPA linealizado mediante la técnica de EER. Una reducción del 66% en la frecuencia de conmutación, comparado con el reductor convencional equivalente. Esta reducción se ha validado experimentalmente obteniéndose una mejora en el rendimiento de entre el 12.4% y el 16% para las especificaciones de este trabajo. La topología y el diseño del convertidor reductor con dos redes de cancelación de rizado en cascada para mejorar el funcionamiento y robustez de la solución con una red de cancelación. La combinación de un convertidor redactor multifase con la técnica de cancelación de rizado para obtener una topología que proporciona una reducción del cociente entre frecuencia de conmutación y ancho de banda de la señal. El proceso de optimización del control del amplificador de envolvente en lazo cerrado para mejorar el funcionamiento respecto a la solución en lazo abierto del convertidor reductor con red de cancelación de rizado. Una herramienta de simulación para optimizar el proceso de diseño del amplificador de envolvente mediante la estimación de las figuras de mérito del RFPA, implementado mediante EER, basada en el diseño del amplificador de envolvente. La integración y caracterización del amplificador de envolvente basado en un convertidor reductor con red de cancelación de rizado en el transmisor de radiofrecuencia completo consiguiendo un elevado rendimiento, entre 57% y 70.6% para potencias de salida de 14.4W y 40.7W respectivamente. Esta tesis se divide en seis capítulos. El primer capítulo aborda la introducción enfocada en la aplicación, los amplificadores de potencia de radiofrecuencia, así como los principales problemas, retos y soluciones existentes. En el capítulo dos se desarrolla el estado del arte de amplificadores de potencia de RF, describiéndose las principales técnicas de diseño, las causas de no linealidad y las técnicas de optimización. El capítulo tres está centrado en las soluciones propuestas para el amplificador de envolvente. El modo de control se ha abordado en este capítulo y se ha presentado una optimización del diseño en lazo cerrado para el convertidor reductor convencional y para el convertidor reductor con red de cancelación de rizado. El capítulo cuatro se centra en el proceso de diseño del amplificador de envolvente. Se ha desarrollado una herramienta de diseño para evaluar la influencia del amplificador de envolvente en las figuras de mérito del RFPA. En el capítulo cinco se presenta el proceso de integración realizado y las pruebas realizadas para las diversas modulaciones, así como la completa caracterización y análisis del amplificador de RF. El capítulo seis describe las principales conclusiones de la tesis y las líneas futuras. ABSTRACT The trend in the telecommunications sector during the last years follow a high increase in the transmission rate of voice, video and mainly in data. To achieve the required levels of data rates, the new modulation standards demand higher bandwidths and have a higher peak to average power ratio (PAPR). These specifications have a direct impact in the low efficiency of the RFPA. An additional factor for the low efficiency of the RFPA is in the power amplifier design. Traditionally, linear classes have been used for the implementation of the power amplifier as they comply with the technical requirements. However, they have a low efficiency, especially in the operating range of signals with a high PAPR. The low efficiency of the transmitter has additional disadvantages as an increase in the cost and size as the cooling system needs to be increased for a base station and a temperature increase and a lower use time for portable devices. Several solutions have been proposed in the state of the art to improve the efficiency of the transmitter as Outphasing, power combiners or Doherty technique. However, the highest potential of efficiency improvement can be obtained using a modulated power supply for the power amplifier, as in the Envelope Tracking and EER techniques. The Envelope Tracking technique is based on the modulation of the power supply of a linear power amplifier to improve the overall efficiency compared to a fixed voltage supply. In the implementation of this technique an additional stage is needed, the envelope amplifier, that will increase the complexity of the RFPA. However, the efficiency of the linear power amplifier will increase and, if designed properly, the RFPA efficiency will be improved. The advantages of this technique are that the envelope amplifier design does not require such a high bandwidth as the envelope signal and that in the integration process a perfect synchronization between envelope and phase is not required. The Envelope Elimination and Restoration (EER) technique, known also as Kahn’s technique, is based on the simultaneous modulation of envelope and phase using a high efficiency switched power amplifier. This solution has the highest potential in terms of the efficiency improvement but also has the most challenging specifications. This solution, proposed in 1952, has not been successfully implemented until the last two decades due to the high demanding requirements for each of the stages as well as for the highly demanding processing and computation capabilities needed. At the system level, a very precise synchronization is required between the envelope and phase paths to avoid a linearity decrease of the system. Several techniques are used to compensate the non-linear effects in amplitude and phase and to improve the rejection of the out of band noise as predistortion, feedback and feed-forward. In order to obtain a high bandwidth and efficient RFPA using either ET or EER, the envelope amplifier stage will have a critical importance. The requirements for this stage are very demanding in terms of bandwidth, linearity and quality of the transmitted signal. Additionally the efficiency should be as high as possible, as the envelope amplifier has a direct impact in the efficiency of the overall system. This thesis is focused on the envelope amplifier stage and the main objective will be the development of high efficiency envelope amplifier solutions that comply with the requirements of the RFPA application. The design and optimization of an envelope amplifier for a RFPA application is a highly referenced research topic, and many solutions that address the envelope amplifier and the RFPA design and optimization can be found in the state of the art. From a high level classification, multiple and single stage envelope amplifiers can be identified. Envelope amplifiers for EER based on multiple stage architecture combine a linear assisted stage and a switched-mode stage, either in a series or parallel configuration, to achieve a very high performance RFPA. However, the complexity of the system increases and the efficiency improvement is limited. A single-stage envelope amplifier has the advantage of a lower complexity but in order to achieve the required bandwidth the switching frequency has to be highly increased, and therefore the performance and the efficiency are degraded. Several techniques are used to overcome this limitation, as the design of integrated circuits that are capable of switching at very high rates or the use of topological solutions, high order filters or a combination of both to reduce the switching frequency requirements. In this thesis it is originally proposed the use of the ripple cancellation technique, applied to a synchronous buck converter, to reduce the switching frequency requirements compared to a conventional buck converter for an envelope amplifier application. Three original proposals for the envelope amplifier stage, based on the ripple cancellation technique, are presented and one of the solutions has been experimentally validated and integrated in the complete amplifier, showing a high total efficiency increase compared to other solutions of the state of the art. Additionally, the proposed envelope amplifier has been integrated in the complete RFPA achieving a high total efficiency. The design process optimization has also been analyzed in this thesis. Due to the different figures of merit between the envelope amplifier and the complete RFPA it is very difficult to obtain an optimized design for the envelope amplifier. To reduce the design uncertainties, a design tool has been developed to provide an estimation of the RFPA figures of merit based on the design of the envelope amplifier. The main contributions of this thesis are: The application of the ripple cancellation technique to a synchronous buck converter for an envelope amplifier application to achieve a high efficiency and high bandwidth EER RFPA. A 66% reduction of the switching frequency, validated experimentally, compared to the equivalent conventional buck converter. This reduction has been reflected in an improvement in the efficiency between 12.4% and 16%, validated for the specifications of this work. The synchronous buck converter with two cascaded ripple cancellation networks (RCNs) topology and design to improve the robustness and the performance of the envelope amplifier. The combination of a phase-shifted multi-phase buck converter with the ripple cancellation technique to improve the envelope amplifier switching frequency to signal bandwidth ratio. The optimization of the control loop of an envelope amplifier to improve the performance of the open loop design for the conventional and ripple cancellation buck converter. A simulation tool to optimize the envelope amplifier design process. Using the envelope amplifier design as the input data, the main figures of merit of the complete RFPA for an EER application are obtained for several digital modulations. The successful integration of the envelope amplifier based on a RCN buck converter in the complete RFPA obtaining a high efficiency integrated amplifier. The efficiency obtained is between 57% and 70.6% for an output power of 14.4W and 40.7W respectively. The main figures of merit for the different modulations have been characterized and analyzed. This thesis is organized in six chapters. In Chapter 1 is provided an introduction of the RFPA application, where the main problems, challenges and solutions are described. In Chapter 2 the technical background for radiofrequency power amplifiers (RF) is presented. The main techniques to implement an RFPA are described and analyzed. The state of the art techniques to improve performance of the RFPA are identified as well as the main sources of no-linearities for the RFPA. Chapter 3 is focused on the envelope amplifier stage. The three different solutions proposed originally in this thesis for the envelope amplifier are presented and analyzed. The control stage design is analyzed and an optimization is proposed both for the conventional and the RCN buck converter. Chapter 4 is focused in the design and optimization process of the envelope amplifier and a design tool to evaluate the envelope amplifier design impact in the RFPA is presented. Chapter 5 shows the integration process of the complete amplifier. Chapter 6 addresses the main conclusions of the thesis and the future work.

Pulmonary Artery-Vein Segmentation in Real and Synthetic CT Images = Segmentación Arteria-Vena Pulmonares en Imágenes de CT Reales y Sintéticas

La tomografía axial computerizada (TAC) es la modalidad de imagen médica preferente para el estudio de enfermedades pulmonares y el análisis de su vasculatura. La segmentación general de vasos en pulmón ha sido abordada en profundidad a lo largo de los últimos años por la comunidad científica que trabaja en el campo de procesamiento de imagen; sin embargo, la diferenciación entre irrigaciones arterial y venosa es aún un problema abierto. De hecho, la separación automática de arterias y venas está considerado como uno de los grandes retos futuros del procesamiento de imágenes biomédicas. La segmentación arteria-vena (AV) permitiría el estudio de ambas irrigaciones por separado, lo cual tendría importantes consecuencias en diferentes escenarios médicos y múltiples enfermedades pulmonares o estados patológicos. Características como la densidad, geometría, topología y tamaño de los vasos sanguíneos podrían ser analizados en enfermedades que conllevan remodelación de la vasculatura pulmonar, haciendo incluso posible el descubrimiento de nuevos biomarcadores específicos que aún hoy en dípermanecen ocultos. Esta diferenciación entre arterias y venas también podría ayudar a la mejora y el desarrollo de métodos de procesamiento de las distintas estructuras pulmonares. Sin embargo, el estudio del efecto de las enfermedades en los árboles arterial y venoso ha sido inviable hasta ahora a pesar de su indudable utilidad. La extrema complejidad de los árboles vasculares del pulmón hace inabordable una separación manual de ambas estructuras en un tiempo realista, fomentando aún más la necesidad de diseñar herramientas automáticas o semiautomáticas para tal objetivo. Pero la ausencia de casos correctamente segmentados y etiquetados conlleva múltiples limitaciones en el desarrollo de sistemas de separación AV, en los cuales son necesarias imágenes de referencia tanto para entrenar como para validar los algoritmos. Por ello, el diseño de imágenes sintéticas de TAC pulmonar podría superar estas dificultades ofreciendo la posibilidad de acceso a una base de datos de casos pseudoreales bajo un entorno restringido y controlado donde cada parte de la imagen (incluyendo arterias y venas) está unívocamente diferenciada. En esta Tesis Doctoral abordamos ambos problemas, los cuales están fuertemente interrelacionados. Primero se describe el diseño de una estrategia para generar, automáticamente, fantomas computacionales de TAC de pulmón en humanos. Partiendo de conocimientos a priori, tanto biológicos como de características de imagen de CT, acerca de la topología y relación entre las distintas estructuras pulmonares, el sistema desarrollado es capaz de generar vías aéreas, arterias y venas pulmonares sintéticas usando métodos de crecimiento iterativo, que posteriormente se unen para formar un pulmón simulado con características realistas. Estos casos sintéticos, junto a imágenes reales de TAC sin contraste, han sido usados en el desarrollo de un método completamente automático de segmentación/separación AV. La estrategia comprende una primera extracción genérica de vasos pulmonares usando partículas espacio-escala, y una posterior clasificación AV de tales partículas mediante el uso de Graph-Cuts (GC) basados en la similitud con arteria o vena (obtenida con algoritmos de aprendizaje automático) y la inclusión de información de conectividad entre partículas. La validación de los fantomas pulmonares se ha llevado a cabo mediante inspección visual y medidas cuantitativas relacionadas con las distribuciones de intensidad, dispersión de estructuras y relación entre arterias y vías aéreas, los cuales muestran una buena correspondencia entre los pulmones reales y los generados sintéticamente. La evaluación del algoritmo de segmentación AV está basada en distintas estrategias de comprobación de la exactitud en la clasificación de vasos, las cuales revelan una adecuada diferenciación entre arterias y venas tanto en los casos reales como en los sintéticos, abriendo así un amplio abanico de posibilidades en el estudio clínico de enfermedades cardiopulmonares y en el desarrollo de metodologías y nuevos algoritmos para el análisis de imágenes pulmonares. ABSTRACT Computed tomography (CT) is the reference image modality for the study of lung diseases and pulmonary vasculature. Lung vessel segmentation has been widely explored by the biomedical image processing community, however, differentiation of arterial from venous irrigations is still an open problem. Indeed, automatic separation of arterial and venous trees has been considered during last years as one of the main future challenges in the field. Artery-Vein (AV) segmentation would be useful in different medical scenarios and multiple pulmonary diseases or pathological states, allowing the study of arterial and venous irrigations separately. Features such as density, geometry, topology and size of vessels could be analyzed in diseases that imply vasculature remodeling, making even possible the discovery of new specific biomarkers that remain hidden nowadays. Differentiation between arteries and veins could also enhance or improve methods processing pulmonary structures. Nevertheless, AV segmentation has been unfeasible until now in clinical routine despite its objective usefulness. The huge complexity of pulmonary vascular trees makes a manual segmentation of both structures unfeasible in realistic time, encouraging the design of automatic or semiautomatic tools to perform the task. However, this lack of proper labeled cases seriously limits in the development of AV segmentation systems, where reference standards are necessary in both algorithm training and validation stages. For that reason, the design of synthetic CT images of the lung could overcome these difficulties by providing a database of pseudorealistic cases in a constrained and controlled scenario where each part of the image (including arteries and veins) is differentiated unequivocally. In this Ph.D. Thesis we address both interrelated problems. First, the design of a complete framework to automatically generate computational CT phantoms of the human lung is described. Starting from biological and imagebased knowledge about the topology and relationships between structures, the system is able to generate synthetic pulmonary arteries, veins, and airways using iterative growth methods that can be merged into a final simulated lung with realistic features. These synthetic cases, together with labeled real CT datasets, have been used as reference for the development of a fully automatic pulmonary AV segmentation/separation method. The approach comprises a vessel extraction stage using scale-space particles and their posterior artery-vein classification using Graph-Cuts (GC) based on arterial/venous similarity scores obtained with a Machine Learning (ML) pre-classification step and particle connectivity information. Validation of pulmonary phantoms from visual examination and quantitative measurements of intensity distributions, dispersion of structures and relationships between pulmonary air and blood flow systems, show good correspondence between real and synthetic lungs. The evaluation of the Artery-Vein (AV) segmentation algorithm, based on different strategies to assess the accuracy of vessel particles classification, reveal accurate differentiation between arteries and vein in both real and synthetic cases that open a huge range of possibilities in the clinical study of cardiopulmonary diseases and the development of methodological approaches for the analysis of pulmonary images.

Closures of positive braids and the Morton-Franks-Williams inequality

We study the Morton-Franks-Williams inequality for closures of simple braids (also known as positive permutation braids). This allows to prove, in a simple way, that the set of simple braids is an orthonormal basis for the inner product of the Hecke algebra of the braid group defined by Kálmán, who first obtained this result by using an interesting connection with Contact Topology. We also introduce a new technique to study the Homflypt polynomial for closures of positive braids, namely resolution trees whose leaves are simple braids. In terms of these simple resolution trees, we characterize closed positive braids for which the Morton-Franks-Williams inequality is strict. In particular, we determine explicitly the positive braid words on three strands whose closures have braid index three.

Design of three-dimensional domain-swapped dimers and fibrous oligomers

Three-dimensional (3D) domain-swapped proteins are intermolecularly folded analogs of monomeric proteins; both are stabilized by the identical interactions, but the individual domains interact intramolecularly in monomeric proteins, whereas they form intermolecular interactions in 3D domain-swapped structures. The structures and conditions of formation of several domain-swapped dimers and trimers are known, but the formation of higher order 3D domain-swapped oligomers has been less thoroughly studied. Here we contrast the structural consequences of domain swapping from two designed three-helix bundles: one with an up-down-up topology, and the other with an up-down-down topology. The up-down-up topology gives rise to a domain-swapped dimer whose structure has been determined to 1.5 Å resolution by x-ray crystallography. In contrast, the domain-swapped protein with an up-down-down topology forms fibrils as shown by electron microscopy and dynamic light scattering. This demonstrates that design principles can predict the oligomeric state of 3D domain-swapped molecules, which should aid in the design of domain-swapped proteins and biomaterials.

Measuring the topology of the universe

Observations of microwave background fluctuations can yield information not only about the geometry of the universe but potentially about the topology of the universe. If the universe is negatively curved, then the characteristic scale for the topology of the universe is the curvature radius. Thus, if we are seeing the effects of the geometry of the universe, we can hope to soon see signatures of the topology of the universe. The cleanest signature of the topology of the universe is written on the microwave sky: There should be thousands of pairs of matched circles. These circles can be used to determine the precise topology and volume of the universe. Because we see hundreds of slices through the fundamental domain of the universe, we can use the microwave observations to reconstruct the initial conditions of the entire universe on the scale of a few megaparsecs.

Retroposon analysis of major cetacean lineages: The monophyly of toothed whales and the paraphyly of river dolphins

SINE (short interspersed element) insertion analysis elucidates contentious aspects in the phylogeny of toothed whales and dolphins (Odontoceti), especially river dolphins. Here, we characterize 25 informative SINEs inserted into unique genomic loci during evolution of odontocetes to construct a cladogram, and determine a total of 2.8 kb per taxon of the flanking sequences of these SINE loci to estimate divergence times among lineages. We demonstrate that: (i) Odontocetes are monophyletic; (ii) Ganges River dolphins, beaked whales, and ocean dolphins diverged (in this order) after sperm whales; (iii) three other river dolphin taxa, namely the Amazon, La Plata, and Yangtze river dolphins, form a monophyletic group with Yangtze River dolphins being the most basal; and (iv) the rapid radiation of extant cetacean lineages occurred some 28–33 million years B.P., in strong accord with the fossil record. The combination of SINE and flanking sequence analysis suggests a topology and set of divergence times for odontocete relationships, offering alternative explanations for several long-standing problems in cetacean evolution.

Deficiency of rds/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of inherited blinding diseases caused by mutations in multiple genes including RDS. RDS encodes rds/peripherin (rds), a 36-kDa glycoprotein in the rims of rod and cone outer-segment (OS) discs. Rom1 is related to rds with similar membrane topology and the identical distribution in OS. In contrast to RDS, no mutations in ROM1 alone have been associated with retinal disease. However, an unusual digenic form of RP has been described. Affected individuals in several families were doubly heterozygous for a mutation in RDS causing a leucine 185 to proline substitution in rds (L185P) and a null mutation in ROM1. Neither mutation alone caused clinical abnormalities. Here, we generated transgenic/knockout mice that duplicate the amino acid substitutions and predicted levels of rds and rom1 in patients with RDS-mediated digenic and dominant RP. Photoreceptor degeneration in the mouse model of digenic RP was faster than in the wild-type and monogenic controls by histological, electroretinographic, and biochemical analysis. We observed a positive correlation between the rate of photoreceptor loss and the extent of OS disorganization in mice of several genotypes. Photoreceptor degeneration in RDS-mediated RP appears to be caused by a simple deficiency of rds and rom1. The critical threshold for the combined abundance of rds and rom1 is ≈60% of wild type. Below this value, the extent of OS disorganization results in clinically significant photoreceptor degeneration.

Biochemical characterization and DNA binding properties of the MocR family member GabR, a PLP-dependent transcription factor

GabR è un fattore di trascrizione chimerico appartenente alla famiglia dei MocR/GabR, costituito da un dominio N-terminale elica-giro-elica di legame al DNA e un dominio effettore e/o di oligomerizzazione al C-terminale. I due domini sono connessi da un linker flessibile di 29 aminoacidi. Il dominio C-terminale è strutturalmente omologo agli enzimi aminotransferasici fold-type I, i quali, utilizzando il piridossal-5’-fosfato (PLP) come cofattore, sono direttamente coinvolti nel metabolismo degli aminoacidi. L’interazione contemporanea di PLP e acido γ-aminobutirrico (GABA) a GabR fa sì che questa promuova la trascrizione di due geni, gabT e gabD, implicati nel metabolismo del GABA. GabR cristallizza come un omodimero con una configurazione testa-coda. Il legame con la regione promotrice gabTD avviene attraverso il riconoscimento specifico di due sequenze dirette e ripetute (ATACCA), separate da uno spacer di 34 bp. In questo studio sono state indagate le proprietà biochimiche, strutturali e di legame al DNA della proteina GabR di Bacillus subtilis. L’analisi spettroscopica dimostra che GabR interagisce con il PLP formando l’aldimina interna, mentre in presenza di GABA si ottiene l’aldimina esterna. L’interazione fra il promotore gabTD e le forme holo e apo di GabR è stata monitorata mediante Microscopia a Forza atomica (AFM). In queste due condizioni di legame è stata stimata una Kd di circa 40 ηM. La presenza di GABA invece, determinava un incremento di circa due volte della Kd, variazioni strutturali nei complessi GabR-DNA e una riduzione del compattamento del DNA alla proteina, indipendentemente dalla sequenza del promotore in esame. Al fine di valutare il ruolo delle caratteristiche topologiche del promotore, sono state inserite cinque e dieci bp all’interno della regione spacer che separa le due sequenze ripetute dirette riconosciute da GabR. I significativi cambiamenti topologici riscontrati nel frammento aggiunto di cinque bp si riflettono anche sulla forte riduzione dell’affinità di legame verso la proteina. Al contrario, l’inserzione di 10 bp provoca solamente l’allontanamento delle sequenze ripetute dirette. L’assenza quindi di cambiamenti significativi nella topologia di questo promotore fa sì che l’affinità di legame per GabR rimanga pressoché inalterata rispetto al promotore non mutato. L’analisi del potenziale elettrostatico superficiale di GabR mostra la presenza di una fascia carica positivamente che si estende lungo un’intera faccia della proteina. Per verificare l’importanza di questa caratteristica di GabR nel meccanismo di interazione al DNA, sono stati preparati ed indagati i mutanti R129Q e K362-366Q, in cui la carica positiva superficiale risultava indebolita. L’affinità di legame dei mutanti di GabR per il DNA era inferiore rispetto alla proteina non mutata, in particolar modo nel mutante K362-366Q. Le evidenze acquisite suggeriscono che la curvatura intrinseca del promotore ed il corretto orientamento delle sequenze sulla doppia elica, più della distanza che le separa, siano critici per sostenere l’interazione con GabR. Oltre a questo, la superficie positiva di GabR è richiesta per accomodare la curvatura del DNA sul corpo della proteina. Alla luce di questo, l’interazione GabR-gabTD è un esempio di come il riconoscimento specifico di sequenze, la topologia del DNA e le caratteristiche strutturali della proteina siano contemporaneamente necessarie per sostenere un’interazione proteina-DNA stabile.

Terminology of metal–organic frameworks and coordination polymers (IUPAC Recommendations 2013)

A set of terms, definitions, and recommendations is provided for use in the classification of coordination polymers, networks, and metal–organic frameworks (MOFs). A hierarchical terminology is recommended in which the most general term is coordination polymer. Coordination networks are a subset of coordination polymers and MOFs a further subset of coordination networks. One of the criteria an MOF needs to fulfill is that it contains potential voids, but no physical measurements of porosity or other properties are demanded per se. The use of topology and topology descriptors to enhance the description of crystal structures of MOFs and 3D-coordination polymers is furthermore strongly recommended.

Asymptotic theory of time varying networks with memory and heterogeneous activation pattern

In this thesis work we develop a new generative model of social networks belonging to the family of Time Varying Networks. The importance of correctly modelling the mechanisms shaping the growth of a network and the dynamics of the edges activation and inactivation are of central importance in network science. Indeed, by means of generative models that mimic the real-world dynamics of contacts in social networks it is possible to forecast the outcome of an epidemic process, optimize the immunization campaign or optimally spread an information among individuals. This task can now be tackled taking advantage of the recent availability of large-scale, high-quality and time-resolved datasets. This wealth of digital data has allowed to deepen our understanding of the structure and properties of many real-world networks. Moreover, the empirical evidence of a temporal dimension in networks prompted the switch of paradigm from a static representation of graphs to a time varying one. In this work we exploit the Activity-Driven paradigm (a modeling tool belonging to the family of Time-Varying-Networks) to develop a general dynamical model that encodes fundamental mechanism shaping the social networks' topology and its temporal structure: social capital allocation and burstiness. The former accounts for the fact that individuals does not randomly invest their time and social interactions but they rather allocate it toward already known nodes of the network. The latter accounts for the heavy-tailed distributions of the inter-event time in social networks. We then empirically measure the properties of these two mechanisms from seven real-world datasets and develop a data-driven model, analytically solving it. We then check the results against numerical simulations and test our predictions with real-world datasets, finding a good agreement between the two. Moreover, we find and characterize a non-trivial interplay between burstiness and social capital allocation in the parameters phase space. Finally, we present a novel approach to the development of a complete generative model of Time-Varying-Networks. This model is inspired by the Kaufman's adjacent possible theory and is based on a generalized version of the Polya's urn. Remarkably, most of the complex and heterogeneous feature of real-world social networks are naturally reproduced by this dynamical model, together with many high-order topological properties (clustering coefficient, community structure etc.).

Magnetic properties and Spin dynamics in magnetic Molecular Rings

Molecular nanomagnets are spin clusters whose topology and magnetic interactions can be modulated at the level of the chemical synthesis. They are formed by a small number of transition metal ions coupled by the Heisenberg's exchange interactions. Each cluster is magnetically isolated from its neighbors by organic ligands, making each unit not interacting with the others. Therefore, we can investigate the magnetic properties of an isolated molecular nanomagnet by bulk measurements. The present thesis has been mostly devoted to the experimental investigation of the magnetic properties and spin dynamics of different classes of antiferromagnetic (AF) molecular rings. This study has been exploiting various techniques of investigations, such as Nuclear Magnetic Resonance (NMR), muon spin relaxation (muSR) and SQUiD magnetometry. We investigate the magnetic properties and the phonon-induced relaxation dynamics of the first regular Cr9 antiferromagnetic (AF) ring, which represents a prototype frustrated AF ring. The magnetically-open AF rings like Cr8Cd are model systems for the study of the microscopic magnetic behaviour of finite AF Heisenberg chains. In this type of system the different magnetic behaviour depends length and on the parity of the chain (odd or even). In order to study the local spin densities on the Cr sites, the Cr-NMR spectra was collected at low temperature. The experimental result confirm the theoretical predictions for the spin configuration. Finally, the study of Dy6, the first rare-earth based ring that has been ever synthesized, has been performed by AC-SQuID and muSR measurements. We found that the dynamics is characterized by more than one characteristic correlation time, whose values depend strongly on the applied field.

Regular Averaging and Regular Extension Operators in Weakly Compact Subsets of Hilbert Spaces

2000 Mathematics Subject Classification: Primary 46E15, 54C55; Secondary 28B20.

Using virtual topology operations to generate analysis topology

Virtual topology operations have been utilized to generate an analysis topology definition suitable for downstream mesh generation. Detailed descriptions are provided for virtual topology merge and split operations for all topological entities. Current virtual topology technology is extended to allow the virtual partitioning of volume cells and the topological queries required to carry out each operation are provided. Virtual representations are robustly linked to the underlying geometric definition through an analysis topology. The analysis topology and all associated virtual and topological dependencies are automatically updated after each virtual operation, providing the link to the underlying CAD geometry. Therefore, a valid description of the analysis topology, including relative orientations, is maintained. This enables downstream operations, such as the merging or partitioning of virtual entities, and interrogations, such as determining if a specific meshing strategy can be applied to the virtual volume cells, to be performed on the analysis topology description. As the virtual representation is a non-manifold description of the sub-divided domain the interfaces between cells are recorded automatically. This enables the advantages of non-manifold modelling to be exploited within the manifold modelling environment of a major commercial CAD system, without any adaptation of the underlying CAD model. A hierarchical virtual structure is maintained where virtual entities are merged or partitioned. This has a major benefit over existing solutions as the virtual dependencies are stored in an open and accessible manner, providing the analyst with the freedom to create, modify and edit the analysis topology in any preferred sequence, whilst the original CAD geometry is not disturbed. Robust definitions of the topological and virtual dependencies enable the same virtual topology definitions to be accessed, interrogated and manipulated within multiple different CAD packages and linked to the underlying geometry.