Asynchronous spike event coding scheme for programmable analogue arrays and its computational applications

This work is the result of the definition, design and evaluation of a novel method to interconnect the computational elements - commonly known as Configurable Analogue Blocks (CABs) - of a programmable analogue array. This method is proposed for total or partial replacement of the conventional methods due to serious limitations of the latter in terms of scalability. With this method, named Asynchronous Spike Event Coding (ASEC) scheme, analogue signals from CABs outputs are encoded as time instants (spike events) dependent upon those signals activity and are transmitted asynchronously by employing the Address Event Representation (AER) protocol. Power dissipation is dependent upon input signal activity and no spike events are generated when the input signal is constant. On-line, programmable computation is intrinsic to ASEC scheme and is performed without additional hardware. The ability of the communication scheme to perform computation enhances the computation power of the programmable analogue array. The design methodology and a CMOS implementation of the scheme are presented together with test results from prototype integrated circuits (ICs)

Analog dithering techniques for highly linear and efficient transmitters

The current thesis is about investigation of new methods and techniques to be able to utilize the switched mode amplifiers, for linear and efficient applications. Switched mode amplifiers benefit from low overlap between the current and voltage wave forms in their output terminals, but they seriously suffer from nonlinearity. This makes it impossible to use them to amplify non-constant envelope message signals, where very high linearity is expected. In order to do that, dithering techniques are studied and a full linearity analysis approach is developed, by which the linearity performance of the dithered amplifier can be analyzed, based on the dithering level and frequency. The approach was based on orthogonalization of the equivalent nonlinearity and is capable of prediction of both co-channel and adjacent channel nonlinearity metrics, for a Gaussian complex or real input random signal. Behavioral switched mode amplifier models are studied and new models are developed, which can be utilized to predict the nonlinear performance of the dithered power amplifier, including the nonlinear capacitors effects. For HFD application, self-oscillating and asynchronous sigma delta techniques are currently used, as pulse with modulators (PWM), to encode a generic RF message signal, on the duty cycle of an output pulse train. The proposed models and analysis techniques were applied to this architecture in the first phase, and the method was validated with measurement on a prototype sample, realized in 65 nm TSMC CMOS technology. Afterwards, based on the same dithering phenomenon, a new linearization technique was proposed, which linearizes the switched mode class D amplifier, and at the same time can reduce the reactive power loss of the amplifier. This method is based on the dithering of the switched mode amplifier with frequencies lower than the band-pass message signal and is called low frequency dithering (LFD). To test this new technique, two test circuits were realized and the idea was applied to them. Both of the circuits were of the hard nonlinear type (class D) and are integrated CMOS and discrete LDMOS technologies respectively. The idea was successfully tested on both test circuits and all of the linearity metric predictions for a digitally modulated RF signal and a random signal were compared to the measurements. Moreover a search method to find the optimum dither frequency was proposed and validated. Finally, inspired by averaging interpretation of the dithering phenomenon, three new topologies were proposed, which are namely DLM, RF-ADC and area modulation power combining, which are all nonlinear systems linearized with dithering techniques. A new averaging method was developed and used for analysis of a Gilbert cell mixer topology, which resulted in a closed form relationship for the conversion gain, for long channel devices

Sparse Time-Frequency Data Analysis: A Multi-Scale Approach

In this work, we further extend the recently developed adaptive data analysis method, the Sparse Time-Frequency Representation (STFR) method. This method is based on the assumption that many physical signals inherently contain AM-FM representations. We propose a sparse optimization method to extract the AM-FM representations of such signals. We prove the convergence of the method for periodic signals under certain assumptions and provide practical algorithms specifically for the non-periodic STFR, which extends the method to tackle problems that former STFR methods could not handle, including stability to noise and non-periodic data analysis. This is a significant improvement since many adaptive and non-adaptive signal processing methods are not fully capable of handling non-periodic signals. Moreover, we propose a new STFR algorithm to study intrawave signals with strong frequency modulation and analyze the convergence of this new algorithm for periodic signals. Such signals have previously remained a bottleneck for all signal processing methods. Furthermore, we propose a modified version of STFR that facilitates the extraction of intrawaves that have overlaping frequency content. We show that the STFR methods can be applied to the realm of dynamical systems and cardiovascular signals. In particular, we present a simplified and modified version of the STFR algorithm that is potentially useful for the diagnosis of some cardiovascular diseases. We further explain some preliminary work on the nature of Intrinsic Mode Functions (IMFs) and how they can have different representations in different phase coordinates. This analysis shows that the uncertainty principle is fundamental to all oscillating signals

Artificial Immune Systems: Principle, Algorithms and Applications

The present thesis aims to make an in-depth study of adaptive identification, digital channel equalization, functional link artificial neural network (FLANN) and Artificial Immune Systems (AIS).Two learning algorithms CPSO and IPSO are also developed in this thesis. These new algorithms are employed to train the weights of a low complexity FLANN structure by way of minimizing the squared error cost function of the hybrid model. These new models are applied for adaptive identification of complex nonlinear dynamic plants and equalization of nonlinear digital channel. Investigation has been made for identification of complex Hammerstein models. To validate the performance of these new models simulation study is carried out using benchmark complex plants and nonlinear channels. The results of simulation are compared with those obtained with FLANN-GA, FLANN-PSO and MLP-BP based hybrid approaches. Improved identification and equalization performance of the proposed method have been observed in all cases

Internet of Things From Hype to Reality

The Internet of Things (IoT) has gained significant mindshare, let alone attention, in academia and the industry especially over the past few years. The reasons behind this interest are the potential capabilities that IoT promises to offer. On the personal level, it paints a picture of a future world where all the things in our ambient environment are connected to the Internet and seamlessly communicate with each other to operate intelligently. The ultimate goal is to enable objects around us to efficiently sense our surroundings, inexpensively communicate, and ultimately create a better environment for us: one where everyday objects act based on what we need and like without explicit instructions

Modeling Cell Dynamics on Micropatterned Substrates with a Cellular Potts Model

Tools from materials science are increasingly used to decrease the variability that often limits the quantitative analysis of cell experiments. Most prominently, micropatterned substrates can be used to normalize cell shape and internal organization. For long-term experiments, however, cells must be able to divide and migrate. This creates the need to design networks of micropatterns that ensure normalization to be maintained even in a dynamic context. The design of such networks requires an efficient model predicting the degree of normalization for dividing and migrating cells. Here we extend earlier formulations of the two-dimensional cellular Potts model with the aim to achieve good agreement with existing cell experiments on cell shape and forces on micropatterns. We show that our model correctly predicts cell spreading, division and migration on micropatterns, both for single cells and cell communities. The inverse problem of network optimization is then addressed with genetic algorithms

Spectrally efficient Non-Orthogonal Multiple Access (NOMA) techniques for future generation mobile systems

With the expectation of over a 1000-fold increase in the number of connected devices by 2020, efficient utilization of the limited bandwidth has become ever more important in the design of mobile wireless systems. Furthermore, the ever-increasing demand for higher data rates has made it necessary for a new waveform design that satisfies not only throughput demands, but network capacity as well. One such technique recently proposed is the non-orthogonal multiple access (NOMA) which utilizes the distance-dependent power domain multiplexing, based on the principles of signal superposition. In this thesis, new spectrally efficient non-orthogonal signal techniques are proposed. The goal of the schemes is to allow simultaneous utilization of the same time frequency network resources. This is achieved by designing component signals in both power and phase domain such that users are precoded or preformed to form a single and uniquely decodable composite signal. The design criteria are based on maximizing either the sum rate or spectral efficiency, minimizing multi-user interference and detection ambiguity, and maximizing the minimum Euclidean distance between the composite constellation points. The design principles are applied in uplink, downlink and coordinated multipoint (CoMP) scenarios. We assume ideal channel state with perfect estimation, low mobility and synchronization scenarios so as to prove the concept and serve as a bound for any future work in non-ideal conditions. Extensive simulations and numerical analysis are carried to show the superiority and compatibility of the schemes. First, a new NOMA signal design called uplink NOMA with constellation precoding is proposed. The precoding weights are generated at the eNB based on the number of users to be superposed. The eNB signals the precoding weights to be employed by the users to adjust their transmission. The adjustments utilize the channel state information estimated from common periodic pilots broadcasted by the eNB. The weights ensure the composite received signal at the eNB belongs to the pre-known constellation. Furthermore, the users precode to the eNB antenna that requires the least total transmit power from all the users. At the eNB, joint maximum likelihood (JML) detection is employed to recover the component signals. As the composite constellation is as that of a single user transmitting that same constellation, multiple access interference can be viewed as absent, which allows multiple users to transmit at their full rates. Furthermore, the power gain achieved by the sum of the component signals maximizes the sum rate. Secondly, the constellation design principle is employed in the downlink scenario. In the scheme, called downlink NOMA with constellation preforming, the eNB preforms the users signal with power and phase weights prior to transmission. The preforming ensures multi-user interference is eliminated and the spectral efficiency maximized. The preformed composite constellation is broadcasted by the eNB which is received by all users. Subsequently, the users perform JML detection with the designed constellation to extract their individual component signals. Furthermore, improved signal reliability is achieved in transmit and receive diversity scenarios in the schemes called distributed transmit and receive diversity combining, respectively. Thirdly, the constellation preforming on the downlink is extended to MIMO spatial multiplexing scenarios. The first MIMO scheme, called downlink NOMA with constellation preforming, each eNB antenna transmits a preformed composite signal composed of a set of multiple users’ streams. This achieves spatial multiplexing with diversity with less transmit antennas, reducing costs associated with multiple RF chains, while still maximizing the sum rate. In the second MIMO scheme, a highly spectrally efficient MIMO preforming scheme is proposed. The scheme, called group layer MIMO with constellation preforming, the eNB preforms to a specific group of users on each transmit antenna. In all the schemes, the users perform JML detection to recover their signals. Finally, the adaptability of the constellation design is shown in CoMP. The scheme, called CoMP with joint constellation processing, the additional degrees of freedom, in form of interfering eNBs, are utilized to enable spatial multiplexing to a user with a single receive antenna. This is achieved by precoding each stream from the coordinating eNB with weights signalled by a central eNB. Consequently, the inter-cell interference is eliminated and the sum-rate maximized. To reduce the total power spent on precoding, an active cell selection scheme is proposed where the precoding is employed on the highest interferers to the user. Furthermore, a power control scheme is applied the design principle, where the objective is to reduce cross-layer interference by adapting the transmission power to the mean channel gain

Role of Pax4 and Pax8 in pancreatic islets physiology and patophysiology

Programa de Doctorado en Biotecnología y Tecnología QuímicaLa Diabetes Mellitus (DM) es una enfermedad metabólica crónica, caracterizada por hiperglucemia debida a un déficit absoluto o parcial en la secreción de insulina por parte de las células ß pancreática. La etiología deriva bien de una destrucción autoinmune de las células ß productoras de insulina (DM Tipo 1; DMT1) o a una combinación entre la resistencia a insulina de los tejidos diana y la secreción insuficiente de insulina por las células ß (DM Tipo 2; DMT2) (1). Un tercer tipo de diabetes, la diabetes gestacional (DMG), se produce cuando durante el embarazo la producción de insulina materna es insuficiente para compensar el incremento de la demanda de esta hormona causado por el desarrollo fetal. Los tratamientos actuales mejoran la calidad de vida pero no evitan las graves complicaciones secundarias (uso inadecuado de la insulina) para el estado de salud general del paciente, o son insuficientes (trasplante clínico de islotes). Más aún, tratamientos alternativos que están en vías de desarrollo están resultando difícilmente reproducibles (células madre progenitoras). Además, estudios epidemiológicos recientes indican que pacientes con DMT2 tienen un mayor riesgo de desarrollar cáncer pancreático, hepático, colorrectal y de mama, deteriorando aún más el estado de salud (2). Alarmantemente, la DM ha alcanzado dimensiones pandémicas. Se prevee que en el año 2030, el 9,9% de la población adulta mundial tendrá diabetes (551 millones de personas) lo que la convierte en la quinta causa de muerte en el mundo (3,4). Esto supone una importante carga económica para los servicios de salud; en 2011, los costes sanitarios debidos a la DM se calcularon en 465 billones de dólares (11% del gasto sanitario) (5). En España, la prevalencia de esta enfermedad supone el 14% (estudio [email protected]) siendo la octava causa de muerte en nuestro país con un 8% de mortalidad. Concretamente, nuestra comunidad se encuentra entre las tasas más altas de prevalencia a nivel nacional con un 12% alcanzándose en Sevilla un 10,2% (6). En conjunto, todos estos datos ponen de manifiesto la gran necesidad de desarrollar estrategias terapéuticas innovadoras encaminadas a preservar o reponer la masa de células ß funcionales en pacientes diabéticos que es lo que se conoce con el concepto de regeneración in vivo. Por tanto, el abordaje terapéutico definitivo para el tratamiento de la DM debería tener como objetivos: 1) bloquear la destrucción de las células ß, 2) reemplazar o regenerar las células ß y 3) preservar la masa y funcionalidad de las células ß. En este fin radica la importancia de este proyecto en el que investigamos la función fisiológica y los mecanismos moleculares subyacentes regulados por los factores de transcripción Pax4 y Pax8 como potenciales agentes clave para una terapia regenerativa de cara al desarrollo de un tratamiento óptimo e innovador para la DM: OBJETIVO 1: determinar el papel fisiológico del factor de transcripción Pax8 en la fisiología del islote pancreático con el fin de caracterizar un nuevo regulador de la plasticidad de dichos islotes durante el embarazo. ANTECEDENTES, METODOLOGÍA Y RESULTADOS OBTENIDOS: varios estudios independientes han detectado Pax8 en islotes humanos y en tumores pancreáticos neuroendocrinos humanos (PNET, pancreatic neuroendocrine tumor) sugiriendo su utilidad como biomarcador de este tipo de tumores (7-9). Sin embargo, recientemente, hemos demostrado la ausencia de expresión de Pax8 en islotes de ratón tanto durante el desarrollo embrionario como en páncreas adulto, mientras que en islotes humanos se encontraron niveles muy bajos. Adicionalmente, en colaboración con las Dras. Rocío Carbonero y Lourdes Gómez (oncóloga y patóloga, respectivamente, del Hospital Virgen del Rocío), tampoco detectamos expresión de este factor de transcripción en PNETs humanos (10,11). Estos datos descartan Pax8 como marcador clínico para la identificación y diagnóstico precoz de este tipo de tumores. No obstante, un estudio de asociación de todo el genoma ha asociado Pax8 con DM tipo 2 en familias afroamericanas (12). Además, una determinación del perfil transcriptómico llevada a cabo en islotes aislados de hembras de ratón embarazadas reveló una fuerte inducción en los niveles de expresión de Pax8 durante la gestación (13). Corroborando este resultado, una mutación en Pax8 que causa hipotiroidismo congénito en tres generaciones de una familia de las Azores, ha sido recientemente asociada con diabetes gestacional leve en uno de los miembros femeninos portadores de esta mutación (14). En conjunto, estos datos clínicos sugieren que Pax8 podría influir en la fisiología del islote bajo condiciones metabólicas específicas tales como el embarazo. Por tanto, para dilucidar el papel funcional de la expresión de Pax8 en islotes de ratón y humanos durante el embarazo, confirmamos en primer lugar que su expresión se incrementaba en islotes de ratón durante el embarazo, alcanzándose a día 14.5 de gestación niveles máximos de expresión de hasta 5 veces superiores que en islotes control. También encontramos que la expresión de Pax8 en islotes humanos aumentaba 5 veces tras 72h de tratamiento con prolactina, hormona utilizada para simular el embarazo en islotes humanos en cultivo. Para determinar la correlación entre la expresión de Pax8 y la proliferación celular, analizamos los niveles de proliferación en islotes humanos en cultivo tras el tratamiento con prolactina. Observamos un aumento transitorio en la proliferación de dichos islotes, incrementándose un máximo de 2 veces tras 48h, de manera que no correlaciona con el máximo de expresión de Pax8. Esto sugiere que este gen puede no estar implicado en replicación celular, sino más bien en la represión de dicha proliferación. Estos datos indican claramente que la expresión de Pax8 puede inducirse en islotes bajo condiciones fisiológicas específicas que suponen un estrés metabólico tales como el embarazo. PERSPECTIVAS FUTURAS: para analizar directamente el papel de Pax8 en la proliferación de los islotes, nuestros futuros planes son evaluar el efecto de la sobre-expresión de este factor de transcripción tanto en islotes humanos y de ratón, como en líneas celulares derivadas de insulinoma. Esta sobreexpresión de Pax8 (ratón y humano) se realizará mediante infección de los islotes con un vector lentiviral creado en nuestro laboratorio. Estos estudios determinarán si Pax8 afecta la proliferación sólo o en combinación con prolactina, o si está implicado en reprimir la proliferación mediada por prolactina. En este último supuesto, silenciaremos Pax8 para analizar el impacto sobre la proliferación. Además (basándonos en los datos preliminares en humanos), intentaremos corroborar que las mutaciones en Pax8 se asocian con DMG. Para ello, se llevará a cabo un screening entre mujeres portadoras de mutaciones en Pax8 en el que se les realizará un análisis clínico retrospectivo para comprobar si algunas de ellas padecieron DMG durante el embarazo. RESULTADOS PREVISTOS (IMPACTO SOCIAL): el objetivo y fin último de nuestro estudio es que, a partir del cribado genético para Pax8, se podrá usar este marcador para determinar la susceptibilidad de desarrollar DMG entre la población femenina. Esto permitirá un seguimiento y/o tratamiento de la población de riesgo para, de esta forma, disminuir la incidencia de DMG. OBJETIVO 2: descifrar los mecanismos moleculares regulados por Pax4 con el fin de obtener nuevos genes y rutas metabólicas implicadas en la regeneración y supervivencia de la célula ß pancreática. ANTECEDENTES, METODOLOGÍA Y RESULTADOS OBTENIDOS: en nuestro laboratorio, mediante el uso de un modelo de ratón transgénico que sobreexpresa Pax4 en las células ß tras un tratamiento con doxiciclina, hemos demostrado que Pax4 protege a este tipo celular frente a apoptosis inducida por estreptozotocina y el consiguiente desarrollo de hiperglucemia (15). Para elucidar los mecanismos por los cuales Pax4 transfiere un fenotipo propenso a la protección, llevamos a cabo un análisis comparativo por microarray de DNA en los islotes de los ratones transgénicos que sobreexpresan Pax4 frente a los que no lo expresan. Los datos del microarray revelan que 770 transcritos estaban aumentados mientras que 505 disminuyeron. Se realizó un enriquecimiento funcional para identificar las vías de señalización significativamente enriquecidas en islotes que sobreexpresaban Pax4 comparándolos con los que no lo expresaban. Tres rutas sobresalieron particularmente en los animales que sobreexpresan Pax4: ciclo celular, p53 y cáncer (rutas KEGG), todas ellas relacionadas directamente con supervivencia celular y proliferación. En cuanto a los genes implicados en el ciclo celular, destacan las ciclinas A2, B2 y D1 las cuales promoverían la replicación. Notablemente, el Gen Inducible por Mitógeno (Mig6) y el inhibidor 1A de las ciclinas dependientes de kinasa, p21, dos ¿frenos¿ moleculares de las vías pro-proliferativas, estaban entre los genes más aumentados. Estos datos sugieren que, aunque las células del islote que expresan Pax4 estén listas para proliferar/sobrevivir, probablemente factores como Mig6 y p21 están reteniendo esas capacidades a menos que sean activadas por determinadas señales fisiológicas. Además, la glutatión peroxidasa 3 (GPX3) fue también uno de los genes más incrementados pudiendo desempeñar un papel clave en la protección de los islotes contra la apoptosis inducida por estrés oxidativo. PERSPECTIVAS FUTURAS: nuestros futuros planes son el análisis de expresión por técnicas moleculares de PCR cuantitativa a tiempo real y análisis inmunohistoquímico de diferentes ciclinas, c-myc, Mig6, p21, p53 y GPX3, entre otros, en islotes de ratones que sobreexpresan Pax4 y de ratones control. Estos estudios elucidarán la ruta metabólica por la cual actúa y ejerce su acción Pax4 en las células ß de los islotes pancreáticos, así como genes modulados por este factor de transcripción y que pueden ser utilizados como potenciales diana para el desarrollo de tratamientos contra la DM. RESULTADOS PREVISTOS (IMPACTO SOCIAL): en definitiva, nuestro objetivo es comprender en detalle la función de Pax4 en la fisiología del islote con el fin de desarrollar nuevos fármacos basados en este factor de transcripción y/o sus dianas mejorando así los tratamientos actuales para la DM.Universidad Pablo de Olavide. Departamento de Biología Molecular e Ingeniería Bioquímic