Dual-loop circuits in postoperative atrial macro re-entrant tachycardias

Background Patients late after open-heart surgery may develop dual-loop reentrant atrial arrhythmias, and mapping and catheter ablation remain challenging despite computer-assisted mapping techniques. Objectives The purpose of the study was to demonstrate the prevalence and characteristics of dual-loop reentrant arrhythmias, and to define the optimal mapping and ablation strategy. Methods Fourty consecutive patients (mean age 52+/-12 years) with intra-atrial reentrant tachycardia (IART) after open-heart surgery (with an incision of the right atrial free wall) were studied. Dual-loop IART was defined as the presence of two simultaneous atrial circuits. Following an abrupt tachycardia change during radiofrequency (RF) ablation, electrical disconnection of the targeted reentry isthmus from the remaining circuit was demonstrated by entrainment mapping. Furthermore, the second circuit loop was localized using electroanatomic mapping and/or entrainment mapping. Results Dual-loop IART was demonstrated in 8 patients (20%, 5 patients with congenital heart disease, 3 with acquired heart disease). Dual-loop IART included an isthmus-dependant atrial flutter combined with a reentry related to the atriotomy scar. The diagnosis of dual-loop IART required the comparison of entrainment mapping before and after tachycardiamodification. Overall, 35 patients had successful RF ablation (88%). Success rates were lower in patients with dual-loop IART than in patient without dual-loop IART. Ablation failures in 3 patients with dual-loop IART were related to the inability to properly transect the second tachycardia isthmus in the right atrial free wall. Conclusions Dual-loop IART is relatively common after heart surgery involving a right atriotomy. Abrupt tachycardia change and specific entrainment mapping maneuvers demonstrate these circuits. Electroanatomic mapping appears to be important to assist catheter ablation of periatriotomy circuits.

Cellular and network mechanisms of rhythm generation in spinal cord circuits

The generation of rhythmic electrical activity is a prominent feature of spinal cord circuits that is used for locomotion and also for circuit refinement during development. The mechanisms involved in rhythm generation in spinal cord networks are not fully understood. It is for example not known whether spinal cord rhythms are driven by pacemaker neurons and if yes, which neurons are involved in this function. We studied the mechanisms involved in rhythm generation in slice cultures from fetal rats that were grown on multielectrode arrays (MEAs). We combined multisite extracellular recordings from the MEA electrodes with intracellular patch clamp recordings from single neurons. We found that spatially restricted oscillations of activity appeared in most of the cultures spontaneously. Such activity was based on intrinsic activity in a percentage of the neurons that could activate the spinal networks through recurrent excitation. The local oscillator networks critically involved NMDA, AMPA and GABA / glycine receptors at subsequent phases of the oscillation cycle. Intrinsic spiking in individual neurons (in the absence of functional synaptic coupling) was based on persistent sodium currents. Intrinsic firing as well as persistent sodium currents were increased by 5-HT through 5-HT2 receptors. Comparing neuronal activity to muscle activity in co-cultures of spinal cord slices with muscle fibers we found that a percentage of the intrinsically spiking neurons were motoneurons. These motoneurons were electrically coupled among each other and they could drive the spinal networks through cholinergic recurrent excitation. These findings open the possibility that during development rhythmic activity in motoneurons is not only involved in circuit refinement downstream at the neuromuscular endplates but also upstream at the level of spinal cord circuits.

Two-dimensional Lattice Gauge Theories with Superconducting Quantum Circuits

A quantum simulator of U(1) lattice gauge theories can be implemented with superconducting circuits. This allows the investigation of confined and deconfined phases in quantum link models, and of valence bond solid and spin liquid phases in quantum dimer models. Fractionalized confining strings and the real-time dynamics of quantum phase transitions are accessible as well. Here we show how state-of-the-art superconducting technology allows us to simulate these phenomena in relatively small circuit lattices. By exploiting the strong non-linear couplings between quantized excitations emerging when superconducting qubits are coupled, we show how to engineer gauge invariant Hamiltonians, including ring-exchange and four-body Ising interactions. We demonstrate that, despite decoherence and disorder effects, minimal circuit instances allow us to investigate properties such as the dynamics of electric flux strings, signaling confinement in gauge invariant field theories. The experimental realization of these models in larger superconducting circuits could address open questions beyond current computational capability.

Neural circuits of emotion regulation: a comparison of mindfulness-based and cognitive reappraisal strategies

Dealing with one's emotions is a core skill in everyday life. Effective cognitive control strategies have been shown to be neurobiologically represented in prefrontal structures regulating limbic regions. In addition to cognitive strategies, mindfulness-associated methods are increasingly applied in psychotherapy. We compared the neurobiological mechanisms of these two strategies, i.e. cognitive reappraisal and mindfulness, during both the cued expectation and perception of negative and potentially negative emotional pictures. Fifty-three healthy participants were examined with functional magnetic resonance imaging (47 participants included in analysis). Twenty-four subjects applied mindfulness, 23 used cognitive reappraisal. On the neurofunctional level, both strategies were associated with comparable activity of the medial prefrontal cortex and the amygdala. When expecting negative versus neutral stimuli, the mindfulness group showed stronger activations in ventro- and dorsolateral prefrontal cortex, supramarginal gyrus as well as in the left insula. During the perception of negative versus neutral stimuli, the two groups only differed in an increased activity in the caudate in the cognitive group. Altogether, both strategies recruited overlapping brain regions known to be involved in emotion regulation. This result suggests that common neural circuits are involved in the emotion regulation by mindfulness-based and cognitive reappraisal strategies. Identifying differential activations being associated with the two strategies in this study might be one step towards a better understanding of differential mechanisms of change underlying frequently used psychotherapeutic interventions.

POPULATION CODING IN LAMINAR CORTICAL CIRCUITS

One of the fundamental questions in neuroscience is to understand how encoding of sensory inputs is distributed across neuronal networks in cerebral cortex to influence sensory processing and behavioral performance. The fact that the structure of neuronal networks is organized according to cortical layers raises the possibility that sensory information could be processed differently in distinct layers. The goal of my thesis research is to understand how laminar circuits encode information in their population activity, how the properties of the population code adapt to changes in visual input, and how population coding influences behavioral performance. To this end, we performed a series of novel experiments to investigate how sensory information in the primary visual cortex (V1) emerges across laminar cortical circuits. First, it is commonly known that the amount of information encoded by cortical circuits depends critically on whether or not nearby neurons exhibit correlations. We examined correlated variability in V1 circuits from a laminar-specific perspective and observed that cells in the input layer, which have only local projections, encode incoming stimuli optimally by exhibiting low correlated variability. In contrast, output layers, which send projections to other cortical and subcortical areas, encode information suboptimally by exhibiting large correlations. These results argue that neuronal populations in different cortical layers play different roles in network computations. Secondly, a fundamental feature of cortical neurons is their ability to adapt to changes in incoming stimuli. Understanding how adaptation emerges across cortical layers to influence information processing is vital for understanding efficient sensory coding. We examined the effects of adaptation, on the time-scale of a visual fixation, on network synchronization across laminar circuits. Specific to the superficial layers, we observed an increase in gamma-band (30-80 Hz) synchronization after adaptation that was correlated with an improvement in neuronal orientation discrimination performance. Thus, synchronization enhances sensory coding to optimize network processing across laminar circuits. Finally, we tested the hypothesis that individual neurons and local populations synchronize their activity in real-time to communicate information about incoming stimuli, and that the degree of synchronization influences behavioral performance. These analyses assessed for the first time the relationship between changes in laminar cortical networks involved in stimulus processing and behavioral performance.

Optically Reconfigurable RF Circuits using Silicon Switches

Mobile and wireless communications systems have become an important part of our everyday lives. These ubiquitous technologies have a profound effect on how we live. People predict bright future to wireless technologies, but it wouldn’t be possible without a hard work of thousands of scientists in the wireless innovation research arena. My Marie Curie project is investigating enabling technologies for future mobile and wireless communications systems

X-parameters based analytical design of non-linear microwave circuits Application to oscillator design

Resumen El diseño clásico de circuitos de microondas se basa fundamentalmente en el uso de los parámetros s, debido a su capacidad para caracterizar de forma exitosa el comportamiento de cualquier circuito lineal. La relación existente entre los parámetros s con los sistemas de medida actuales y con las herramientas de simulación lineal han facilitado su éxito y su uso extensivo tanto en el diseño como en la caracterización de circuitos y subsistemas de microondas. Sin embargo, a pesar de la gran aceptación de los parámetros s en la comunidad de microondas, el principal inconveniente de esta formulación reside en su limitación para predecir el comportamiento de sistemas no lineales reales. En la actualidad, uno de los principales retos de los diseñadores de microondas es el desarrollo de un contexto análogo que permita integrar tanto el modelado no lineal, como los sistemas de medidas de gran señal y los entornos de simulación no lineal, con el objetivo de extender las capacidades de los parámetros s a regímenes de operación en gran señal y por tanto, obtener una infraestructura que permita tanto la caracterización como el diseño de circuitos no lineales de forma fiable y eficiente. De acuerdo a esta filosofía, en los últimos años se han desarrollado diferentes propuestas como los parámetros X, de Agilent Technologies, o el modelo de Cardiff que tratan de proporcionar esta plataforma común en el ámbito de gran señal. Dentro de este contexto, uno de los objetivos de la presente Tesis es el análisis de la viabilidad del uso de los parámetros X en el diseño y simulación de osciladores para transceptores de microondas. Otro aspecto relevante en el análisis y diseño de circuitos lineales de microondas es la disposición de métodos analíticos sencillos, basados en los parámetros s del transistor, que permitan la obtención directa y rápida de las impedancias de carga y fuente necesarias para cumplir las especificaciones de diseño requeridas en cuanto a ganancia, potencia de salida, eficiencia o adaptación de entrada y salida, así como la determinación analítica de parámetros de diseño clave como el factor de estabilidad o los contornos de ganancia de potencia. Por lo tanto, el desarrollo de una formulación de diseño analítico, basada en los parámetros X y similar a la existente en pequeña señal, permitiría su uso en aplicaciones no lineales y supone un nuevo reto que se va a afrontar en este trabajo. Por tanto, el principal objetivo de la presente Tesis consistiría en la elaboración de una metodología analítica basada en el uso de los parámetros X para el diseño de circuitos no lineales que jugaría un papel similar al que juegan los parámetros s en el diseño de circuitos lineales de microondas. Dichos métodos de diseño analíticos permitirían una mejora significativa en los actuales procedimientos de diseño disponibles en gran señal, así como una reducción considerable en el tiempo de diseño, lo que permitiría la obtención de técnicas mucho más eficientes. Abstract In linear world, classical microwave circuit design relies on the s-parameters due to its capability to successfully characterize the behavior of any linear circuit. Thus the direct use of s-parameters in measurement systems and in linear simulation analysis tools, has facilitated its extensive use and success in the design and characterization of microwave circuits and subsystems. Nevertheless, despite the great success of s-parameters in the microwave community, the main drawback of this formulation is its limitation in the behavior prediction of real non-linear systems. Nowadays, the challenge of microwave designers is the development of an analogue framework that allows to integrate non-linear modeling, large-signal measurement hardware and non-linear simulation environment in order to extend s-parameters capabilities to non-linear regimen and thus, provide the infrastructure for non-linear design and test in a reliable and efficient way. Recently, different attempts with the aim to provide this common platform have been introduced, as the Cardiff approach and the Agilent X-parameters. Hence, this Thesis aims to demonstrate the X-parameter capability to provide this non-linear design and test framework in CAD-based oscillator context. Furthermore, the classical analysis and design of linear microwave transistorbased circuits is based on the development of simple analytical approaches, involving the transistor s-parameters, that are able to quickly provide an analytical solution for the input/output transistor loading conditions as well as analytically determine fundamental parameters as the stability factor, the power gain contours or the input/ output match. Hence, the development of similar analytical design tools that are able to extend s-parameters capabilities in small-signal design to non-linear ap- v plications means a new challenge that is going to be faced in the present work. Therefore, the development of an analytical design framework, based on loadindependent X-parameters, constitutes the core of this Thesis. These analytical nonlinear design approaches would enable to significantly improve current large-signal design processes as well as dramatically decrease the required design time and thus, obtain more efficient approaches.

First steps in the discovery of patterns in the academic results of telecommunication engineering students in the subjects Analysis of Circuits and Mathematics

In this paper, the results of six years of research in engineering education, in the application of the European Higher Education Area (EHEA) to improve the performance of the students in the subject Analysis of Circuits of Telecommunication Engineering, are analysed taking into consideration the fact that there would be hidden variables that both separate students into subgroups and show the connection among several basic subjects such as Analysis of Circuits (AC) and Mathematics (Math). The discovery of these variables would help us to explain the characteristics of the students through the teaching and learning methodology, and would show that there are some characteristics that instructors do not take into account but that are of paramount importance

The evolution of the brain, the human nature of cortical circuits and intellectual creativity

The tremendous expansion and the differentiation of the neocortex constitute two major events in the evolution of the mammalian brain. The increase in size and complexity of our brains opened the way to a spectacular development of cognitive and mental skills. This expansion during evolution facilitated the addition of microcircuits with a similar basic structure, which increased the complexity of the human brain and contributed to its uniqueness. However, fundamental differences even exist between distinct mammalian species. Here, we shall discuss the issue of our humanity from a neurobiological and historical perspective.

Artificial cognitive control system based on the shared circuits model of sociocognitive capacities. A first approach

sharedcircuitmodels is presented in this work. The sharedcircuitsmodelapproach of sociocognitivecapacities recently proposed by Hurley in The sharedcircuitsmodel (SCM): how control, mirroring, and simulation can enable imitation, deliberation, and mindreading. Behavioral and Brain Sciences 31(1) (2008) 1–22 is enriched and improved in this work. A five-layer computational architecture for designing artificialcognitivecontrolsystems is proposed on the basis of a modified sharedcircuitsmodel for emulating sociocognitive experiences such as imitation, deliberation, and mindreading. In order to show the enormous potential of this approach, a simplified implementation is applied to a case study. An artificialcognitivecontrolsystem is applied for controlling force in a manufacturing process that demonstrates the suitability of the suggested approach

Oscillatory genetic circuits: new designs and mathematical models

Introduction and motivation: A wide variety of organisms have developed in-ternal biomolecular clocks in order to adapt to cyclic changes of the environment. Clock operation involves genetic networks. These genetic networks have to be mod¬eled in order to understand the underlying mechanism of oscillations and to design new synthetic cellular clocks. This doctoral thesis has resulted in two contributions to the fields of genetic clocks and systems and synthetic biology, generally. The first contribution is a new genetic circuit model that exhibits an oscillatory behav¬ior through catalytic RNA molecules. The second and major contribution is a new genetic circuit model demonstrating that a repressor molecule acting on the positive feedback of a self-activating gene produces reliable oscillations. First contribution: A new model of a synthetic genetic oscillator based on a typical two-gene motif with one positive and one negative feedback loop is pre¬sented. The originality is that the repressor is a catalytic RNA molecule rather than a protein or a non-catalytic RNA molecule. This catalytic RNA is a ribozyme that acts post-transcriptionally by binding to and cleaving target mRNA molecules. This genetic clock involves just two genes, a mRNA and an activator protein, apart from the ribozyme. Parameter values that produce a circadian period in both determin¬istic and stochastic simulations have been chosen as an example of clock operation. The effects of the stochastic fluctuations are quantified by a period histogram and autocorrelation function. The conclusion is that catalytic RNA molecules can act as repressor proteins and simplify the design of genetic oscillators. Second and major contribution: It is demonstrated that a self-activating gene in conjunction with a simple negative interaction can easily produce robust matically validated. This model is comprised of two clearly distinct parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the oscillator dynamics are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this study is that a simple and usual negative interaction, such as degradation, se¬questration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. At the genetic level, this means that an explicit negative feedback loop is not necessary. Unlike many genetic oscillators, this model needs neither cooperative binding reactions nor the formation of protein multimers. Applications and future research directions: Recently, RNA molecules have been found to play many new catalytic roles. The first oscillatory genetic model proposed in this thesis uses ribozymes as repressor molecules. This could provide new synthetic biology design principles and a better understanding of cel¬lular clocks regulated by RNA molecules. The second genetic model proposed here involves only a repression acting on a self-activating gene and produces robust oscil¬lations. Unlike current two-gene oscillators, this model surprisingly does not require a second repressor gene. This result could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. Possible follow-on research directions are: validate models in vivo and in vitro, research the potential of second model as a genetic memory, investigate new genetic oscillators regulated by non-coding RNAs and design a biosensor of positive feedbacks in genetic networks based on the operation of the second model Resumen Introduccion y motivacion: Una amplia variedad de organismos han desarro-llado relojes biomoleculares internos con el fin de adaptarse a los cambios ciclicos del entorno. El funcionamiento de estos relojes involucra redes geneticas. El mo delado de estas redes geneticas es esencial tanto para entender los mecanismos que producen las oscilaciones como para diseiiar nuevos circuitos sinteticos en celulas. Esta tesis doctoral ha dado lugar a dos contribuciones dentro de los campos de los circuitos geneticos en particular, y biologia de sistemas y sintetica en general. La primera contribucion es un nuevo modelo de circuito genetico que muestra un comportamiento oscilatorio usando moleculas de ARN cataliticas. La segunda y principal contribucion es un nuevo modelo de circuito genetico que demuestra que una molecula represora actuando sobre el lazo de un gen auto-activado produce oscilaciones robustas. Primera contribucion: Es un nuevo modelo de oscilador genetico sintetico basado en una tipica red genetica compuesta por dos genes con dos lazos de retroa-limentacion, uno positivo y otro negativo. La novedad de este modelo es que el represor es una molecula de ARN catalftica, en lugar de una protefna o una molecula de ARN no-catalitica. Este ARN catalitico es una ribozima que actua despues de la transcription genetica uniendose y cortando moleculas de ARN mensajero (ARNm). Este reloj genetico involucra solo dos genes, un ARNm y una proteina activadora, aparte de la ribozima. Como ejemplo de funcionamiento, se han escogido valores de los parametros que producen oscilaciones con periodo circadiano (24 horas) tanto en simulaciones deterministas como estocasticas. El efecto de las fluctuaciones es-tocasticas ha sido cuantificado mediante un histograma del periodo y la función de auto-correlacion. La conclusion es que las moleculas de ARN con propiedades cataliticas pueden jugar el misnio papel que las protemas represoras, y por lo tanto, simplificar el diseno de los osciladores geneticos. Segunda y principal contribucion: Es un nuevo modelo de oscilador genetico que demuestra que un gen auto-activado junto con una simple interaction negativa puede producir oscilaciones robustas. Este modelo ha sido estudiado y validado matematicamente. El modelo esta compuesto de dos partes bien diferenciadas. La primera parte es un lazo de retroalimentacion positiva creado por una proteina que se une al promotor de su propio gen activando la transcription. La segunda parte es una interaction negativa en la que una molecula represora evita la union de la proteina con el promotor. Un estudio estocastico muestra que el sistema es robusto al ruido. Un estudio determinista muestra que la dinamica del sistema es debida principalmente a dos tipos de biomoleculas: la proteina, y el complejo formado por el represor y esta proteina. La conclusion principal de este estudio es que una simple y usual interaction negativa, tal como una degradation, un secuestro o una inhibition, actuando sobre el lazo de retroalimentacion positiva de un solo gen es una condition suficiente para producir oscilaciones robustas. Un gen es suficiente y el lazo de retroalimentacion positiva no necesita activar a un segundo gen represor, tal y como ocurre en los relojes actuales con dos genes. Esto significa que a nivel genetico un lazo de retroalimentacion negativa no es necesario de forma explicita. Ademas, este modelo no necesita reacciones cooperativas ni la formation de multimeros proteicos, al contrario que en muchos osciladores geneticos. Aplicaciones y futuras lineas de investigacion: En los liltimos anos, se han descubierto muchas moleculas de ARN con capacidad catalitica. El primer modelo de oscilador genetico propuesto en esta tesis usa ribozimas como moleculas repre¬soras. Esto podria proporcionar nuevos principios de diseno en biologia sintetica y una mejor comprension de los relojes celulares regulados por moleculas de ARN. El segundo modelo de oscilador genetico propuesto aqui involucra solo una represion actuando sobre un gen auto-activado y produce oscilaciones robustas. Sorprendente-mente, un segundo gen represor no es necesario al contrario que en los bien conocidos osciladores con dos genes. Este resultado podria ayudar a clarificar los principios de diseno de los relojes celulares naturales y constituir una nueva y eficiente he-rramienta para crear osciladores geneticos sinteticos. Algunas de las futuras lineas de investigation abiertas tras esta tesis son: (1) la validation in vivo e in vitro de ambos modelos, (2) el estudio del potential del segundo modelo como circuito base para la construction de una memoria genetica, (3) el estudio de nuevos osciladores geneticos regulados por ARN no codificante y, por ultimo, (4) el rediseno del se¬gundo modelo de oscilador genetico para su uso como biosensor capaz de detectar genes auto-activados en redes geneticas.

Suitability of artificial neural networks for designing LoC circuits

he simulation of complex LoC (Lab-on-a-Chip) devices is a process that requires solving computationally expensive partial differential equations. An interesting alternative uses artificial neural networks for creating computationally feasible models based on MOR techniques. This paper proposes an approach that uses artificial neural networks for designing LoC components considering the artificial neural network topology as an isomorphism of the LoC device topology. The parameters of the trained neural networks are based on equations for modeling microfluidic circuits, analogous to electronic circuits. The neural networks have been trained to behave like AND, OR, Inverter gates. The parameters of the trained neural networks represent the features of LoC devices that behave as the aforementioned gates. This would mean that LoC devices universally compute.

Synchronizing chaotic optically-programmable digital circuits

In this paper an approach to the synchronization of chaotic circuits has been reported. It is based on an optically programmable logic cell and the signals involved are fully digital. It is based on the reception of the same input signal on sender and receiver and from this approach, with a posterior correlation between both outputs, an identical chaotic output is obtained in both systems. No conversion from analog to digital signals is needed. The model here presented is based on a computer simulation.

First order mem-circuits: modeling, nonlinear oscillations and bifurcations

This paper presents a theoretical framework intended to accommodate circuit devices described by characteristics involving more than two fundamental variables. This framework is motivated by the recent appearance of a variety of so-called mem-devices in circuit theory, and makes it possible to model the coexistence of memory effects of different nature in a single device. With a compact formalism, this setting accounts for classical devices and also for circuit elements which do not admit a two-variable description. Fully nonlinear characteristics are allowed for all devices, driving the analysis beyond the framework of Chua and Di Ventra We classify these fully nonlinear circuit elements in terms of the variables involved in their constitutive relations and the notions of the differential- and the state-order of a device. We extend the notion of a topologically degenerate configuration to this broader context, and characterize the differential-algebraic index of nodal models of such circuits. Additionally, we explore certain dynamical features of mem-circuits involving manifolds of non-isolated equilibria. Related bifurcation phenomena are explored for a family of nonlinear oscillators based on mem-devices.