Application of Signal Advance Technology to Electrophysiology

Medical instrumentation used in diagnosis and treatment relies on the accurate detection and processing of various physiological events and signals. While signal detection technology has improved greatly in recent years, there remain inherent delays in signal detection/ processing. These delays may have significant negative clinical consequences during various pathophysiological events. Reducing or eliminating such delays would increase the ability to provide successful early intervention in certain disorders thereby increasing the efficacy of treatment. In recent years, a physical phenomenon referred to as Negative Group Delay (NGD), demonstrated in simple electronic circuits, has been shown to temporally advance the detection of analog waveforms. Specifically, the output is temporally advanced relative to the input, as the time delay through the circuit is negative. The circuit output precedes the complete detection of the input signal. This process is referred to as signal advance (SA) detection. An SA circuit model incorporating NGD was designed, developed and tested. It imparts a constant temporal signal advance over a pre-specified spectral range in which the output is almost identical to the input signal (i.e., it has minimal distortion). Certain human patho-electrophysiological events are good candidates for the application of temporally-advanced waveform detection. SA technology has potential in early arrhythmia and epileptic seizure detection and intervention. Demonstrating reliable and consistent temporally advanced detection of electrophysiological waveforms may enable intervention with a pathological event (much) earlier than previously possible. SA detection could also be used to improve the performance of neural computer interfaces, neurotherapy applications, radiation therapy and imaging. In this study, the performance of a single-stage SA circuit model on a variety of constructed input signals, and human ECGs is investigated. The data obtained is used to quantify and characterize the temporal advances and circuit gain, as well as distortions in the output waveforms relative to their inputs. This project combines elements of physics, engineering, signal processing, statistics and electrophysiology. Its success has important consequences for the development of novel interventional methodologies in cardiology and neurophysiology as well as significant potential in a broader range of both biomedical and non-biomedical areas of application.

Reply to the editor

We appreciate the comments and concerns expressed by Arakawa and colleagues regarding our article, titled “Pulsatile control of rotary blood pumps: Does the modulation waveform matter?”1 Unfortunately, we have to disagree with Arakawa and colleagues. As is obvious from the title of our article, it investigates the effect of different waveforms on the heart–device interaction. In contrast to the authors' claim, this is the first article in the literature that uses basic waveforms (sine, triangle, saw tooth, and rectangular) with different phase shifts to examines their impact on left ventricular unloading. The previous publications2, 3 and 4 just varied the pump speed during systole and diastole, which was first reported by Bearnson and associates5 in 1996, and studied its effect on aortic pressure, coronary flow, and end-diastolic volume. We should mention that dp/dtmax is a load-sensitive parameter of contractility and not representative for the degree of unloading. Moreover, none of the aforementioned reports has studied mechanical unloading and in particular the stroke work of the left ventricle. Our method is unique because we do not just alternate between high and low speed but have accurate control of the waveform because of the direct drive system of Levitronix Technologies LLC (Waltham, Mass) and a custom-developed pump controller. Without referring, Arakawa and associates state “several previous studies have already reported the coronary flow diminishes as the left ventricular assist device support increases.” It should be noted that all the waveforms used in our study have 2000 rpm average value with 1000 rpm amplitude, which is not an excessive speed for the CentriMag rotary pump (Levitronix) to collapse the ventricle and diminish the coronary flow. We agree with Arakawa and coworkers that there is a need for a heart failure model to come to more relevant results with respect to clinical expectations. However, we have explored many existing models, including species and breeds that have a native proneness to cardiomyopathy, but all of them differ from the genetic presentation in humans. We certainly do not believe that the use of microembolization, in which the coronary circulation is impaired by the injection of microspheres, would form a good model from which to draw conclusions about coronary flow change under different loading conditions. A model would be needed in which either an infarct is created to mimic ischemic heart failure or the coronary circulation remains untouched to simulate, for instance, dilated cardiomyopathy. Furthermore, in discussion we clearly mention that “lack of heart failure is a major limitation of our study.” We also believe that unloading is not the only factor of the cardiac functional recovery, and an excessive unloading of the left ventricle might lead to cardiac tissue atrophy. Therefore, in our article we mention that control of the level of cardiac unloading by assist devices has been suggested as a mechanical tool to promote recovery, and more studies are required to find better strategies for the speed modulation of rotary pumps and to achieve an optimal heart load control to enhance myocardial recovery. Finally, there are many publications about pulsing rotary blood pumps and it was impossible to include them all. We preferred to reference some of the earlier basic works such as an original research by Bearnson and coworkers5 and another article published by our group,6 which is more relevant.

Motile response patterns and ultrastructural observations of the isolated outer hair cell

The tonotopic organization of the mammalian cochlea is accompanied by structural gradients which include the somatic lengths of outer hair cells (OHCs). These receptors rest upon the vibrating portion of the basilar membrane and have been reported to exhibit motile responses following chemical and electrical stimulation. These movements were examined in detail in this dissertation. It was found that isolated OHCs cultured in vitro respond to chemical depolarization with slow tonic movements, and to electrical waveforms with bi-directional, frequency following movements extending from DC to at least 10 kHz.^ Slow contractions were also elicited following electrical stimulation, bath incubation in carbachol (a cholinergic agonist), and increases in extracellular K+ concentration as little as 50 mM.^ Isolated OHCs display anatomical features which are remarkable when contrasted with those prepared from intact receptor organs. A complex structure located between the cuticular plate and the nuclear membrane was consistently observed and was examined by serial cross-sections which revealed a network of non-membrane bound densities. This corresponded to a granular complex seen at the light microscope level. The complex was composed of dense regions of organelles, striated structures embedded within the core, and a circumferential network of microtubules residing in the peri-nuclear portion of the cell. In cells which had lost their nuclear attachment to the terminal synaptic body, the granular complex could be made to contract without effecting any change in cellular length, implying that the complex may be the driving force behind certain aspects of the motile response.^ Most cells displayed movements which revealed asymmetries analogous to those reported for OHC receptor potentials in vivo. The contraction phase (for longer cells) was shown to have a small time constant (approximately 400 microseconds) and saturated with limited displacements. The expansion phase had time constants as large as 1.3 milliseconds but yielded displacements as much as 60 percent larger than those seen for contractions.^ Additional waveform characteristics seen in the in vivo response could be emulated either by biasing the cell's resting length with either direct current, triggering contractions via large electrical displacements, or incubation with depolarizing compounds.^ Alternatively, short (20-30 um) cells revealed more linear response characteristics to the probe stimulus. Partial saturation was achieved and revealed a DC component which was opposite in polarity to that seen in longer cells. (Abstract shortened with permission of author.) ^

Phase Structure of Radar Stratigraphic Horizons Within Antarctic Firn

We have recorded reflection profiles of firn through large areas of West Antarctica and part of the East Antarctic plateau using 400 MHz short-pulse radar. The locations show accumulation rates that vary from well above to well below the vertical radar resolution. Most reflection horizons have extensive lateral continuity, and are composed of distinctive wavelets with a consistent phase polarity sequence within their successive half-cycles. We modeled these waveforms, and conclude that they arise from thin, double layers of ice over hoar, which is consistent with the standard model of firn stratification. In addition, we conclude that ice/hoar layers are extensive throughout West Antarctica and also present (although more sparsely) beneath the Antarctic Plateau.

Stratigraphic Continuity in 400 Mhz Short-Pulse Radar Profiles of Firn in West Antarctica

We track dated firn horizons within 400 MHz short-pulse radar profiles to find the continuous extent over which they can be used as historical benchmarks to study past accumulation rates in West Antarctica. The 30-40 cm pulse resolution compares with the accumulation rates of most areas. We tracked a particular set that varied from 30 to 90 m in depth over a distance of 600 km. The main limitations to continuity are fading at depth, pinching associated with accumulation rate differences within hills and valleys, and artificial fading caused by stacking along dips. The latter two may be overcome through multi-kilometer distances by matching the relative amplitude and spacing of several close horizons, along with their pulse forms and phases. Modeling of reflections from thin layers suggests that the - 37 to - 50 dB range of reflectivity and the pulse waveforms we observed are caused by the numerous thin ice layers observed in core stratigraphy. Constructive interference between reflections from these close, high-density layers can explain the maintenance of reflective strength throughout the depth of the firn despite the effects of compaction. The continuity suggests that these layers formed throughout West Antarctica and possibly into East Antarctica as well.

Zazen meditation and no-task resting EEG compared with LORETA intracortical source localization

Meditation is a self-induced and willfully initiated practice that alters the state of consciousness. The meditation practice of Zazen, like many other meditation practices, aims at disregarding intrusive thoughts while controlling body posture. It is an open monitoring meditation characterized by detached moment-to-moment awareness and reduced conceptual thinking and self-reference. Which brain areas differ in electric activity during Zazen compared to task-free resting? Since scalp electroencephalography (EEG) waveforms are reference-dependent, conclusions about the localization of active brain areas are ambiguous. Computing intracerebral source models from the scalp EEG data solves this problem. In the present study, we applied source modeling using low resolution brain electromagnetic tomography (LORETA) to 58-channel scalp EEG data recorded from 15 experienced Zen meditators during Zazen and no-task resting. Zazen compared to no-task resting showed increased alpha-1 and alpha-2 frequency activity in an exclusively right-lateralized cluster extending from prefrontal areas including the insula to parts of the somatosensory and motor cortices and temporal areas. Zazen also showed decreased alpha and beta-2 activity in the left angular gyrus and decreased beta-1 and beta-2 activity in a large bilateral posterior cluster comprising the visual cortex, the posterior cingulate cortex and the parietal cortex. The results include parts of the default mode network and suggest enhanced automatic memory and emotion processing, reduced conceptual thinking and self-reference on a less judgmental, i.e., more detached moment-to-moment basis during Zazen compared to no-task resting.

Distortion-free enhancement of terahertz signals measured by electro-optic sampling. I. Theory

We present three methods for the distortion-free enhancement of THz signals measured by electro-optic sampling in zinc blende-type detector crystals, e.g., ZnTe or GaP. A technique commonly used in optically heterodyne-detected optical Kerr effect spectroscopy is introduced, which is based on two measurements at opposite optical biases near the zero transmission point in a crossed polarizer detection geometry. In contrast to other techniques for an undistorted THz signal enhancement, it also works in a balanced detection scheme and does not require an elaborate procedure for the reconstruction of the true signal as the two measured waveforms are simply subtracted to remove distortions. We study three different approaches for setting an optical bias using the Jones matrix formalism and discuss them also in the framework of optical heterodyne detection. We show that there is an optimal bias point in realistic situations where a small fraction of the probe light is scattered by optical components. The experimental demonstration will be given in the second part of this two-paper series [J. Opt. Soc. Am. B, doc. ID 204877 (2014, posted online)].

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

Estimación de la Reflectividad del Multitrayecto en Entornos Urbanos en Radares de Apertura Sintética

Synthetic Aperture Radar (SAR) images a target region reflectivity function in the multi-dimensional spatial domain of range and cross-range. SAR synthesizes a large aperture radar in order to achieve finer azimuth resolution than the one provided by any on-board real antenna. Conventional SAR techniques assume a single reflection of transmitted waveforms from targets. Nevertheless, today¿s new scenes force SAR systems to work in urban environments. Consequently, multiple-bounce returns are added to direct-scatter echoes. We refer to these as ghost images, since they obscure true target image and lead to poor resolution. By analyzing the quadratic phase error (QPE), this paper demonstrates that Earth¿s curvature influences the defocusing degree of multipath returns. In addition to the QPE, other parameters such as integrated sidelobe ratio (ISLR), peak sidelobe ratio (PSLR), contrast and entropy provide us with the tools to identify direct-scatter echoes in images containing undesired returns coming from multipath.

Multipath Reflectivity Estimation in Urban Environments for Synthetic Aperture Radar Images

Synthetic Aperture Radar (SAR) images a target region reflectivity function in the multi-dimensional spatial domain of range and cross-range. SAR synthesizes a large aperture radar in order to achieve a finer azimuth resolution than the one provided by any on-board real antenna. Conventional SAR techniques assume a single reflection of transmitted waveforms from targets. Nevertheless, today¿s new scenes force SAR systems to work in urban environments. Consequently, multiple-bounce returns are added to directscatter echoes. We refer to these as ghost images, since they obscure true target image and lead to poor resolution. By analyzing the quadratic phase error (QPE), this paper demonstrates that Earth¿s curvature influences the defocusing degree of multipath returns. In addition to the QPE, other parameters such as integrated sidelobe ratio (ISLR), peak sidelobe ratio (PSLR), contrast (C) and entropy (E) provide us with the tools to identify direct-scatter echoes in images containing undesired returns coming from multipath.

Técnica de Inversión Temporal para la Mejora del Enfocado de Imágenes SAR en Entornos Urbanos

Conventional SAR (Synthetic Aperture Radar) techniques only consider a single reflection of transmitted waveforms from targets. Nevertheless, today?s new applications force SAR systems to work in much more complex scenes such as urban environments. As a result, multiple-bounce returns are additionally superposed to direct echoes. We refer to these as ghost images, since they obscure true target image and lead to poor resolution. By applying Time Reversal concept to SAR imaging (TR-SAR), it is possible to reduce considerably ?or almost mitigate? ghosting artifacts, recovering the lost resolution due to multipath effects. Furthermore, some focusing indicators such as entropy (E), contrast (C) and Rényi entropy (RE) provide us a good focusing criterion when using TR-SAR.

New Technique for Static Target Detection in Dense-Multipath Urban Environments

Synthetic Aperture Radar (SAR) images a target region reflectivity function in the multi-dimensional spatial domain of range and cross-range with a finer azimuth resolution than the one provided by any on-board real antenna. Conventional SAR techniques assume a single reflection of transmitted waveforms from targets. Nevertheless, new uses of Unmanned Aerial Vehicles (UAVs) for civilian-security applications force SAR systems to work in much more complex scenes such as urban environments. Consequently, multiple-bounce returns are additionally superposed to direct-scatter echoes. They are known as ghost images, since they obscure true target image and lead to poor resolution. All this may involve a significant problem in applications related to surveillance and security. In this work, an innovative multipath mitigation technique is presented in which Time Reversal (TR) concept is applied to SAR images when the target is concealed in clutter, leading to TR-SAR technique. This way, the effect of multipath is considerably reduced ?or even removed?, recovering the lost resolution due to multipath propagation. Furthermore, some focusing indicators such as entropy (E), contrast (C) and Rényi entropy (RE) provide us with a good focusing criterion when using TR-SAR.

Electrooptic characterization of tunable cylindrical liquid crystal lenses

In this work, one-dimensional arrays of cylindrical adaptive liquid crystal lenses were manufactured and characterized; and test devices were filled with nematic liquid crystal. Comb interdigitated electrodes were designed as a mask pattern for the control electrode on the top glass substrates. A radial graded refractive index along each microsized lens was achieved by fabricating a layer of high resistance sheet deposited as a control electrode. These tunable lenses were switched by applying amplitude and frequency optimized waveforms on the control electrode. Phase profiles generated by the radial electric field distribution on each lens were measured by a convectional interferometric technique.

Sintetizador analógico en Arduino

Este proyecto consiste en el diseño y construcción de un sintetizador basado en el chip 6581 Sound Interface Device (SID). Este chip era el encargado de la generación de sonido en el Commodore 64, ordenador personal comercializado en 1982, y fue el primer sintetizador complejo construido para ordenador. El chip en cuestión es un sintetizador de tres voces, cada una de ellas capaz de generar cuatro diferentes formas de onda. Cada voz tiene control independiente de varios parámetros, permitiendo una relativamente amplia variedad de sonidos y efectos, muy útil para su uso en videojuegos. Además está dotado de un filtro programable para conseguir distintos timbres mediante síntesis sustractiva. El sintetizador se ha construido sobre Arduino, una plataforma de electrónica abierta concebida para la creación de prototipos, consistente en una placa de circuito impreso con un microcontrolador, programable desde un PC para que realice múltiples funciones (desde encender LEDs hasta controlar servomecanismos en robótica, procesado y transmisión de datos, etc.). El sintetizador es controlable vía MIDI, por ejemplo, desde un teclado de piano. A través de MIDI recibe información tal como qué notas debe tocar, o los valores de los parámetros del SID que modifican las propiedades del sonido. Además, toda esa información también la puede recibir de un PC mediante una conexión USB. Se han construido dos versiones del sintetizador: una versión “hardware”, que utiliza el SID para la generación de sonido, y otra “software”, que reemplaza el SID por un emulador, es decir, un programa que se comporta (en la medida de lo posible) de la misma manera que el SID. El emulador se ha implementado en un microcontrolador Atmega 168 de Atmel, el mismo que utiliza Arduino. ABSTRACT. This project consists on design and construction of a synthesizer which is based on chip 6581 Sound Interface Device (SID). This chip was used for sound generation on the Commodore 64, a home computer presented in 1982, and it was the first complex synthesizer built for computers. The chip is a three-voice synthesizer, each voice capable of generating four different waveforms. Each voice has independent control of several parameters, allowing a relatively wide variety of sounds and effects, very useful for its use on videogames. It also includes a programmable filter, allowing more timbre control via subtractive synthesis. The synthesizer has been built on Arduino, an open-source electronics prototyping platform that consists on a printed circuit board with a microcontroller, which is programmable with a computer to do several functions (lighting LEDs, controlling servomechanisms on robotics, data processing or transmission, etc.). The synthesizer is controlled via MIDI, in example, from a piano-type keyboard. It receives from MIDI information such as the notes that should be played or SID’s parameter values that modify the sound. It also can receive that information from a PC via USB connection. Two versions of the synthesizer have been built: a hardware one that uses the SID chip for sound generation, and a software one that replaces SID by an emulator, it is, a program that behaves (as far as possible) in the same way the SID would. The emulator is implemented on an Atmel’s Atmega 168 microcontroller, the same one that is used on Arduino.

Validation Study of the Use of Matlab/Simulink Synchronous-Machine Block for Accurate Power-Plant Stability Studies

This paper presents results of the validity study of the use of MATLAB/Simulink synchronous-machine block for power-system stability studies. Firstly, the waveforms of the theoretical synchronous-generator short-circuit currents are described. Thereafter, the comparison between the currents obtained through the simulation model in the sudden short-circuit test, are compared to the theoretical ones. Finally, the factory tests of two commercial generating units are compared to the response of the synchronous generator simulation block during sudden short-circuit, set with the same real data, with satisfactory results. This results show the validity of the use of this generator block for power plant simulation.