A miniaturized, highly sensitive polarimeter as detector in an implantable glucose probe. II. Opto-electronic amplification and processing of measuring signals]

There is a clinical requirement for an implantable telemetric probe for monitoring glucose levels in humans. This probe can measure the glucose content of the intercellular tissue fluid, which reflects glucose levels in the blood. The lifespan of such an implantable probe should be maximal, so that presumably only physical measuring detectors, but not aging-sensitive bio-sensors can be considered. We are in the process of developing a very sensitive miniaturised detector based on polarimetry, capable of determining the measuring parameter--the spatial orientation of the in-plane vibration of a polarised light beam--with high accuracy. This is necessary for our purpose, since the physiological and pathological glucose levels modify in in-plane vibration by only a tiny angle of rotation. The high level of accuracy is achieved by various specific mechanisms both of the measuring parameters and the electric signal. Two suitable optoelectronic amplification methods are described. The first makes use of the ratio of the signal provided by the intensity of two consecutive beams, derived from the original light beam with the aid of a beam splitter. In this way, the sensitivity of determining the spatial position of the in-plane vibration of the polarised light beam can be increased by up to 50-fold in comparison with a "simple" polarimetry. The second method requires two very closely approximated (quasi united) or actually united beams from two sources, which are both "fixed-phase" time-coupled and quantitatively periodically intensity-modulated in opposite sense. Together with the already-mentioned ratio of the intensity signals of two consecutive beams, a periodically modulated signal generated from the individual signals is derived from this quasi-unified beam that enables the use of a phase sensitive rectifier-amplifier (lock-in amplifier) with its enormous amplification factor and noise elimination in the following circuitry.     

Chaotic based reconstructed phase space features for detecting ventricular fibrillation

Among the variety of cardiac arrhythmias, ventricular fibrillation (VF) and ventricular tachycardia (VT) are life-threatening; thus, accurate classification of these arrhythmias is a crucial task for cardiologists. Nevertheless, VT and VF signals are very similar in the time domain and accurate distinguishing these signals with naked eyes in some cases is impossible. In this paper, a novel self-similarity image-based scheme is introduced to classify the underlying information of VT, VF and normal electrocardiogram (ECG) signals. In this study, VT, VF and normal ECG signals are selected from CCU of the Royal Infirmary of Edinburgh and MIT-BIH datasets. According to the time delay method, signal samples can be assigned to state variables and a trajectory can be achieved. To extract the proposed self-similarity feature, first, two different trajectories from each signal trial are drawn according to two different delay time values. The two-dimensional state space of each trial trajectory is considered as an image. Therefore, two trajectory images are produced for each signal. Number of visited pixels in the first image is determined and is subtracted from that of the second image as the self-similarity feature of that signal. Moreover, another scheme is proposed to have a better estimation of self-similarity in which the logical AND operator is applied to both images (matrices) of each ECG trial. The third proposed criterion is similar to box counting method by this difference that each pixel is assigned a weight according to the trajectory density at that point and finally visited weighted pixels are counted. To classify VF from VT and normal ECG, a threshold is determined through the cross validation phase under the Receiver Operating Characteristic (ROC) criterion. To assess the proposed methods, the mentioned signals are classified using the-state-of-art chaotic features such as correlation dimension, the largest Lyapunov exponent and Approximate Entropy (ApEn). Experimental results indicate superiority of the proposed method in classifying the VT, VF and normal ECG signals compared to present traditional schemes. In addition, computational complexity of the introduced methods is very low and can be implemented in real-time applications.     

Binaural masking and sensitivity to interaural delay in the inferior colliculus.

The binaural masking level difference (BMLD) is a psychophysical effect whereby signals masked by a noise at one ear become unmasked by sounds reaching the other. BMLD effects are largest at low frequencies where they depend on signal phase, suggesting that part of the physiological mechanism responsible for the BMLD resides in cells that are sensitive to interaural time disparities. We have investigated a physiological basis for unmasking in the responses of delay-sensitive cells in the central nucleus of the inferior colliculus in anaesthetized guinea pigs. The masking effects of a binaurally presented noise, as a function of the masker delay, were quantified by measuring the number of discharges synchronized to the signal, and by measuring the masked threshold. The noise level for masking was lowest at the best delay for the noise. The mean magnitude of the unmasking across our neural population was similar to the human psychophysical BMLD under the same signal and masker conditions.     

Electron spin echo studies on chloroplasts. Spectral characteristics of electron transport components and light-induced transients

Electron-spin resonance echoes are used to study the complex overlapping ESR spectra of whole chloroplasts. By varying the repetition rate of the microwave pulse sequence, delay time, and pulse width, signals with different longitudinal and transverse relaxation times were extracted. We have identified the echo signals due to plastocyanin and ferredoxins. In addition, we have found a strong signal at g = 4.3, that possibly arises from distorted cytochrome, and weak signals in the region g = 6-9. The strong echo signal at g = 2.0047 (Signal II), is made up of at least three "dark" components that differ in their relaxation times. Upon illumination at 1.2 K several of the echo signals including Signal II show reversible light-induced components. The kinetics of these transients depend on the addition of 3(3,4-dichlorophenyl)-1,1-dimethyl urea. Part of the transients are believed to arise from cyclic electron flow around Photosystem I.     

Estimation of monopolar signals from sphincter muscles and removal of common mode interference

The detection of surface electromyogram (EMG) by multi-electrode systems is applied in many research studies. The signal is usually recorded by means of spatial filters (linear combination of the potential under at least two electrodes) with vanishing sum of weights. Nevertheless, more information could be extracted from monopolar signals measured with respect to a reference electrode away from the muscle. Under certain conditions, surface EMG signal along a curve parallel to the fibre path has zero mean (property approximately satisfied when EMG is sampled by an array of electrodes that covers the entire support of the signal in space). This property allows estimating monopolar from single differential (SD) signals by pseudoinversion of the matrix relating monopolar to SD signals. The method applies to EMG signals from the external anal sphincter muscle, recorded using a specific cylindrical probe with an array of electrodes located along the circular path of the fibres. The performance of the algorithm for the estimation of monopolar from SD signals is tested on simulated signals. The estimation error of monopolar signals decreases by increasing the number of channels. Using at least 12 electrodes, the estimation error is negligible. The method applies to single fibre action potentials, single motor unit action potentials, and interference signals.The same method can also be applied to reduce common mode interference from SD signals from muscles with rectilinear fibres. In this case, the last SD channel defined as the difference between the potentials of the last and the first electrodes must be recorded, so that the sum of all the SD signals vanishes. The SD signals estimated from the double differential signals by pseudoinvertion are free of common mode.     

Signalling plasticity and energy saving in a tropical bushcricket

Males of the tropical bushcricket Mecopoda elongata synchronize their acoustic advertisement signals (chirps) in interactions with other males. However, synchrony is not perfect and distinct leader and follower roles are often maintained. In entrainment experiments in which conspecific signals were presented at various rates, chirps displayed as follower showed notable signal plasticity. Follower chirps were shortened by reducing the number and duration of syllables, especially those of low and medium amplitude. The degree of shortening depended on the time delay between leader and follower signals and the sound level of the entraining stimulus. The same signal plasticity was evident in male duets, with the effect that the last syllables of highest amplitude overlapped more strongly. Respiratory measurements showed that solo singing males producing higher chirp rates suffered from higher metabolic costs compared to males singing at lower rates. In contrast, respiratory rate was rather constant during a synchronous entrainment to a conspecific signal repeated at various rates. This allowed males to maintain a steady duty cycle, associated with a constant metabolic rate. Results are discussed with respect to the preference for leader signals in females and the possible benefits males may gain by overlapping their follower signals in a chorus.     

Background suppression in frequency-domain fluorometry

Gated detection is often used in time-domain measurements of long-lived fluorophores for suppression of interfering short-lived autofluorescence. However, no direct method has been available for gated detection and background suppression when using frequency-domain fluorometry. We describe a direct method for real-time suppression of autofluorescence in frequency-domain fluorometry. The method uses a gated detector and the sample is excited by a pulsed train. The detector is gated on following each excitation pulse after a suitable time delay for decay of the prompt autofluorescence. Under the same experimental conditions a detectable reference signal is obtained by using a long lifetime standard with a known decay time. Because the sample and reference signals are measured under identical excitation, gating and instrumental conditions, the data can be analyzed as usual for frequency-domain data without further processing. We show by simulations that this method can be used to resolve single and multiexponential decays in the presence of short lifetime autofluorescence.     

The depletion of protein signals in metabonomics analysis with the WET-CPMG pulse sequence

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical tool capable of providing a comprehensive metabolic profile of biofluids such as urine, plasma, and serum. Unfortunately, when measuring serum and plasma, the high protein concentration can obscure the signals originating from low molecular weight metabolites. We evaluated the use of different parameters within the Carr-Purcell-Meiboom-Gill (CPMG) pulse train of fast spin-echoes to remove the macromolecular signal contribution in one-dimensional proton (1H) NMR spectra. Experimental parameters such as the refocusing delay in the CPMG pulse train, pulse miscalibration, and recycle time were examined to assess the ability to remove the protein signals from the spectrum without causing a deleterious effect on the signals originating from free, low molecular weight metabolites. The 1H-NMR spectra of a variety of serum samples spiked with 2'-deoxyadenosine were acquired using various acquisition parameters. Our results show that the delay used in the CPMG spin-echo and the combination of the acquisition pulse flip angle and recycle time are the two major factors affecting the observed metabolite signal amplitudes in the resulting 1H-NMR spectrum.     

A rapid algorithm for processing digital physiologic signals: Application to skeletal muscle contractions

Quantifying mechanical output is fundamental to understanding metabolism that fuels muscle contraction and more recent attempts to understand signal transduction and gene regulation. The latter requires long-term application of exercise protocols that result in large amounts of data on muscle performance. The purpose of this study was to develop software for automated quantification of skeletal muscle contractions. An in situ mouse sciatic nerve stimulation model was used to produce contractions over a broad range of frequencies and recorded as both digital and analog signals using a PC analog to digital converter board and chart recorder, respectively. Spectral analysis of the noise components formed the basis for designing a smoothing Chebyshev filter. Algorithms implemented in custom software identified twitches and estimated baseline levels from the smoothed signal. The time to peak force, peak force, tension-time integral, and half-relaxation time were determined for each twitch after baseline correction. The automated results were compared to those obtained from manual measurements of the analog signal. Bland–Altman analysis of the parameters computed from digital signals compared with the corresponding measurements by manual planometry demonstrates the agreement of the digital processing algorithm with planometry over a wide range of twitch characteristics. This program may also be used to study the mechanics of other preparations from isolated muscles, human proximal limb performance, and other digital physiologic signals. Adaptation of the filter function is required to apply the analysis to another experimental apparatus with differing noise characteristics. A full version of the program and instructions for its use are available for download at www.rad.msu.edu.     

中国东部温带植被生长季节的空间外推估计

利用地面植物物候和遥感归一化差值植被指数（NDVI）数据,以及一种物候-遥感外推方法,实现植被生长季节从少数站点到较多站点的空间外推。结果表明：（1）在1982～1993年期间,中国东部温带地区植被生长季节多年平均起讫日期的空间格局与春季和秋季平均气温的空间格局相关显著;（2）在不同纬度带和整个研究区域,植被生长季节结束日期呈显著推迟的趋势,而开始日期则呈不显著提前的趋势,这与欧洲和北美地区植被生长季节开始日期显著提前而结束日期不显著推迟的变化趋势完全不同;（3）北部纬度带的植被生长季节平均每年延长1．4～3．6d,全区的植被生长季节平均每年延长1．4d,与同期北半球和欧亚大陆植被生长季节延长的趋势数值相近;（4）植被生长季节结束日期的显著推迟与晚春至夏季的区域性降温有关,而植被生长季节开始日期的不显著提前则与晚冬至春季气温趋势的不稳定变化有关;（5）在年际变化方面,植被生长季节开始和结束日期分别与2～4月份平均气温和5～6月份平均气温呈负相关关系。     

Time-resolved absorption and fluorescence from the bacteriorhodopsin photocycle in the nanosecond time regime

Picosecond transient absorption (PTA) in the 568-660-nm region is measured over the initial 80 ns of the bacteriorhodopsin photocycle. After photocycle initiation with 573-nm excitation (7-ps pulsewidth), these PTA data reflect the formation during the initial 40 ps of two long-recognized intermediates with red-shifted (relative to that of BR-570) absorption bands, namely J-625 and K-590. PTA signals at 568, 628, and 652 nm are unchanged for the remainder of the 80-ns photocycle interval measured, demonstrating that no other intermediates, including the proposed KL, are observable by absorption changes. Picosecond time-resolved fluorescence (PTRF), measured at 740 nm, is initiated by 7 ps excitation of the species present at various time delays after the photocycle begins. PTRF signals change rapidly over the initial 40 ps, reflecting, first, the depletion of the ground state BR-570 population and, subsequently, the formation of K-590. The PTRF signal then decreases monotonically with a time constant of 5.5 ± 0.5 ns from its maximum near a 50-ps delay until it reaches a minimum at a delay of ≈ 13 ns. For time delays between 13 and 80 ns, the PTRF signal remains unchanged and slightly higher than that measured from BR-570 alone. The rapid decrease in PTRF signals over the same photocycle interval in which the PTA signals remain unchanged suggests that the retinal-protein interactions involving electronically excited K-590 (K*) are being significantly altered.     

A dual-luciferase reporter system for studying recoding signals.

A new reporter system has been developed for measuring translation coupling efficiency of recoding mechanisms such as frameshifting or readthrough. A recoding test sequence is cloned in between the renilla and firefly luciferase reporter genes and the two luciferase activities are subsequently measured in the same tube. The normalized ratio of the two activities is proportional to the efficiency with which the ribosome "reads" the recoding signal making the transition from one open reading frame to the next. The internal control from measuring both activities provides a convenient and reliable assay of efficiency. This is the first enzymatic dual reporter assay suitable for in vitro translation. Translation signals can be tested in vivo and in vitro from a single construct, which allows an intimate comparison between the two systems. The assay is applicable for high throughput screening procedures. The dual-luciferase reporter system has been applied to in vivo and in vitro recoding of HIV-1 gag-pol, MMTV gag-pro, MuLV gag-pol, and human antizyme.     

Comparison of secretory responses as measured by membrane capacitance and by amperometry.

We have compared capacitance and amperometric measurements in bovine chromaffin cells when secretion was elicited by flash photolysis of caged-calcium or step depolarizations. Total amperometric charge depended linearly on the amount of capacitance increase in both types of experiments. Furthermore, the properties of resolvable amperometric spikes after flashes were comparable to those observed after depolarizations, and their timing was compatible with the rate of capacitance increase. For a more detailed comparison, we used Monte Carlo simulations of multiple amperometric events occurring randomly over the surface of a sphere and summing together, to generate a reference amperometric signal for a given measured capacitance increase. Even after correction for endocytotic processes, the time courses of the integrated experimental records lagged behind the integrated Monte Carlo records by approximately 50 ms in flash and depolarization experiments. This delay was larger by approximately 40 ms than what can be expected from the "pre-foot delay" or the foot duration. Possible sources for the remaining delay could be diffusional barriers like the patch-pipette and the chamber bottom, which are not taken into account in the model. We also applied a novel type of fluctuation analysis to estimate the relative quantum size of an amperometric event. On average the estimates from experimental amperometric traces, in both flash and depolarization experiments, were 3-5 times smaller than estimates from simulated ones. This discrepancy can be due to contributions to the amperometric current from small vesicles, preferred release from cellular regions orientated toward the chamber bottom, or abundance of "foot-only" events. In conclusion, amperometric signals in flash and depolarization experiments displayed similar delayed average time courses and a lower estimate for the relative quantum size compared to the modeled amperometric signals. However, individual amperometric spikes were in agreement with expectations derived from capacitance signals.     

Segmentation of heart sounds based on dynamic clustering

The heart sound signal is first separated into cycles, where the cycle detection is based on an instantaneous cycle frequency. The heart sound data of one cardiac cycle can be decomposed into a number of atoms characterized by timing delay, frequency, amplitude, time width and phase. To segment heart sounds, we made a hypothesis that the atoms of a heart sound congregate as a cluster in time–frequency domains. We propose an atom density function to indicate clusters. To suppress clusters of murmurs and noise, weighted density function by atom energy is further proposed to improve the segmentation of heart sounds. Therefore, heart sounds are indicated by the hybrid analysis of clustering and medical knowledge. The segmentation scheme is automatic and no reference signal is needed. Twenty-six subjects, including 3 normal and 23 abnormal subjects, were tested for heart sound signals in various clinical cases. Our statistics show that the segmentation was successful for signals collected from normal subjects and patients with moderate murmurs.     

Echo delay versus spectral cues for temporal hyperacuity in the big brown bat,Eptesicus fuscus

Big brown bats can discriminate between echoes that alternate in delay (jitter) by as little as 10–15 ns and echoes that are stationary in delay. This delay hyperacuity seems so extreme that it has been rejected in favor of an explanation in terms of artifacts in echoes, most likely spectral in nature, that presumably are correlated with delay. Using different combinations of digital, analog, and cable delays, we dissociated the overall delay of jittering echoes from the size of the analog component of delay, which alone is presumed to determine the strength of the apparatus artifact. The bats' performance remains invariant with respect to the overall delay of the jittering echoes, not with respect to the amount of analog delay. This result is not consistent with the possible use of delay-related artifacts produced by the analog delay devices. Moreover, both electronic and acoustic measurements disclose no spectral cues or impedance-mismatch reflections in delayed signals, just time-delays. The absence of artifacts from the apparatus and the failure of overlap and interference from reverberation to account for the 10-ns result means that closing the gap between the level of temporal accuracy plausibly explained from physiology and the level observed in behavior may require a better understanding of the physiology.Abbreviations FM frequency-modulated - XCR cross-correlation function     

A computational analysis of separating motion signals in transparent random dot kinematograms

When multiple motion directions are presented simultaneously within the same region of the visual field human observers see motion transparency. This perceptual phenomenon requires from the visual system to separate different motion signal distributions, which are characterised by distinct means that correspond to the different dot directions and variances that are determined by the signal and processing noise. Averaging of local motion signals can be employed to reduce noise components, but such pooling could at the same time lead to the averaging of different directional signal components, arising from spatially adjacent dots moving in different directions, which would reduce the visibility of transparent directions. To study the theoretical limitations of encoding transparent motion by a biologically plausible motion detector network, the distributions of motion directions signalled by a motion detector model (2DMD) were analysed here for Random Dot Kinematograms (RDKs). In sparse dot RDKs with two randomly interleaved motion directions, the angular separation that still allows us to separate two directions is limited by the internal noise in the system. Under the present conditions direction differences down to 30 deg could be separated. Correspondingly, in a transparent motion stimulus containing multiple motion directions, more than eight directions could be separated. When this computational analysis is compared to some published psychophysical data, it appears that the experimental results do not reach the predicted limits. Whereas the computer simulations demonstrate that even an unsophisticated motion detector network would be appropriate to represent a considerable number of motion directions simultaneously within the same region, human observers usually are restricted to seeing not more than two or three directions under comparable conditions. This raises the question why human observers do not make full use of information that could be easily extracted from the representation of motion signals at the early stages of the visual system.     

Miniaturization capable, very sensitive polarimeter as detector of an implantable glucose probe. I. Optical amplification of the measuring value]

From a clinical point of view, an implantable telemetric probe for monitoring the blood glucose profile is highly desirable. It should be capable of monitoring the blood glucose level continuously or at regular brief intervals, if necessary requirement-controlled. Apart from blood, measurement can also be made in intercellular tissue fluid, for example, in subcutaneous connective and fatty tissue, because this fluid accurately reflects blood glucose levels after only a brief, but negligible, time lag. Since the functional lifespan of an implantable probe is of decisive importance, only physical sensors, but not bio-sensors can be considered. We are in the process of developing a very sensitive miniaturised detector based on polarimetry, capable of determining the measuring parameter--the spatial orientation of the in-plane vibration of a polarised light beam--with extreme accuracy. This is a very important point, since the physiological and pathological glucose levels modify the in-plane vibration by only a very tiny angle of rotation. The high level of accuracy is achieved by various specific optical amplification mechanisms, and amplification of the electric signal. Two purely optical amplification methods are described here. Simple linear elongation of the optical path of a laser beam within the sample, resulting in a proportional amplification of the measuring signal, is obviously strictly limited in an implantable probe. We therefore developed a technique that preserves the polarisation state of the light beam during reflection. This technique makes possible multiple passage of the light beam through the fluid being sensed, thus elongating the optical path by "folding" the light beam without the need to enlarge the measuring cuvette. In a second possibility, enlargement of the rotation angle can be achieved by reflecting the light beam from a suitable surface, when the orthogonal components of the polarised light beam are reflected to different extents.     

Enabling High Grayscale Resolution Displays and Accurate Response Time Measurements on Conventional Computers

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments in vision research require displays with more than 12 bits of luminance resolution. Several solutions are available. Bit++ ¹ and DataPixx ² use the Digital Visual Interface (DVI) output from graphics cards and high resolution (14 or 16-bit) digital-to-analog converters to drive analog display devices. The VideoSwitcher ³ described here combines analog video signals from the red and blue channels of graphics cards with different weights using a passive resister network ⁴ and an active circuit to deliver identical video signals to the three channels of color monitors. The method provides an inexpensive way to enable high-resolution monochromatic displays using conventional graphics cards and analog monitors. It can also provide trigger signals that can be used to mark stimulus onsets, making it easy to synchronize visual displays with physiological recordings or response time measurements.Although computer keyboards and mice are frequently used in measuring response times (RT), the accuracy of these measurements is quite low. The RTbox is a specialized hardware and software solution for accurate RT measurements. Connected to the host computer through a USB connection, the driver of the RTbox is compatible with all conventional operating systems. It uses a microprocessor and high-resolution clock to record the identities and timing of button events, which are buffered until the host computer retrieves them. The recorded button events are not affected by potential timing uncertainties or biases associated with data transmission and processing in the host computer. The asynchronous storage greatly simplifies the design of user programs. Several methods are available to synchronize the clocks of the RTbox and the host computer. The RTbox can also receive external triggers and be used to measure RT with respect to external events. Both VideoSwitcher and RTbox are available for users to purchase. The relevant information and many demonstration programs can be found at http://lobes.usc.edu/.     

Localization of a sum of acoustic signals in air by the northern fur seal]

The localization of a sum of acoustic signals by two northern fur seals in air depending on sound parameters was investigated using the method of instrumental conditioned reflexes with food reinforcement. It was found that sound perception of northern fur seal proceeds by the binaural mechanism. The time/intensity interchange coefficient was 570 microseconds/dB for series of clicks (with amplitude maximum at 1 kHz) and 250 microseconds/dB for tonal impulses with a frequency of 1 kHz. With click amplitudes being equal, the number of approaches of the animal to the source of the first signal reached a 75% level at a delay of the second signal 0.07 ms (the minimum delay); with a delay of 6 ms (the maximum delay) and more, the fur seal, probably hears two separate signals. The minimum delay depended little on the duration of tonal impulses (with a frequency of 1 kHz) and was 0.3-0.7 ms; the maximum delay was 9-11 ms for tonal impulses with a duration of 3 ms and 37-40 ms with impulse duration 20 ms. The precedence effect became apparent at a greater delay for smooth fronts of impulses than for rectangular fronts.     

Development of a 3‐dimensional tissue lung phantom of a preterm infant for optical measurements of oxygen—Laser‐detector position considerations

There is a need to further improve the clinical care of our most vulnerable patients—preterm infants. Novel diagnostic and treatment tools facilitate such advances. Here, we evaluate a potential percutaneous optical monitoring tool to assess the oxygen and water vapor content in the lungs of preterm babies. The aim is to prepare for further clinical studies by gaining a detailed understanding of how the measured light intensity and gas absorption signal behave for different possible geometries of light delivery and receiver. Such an experimental evaluation is conducted for the first time utilizing a specially developed 3‐dimensional‐printed optical phantom based on a geometry model obtained from computer tomography images of the thorax (chest) of a 1700‐g premature infant. The measurements yield reliable signals for source–detector distances up to about 50 mm, with stronger gas absorption signals at long separations and positions related to the lower part of the lung, consistent with a larger relative volume of this. The limitations of this study include the omission of scattering tissue within the lungs and that similar optical properties are used for the wavelengths employed for the 2 gases, yielding no indication on the optimal wavelength pair to use.