WaveletQuant,an improved quantification software based on wavelet signal threshold de-noising for labeled quantitative proteomic analysis

Background  

Quantitative proteomics technologies have been developed to comprehensively identify and quantify proteins in two or more complex samples. Quantitative proteomics based on differential stable isotope labeling is one of the proteomics quantification technologies. Mass spectrometric data generated for peptide quantification are often noisy, and peak detection and definition require various smoothing filters to remove noise in order to achieve accurate peptide quantification. Many traditional smoothing filters, such as the moving average filter, Savitzky-Golay filter and Gaussian filter, have been used to reduce noise in MS peaks. However, limitations of these filtering approaches often result in inaccurate peptide quantification. Here we present the WaveletQuant program, based on wavelet theory, for better or alternative MS-based proteomic quantification.     

Analyzing gastrocnemius EMG-activity and sway data from quiet and perturbed standing.

In an experiment, we combined force plate measurements and surface EMG in studying quiet and perturbed standing, involving MS (Multiple sclerosis) and controls. The aim of this paper is to report the results thus obtained on the relation between filtered gastrocnemius (GA) EMG and the anterior-posterior center-of-pressure (A/P COP) coordinate. The main finding is the good correspondence between A/P COP and the filtered GA EMG in the low frequency range. The EMG envelope was calculated using a zero-lag filter. Combining this with time shifts around 250-350 ms produced a high correlation (85.5+/-8.4%) between the GA-EMG envelope and the A/P COP. This EMG-COP relation was closest when using a low cut-off frequency value around 1 Hz in calculating the EMG envelope. Based on this filtering procedure we estimated the average EMG-COP time shift to be 283+/-43 ms between the GA-EMG envelope and A/P COP (which "lags" behind EMG envelope). This shift is consistent with the 1 Hz cut-off and phase shift produced by a corresponding critically damped second-order filter, and is about twice the corresponding twitch time. These results suggest that GA is to a large extent responsible for the phasic control of the anterior-posterior balance during quiet standing. A small difference (p<0.03) was found between mean time shift thus obtained for controls (n=4) and MS (n=6) while sway area showed a major difference (p<0.01). The paper also compares three alternative filters for numerical calculation of the EMG-envelope.     

Electromyographic response is altered during robotic surgical training with augmented feedback

There is a growing prevalence of robotic systems for surgical laparoscopy. We previously developed quantitative measures to assess robotic surgical proficiency, and used augmented feedback to enhance training to reduce applied grip force and increase speed. However, there is also a need to understand the physiological demands of the surgeon during robotic surgery, and if training can reduce these demands. Therefore, the goal of this study was to use clinical biomechanical techniques via electromyography (EMG) to investigate the effects of real-time augmented visual feedback during short-term training on muscular activation and fatigue. Twenty novices were trained in three inanimate surgical tasks with the da Vinci Surgical System. Subjects were divided into five feedback groups (speed, relative phase, grip force, video, and control). Time- and frequency-domain EMG measures were obtained before and after training. Surgical training decreased muscle work as found from mean EMG and EMG envelopes. Grip force feedback further reduced average and total muscle work, while speed feedback increased average muscle work and decreased total muscle work. Training also increased the median frequency response as a result of increased speed and/or reduced fatigue during each task. More diverse motor units were recruited as revealed by increases in the frequency bandwidth post-training. We demonstrated that clinical biomechanics using EMG analysis can help to better understand the effects of training for robotic surgery. Real-time augmented feedback during training can further reduce physiological demands. Future studies will investigate other means of feedback such as biofeedback of EMG during robotic surgery training.     

Neural Mechanisms of Cortical Motion Computation Based on a Neuromorphic Sensory System

The visual cortex analyzes motion information along hierarchically arranged visual areas that interact through bidirectional interconnections. This work suggests a bio-inspired visual model focusing on the interactions of the cortical areas in which a new mechanism of feedforward and feedback processing are introduced. The model uses a neuromorphic vision sensor (silicon retina) that simulates the spike-generation functionality of the biological retina. Our model takes into account two main model visual areas, namely V1 and MT, with different feature selectivities. The initial motion is estimated in model area V1 using spatiotemporal filters to locally detect the direction of motion. Here, we adapt the filtering scheme originally suggested by Adelson and Bergen to make it consistent with the spike representation of the DVS. The responses of area V1 are weighted and pooled by area MT cells which are selective to different velocities, i.e. direction and speed. Such feature selectivity is here derived from compositions of activities in the spatio-temporal domain and integrating over larger space-time regions (receptive fields). In order to account for the bidirectional coupling of cortical areas we match properties of the feature selectivity in both areas for feedback processing. For such linkage we integrate the responses over different speeds along a particular preferred direction. Normalization of activities is carried out over the spatial as well as the feature domains to balance the activities of individual neurons in model areas V1 and MT. Our model was tested using different stimuli that moved in different directions. The results reveal that the error margin between the estimated motion and synthetic ground truth is decreased in area MT comparing with the initial estimation of area V1. In addition, the modulated V1 cell activations shows an enhancement of the initial motion estimation that is steered by feedback signals from MT cells.     

Orientation enhancement in early visual processing can explain time course of brightness contrast and White’s illusion

Dynamics of orientation tuning in V1 indicates that computational model of V1 should not only comprise of bank of static spatially oriented filters but also include the contribution for dynamical response facilitation or suppression along orientation. Time evolution of orientation response in V1 can emerge due to time- dependent excitation and lateral inhibition in the orientation domain. Lateral inhibition in the orientation domain suggests that Ernst Mach’s proposition can be applied for the enhancement of initial orientation distribution that is generated due to interaction of visual stimulus with spatially oriented filters and subcortical temporal filter. Oriented spatial filtering that appears much early ( $<$ 70 ms) in the sequence of visual information processing can account for many of the brightness illusions observed at steady state. It is therefore expected that time evolution of orientation response might be reflecting in the brightness percept over time. Our numerical study suggests that only spatio-temporal filtering at early phase can explain experimentally observed temporal dynamics of brightness contrast illusion. But, enhancement of orientation response at early phase of visual processing is the key mechanism that can guide visual system to predict the brightness by “Max-rule” or “Winner Takes All” (WTA) estimation and thus producing White’s illusions at any exposure.     

Evaluation of some nonrecursive digital filters for signals of auditory evoked responses

Auditory brain stem evoked responses are routinely used in audiology and otoneurology. Because recordings include more or less noise, the signals of evoked responses need digital filtering to suppress the noise. Nonrecursive digital filters are often the best since they can be organized to have no phase shift, which is essential in order not to distort sensitive parameters, as latency, in evoked responses. We have studied effects of some nonrecursive digital filters on the latency parameters of evoked responses. It turned out that digital filtering can have considerable influence on latencies, and thus the choice of appropriate filters is crucial.     

Attention-like processes underlying optomotor performance in a Drosophila choice maze

The authors present a novel paradigm for studying visual responses in Drosophila. An eight-level choice maze was found to reliably segregate fly populations according to their responses to moving stripes displayed on a computer screen. Visual responsiveness was robust in wild-type flies, and performance depended on salience effects such as stimulus color and speed. Analysis of individual fly choices in the maze revealed that stereotypy, or choice persistence, contributed significantly to a strain's performance. On the basis of these observations, the authors bred wild-type flies for divergent visual phenotypes by selecting individual flies displaying extreme stereotypy. Selected flies alternated less often in the sequential choice maze than unselected flies, showing that stereotypy could evolve across generations. The authors found that selection for increased stereotypy impaired flies' responsiveness to competing stimuli in tests for attention-like behavior in the maze. Visual selective attention was further investigated by electrophysiology, and it was found that increased stereotypy also impaired responsiveness to competing stimuli at the level of brain activity. Combined results present a comprehensive approach to studying visual responses in Drosophila, and show that behavioral performance involves attention-like processes that are variable among individuals and thus sensitive to artificial selection.     

Recursive implementations of temporal filters for image motion computation

 Efficient algorithms for image motion computation are important for computer vision applications and the modelling of biological vision systems. Intensity-based image motion computation proceeds in two stages: the convolution of linear spatiotemporal filter kernels with the image sequence, followed by the non-linear combination of the filter outputs. If the spatiotemporal extent of the filter kernels is large, then the convolution stage can be very intensive computationally. One effective means of reducing the storage required and computation involved in implementing the temporal convolutions is the introduction of recursive filtering. Non-recursive methods require the number of frames of the image sequence stored at any given time to be equal to the temporal extent of the slowest temporal filter. In contrast, recursive methods encode recent stimulus history implicitly in the values of a small number of variables updated through a series of feedback equations. Recursive filtering reduces the number of values stored in memory during convolution and the number of mathematical operations involved in computing the filters' outputs. This paper extends previous recursive implementations of gradient- and correlation-based motion analysis algorithms [Fleet DJ, Langley K (1995) IEEE PAMI 17: 61–67; Clifford CWG, Ibbotson MR, Langley K (1997) Vis Neurosci 14: 741–749], describing a recursive implementation of causal band-pass temporal filters suitable for use in energy- and phase-based algorithms for image motion computation. It is shown that the filters' temporal frequency tuning curves fit psychophysical estimates of the temporal properties of human visual filters [Hess RF, Snowden RJ (1992) Vision Res 32: 47–60]. Received: 20 April 1999 /Accepted in revised form: 8 November 1999     

An ASIC-chip for stereoscopic depth analysis in video-real-time based on visual cortical cell behavior

In a stereoscopic system both eyes or cameras have a slightly different view. As a consequence small variations between the projected images exist ("disparities") which are spatially evaluated in order to retrieve depth information. We will show that two related algorithmic versions can be designed which recover disparity. Both approaches are based on the comparison of filter outputs from filtering the left and the right image. The difference of the phase components between left and right filter responses encodes the disparity. One approach uses regular Gabor filters and computes the spatial phase differences in a conventional way as described already in 1988 by Sanger. Novel to this approach, however, is that we formulate it in a way which is fully compatible with neural operations in the visual cortex. The second approach uses the apparently paradoxical similarity between the analysis of visual disparities and the determination of the azimuth of a sound source. Animals determine the direction of the sound from the temporal delay between the left and right ear signals. Similarly, in our second approach we transpose the spatially defined problem of disparity analysis into the temporal domain and utilize two resonators implemented in the form of causal (electronic) filters to determine the disparity as local temporal phase differences between the left and right filter responses. This approach permits video real-time analysis of stereo image sequences (see movies at http://www.neurop.ruhr-uni-bochum.de/Real- Time-Stereo) and a FPGA-based PC-board has been developed which performs stereo-analysis at full PAL resolution in video real-time. An ASIC chip will be available in March 2000.     

Hybrid filtering to rescue stable oscillations from noise-induced chaos in continuous cultures of budding yeast

In large-scale fermentations with oscillating microbial cultures, noise is commonly present in the feed stream(s). As this can destabilize the oscillations and even generate chaotic behavior, noise filters are employed. Here three types of filters were compared by applying them to a noise-affected continuous culture of Saccharomyces cerevisiae with chaotic oscillations. The aim was to restore the original noise-free stable oscillations. An extended Kalman filter was found to be the least efficient, a neural filter was better and a combined hybrid filter was the best. In addition, better filtering of noise was achieved in the dilution rate than in the oxygen mass transfer coefficient. These results suggest the use of hybrid filters with the dilution rate as the manipulated variable for bioreactor control.     

Evaluation of Argos Telemetry Accuracy in the High-Arctic and Implications for the Estimation of Home-Range Size

Animal tracking through Argos satellite telemetry has enormous potential to test hypotheses in animal behavior, evolutionary ecology, or conservation biology. Yet the applicability of this technique cannot be fully assessed because no clear picture exists as to the conditions influencing the accuracy of Argos locations. Latitude, type of environment, and transmitter movement are among the main candidate factors affecting accuracy. A posteriori data filtering can remove “bad” locations, but again testing is still needed to refine filters. First, we evaluate experimentally the accuracy of Argos locations in a polar terrestrial environment (Nunavut, Canada), with both static and mobile transmitters transported by humans and coupled to GPS transmitters. We report static errors among the lowest published. However, the 68^th error percentiles of mobile transmitters were 1.7 to 3.8 times greater than those of static transmitters. Second, we test how different filtering methods influence the quality of Argos location datasets. Accuracy of location datasets was best improved when filtering in locations of the best classes (LC3 and 2), while the Douglas Argos filter and a homemade speed filter yielded similar performance while retaining more locations. All filters effectively reduced the 68^th error percentiles. Finally, we assess how location error impacted, at six spatial scales, two common estimators of home-range size (a proxy of animal space use behavior synthetizing movements), the minimum convex polygon and the fixed kernel estimator. Location error led to a sometimes dramatic overestimation of home-range size, especially at very local scales. We conclude that Argos telemetry is appropriate to study medium-size terrestrial animals in polar environments, but recommend that location errors are always measured and evaluated against research hypotheses, and that data are always filtered before analysis. How movement speed of transmitters affects location error needs additional research.     

Matched filtering in motion detection and discrimination

When humans detect and discriminate visual motion, some neural mechanism extracts the motion information that is embedded in the noisy spatio-temporal stimulus. We show that an ideal mechanism in a motion discrimination experiment cross-correlates the received waveform with the signals to be discriminated. If the human visual system uses such a cross-correlator mechanism, discrimination performance should depend on the cross-correlation between the two signals. Manipulations of the signals' cross-correlation using differences in the speed and phase of moving gratings produced the predicted changes in the performance of human observers. The cross-correlator's motion performance improves linearly as contrast increases and human performance is similar. The ideal cross-correlator can be implemented by passing the stimulus through linear spatio-temporal filters matched to the signals. We propose that directionally selective simple cells in the striate cortex serve as matched filters during motion detection and discrimination.     

Spike-Triggered Covariance Analysis Reveals Phenomenological Diversity of Contrast Adaptation in the Retina

When visual contrast changes, retinal ganglion cells adapt by adjusting their sensitivity as well as their temporal filtering characteristics. The latter has classically been described by contrast-induced gain changes that depend on temporal frequency. Here, we explored a new perspective on contrast-induced changes in temporal filtering by using spike-triggered covariance analysis to extract multiple parallel temporal filters for individual ganglion cells. Based on multielectrode-array recordings from ganglion cells in the isolated salamander retina, we found that contrast adaptation of temporal filtering can largely be captured by contrast-invariant sets of filters with contrast-dependent weights. Moreover, differences among the ganglion cells in the filter sets and their contrast-dependent contributions allowed us to phenomenologically distinguish three types of filter changes. The first type is characterized by newly emerging features at higher contrast, which can be reproduced by computational models that contain response-triggered gain-control mechanisms. The second type follows from stronger adaptation in the Off pathway as compared to the On pathway in On-Off-type ganglion cells. Finally, we found that, in a subset of neurons, contrast-induced filter changes are governed by particularly strong spike-timing dynamics, in particular by pronounced stimulus-dependent latency shifts that can be observed in these cells. Together, our results show that the contrast dependence of temporal filtering in retinal ganglion cells has a multifaceted phenomenology and that a multi-filter analysis can provide a useful basis for capturing the underlying signal-processing dynamics.     

视觉运动图象滤波模型及其实时模拟

在充满生存竞争的动物世界,视觉的伪装与反伪装现象随处可见,视觉反伪装的原理是什么？本文对Ｒｅｉｃｈａｒｄｔ的图形－背景相对运动分辨模型加以发展,提出了视觉反伪装功能的运动图象滤波器模型。为了检验此模型,我们建立了一个生物学似真的实时运动信息加工神经网络电子装置,实现了实时、高分辨运动目标图象滤波。与Ｍｅａｄ的人工视网膜的运动目标图象检测功能相比,检测的运动目标图象的分辨率有很大提高,而噪声水平显著降低,克服了人工视网膜的一些局限性。     

The importance of optical optimization in whole slide imaging (WSI) and digital pathology imaging

In the last 10 years, whole slide imaging (WSI) has seen impressive progress not only in image quality and scanning speed but also in the variety of systems available to pathologists. However, we have noticed that most systems have relatively simple optics axes and rely on software to optimize image quality and colour balance. While much can be done in software, this study examines the importance of optics, in particular optical filters, in WSI.Optical resolution is a function of the wavelength of light used and the numerical aperture of the lens system (Resolution = (f) wavelength/2 NA). When illumining light is not conditioned correctly with filters, there is a tendency for the wavelength to shift to longer values (more red) because of the characteristics of the lamps in common use. Most microscopes (but remarkably few WSI devices) correct for this with ND filter for brightness and Blue filter (depends on the light source) for colour correction.Using H&E slides research microscopes (Axiophot, Carl Zeiss MicroImaging, Inc. NY. Eclipse 50i., Nikon Inc. NY) at 20x, an attached digital camera (SPOT RT741 Slider Color, Diagnosis Instruments., MI USA), and a filter set, we examined the effect of filters and software enhancement on digital image quality. The focus value (as evaluated by focus evaluation software developed in house and SPOT imaging Software v4.6) was used as a proxy for image quality. Resolution of tissue features was best with the use of both the Blue and ND filters (in addition to software enhancement). Images without filters but with software enhancement while superficially good, lacked some details of specimen morphology and were unclear compared with the images with filters.The results indicate that the appropriate use of optical filters could measurably improve the appearance and resolution of WSI images.     

Development and application of new positively charged filters for recovery of bacteriophages from water

Electronegative and electropositive filters were compared for the recovery of indigenous bacteriophages from water samples, using the VIRADEL technique. Fiber glass and diatomaceous earth filters displayed low adsorption and recovery, but an important increase of the adsorption percentage was observed when the filters were treated with cationic polymers (about 99% adsorption). A new methodology of virus elution was developed in this study, consisting of the slow passage of the eluent through the filter, thus increasing the contact time between eluent and virus adsorbed on the filters. The use of this technique allows a maximum recovery of 71.2% compared with 46.7% phage recovery obtained by the standard elution procedure. High percentages (over 83%) of phage adsorption were obtained with different filters from 1-liter aliquots of the samples, except for Virosorb 1-MDS filters (between 1.6 and 32% phage adsorption). Phage recovery by using the slow passing of the eluent depended on the filter type, with recovery ranging between 1.6% for Virosorb 1-MDS filters treated with polyethyleneimine and 103.2% for diatomaceous earth filters treated with 0.1% Nalco.     

A model of time estimation and error feedback in predictive timing behavior

Two key features of sensorimotor prediction are preprogramming and adjusting of performance based on previous experience. Oculomotor tracking of alternating visual targets provides a simple paradigm to study this behavior in the motor system; subjects make predictive eye movements (saccades) at fast target pacing rates (>0.5 Hz). In addition, the initiation errors (latencies) during predictive tracking are correlated over a small temporal window (correlation window) suggesting that tracking performance within this time range is used in the feedback process of the timing behavior. In this paper, we propose a closed-loop model of this predictive timing. In this model, the timing between movements is based on an internal estimation of stimulus timing (an internal clock), which is represented by a (noisy) signal integrated to a threshold. The threshold of the integrate-to-fire mechanism is determined by the timing between movements made within the correlation window of previous performance and adjusted by feedback of recent and projected initiation error. The correlation window size increases with repeated tracking and was estimated by two independent experiments. We apply the model to several experimental paradigms and show that it produces data specific to predictive tracking: a gradual shift from reaction to prediction on initial tracking, phase transition and hysteresis as pacing frequency changes, scalar property, continuation of predictive tracking despite perturbations, and intertrial correlations of a specific form. These results suggest that the process underlying repetitive predictive motor timing is adjusted by the performance and the corresponding errors accrued over a limited time range and that this range increases with continued confidence in previous performance.     

Development and application of new positively charged filters for recovery of bacteriophages from water.

Electronegative and electropositive filters were compared for the recovery of indigenous bacteriophages from water samples, using the VIRADEL technique. Fiber glass and diatomaceous earth filters displayed low adsorption and recovery, but an important increase of the adsorption percentage was observed when the filters were treated with cationic polymers (about 99% adsorption). A new methodology of virus elution was developed in this study, consisting of the slow passage of the eluent through the filter, thus increasing the contact time between eluent and virus adsorbed on the filters. The use of this technique allows a maximum recovery of 71.2% compared with 46.7% phage recovery obtained by the standard elution procedure. High percentages (over 83%) of phage adsorption were obtained with different filters from 1-liter aliquots of the samples, except for Virosorb 1-MDS filters (between 1.6 and 32% phage adsorption). Phage recovery by using the slow passing of the eluent depended on the filter type, with recovery ranging between 1.6% for Virosorb 1-MDS filters treated with polyethyleneimine and 103.2% for diatomaceous earth filters treated with 0.1% Nalco.     

Voluntary stepping behavior under single- and dual-task conditions in chronic stroke survivors: A comparison between the involved and uninvolved legs

ObjectiveIf balance is lost, quick step execution can prevent falls. Research has shown that speed of voluntary stepping was able to predict future falls in old adults. The aim of the study was to investigate voluntary stepping behavior, as well as to compare timing and leg push-off force–time relation parameters of involved and uninvolved legs in stroke survivors during single- and dual-task conditions. We also aimed to compare timing and leg push-off force–time relation parameters between stroke survivors and healthy individuals in both task conditions.MethodsTen stroke survivors performed a voluntary step execution test with their involved and uninvolved legs under two conditions: while focusing only on the stepping task and while a separate attention-demanding task was performed simultaneously. Temporal parameters related to the step time were measured including the duration of the step initiation phase, the preparatory phase, the swing phase, and the total step time. In addition, force–time parameters representing the push-off power during stepping were calculated from ground reaction data and compared with 10 healthy controls.ResultsThe involved legs of stroke survivors had a significantly slower stepping time than uninvolved legs due to increased swing phase duration during both single- and dual-task conditions. For dual compared to single task, the stepping time increased significantly due to a significant increase in the duration of step initiation. In general, the force time parameters were significantly different in both legs of stroke survivors as compared to healthy controls, with no significant effect of dual compared with single-task conditions in both groups.ConclusionsThe inability of stroke survivors to swing the involved leg quickly may be the most significant factor contributing to the large number of falls to the paretic side. The results suggest that stroke survivors were unable to rapidly produce muscle force in fast actions. This may be the mechanism of delayed execution of a fast step when balance is lost, thus increasing the likelihood of falls in stroke survivors.