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A model of frequency discrimination with optimal processing of auditory nerve spike intervals.

This paper investigates phase-lock coding of frequency in the auditory system. One objective with the current model was to construct an optimal central estimation mechanism able to extract frequency directly from spike trains. The model bases estimates of the stimulus frequency on inter-spike intervals of spike trains phase-locked to a pure tone stimulus. Phase-locking is the tendency of spikes to cluster around multiples of the stimulus period. It is assumed that these clusters have Gaussian distributions with variance that depends on the amount of phase-locking. Inter-spike intervals are then noisy measurements of the actual period of the stimulus waveform. The problem of estimating frequency from inter-spike intervals can be solved optimally with a Kalman filter. It is shown that the number of inter-spike intervals observed in the stimulus interval determines frequency discrimination at low frequencies, while the variance of spike clusters dominates at higher frequencies. Timing information in spike intervals is sufficient to account for human frequency discrimination performance up to 5000 Hz. When spikes are available on each stimulus cycle, the model can accurately predict frequency discrimination thresholds as a function of frequency, intensity and duration.

Acoustic Stimulation↗

Variations in backward masking with different masking stimuli: II. The effects of spatially quantised masks in the light of local contour interaction, interchannel inhibition, perceptual retouch, and substitution theories.

In part I we showed that with spatially non-overlapping targets and masks both local metacontrast-like interactions and attentional processes are involved in backward masking. In this second part we extend the strategy of varying the contents of masks to pattern masking where targets and masks overlap in space, in order to compare different masking theories. Images of human faces were backward-masked by three types of spatially quantised masks (the same faces as targets, faces different from targets, and Gaussian noise with power spectra typical for faces). Configural characteristics, rather than the spectral content of the mask, predicted the extent of masking at relatively long stimulus onset asynchronies (SOAs). This poses difficulties for the theory of transient-on-sustained inhibition as the principal mechanism of masking and also for local contour interaction being a decisive factor in pattern masking. The scale of quantisation had no effect on the masking capacity of noise masks and a strong effect on the capacity of different-face masks. Also, the decrease of configural masking with an increase in the coarseness of the quantisation of the mask highlights ambiguities inherent in the re-entrance-based substitution theory of masking. Different masking theories cannot solve the problems of masking separately. They should be combined in order to create a complex, yet comprehensible mode of interaction for the different mechanisms involved in visual backward masking.

Attention↗

A parametric family of correlation structures for the analysis of longitudinal data.

In epidemiological settings, we are often faced with numerous short time series, and a parsimonious parametrization of the correlation structure is desired in order to optimize the efficiency of the estimation procedure. We propose a damped exponential correlation structure for modeling multivariate Gaussian outcomes. The correlation between two observations separated by s units of time is modeled as gamma s theta, where gamma is the correlation between elements separated by one s-unit, and theta is a damping parameter. For (theta = 0), (theta = 1), and theta----infinity), the correlation structures of compound symmetry, first-order autoregressive, and first-order moving average processes are obtained. Although the AR(2) dependency structure, and the combination of random effects and AR(1) errors are not special cases of the proposed parametric family, these structures can be well approximated within the family for short time series. Maximum likelihood methods for parameter estimation and interpretations of intermediate models (0 less than theta less than 1) are discussed in the context of modeling pulmonary function in an adult population in The Netherlands and T-cell subsets in homosexual men infected with human immunodeficiency virus Type I.

Adult↗

[Quantitative processing of results of uniparametric fluorescent flow analysis of human chromosomes].

The proposed procedure of computer analysis of the flow karyotype data, obtained in human chromosomes studies, is able to provide information about the basic parameters of the karyotypes: the positions of the peaks (corresponding to the relative size of chromosomes), peaks areas (relative number of chromosomes in the sample), coefficients of variation (CV) of the peaks--possible differences between homologous chromosomes. The analysis is based on the assumption that all chromosomal components of the experimental distributions are normal (Gaussians). The algorithm of the analysis uses a combination of two approaches: truncation method and least squares method. As the flow data are "contaminated" by background components, special tools for filtering off the contaminating signals were designed including the original integral Fourier filtering procedure. This analysis is realized in a program package utilizing IBM-compatible PCs. The user is able to get the desired parameters for most chromosomes of the karyotype under study from univariate flow data: differences between particular homologous chromosomes, presence of chromosome aberrations, extra chromosomes, etc., since structural aberrations and chromosome number variation lead to specific changes of the parameters of chromosome-related components.

Algorithms↗

Glycoforms of beta-lactoglobulin with improved thermostability and preserved structural packing.

In this article we show how various degrees of glycosylation can be used to control the thermal stability of proteins. The primary amines of beta-lactoglobulin were glycosylated with glucose or fructose within a range of non-denaturing reaction parameters. The modified fractions were characterized and analyzed for structural stability and hydrophobic exposure. The modification procedure gave rise to the production of glycoproteins with a well-defined Gaussian distribution, where glucose appeared more reactive than fructose. The integrity of the secondary, tertiary, and quaternary structures remained unaffected by the modification procedure. However, upon heating the stability of the modified fractions increased up to 6 K. Here we demonstrate the effects on the thermodynamic properties of proteins by glycosylation; this work serves as a first step in understanding and controlling the process underlying aggregation of glycosylated proteins.

Fructose↗

Derivation of a microscopic theory of barriers and activated hopping transport in glassy liquids and suspensions.

A recently proposed microscopic activated barrier hopping theory [K. S. Schweizer and E. J. Saltzman, J. Chem. Phys. 119, 1181 (2003)] of slow single-particle dynamics in glassy liquids, suspensions, and gels is derived using nonequilibrium statistical mechanics. Fundamental elements underlying the stochastic nonlinear Langevin equation description include an inhomogeneous liquid or locally solid-state perspective, dynamic density-functional theory (DDFT), a local equilibrium closure, and a coarse-grained free-energy functional. A dynamic Gaussian approximation is not adopted which is the key for avoiding a kinetic ideal glass transition. The relevant excess free energy is of a nonequilibrium origin and is related to dynamic force correlations in the fluid. The simplicity of the approach allows external perturbations to be rather easily incorporated. Dynamic heterogeneity enters naturally via mobility fluctuations associated with the stochastic barrier-hopping process. The derivation both identifies the limitations of the theory and suggests new avenues for its systematic improvement. Comparisons with ideal mode-coupling theory, alternative DDFT approaches and a field theoretic path-integral formulation are presented.

Journal Article↗

Field statistics of two vectorially superposed wave populations.

Field statistics of observed waves and radiation constrain the physics of the emission process and source region. However, data often contain two or more superposed signals or a signal superposed on a noise background, creating difficulties for interpretation. Here, the combined probability distribution of the field formed by vector superposition of two signals, each with specified statistics, is written as a double integral with integrable singularities. The analytic result and its numerical solutions for combinations of Gaussian and lognormally distributed signals show that these predictions differ from those for field or intensity convolution and from the individual wave distributions. At high fields, the combined distribution takes the qualitative form of the dominant individual distribution (which is localized or otherwise extends to larger fields) but develops a significant tail at low fields due to vector superposition of almost antiparallel fields with similar magnitudes. It is shown that very nearly power-law distributions can develop in significant field domains, despite neither component distribution being power law. This is relevant to alternative interpretations in terms of self-organized criticality and certain modulational wave instabilities. The formalism is then applied to observations of the Vela pulsar, resulting in greatly improved fits to data and different interpretations. Specifically, the results are strong evidence that stochastic growth theory (SGT) is relevant and that the approximate power-law statistics found at some phases are not intrinsic but rather due to vector convolution of a Gaussian background with a lognormal; the latter is interpretable in terms of SGT. The field statistics are consistent with the emission mechanism being a direct linear instability or indirect generation via linear mode conversion of nonescaping waves driven by a linear instability. They are inconsistent with nonlinear self-focusing instabilities generating the observed pulsar radiation. This formalism and its results should also be widely applicable to other types of wave growth in inhomogeneous media.

Journal Article↗

The high-mosaicity illusion: revealing the true physical characteristics of macromolecular crystals.

Typical measurements of macromolecular crystal mosaicity are dominated by the characteristics of the X-ray beam and as a result the mosaicity value given during data processing can be an artifact of the instrumentation rather than the sample. For physical characterization of crystals, an experimental system and software have been developed to simultaneously measure the diffraction resolution and mosaic spread of macromolecular crystals. The contributions of the X-ray beam to the reflection angular widths were minimized by using a highly parallel, highly monochromatic synchrotron source. Hundreds of reflection profiles over a wide resolution range were rapidly measured using a charge-coupled device (CCD) area detector in combination with superfine phi-slicing data collection. The Lorentz effect and beam contributions were evaluated and deconvoluted from the recorded data. Data collection and processing is described. From 1 degrees of superfine phi-slice data collected on a crystal of manganese superoxide dismutase, the mosaicities of 260 reflections were measured. The average mosaicity was 0.0101 degrees (s.d. 0.0035 degrees ) measured as the full-width at half-maximum (FWHM) and ranged from 0.0011 to 0. 0188 degrees. Each reflection profile was individually fitted with two Gaussian profiles, with the first Gaussian contributing 55% (s.d. 9%) and the second contributing 35% (s.d. 9%) of the reflection. On average, the deconvoluted width of the first Gaussian was 0.0054 degrees (s.d. 0.0015 degrees ) and the second was 0.0061 degrees (s. d. 0.0023 degrees ). The mosaicity of the crystal was anisotropic, with FWHM values of 0.0068, 0.0140 and 0.0046 degrees along the a, b and c axes, respectively. The anisotropic mosaicity analysis indicates that the crystal is most perfect in the direction that corresponds to the favored growth direction of the crystal.

Crystallography, X-Ray↗

Superresolution and convergence properties of the expectation-maximization algorithm for maximum-likelihood deconvolution of incoherent images.

Computational optical-sectioning microscopy with a nonconfocal microscope is fundamentally limited because the optical transfer function, the Fourier transform of the point-spread function, is exactly zero over a conic region of the spatial-frequency domain. Because of this missing cone of optical information, images are potentially artifactual. To overcome this limitation, superresolution, in the sense of band extrapolation, is necessary. I present a frequency-domain analysis of the expectation-maximization algorithm for maximum-likelihood image estimation that shows how the algorithm achieves this band extrapolation. This analysis gives the theoretical absolute bandwidth of the restored image; however, this absolute value may not be realistic in many cases. Then a second analysis is presented that assumes a Gaussian point-spread function and a specimen function and shows more realistic behavior of the algorithm and demonstrates some of its properties. Experimental results on the superresolving capability of the algorithm are also presented.

Algorithms↗

An automated diagnostic system for tubular carcinoma of the breast--an overview of approach and considerations.

A computer-based automated histopathology recognition system was developed to distinguish benign from malignant lesions. Tubular carcinoma of the breast, which has several reactive and neoplastic mimics, was selected as a model. Archival stained tumour sections from the United Kingdom National External Quality Assurance Scheme for breast pathology and supplementary material from external pathologists formed the study population. A diagnostic process similar to that employed by the histopathologist was adopted, viz, low-power feature extraction and analysis by cluster/glandular groupings followed by high-power confirmation. To circumvent problems of stain variability, greyscale quantisation of images was achieved through Karhunen-Loeve transformation with results suggesting that histological stains provide information primarily through contrast and not colour. Mean nearest neighbour and variance of cell nuclei distances were found to be 100% effective in distinguishing images which contained diffuse tumour, and no clustering. Gaussian smoothing followed by minimum variance quantisation allowed segmentation of gland clusters. Perona-Malik nonlinear diffusion filter employed prior to intensity thresholding and morphological filtering was 92% (7330/7973) effective in segmenting individual glands. In a set of 62 benign and 52 malignant gland clusters, the features found to discriminate tubular carcinoma from benign conditions included > 20% of glands with sharp-angled edge, cluster area > 150,000 pixels, ratio total gland area:total cluster area < 0.14, > 60 glands per cluster and the ratio average malignant gland area:benign gland area < 0.5. Suspicious clusters were subjected to high-power feature analysis for nuclear morphology, nucleoli detection and basement membrane assessment. Watershed thresholding achieved nuclear segmentation and nuclear area > 1.3x mean benign nuclear area was found to have a malignant likelihood ratio of 14.5. Progressive thresholding was used to detect nucleoli. Basement membrane was accentuated by colour segmentation and demonstrated 0.96 sensitivity, 0.89 specificity and 0.92 positive predictive value for distinguishing malignancy.

Adenocarcinoma↗

Monitoring change in the three-dimensional shape of the human left ventricle.

BACKGROUND: Characterizing left ventricular (LV) remodeling after myocardial infarction or LV shape change resulting from LV shape-restoration operation can yield valuable prognostic information. However, current methods measure only global parameters of LV shape. METHODS: We developed and validated a method for measuring change in regional LV shape by aligning a patient's follow-up 3-dimensional LV surface reconstruction to baseline surface. We tested the diagnostic power of 6 distance functions to detect a known shape deformation. To create the test data, the LV endocardial surface of a control subject was reconstructed using 3-dimensional echocardiographic techniques. The surface was deformed 9 different ways to model LV dilation (3 different locations and severities). Normal shape variability was defined from 18 serial studies of 6 control subjects. The severity of regional dilation was computed as the orthogonal distance between the aligned baseline and deformed LV surfaces. Deformation was quantified according to regional location using the 16-segment map of the LV. RESULTS: Normal LV shape variability was 3.38 mm. The LV deformations ranged from 2.95 to 8.02 mm. Gaussian distance function produced the highest accuracy for measuring deformation distances (P <.005 by analysis of variance). In addition, the gaussian function correctly identified the location of the maximum deformation in 6 of the 9 distorted surfaces. In the 3 remaining surfaces, the gaussian alignment selected an adjacent basal segment with a similar deformation distance (mean error: 0.2 +/- 0.17 mm). The gaussian function's accuracy in pinpointing the deformation equaled or exceeded the performance of the other 5 functions tested. CONCLUSION: This new method of aligning 3-dimensional LV surfaces in space facilitates detecting, measuring, and localizing regional shape change in the human LV independent of anatomic landmarks or geometric references. Potential applications include quantitative monitoring of change in regional LV shape after a pathologic process and/or surgical procedure to document efficacy of treatment and to assess prognosis.

Echocardiography, Three-Dimensional↗

Atmospheric dispersion and deposition of 131I released from the Hanford Site.

Approximately 2.6 x 10(4) TBq (700,000 Ci) of 131I were released to the air from reactor fuel processing plants on the Hanford Site in southcentral Washington State from December 1944 through December 1949. The Hanford Environmental Dose Reconstruction Project developed a suite of codes to estimate the doses that might have resulted from these releases. The Regional Atmospheric Transport Code for Hanford Emission Tracking (RATCHET) computer code is part of this suite. The RATCHET code implements a Lagrangian-trajectory, Gaussian-puff dispersion model that uses hourly meteorological and release rate data to estimate daily time-integrated air concentrations and surface contamination for use in dose estimates. In this model, iodine is treated as a mixture of three species (inorganic gases, organic gases, and particles). Model deposition parameters are functions of the mixture and meteorological conditions. A resistance model is used to calculate dry deposition velocities. Equilibrium between concentrations in the precipitation and the air near the ground is assumed in calculating wet deposition of gases, and irreversible washout of the particles is assumed. RATCHET explicitly treats the uncertainties in model parameters and meteorological conditions. Uncertainties in 131I release rates and partitioning among the nominal species are treated by varying model input. The results of 100 model runs for December 1944 through December 1949 indicate that monthly average air concentrations and deposition have uncertainties ranging from a factor of two near the center of the time-integrated plume to more than an order of magnitude near the edge. These results indicate that approximately 10% of the 131I released to the atmosphere decayed during transit in the study area, approximately 56% was deposited within the study area, and the remaining 34% was transported out of the study area while still in the air.

Air Pollutants, Radioactive↗

Correlation between time functions of sound pressure, masking, and OAE suppression.

Periodic sound-pressure time functions with frequency components below 50 Hz were used to measure within their period (a) the temporal course of masking, called a masking-period pattern (MPP), and (b) the temporal course of suppression of delayed evoked otoacoustic emissions, called a suppression-period pattern (SPP). Three different time functions were used: an alternating Gaussian impulse, its first integral, and its second integral. In each case, the course of the SPP is a mirror image of that of the MPP: Small masking corresponds to small suppression, while strong masking coincides with almost total suppression. Since otoacoustic emissions are assumed to have their origin in the inner ear, it can be argued that simultaneous masking, an effect including central processing, is very strongly based on peripheral processes located in the cochlea. Both MPP and SPP are closely related to the second derivative of the sound-pressure time function.

Humans↗

Beam shaping of focused partially coherent beams by use of the spatial coherence effect.

We demonstrate that when a partially coherent beam with a Gaussian intensity distribution is focused by a lens, the desired partially coherent flat-topped intensity distribution or doughnut-shaped intensity distribution at the geometrical focus can be generated by choice of appropriate form of spectral degree of coherence. We provide a novel approach to beam shaping of a partially coherent beam and offer new schemes for their potential applications such as material processing, optical therapy, and optical tweezers.

Journal Article↗

Using serial imaging data to model variabilities in organ position and shape during radiotherapy.

A model is proposed for incorporating the effects of organ motion into the calculation of dose in a statistical fashion based on serial imaging measurements of organ motion. These measurements can either come from a previously studied population of patients, or they can be specific to the particular patient undergoing therapy. The statistical distribution underlying the measurements of organ motion, including the changes in organ shape, is reconstructed non-parametrically without requiring any assumptions about its functional form. The model is thus capable of simulating organ motions that are not present in the original measurements, yet nonetheless come from the same underlying statistical distribution. The present model overcomes two particular limitations of many organ motion models: (a) the fact that they do not account for changes in organ shape, and (b) the fact that they make physically unrealistic assumptions about the functional form of the statistical distribution of organ motion, such as assuming that it is Gaussian. The present model can form the foundation of methods for the more accurate and clinically relevant calculation of the dose to the target volume and normal tissues.

Algorithms↗

Noise adaptation in integrate-and fire neurons.

The statistical spiking response of an ensemble of identically prepared stochastic integrate-and-fire neurons to a rectangular input current plus gaussian white noise is analyzed. It is shown that, on average, integrate-and-fire neurons adapt to the root-mean-square noise level of their input. This phenomenon is referred to as noise adaptation. Noise adaptation is characterized by a decrease in the average neural firing rate and an accompanying decrease in the average value of the generator potential, both of which can be attributed to noise-induced resets of the generator potential mediated by the integrate-and-fire mechanism. A quantitative theory of noise adaptation in stochastic integrate-and-fire neurons is developed. It is shown that integrate-and-fire neurons, on average, produce transient spiking activity whenever there is an increase in the level of their input noise. This transient noise response is either reduced or eliminated over time, depending on the parameters of the model neuron. Analytical methods are used to prove that nonleaky integrate-and-fire neurons totally adapt to any constant input noise level, in the sense that their asymptotic spiking rates are independent of the magnitude of their input noise. For leaky integrate-and-fire neurons, the long-run noise adaptation is not total, but the response to noise is partially eliminated. Expressions for the probability density function of the generator potential and the first two moments of the potential distribution are derived for the particular case of a nonleaky neuron driven by gaussian white noise of mean zero and constant variance. The functional significance of noise adaptation for the performance of networks comprising integrate-and-fire neurons is discussed.

Acclimatization↗

Some quantitative hemispheric EEG measures reflecting the affective profile of students differing in university academic success.

Quantitative measurements of the integrated epoch based EEG amplitudes obtained from two groups of university students differing in academic success during an eyes close, relaxed state revealed significantly higher right/left amplitude variance ratios and more right hemispheric non-Gaussian cumulated amplitude distributions among unsuccessful students. These data, which resemble patterns often found in depression, are consistent with, and appear to reflect specific affective differences that emerge using a concurrently administered, conventional psychometric inventory (Beck Depression Inventory) as well as a subjective self-assessment questionnaire. The results of this study may be useful in further elaborating the nature in which right hemispheric brain processes serve to mediate affective behavior, as well as influence academic performance.

Achievement↗

Dynamics of the ganglion cell response in the catfish and frog retinas.

Responses were evoked from ganglion cells in catfish and frog retinas by a Gaussian modulation of the mean luminance. An algorithm was devised to decompose intracellularly recorded responses into the slow and spike components and to extract the time of occurrence of a spike discharge. The dynamics of both signals were analyzed in terms of a series of first-through third-order kernels obtained by cross-correlating the slow (analog) or spike (discrete or point process) signals against the white-noise input. We found that, in the catfish, (a) the slow signals were composed mostly of postsynaptic potentials, (b) their linear components reflected the dynamics found in bipolar cells or in the linear response component of type-N (sustained) amacrine cells, and (c) their nonlinear components were similar to those found in either type-N or type-C (transient) amacrine cells. A comparison of the dynamics of slow and spike signals showed that the characteristic linear and nonlinear dynamics of slow signals were encoded into a spike train, which could be recovered through the cross-correlation between the white-noise input and the spike (point process signals. In addition, well-defined spike correlates could predict the observed slow potentials. In the spike discharges from frog ganglion cells, the linear (or first-order) kernels were all inhibitory, whereas the second-order kernels had characteristics of on-off transient excitation. The transient and sustained amacrine cells similar to those found in catfish retina were the sources of the nonlinear excitation. We conclude that bipolar cells and possibly the linear part of the type-N cell response are the source of linear, either excitatory or inhibitory, components of the ganglion cell responses, whereas amacrine cells are the source of the cells' static nonlinearity.

Animals↗