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Genetics supersedes epigenetics in colon cancer phenotype.

A CpG island DNA methylator phenotype has been postulated to explain silencing of the hMLH1 DNA mismatch repair gene in cancer of the microsatellite mutator phenotype. To evaluate this model, we analyzed methylation in CpG islands from six mutator and suppressor genes, and thirty random genomic sites, in a panel of colorectal cancers. Tumor-specific somatic hypermethylation was a widespread age-dependent process that followed a normal Gaussian distribution. Because there was no discontinuity in methylation rate, our results challenge the methylator phenotype hypothesis and its hypothetical pathological underlying defect. We also show that the mutator phenotype dominates over the gradual accumulation of DNA hypermethylation in determining the genotypic features that govern the phenotypic peculiarities of colon cancer of the mutator pathway.

Adaptor Proteins, Signal Transducing↗

Efficient classical simulation of continuous variable quantum information processes.

We obtain sufficient conditions for the efficient simulation of a continuous variable quantum algorithm or process on a classical computer. The resulting theorem is an extension of the Gottesman-Knill theorem to continuous variable quantum information. For a collection of harmonic oscillators, any quantum process that begins with unentangled Gaussian states, performs only transformations generated by Hamiltonians that are quadratic in the canonical operators, and involves only measurements of canonical operators (including finite losses) and suitable operations conditioned on these measurements can be simulated efficiently on a classical computer.

Journal Article↗

Perceptuomotor bias in the imitation of steady-state vowels.

Previous studies suggest that speakers are systematically inaccurate, or biased, when imitating self-produced vowels. The direction of these biases in formant space and their variation may offer clues about the organization of the vowel perceptual space. To examine these patterns, three male speakers were asked to imitate 45 self-produced vowels that were systematically distributed in F1/F2 space. All three speakers showed imitation bias, and the bias magnitudes were significantly larger than those predicted by a model of articulatory noise. Each speaker showed a different pattern of bias directions, but the pattern was unrelated to the locations of prototypical vowels produced by that speaker. However, there were substantial quantitative regularities: (1) The distribution of imitation variability and bias magnitudes were similar for all speakers, (2) the imitation variability was independent of the bias magnitudes, and (3) the imitation variability (a production measure) was commensurate with the formant discrimination limen (a perceptual measure). These results indicate that there is additive Gaussian noise in the imitation process that independently affects each formant and that there are speaker-dependent and potentially nonlinguistic biases in vowel perception and production.

Adolescent↗

Vascular development, pulse pressure, and the mechanisms of hypertension.

For a given cardiac function, the cyclic blood pressure (BP) curve results from 2 different phenotypes: the mean arterial pressure (MAP), a steady component reflecting the resistance of the microvascular network, and pulse pressure (PP), another component corresponding to large artery stiffness and wave reflections. Around birth, cardiovascular (CV) survival is critically influenced by the coupling between the heart and thoracic aorta, and hence, the adequacy of the Windkessel function, the magnitude of aortic elastin accumulation and the PP level. The maturation of the aortic trunk and its branches results from adaptative mechanisms involving shear and tensile stress, with major potential consequences on heart rate control, transit of wave reflections, and coronary perfusion. An adequate optimization of the Windkessel function, and hence PP, diastolic coronary perfusion and CV survival needs a critical MAP level to be reached in each individual during the postnatal period. The achievement of this MAP level requires the development of multiple resistance segments of the microvascular network, particularly within the kidney. Translated in adult populations, this pathophysiological process gives rise to a Gaussian BP distribution, with individuals remaining in the same BP percentile from birth onward (BP tracking). We suggest that hypertension results from early developmental vascular mechanisms that direct BP toward the higher percentiles of the Gaussian distribution curve.

Aging↗

Eliminating background noise effect in micro-resolution particle image velocimetry.

A novel method is developed to improve the accuracy of micro-resolution particle image velocimetry (PIV) in microfluidics measurements. This method utilizes the Laplacian of Gaussian method and image-processing techniques to eliminate the background scattering noise. A high signal-to-noise ratio image has been obtained. This technique is especially suitable for improving micro-resolution PIV in micro, two-, or multiphase flow conditions, such as for submicron bubbly flow measurements in a microchannel. The method can easily be implemented with minimal modification of the conventional PlV system. The results of simulation and experiments demonstrated the feasibility of this, to our knowledge, new method.

Journal Article↗

Direct comparison of spatially normalized PET and SPECT scans in Alzheimer's disease.

UNLABELLED: Hexamethylpropyleneamine oxime (HMPAO) SPECT and 18F-FDG PET depict similar aspects of perfusion and metabolic abnormalities in Alzheimer's disease (AD), but the correspondence between them is not known in detail. We therefore used statistical parametric mapping to detect and compare abnormal brain areas objectively and quantitatively. METHODS: Twenty-six patients with probable AD (mean age +/- SD, 66 +/- 9 y; mean Mini-Mental State Examination score, 22.5 +/- 4.2) and 6 nondemented healthy volunteers (mean age, 63 +/- 11 y) were studied with HMPAO SPECT and 18F-FDG PET. All images underwent the same processing steps, including 12-mm gaussian smoothing, spatial normalization, and z transformation with respect to normal average and SD. Thresholding of z maps was used to detect abnormal voxels. RESULTS: The overall correlation between PET and SPECT across the entire brain was significant but not close (average r = 0.43). The best correspondence was found in the temporoparietal and posterior cingulate association cortices. There, the number of abnormal voxels for PET correlated strongly with the number for SPECT (r = 0.90 at a z threshold of -2.25), but tracer uptake reductions were significantly more pronounced for PET than for SPECT. Discordant findings were most frequently seen in the temporobasal and orbitofrontal areas (PET low, SPECT high) and in the cerebellum, parahippocampal cortex, and midcingulate cortex (PET high, SPECT low). The correlation between dementia severity and the number of abnormal voxels was closer for PET than for SPECT. Separation of patients from healthy volunteers by counting the number of abnormal voxels was possible over a much wider range of z thresholds with PET than with SPECT. CONCLUSION: Correspondence between 18F-FDG PET and HMPAO SPECT is limited to the main finding of temporoparietal and posterior cingulate functional impairment in mild to moderate AD. The distinction between healthy volunteers and patients is less sensitive to threshold selection with PET than with SPECT, and findings in the frontal, temporobasal, and temporomesial cortices and in the cerebellum may differ between the 2 techniques.

Aged↗

Proton MR spectroscopic characteristics of pediatric pilocytic astrocytomas.

PURPOSE: We report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy. METHODS: Eight children with pilocytic astrocytomas were studied with proton MR spectroscopy. The selected sampling volume was approximately 4 cm3, obtained from solid tumor. To localize the sampling volume, we used point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) techniques to acquire long- and short-TE spectra, respectively. Spectra from PRESS and STEAM sequences were processed using Lorentzian-to-Gaussian transformation and exponential apodization, respectively. For PRESS (2000/270) spectra, peaks of creatine, choline, N-acetylaspartate (NAA), and lactate resonances were integrated; for STEAM (2000/20) spectra, we measured the amplitude of the peaks at 3.2, 2.0, 1.3 and 0.9 ppm. RESULTS: An elevated lactate doublet was observed in the PRESS spectra. The choline/NAA ratio was 3.40. The amplitude ratios of the lipid pattern (0.9, 1.3 and 2.0 ppm) to choline were all below one. CONCLUSION: Despite the benign histology of the tumor, which generally lacks necrosis, a lactate signal was detected in all eight patients studied. A dominant lipid pattern was not observed.

Aspartic Acid↗

Solvable Markov random field model in color image restoration.

We propose a scheme for image restoration of full color images by means of a solvable probabilistic model in the red-green-blue space. A special case of our solvable probabilistic model is equivalent to a multicomponent Gaussian model in the statistical mechanics. Exact closed expressions of the evidence and the expectation value of intensity at each pixel in our solvable probabilistic model can be obtained by using multidimensional Gaussian integral formulas and a discrete Fourier transform. In the present paper, the degradation process is assumed to be an additive white Gaussian noise. Hyperparameters are determined so as to maximize the evidence that is expressed in terms of the partition function in our solvable probabilistic model. This work is a pioneering work for the Bayesian approach to the color image restoration by means of the statistical-mechanical technique.

Journal Article↗

Simulation of artificial vision, III: do the spatial or temporal characteristics of stimulus pixelization really matter?

PURPOSE: In preceding studies, simulations of artificial vision were used to determine the basic parameters for visual prostheses to restore useful reading abilities. These simulations were based on a simplified procedure to reduce stimuli information content by preprocessing images with a block-averaging algorithm (square pixelization). In the present study, how such a simplified algorithm affects reading performance was examined. METHODS: Five to six volunteers with normal vision were asked to read full pages of text with a 10 degrees x 7 degrees viewing window stabilized in central vision. In a first experiment, reading performance with off-line and real-time square pixelizations was compared at different resolutions. In a second experiment, off-line square pixelization was compared with off-line Gaussian pixelization with various degrees of overlap. In a third experiment, real-time square pixelization was compared with real-time Gaussian pixelization. RESULTS: Results from the first experiment showed that real-time square pixelization required approximately 30% less information (pixels) than its off-line counterpart. Results from the second experiment, using off-line processing, revealed a restricted range of Gaussian widths for which performances were equivalent or significantly better than that obtained with square pixelization. The third experiment demonstrated, however, that reading performances were similar in both real-time pixelization conditions. CONCLUSIONS: This study reveals that real-time stimulus pixelization favors reading performance. Performance gains were moderate, however, and did not allow for a significant (e.g., twofold) reduction of the minimum resolution (400-500 pixels) needed to achieve useful reading abilities.

Adult↗

The genetics of quantifiable homeostasis: I. The general issues.

Some fundamental issues in developing the quantitative genetics of heritable traits are addressed. Such a trait must be capable of being represented as a quantity. Choice of the metric can be satisfactorily made only in the light of some insight into the nature of the trait and what its revealing characteristics may be. This insight is likely to change as more is known about the process, so the form and detail of the analysis is not static but perhaps continually evolving. Much has been made out of sample means and, at a more sophisticated level, Galton-Fisher theory (the analysis of the first two moments of multivariate Gaussian variates). However, at least some processes seriously violate the assumptions underlying that theory. One such group comprises traits in which the means are unvarying and the genetic message lies in other aspects of the distribution; in these circumstances the standard summary statistics such as heritability, regression, and correlation may be totally uninformative, distracting, or even misleading. This paradox is illustrated by reference to homeostasis, where the Mendelian component lies, not in the mean, but in the degree of laxity of control. Since estimating higher moments is notoriously imprecise, the suggested remedy is the familial and commonsense one of exploring the genetics of the intermediate states and underlying mechanisms and not only that of the resultant ("bottom-line") phenotype. In our chosen problem, the task of relating the outcome to the basic mechanism of inheritance calls for a detailed understanding of the homeostasis involved.

Genetic Diseases, Inborn↗

Renyi entropy measures of heart rate Gaussianity.

Sample entropy and approximate entropy are measures that have been successfully utilized to study the deterministic dynamics of heart rate (HR). A complementary stochastic point of view and a heuristic argument using the Central Limit Theorem suggests that the Gaussianity of HR is a complementary measure of the physiological complexity of the underlying signal transduction processes. Renyi entropy (or q-entropy) is a widely used measure of Gaussianity in many applications. Particularly important members of this family are differential (or Shannon) entropy (q = 1) and quadratic entropy (q = 2). We introduce the concepts of differential and conditional Renyi entropy rate and, in conjunction with Burg's theorem, develop a measure of the Gaussianity of a linear random process. Robust algorithms for estimating these quantities are presented along with estimates of their standard errors.

Algorithms↗

A least-squares error minimization approach in the determination of ferric ion diffusion coefficient of Fricke-infused dosimeter gels.

A least-squares error minimization approach was adopted to assess ferric ion diffusion coefficient of Fricke-agarose gels. Ferric ion diffusion process was modeled as a Gaussian-shaped degradation kernel operating on an initial concentration distribution. Diffusion coefficient was iteratively determined by minimizing the error function defined as the difference between the theoretically calculated and the experimentally measured dose distributions. A rapid MR image-based differential gel dosimetry technique that time resolves the evolution of the ferric ion diffusion process minimizes smearing of the dose distribution. Our results showed that for a Fricke-agarose gel contained 1 mM ammonium ferrous sulfate, 1% agarose, 1 mM sodium chloride, and 50 mM sulfuric acid, its ferric ion diffusion coefficient is (1.59 +/- 0.28) x 10(-2) cm2 h(-1) at room temperature. This value falls within the 1.00-2.00 x 10(-2) cm2 h(-1) range previously reported under varying gelling ingredients and concentrations. This method allows a quick, nondestructive evaluation of the ferric ion diffusion coefficient that can be used in conjunction with the in situ gel dosimetry experiment to provide a practical diffusion characterization of the dosimeter gel.

Diffusion↗

Spiral CT image deblurring for cochlear implantation.

Cochlear implantation is the standard treatment for profound hearing loss. Preimplantation and postimplantation spiral computed tomography (CT) is essential in several key clinical and research aspects. The maximum image resolution with commercial spiral CT scanners is insufficient to define clearly anatomical features and implant electrode positions in the inner ear. In this paper, we develop an expectation-maximization (EM)-like iterative deblurring algorithm to achieve spiral CT image super-resolution for cochlear implantation, assuming a spatially invariant linear spiral CT system with a three-dimensional (3-D) separable Gaussian point spread function (PSF). We experimentally validate the 3-D Gaussian blurring model via phantom measurement and profile fitting. The imaging process is further expressed as convolution of an isotropic 3-D Gaussian PSF and a blurred underlying volumetric image. Under practical conditions, an oblique reconstructed section is approximated as convolution of an isotropic two-dimensional (2-D) Gaussian PSF and the corresponding actual cross section. The spiral CT image deblurring algorithm is formulated with sieve and resolution kernels for suppressing noise and edge artifacts. A typical cochlear cross section is used for evaluation, demonstrating a resolution gain up to 30%40% according to the correlation criterion. Physical phantoms, preimplantation and postimplantation patients are reconstructed into volumes of 0.1-mm cubic voxels. The patient images are digitally unwrapped along the central axis of the cochlea and the implanted electrode array respectively, then oblique sections orthogonal to the central axis formed. After deblurring, representation of structural features is substantially improved in all the cases.

Algorithms↗

Computed resolution and relative specific radioactivities of radiolabelled proteins synthesized by isolated gastric mucosal cells.

1. By radiolabelling, polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate and fluorography, more than 50 soluble proteins in the molecular-weight range 15000-100000 were shown to continue to be synthesized after cells had been isolated from rat gastric mucosa. 2. Densitometric measurements of stained gels and fluorographic films were processed by computer to resolve individual overlapping Gaussian peaks corresponding to the protein bands. 3. Comparison of resolved peak areas of radioactivity and staining showed certain bands to have characteristically high relative specific radioactivities. 4. The computer programs (in FORTRAN) permit the analysis of a single densitometric trace or the simultaneous comparison of a corresponding pair of densitometric records of stained gels, or of fluorographic films, or a combination. Central processing unit time is used economically. 5. The programs identify the Gaussian components that contribute to the records and estimate their means, standard deviations and enclosed areas. These estimates are improved by a piecewise iterative method that minimizes the errors between the calculated and the experimental data. 6. Relative specific radioactivities are calculated as the normalized ratio of the area of a fluorographic film peak and the area of the corresponding stained gel peak. The computer programs have been deposited as Supplementary Publication SUP 50094 (55 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1978) 169, 5.

Animals↗

Nonlinear prediction for Gaussian mixture image models.

Prediction is an essential operation in many image processing applications, such as object detection and image and video compression. When the images are modeled as Gaussian, the optimal predictor is linear and easy to obtain. However, image texture and clutter are often non-Gaussian, and, in such cases, optimal predictors are difficult to obtain. In this paper, we derive an optimal predictor for an important class of non-Gaussian image models, the block-based multivariate Gaussian mixture model. This predictor has a special nonlinear structure: it is a linear combination of the neighboring pixels, but the combination coefficients are also functions of the neighboring pixels, not constants. The efficacy of this predictor is demonstrated in object detection experiments where the prediction error image is used to identify "hidden" objects. Experimental results indicate that when the background texture is nonlinear, i.e., with fast-switching gray-level patches, it performs significantly better than the optimal linear predictor.

Algorithms↗

Vector-valued image regularization with PDEs: a common framework for different applications.

In this paper, we focus on techniques for vector-valued image regularization, based on variational methods and PDEs. Starting from the study of PDE-based formalisms previously proposed in the literature for the regularization of scalar and vector-valued data, we propose a unifying expression that gathers the majority of these previous frameworks into a single generic anisotropic diffusion equation. On one hand, the resulting expression provides a simple interpretation of the regularization process in terms of local filtering with spatially adaptive Gaussian kernels. On the other hand, it naturally disassembles any regularization scheme into the smoothing process itself and the underlying geometry that drives the smoothing. Thus, we can easily specialize our generic expression into different regularization PDEs that fulfill desired smoothing behaviors, depending on the considered application: image restoration, inpainting, magnification, flow visualization, etc. Specific numerical schemes are also proposed, allowing us to implement our regularization framework with accuracy by taking the local filtering properties of the proposed equations into account. Finally, we illustrate the wide range of applications handled by our selected anisotropic diffusion equations with application results on color images.

Algorithms↗

A statistical mechanical analysis of postural sway using non-Gaussian FARIMA stochastic models.

In this paper, postural sway is modeled using a fractional autoregressive integrated moving average (FARIMA) family of models: the center-of-pressure (COP) motion is viewed in terms of a self-similar, anti-persistent random-walk process, obtained by fractionally summating non-Gaussian random variables, whose correlation structure for small time lags is shaped by a linear time-invariant low-pass filter. The model parameters are: the strength of the stochastic driving, e.g., the root mean square (rms) value of the time-difference COP motion; the DC gain, damping ratio and natural frequency of the filter; the Hurst exponent, which measures the random-walk antipersistence magnitude. In the proposed modeling procedure, a graphical estimator for determining the Hurst exponent is cascaded to a method for matching autoregressive (AR) models to fractionally difference COP motion via higher order cumulants. The effect of the presence or absence of vision on the model parameter values is discussed with regard to data from experiments on healthy young adults.

Adult↗

Automatic segmentation of liver structure in CT images.

The segmentation and three-dimensional representation of the liver from a computed tomography (CT) scan is an important step in many medical applications, such as in the surgical planning for a living-donor liver transplant and in the automatic detection and documentation of pathological states. A method is being developed to automatically extract liver structure from abdominal CT scans using a priori information about liver morphology and digital image-processing techniques. Segmentation is performed sequentially image-by-image (slice-by-slice), starting with a reference image in which the liver occupies almost the entire right half of the abdomen cross section. Image processing techniques include gray-level thresholding, Gaussian smoothing, and eight-point connectivity tracking. For each case, the shape, size, and pixel density distribution of the liver are recorded for each CT image and used in the processing of other CT images. Extracted boundaries of the liver are smoothed using mathematical morphology techniques and B-splines. Computer-determined boundaries were compared with those drawn by a radiologist. The boundary descriptions from the two methods were in agreement, and the calculated areas were within 10%.

Biophysical Phenomena↗