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PubMed1993

Multiple alignment of sequences on parallel computers.

A software package that allows one to carry out multiple alignment of protein and nucleic acid sequences of almost unlimited length and number of sequences is developed on C-DAC parallel computer--a transputer-based machine. The farming approach is used for data parallelization. The speed gains are almost linear when the number of transputers is increased from 4 to 64. The software is used to carry out multiple alignment of 100 sequences each of alpha-chain and beta-chain of hemoglobin and 83 cytochrome c sequences. The signature sequence of cytochrome c was found to be PGTKMXF. The single parameter, multiple alignment score, S, has been used to categorize proteins in different subfamilies and groups.

Algorithms↗
PubMed1994

Performance assessment of coupled tests: the effects of statistical non-independence.

Limited to two-test associations (series and parallel schemes), the effects of statistical non-independence were studied through a mathematical approach and an experimentally-based evaluation. Both procedures were applied to results for total hormones and free fractions in euthyroid and dysthyroid subjects. Assuming independence, the sensitivity of combined tests was found to increase in parallel coupling, and to decrease, symmetrically, in series coupling, depending critically on the degree of between-test correlation and on the value of single test sensitivity (the opposite modifications obviously occur for specificity). A more complicated situation resulted for the predictive value of test associations, where a prediction based on a mathematical model was found not to be generally valid; in this case, calculations using the correct values of conditional probabilities of coupled tests seemingly remain the safest procedure.

Algorithms↗
PubMed1992

Limitations of Augustinsson plots.

The Augustinsson plot transforms the Michaelis-Menten equation by graphing velocity, v, as a function of velocity/substrate, v/s. The plot is linear with a negative slope for a single class of saturable sites and curvilinear for multiple classes of sites. Statistically, Augustinsson plots suffer from the limitation that there is no true independent variable. Experimental errors form a Gaussian distribution that rests neither parallel to the v axis nor v/s axis, but rather along a line emanating from the origin. Widening the range of s values produces increasingly large errors in the calculated Km and Vm values, especially when multiple sites are present. Exact data containing no error produces accurate constants using either the Michaelis-Menten or Augustinsson equation. With Km and Vm constants previously derived by fitting data with the statistically valid Michaelis-Menten equation, the Augustinsson plot may be used accurately to display multiple site data.

Algorithms↗
PubMedDate not supplied

Optimization of the dose delivery in a few field techniques using radiobiological objective functions.

A method for finding optimal primary fluence profiles for multiple field external beam radiation therapy techniques has been developed using a radiobiologically based objective function that quantifies the probability of achieving complication-free tumor control, P+. The objective function P+ has the valuable property of giving the highest possible dose to the tumor without causing severe damage to normal tissues at risk. This radiobiologically based objective function selects suitable dose levels but also takes into account the dose homogeneity in the target volume to the extent that it is not causing an excessive risk of local recurrence or damage to surrounding normal tissues. The biological parameters used can either be patient specific, as determined by a predictive assay on biopsy specimens, or taken from a library of radiobiological parameter values characteristic for different tissue types of a reference patient. In its present form the method can be used to determine the optimum incident photon fluence profiles for each beam. The method has been used to investigate for a given target volume a large number of combinations of beam entry directions to find the best beam orientations with respect to the probability of achieving complication-free tumor control. It is demonstrated that when nonuniform dose delivery is available it is unsuitable to combine parallel opposed beams in two-beam techniques and to a lesser extent also to use perpendicular beams. In two-beam techniques the best angle between the beams is generally in the 100 degrees-120 degrees range. The major symmetry characteristics of the P+ phase space for two-beam techniques are also identified. The method can easily be extended from two to three dimensions and noncoplanar geometry, but it is presented here in its two-dimensional form for clarity and speed of calculation.

Algorithms↗
PubMed1995

Computing with dynamic attractors in neural networks.

In this paper we report on some new architectures for neural computation, motivated in part by biological considerations. One of our goals is to demonstrate that it is just as easy for a neural net to compute with arbitrary attractors--oscillatory or chaotic--as with the more usual asymptotically stable fixed points. The advantages (if any) of such architectures are currently being investigated; but it seems reasonable that the much richer dynamics of recurrent networks, so obvious in recordings of brain activity, must be useful for something. On the other hand, the constraints of computing with biological wet-ware may make chaotic dynamics unavoidable in complex nervous systems. We hypothesize also that the as yet unrivaled capabilities of the human brain derive from an ability to integrate both analog intuitive pattern recognition operations, and digital symbolic logical operations at the ground level of its hardware. To investigate these possibilities, we have constructed a parallel distributed processing architecture inspired by the structure and dynamics of cerebral cortex. The construction assumes that cortex is a set of coupled associative memories with dynamic attractors. It is guided also by a particular concept of the physical structure required of macroscopic computational systems in general for reliable computation in the presence of noise. Our challenge is to accomplish real tasks that brains can do, using ordinary differential equations, in networks that are as faithful as possible to the known anatomy and dynamics of cortex.

Algorithms↗
PubMed1993

An evaluation of two methods of anatomical alignment of radiotherapy portal images.

PURPOSE: Two techniques have been developed at our institution to allow anatomical registration of digitized portal images to a simulation film. Accuracy of the portal image alignment methods is tested and single intrauser and multiple interuser variation is examined using each technique. METHODS AND MATERIALS: Method one requires the identification of anatomical fiducial points on a simulation image and its corresponding portal image. The parameters required to align the corresponding points are calculated by a least squares fit algorithm. Method two uses an anatomical template generated from the simulation image and superimposing it upon a portal image. The template is then adjusted by a computer mouse to obtain the best subjective anatomical fit on the portal image. Megavoltage portal images of a skull phantom with various known shifts and eight clinical image files were aligned by each method. Each data set was aligned several times by both a single user and multiple users. RESULTS: Alignment of the anatomical phantom portal images demonstrates an accuracy of less than 0.8 +/- 0.9 mm and 0.7 +/- 1.0 degrees with either method. As out of plane rotation increased from 0 to 5 degrees, simulating out of plane malpositioning, alignment orthogonal to the plane of rotation worsened to 1.5 +/- 1.1 mm with the point method and 2.4 +/- 1.6 mm with the template method. Alignment parallel to the axis of the gantry rotation was insensitive to this change and remained constant as did the rotational alignment parameters. For the clinical image files the magnitude of variation for a single user is typically less than +/- 1 mm or +/- 1 degree. The magnitude of variation of alignment increased when multiple users aligned the same image files. The variation was dependent upon anatomical site and to a lesser degree the method of alignment used. The root mean square deviation of translational shifts range from +/- 0.68 mm when using the template method in the pelvis to as high as +/- 2.94 mm with the template method to align abdominal portal images. In the thorax and pelvis translational alignments along the horizontal axis were more precise than along the vertical axis. Multiple user variability was in part due to poor image quality, user experience, non rigidity of the anatomical features, and the difficulty in locating an exact point on a continuous anatomical structure. CONCLUSION: In well controlled phantom studies both the fiducial point and template method provide similar and adequate results. The phantom studies show that alignment error and variance increase with distortion in anatomical features secondary to out of plane rotations. In clinical situations intrauser variation is small, however, multiple interuser variation is larger. The magnitude of variation is dependent upon the anatomical site aligned.

Computer Simulation↗
PubMed1995

A two-dimensional kinematic model of the lumbrical in the human finger.

The functioning of the lumbrical muscle in the human finger is difficult to visualise. This is mainly due to the fact that the origin and insertion of the lumbrical is on tendons of other motors (the deep flexor and the extensor assembly, respectively), instead of on bone. In this paper the functioning of the lumbrical in the human finger is kinematically investigated by explicitly considering the slackness or tautness of tendon parts which are in parallel or in series with the lumbrical, and by deriving from a standard finger model equivalent representations from which the functioning of the lumbrical is visually more clear. These models are used to review and interpret the results of previous studies. Further, it is indicated that the lumbrical is in an ideal position to contribute to the control of certain fast movements, as may be of importance for the musician, and that its role in other fast movements may be limited because of its large displacements (contraction speed).

Algorithms↗
PubMedDate not supplied

Effects of high-dose medroxyprogesterone acetate and various other steroid hormones on plasma membrane lipid mobility in CAMA-1 mammary cancer cells.

The influence of medroxyprogesterone acetate (MPA) and various other steroid hormones on the lateral diffusion of the fluorescent lipid probe 1-acyl-2-(N-4-nitrobenzo-2-oxa-1.3-diazolyl)-aminocarpropylphos phatidylcholine (NBD-PC) in the plasma membrane of intact mammary cancer cells (CAMA-1 cell line) has been studied by fluorescence recovery after photobleaching technique. Incubation of cells with MPA in serum free medium at ambient temperature for 1 hr led to a significant decrease in the lateral diffusion coefficient of NBD-PC. MPA induced this change over a limited concentration range with 10(-7)-10(-5) mol/l near-maximal or maximal effects, and 10(-8) mol/l exhibiting no effect. Exposure of the CAMA-1 cells to 10(-7) mol/l MPA in undiluted serum induced a significant effect following 1.5 hr of treatment with no increase in effectiveness up to 4 hr of incubation. As compared to MPA, the other steroids tested were less effective or ineffective. The influence on lateral lipid mobility diminished as follows: MPA greater than progesterone greater than 5a-DHT approximately 17 beta-estradiol greater than dexamethasone, and roughly seems to parallel their lipid solubility as estimated by partition coefficients in an n-octanol-water system. Any involvement of classical steroid hormone receptors in the mechanism of membrane action could be excluded. Nongenomic steroid effects on the plasma membrane are assumed. As the structure and function of biomembranes are modulated by lipid-bilayer fluidity and membranes crucially participate in nearly all aspects of cell biology, it is concluded that direct interactions of MPA with membranes potentially play a role in the antitumor activity of the compound.

Algorithms↗
PubMed2026

SNaQ.jl: Improved scalability for level-1 phylogenetic network inference.

MOTIVATION: Phylogenetic networks represent complex biological scenarios that are overlooked in trees, such as hybridization and horizontal gene transfer. Although numerous methods have been developed for phylogenetic network inference, their scalability is severely limited by the computational demands of likelihood optimization and the vastness of network space. Composite (or pseudo-) likelihood approaches like SNaQ have improved computational tractability for network inference, but they remain inadequate for datasets of sizes routinely handled by tree inference methods. RESULTS: Here, we introduce SNaQ.jl, a new standalone Julia package with the composite likelihood inference originally implemented within PhyloNetworks.jl as well as new scalability features that enhance computational efficiency through (i) parallelization of quartet likelihood calculations during composite likelihood computation, (ii) weighted random selection of quartets, and (iii) probabilistic decision-making during network search. Through a simulation study and empirical data analysis, we show that this new version of SNaQ.jl (version 1.1) improves average runtimes by up to 499% on average with no change in function parameters or method accuracy. AVAILABILITY AND IMPLEMENTATION: SNaQ.jl is a new open source Julia package available at https://github.com/JuliaPhylo/SNaQ.jl.

Phylogeny↗
PubMedDate not supplied

MR color mapping of myelin fiber orientation.

Diffusion of water in brain white matter has been shown to be anisotropic: Water mobility is lower when measured perpendicular to the fiber direction rather than parallel to it. This feature was used to produce images of the myelin fiber orientation. Coronal and sagittal MR diffusion images were obtained in volunteers using an echo-planar imaging sequence sensitized to molecular diffusion in perpendicular directions. Color-coded images of myelin orientation were then generated by combining these images together. The orientation of the white matter tracts was found to be in excellent agreement with known anatomy. Myelin fiber orientation mapping may offer a new perspective to evaluate white matter disorders.

Algorithms↗
PubMed1993

Cellular automaton simulation of pulsed field gel electrophoresis.

We describe simulation techniques well suited to detailed investigation of the microscopic behavior of DNA during electrophoretic separation in the diffusive regime. Long polymers moving diffusively in a medium are simulated using microscopic Monte-Carlo steps. Simulations rely upon a recently introduced two-space abstract polymer that enables fine-grained massively parallel simulation. Tests of the two-space polymer dynamics are reviewed. The scaling with polymer length of the size and relaxation time of isolated polymers are shown to agree with universal scaling relations. The relaxation time is found to be significantly faster than the alternative bond-fluctuation method. Simplicity of implementation enables simulation on cellular automaton machines (CAM) including CAM-6, and a prototype of the new CAM-8, as well as other massively parallel architectures. Preliminary simulations of polymers migrating under an external field through a random medium of obstacles in two dimensions are described. Two sequences of simulations are performed, with different obstacle densities corresponding to pore sizes larger and smaller than the polymer radius of gyration. In the dilute medium polymers are characteristically draped on single obstacles. In the denser medium draping across multiple obstacles results in reduced orientation in the field direction. A demonstration of rapid 90 degrees field direction switching results in polymer motion toward the expected intermediate direction.

Algorithms↗
PubMed1992

Evidence for a generalized Laguerre transform of temporal events by the visual system.

It is generally assumed that the early visual processing is constituted by a set of filters operating in parallel. In this respect the visual system performs a transform, generating a code of the characteristics of the input signal. Recently, it has been suggested that the coding of the spatial characteristics by the visual system can be described by a Hermite transform (Martens, 1990a, b). It was also suggested that a three-dimensional Hermite transform can be used to code spatiotemporal events. In contrast to this latter suggestion, we argue that the coding of temporal events takes the form of a generalized Laguerre transform. We review psychophysical evidence supporting this hypothesis.

Algorithms↗
PubMed1987

HOMED: a homologous sequence editor.

The alignment of homologous sequences with each other and their display has proved a difficult task, despite a frequent requirement for this process. HOMED enables related sequences to be edited and listed in parallel with each other. The editor function uses a full screen editor which emulates the text editors KED and EDT (on PDP-11 and VAX-11 respectively) and which can be adapted to emulate other text editors. This emulation has been adopted to simplify user learning of editing functions. HOMED provides functions for listing the sequences in a variety of formats and for generating a consensus sequence as well as providing a series of tools for maintenance of the sequence database. HOMED has been implemented in Pascal in a modular fashion to enhance portability.

Algorithms↗
PubMed1995

A direct Fourier method (DFM) for X-ray tomographic reconstructions and the accurate simulation of sinograms.

This article illustrates the reconstruction of tomographic images by a direct Fourier method (DFM) and the results obtained from simulations and from experimental X-ray sinograms. The implementation of DFM, especially with regard to the resampling of the 2D Fourier transform, is based on a technique of Shannon reconstruction, devised by the authors, and on novel interpolating kernels. A short account is given on the principles and the implementation aspects of the interpolation technique. The DFM protocol developed by the authors has been tested, both for parallel and fan geometry, on simulated sinograms obtained from real images and from phantoms. The technique used to compute accurate projections is also described, since it might be useful in restoring missing parts of sinograms with processes based on 'projections on convex sets' (POCS) techniques. The results obtained from simulations and from the raw data of a third generation tomograph are presented and discussed. A comparison among reconstructions obtained from complete sinograms and from half of them suggests that adequate images could be obtained with a radiation dose lower than that used to obtain the experimental sinograms.

Algorithms↗
PubMedDate not supplied

Surgery for small liver cancers.

During the last 16 years, we have resected small hepatocellular carcinomas (HCCs) measuring 5 cm or less from 362 patients, 266 of whom also had liver cirrhosis. The operative and hospital mortality rate were 1.7% and 1.9%, respectively. These showed a gradual decrease year by year in parallel with reduction of intraoperative blood loss achieved by the selective vascular occlusion technique and Pringle method. In 1989, 87% of hepatectomy patients were discharged without the need for whole blood transfusion, and 5-year survival was 43.7%. Tumor size, number of tumors, intrahepatic metastasis, vascular invasion, and capsular invasion were significant prognostic factors. Edmondson grade and the operative procedure employed were significantly related to outcome. Our standard policy for selection of operative procedures and perioperative care is described, and the selection of treatment modalities is discussed.

Adult↗
PubMed1993

An improved estimator of spontaneous mutation rates in Luria-Delbrück fluctuation experiments.

In estimating the spontaneous mutation rate, mu, in cultured mammalian cells, the number of mutant cells in several parallel cultures, each a clone from a single cell, is determined. Luria and Delbrück (1943), and subsequently Lea and Coulson (1949), proposed several estimators of mu using data from such experiments. These methods of analysis were originally proposed to apply to mutants arising in microbial cultures, and some of the limitations in applying them to mammalian cell cultures have been outlined by Featherstone et al. (1987), and by Kendal and Frost (1988). For a given value of mu, the number of mutants, r, found in a culture is exceedingly variable, so that r contains very little information concerning mu. It is important, therefore, that an estimator of mu be efficient; that it not waste the limited information available in the experimental data. To this end, a new estimator is proposed which compounds the information previously utilized by the so-called P0 and median estimators. Using a spreadsheet program such as that available with MINITAB, the algorithm can be programmed in as few as 26 instructions. Tested against simulated data across a range of values of mu, the proposed compound estimator is more efficient than the currently used estimators.

Algorithms↗
PubMedDate not supplied

Simultaneous reconstruction, segmentation, and edge enhancement of relatively piecewise continuous images with intensity-level information.

A multinomial image model is proposed which uses intensity-level information for reconstruction of contiguous image regions. The intensity-level information assumes that image intensities are relatively constant within contiguous regions over the image-pixel array and that intensity levels of these regions are determined either empirically or theoretically by information criteria. These conditions may be valid, for example, for cardiac blood-pool imaging, where the intensity levels (or radionuclide activities) of myocardium, blood-pool, and background regions are distinct and the activities within each region of muscle, blood, or background are relatively uniform. To test the model, a mathematical phantom over a 64 x 64 array was constructed. The phantom had three contiguous regions. Each region had a different intensity level. Measurements from the phantom were simulated using an emission-tomography geometry. Fifty projections were generated over 180 degrees, with 64 equally spaced parallel rays per projection. Projection data were randomized to contain Poisson noise. Image reconstructions were performed using an iterative maximum a posteriori probability procedure. The contiguous regions corresponding to the three intensity levels were automatically segmented. Simultaneously, the edges of the regions were sharpened. Noise in the reconstructed images was significantly suppressed. Convergence of the iterative procedure to the phantom was observed. Compared with maximum likelihood and filtered-backprojection approaches, the results obtained using the maximum a posteriori probability with the intensity-level information demonstrated qualitative and quantitative improvement in localizing the regions of varying intensities.

Algorithms↗
PubMed1990

Tomography using a rotating slant-hole collimator and a large number of projections.

A tomographic method using a limited-view angle has been evaluated. In studies using a gamma camera and a rotating 30-degree slant-hole (RSH) collimator, 64 projection images were registered. A special filtered backprojection technique was used for reconstruction of section images parallel to the collimator face. Resolution within such sections was 0.6 cm, 3 cm from the collimator face and 1.3 cm at 18 cm. Depth resolution was 2.2 cm at 3 cm and 5.1 cm at 18 cm. Spacing between section images was regular and geometric distortion negligible. Short-axis section images of a myocardium in vivo were qualitatively comparable or better than those obtained with single-photon emission computed tomography. Degradation in the posterior wall due to attenuation and scatter was less. Section images of the facial bones and a hip joint further demonstrated the tomographic capability of the method.

Algorithms↗