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PubMed1991

A distributed-parameter model of the myelinated nerve fiber.

This paper presents a new model for the characterization of electrical activity in the nodal, paranodal and internodal regions of isolated amphibian and mammalian myelinated nerve fibers. It differs from previous models in the following ways: (1) in its ability to incorporate detailed anatomical and electrophysiological data; (2) in its approach to the myelinated nerve fiber as a multi-axial cable; and (3) in the numerical algorithm used to obtain distributed model equation solutions for potential and current. The morphometric properties are taken from detailed electron microscopic anatomical studies (Berthold & Rydmark, 1983a, Experientia 39, 964-976). The internodal axolemma is characterized as an excitable membrane and model-generated nodal and internodal membrane action potentials are presented. A system of describing equations for the equivalent network model is derived, based on the application of Kirchoff's Current Law, which take the form of multiple cross-coupled parabolic partial differential equations. An implicit numerical integration method is developed and the numerical solution implemented on a parallel processor. Non-uniform spatial step sizes are used, enabling detailed representation of the nodal region while minimizing the number of total segments necessary to represent the overall fiber. Conduction velocities of 20.2 m sec-1 at 20 degrees C for a 15 microns diameter amphibian fiber and 57.6 m sec-1 at 37 degrees C for a 17.5 microns diameter mammalian fiber are achieved, which agrees qualitatively with published experimental data at similar temperatures (Huxley & Stämpfli, 1949, J. Physiol., Lond. 108, 315-339; Rasminsky, 1973, Arch, Neurol. 28, 287-292). The simulation results demonstrate the ability of this model to produce detailed representations of the transaxonal, transmyelin and transfiber potentials and currents, as well as the longitudinal extra-axonal, periaxonal and intra-axonal currents. Also indicated is the potential contribution of the paranodal axolemma to nodal activity as well as the presence of significant longitudinal currents in the periaxonal space adjacent to the node of Ranvier.

Action Potentials↗
PubMed1998

Porcine cerebroside sulfate activator (saposin B) secondary structure: CD, FTIR, and NMR studies.

Cerebroside sulfate activator protein (CSAct or saposin B) is one of a group of heat stable, low-molecular-weight proteins that appear to share a common structural motif. These have been referred to as saposin-like proteins and are thought to share a multiple amphipathic helical barrel structure with a conserved pattern of disulfide linkages. Porcine kidney CSAct was prepared in high purity and consisted of three major glycosylated subforms. The protein was studied by physical-chemical methods and evaluated by various methods for structural prediction. All suggest that CSAct has high amounts of alpha-helical conformation and little if any beta-sheet. Circular dichroism (CD) studies indicate 45-50% helical conformation depending on buffer and temperature. There was only a moderate loss in helical content with increasing temperature and no indication of thermal denaturation. Fourier transform infrared spectroscopy (FTIR) measurements on deuterium hydrated self-films also indicated a predominantly helical structure. Helical axis orientation was investigated by both oriented CD and FTIR dichroism, which suggested that the helical axes were roughly parallel and oriented along the axis of the surface on which the self-films had been deposited. One-dimensional nuclear magnetic resonance spectra showed large chemical shift dispersion, indicating a defined tertiary structure with little variation between 6 and 85 degrees C. NOESY spectra failed to show the strong NOE cross peaks expected for a highly helical conformation. This may indicate short-term conformational flexibility within the helices or molecular aggregation at the high protein concentrations employed. These observations are consistent with the 3-4-helix bundle motif suggested for saposin-like proteins by various predictive algorithms.

Algorithms↗
PubMed1988

Binding of the bovine basic pancreatic trypsin inhibitor (Kunitz) to human alpha-, beta- and gamma-thrombin; a kinetic and thermodynamic study.

Kinetic and thermodynamic parameters for the binding of the bovine basic pancreatic trypsin inhibitor (BPTI, Kunitz inhibitor) to human alpha-, beta- and gamma-thrombin have been determined, between 5 and 45 degrees C, at pH 7.5. BPTI-binding properties to human thrombins have been analyzed in parallel with those of serine (pro)enzymes acting on cationic and non-cationic substrates, with particular reference to the bovine beta-trypsin/BPTI system. The observed binding behaviour of BPTI to human alpha-, beta- and gamma-thrombin has been related to the inferred stereochemistry of the enzyme/inhibitor contact region(s).

Algorithms↗
PubMed1993

A hardware efficient cascadable chip set for ANN's with on-chip backpropagation.

In this paper, an analogue, cascadable, CMOS chip set for artificial neural networks is presented. The chip set (a synapse chip and a neuron chip) offer on-chip back-propagation learning in a fully parallel, layered, feedforward network of arbitrary size and topology. The learning scheme is implemented with no extra circuits at the synapse sites (compared to the system without the learning scheme) and extra circuits of a complexity only about the same as the neurons at the neuron sites. Also, no additional wiring is required by the learning scheme. Measurements on an experimental chip set are presented.

Algorithms↗
PubMed1997

Developments in cardiovascular ultrasound: Part 1: Signal processing and instrumentation.

One of the major contributions to the improvement of spectral Doppler and colour flow imaging instruments has been the development of advanced signal-processing techniques made possible by increasing computing power. Model-based or parametric spectral estimators, time-frequency transforms, station-arising algorithms and spectral width correction techniques have been investigated as possible improvements on the FFT-based estimators currently used for real-time spectral estimation of Doppler signals. In colour flow imaging some improvement on velocity estimation accuracy has been achieved by the use of new algorithms but at the expense of increased computational complexity compared with the conventional autocorrelation method. Polynomial filters have been demonstrated to have some advantages over IIR filters for stationary echo cancellation. Several methods of velocity vector estimation to overcome the problem of angle dependence have been studied, including 2D feature tracking, two and three beam approaches and the use of spectral width in addition to mean frequency. 3D data acquisition and display and Doppler power imaging have also been investigated. The use of harmonic imaging, using the second harmonic generated by encapsulated bubble contrast media, seems promising particularly for imaging slow flow. Parallel image data acquisition using non-sequential scanning or broad beam transmission, followed by simultaneous reception along a number of beams, has been studied to speed up 'real-time' imaging.

Blood Flow Velocity↗
PubMed1994

A variable-resolution rotate-only computed tomography scanner.

The Rotoscan is a computed tomography scanner that combines the advantages of variable geometric resolution and adjustable size of measurement diameter of translate-rotate scanners with the improved speed of rotate-only scanners. Because of the small number of only 26 detectors used for this scanner, a special data collection scheme of multiple rotations with interleaved detector positions was employed. In order to avoid angular data interpolation after reordering of the projections from the fan- to a parallel-beam geometry, the detectors were incrementally moved at a right angle to the centerline of the fan rather than rotated about the source. The measurement time of 40 s for one cross-section is comparable to that of second-generation systems. However, for longer measurement diameters, the measurement time for second-generation systems increases, whereas that of the Rotoscan remains constant.

Algorithms↗
PubMed1994

Nutrition support, supplementation, and replacement.

Nutrition support in acute, chronic, or home care settings can be implemented successfully by the well-informed primary care physician, who often is the first to identify poor nutritional health in his or her patients. Using established protocols for the identification or of risk factors and indicators of malnutrition, specific alerts to the need for nutrition support are presented. The logical approach to nutrition support interventions through four stages representing the gradual increase in complexity and cost, paralleling the progressive inability to use regular foods and the gastrointestinal tract are discussed. Specific, practical measures that can be recommended and implemented by the primary care physician managing the older person are presented. The ethical, legal, and home health aspects of nutrition support in the care of the older American by the primary care physician are also reviewed.

Aged↗
PubMed1995

Analytical expressions for the NMR apparent diffusion coefficients in an anisotropic system and a simplified method for determining fiber orientation.

NMR measurements of anisotropic diffusion were studied using a three-dimensional random-walk model. It was found that the apparent diffusion coefficient can be expressed in a canonical form as the product of a diagonal matrix, an orthonormal rotation matrix, and a vector representing the encoding magnetic field gradient. The diffusion coefficient can be interpreted as the sum of the corresponding coefficients measured along the principal diffusion axes, weighted by the squares of the directional cosines of the encoding direction with respect to the principal axes. The analysis revealed that determining the orientation of anisotropy, in a cylindrically symmetric system, requires a minimum of four diffusion measurements. A special pulse sequence which minimized gradient cross-terms and possible restricted diffusion effects was used to characterize diffusion anisotropy in cut chicken gizzards. Diffusion coefficients parallel to the muscle fibers were found to be approximately two to three times larger than those in the transverse direction. Furthermore, the method was successful in detecting the angular change when the sample was rotated by 30 degrees. Results indicate that the proposed approach to measure fiber orientation is valid and may be used to improve the time efficiency of diffusion anisotropy measurements.

Algorithms↗
PubMed1998

A new three-dimensional finite-difference bidomain formulation for inhomogeneous anisotropic cardiac tissues.

Bidomain modeling of cardiac tissues provides important information about various complex cardiac activities. The cardiac tissue consists of interconnected cells which form fiber-like structures. The fibers are arranged in different orientations within discrete layers or sheets in the tissue, i.e., the fibers within the tissue are rotated. From a mathematical point of view, this rotation corresponds to a general anisotropy in the tissue's conductivity tensors. Since the rotation angle is different at each point, the anisotropic conductivities also vary spatially. Thus, the cardiac tissue should be viewed as an inhomogeneous anisotropic structure. In most of the previous bidomain studies, the fiber rotation has not been considered, i.e., the tissue has been modeled as a homogeneous orthotropic medium. In this paper, we describe a new finite-difference bidomain formulation which accounts for the fiber rotation in the cardiac tissue and hence allows a more realistic modeling of the cardiac tissue. The formulation has been implemented on the data-parallel CM-5 which provides the computational power and the memory required for solving large bidomain problems. Details of the numerical formulation are presented together with its validation by comparing numerical and analytical results. Some computational performance results are also shown. In addition, an application of this new formulation to provide activation patterns within a tissue slab with a realistic fiber rotation is demonstrated.

Algorithms↗
PubMed1995

Nonlinear models of the first synapse in the light-adapted fly retina.

1. Randomly modulated light stimuli were used to characterize the nonlinear dynamic properties of the synapse between photoreceptors and large monopolar neurons (LMC) in the fly retina. Membrane potential fluctuations produced by constant variance contrast stimuli were recorded at eight different levels of background light intensity. 2. Representation of the photoreceptor-LMC input-output data in the form of traditional characteristic curves indicated that synaptic gain was reduced by light adaptation. However, this representation did not include the time-dependent properties of the synaptic function, which are known to be nonlinear. Therefore nonlinear systems analysis was used to characterize the synapse. 3. The responses of photoreceptors and LMCs to random light fluctuations were characterized by second-order Volterra series, with kernel estimation by the parallel cascade method. Photoreceptor responses were approximately linear, but LMC responses were clearly nonlinear. 4. Synaptic input-output relationships were measured by passing the light stimuli to LMCs through the measured photoreceptor characteristics to obtain an estimate of the synaptic input. The resulting nonlinear synaptic functions were well characterized by second-order Volterra series. They could not be modeled by a linear-nonlinear-linear cascade but were better approximated by a nonlinear-linear-nonlinear cascade. 5. These results support two possible structural models of the synapse, the first having two parallel paths for signal flow between the photoreceptor and LMC, and the second having two distinct nonlinear operations, occurring before and after chemical transmission. 6. The two models were cach used to calculate the synaptic gain to a brief change in photoreceptor membrane potential. Both models predicted that synaptic gain is reduced by light adaptation.

Adaptation, Ocular↗
PubMed1994

Distributed machine learning: scaling up with coarse-grained parallelism.

Machine learning methods are becoming accepted as additions to the biologists data-analysis tool kit. However, scaling these techniques up to large data sets, such as those in biological and medical domains, is problematic in terms of both the required computational search effort and required memory (and the detrimental effects of excessive swapping). Our approach to tackling the problem of scaling up to large datasets is to take advantage of the ubiquitous workstation networks that are generally available in scientific and engineering environments. This paper introduces the notion of the invariant-partitioning property--that for certain evaluation criteria it is possible to partition a data set across multiple processors such that any rule that is satisfactory over the entire data set will also be satisfactory on at least one subset. In addition, by taking advantage of cooperation through interprocess communication, it is possible to build distributed learning algorithms such that only rules that are satisfactory over the entire data set will be learned. We describe a distributed learning system, CorPRL, that takes advantage of the invariant-partitioning property to learn from very large data sets, and present results demonstrating CorPRL's effectiveness in analyzing data from two databases.

Database Management Systems↗
PubMed1995

A novel transverse gradient coil design for high-resolution MR imaging.

The authors describe a new gradient coil design for high resolution human, animal, specimen, or phantom imaging with high gradient efficiency and a large region of excellent gradient uniformity. Important features of our new design are the simple analytical description of the wire patterns that comprise the design, and ease of construction. Wires are spaced in a sinusoidal distribution around the circumference of the cylinder, and curved in an arcsin shape along the length of the cylinder. This coil produces a magnetic field pointing in a direction transverse to the axis of the coil with a gradient in the direction parallel to the axis of the coil. The same arcsin coil can be used to create a magnetic field pointing in a direction parallel to its axis with a gradient in a direction perpendicular to the coil axis. A prototype coil was constructed; field and inductance calculations were verified. Geometric variations on this coil design were modeled and their performance characteristics compared. This coil design is ideal for rapid implementation of a transverse gradient coil, since no specialized design software is required.

Algorithms↗
PubMed1995

Role of prostate-specific antigen density after applying age-specific prostate-specific antigen reference ranges.

OBJECTIVES: To determine the potential role of prostate-specific antigen (PSA) density (PSAD) in the early detection of prostate carcinoma if we apply age-specific PSA reference ranges (2.5 ng/mL or less for ages 40 to 49 years, 3.5 or less for ages 50 to 59, 4.5 or less for ages 60 to 69, and 6.5 or less for ages 70 to 79. METHODS: We retrospectively reviewed 3234 cases referred to us by urologists for transrectal ultrasound (TRUS) between January 1, 1991, and September 28, 1993. We included 2429 patients in the study, ages 40 to 79 years, with Hybritech or Abbott IMx serum PSA determinations and without previously diagnosed prostate cancer. We performed digital rectal examination (DRE) and TRUS in all cases, and TRUS-guided biopsies when indicated. We used stringent criteria to define 736 cases without clinical evidence of malignancy that were designated as a "benign group." RESULTS: In the benign group, we found serum PSA to increase with age in parallel with the increase in prostate volume with age (r = 0.25 and r = 0.26, respectively). The association between serum PSA and prostate volume was stronger (r = 0.46). Using multiple regression analysis, prostate volume accounted for 18% of the variation in serum PSA, whereas age accounted for only an additional 2%. PSAD, which directly relates serum PSA to prostate volume, showed a weak association with age (r = 0.1). In the entire study population of 2429 cases, 555 patients had negative DRE and TRUS results and a serum PSA level between the age-specific upper limit of normal and 10.0 ng/mL. According to the proposed age-specific algorithm, these patients would have required automatic biopsies. Of these, 315 cases (56.8%) still had a PSAD of less than 0.15. We performed biopsies in 108 of these 315 and detected only two cancers, for a positive biopsy rate (PBR) of 1.9%. The remaining 240 cases had a PSAD of 0.15 or higher, and we performed biopsies in 217 of these cases and detected 59 cancers, for a PBR of 27.2%. CONCLUSIONS: The use of age-specific PSA reference ranges does not totally account for the effect of prostate volume on serum PSA. Therefore PSAD can still be used to reduce safely the number of biopsies performed in patients with negative DRE and TRUS results and a serum PSA level 10.0 ng/mL or less and above the age-specific upper limit of normal.

Adult↗
PubMed1997

National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices.

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first child multisite cooperative agreement treatment study of children conducted by the National Institute of Mental Health, Rockville, Md. It examines the long-term effectiveness of medication vs behavioral treatment vs both for treatment of ADHD and compares state-of-the-art treatment with routine community care. In a parallel-groups design, 576 children (age, 7-9 years) with ADHD (96 at each site) are thoroughly assessed and randomized to 4 conditions: (1) medication alone, (2) psychosocial treatment alone, (3) the combination of both, (4) or community comparison. The first 3 groups are treated for 14 months and all are reassessed periodically for 24 months. Designers met the following challenges: framing clinically relevant primary questions; defining the target population; choice, intensity, and integration and combination of treatments for fair comparisons; combining scientific controls and standardization with clinical flexibility; and implementing a controlled clinical trial in a nonclinical setting (school) controlled by others. Innovative solutions included extensive decision algorithms and manualized adaptations of treatments to specific needs.

Attention Deficit Disorder with Hyperactivity↗
PubMed1994

Some approaches to the analysis of recurrent event data.

Methodological research in biostatistics has been dominated over the last twenty years by further development of Cox's regression model for life tables and of Nelder and Wedderburn's formulation of generalized linear models. In both of these areas the need to address the problems introduced by subject level heterogeneity has provided a major motivation, and the analysis of data concerning recurrent events has been widely discussed within both frameworks. This paper reviews this work, drawing together the parallel development of 'marginal' and 'conditional' approaches in survival analysis and in generalized linear models. Frailty models are shown to be a special case of a random effects generalization of generalized linear models, whereas marginal models for multivariate failure time data are more closely related to the generalized estimating equation approach to longitudinal generalized linear models. Computational methods for inference are discussed, including the Bayesian Markov chain Monte Carlo approach.

Algorithms↗
PubMed1994

Evaluation and quality control of a commercial 3-D dose compensator system.

A commercially available software/hardware system for automated design and fabrication of three-dimensional dose compensator molds has been tested for accuracy and precision as well as for its ability to provide adequate dose compensation at depth. To date, we have used this system to treat more than 50 patients with either head and neck or lung malignancies. In 19 head and neck patients (38 compensators) the use of a customized compensator resulted in an average reduction of dose variance in the target volume from 13.8% (range of 7%-21%) with uncompensated parallel-opposed fields to 4.5% (2%-7%) with custom-compensated parallel-opposed fields. A similar reduction was seen in the dose variation across lung tumor volumes. The custom compensators were also tested for accuracy of fabrication and positioning; both were found to be accurate within +/- 1 mm of the design specifications for all compensators tested. Last, the dosimetric properties of the compensators were studied. The ratios of measured open-beam dose profiles to measured compensated-beam dose profiles were compared with the ratio of similar profiles calculated with a treatment planning system. These ratios were equal within +/- 2.9%, thus providing evidence of the fidelity of the compensator to its design and the accuracy of the treatment planning algorithm that designs 34 each compensator.

Algorithms↗
PubMed1996

GEOMETRY: a software package for nucleotide sequence analysis using statistical geometry in sequence space.

GEOMETRY is a software package for the analysis of nucleotide sequences using the method of statistical geometry in sequence space. The package consists of programs performing estimation of the average geometry of sequence quartets, analysis of positional variability and computer simulation of parallel and tree-like sequence divergence with user-defined parameters. It provides an independent tool for evaluation of the reliability of conventional phylogenetic trees and calibration of the time of sequence divergence. GEOMETRY may be of interest for all scientists engaged in the study of molecular phylogeny. The package is available by anonymous FTP from ftp.bionet.nsk.su, directory /incoming/molevol/geom.exe, and will be available from EMBL file server (URL: http://@www.ebi.ac.uk)

Algorithms↗
PubMed1991

Parallel cascade identification and kernel estimation for nonlinear systems.

We consider the representation and identification of nonlinear systems through the use of parallel cascades of alternating dynamic linear and static nonlinear elements. Building on the work of Palm and others, we show that any discrete-time finite-memory nonlinear system having a finite-order Volterra series representation can be exactly represented by a finite number of parallel LN cascade paths. Each LN path consists of a dynamic linear system followed by a static nonlinearity (which can be a polynomial). In particular, we provide an upper bound for the number of parallel LN paths required to represent exactly a discrete-time finite-memory Volterra functional of a given order. Next, we show how to obtain a parallel cascade representation of a nonlinear system from a single input-output record. The input is not required to be Gaussian or white, nor to have special autocorrelation properties. Next, our parallel cascade identification is applied to measure accurately the kernels of nonlinear systems (even those with lengthy memory), and to discover the significant terms to include in a nonlinear difference equation model for a system. In addition, the kernel estimation is used as a means of studying individual signals to distinguish deterministic from random behaviour, in an alternative to the use of chaotic dynamics. Finally, an alternate kernel estimation scheme is presented.

Algorithms↗