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At least 253 records · Page 14Linked to original sources

PubMedDate not supplied

A computer model of denervation-reinnervation in skeletal muscle.

A computer model of the process of denervation and complete reinnervation of skeletal muscle has been developed for the purpose of exploring underlying mechanisms and for use in the development of new clinical and research tools for evaluating neuromuscular disease. Progressive motor neuron death and reinnervation in this model reproduces the fiber-type grouping, increased fiber density, and minimal increase of motor unit size seen in human chronic denervating diseases. Studies using the model suggest that (1) preferential involvement of motor units of one type could account for the abnormal fiber-type proportions observed in some diseases, (2) reinnervation by axons innervating adjacent fibers is compatible with single fiber multielectrode study results in that it does not produce a large increase in motor unit area, and (3) such reinnervation is sufficient to account for the increases in motor unit density that have been observed. The model has also been used in the development and testing of the Codispersion Index, a measure of the codistribution of two fiber types, which is useful in detecting fiber-type grouping.

Algorithms↗

PubMed1999

Computational modeling of high-level cognition and brain function.

This article describes a computational modeling architecture, 4CAPS, which is consistent with key properties of cortical function and makes good contact with functional neuroimaging results. Like earlier cognitive models such as SOAR, ACT-R, 3CAPS, and EPIC, the proposed cognitive model is implemented in a computer simulation that predicts observable variables such as human response times and error patterns. In addition, the proposed 4CAPS model accounts for the functional decomposition of the cognitive system and predicts fMRI activation levels and their localization within specific cortical regions, by incorporating key properties of cortical function into the design of the modeling system.

Brain↗

PubMed2003

Study of unipolar electrogram morphology in a computer model of atrial fibrillation.

INTRODUCTION: Electrograms exhibit a wide variety of morphologies during atrial fibrillation (AF). The basis of these time courses, however, is not completely understood. In this study, data from computer models were studied to relate features of the signals to the underlying dynamics and tissue substrate. METHODS AND RESULTS: A computer model of entire human atria with a gross fiber architecture based on histology and membrane kinetics based on the Courtemanche et al. atrial model was developed to simulate paced activation and simulated AF. Unipolar electrograms were computed using a current source approximation at 256 sites in right atrium, to simulate a mapping array. The results show the following: (1) In a homogeneous and isotropic tissue, the presence of highly asymmetric electrograms is rare (<2%), although there is a marked variability in amplitude and symmetry. (2) The introduction of anisotropy increases this variability in symmetry and amplitude of the, electrograms especially for propagation across fibers. The percentage of highly asymmetric electrograms increases to 12% to 15% for anisotropy ratios greater than 3:1. (3) Multiphasic and fractionated electrograms are rarely seen in the model with uniform properties but are more common (15%-17%) in a model including regions with abrupt changes in conductivity. Beat-to-beat variations in the occurrence of multiphasic signals are possible with fixed anatomic heterogeneity, due to beat-to-beat variations in the direction of the wavefront relative to the heterogeneity. CONCLUSION: Analysis of the amplitude and symmetry of unipolar atrial electrograms can provide information about the electrophysiologic substrate maintaining AF.

Algorithms↗

PubMed2001

Corannulene as a Lewis base: computational modeling of protonation and lithium cation binding.

A computational modeling of the protonation of corannulene at B3LYP/6-311G(d,p)//B3LYP/6-311G(d,p) and of the binding of lithium cations to corannulene at B3LYP/6-311G(d,p)//B3LYP/6-31G(d,p) has been performed. A proton attaches preferentially to one carbon atom, forming a sigma-complex. The isomer protonated at the innermost (hub) carbon has the best total energy. Protonation at the outermost (rim) carbon and at the intermediate (bridgehead rim) carbon is less favorable by ca. 2 and 14 kcal mol(-)(1), respectively. Hydrogen-bridged isomers are transition states between the sigma-complexes; the corresponding activation energies vary from 10 to 26 kcal mol(-)(1). With an empirical correction obtained from calculations on benzene, naphthalene, and azulene, the best estimate for the proton affinity of corannulene is 203 kcal mol(-)(1). The lithium cation positions itself preferentially over a ring. There is a small energetic preference for the 6-ring over the 5-ring binding (up to 2 kcal mol(-)(1)) and of the convex face over the concave face (3-5 kcal mol(-)(1)). The Li-bridged complexes are transition states between the pi-face complexes. Movement of the Li(+) cation over either face is facile, and the activation energy does not exceed 6 kcal mol(-)(1) on the convex face and 2.2 kcal mol(-)(1) on the concave face. In contrast, the transition of Li(+) around the corannulene edge involves a high activation barrier (24 kcal mol(-)(1) with respect to the lowest energy pi-face complex). An easier concave/convex transformation and vice versa is the bowl-to-bowl inversion with an activation energy of 7-12 kcal mol(-)(1). The computed binding energy of Li(+) to corannulene is 44 kcal mol(-)(1). Calculations of the (7)Li NMR chemical shifts and nuclear independent chemical shifts (NICS) have been performed to analyze the aromaticity of the corannulene rings and its changes upon protonation.

Journal Article↗

PubMed1969

Construction of biochemical computer models.

This paper described methods for constructing (digital) computer models of biochemical systems when the main object is to investigate the system itself, and not to fit experimental data (e.g., from tracer kinetics) to a set of equations. The author describes model-building as an art which is difficult to communicate, but nevertheless gives valuable tips on the conceptual and practical aspects, from his own considerable experience.

Journal Article↗

PubMed1977

A computational model of cerebellar cortex and peripheral muscle.

A computational model, suitable for analytical or machine simulation studies, is developed for a specific cerebellar loop, the pathway from muscle fibre stretch receptors to the cerebellar cortex and back again. The model adheres to physiological data from the cat, and employs features from several existing models, including a single neuron model developed and tested earlier. Also included is a mechanical equivalent to an idealised muscle, in this case a rectangular array of muscle fibres which map 1-to-1 onto the array of compartments which form the cerebellar cortex. Much of the literature on cerebellar models is briefly reviewed, as are several key physiological experiments.

Animals↗

PubMedDate not supplied

Software for pest-management science: computer models and databases from the United States Department of Agriculture-Agricultural Research Service.

We present an overview of USDA Agricultural Research Service (ARS) computer models and databases related to pest-management science, emphasizing current developments in environmental risk assessment and management simulation models. The ARS has a unique national interdisciplinary team of researchers in surface and sub-surface hydrology, soil and plant science, systems analysis and pesticide science, who have networked to develop empirical and mechanistic computer models describing the behavior of pests, pest responses to controls and the environmental impact of pest-control methods. Historically, much of this work has been in support of production agriculture and in support of the conservation programs of our 'action agency' sister, the Natural Resources Conservation Service (formerly the Soil Conservation Service). Because we are a public agency, our software/database products are generally offered without cost, unless they are developed in cooperation with a private-sector cooperator. Because ARS is a basic and applied research organization, with development of new science as our highest priority, these products tend to be offered on an 'as-is' basis with limited user support except for cooperating R&D relationship with other scientists. However, rapid changes in the technology for information analysis and communication continually challenge our way of doing business.

Agriculture↗

PubMed2003

A computer model of rigidity and related motor dysfunction in Parkinson's disease.

This work explores the involvement of spinal circuits in the generation of parkinsonian rigidity and related motor dysfunction. A computer model of spinal proprioceptive input processing, derived from previous work on spasticity modeling, was adapted to the simulation of parkinsonian rigidity. Model parameters were varied to generate simulations reproducing experimental data obtained using the pendulum test of the leg in 10 parkinsonian patients and 3 healthy subjects. Convenient reproductions of experimental traces in rigidity were obtained by the combination of a low reflex gain and a decrease in reflex threshold. These findings are consistent with studies reporting an increase of spinal interneuron excitability and proprioception deficits in Parkinson's disease (PD). Moreover, as the threshold parameter was much lowered, our model generated typical features of parkinsonian resting tremor, endorsing the hypothesis of a participation of a spinal oscillator in this disorder. Finally, tuning the reflex gain during simulations of rigidity resulted in the generation of active movement, opening some hypotheses on pathophysiology of motor dysfunction in PD, and notably, of akinesia. More generally, this work accredits the hypothesis of the involvement of an aperiodic, altered supra-spinal motor drive in PD, resulting in spinal dysfunction, through specific descending motor pathways. This may lead to a search for new (spinal) pharmacological targets in PD. It emphasizes further the value of computer modeling in understanding motor control in health and disease.

Computer Simulation↗

PubMed1987

Computer modeling of clinical judgment.

Four main developments leading to computer modeling of clinical judgment are described in this paper. These include information processing psychology, clinical vs. statistical prediction studies, behavioral decision theory, and Bayesian decision analysis approaches. One clear catalyst in these developments has been the computer, which has been used as an information management tool rather than a data-processing device. Future directions of these efforts are delineated, and problems as well as prospects of computerizing clinical judgment are described.

Artificial Intelligence↗

PubMedDate not supplied

[Computer modeling of information processing mechanisms in the olfactory system. III. Reproduction of psychophysical phenomena by the olfactory bulb model].

Psychophysical phenomena typical of olfaction were reproduced using a computer model of olfactory bulb. The procedure of numerical experiments is described. The model reproduces the following phenomena: fusion of odors, strong and weak odors, suppression of weak odors by strong odors, indemnity of odors, changes in odor with time, consecutive olfactory images, sensibilization, consecutive olfactory constrast, and synergims. It was concluded that computer-assisted experimentation in combination with neurophysiological and psychophysical experiments can considerably increase the efficiency of research of odorants and the olfaction process.

Computer Simulation↗

PubMed2001

Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin.

A computational model of the transmembrane domain of the human 5-HT4 receptorcomplexed with the GR113808 antagonist was constructed from the crystal structure of rhodopsin and the putative residues of the ligand-binding site, experimentally determined by site-directed mutagenesis. The recognition mode of GR113808 consist of: (i) the ionic interaction between the protonated amine and Asp3.32; (ii) the hydrogen bond between the carbonylic oxygen and Ser5.43; (iii) the hydrogen bond between the ether oxygen and Asn6.55; (iv) the hydrogen bond between the C-H groups adjacent to the protonated piperidine nitrogen and the pi electrons of Phe6.51; and (v) the pi-sigma aromatic-aromatic interaction between the indole ring and Phe6.52. This computational model offers structural indications about the role of Asp3.32, Ser5.43, Phe6.51, Phe6.52, and Asn6.55 in the experimental binding affinities. Asp3.32Asn mutation does not affect the binding of GR113808 because the loss of binding affinity from an ion pair to a charged hydrogen bond is compensated by the larger energetical penalty of Asp to disrupt its side chain environment in the ligand-free form, and the larger interaction between Phe6.51 and the piperidine ring of the ligand in the mutant receptor. In the Phe6.52Val mutant the indole ring of the ligand replaces the interaction with Phe6.52 by a similarly intense interaction with Tyr5.38, with no significant effect in the binding of GR113808. The mutation of Asn6.55 to Leu replaces the hydrogen bond of the ether oxygen of the ligand from Asn6.55 to Cys5.42, with a decrease of binding affinity that approximately equals the free energy difference between the SH...O and NH...O hydrogen bonds. Because these residues are also present in the other members of the neurotransmitter family of G protein-coupled receptors, these findings will also serve for our understanding of the binding of related ligands to their cognate receptors.

Amino Acid Sequence↗

PubMed2001

A computational model for estimating the mechanics of horizontal flapping flight in bats: model description and validation.

We combine three-dimensional descriptions of the movement patterns of the shoulder, elbow, carpus, third metacarpophalangeal joint and wingtip with a constant-circulation estimation of aerodynamic force to model the wing mechanics of the grey-headed flying fox (Pteropus poliocephalus) in level flight. Once rigorously validated, this computer model can be used to study diverse aspects of flight. In the model, we partitioned the wing into a series of chordwise segments and calculated the magnitude of segmental aerodynamic forces assuming an elliptical, spanwise distribution of circulation at the middle of the downstroke. The lift component of the aerodynamic force is typically an order of magnitude greater than the thrust component. The largest source of drag is induced drag, which is approximately an order of magnitude greater than body form and skin friction drag. Using this model and standard engineering beam theory, we calculate internal reaction forces, moments and stresses at the humeral and radial midshaft during flight. To assess the validity of our model, we compare the model-derived stresses with our previous in vivo empirical measurements of bone strain from P. poliocephalus in free flapping flight. Agreement between bone stresses from the simulation and those calculated from empirical strain measurements is excellent and suggests that the computer model captures a significant portion of the mechanics and aerodynamics of flight in this species.

Animals↗

PubMed2005

Non-linear fluid-coupled computational model of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: The dynamics of the mitral valve result from the synergy of left heart geometry, local blood flow and tissue integrity. Herein is presented the first coupled fluid-structure computational model of the mitral valve in which valvular kinematics result from the interaction of local blood flow and a continuum representation of valvular microstructure. METHODS: The diastolic geometry of the mitral valve was assembled from previously published experimental data. Anterior and posterior leaflets were modeled as networks of entangled collagen fibers, embedded in an isotropic matrix. The resulting non-linear continuum description of mitral tissue was implemented in a three-dimensional membrane formulation. Chordal tension-only behavior was defined from experimental tensile tests. The computational model considered the valve immersed in a domain of Newtonian blood, with an experimentally determined viscosity corresponding to a shear rate of 180 s(-1) at 37 degrees C. Ventricular and atrial pressure curves were applied to ventricular and atrial surfaces of the blood domain. RESULTS: Peak closing flow and volume were 51 ml/s and 1.17 ml, respectively. Papillary muscle force ranged dynamically between 0.0 and 2.6 N. Acoustic pressure (RMS) was found to be 3.3 Pa, with a peak frequency of 72 Hz at 0.064 s from the onset of systole. Model predictions showed excellent agreement with available transmitral flow, papillary force and first heart sound (S1) acoustic data. CONCLUSION: The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent a significant advance in computational studies of the mitral valve. This model will be the foundation for future computational studies on the effect of pathophysiological tissue alterations on mitral valve competence.

Algorithms↗

PubMed1994

Computer modeling of siphoning for CSF shunt design evaluation.

A computer model of the cerebrospinal fluid (CSF) compartment and various shunt designs was developed to simulate CSF dynamics, particularly in the upright position in which siphoning is known to occur. This novel mathematical model of the CSF compartment incorporates negative pressure and volume components that permit simulation of siphoning. The model was tested with data from a previously reported animal experiment. The correspondence between the model simulation and the reported intracranial pressure and CSF shunt flow rate was very good. A simulation of a shunted hydrocephalic patient in the recumbent and upright position was then carried out to examine the effects of a standard shunt valve, an externally adjustable valve, a variable resistance valve, and an antisiphon device. The resulting pressure profiles, which conformed to previously reported data, indicate that this model would be useful for the evaluation of current and future shunt designs.

Brain↗

PubMed1992

Intra-blood-brain barrier synthesis of IgG: comparison of IgG synthesis formulas in a computer model and in 1,629 consecutive specimens.

We evaluated four formulas for estimating the intra-blood-brain barrier (IBBB) synthesis of IgG in a computer model of two types of BBB damage and in 1,629 consecutively received pairs of CSF and serum. These four formulas were the IgG synthesis rate (SR), IgG(loc) (ie, local), IgG index, and IgG extended index. Results from the 1,629 specimens and the computer model of type 2 BBB damage (partial or total loss of selective filtration) accurately predicted problems encountered with the IgG SR in clinical practice. In both the model and with the results from the 1,629 specimens, the combination of the IgG(loc) and IgG index formulas minimized the possibility of false-positive and false-negative results and yielded the most reliable results for IBBB synthesis of IgG in the presence or absence of increased permeability of the BBB. Additional studies with detailed clinical correlations will allow an accurate assessment of how effectively this combination of formulas can help to rule in or out the diagnosis of a particular disease or inflammatory condition of the CNS.

Albumins↗

PubMed2006

Enabling computer models of the heart for high-performance computers and the grid.

Although it is now feasible to compute multi-cellular models of the heart on a personal desktop or laptop computer, it is not feasible to undertake the detailed sweeps of high-dimensional parameter spaces required if we are to undertake in silico experimentation of the complex processes that constitute heart disease. For this research, modelling requirements move rapidly beyond the limit of commodity computers' resource both in terms of their memory footprint and the speed of calculation, so that multi-processor architectures must be considered. In addition, as such models have become more mature and have been validated against experimental data, there is increasing pressure for experimentalists to be able to make use of these models themselves as a key tool for hypothesis formulation and in planning future experimental studies to test those hypotheses. This paper discusses our initial experiences in a large-scale project (the Integrative Biology (IB) e-Science project) aimed at meeting these dual aims. We begin by putting the research in context by describing in outline the overall aims of the IB project, in particular focusing on the challenge of enabling novice users to make full use of high-performance resources without the need to gain detailed technical expertise in computing. We then discuss our experience of adapting one particular heart modelling package, Cellular Open Resource, and show how the solving engine of this code was dissected from the rest of the package, ported to C++ and parallelized using the Message-Passing Interface. We show that good parallel efficiency and realistic memory reduction can be achieved on simple geometries. We conclude by discussing lessons learnt in this process.

Action Potentials↗

PubMed2002

The effect of thermodynamic data on computer model predictions of uranium speciation in natural water systems.

Computer models have found widespread application in order to help elucidate and predict changes in environmental systems. One such application is the prediction of trace metal speciation in aqueous systems. This is achieved by solving a set of non-linear equations involving equilibrium constants for all the components in the system, within mass and charge balance constraints. In this study a comparison of the predicted uranium speciation from two computer programs, WHAM and PHREEQCI, is used to illustrate the effect variations in thermodynamic data can have on the models produced. Using the original thermodynamic data provided with the models, WHAM predicted the UO2(2+) ion as the major species (84%) while PHREEQCI predicted UO2(HPO4)2(2-) as the major species (86%). Substituting uranium data from the Nuclear Energy Agency Thermochemical Database project (NEA-TDB) into both programs produced similar results from each program, with UO2F+ predicted to dominate (68%) in a groundwater sample. Natural water samples often contain humic substances. The possible interaction of such substances with uranium was also modelled. The WHAM program includes a discreet site electrostatic humic substance model, however in order to use the PHREEQCI program to model humic substance interactions, a 'model fulvic acid' dataset was added to the program. These models predicted 85 to 98% uranium-humic substance species at neutral pH. This indicates that humic substances do need to be taken into account when modelling uranium speciation in natural water samples.

Computer Simulation↗

PubMed1993

A computational model of the HBK2 potassium channel ion pore.

A computational model of the putative ion pore region of the HBK2 potassium channel was developed. Utilizing experimentally derived constraints, conformations corresponding to both the open and closed states of the ion pore were determined. Also, a conformational basis for the different sensitivites of the internal and external tetraethylammonium binding sites has been proposed. The model presented here suggests a role for other regions of the HBK2 protein in determining the ion pore conformation.

Amino Acid Sequence↗