SEARCH · PubMed Health

Results for “Computer Simulation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

PubMed1991

Model and computer simulations of the motion of DNA molecules during pulse field gel electrophoresis.

A model is presented for the motion of individual molecules of DNA undergoing pulse field gel electrophoresis (PFGE). The molecule is represented by a chain of charged beads connected by entropic springs, and the gel is represented by a segmented tube surrounding the beads. This model differs from earlier reptation/tube models in that the tube is allowed to leak in certain places and the chain can double over and flow out of the side of the tube in kinks. It is found that these kinks often lead to the formation of U shapes, which are a major source of retardation in PFGE. The results of computer simulations using this model are compared with real DNA experimental results for the following cases: steady field motion as seen in fluorescence microscopy, mobility in steady fields, mobility in transverse field alternation gel electrophoresis (TFAGE), mobility in field inversion gel electrophoresis (FIGE), and linear dichroism (LD) of DNA in agarose gels during PFGE. Good agreement between the simulations and the experimental results is obtained.

Chemical Phenomena↗

PubMed1996

Computational simulations of local vascular heparin deposition and distribution.

Local vascular drug delivery systems provide elevated concentrations in target arterial tissues while minimizing systemic side effects; however, definition of their precise pharmacokinetics remains elusive. The standard labeled tracer assays used in experimental vascular pharmacokinetic studies of these systems are limited because they quantify the arterial average drug concentration as opposed to transmural concentration profiles, require many animal experiments to elucidate the time-varying deposition, and track label rather than intact biologically active drug. In this study, computational simulations of drug deposition and distribution in vascular tissues after release from these systems have provided two important insights. First, simulations of arteries that were uniformly loaded with heparin predicted that most of the drug is cleared in < 1 h, illustrating the need for sustained modes of delivery. Second, some of the limitations of labeled tracers can be over come by combining experimental data with simulations that provided high spatial resolution. This enabled us to describe the kinetics of the deposited drug and distinguish soluble from reversibly bound and internalized drug within cells. The latter can help differentiate biologically viable drug from its committed inactive form or metabolites. These points have been illustrated through simulations of a novel endovascular hydrogel heparin-delivery system that has been applied to the porcine coronary artery. The basic models used in these simulations are generalized, and with the appropriate boundary conditions, binding and distribution constants can be used to study the physical interactions between any compound and tissue.

Animals↗

PubMed2006

Computer simulation of visual outcomes of wavefront-only corneal ablation.

PURPOSE: To evaluate the effectiveness, predicted visual outcome, and limitations of a corneal ablation algorithm that uses wavefront aberration measurement alone without the need for corneal shape information. SETTING: Contact Lens and Visual Optical Laboratory, School of Optometry, Queensland University of Technology, Brisbane, Australia. METHODS: Corneal topography and wavefront error data from 22 eyes of 11 potential refractive surgery candidates were used. A computer simulation of the corneal ablation was performed, and the predicted postoperative visual outcome was assessed by calculating the resulting wavefront root-mean-square (RMS) values and visual Strehl ratios. Additionally, the effect of ablation alignment error was examined. Finally, the visual outcomes of the wavefront-only corneal ablations were compared to those in an age-matched group of 20 emmetropic patients. RESULTS: Significant improvement in total and higher-order wavefront RMS was achieved postoperatively in both an ideal setting and in the case of ablation alignment errors. The predicted improvement in visual Strehl ratio in the potential refractive surgery candidates was significantly better than that in the untreated emmetropes. After additional simulated decentration of the pupil center by 150 microm, the result was slightly worse, but the change was found to not be significant when compared to the retinal image quality of emmetropes. CONCLUSIONS: Wavefront-only corneal ablation algorithms could potentially lead to significantly better visual outcomes than those normally encountered in untreated emmetropes, provided that the alignment error is not large. The presented methodology may be used as a screening tool to predict patients' visual outcomes before the surgery.

Adolescent↗

PubMed1997

Biological variation of International Normalized Ratio for prothrombin times, and consequences in monitoring oral anticoagulant therapy: computer simulation of serial measurements with goal-setting for analytical quality.

Oral anticoagulant therapy (OAT) has a well-established efficacy in prophylaxis and treatment of thromboembolic disorders. Because complications are related to intensity of OAT, optimal control of treatment is mandatory. In studies of OAT, as many as 30% of International Normalized Ratio (INR) measurements for prothrombin times fall outside the therapeutic interval. Preanalytical, analytical, and biological variation all contribute to this. Computer simulations of serial INR measurements were performed for various assumed in-treatment setpoints within the therapeutic interval INR 2.0-3.0 and for an "in-treatment within-subject variation" (CV) of 10.1%. Results are presented in difference plots with therapeutic intervals and critical differences. If the in-treatment setpoint is mid-interval (INR = 2.5), only 5% of simulated INR values fall outside the therapeutic interval. Setpoints deviating from the mid-interval and increases in the in-treatment within-subject variation considerably increase the number of observations outside the therapeutic interval and the critical differences. In conclusion, random variation, biological or analytical, and setpoints (targets) deviating from mid-interval explain a substantial number of the INR values outside therapeutic intervals observed in clinical studies. Analytical imprecision should be kept < 5% and analytical bias < +/- 0.2 INR.

Administration, Oral↗

PubMed2006

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome.

BACKGROUND: Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? METHODS: The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. RESULTS: Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5%-95% percentiles $42,259-$83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. CONCLUSION: ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS.

Computer Simulation↗

PubMed1982

A theory for the origin of a self-replicating chemical system. II. Computer simulation of the autogen.

In order to better understand the feasibility and limitations of the autogen (White 1980), a computer simulation based on the fluctuating clay environment was used to test whether autocatalytic growth would occur under various conditions. The results suggest that overall accuracies of replication and translation in the range of 90% and 10%, and protoenzyme turnover numbers of 10--120 monomers/protoenzyme/day are adequate for exponential growth. Nucleation of the components of the autogen from random background oligomers would be extremely rapid if oligomers lengths 2--6 were adequately functional, whereas oligomer lengths much greater than 10 are prohibited. The autogen would most likely nucleate and grow to dominance either rapidly (10--100 cycles of roughly 1 day each) or not at all.

Computers↗

PubMed1999

A multi-gate time-of-flight technique for estimation of temperature distribution in heated tissue: theory and computer simulation.

Non-invasive determination of temperature distribution in biological media is important in many heating-related studies, such as thermal treatment. In this paper, we present an in vitro ultrasound technique for estimation of temperature distribution in heated tissue. Our technique consists of two major steps: (1) using multiple time gates to track echo signals scattered from tissue regions at different depths; (2) estimating temperature distribution based on heating-induced changes of arrival times of echo signals scattered from the targeted tissue regions. We use the conventional cross-correlation approach to track echoes. For temperature estimation, we have developed an iterative method that takes into account the influences of thermal expansion and heating-induced change in the speed of sound on the time of flight. We have introduced a concept of thermal sensitivity of the time of flight and used it to derive a theoretical formula that relates the achievable accuracy on the estimation of tissue temperature to seven parameters. The seven parameters are tissue thermal sensitivity of the time of flight, signal-to-noise ratio, bandwidth and center frequency of the signal, degree of signal decorrelation induced by changes in tissue physical properties during tissue heating, and widths and spacing of the time gates. We tested our technique by computer simulation, using a random discrete scatterer model and temperature distribution data acquired in our laser heating experiments on prostate tissue of live dog. Simulation results showed that our technique could accurately estimate the temperature distribution in the heated tissue. Our technique is fast in terms of computation and could be used as a research tool for in vitro real-time monitoring of temperature distribution in tissue under hyperthermal heating.

Acoustics↗

PubMed1987

Effectiveness of a salt transport cascade in the renal medulla: computer simulations.

Based on morphological observations, it has been concluded that the upper parts of the long descending limbs of Henle's loops should be able to secrete salts into the tubular fluid (Kriz, W. Federation Proc. 42:2379-2385, 1983). In the same article, a hypothesis is given depicting how this active transport in concert with certain characteristics of the medullary architecture might produce a transport cascade toward the papillary tip, thus supporting the accumulation of salts in this region. The effectiveness of the proposed mechanism can be judged by a mathematical model only. The computer simulations of the present study demonstrate that this mechanism indeed leads to an increase of the concentrating capability of the renal countercurrent system.

Biological Transport, Active↗

PubMed1988

A computer simulation of hearing aid response and the effects of ear canal size.

The response of a hearing aid is affected by many factors which include the head and outer ear, the microphone, amplifier, and receiver used in the hearing aid, the properties of the ear canal and the eardrum, and acoustic feedback through the vent. This article presents a computer simulation of an in-the-ear (ITE) hearing aid that includes all of the above factors. The simulation predicts the pressure at the eardrum for a frontal free-field sound source. The computer model was then used to determine the effects on the hearing aid response due to variations in the size of the ear canal. The simulation indicates that, for an unvented hearing aid, changes in the size of the ear canal shift the overall sound-pressure level at the eardrum but have only small effects on the shape of the frequency response. The situation is more complicated when a vent is present, however, since changes in the size of the ear canal that cause apparently small perturbations in the acoustic feedback signal may, nonetheless, have large effects on the overall system response.

Computer Simulation↗

PubMed2005

The operant reserve: a computer simulation in (accelerated) real time.

In Skinner's Reflex Reserve theory, reinforced responses added to a reserve depleted by responding. It could not handle the finding that partial reinforcement generated more responding than continuous reinforcement, but it would have worked if its growth had depended not just on the last response but also on earlier responses preceding a reinforcer, each weighted by delay. In that case, partial reinforcement generates steady states in which reserve decrements produced by responding balance increments produced when reinforcers follow responding. A computer simulation arranged schedules for responses produced with probabilities proportional to reserve size. Each response subtracted a fixed amount from the reserve and added an amount weighted by the reciprocal of the time to the next reinforcer. Simulated cumulative records and quantitative data for extinction, random-ratio, random-interval, and other schedules were consistent with those of real performances, including some effects of history. The model also simulated rapid performance transitions with changed contingencies that did not depend on molar variables or on differential reinforcement of inter-response times. The simulation can be extended to inhomogeneous contingencies by way of continua of reserves arrayed along response and time dimensions, and to concurrent performances and stimulus control by way of different reserves created for different response classes.

Computer Simulation↗

PubMedDate not supplied

Computer simulations of the electric interactions between the phospholipid head-groups and ionic admixtures in the membrane surface.

Some phospholipids (e.g. lecithin) form a system of electric dipoles on the membrane surface layer. In the case of lecithin the positive dipole charge is located on the choline and the negative one on the phosphoric molecule group. These dipoles are arranged almost parallel to the membrane surface. Taking the dipole membrane structure as a base for further investigations, a computer model of the electrostatic interaction between the dipole system and the ionic admixture was investigated. The model presumes hexagonal centered or a rectangular flat geometry of the 121 dipoles distribution. The dipoles may rotate freely around round the motionless symmetry axis perpendicular to the system surface. The initial state is given by fixing the geometry of the dipole matrix and ionic admixture distribution. Subsequently this system underwent a computer simulation which consisted of a calculation of resultant force moments acting on each dipole caused by other dipoles and ions. These force moments lead the system to the equilibrium state (minimum of the binding energy). The minimum energy value of the dipoles system depends on concentration and charge of the admixtured ions. The results of repeated simulations indicate that the system achieve the least of all binding energy (the most stable equilibrium state) at 1.5% concentration of admixtured ions in case of ion charge equal to 1Q (where Q denotes arbitrary unit of ion charge) and at 2.5% concentration of admixtured ions in case of ion charge equal to 2Q. The calculated results are in a good agreement with the experimental.

Computer Simulation↗

PubMed1979

A theoretical approach to precipitin reactions: insight from computer simulation.

The theoretical consequences of different hypotheses of the mechanism of precipitin reactions have been evaluated by means of computer simulation. It has been found that the formation of compositionally different complexes in different antigen/antibody mixtures provides a valid explanation of the zoning phenomenon, but this concept fails to explain the absence of free antigen and of antigen in soluble complexes at the point of maximum percipitation. It is found that the following hypothesis provides an improved qualitative and quantitative explanation of percipitin reactions. In the first stage of the total reaction a series of compositionally different complexes is formed. As the second stage of the total reaction two kinds of processes are proposed. Inherently insoluble complexes precipitate causing the remaining soluble complexes to participate in mutual rearrangements to re-establish a new state of equilibrium in the supernatant. The inherently insoluble complexes, moreover, create a hydrophobic phase, distinct from the supernatant and cause the remaining otherwise soluble complexes to distribute themselves between the two phases according to a partition coefficient. A mathematical apparatus to study the consequences of this hypothesis is presented, and it is demonstrated that the features of precipitin curves can be explained nearly completely this way.

Antigen-Antibody Complex↗

PubMed2004

Modeling and computer simulations of tumor growth and tumor response to radiotherapy.

A model of tumor growth and tumor response to radiation is introduced in which each tumor cell is taken into account individually. Each cell is assigned a set of radiobiological parameters, and the status of each cell is checked in discrete intervals. Tumor proliferation is governed by the cell cycle times of tumor cells, the growth fraction, the apoptotic capacity of the tumor, and the degree of tumor angiogenesis. The response of tumor cells to radiation is determined by the radiosensitivities and the oxygenation status. Computer simulation is performed on a 3D rigid cubic lattice, starting out from a single tumor cell. Random processes are simulated by Monte Carlo methods. Short cell cycle time, high growth fraction, and tumor angiogenesis all increase tumor proliferation rates. Accelerated time-dose patterns result in lower total doses needed for tumor control, but the extent of dose reduction depends on the kinetics and the radiosensitivities of tumor cells. Tumor angiogenesis alters fully oxygenated and hypoxic fractions within the tumor and subsequently affects the radiation response. It is demonstrated for selected radiobiological parameters that the simulation tools are suitable to quantitatively assess the total doses needed for tumor control. Using the simulation tools, it is feasible to simulate time-dependent effects during fractionated radiotherapy and to compare different time-dose patterns in terms of their tumor control.

Cell Division↗

PubMed2004

Toward large-scale modeling of the microbial cell for computer simulation.

In the post-genomic era, the large-scale, systematic, and functional analysis of all cellular components using transcriptomics, proteomics, and metabolomics, together with bioinformatics for the analysis of the massive amount of data generated by these "omics" methods are the focus of intensive research activities. As a consequence of these developments, systems biology, whose goal is to comprehend the organism as a complex system arising from interactions between its multiple elements, becomes a more tangible objective. Mathematical modeling of microorganisms and subsequent computer simulations are effective tools for systems biology, which will lead to a better understanding of the microbial cell and will have immense ramifications for biological, medical, environmental sciences, and the pharmaceutical industry. In this review, we describe various types of mathematical models (structured, unstructured, static, dynamic, etc.), of microorganisms that have been in use for a while, and others that are emerging. Several biochemical/cellular simulation platforms to manipulate such models are summarized and the E-Cell system developed in our laboratory is introduced. Finally, our strategy for building a "whole cell metabolism model", including the experimental approach, is presented.

Biotechnology↗

PubMed1999

Computer simulation of microphase separation in ionic copolymers.

The formation of lamella microphases in symmetric neutral-ionic block copolymers has been investigated by constant volume-constant temperature (NVT) molecular-dynamics computer simulations using a generic coarse-grain model. Computations of counterion diffusion, pressure tensor, and the anisotropy of the structure factor are used to characterize the order-disorder transition (ODT). There is strong counterion condensation on the ionic blocks at temperatures well above the ODT; this creates a slight imbalance in the volume composition of the two blocks and results in a perforated lamella structure in the microphase. Below the ODT counterion diffusion is decoupled from the chain motions but is strongly anisotropic due to the microphase morphology. The high counterion diffusional mobility is discussed in terms of the relatively low value of the glass transition for the ionic blocks.

Journal Article↗

PubMed1998

Topographic mapping in the retinotectal projection by means of complementary ligand and receptor gradients: a computer simulation study.

Based on recent experimental studies of complementary gradients of receptor density (R) on the retinal surface and ligand density (L) on the tectal surface, and mapping of the high point on the receptor gradient to the low point on the ligand and vice versa, the servomechanism model was constructed involving a mechanism for the retinal axon to reach its target automatically sensing a difference between the signal strength (R.L) and the standard value (S). Computer simulations based on the model demonstrated desired two-dimensional topographic mapping of the retinal axons on the tectum, and explained three strange behaviors of the retinal axons that had been observed in stripe assays for retinal axons using stripes composed of tectal membrane fragments: repulsive behaviors of the retinal axons by the ligand substances, uncertainty of the nasal axons whether or not they show regional selectivity between substances of anterior and posterior tecta, and abrupt transition of growth of the axons originating at continuously varied retinal positions on the stripes having graded ligand density. Finally we suggested what is to be improved in stripe assays with the artificial gradient of the tectal membrane fragments.

Animals↗

PubMed2006

[Computer simulation study of the re-entry mechanisms in one-dimensional ischaemic myocardium].

Torsades de Pointes is a kind of severe ventricular arrhythmia. Myocardial ischaemia is one of the major causes leading to TdP. In this paper the mechanisms of the TdP were quantitatively studied under the condition of ischaemia based on the Noble98 dynamic model of the ventricular action potential. The study was conducted on one-dimensional homogeneous myocardium with the method of computer simulation. The models were firstly developed to simulate the lower excitability, extracellular accumulation of the K+ concentration or the decreased gap junctions in ischaemic myocardium. By separately reducing the Na+ conductance, increasing the extracellular K+ concentration or decreasing the conductance of the gap junctions enabled us to study the effect of each change in isolation. Then different degrees of ischaemic models were established to study their physiological features. The study showed that the conduction velocity became slower with the ischaemia aggravation, the action potential duration became shorter and the width of the vulnerable window obviously became larger than the normal conditions. The results illustrated that ischaemia was easily leading to unidirectional conduction block and resulted in re-entry and arrhythmias.

Computer Simulation↗

PubMedDate not supplied

A computer simulation study of isometric contraction of latissimus dorsi muscle used for cardiac assistance.

This study was designed to investigate the feasibility of a skeletal muscle pump employing latissimus dorsi muscle (LDM) for cardiac assistance. We developed and used a 2-dimensional mathematical model for LDM to investigate how the size of pneumatic balloons (30, 38, and 45 ml) and the three different locations (proximal, center, and distal) affect the pressure applied to the balloon by LDM. The computer simulation was performed by coding a visco-elastic and nonlinear 2-dimensional program that employed the finite element method (FEM). The muscle specific parameters of LDM were obtained from animal experiment results. The model is based on Hill's characteristic equation and composed of a contractile component and a passive element. The simulation results indicated that the intermediate and largest sized balloon lead to the highest and the lowest power (volume reduction per unit time interval), respectively. On the other hand, when the balloon is inserted in the distal LDM, the power is lower than in the other two positions, regardless of the balloon size. The above results suggest that the optimal size of the balloon should be selected depending on the muscle specific parameters of the actuator, and that the balloon should be inserted either in the proximal portion or center of the actuator.

Animals↗