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At least 649 records · Page 36Linked to original sources

PubMed2001

Computer-simulation studies on roles of potassium currents in neurotransmission of the auditory nerve.

Our previous work showed that action potentials (APs) fired in spiral ganglion (SG) neurons broaden gradually as a result of cumulative inactivation of the potassium current (I(K)), or with the application of a tinnitus-inducing drug (quinine). These results led us to speculate that AP width could affect neurotransmission of the auditory nerve under both normal and pathological conditions. This study used both experimental and theoretical approaches to test this hypothesis. We first measured the effect of AP broadening on Ca2+ entry into SG neurons. The effect of pre-synaptic AP broadening on post-synaptic responses was then assessed using computer-simulations. Results showed that wider presynaptic APs augmented responses of all types of postsynaptic glutamatergic receptors mainly by amplifying responses of postsynaptic receptors whose locations were not well aligned with the presynaptic release sites. A cumulative inactivation of I(K) in SG neurons significantly enhanced the responses of kainate receptors at all spike rates, while the augmentations for the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartic acid receptors were most prominent below 100 spikes/s. These modeling results suggest that, in addition to the AP firing rate and timing, the width of APs could affect the neurotransmission of the auditory nerve under both normal and pathological conditions.

Action Potentials↗

PubMed1980

Computer simulation of Gumboro disease outbreak. IV. Epizootics obtained by mode G-4 with flock size, age and immunity changed.

For the computer simulation of Gumboro disease outbreak by Model G-4 a program was written in FORTRAN. Of over twenty parameters involved in the model, the following three were used as input variables: (1) age of chickens at housing a1 (= 1 and 21); (2) size of flock at housing, N(a1) (= 100 and 1,000); and (3) geometric mean of the level of parentally conferred immunity at hatching, G(1) (= 0, 2, 8, and 32). The outputs were the graphic images demonstrating the chronological changes in a flock of innate resistance, parentally conferred immunity, and their sum, and the epizootic patterns composed of numbers of chickens at subclinical stage, clinically diseased, recovered, condemned, etc. at each age. As a result, stronger epizootics were produced at a lower level of parentally conferred immunity, and a higher age and a larger size of flocks. It was suggested that the subclinical stage might not be understood as an inapparent infection, and that a further postulate on the infection might be necessary to be introduced into this model to increase the practical utility, as well as the theoretical soundness, of this series of studies.

Age Factors↗

PubMed1996

Age-at-interview bias in anticipation studies: computer simulations and an example with panic disorder.

The phenomenon of anticipation has received considerable interest recently, especially among researchers investigating the genetics of psychiatric disorders. Anticipation can involve an earlier age at onset, greater severity, and/or a higher number of affected individuals in successive generations within a family. There is some controversy concerning detection of age-at-onset anticipation, due to problems of sampling bias, which may account for the phenomenon by preferentially sampling either lateronset parents or earlier-onset children. One source of bias that has not been explicitly investigated is differential age at interview between parent and child, such that parents have passed through more of the risk period than their offspring. We conducted a computer simulation study of affected parent-child pairs to determine whether, for realistic age-at-onset and age-at-interview distributions, this source of bias is a serious one. Our results show that the timing of diagnostic assessment can strongly affect the ascertainment of parent-child pairs, to produce a severely biased sample exhibiting apparent anticipation. Under realistic assumptions, an investigator may face a greatly increased risk of false positives (i.e. detecting anticipation when none exists). For example, a nominal 5% significance level may correspond to true p values as high as 50% or even approaching 100%. We conclude with an application to existing data on panic disorder.

Adult↗

PubMed1995

BULLET: a computer simulation of shotgun DNA sequencing.

BULLET is a computer program that simulates shotgun sequencing of DNA. The program has been used to simulate the sequencing of DNA fragments from 2 to 30 kb. To obtain 80% single or double-stranded sequence, a doubling of the DNA fragment size necessitates twice the number of sequencing reactions. However, a similar linear relationship does not apply to the determination of 100% single or double-stranded sequence. Data from BULLET were used to derive simple linear formulae that estimate the number of sequencing reactions necessary to partially sequence a fragment of DNA irrespective of size. When 80% of the double-stranded sequence has been determined, approximately 98% of single-stranded sequence will be known. This is a reasonable point to change to a more directed strategy of DNA sequencing.

Algorithms↗

PubMed1989

Use of a computer simulation to evaluate a seminar on child abuse.

A computerized patient simulation was used to evaluate the effectiveness of a seminar on child abuse in changing students' behavior in assessing the problem and developing a treatment plan. The CAMPS system (DACIS Software) was selected because it allows students freedom to follow any pathway in selecting over 500 items of history, physical examination, laboratory, and treatments. In interacting with this simulation, students demonstrated how they integrate their knowledge into a clinical setting. The three-hour seminar covered the topics of physical and sexual abuse, patient neglect, and utilization of community resources for treatment. The control (n = 43) and experimental (n = 38) groups, enrolled in an introductory course in pediatrics, were given references to read about child abuse as part of the core curriculum, but they may or may not have had exposure to patients in their clinical work. Only the experimental group attended the seminar. As part of the course evaluation program, both groups interacted with eight computer simulations, two of which involved cases of child abuse. In the classic case of child abuse, the control and experimental groups had similar results. In the more difficult diagnostic problem (shaken baby), the groups differed significantly in total score, cost of the evaluation, and percentage of correct diagnosis.

Child↗

PubMedDate not supplied

Computer simulation of sensorless fuzzy control of a rotary blood pump to assure normal physiology.

Rotary blood pumps have been considered effective permanently implantable devices. However, control of such pumps is quite complicated. Sensorless control of pump flow is required because no invasive flow or pressure sensors are wanted. Whereas insufficient pump output can cause underperfusion and should be avoided, overpumping may cause ventricular collapse and must be prevented. An intelligent physiologic control algorithm is highly desirable to reach optimal pump output based on physiologic requirements. We present an intelligent physiologic control mechanism for the blood pump allowing it to achieve normal physiology. Sensorless control of pump flow is gained by analysis of the electric motor current and speed. The required pump output flow is chosen based on heart rate, and an intelligent fuzzy logic based control mechanism is developed to adjust the motor input so that the pump output can reach required flow while also preventing the occurrence of ventricular suction or cannular collapse. Computer simulation was carried out, and the results indicate that the proposed algorithms can achieve required pump flow to obtain normal physiology, whereas overpumping can be prevented to provide safe operation.

Algorithms↗

PubMed1987

Nonuniformity of nucleotide substitution rates in molecular evolution: computer simulation and analysis of 5S ribosomal RNA sequences.

The effects of temporal (among different branches of a phylogeny) and spatial (among different nucleotide sites within a gene) nonuniformities of nucleotide substitution rates on the construction of phylogenetic trees from nucleotide sequences are addressed. Spatial nonuniformity may be estimated by using Shannon's (1948) entropy formula to measure the Relative Nucleotide Variability (RNV) at each nucleotide site in an aligned set of sequences; this is demonstrated by a comparative analysis of 5S rRNAs. New methods of constructing phylogenetic trees are proposed that augment the Unweighted Pair-Group Using Arithmetic Averages (UPGMA) algorithm by estimating and compensating for both spatial and temporal nonuniformity in substitution rates. These methods are evaluated by computer simulations of 5S rRNA evolution that include both kinds of nonuniformities. It was found that the proposed Reference Ratio Method improved both the ability to reconstruct the correct topology of a tree and also the estimation of branch lengths as compared to UPGMA. A previous method (Farris et al. 1970; Klotz et al. 1979; Li 1981) was found to be less successful in reconstructing topologies when there is high probability of multiple mutations at some sites. Phylogenetic analyses of 5S rRNA sequences support the endosymbiotic origins of both chloroplasts and mitochondria, even though the latter exhibit an accelerated rate of nucleotide substitution. Phylogenetic trees also reveal an adaptive radiation within the eubacteria and another within the eukaryotes for the origins of most major phyla within each group during the Precambrian era.

Animals↗

PubMed1997

Use of computer simulation to evaluate a putative cluster of genetic or teratologic outcomes: adjustment for "multiple hypotheses" and application to a reported excess of Down's syndrome.

The identification of an apparent excess of a genetic outcome in a particular area and/or a particular time often provokes considerable public alarm about the presence of an environmental mutagen. It is often difficult to determine in any particular case whether the observation, whatever its nominal statistical significance, is due to chance concatenation of events or to an environmental factor. Statistical evaluation is made more difficult by the profuse number of possible hypotheses that could have triggered concern about an excess. This renders it difficult to calculate the actual probability of the observation (or one more extreme). By attempting to identify similar types of outcomes that could have provoked an apparent excess and then undertaking computer simulations assuming random deviations from a constant rate, one may attempt to adjust for the problem of multiple hypotheses. We apply this approach to a reported excess of Down's syndrome in Norway in 1985-1986 in younger mothers, and conclude that there is a high probability that it arose by chance.

Adolescent↗

PubMed1983

Computer simulation of the cardiac conduction system.

A discrete computer model simulating the operation of the cardiac impulse transmission apparatus and the electropotential changes of the heart musculature has been developed on a NORD-100 minicomputer. The model is written in NORD-FORTRAN and allows description of practically all basic pathologies of the transmission apparatus. A simulated ECG curve is produced in each case. The current version of the model is especially suited for studies of heart rhythms. Pacemaker descriptions (of most important pacemaker types) have been introduced into the model and the computer computations make it possible to assess the effects of different pacemaker modes under different pathological situations. The principles on which the model is based is described and the paper shows concisely several examples in the form of simulated ECG records.

Arrhythmias, Cardiac↗

PubMed1994

A computer simulation accounting for dissimilar electrophoretic behavior between two similarly curved DNA fragments due to a difference in arc-length.

Arc-shaped bent DNA fragments of the same predicted planar curvature but differing in length by 20% were compared in regard to their mobilities in 3 to 10% polyacrylamide. The longer (155 bp) fragment is retarded far more severely than the shorter (124 bp) fragment. The effect of gel concentration in promoting the retardation is far more pronounced for the 155 bp than for the 124 bp fragment. Moreover, a temperature change from 25 degrees C to 4 degrees C does not substantially affect the gel concentration dependent mobility of the 124 bp fragment while it increases the retardation of the 155 bp fragment greatly. The strong increase in retardation brought about by a mere 20% increase in the length of the arc was accounted for by a simple computer simulation of gel electrophoresis which considered the rate of passage of arc-shaped objects through a two-dimensional array of disc-shaped obstacles. Since the simulation relies exclusively on geometric factors, its success in predicting the behavior of the 124 and 155 bp DNA fragments suggests that geometric factors are largely responsible for their electrophoretic properties. The simulation can account for the strong temperature effect on the retardation of a model of the 155 bp DNA in polyacrylamide gels by showing that a decreased degree of random motion has a profound effect on the modeled 155 bp particle, but not on the modeled 124 bp DNA.

Computer Simulation↗

PubMed1981

Computer simulation and experimental analysis of unipolar epicardial potentials in relation to the direction of propagation of the excitation.

A theoretical model for computer simulation has been introduced to predict the unipolar epicardial potentials corresponding to the different angles of propagation of the excitation wavefront. The simulated waveforms were compared with those observed in the animal experiments. In these experiments three unipolar epicardial potentials and one intramural potential were recorded using a thumbtack electrode with and without bipolar epicardial pacing. The direction of the propagation of the excitation was determined from the arrival time of the recorded waveforms. There was a close correspondence between the observed and the simulated waveforms. Furthermore, it was attempted to establish a quantitative relationship between the unipolar potential waveshape and the angle of propagation theta of the excitation. The difference between the positive and the negative peak normalized by the peak-to-peak height was used to define the change in the waveshape. A distinct relation was found to exist between the normalized difference R and the angle theta for the simulated potentials. There was a good correlation (r = 0.96 for n = 85) between angle theta 1 calculated from the arrival times and theta 2 determined from R, which suggest that the angle theta can be estimated from the unipolar epicardial potentials alone, without using any intramural electrode.

Action Potentials↗

PubMed1993

Use of pharmacologic data and computer simulations to design an efficacy trial of intravesical mitomycin C therapy for superficial bladder cancer.

Treatment of superficial bladder cancers by intravesical mitomycin C (MMC) chemotherapy gives a varying and incomplete response. Our recent pharmacokinetics and pharmacodynamics studies have shown that treatment effectiveness is limited by drug degradation in acidic urine and by drug dilution due to residual urine volume and urine production. A model was developed to predict drug exposure in tumors in the bladder wall and to correlate drug exposure with antitumor effect. The model is based on the known pharmacokinetic data in patients treated with intravesical chemotherapy, drug-penetration data in the bladder wall of patients undergoing radical cystectomy, and pharmacodynamic data on patients' bladder-tumor chemosensitivity. Computer simulations based on the model were generated. The simulations predicted that changes in treatment parameters would affect the therapeutic outcome in the following rank order: dose > residual volume > urine production > dosing volume > urine pH > dwell time. Tissue exposure could be enhanced by increased dose, complete bladder emptying, reduced fluid intake, use of the minimal dosing volume, and alkalinization of the urine to a neutral pH. Increasing the dwell time from 2 to 4 h gave an insignificant improvement and posed a compliance problem. The selected optimized regimen of a 40-mg dose, no residual volume, 0.62-ml/min urine production, a 20-ml dosing volume, and alkaline urine pH yielded a calculated 8.5-fold increase in tissue exposure over that achieved by the standard regimen, which consisted of a 20-mg dose, 32-ml residual volume, 1.5-ml/min urine production, a 20-ml dosing volume, and acidic urine pH. On the basis of previously established pharmacodynamic data, we hypothesize that the increase in tissue exposure in the optimized treatment would result in a 20% improvement over the standard therapy along with an increase in the recurrence-free rate from 56% to 76% of patients. A phase III efficacy trial comparing the optimized and standard regimens is proposed.

Administration, Intravesical↗

PubMed1999

Computer Simulation of the Aggregation and Sintering Restructuring of Fractal-like Clusters Containing Limited Numbers of Primary Particles.

A random particle computer simulation (in three dimensions) was conducted to investigate the structure and aggregation characteristics of small clusters (containing limited numbers of primary particles per cluster). Though an individual cluster of small size does not satisfy the power law, it was found that these aggregated clusters are fractal-like and comply with the fractal power law form in a statistical sense. This statistically averaged fractal dimension decreases as the clusters become smaller. A cluster-restructuring model is further developed to simulate the topological evolution of dendritic structured materials due to sintering at high temperatures. Results indicate that the cluster fractal dimension increases as sintering proceeds for small clusters, in contrast to results for large clusters wherein the topology is retained and the fractal dimension remains constant. A relationship of the fractal dimension change with the normalized surface area of dendrites for different-sized clusters is established. Copyright 1999 Academic Press.

Journal Article↗

PubMed1986

Comparison of four single-point phenytoin dosage prediction techniques using computer-simulated pharmacokinetic values.

The predictive abilities of the following four single-point phenytoin dosage adjustment methods were compared using computer-simulated data: the Bayesian feedback method of Vozeh et al. (B), a linearized version of the Bayesian method (LB), the population-clearance method of Graves et al. (G), and the Rambeck nomogram (R). A series of 512 "subjects" with normally distributed values for volume of distribution, weight, and the Michaelis-Menten variables Vmax and Km were simulated. The steady-state serum concentration (SSSC) resulting from the administration of a standard dose of phenytoin sodium (5 mg/kg/day) was calculated, and "subjects" with SSSCs less than or equal to 12 mg/L or greater than or equal to 17 mg/L were entered in the study. If the concentration was greater than 50 mg/L or the standard dosage exceeded Vmax, the dosage was reduced empirically by 25%. Normally distributed random errors were introduced into the SSSC values to simulate actual patient data. The pharmacokinetic values, dosages, and SSSCs were used for predicting the dosage required to attain an SSSC of 14.9 mg/L. In the unstratified population, the mean error and mean-squared error were lowest for methods G and B, followed by methods LB and R. Methods B and LB gave the highest percentages of satisfactory dosage predictions based on the resultant SSSC value. The performance of all methods was superior at initial SSSCs greater than 8 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1988

Computer simulations of the effect of non-inactivating sodium channels on the electric behavior of excitable cells.

Non-inactivating sodium channels have been discovered in various cell types. Additionally, normal voltage-gated sodium channels can be induced to lose their ability to inactivate by treatment with proteolytic enzymes, with certain chemical reagents, or with toxins. The presence of non-inactivating sodium channels in the outer membrane of a cell is expected to profoundly modify the electrical properties of the cell, because the electrical depolarization of the cell and the opening of these channels reciprocally reinforce each other without intrinsic control. The normal resting state may thus be destabilized and a new resting state at depolarized resting potentials may become possible. In this study, computer simulations were carried out to systematically explore the patterns of behavior of excitable cells which have non-inactivating sodium channels in their plasma membrane. The cells were assumed to be space clamped and the relevant Hodgkin and Huxley equations were assumed to describe the electrical behavior of the cells, except that some or all of the sodium channels could not inactivate. The sodium currents were thus represented by the sum of two terms: FI.gNa.m3.h.(V-ENa) + (1-FI).gNa.m3(V-ENa), where FI(0 less than or equal to FI less than or equal to 1) is the fraction of sodium channels which inactivate normally, and the other symbols have their usual significance. The behavior of non-inactivating sodium channels created by pronase treatment or reaction with chemical reagents was found to conform with that predicted by the second term in this expression. The simulations thus quantitatively apply to excitable cells thus treated, but may serve additionally to qualitatively illustrate patterns of electrical activity induced by non-inactivating sodium channels also in other cases. A variety of possible types of electrical behavior was obtained: Normal behavior, including capability of firing action potentials, requires values of FI which are not far from unity, the permissible range depending on the fully activated potassium ion conductance, gK. Bistability, at which the cell may exist in one of two stable states of different resting potential, occurs when the value of FI is lowered. Transitions from the polarized to the depolarized resting states, and vice versa, may be brought about by depolarizing and hyperpolarizing triggers, respectively. Such behavior is like that of memory storage devices. Monostability at depolarized potentials is favored by low FI values and can occur if gK is less than the Hodgkin and Huxley value.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed2002

Examining the effects of tobacco treatment policies on smoking rates and smoking related deaths using the SimSmoke computer simulation model.

OBJECTIVES: To develop a simulation model to predict the effects of different smoking treatment policies on quit rates, smoking rates, and smoking attributable deaths. METHODS: We first develop a decision theoretic model of quitting behaviour, which incorporates the decision to quit and the choice of treatment. A model of policies to cover the costs of different combinations of treatments and to require health care provider intervention is then incorporated into the quit model. The policy model allows for the smoker to substitute between treatments and for policies to reduce treatment effectiveness. The SimSmoke computer simulation model is then used to examine policy effects on smoking rates and smoking attributable deaths. RESULTS: The model of quit behaviour predicts a population quit rate of 4.3% in 1993, which subsequently falls and then increases in recent years to 4.5%. The policy model suggests a 25% increase in quit rates from a policy that mandates brief interventions and the coverage of all proven treatments. Smaller effects are predicted from policies that mandate more restricted coverage of treatments, especially those limited to behavioural treatment. These policies translate into small reductions in the smoking rate at first, but increase to as much as a 5% reduction in smoking rates. They also lead to substantial savings in lives. CONCLUSIONS: Tobacco treatment policies, especially those with broad and flexible coverage, have the potential to increase smoking cessation substantially and decrease smoking rates in the short term, with fairly immediate reductions in deaths.

Computer Simulation↗

PubMed1996

Biospeciation, by potentiometry and computer simulation, of Sm-EDTMP, a bone tumor palliative agent.

153Sm-EDTMP (ethylenediaminetetra(methylenephosphonic) acid) is of considerable interest as a bone therapeutic radiopharmaceutical but its properties in solution are not yet well characterized. The protonation constants of EDTMP and the formation constants of the complexes of Sm-EDTMP have accordingly been measured potentiometrically by glass electrode titrations at 25 degrees C in 0.15 M NaCl. Six protonation constants (log beta 011 = 9.638, log beta 012 = 17.330, log beta 013 = 23.597, 10g beta 014 = 28.636, log beta 015 = 31.501, log beta 016 = 32.624) and the formation constants of the [Sm(EDTMP)H-1]6-(log beta 11-1 = 4.865), [SmEDTMP]5-(log beta 110 = 12.018), [Sm(EDTMP)H]4- (log beta 111 = 17.892) and [Sm(EDTMP)H2]3- (log beta 112 = 23.437) complexes were determined. Computer simulations indicate that the [SmEDTMP]5- and the hydroxy [Sm(EDTMP)H-1]6- species are the major Sm(III) complexes formed in blood plasma, which explains the high degree of localization in the kidney and urine observed in biodistribution studies. Calcium ions are probably the major competitor for EDTMP in blood plasma. As the presence of secondary skeletal metastases results in a high rate of bone turnover, it is possible that the high concentration of calcium at these sites encourages localization of 153Sm-EDTMP.

Bone Neoplasms↗

PubMed1987

Gamma-irradiation of homodeoxyoligonucleotides 32P-labelled at one end: computer simulation of the chain length distribution of the radioactive fragments.

Electrophoresis on polyacrylamide gels of the fragments resulting from gamma-irradiation of single-stranded oligodeoxyribonucleotides labelled at their 5'- or 3'-end proved to be a potent tool for the analysis of the radiation-induced chain breakage of DNA. Owing to the fact that the oligonucleotide may be ruptured at more than one site, the counting of the electrophoresis bands must be corrected and it is necessary to assess the influence of the cleavage position on the band intensities. A complicating factor is the inhomogeneity of the system due to the presence of the four bases A, T, C and G. To circumvent this problem, the homooligodeoxyribonucleotides (dA)15, (dC)15, (dT)15 were used as experimental probes. They were gamma-irradiated in solution, heated in alkali and the resulting fragments separated by gel electrophoresis. A computer simulation of the band intensities was compiled based on the general assumption that the chain breakage is homogeneous. The experimental results obtained from the homooligodeoxyribonucleotides labelled at either the 5' or the 3'-end are in excellent agreement with theoretical calculations. Abacus giving the gel band intensities (percentage) against the nucleotide positions and the remaining intensity of the original oligonucleotide have been obtained.

Computer Simulation↗