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Results for “Computer Simulation”

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At least 343 records · Page 19Linked to original sources

PubMed1994

Estimation of growth hormone secretory patterns in children with use of a numerical deconvolution technique: experimental design with use of computer simulation.

Growth hormone (GH) secretion rates were estimated from 24-hour plasma GH concentration profiles using a model-based numerical deconvolution method. The basic kinetic parameters describing GH distribution and elimination were obtained from studies using single intravenous injections in GH-deficient children. Computer simulation techniques were used to produce 24-hour GH secretion profiles, which could serve as reference curves for analysis of the impact of certain practical aspects of the estimation of GH secretion, such as the method of blood sampling (discrete or integrated), sampling frequency and analytical errors. The results show that sampling intervals of 20 min are acceptable even in the presence of analytical errors, and that with this sampling interval, discrete blood sampling does not seem to be preferable to continuous withdrawal of blood.

Blood Specimen Collection↗

PubMed1992

Computer simulations of EPSP-spike (E-S) potentiation in hippocampal CA1 pyramidal cells.

Long-term potentiation of hippocampal excitatory synapses is often accompanied by an increase in the probability of spiking to an EPSP of fixed strength (E-S potentiation). We used computer simulations of a CA1 pyramidal neuron to test the plausibility of the hypothesis that E-S potentiation is caused by changes in dendritic excitability. These changes were simulated by adding "hot spots" of noninactivating voltage-sensitive Ca2+ conductance to various dendritic compartments. This typically caused spiking in response to previously subthreshold synaptic inputs. The magnitude of the simulated E-S potentiation depended on the passive electrical properties of the cell, the excitability of the soma, and the relative locations on the dendrites of the synaptic inputs and hot spots. The specificity of the simulated E-S potentiation was quantified by colocalizing the hot spots with a subset (40 of 80) of the synaptic contacts, denoted "tetanized," and then comparing the effects of the hot spots on these and the remaining (untetanized) synaptic contacts. The simulated E-S potentiation tended to be specific to the tetanized input if the untetanized contacts were, on average, electrically closer to the soma than the tetanized contacts. Specificity was also high if the tetanized and untetanized contacts were segregated to different primary dendrites. The results also predict, however, that E-S potentiation by this mechanism will appear to be nonspecific (heterosynaptic) if the synapses of the untetanized input are sufficiently far from the soma relative to the tetanized synapses. Experimental confirmation of this prediction would support the hypothesis that changes in postsynaptic excitability can contribute to hippocampal E-S potentiation.

Animals↗

PubMed1995

Biological significance of tumor thickness. Theoretical considerations based on computer simulation.

Maximum vertical tumor thickness is a highly significant prognostic criterion in cutaneous melanoma. To date, little is known about the problem, why thick lesions are more capable of metastatic spread than thin ones. To evaluate theoretical possibilities of the biological impact of thick lesions, computer simulation of tumor growth was performed. In a set of 35,000 simulated tumors, the thickness of the resulting tumor was measured and the functional simulation settings contributing to tumor thickness were identified by statistical methods. It turned out that in this theoretical model of tumor growth, besides time, which is the most important factor, other factors contribute to tumor thickness. These are tumor cell motility, particularly when stimulated by stromal elements, a decreased rate of tumor cell loss, and pronounced proliferation associated with high numbers of cell cycle generations in the tumor cells. These findings are in agreement with experimental data indicating that metastatic capacity may depend on increased motility, stroma-induced motility stimulation, evasion from the host immune system, and genetic instability manifesting during cell cycling. Thus the observations may help to clarify the relationship of vertical tumor thickness and poor clinical outcome in cutaneous melanomas.

Cell Cycle↗

PubMed1993

Computer simulations of the differentiated pay structure model.

The differentiated pay structure (DPS) model determines a nurse's base pay on the basis of education, position, and expertise level, adjusting that base for part-time employment, differentials for nonbusiness hours, and single payment bonuses to reward longevity. Using computer simulations, the model was tested with data from two urban hospitals. The findings show that the model can be applied in a manner that is acceptable in terms of budget. By using the DPS model, administration can compensate for those objective employee behaviors that employers value the most.

Computer Simulation↗

PubMed1996

Production of proteinase A by Saccharomyces cerevisiae in a cell-recycling fermentation system: experiments and computer simulations.

Overproduction of proteinase A by recombinant Saccharomyces cerevisiae was investigated by cultivations in a cell-recycling bioreactor. Membrane filtration was used to separate cells from the broth. Recycling ratios and dilution rates were varied and the effect on enzyme production was studied both experimentally and by computer simulations. Experiments and simulations showed that cell mass and product concentration were enhanced by high ratios of recycling. Additional simulations showed that the proteinase A concentration decreased drastically at high dilution rates and the optimal volumetric productivities were at high dilution rates just below washout and at high ratios of recycling. Cell-recycling fermentation gave much higher volumetric productivities and stable product concentrations in contrast to simple continuous fermentation.

Aspartic Acid Endopeptidases↗

PubMed1990

A model for computer simulation of P-glycoprotein and transmembrane delta pH-mediated anthracycline transport in multidrug-resistant tumor cells.

Anthracycline resistance in multidrug-resistant (MDR) tumor cells is due in part to a reduced cellular drug accumulation. Using a simple kinetic model and numerical computer simulations, we have analyzed mathematically the following possible mechanisms controlling fluxes of the membrane permeable anthracyclines in MDR cells: (1) active outward transport via a specific drug transporter (P-glycoprotein), (2) exocytotic drug export via the endosomal vesicle system, and (3) pH-gradients across the plasma membrane. Model calculations were based on morphometric and kinetic data previously presented in the literature for daunorubicin transport in wild-type Ehrlich ascites tumor cells (EHR2) and the corresponding daunorubicin (DNR)-resistant cell line EHR2/DNR+. The results confirm the possible importance of the cell-surface pH in controlling DNR accumulation in the cells. With P-glycoprotein as the main efflux pump, a catalytic constant of the protein greater than 40 mol DNR transported/mol protein per min is predicted by the model calculations. Changes in the drug binding affinity of P-glycoprotein (Km = 10(-9)-10(-6) M) is of little importance in influencing its effectiveness to reduce DNR accumulation, which could explain the broad substrate specificity of the MDR efflux pump system. The conditions to evaluate unidirectional fluxes of DNR across the plasma membrane in cells with active P-glycoprotein are defined. An efflux mechanism which relies solely on pH-dependent drug trapping in a pH 5 endosomal compartment by a simple diffusion process followed by exocytosis, appears inadequate to account for the high rate of DNR efflux in EHR2/DNR+ cells.

Animals↗

PubMed1993

Estimates by computer simulation of genetic distances from comparisons of RNAse A mismatch cleavage patterns.

The RNAse A mismatch cleavage method was used to analyze genomic variability in RNA and DNA systems. However, there is no method which relates the digestion patterns observed to the extent of genetic variation. Here we report computer simulations which provide a simple estimator of genetic distances from the comparison of RNAse A digestion patterns. The results show that the number of non-shared fragments is proportional to the number of mutations between each pair of sequences compared. This prediction is supported by the comparison of the RNAse A mismatch patterns and the nucleotide sequences of a set of influenza A (H3N2) hemagglutinin genes. The procedure allows a quantitative and reliable use of the RNAse A mismatch cleavage method.

Computer Simulation↗

PubMed1991

Applications of a computer simulation model of the natural history of CD4 T-cell number in HIV-infected individuals.

Data from the Multicenter AIDS Cohort Study (MACS) of 1637 gay men, recruited in 1984 and 1985 in Los Angeles and followed at 6-monthly intervals, are used to develop a computer simulation model of the typical pattern of CD4 T-cell number changes in HIV-infected AIDS-free subjects. The empirical model incorporates the following features: (1) within-person and between-person variability in CD4 measurements; (2) variation in the rates of decline of CD4 values; (3) variation in the level of CD4 at which clinical AIDS is diagnosed, and (4) greater absolute variation in CD4 values in men with high CD4 levels compared with men with low CD4 values. Three applications of the model to assist in the design and interpretation of clinical trials are given. Further applications to clinical trials and to estimate the current and future spectrum of HIV-mediated immunological disease in the USA, as measured by the CD4 values, are discussed.

Biomarkers↗

PubMed1991

Computer simulation analysis of morphological patterns in human melanocytic skin tumours.

Tumour cell proliferation and particularly tumour cell motility are considered to be essential pre-requisites for invasive tumour growth. Despite abundant in vitro data on tumour cell motility, the behaviour of tumour cells in complex human tumour tissues is yet unknown. In this study, estimates of proliferation and motility are statistically derived from morphological tumour patterns in human melanocytic skin tumours. Two-dimensional, discrete, random computer simulations of tumour growth were carried out in order to determine the influence of tumour cell proliferation and motility on morphological patterns. A set of binary morphological criteria turned out to facilitate a significant estimate of the relative probabilities of motility and proliferation (CART analysis). When the same morphological criteria were applied to H & E stained slides of 45 melanocytic skin tumours, benign common nevi showed a predominance of motility, whereas primary and metastatic malignant melanoma revealed a predominance of proliferation. The direct assessment of the number of proliferating cells by Ki-67 staining shows a steep increase from benign nevi to primary and metastatic melanoma. These data provide first evidence that in benign common nevi the overall motility exceeds the very low degree of proliferation, whereas in malignant melanocytic tumours proliferation considerably exceeds tumour cell motility.

Cell Division↗

PubMed1997

Computer simulation to support policy making in the control of pseudorabies.

A further integration of international markets makes a coordinated policy against contagious animal infections increasingly important. In the future, stricter demands are to be expected concerning the control and eradication of such infections. To anticipate these demands, a computer simulation model is created in which scenarios can be evaluated with respect to epidemiological and economic effects of the infections and control strategies. In this paper, the simulation model is described for Pseudorabies in swine. In the model, the population of herds is subdivided into two main herd types: breeding and finishing. Each herd is in one of 24 states per herd type. The states are based on (1) the reproduction ratio R which is the number of secondary cases caused by one infectious herd, (2) the prevalence for each value of R and (3) the expected number of infectious animals in an infectious herd within each prevalence range and for each R. The different values of R are based on experiments and field data in which different vaccination strategies were used. The transition matrix with the probabilities of every transition from one state to another is calculated on a weekly base. With this matrix the distribution of herds over states from week to week is derived. To include a dynamic element in the transition probabilities, the number of newly infectious herds per week is a function of animal and other contacts, including aerial, material and personal contacts. Calculations show that the infection in the Dutch swine population will not disappear without vaccination. With a vaccination scheme in which sows are vaccinated 3 times per year and fattening pigs 1 time per cycle the infection will ultimately be eradicated, but 2 vaccinations per cycle for fattening pigs are needed to eradicate the infection within an acceptable timespan (i.e. 2 to 3 years). The latter strategy will become compulsory in the Netherlands from October 1st 1995.

Animals↗

PubMed1994

Importance of collateral vessels in aortic coarctation: computer simulation at rest and exercise using transmission line elements.

Coarctation of the aorta causes arterial hypertension in the upper body and a low blood pressure downstream. Collateral blood vessels compensate by reducing the downstream pressure drop. To study the effect of various coarctation and collateral properties, we designed a computer model of the arterial circulation. The model contains a flow source and a library of subroutines for the lines and connectors. Distributed friction and wall viscoelasticity effects are included. Computer simulation was performed, using published values for vessel dimensions, in an arterial model with a coarctation and one lumped collateral. Rest and two levels of exercise (by increased heart rate) were studied. Without a collateral, we found the downstream pressure of the model was extremely dependent on the size of the coarctation. A collateral vessel reduced the pressure difference between the up- and downstream circulations. For a severe coarctation, the length and the diameter of the collateral were the main factors determining the downstream pressure and flow, whereas wall stiffness of the collateral had little influence. The relationship between mean pressure drop and cardiac output in coarctation was also dependent on the peripheral resistance in different flow beds, especially during exercise.

Aortic Coarctation↗

PubMed1994

Computer simulations of the effects of different synaptic input systems on the steady-state input-output structure of the motoneuron pool.

1. The effects of different types of synaptic input on the steady-state input-output relations of the mammalian motoneuron pool were investigated by the use of computer simulations. The properties of the simulated motor units and their synaptic inputs were based as closely as possible on the experimental data from studies in the cat hindlimb. 2. Three basic types of synaptic input systems were simulated: postsynaptic, presynaptic, and neuromodulatory. The effects of these inputs on three aspects of the system input-output structure were studied: gain, precision, and motor-unit type utilization. 3. The gain analyses were based on a simulation of the steady-state homonymous Ia input. The gain of this steady-state Ia "reflex" was found to be determined largely by the slope of the pool input-output function. Precision was evaluated in two ways, from the amplitudes of the quantal steps due to motor-unit recruitment and from the sensitivity of the input-output function to noise. The pattern of motor-unit type utilization allowed indirect assessment of fatigue resistance: the larger the percentage of force generated by FF units, the lower the fatigue resistance. 4. A uniformly distributed input (i.e., one that generates equal input in all motoneurons) generates outputs that are solely determined by the intrinsic properties of the motor units. Thus the gain, precision, and motor-unit type patterns generated by a uniform input were used as the basis with which the effects of all other input systems were compared. 5. Postsynaptic excitatory inputs with nonuniform distributions within the pool did influence gain. The greatest effect was the increase mediated by the rubrospinal excitatory input (27% increase at 30% of maximal force). However, this input also greatly decreased both fatigue resistance and precision, due to increased activation of FF units at low force levels. In contrast, the Ia input slightly decreased gain (12% decrease at 30% of maximum force) while slightly increasing fatigue resistance and precision. 6. The simulated neuromodulatory input was based on the monoaminergic reticulospinal effect on motoneurons. Gain was generally increased by the monoaminergic input. However, the magnitude of the increase strongly depended on whether the monoaminergic effects were largest on S units (giving a 20% increase at 30% of maximum force), equal on all types (52%), or largest on FF units (102%). Presynaptic inhibition reduced gain with no effect whatsoever on fatigue resistance or precision. 7. Therefore Ia reflex gain was modifiable by all three types of input: postsynaptic, presynaptic, and neuromodulatory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Using the standard staircase to measure the point of subjective equality: a guide based on computer simulations.

In experiments that measure a point of subjective equality, it is necessary to employ a psychophysical technique that measures the 50% point (P50) on the psychometric function. The standard staircase is an attractive candidate, because its simplicity makes it easy to understand and implement. However, Pentland (1980, Perception & Psychophysics, 28, 377-379) found his own maximum likelihood method (Best PEST) to be considerably less variable than the standard staircase. Here, computer simulations were used to study the effects of manipulating several parameters of the standard staircase in order to try to find a variant that would be competitive with the performance of Best PEST. A graphical summary of some of the standard staircase implementations that were found to be most stable is presented in order that investigators may choose easily the parameters best suited to their requirements. A comparison with an implementation of Pentland's Best PEST failed to replicate Pentland's finding, suggesting that investigators should have no misgivings about the standard staircase in experiments that measure a point of subjective equality.

Algorithms↗

PubMed1997

Formation of the branching pattern of blood vessels in the wall of the avian yolk sac studied by a computer simulation.

The present study was performed to provide data to support the notion previously believed but not proved experimentally or theoretically, that blood vessels are formed by the selection of capillaries in the network. In an attempt to understand the mechanism of formation of blood vessel branching structures, the transformation of a capillary network to a branching system in the wall of quail yolk sac was successively recorded by a series of photographs, and a computer simulation was carried out for the process of in vivo vascularization based on the photographs. The simulation demonstrated that a positive feedback system participated in the formation of a branching structure. That is, vessels which had been much used were enlarged, whereas less used vessels were reduced in their size and finally extinguished. The enlarged vessels became major components of the branching system. As the body of an embryo grew, it was observed that polygonal capillary networks enlarged, which led each polygon of the network to divide into a few finer polygons. Then, some of the capillary vessels were again selected and formed a branching system. This process repeated during the body growth, indicating that the vascular system developed adaptively to the body growth. A region where the growth was fast, received much blood flow and produced finer networks of capillaries. Thus, it was experimentally demonstrated for the first time that capillaries in the network are successively selected by a positive feedback mechanism and form blood vessels.

Animals↗

PubMed1995

Application of R-charts to detection of random errors: a computer simulation study.

The application of R-charts to quality control in clinical chemistry was investigated. These charts are widely used in statistical process control and plot the range (ie the difference between the highest and the lowest values) of a set of controls. A set of five control serums was considered. A computer simulation program was developed for this investigation. It showed a power function that is remarkably insensitive to systematic errors. Consequently these charts may be a useful tool in discriminating between systematic and random errors, helping the trouble-shooting significantly, if used concurrently with Levey-Jennings' charts. Nevertheless, as several control samples are necessary, this technique is not cost-effective for short analytical runs.

Bias↗

PubMedDate not supplied

Use of computer simulations for quantitation of 31P ISIS MRS results.

The difficulties in quantitation of in vivo 31P spectra are exacerbated by the fact that, in general, coils with inhomogeneous B1 fields are used with in vivo samples. A general method for quantitation of in vivo 31P MRS results obtained with the ISIS localization method was developed using computer simulations. The simulation calculates the preparation of the sample magnetization throughout the sample by the ISIS pulse sequence, as well as the sensitivity of signal reception. The calculation accounts for both the B1 field and the B0 gradients applied to the sample. The sensitivity of the experiment is expressed by integration of the simulated signal over the sample, assuming a homogeneous sample. The primary advantage of this approach is that a separate localization experiment on a phantom of known concentration is not required each time parameters of the localization experiment, such as dimensions or location of the localized volume, are altered. In addition, the simulations indicate the degree of contamination (signal from outside of the localized volume) that occurs, and provide a means of comparing different executions of the ISIS experiment. Experiments were performed on phantoms to verify the simulations, and experimental results on human brain and liver are reproduced to show that this approach provides reasonable estimates of metabolite levels in terms of molar concentrations.

Computer Simulation↗

PubMed1990

[Basic study on criteria for the reactivity of non-stress tests by means of computer simulation].

The non-stress test has become one of the most popular tests for antenatal surveillance in modern obstetrics. However, the fact that there are so many criteria for 'reactivity' in this test has made it rather difficult to interpret the results of these tests and compare them with each other. Using computer simulation of the occurrence of acceleration in fetal heart beats, the sensitivity and specificity of eight criteria which are in general use were studied. Diagnosis by Brown's criteria produced the best results for both sensitivity and specificity, but the long time necessary for this test is a drawback. However, the predictive value positive (probability of poor fetal outcome with nonreactivity) is only 62% even according to Brown's criteria when the test is done for antenatal care screening of an unrestricted population. The results of the test are far more convincing when it is reactive because the predictive value negative is more than 96%, even when strictly interpreted.

Computer Simulation↗

PubMedDate not supplied

[Teaching medical diagnosis by computer simulation].

A program of computer-assisted teaching, called AEDM, has been developed to simulate, with a conversational type terminal, the natural process of medical decision making. This system rests on two softwares, 'teaching' and 'inquiring', with 10 000 PASCAL instructions and the database of a computer-assisted diagnostic system (about 100 MO). The study describes the objectives and the characteristics of a system based on a simulation program; using natural procedures and non-specialized software is useful to develop computer-assisted teaching concerning different fields of pathology.

Computer-Assisted Instruction↗