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Results for “Computer Simulation”

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At least 325 records · Page 18Linked to original sources

PubMed1987

Computer simulation of T3/T7 phage infection using lag times.

A minimal mechanism is proposed which describes the transcriptional and translational processes for four phage proteins (RNA polymerase, DNase, primase and DNA polymerase) involved in T3/T7 DNA replication. Phage DNA replication is also included. It is shown how lag times may be incorporated into a kinetic mechanism. The distinct three-stage transport of phage DNA into the bacterial host (E. coli) is considered. DNA transport is assumed to be rate-determining for the transcription of class I and II proteins. Transcriptional and translational lag times have been calculated on the basis of available gene mapping of T7 phages. The kinetic behavior of T7 and T3 phage infection is practically identical. The hydrolysis of bacterial DNA by phage DNase (endonculease and exonuclease) as well as the subsequent phosphorylation to the deoxymononucleoside triphosphates are assumed to be rate-determining in phage DNA replication. Good agreement with experiment is obtained in our computer simulations.

Computer Simulation↗

PubMed1990

Computer simulation of a cytosolic calcium oscillator.

A new interpretation of existing data permits us to define a model capable of accounting for agonist-induced Ca2+ oscillations in the cytosol of electrically non-excitable cells. The model only requires one Ca2+ store, which contains Ca2+ channels controlled by inositol 1,4,5-trisphosphate and Ca2+. Computer simulations may generate different experimentally observed patterns of Ca2+ oscillations.

Calcium↗

PubMed1991

Computer simulations and experimental studies of gel mobility patterns for weak and strong non-cooperative protein binding to two targets on the same DNA: application to binding of tet repressor variants to multiple and single tet operator sites.

A series of computer simulations of gel patterns assuming non-cooperative binding of a protein to two targets on the same DNA fragment was performed and applied to interprete gel mobility shift experiments of Tet repressor-tet operator binding. While a high binding affinity leads to the expected distribution of free DNA, DNA bound by one repressor dimer and DNA bound by two repressor dimers, a lower affinity or an increased electrophoresis time results in the loss of the band corresponding to the singly occupied complex. The doubly occupied complex remains stable under these conditions. This phenomenon is typical for protein binding to DNA fragments with two identical sites. It results from statistical disproportionation of the singly occupied complex in the gel. The lack of the singly occupied complex is commonly taken to indicate cooperative binding, however, our analysis shows clearly, that cooperativity is not needed to interprete these results. Tet repressor proteins and small DNA fragments with two tet operator sites have been prepared from four classes of tetracycline resistance determinants. The results of gel mobility shift analyses of various complexes of these compounds confirm the predictions. Furthermore, calculated gel patterns assuming different gel mobilities of the two singly occupied complexes show discrete bands only if the electrophoresis time is shorter than the inverse of the microscopic dissociation rate constant. Simulations assuming increasing dissociation rates predict that the two bands first merge into one, which then disappears. This behavior was verified by gel mobility analyses of Tet repressor-tet operator titrations at increased salt concentrations as well as by direct footprinting of the complexes in the gel. It is concluded that comparison of the intensities of the single and the double occupation bands allow a rough estimation of the dissociation rate constant. On this basis the sixteen possible Tet repressor-tet operator combinations can be ordered with decreasing binding affinities by a simple gel shift experiment. The implications of these results for gel mobility analyses of other protein-DNA complexes are discussed.

Binding Sites↗

PubMed1980

Computer simulation of metal ion equilibria in biofluids. Part 3. Trace metal supplementation in total parenteral nutrition.

Computer simulation models have been developed to investigate the effect of intravenous infusions of nutritive amino acid solutions metal equilibria in plasma. The distribution of Ca(II), Mg(II), Zn(II), Cu(II), and Mn(II) among the ligands in the nutritive fluid is calculated and used to estimate the amounts of each metal that should be included in future preparations.

Amino Acids↗

PubMed1983

Computer simulation of metabolism in palmitate-perfused rat heart. II. Behavior of complete model.

Intermediary metabolism in rat hearts perfused with 11 mM glucose plus 1 mM palmitate was simulated by a computer model. Several enzyme submodels in a previous version of the isolated rat heart computer model were improved, and a new fatty acid oxidation pathway model was added. Compartmentation of metabolites in a pseudo-stationary state was calculated, and its implications are discussed, e.g., citrate level may not regulate glycolysis because it is mostly mitochondrial. Citrate synthetase, controlled largely by its inhibitors, is of key importance in regulating fatty acid metabolism. The response of aconitase to the mitochondrial Mg2+ level is of major importance in setting both the mitochondrial citrate and isocitrate levels. Pyruvate dehydrogenase is about 96% in the inactive phosphorylated form, and the active form is also 15% inhibited by products, severely limiting pyruvate oxidation and causing preferential utilization of palmitate as the metabolic fuel. The simulation is consistent with a creatine phosphate shuttle which delivers high energy phosphate to the site of its utilization for mechanical work.

Animals↗

PubMed1989

The relationship between connectivity and tolerance as revealed by computer simulation of the immune network: some lessons for an understanding of autoimmunity.

According to a classical, antigen-driven view of the immune system, autoimmunity is due to the presence of self-reactive lymphocyte clones which have not been eliminated. However, computer simulations of the immune network show that the greater the degree of connectivity of a clone, the greater its degree of tolerance to chronic antigenic stimulation. This tolerance does not correspond to an absence of response on the part of the system as a whole. On the contrary, stimulation by a 'tolerogenic antigen' results in widespread modification and overall activation of the whole network. This suggests that on an autopoietic network view of the immune system, autoimmunity arises not because of the presence of self-reactive clones, which is completely normal, but because such clones are inadequately connected to the network. This amounts to a complete reversal in perspective, whose significance for the clinical treatment of autoimmunity and the future of immunology is discussed.

Animals↗

PubMed1995

Computer simulation of the propagation of contrast medium in a coronary artery during one cardiac cycle.

In some angiographic methods for measurement of mean coronary flow in ml/min, a threshold is applied to 'concentration-distance' curves obtained from a constant rate injection by computing the intravascular contrast medium concentration along the main coronary branches. If the shape of the velocity profile would remain parabolic throughout the cardiac cycle, the correct threshold value would be '50% of the concentration at the injection site'. But, coronary flow being strongly pulsatile, the shape of the velocity profile must be expected to vary appreciably within the cardiac phase. In order to investigate if a single, appropriate threshold value nevertheless exists for a great variety of coronary flow pulses and velocity profiles, the spreading of contrast medium injected continuously in a tube perfused by a time varying flow Q(t) was studied by computer simulation. While the particular time courses of flow and velocity profile appear to be of secondary importance, the ratio 'injection rate to peak coronary flow' has a major impact. If it is equal to or greater than 1, a threshold value of 47% is the best choice. If the ratio is markedly less than 1, no appropriate threshold exists and use of the 47% threshold will result in considerable flow underestimations. This was fully confirmed by measurements of absolute coronary flow performed in patients.

Blood Flow Velocity↗

PubMed1985

Reticular formation of the lower brainstem. A common system for cardio-respiratory and somatomotor functions. Considerations aided by computer simulations.

Parallel investigations were done using the reticular formation of the lower brainstem of dogs and computer simulated neuronal networks with properties of reticular neurones. By the aid of the simulations, understanding of the functional organisation of the common brainstem system, reticular formation and the experiments performed were optimized. The fact that discharge sequences of model neurones are very similar to those of reticular neurones was proved by interval histograms and covariance histograms. Discharges of neighbouring reticular neurones tend to be strongly coupled. In the model the discharges of the neurones could be coupled by common afferent inflows. Physiologically, neighbouring reticular neurones receive common afferents from peripheral somato-sensory systems. Neighbouring neurones with strongly coupled discharging are organized in subpopulations. The configurations of the subpopulations are determined by number and type of afferents actively influencing neurones and by the level of intrinsic activity of the network. Signal processing and transfer by neuronal subpopulations depend on the level of activity and on the degree of coupled discharging, i.e. the local organisation of the neurones.

Afferent Pathways↗

PubMed1984

On computer simulation methods used to study models of two-component lipid bilayers.

We show that the use of a computer simulation method introduced to calculate the equilibrium thermodynamic properties of a model of a two-component lipid bilayer membrane [Freire, E., & Snyder, B. (1980) Biochemistry 19, 88-94] is incorrect. This is done by comparing the method to that of Metropolis, which has been proven to generate equilibrium distribution of that model, and by showing that back-processes have been omitted in the implicit master equation of Freire and Snyder. We have illustrated this explicitly by first generating distributions according to the method of Freire and Snyder and then allowing the system to relax via the Kawasaki method, which uses the technique of Metropolis. We show that relaxation to a different distribution occurs. We also remark that the cluster distributions generated by the Freire-Snyder method are substantially different from those occurring in equilibrium distributions. Thus, conclusions about equilibrium thermodynamic properties such as specific heats and transition enthalpies or about transport properties or cluster properties at equilibrium cannot be drawn from the results obtained by using this method. Finally, we point out that the method of Freire and Snyder is appropriate to so-called aggregation models, which have been used to study irreversible growth; and we suggest biological systems that might be simulated by their method.

Computers↗

PubMed1994

On the mechanisms of growth cone locomotion: modeling and computer simulation.

In this paper we put forward a model for growth-cone locomotion in which the actin cytoskeleton is represented by a two-dimensional contractile network and the growth-cone membrane is represented by contractile segments coupled with the actin network. Our computer simulation suggests that many mechanisms, such as the actin polymerization and depolymerization, the attachment of actin filaments to the substratum, the transformation of the growth-cone neck into the axon, and the axonal transport, co-operate to generate growth-cone movement.

Actins↗

PubMed1993

Computer simulation of tumour cell invasion by a stochastic growth model.

The structure and function of biological systems are considered to be closely related. The present study addresses the question of how histological patterns of tumours are related to specific functional properties of the tumour cells. A mathematical model was developed, which facilitates the simulation of tumour growth and invasion by computer. The degree of cell division, migration and death can be interactively set and the simulation results can be observed on the screen. Additionally, these basic functional properties of a particular cell can be influenced by autocrine and paracrine factors. The study shows that the resulting morphological patterns closely depend on the preset functional properties of the tumour cells. Furthermore, each autocrine or paracrine factor, or combinations of these factors, induce peculiar modifications of the tumour pattern. These results provide evidence that histological tumour patterns reflect functional properties of the tumour cells and their interaction with the micro-environment. Qualitative and quantitative comparison of real tumour specimens with patterns simulated by computer may thus provide a logical base for a functional interpretation of static histological images.

Cell Death↗

PubMed1997

The EWMA control chart: properties and comparison with other quality-control procedures by computer simulation.

A quality-control chart based on exponentially weighted moving averages (EWMA) has, in the past few years, become a popular tool for controlling inaccuracy in industrial quality control. In this paper, I explain the principles of this technique, present some numerical examples, and by computer simulation compare EWMA with other control charts currently used in clinical chemistry. The EWMA chart offers a flexible instrument for visualizing imprecision and inaccuracy and is a good alternative to other charts for detecting inaccuracy, especially where small shifts are of interest. Detection of imprecision with EWMA charts, however, requires special modification.

Algorithms↗

PubMed1991

How many probes are needed for HLA-DPB1 typing with sequence-specific oligonucleotide probes? A theoretical approach using computer simulation.

HLA-DP genotyping with sequence-specific oligonucleotides is used to detect known sequence variations in the polymorphic segments of the DPB1 second exon. This approach is a valuable method replacing the tedious cellular definition of DP polymorphism. We have addressed, by computer simulation, the question: what is the minimum number of probes needed to provide an unambiguous assignment of HLA-DP alleles by genotyping of heterozygous individuals? We were able to reduce the number of probes in a set defining the presently known 22 different alleles and most of the heterozygous combinations to 18 probes. Only two pairs of allelic combinations cannot be distinguished by this method, neither with our optimized set of probes nor with any larger set comprising probes of reasonable length. This is because two pairs of alleles may be the result of a reciprocal genetic exchange. These two pairs, however, could be distinguished by family analysis, direct sequencing, or DNA amplification using specific primers chosen from the polymorphic ends of the DPB1 second exon.

Alleles↗

PubMedDate not supplied

Computational simulations of mitral regurgitation quantification using the flow convergence method: comparison of hemispheric and hemielliptic formulae.

Mitral regurgitation results from the incomplete closure of the mitral valve, and the noninvasive diagnosis of this disease remains an important clinical goal. In this study, steady flow computer simulations were used to evaluate flow convergence method for flow rate estimation. The hemispheric and hemielliptic formulae were compared for accuracy in the presence of complicating factors such as ventricular confinement, orifice shape, and aortic outflow. Results showed that in the absence of aortic outflow and ventricular confinement, there was a plateau zone where the hemispheric formula approximated the true flow rate, independent of orifice shape. However, in the presence of complicating factors such as aortic outflow and ventricular confinement, there was no clear zone where the hemispheric formula could be applied. The hemielliptic formula, however, worked in all cases, regardless of chamber size or magnitude of aortic outflow. Therefore, application of the hemielliptic formula should be considered in future clinical studies.

Aorta, Thoracic↗

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↗