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At least 613 records · Page 34Linked to original sources

PubMed1994

The 'shortmer' approach to nucleic acid sequence analysis. I: Computer simulation of sequencing projects to find economical primer sets.

In principle it is most economical to sequence large DNA fragments consecutively ('primer walking'), provided there is an immediate supply of sequencing primers. To solve the problem of primer supply we previously suggested generating a bank of short oligonucleotide primers ('shortmers'). In every sequencing reaction shortmers would have to be selected from this bank that are suitable to hybridize adjacently on the sequencing template. After their ligation the shortmers would form a long, and hence more specific, primer in the subsequent sequencing reaction. In the present study a computer simulation of large sequencing projects revealed a reduced set of approximately 12,000 selected octanucleotides (out of all 65,536) retaining maximum priming flexibility and minimum redundant information on the simulated sequence analyses. Establishing routine protocols for nucleic acid sequencing following the shortmer approach will abolish the tightest bottleneck of the consecutive sequencing route (primer supply) and hence may render this general scheme more attractive than the shotgun sequencing scheme. A twofold (or more) speed-up of genome sequencing projects by the shortmer approach may be assumed.

Algorithms↗

PubMed1978

Burst generation by electrically coupled network in the snail helisoma: analysis using computer simulation.

The effectiveness of electrical coupling between neurons as a mechanism for mediating single and repetitive bursts is investigated here using computer simulation. The cyberchron network in the snail Helisoma generates repetitive bursts controlling the animal's feeding behavior and served as the basic model for the simulation studies described in this paper. The action potential properties of individual neurons were modeled by the Rall equations describing generalized action potentials. Several properties of electrical coupling and its role in burst generation were demonstrated, including: (1) A neuron in an electrically coupled network can generate action potentials at a higher frequency than an isolated neuron with similar membrane properties due to the loading through the electrical junctions. However, the ability of electrically coupled neurons to generate high-frequency bursts of action potentials requires a concomitantly greater amount of driving current to overcome the junctional loading. (2) Temporal and spatial summation of synaptic input onto a neuron is maintained at its most effective level because the postsynaptic current is integrated across the long postsynaptic membrane time constant. (3) Initial simulations concentrated on a pair of electrically coupled neurons which were below threshold. Stimulation of one of the two neurons with a short pulse resulted in a reverberation or regenerative excitation between the two neurons. The reverberation terminated after a number of action potentials dependent on the specific model parameters. Similar results were obtained with a network containing a greater number (20) of model neurons if approximately one-half of the neurons were stimulated simultaneously. However, none of the cases studied produced more than a single discrete burst. (4) Simulations were also conducted on 20-neuron networks containing two subpopulations of model neurons differing in their values of coupling resistance and excitability. Some networks of this type required stimulation of only one cell to make the two subpopulations of model neurons reverberate with one another. Such simulations suggest the possibility that 'preferred' input pathways involving a small number of neurons would be capable of 'turning on' the activity of the entire network.

Animals↗

PubMed1997

Computer simulation of cerebral blood flow in moyamoya and the results of surgical therapies.

Moyamoya is the disease which involves the terminal portions of the internal carotid or origins of the middle or anterior cerebral arteries. The posterior communicating arteries are also involved, but not the vertebrals or the basilar artery. The disease occurs more commonly in females than males and it has two age peaks at less than 10 and 40 years. Over the years many treatment options or procedures have been advocated for this disease either with direct bypasses or indirect revascularization procedures or both in combination. Whether one procedure is better than another is a matter of question and still to be determined. Along with it, there are various diagnostic and research work have been done for the etiology and the management of this disease. We have tried to implement a computer model of cerebral blood flow in order to assess and predict the flow in this disease process. At this time to know and predict the effectivity of certain types of offered treatment of Moyamoya disease is only to evaluate patients clinically with long term follow ups and at some interval after surgery with angiography or blood flow determinations. This study tries to focus on the use of computerized model of predicting cerebral blood flow which tries to assess the cerebral flow and decide which treatment option would be the best for a particular patient. After various computer simulations the blood flow following each treatment option is detected and the situation which offers the best treatment in a particular case is offered to the patient. To confirm the use of utility of this computer model a larger population of patients with Moyamoya disease need to be evaluated.

Adult↗

PubMed1981

Computer simulation of the dynamics of cell populations.

A modified version of the program of Valleron and Friendel is presented for the computer simulation of growing populations of cells. The method effects a sizable reduction of the storage requirement and allows one to follow the growth and division of cell clones for a large number of generations. Moreover, it is particularly useful to simulate specific biological events assumed to occur in the cell under various hypotheses and to compare them. Examples of this are also given.

Animals↗

PubMed1991

Reconstruction of hippocampal granule cell electrophysiology by computer simulation.

A model of the hippocampal granule cells was created that closely approximated most of the measured intracellular responses from a neuron under a variety of stimulus conditions. This model suggests that: (1) A simple, four-conductance model can account for most of the intracellular behavior of these neurons. (2) The repolarization mechanism in granule cells may be different from that in squid axons. A weak potassium conductance may be present in hippocampal granule neurons, which simultaneously give rise to a small, passive depolarizing afterpotential. (3) The strength duration properties may assist in identifying the electronic and sodium channel properties with short stimulus pulse widths. (4) Repetitive firing responses are highly dependent on the cell's recent history of activation and the regulation of the slow potassium conductance and calcium dynamics. (5) The anodic break response is probably not a property of typical granule cells. Through thorough and precise comparison of experimental and model responses, computer simulations can help assembling channel information into verifiable models that accurately reproduce intracellular data.

Action Potentials↗

PubMed1997

A minimal model for calcium signal generated by tyrosine kinase and G protein linked receptors; a stochastic computer simulation with CALSIM.

A software was designed to simulate the calcium signal following hormone or growth factor stimulation in epithelial cells. The software written in C runs on a PC under Windows environment. It is based on a Markov process where the dynamic of the system is characterised by phenomenological transition probabilities. Moreover a minimal model is proposed to analyse the role of plasma channels and IP3 receptors, together with the opposite action of the CaATPase pumps, in the cytosolic and endoplasmic reticulum (ER) calcium signal control. The simulation is applied on the calcium response following stimulation by carbacol (protein G coupled receptors) or epidermal growth factor (tyrosine kinase type receptors) in A431 epithelial cells. The experimental calcium signals can be grouped in three classes; a spike and a return to the basal level (signal A), a spike and a decrease to a plateau level (signal B) or a slow increase to a plateau (signal C). Epidermal growth factor induces signal A and B while carbacol gives signal B and C. When a 'pseudo' steady state is reached oscillations occur. Computer simulations show that signal A can result from the activation of IP3 receptors while signal C would result from the activation of the plasma channels; signal B appears as the additive contribution of both channels, while oscillations are compatible with a calcium induced calcium release mechanism. Simulations suggest that the calcium dynamic in the ER is a mirror of cytosolic calcium but that a simple way to produce similar calcium elevation in these two compartments is to activate plasma channels. Implications of such a mechanism is discussed.

Adenocarcinoma↗

PubMed1997

Conformational analysis of potent sweet taste ligands by nuclear magnetic resonance, computer simulations and X-ray diffraction studies.

Four potent sweet-tasting molecules, N-(3,3-dimethylbutyl)-L-aspartyl-L-phenylalanine methylester 1 (7000 times more potent than sucrose), N-(3,3-dimethylbutyl)-L-aspartyl-D-valine (S)-alpha-ethylbenzylamide 2 (3000 time more potent than sucrose), L-aspartyl-D-valine (R)-alpha-methoxymethylbenzylamide 3 (1350 times more potent than sucrose and L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide 4 (2500 times more potent than sucrose) were studied by 1H NMR and computer simulations. These flexible molecules adopt multiple conformations in solution. The "L-shaped" structure, which we believe to be responsible for sweet taste is accessible to all four compounds in solution. Extended conformations with the AH and B-containing moieties in the +y-axis and the hydrophobic group X pointing in the y-axis have also been observed for all four sweeteners. For compounds 1 and 3, the solid-state conformations were determined by X-ray diffraction studies. These results demonstrate that compounds 1 and 3 adopt an "L-shaped" structure even in the crystalline state. The extraordinary potency of the N-alkylated compound 1 compared with the unsubstituted Asp-Phe-OMe may be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the "L-shaped" structure.

Computer Simulation↗

PubMed1994

In vivo/in vitro correlation of intravitreal delivery of drugs with the help of computer simulation.

The elimination of dexamethasone sodium m-sulfobenzoate, DMSB, following intravitreal injection, was measured in rabbit vitreous body under in vivo and in vitro conditions. The rate of elimination in vivo was appreciably greater than that in vitro, indicating that the in vivo data include not only the elimination due to metabolism/degradation in the vitreous humor, but also the elimination through the surrounding tissues such as the posterior aqueous humor, the retina/choroid/sclera membrane, and the lens. A general mathematical model based on Fick's second law of diffusion was developed for describing the pharmacokinetics of the intravitreal injection of DMSB. The model parameters were independently determined from a set of in vitro experiments. The in vivo data of elimination of DMSB following intravitreal injection agreed with the profiles calculated from the mathematical model, together with the model parameters determined from the in vitro experiments. The present in vivo/in vitro correlation, with the help of computer simulation, can be used for optimizing the therapeutic systems of intravitreal drug delivery.

Animals↗

PubMed1997

Using computer simulated results of a bulk drug substance assay to determine acceptance criteria for method validation.

PURPOSE: To determine the statistical variability expected for a well designed HPLC assay of a bulk drug substance (BDS). The results are used to develop appropriate acceptance criteria for a method validation protocol as well as to evaluate the level of uncertainty expected for assay results using a variety of sampling/injection schemes. METHODS: Computer simulation was used to generate a large quantity of data and the variability of the mock results was evaluated. Error propagation was also calculated, whenever possible, to confirm results obtained from the simulations. RESULTS: Protocol acceptance criteria were developed that were consistent with the expected variability for data resulting from the execution of the validation protocol. In certain cases simulations provided the only avenue of obtaining results that could not otherwise be readily determined. CONCLUSIONS: Computer modeling can be used to obtain suitable acceptance criteria for validation results which are consistent with method variability. This is particularly significant in the case of linearity where it has been difficult to develop acceptance criteria based on anything other than analyst intuition and experience. Assay simulations clearly demonstrated that the variability expected for a typical BDS assay is large relative to the average specification range and therefore little insight about relative purity can be gained comparing individual passing assay results.

Chromatography, High Pressure Liquid↗

PubMed1987

How many genes to start with? A computer simulation about the origin of life.

A geneticist's view on the origin of life would focus on individual nucleic acid molecules rather than on their concentrations, on stochastics rather than on differential equations. The 'package model' envisages primordial compartments that contain ensembles of primordial genes. These are replicated independently from each other. During package fission they are distributed to two daughter packages. Packages with a complete ensemble of genes can continue to propagate. However, mutations as well as the stochastic nature of replication and package fission occasionally cause arising packages to miss genes from the ensemble, thus resulting in the death of those packages. A computer simulation, considering the complementarity of RNA as well as abortive termination of replication, yielded results that are similar to those of a preliminary simulation irrespective of these parameters: the results suggest that life could not have started with more than 3 genes, or else the primordial replicase would have to achieve at least a reduction of the replicational error rate by a factor of 13 and a reduction of undue chain termination by a factor of 10 to 25.

Computer Simulation↗

PubMed1997

Mechanism and computer simulation of a new robot hand for potential use as an artificial hand.

A prosthetic hand is essential to provide rehabilitation for individuals who lose a hand. A prosthetic hand serves two purposes: cosmetic and functional. In this paper, a prototype of the artificial hand with an emphasis on the functionality purpose is presented. A new mechanism, the NTU-Hand (NTU-Hand, patent number 107115, Taiwan, R.O.C.), which has 5 fingers with 17 degrees of freedom, has been designed and fabricated in our laboratory. Due to the special design of the mechanism, the hand has an uncoupled configuration in which each finger and joint are all individually driven. The size of the hand is almost the same as a human hand. All actuators, mechanical parts, and sensors are on the hand. The compact design makes it feasible to adapt the hand to the injured wrist. A computer simulation with three-dimensional graphics was also built to evaluate the manipulative range of the artificial hand. From the results of this simulation, the relationship between the hand and the grasped object in a specific viewpoint can be obtained.

Artificial Limbs↗

PubMed1996

Computer simulation of PPF distribution under blue and red LED light source for plant growth.

The superimposed pattern of "luminescence spectrum of blue light emitting diode (LED)" and "that of red LED", corresponds well to light absorption spectrum of chlorophyll. If these two kinds of LED are used as a light source, various plant cultivation experiments are possible. The cultivation experiments which use such light sources are becoming increasingly active, and in such experiments, it is very important to know the distribution of the photosynthetic photon flux (PPF) which exerts an important influence on photosynthesis. Therefore, we have developed a computer simulation system which can visualize the PPF distribution under a light source equipped with blue and red LEDs. In this system, an LED is assumed to be a point light source, and only the photons which are emitted directly from LED are considered. This simulation system can display a perspective view of the PPF distribution, a transverse and a longitudinal section of the distribution, and a contour map of the distribution. Moreover, a contour map of the ratio of the value of the PPF emitted by blue LEDs to that by blue and red LEDs can be displayed. As the representation is achieved by colored lines according to the magnitudes of the PPF in our system, a user can understand and evaluate the state of the PPF well.

Agriculture↗

PubMed2001

A computer simulation model for cost-effectiveness analysis of mass screening for Type 2 diabetes mellitus.

The cost-effectiveness analysis of mass screening for Type 2 diabetes mellitus (DM) was performed to elucidate whether, who and how often it should be conducted in Taiwan. A series of Markov process was developed to model the disease natural history of Type 2 DM. A hypothetical cohort with 30,000 residents aged over 30 years in Taiwan was randomly assigned to three arms of screening regimes, biennial, five-yearly and the control group. A Monte Carlo computer simulation was performed to calculate effectiveness of two screening regimes compared with the control group. Direct costs and utilities were incorporated to each corresponding state to calculate the incremental costs per life-years gained and per quality-adjusted life-years (QALYs) for biennial and five-yearly screening regimes. The incremental costs for biennial screening regime were estimated at $26,750 per life-year gained, and $17,833 per QALY. The corresponding figures for five-yearly screening regime were $10,531 per life-year gained and $17,113 per QALY. The incremental costs per life-year gained and per QALY increase with age, ranging from $17,238 for aged 30-39 years to $54,700 for aged over 70 years and from $9193 to 36,467, respectively. In conclusion, mass screening for Type 2 DM, especially in younger subjects, with 5-year inter-screening interval is cost-effective in Taiwan.

Computer Simulation↗

PubMed2000

Molecular determinants of MAO selectivity in a series of indolylmethylamine derivatives: biological activities, 3D-QSAR/CoMFA analysis, and computational simulation of ligand recognition.

A series of indolylmethylamine derivatives were assayed toward MAO-A and MAO-B inhibition. The K(i) values of these compounds are in the range from 0.8 to >10(6) nM for MAO-A or from 0.75 to 476000 nM for MAO-B. The most selective MAO-A or MAO-B inhibitors elicit a ratio of K(i) in the order of 1500 or 1000, respectively. Comparison of MAO-A and MAO-B CoMFA models showed that both the steric and electrostatic properties at the 5 position of the indole ring are determinant for MAO selectivity. Computational simulations of the complex between this part of the ligand and Phe-208 of MAO-A or Ile-199 of MAO-B, experimentally identified as responsible for substrate selectivity, allowed us to further characterize the nature of these enzyme-inhibitor interactions.

Amines↗

PubMed2000

Computer simulation analysis suggests weak balancing selection operative at the MICA locus.

A high degree of polymorphism has been reported at the major histocompatibility class I chain-related gene A (MICA) locus, which is located 46 kb away from HLA-Bin the human major histocompatibility complex (MHC) class I region. Although it is known that the polymorphisms at the conventional MHC class I loci have been maintained by balancing selection, it is unclear whether positive natural selection is also operative in maintaining the polymorphism at the MICA locus. In order to explain the degree of polymorphism at the MICA locus, a computer simulation study was carried out. The high degree of polymorphism at the MICA locus (heterozygosity and number of polymorphic residues) could not be explained solely by balancing selection at the HLA-B locus even if no recombination was assumed between MICA and HLA-B. Although there is no definite evidence indicating that balancing selection is operative at the MICA locus, our results suggest that the MICA gene is subject to weak balancing selection.

Alleles↗

PubMed2000

Computer simulation approach to the quantification of immunogold labelling on plasma membrane of cultured neurons.

Cell culture is a convenient model system to study the expression of plasma membrane-bound proteins in nerve cells. Analysing it with an ultrastructural detail researchers often apply transmission electron microscopy together with immunogold labelling. Plasma membrane profiles are one-dimensional (1D) and provide little information about the topography of membrane-bound proteins. In order to convert 1D estimates of spatial arrangement for preembedding immunogold labelled proteins into two-dimensional (2D) quantities, namely the 2D pattern and density of labelling, this paper presents a simple computer simulation technique. This technique is based on a mathematical model permitting a simulated immunogold labelled membrane to be sampled in a way similar to microtome sectioning. An interlabel distance (ILD) estimate is used to define the position of immunogold particles in membrane profiles. In order to interpret experimental ILD measurements the simulated distribution best fit to the experimental data is selected and the corresponding 2D density and pattern of particle scattering are considered to explain the real situation. Various parameters including a cell section thickness, immunogold particle size etc can be adjusted to suit the demands of a particular experiment. The technique was applied to quantify the NCAM preembedding immunogold labelling in the plasma membrane of cultured rat hippocampal neurons.

Animals↗

PubMed2003

Evidence for dynamic heterogeneities in computer simulations of miscible polymer blends.

The controversial origins of the unusual dynamics of miscible polymer blends are incisively probed through computer simulations. The distribution of mobilities experienced by a probe monomer in a miscible blend of chains with disparate glass transition temperatures is found to be much broader than in the pure polymers, providing clear evidence for local concentration variations in the mixture. These concentration fluctuations yield distinctly different temperature dependences for the dynamics of the two different components, in a manner that closely mimics experiments.

Journal Article↗

PubMed1991

Quantitative study of the susceptibility difference between trabecular bone and bone marrow: computer simulations.

Inherent differences in tissue magnetic susceptibility produce inhomogeneities in the static magnetic field which give rise to an additional dephasing of the transverse magnetization in gradient-echo images. The enhanced dephasing of the signal results in an increase of the apparent relaxation rate 1/T2* and a corresponding decrease in signal intensity. These effects have been used to explain the regional loss of marrow signal intensity in the appendicular skeleton, where in the presence of trabecular bone in the proximal tibia there is an enhanced loss of signal compared to the tibial shaft where there is no trabeculation. It has been postulated that differences in tissue magnetic susceptibility arising due to the marrow--trabeculae interface give rise to magnetic field inhomogeneities and a reduced T2*. In this study computer simulations are used to determine whether susceptibility differences comparable to that between trabecular bone and tissue relate to the reduction of tissue T2* and whether the reduction in T2* is also related to the concentration and magnitude of susceptibility differences. In addition the effects of the spatial distribution of these particulate discontinuities in susceptibility on the measured relaxation time T2* are also estimated. This model demonstrates that 1/T2* increases as the number density and magnitude of such susceptibility differences increase. In a pixel of linear dimension L consisting of material simulating tissue water, the presence of circular point susceptibility differences of dimension 0.001 L with magnetic susceptibility equivalent to trabecular bone, 1/T2*, increases at a rate of 1.60 x 10(-2) s-1/N for N ranging from 25-2500. Differences in magnetic susceptibility that are less than that between soft tissue and trabecular bone are also modeled and the simulations demonstrate that differences in magnetic susceptibility, much lower than that between trabecular bone and tissue equivalent interfaces, also produce a relaxation rate enhancement in gradient-echo images.

Bone Marrow↗