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PubMed1984

A mathematical overview of a computer simulation model of maternity histories with illustrative examples.

A mathematical overview of a stochastic computer simulation model of maternity histories is provided. Various components of human reproduction are accommodated in the model through distributions of waiting times among live births. Included in these components are distributions of age at first marriage in a cohort of women, waiting times to pregnancy for fecundable women, and the lengths of infecundable periods following live births. Probabilities that pregnancies end in either a live birth, induced abortion, or some other type of outcome are also included. Elements of renewal theory and semi-Markov processes in discrete time were the basic mathematical concepts used in the construction of the model. A brief description of an interactive software package called MATHIST, which may be used to implement the model on a computer, is also included. Four illustrative computer runs with MATHIST, pertinent to the operation of family planning programmes in Africa, are also described and discussed.

Adult↗
PubMed1986

Transformation of a polygonal cellular pattern during sexual maturation of the avian oviduct epithelium: computer simulation.

A peculiar cellular pattern resembling a checkerboard has been observed on the luminal surface of the oviduct epithelium of an adult Japanese quail. The epithelium is a monolayer cell sheet and consists of two types of columnar cells, ciliated cells (C-cells) and gland cells (G-cells) assembled in alternating blocks. The pattern develops, during sexual maturation, from a kagome-like pattern (in which large C-cells are surrounded by small G-cells) characteristic of the immature oviduct. In the present paper, computer simulations of the pattern transformation from kagome to checkerboard were performed assuming a few properties of individual cells. The adult checkerboard-like pattern is not strictly rectangular, but is deformed toward a honeycomb pattern. In theoretical considerations the assumption that adhesion is stronger between unlike cells than between like cells formed an ideal checkerboard pattern, because all cell boundaries in it are edges along which unlike cells meet. On the other hand, a honeycomb pattern formed after assuming that the boundary length of the cellular pattern is minimized (caused by contraction of bundles of microfilaments running along lateral boundaries of the columnar epithelial cell while keeping contact between neighbouring cells). The actual checkerboard-like pattern was considered to be in a balanced state between the effects of (1) the strong adhesion between unlike cells, and (2) the boundary contraction. Using a computational analysis, this consideration enabled us to obtain a quantitative parameter value for the difference between cell adhesions of unlike cells and of like cells. C-cells divided once during the kagome-checkerboard transformation, while G-cells did not divide. We performed computer simulations starting with the kagome pattern in which all C-cells divided once. The computer program of the boundary shortening procedure we used involved the quantitative parameter value for differential cell adhesion obtained as described above. A checkerboard pattern was successfully generated in the simulation. It is concluded that the strong adhesion between unlike cells and the boundary shortening have important roles in formation and maintenance of the kagome and checkerboard patterns of the avian oviduct epithelium.

Animals↗
PubMed2004

Phase diagram of water from computer simulation.

The phase diagram of water as obtained from computer simulations is presented for the first time for two of the most popular models of water, TIP4P and SPC/E. This Letter shows that the prediction of the phase diagram is an extremely stringent test for any water potential function, and that it may be useful in developing improved potentials. The TIP4P model provides a qualitatively correct description of the phase diagram, unlike the SPC/E model which fails in this purpose. New behavior not yet observed experimentally is predicted by the simulations: the existence of metastable reentrant behavior in the melting curves of the low density ices (I,III,V) such that it could be possible to transform them into amorphous phases by adequate changes in pressure.

Journal Article↗
PubMed2004

Reaching long-term goals based on local interaction between an organism and the environment: computer simulations based on adaptive behavior.

An agent-based computer simulation created using the adaptive-behavior approach has shown that in some cases it is possible to reach a long-term goal (defined here as a desirable place far removed from the agent in time and in space) without necessarily having an exhaustive, predefined plan of action, but rather by using a set of rules on sensorimotor couplings that govern the organism's local interaction with its environment. We used an agent-based simulation program that emulated a two-dimensional microworld in which agents interacted with their environment and other agents through a set of sensorimotor couplings to reach a long-term goal. The main hypothesis was that the sensorimotor coupling, which consisted of following other agents, led to the emergence of collective behavior that enabled the agents to attain the long-term goal. We systematically varied the sensorimotor couplings that allowed agents to follow other agents, agents' perceptual field length, and the number of obstacles. In total, there were 160 independent simulations for each design cell. Analysis supported the hypothesis and suggested that, in addition to the process of reaching long-term goals, other cognitive processes, such as categorization, memory, and reasoning, can be reconsidered bearing in mind the emergence of behavior and an approach based on interaction between the organism and its environment.

Adaptation, Physiological↗
PubMed1997

Eimeria acervulina: influence of corticosterone-induced immunosuppression on oocyst shedding and production characteristics in broilers, and correlation with a computer simulation model.

An experiment was conducted to investigate the effects of immune responsiveness on excretion of oocysts after E. acervulina infection and subsequent effects on production characteristics of broilers (Gallus domesticus). These effects were determined in broilers repeatedly infected with 2.85 x 10(3) oocysts of E. acervulina and treated with various dosages of corticosterone in the diet (0, 10, 20 and 30 p.p.m.). Corticosterone treatment did not have an effect on the peak oocyst excretion, although it was administered from 4 days before initial infection. The number of oocysts excreted shortly after the peak and the length of the excretion period were increased in corticosterone-treated groups. The absence of a difference in peak oocyst excretion was ascribed to the existence of a time-lag between first contact with the parasite and rate of development of protective immunity. In a recently developed computer simulation model this period was assumed to be 5 days. Assuming that immunosuppression, through corticosterone, is only effective when protective immunity is in operation, the results indicate a time-lag of at least a few days, which supports the inclusion of such a time-lag in the computer simulation model. General immunosuppressive effects of the corticosterone treatment, monitored by antibodies and mitogen-induced lymphocyte stimulation confirmed that immunosuppression occurred shortly after medication started. Infection did not have a significant influence on production characteristics in animals without dietary corticosterone. However, with increasing corticosterone levels the negative effects of infection on production also increased.

Animals↗
PubMed1984

Computer simulation of purine metabolism.

A computer model of purine metabolism, including catabolism, salvage pathways and interconversion among nucleotides, is given. Steady-state rate equations corresponding to metabolic enzymes are written based on information from the literature about their kinetic behaviour. Numerical integration of this set of equations is performed employing selected parameters taken from the literature. After stabilization of purine compound concentrations is reached, simulation of enzyme deficit and enzyme overproduction is carried out. The latter is calculated by varying specified maximum velocities in the numerical integration. A pattern of intermediate metabolite concentrations is found. These results form a basis for the comparison of normal patterns or patterns reflecting the effects of inborn errors of metabolism. The aim of this paper is to demonstrate the usefulness of this computer simulation method in complex metabolism pathways.

5'-Nucleotidase↗
PubMed1991

Simulated bipolar cells in fovea of human retina. I. Computer simulation.

This static bipolar cell (BC) model of the human fovea is based on a number of reasonable assumptions. The human fovea is directly responsible for visual acuity and color vision. The fovea can be considered as having two parts; a central fovea with only red- and green-sensitive cones and a parafovea with blue-sensitive cones added to the other two. A cone mosaic can be precisely organized spatially into unit hexagons that specify inputs to horizontal cells (HC) and BCs. The retina up to and including BCs is piece-wise linear, i.e. at a given steady-state adapting light intensity BC outputs are linear functions of the physical image. BC centers receive inputs directly from weighted cones, while antagonistic surrounds receive inverted inputs from HCs. Appropriate optical and chromatic filtering due to the eye that are taken from human data are incorporated into the model. Chromatic aberrations are simulated by three separate point spread functions that also are taken from human data. Automatic gain control of cones is a function of intensity and wavelength of the steady adapting light.

Color Perception↗
PubMed2000

Computer simulation of the mechanical stimulation of the saccular membrane of bullfrog.

A three-dimensional computer simulation of the experiment (Benser M. E., Issa N.P., Hudspeth A.J., 1993. Hear. Res. 68, 243-252), devoted to the mechanical stimulation of the surface of saccular membrane of bullfrog with the otoconial mass removed was carried out by finite-element method. Comparison of the calculated distribution of the membrane displacements with the experimental data indicates that the gel layer of the saccular membrane is inhomogeneous. Its lower, thin (6-10 microm) sublayer bordering the macular surface has the smaller Young's modulus which is 20 times less than the modulus of the upper part of the gel membrane (2.5x10(2) N/m(2) and 6.6x10(3) N/m(2), respectively). Possible consequences of this result and modification of the experiment are being discussed. The estimates based on the results of simulation support the conclusion that hair bundle stiffness may dominate the elastic reactance to otolithic membrane shear (Benser et al., 1993).

Animals↗
PubMed1999

Continuous computer simulation analysis of the cost-effectiveness of screening and treating diabetic retinopathy.

This paper analyzes the cost-effectiveness of screening and treating diabetic retinopathy (DR) by simulating the disease progress continuously with existing data. A new computer simulation based on Monte Carlo techniques and logistic transformation follows cohorts from diabetes onset until death in five care scenarios. For younger-onset patients, ophthalmic care reduces the prevalence of blindness by 52% or greater while savings in disability facilities and production losses surpass direct costs. For older-onset patients, less favorable results appear. Financial benefits surpass costs for juvenile-onset patients. For other patients, the net costs of ophthalmic care seem lower than in other health care programs.

Blindness↗
PubMedDate not supplied

Computer simulation of the human respiratory system for educational purposes.

The main objective of this study was the development of a computer simulation system for the human respiratory system, in order to educate students of nursing. This approach was based on existing mathematical models and on our own constructed specific functions. For the development of this educational tool the appropriate software packages were used according to the special demands of this process. This system is called ReSim (Respiratory Simulation) and consists of two parts: the first part deals with pulmonary volumes and the second one represents the mechanical behavior of lungs. The target group evaluated ReSim. The outcomes of the evaluation process were positive and helped us realize the system characteristics that needed improvements. Our basic conclusion is that the extended use of such systems supports the educational process and offers new potential for learning.

Anatomy↗
PubMed1986

Testing models of insulin binding in rat adipocytes using network thermodynamic computer simulations.

Many different models have been proposed to explain the complex binding behavior of insulin to its receptor, but a systematic comparison of models with experimental results is lacking. We have used network thermodynamic computer simulations to compare models of insulin binding against the results of several experimental tests designed to differentiate between the models. Six models of insulin binding were tested (simple, diffusion-reaction, conversion, dissociation, heterogeneous site, and two-step intramembrane) against results reported in the literature for isolated rat adipocytes. Although still a matter of experimental controversy, the criteria selected for modeling were curvilinear Scatchard plots, bi-or multi-exponential dissociation, insulin-accelerated dissociation, lack of dependence of the overall dissociation constant on receptor number, and receptor reserve. Using a given set of parameter values most appropriate for each model, none was able to account for all of the observed experimental results. This indicates both the complexity of the binding reaction and the need for further model development. The approach of using computer simulations to systematically test models against experimental results affords not only insight into the critical features of a model enabling it to pass a test, but also indicates potential experiments which might differentiate between models.

Adipose Tissue↗
PubMed1988

Compliance in microcomputer-assisted conventional insulin therapy: computer simulation study results.

Compliance in diabetes self-management is a complex issue. It involves the interdependent daily actions of self-measurement of blood glucose and adherence to a prescribed schedule of daily activities. This impacts strongly on lifestyle because it necessitates precise meal timing as well as control of size and carbohydrate content. We sought to identify how strongly relaxing the lifestyle constraints per se would impact the ability to achieve improved metabolic control. To isolate these effects from those that result from poor measurement compliance, we used a computer simulator called OMNI et al. Furthermore, to standardize the "clinical" therapy, a second microprocessor device called an "Insulin Dosage Computer" was used to adjust insulin doses based on the usual clinical practice of four times a day precibal blood glucose measurements. Ten type 1 diabetic patients were stimulated and each followed for 120 simulated days. In each such subject, the simulation was repeated three times to include three different levels of lifestyle compliance ranging from excellent to poor. In all three protocols, starting from a level of poor control of diabetes, mean blood glucose values were significantly improved without significant differences after 120 days of computer-simulated treatment. Only the standard deviations, expressing the fluctuations of blood glucose and hence its stability, increased with decreasing lifestyle compliance. This computer simulation predicts that consistent self-monitoring of four blood glucose values per day is the cornerstone of diabetic self-control and that the use of these data according to a standardized therapeutic algorithm for insulin adjustment may successfully stabilize even patients with poor lifestyle compliance. Clinical studies must follow.

Blood Glucose↗
PubMed1997

Computer simulation studies of biological membranes: progress, promise and pitfalls.

Because of the complexity of biological membranes, computer simulations are useful adjuncts to experimental work in their study. Simulations of model membranes have provided new insights. Progress in simulating more biologically realistic membranes will require further development of statistical mechanical theory applied specifically to these systems, in conjunction with the use of powerful computers.

Biochemistry↗
PubMed2002

Investigating the distribution of prostate cancer using three-dimensional computer simulation.

The objective of this work was to investigate the distribution of prostate cancer using three-dimensional (3-D) computer simulation. Two hundred and eighty-one 3-D computer prostate models were constructed from radical prostatectomy specimens. An algorithm was developed which divided each model into 24 symmetrical regions, and it then detected the presence of tumor within an individual region. The distribution rate of prostate cancer was assessed within each region of all 281 prostate models, and the difference between the rates was statistically analyzed using Mantel-Haenszel methodology. There was a statistically significant higher distribution rate of cancer in the posterior half (57.2%) compared to the anterior half ( 40.5%; P=0.001). The base regions (36.8%) had a statistically significant lower distribution rate than either the mid regions (56.3%; P=0.001) or the apical regions (53.5%; P=0.001). The mid regions did have a statistically significant higher distribution rate compared to the apical regions (P=0.032). There was no statistically significant difference between the distribution rate on the left half (48.5%) compared to that on the right half (49.2%; P=0.494). The spatial distribution of prostate cancer can be analyzed using 3-D computer prostate models. The results illustrate that prostate cancer is least commonly located in the anterior half and base regions of the prostate. Through an analysis of the spatial distribution of prostate cancer, we believe that new optimal biopsy strategies and techniques can be developed.

Biopsy↗
PubMed1996

Computer simulation of shared input among projection neurons in the dorsal cochlear nucleus.

Computer simulations of a network model of an isofrequency patch of the dorsal cochlear nucleus (DCN) were run to explore possible mechanisms for the level-dependent features observed in the cross-correlograms of pairs of type IV units in the cat and nominal type IV units in the gerbil DCN. The computer model is based on the conceptual model (of a cat) that suggests two sources of shared input to DCN's projection neurons (type IV units): excitatory input for auditory nerves and inhibitory input from interneurons (type II units). Use of tonal stimuli is thought to cause competition between these sources resulting in the decorrelation of type IV unit activities at low levels. In the model, P-cells (projection neurons), representing type IV units, receive inhibitory input from I-cells (interneurons), representing type II units. Both sets of model neurons receive a simulated excitatory auditory nerve (AN) input from same-CF AN fibers, where the AN input is modeled as a dead-time modified Poisson process whose intensity is given by a computationally tractable discharge rate versus sound pressure level function. Subthreshold behavior of each model neuron is governed by a set of normalized state equations. The computer mode has previously been shown to reproduce the major response properties of both type IV and type II units (e.g., rate-level curves and peri-stimulus time histograms) and the level-dependence of the functional type II-type IV inhibitory interaction. This model is adapted for the gerbil by simulating a reduced population of I-cells. Simulations were carried out for several auditory nerve input levels, and cross-correlograms were computed from the activities of pairs of P-cells for a complete (cat model) and reduced (gerbil model) population of I-cells. The resultant correlograms show central mounds (CMs), indicative of either shared excitatory or inhibitory input, for both spontaneous and tone-evoked driven activities. Similar to experimental results, CM amplitudes are a non-monotonic function of level and CM widths decrease as a function of level. These results are consistent with the hypothesis that shared excitatory input correlates the spontaneous activities of type IV units adn shared inhibitory input correlates their driven activities. The results also suggest that the decorrelation of the activities of type IV units can result from a reduced effectiveness of the AN input as a function of increasing level. Thus, competition between the excitatory and inhibitory inputs is not required.

Animals↗
PubMed1999

Computer simulation of particle separation based on non-equilibrium swelling.

Steric/hyperlayer field-flow fractionation (FFF) is an established analytical technique for separating and characterizing particles in the 1-100 microns diameter range. The separation can be based on differences in size, density, shape and mechanical properties of the particles. In the course of an analysis of the water transporter system of Chinese hamster ovary (CHO) cells and one of their high permeability mutants, the first successful attempt was made to use the steric/hyperlayer FFF system for the purpose of separating particles based on a time-dependent property, namely, the differential swelling of the two cell types. The present study was undertaken to simulate numerically the separation and suggest selection of operating conditions to minimize repetitive experiments. The computer simulation was developed using Maple V, a symbolic computing environment. It is shown that the model is able to predict an optimal velocity of carrier buffer that maximizes resolution. Predicted velocity/resolution pairs are in good agreement with available experimental data. Empirical models for the lift forces encountered in such FFF experiments, and for the zone broadening observed in work with cell sized particles, form the basis for this model.

Animals↗
PubMed1987

Reduction of community alcohol problems: computer simulation experiments in three counties.

A series of alcohol abuse prevention strategies was evaluated using computer simulation for three counties in the United States: Wake County, North Carolina, Washington County, Vermont and Alameda County, California. A system dynamics model composed of a network of interacting variables was developed for the pattern of alcoholic beverage consumption in a community. The relationship of community drinking patterns to various stimulus factors was specified in the model based on available empirical research. Stimulus factors included disposable income, alcoholic beverage prices, advertising exposure, minimum drinking age and changes in cultural norms. After a generic model was developed and validated on the national level, a computer-based system dynamics model was developed for each county, and a series of experiments was conducted to project the potential impact of specific prevention strategies. The project concluded that prevention efforts can both lower current levels of alcohol abuse and reduce projected increases in alcohol-related problems. Without such efforts, already high levels of alcohol-related family disruptions in the three counties could be expected to rise an additional 6% and drinking-related work problems 1-5%, over the next 10 years after controlling for population growth. Of the strategies tested, indexing the price of alcoholic beverages to the consumer price index in conjunction with the implementation of a community educational program with well-defined target audiences has the best potential for significant problem reduction in all three counties.

Adolescent↗
PubMed1991

Computer simulations of N-methyl-D-aspartate receptor-induced membrane properties in a neuron model.

1. To evaluate the role of N-methyl-D-aspartate (NMDA) receptors in simulations of the lamprey spinal locomotor network, we developed a computer-simulated electrical model of a neuron that contains NMDA channels in addition to voltage-gated Na+, K+, and Ca2+ channels and Ca(2+)-activated K+ channels [K(Ca) channels]. 2. The voltage dependence of the Mg2+ block of the Na(+)-K+ current flow through the NMDA channel was modeled according to a scheme of open-channel block. To account for the regulation of K(Ca) channels by NMDA and membrane voltage, we modeled two separate Ca2+ pools that had different voltage dependencies and dynamics. 3. Pacemaker-like membrane potential oscillations could be elicited in the model neuron, which resembled those observed experimentally in the presence of bath-applied NMDA and tetrodotoxin. The effect of changing different channel parameters were tested to determine under which conditions such membrane potential oscillations could occur. 4. The oscillation amplitude was determined by the potential levels at which the NMDA channels and voltage-dependent K+ channels, respectively, were activated. The oscillation frequency and the relative durations of the de- and hyperpolarized phases of the oscillations were determined by the balance between the depolarizing (NMDA channels) and hyperpolarizing [K(Ca) channels] currents. 5. Simulated alterations of the Mg2+ concentration and the K+ conductance as well as injection of constant current caused changes of the oscillations corresponding to those observed experimentally. The de- and hyperpolarizing phases could be reset by brief current pulses. 6. We conclude that the present model can account for the effects of bath-applied NMDA on spinal neurons. This permits an incorporation of NMDA-receptor-mediated properties in simulation models of the lamprey locomotor network.

Action Potentials↗