PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “computational modelling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

Computer modeling of the oxygen supply and demand of cells of the avian growth cartilage.

We have used computer modeling studies to investigate the oxygen supply to the prehypertrophic and hypertrophic regions of avian growth plate. We measured experimentally the characteristics of the oxygen consumption of chondrocytes at different oxygen tensions. The oxygen consumption decreases at low oxygen tensions. This relation between oxygen tension and oxygen consumption serves as a protective mechanism that prevents the cells in the prehypertrophic zone from becoming anoxic in the regions farthest from the blood vessels. The results of the calculations, when combined with redox measurements of the cells in the growth plate, indicate that the metabolism of the chondrocytes is not controlled simply by the available oxygen supply.

Animals↗

Computational model of the role of sensory disorganization in focal task-specific dystonia.

We present a new computational model for the development of task-specific focal dystonia. The purpose of the model is to explain how altered sensory representations can lead to abnormal motor behavior. Dystonia is described as the result of excessive gain through a sensorimotor loop. The gain is determined in part by the sensory cortical area devoted to each motor function, and behaviors that lead to abnormal increases in sensory cortical area are predicted to lead to dystonia. Properties of dystonia including muscular co-contraction, overflow movements, and task specificity are predicted by properties of a linear approximation to the loop transformation. We provide simulations of several different mechanisms that can cause the gain to exceed 1 and the motor activity to become sustained and uncontrolled. The model predicts that normal plasticity mechanisms may contribute to worsening of symptoms over time.

Dystonic Disorders↗

A computational model of anterior cingulate function in speeded response tasks: effects of frequency, sequence, and conflict.

A growing body of evidence from functional neuroimaging and computational modeling studies indicates that the anterior cingulate cortex (ACC) detects the presence of response conflict and conveys this information to other brain regions, enabling subsequent adjustments in cognitive control. The present study examined previous empirical findings of increased ACC for low-frequency stimuli across three distinct speeded response tasks (two-alternative forced choice, go/no-go, and oddball). Simulations conducted in a neural network model incorporating sequential priming mechanisms (developed in Cho et al., 2002) confirmed that a computational measure of response conflict was higher on low-frequency trials across all three tasks. In addition, the model captured detailed aspects of behavioral reaction time and accuracy data, predicted the dynamics of ACC activity related to trial sequence effects, and provided evidence for the functional role of conflict information in performance monitoring and optimization. The results indicate that the conflict-monitoring hypothesis, augmented by mechanisms for encoding stimulus history, can explain key phenomena associated with performance in sequential speeded response tasks.

Adolescent↗

A computer model for the analysis of DNA replication intermediates by two-dimensional agarose gel electrophoresis.

We present a computer model to predict the patterns expected for the replication intermediates (RIs) of DNA fragments analyzed by neutral/neutral two-dimensional (2D) agarose gel electrophoresis. The model relies on the mode of replication (uni- or bi-directional), the electrophoretic mobility of linear DNA fragments and the retardation caused by the three-dimensional shape of non-linear molecules. The utility of this model is demonstrated with two examples: replication analysis of the plasmids pBR322 and pHH5.8 in Escherichia coli after digestions with EcoRI and HindIII, respectively.

Computer Simulation↗

Computational models of the basal ganglia.

Computer simulation studies and mathematical analysis of models of the basal ganglia are being used increasingly to explore theories of basal ganglia function. We review the implications of these new models for a general understanding of basal ganglia function in normal as well as in diseased brains. The focus is on their functional similarities rather than on the details of mathematical methodologies and simulation techniques. Most of the models suggest a vital role for the basal ganglia in learning. Although this interest in learning is partly driven by experimental results associating the acute firing of dopamine cells with reward prediction in monkeys, some of the models have preceded the electrophysiological results. Another common theme of the models is selection. In this case, the striatum is seen as detecting and selecting cortical contexts for access to basal ganglia output. Although the behavioral consequences of this selection are hard to define, the models provide frameworks within which to explore these ideas empirically. This provides a means of refining our understanding of basal ganglia function and to consider dysfunction within the new logical frameworks.

Animals↗

Development of a computer model using the EGS4 simulation code to calculate scattered X-rays through some materials.

In this paper a computer model based on the use of the well-known Monte Carlo simulation code EGS4 was developed to simulate the scattering of polyenergetic X-ray beams through some materials. These materials are: lucite, polyethylene, polypropylene and aluminium. In particular, the ratio of the scattered to total X-ray fluence (scatter fraction) has been calculated for X-ray beams in the energy region 30-120 keV. In addition scatter fractions have been determined experimentally using a polyenergetic superficial X-ray unit. Comparison of the measured and the calculated results has been performed. The Monte Carlo calculations have also been carried out for water, bakelite and bone to examine the dependence of scatter fraction on the density of the scatterer. Good agreement (estimated statistical error < 5%) was obtained between the measured and the calculated values of the scatter fractions for materials with Z < 20 that were studied in this paper.

Absorptiometry, Photon↗

Computer model for cryosurgery of the prostate.

The objective of this study was to devise an interactive tool to assist in cryoablation therapy through computer modeling, simulation, and visualization. CryoSim, a software package, accepts a set of acquired and processed three-dimensional ultrasound images, then models heat diffusion (formation of the iceball) based on numerical approximation of the heat equation and knowledge of the thermal properties of the underlying tissues. Results of cryoexperiments were found to be significantly similar to those generated by CryoSim. Therefore, CryoSim provides a viable technique for predicting the outcome of cryosurgery, and establishes a platform for future automation of cryosurgery.

Animals↗

Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors.

We present a computational model that offers an integrated quantitative, dynamic, and topological representation of intracellular signal networks, based on known components of epidermal growth factor (EGF) receptor signal pathways. The model provides insight into signal-response relationships between the binding of EGF to its receptor at the cell surface and the activation of downstream proteins in the signaling cascade. It shows that EGF-induced responses are remarkably stable over a 100-fold range of ligand concentration and that the critical parameter in determining signal efficacy is the initial velocity of receptor activation. The predictions of the model agree well with experimental analysis of the effect of EGF on two downstream responses, phosphorylation of ERK-1/2 and expression of the target gene, c-fos.

Computational Biology↗

Individual-based computational modeling of smallpox epidemic control strategies.

In response to concerns about possible bioterrorism, the authors developed an individual-based (or "agent-based") computational model of smallpox epidemic transmission and control. The model explicitly represents an "artificial society" of individual human beings, each implemented as a distinct object, or data structure in a computer program. These agents interact locally with one another in code-represented social units such as homes, workplaces, schools, and hospitals. Over many iterations, these microinteractions generate large-scale macroscopic phenomena of fundamental interest such as the course of an epidemic in space and time. Model variables (incubation periods, clinical disease expression, contagiousness, and physical mobility) were assigned following realistic values agreed on by an advisory group of experts on smallpox. Eight response scenarios were evaluated at two epidemic scales, one being an introduction of ten smallpox cases into a 6,000-person town and the other an introduction of 500 smallpox cases into a 50,000-person town. The modeling exercise showed that contact tracing and vaccination of household, workplace, and school contacts, along with prompt reactive vaccination of hospital workers and isolation of diagnosed cases, could contain smallpox at both epidemic scales examined.

Adult↗

Computational modeling to predict the temporal regulation of chondrocyte metabolism in response to various dynamic compression regimens.

Based on previously published experimental work, computational models were developed to simulate the effect of different dynamic compression regimens on the activity of chondrocytes seeded in agarose constructs. In particular, the balance between proliferation and matrix synthesis can be adjusted by applying different intervals of continuous or intermittent mechanical compression. A phenomenological compartment based-modeling approach was used as first model. A more mechanistic cell cycle model was used as the second model. The compartment-based modeling approach was found to be useful in representing a balance between proliferation and proteoglycan synthesis, when the effect of a certain stimulation protocol is known. In order to predict the response to different intervals of mechanical stimulation, however, a more mechanistic cell cycle-based approach is required. The cell cycle model supports an important role of the onset of loading. In addition, an inhibitory effect of further loading is required, which is more likely to be related to cell cycle progression velocity than to a decreased probability of commitment to the cell cycle. The mechanisms behind this inhibitory effect and the computational implementation, however, require further investigation.

Animals↗

Three-dimensional computer model of the entire human heart for simulation of reentry and tachycardia: gap phenomenon and Wolff-Parkinson-White syndrome.

A computer model of the entire human heart has been developed for simulation of the excitation and repolarization process. Spatial distribution of refractory periods and conduction velocities in the different cardiac tissues, the anisotropy of conduction in the ventricles, and the cycle length dependence of refractory periods and conduction velocities are taken into account. The algorithm calculating the activation process is based on a modified version of Huygen's principle for constructing wavefronts. This study presents simulations concerning the gap phenomenon of the conduction system and the initiation of tachycardias in a heart with Wolff-Parkinson-White syndrome. Results are compared for different basic cycle lengths and for normal and prolonged refractory periods in the His-Purkinje system. The gap phenomenon was found to be present only when using the prolonged refractory periods in the His-Purkinje-system at a cycle length of 700 ms. Induction of tachycardia by a single extrastimulus in the high right atrium in a heart with a bidirectionally conducting accessory pathway is possible by properly timed extrastimuli. The coupling interval of the stimulus for initiating a reentrant tachycardia depends on the cycle length, the conduction velocities and the set of refractory periods used. The same parameters determine whether or not a gap phenomenon in atrioventricular conduction occurs. The model may be useful for investigating similar questions concerning the reentry phenomena of tachycardia.

Atrioventricular Node↗

Symposium on computer modelling for anatomists and clinicians.

The following review articles are based on presentations given at a Symposium on Computer Modelling for Anatomists and Clinicians held in July 1997 at the Department of Anatomy, University of Edinburgh. The Symposium formed part of the Summer Meeting of the Anatomical Society of Great Britain and Ireland. There were 6 invited speakers, and 4 of these have produced review articles which are published in this issue of the Journal. In 3 of the presentations, recent advances in the use of 3D methodology to analyse mouse and human developmental anatomy were described. The reviews by Kaufman et al. and Baldock et al. (the latter to be published in a forthcoming issue of the Journal) complement each other in that they describe different aspects of a collaborative project (the Mouse Atlas Project, or MAP) involving the preparation of a text database of mouse developmental anatomy and a digital Atlas of normal mouse development. In the first of these presentations the principles underlying the methodology employed to reconstruct a range of early post-implantation mouse embryos spanning the stages between the primitive streak and the early limb-bud that had previously been serially sectioned was briefly described. Because of the efficiency of the computer technology involved (termed the warping program), the grey level images of the embryo histology could be arbitrarily resectioned to view the embryo as if sectioned in any orientation. Furthermore, all anatomically-defined tissues could be individually delineated (or painted) and viewed either in isolation or in combination with other appropriately labelled tissues and organs.

Journal Article↗

HIV transmission during invasive radiologic procedures: estimate based on computer modeling.

OBJECTIVE: The primary purpose of this study was to estimate the risk of HIV transmission from physicians to patients during invasive radiologic procedures and to compare this estimate with those previously derived for surgical procedures so that policy on possible practice restrictions can be decided. The risk of HIV transmission from patient to physician, including cumulative career risk for interventional radiologists, was also estimated. MATERIALS AND METHODS: The risk of HIV transmission from physician to patient and vice versa was estimated with computer modeling techniques, using available data on prevalence of HIV infection, rates of injury during invasive radiologic procedures, and risk of viral transmission after an exposure. Cumulative career risk of occupational infection was estimated with a computer simulation model. RESULTS: If the physician's HIV status is unknown, the risk of transmission of HIV to a patient during a procedure is estimated to be 0.03 per million procedures (95% confidence interval, 0-3.8 per million procedures). If the physician is known to be HIV-positive, the risk of transmission to a patient is estimated to be 7.5 per million procedures (95% confidence interval, 0-15.3 per million procedures). The estimated risk of transmission from patient to physician ranges from 0.03 to 7.5 per million for a single procedure, and the cumulative risk of occupational HIV infection over 30 years is estimated to be 0.009-16%. CONCLUSION: The estimated risk of HIV transmission from physician to patient during invasive radiologic procedures is so low that global practice restrictions on HIV-infected interventional radiologists are not warranted. As recommended by the American Medical Association and the Centers for Disease Control, decisions on possible practice restrictions should be made on a case-by-case basis rather than a priori. The risk of HIV transmission from patient to physician is also low, but real. The cumulative career risk of occupational infection with HIV may vary widely based on individual circumstances and the patient population served.

Computer Simulation↗

A computer model of neural processes observed in the cat motor cortex during performance of an operant movement.

This report describes a computer model of a "column" in the cat motor cortex. The model includes two layers of two-segment pyramidal neurons with two groups of inhibitory interneurons in each layer, which selectively control the somatic and dendritic segments of the pyramidal cells. In this model, neurons include active sodium, calcium, and several types of potassium currents. Excitatory connections between neurons are of the AMPA and NMDA types, while collateral connections between neurons of the upper layer are mainly of the NMDA type; connections between neurons in the lower layer are of the AMPA type. All inhibitory connections are of the GABA(A) type. The model reproduces the main neuronal processes seen in the cat motor cortex during performance of an operant movement. Pyramidal neurons of the upper layer generate primary and secondary responses to external stimuli. As in real experiments, secondary NMDA-dependent responses appear when GABA(A) inhibition is weakened and disappear when stimulation is increased; these properties of secondary responses are only reproduced when NMDA receptors are located in the terminals of collateral connections. Using only rapid NMDA-independent connections, neurons in the lower layer generate a slow bell-shaped wave of excitation (a "motor command"), which is formed by sequential activation of neurons with dendritic trees of different sizes.

Algorithms↗

Urine saturation with calcium salts in normal subjects and idiopathic calcium stone-formers estimated by an improved computer model system.

The state of saturation of urine with calcium salts has been estimated by means of a computer model system whose accuracy has been improved by the use of stability constants of 31 complexes which were re-determined at 37 degrees C and at the actual ionic strength of urine. The experimental determination of the concentration solubility products of calcium oxalate monohydrate (CaOx) and of calcium hydrogen phosphate dihydrate (bsh) allows an expression of the saturation degree as free concentration product ratio beta CaOx and beta bsh. Morning urine samples from 50 healthy controls and 50 idiopathic calcium stone-formers and 24 h urines from 40 normal subjects and 192 stone-formers, taking normal diet were investigated by this technique. From our results urine supersaturation with calcium oxalate salts seems to play an important role in calcium stone disease. Hypercalciuria and hyperoxaluria seem to be the main pathological features in this regard. The data concerning beta bsh values have not confirmed previous reports in which this parameter was found to be increased in stone-formers.

Calcium↗

[Acoustic analysis of certain consonants using a computed model of the peripheral auditory system].

Stop consonants [p], [t], [k] and a fricative [s] were acoustically analyzed using a computed model of the peripheral auditory system in 12 normal subjects and 12 patients with tumors of the tongue who had undergone surgical resection and reconstruction. The model is a combination of the cochlear model that consists of 28 FIR filters (Delgutte) and the inner hair-cell/auditory nerve synapse model (Meddis), with some modification. It simulates firing of the auditory nerve in every channel related to the FIR filters in response to an input voice signal. Phonetic characteristics of the tested consonants were more clearly visualized by observing firing patterns and voice onset time (VOT) using this auditory model than with use of the conventional soundspectrogram. In patients with tumors of the tongue, the degree of distorted articulation and the area of surgical resection were significantly related to obscurity of the phonetic characteristics of the stop consonants [t] and [k]. Acoustic analysis using this auditory model may serve as a useful tool for voice analysis in research and in the clinical field.

Computer Simulation↗

A computer model to analyze the cost-effectiveness of hormone replacement therapy.

This paper gives a detailed presentation of a computer model for evaluating the cost-effectiveness (CE) of hormone replacement therapy (HRT), describing the model's design, structure, and data requirements. The model needs data specified for costs, quality of life, risks, and mortality rates. As an illustration, the CE of HRT in Sweden is calculated. Two treatment strategies are evaluated for asymptomatic women: estrogen-only therapy and estrogen combined with a progestin. The model produces similar results compared with earlier studies. The CE ratios improve with the size of the risk reduction and generally with age. Further, estrogen-only therapy is associated with a lower cost per gained effectiveness unit compared with combined therapy. Uncertainty surrounding the long-term effects of HRT means that the CE estimates should be interpreted carefully. The model permits the inclusion of indirect costs and costs in added life-years, allowing the analysis to be made from a societal perspective, which is an improvement relative to previous studies.

Aged↗

The study of G-protein coupled receptor oligomerization with computational modeling and bioinformatics.

To achieve a structural context for the analysis of G-protein coupled receptor (GPCR) oligomers, molecular modeling must be used to predict the corresponding interaction interfaces. The task is complicated by the paucity of detailed structural data at atomic resolution, and the large number of possible modes in which the bundles of seven transmembrane (TM) segments of the interacting GPCR monomers can be packed together into dimers and/or higher-order oligomers. Approaches and tools offered by bioinformatics can be used to reduce the complexity of this task and, combined with computational modeling, can serve to yield testable predictions for the structural properties of oligomers. Most of the bioinformatics methods take advantage of the evolutionary relation that exists among GPCRs, as expressed in their sequences and measurable in the common elements of their structural and functional features. These common elements are responsible for the presence of detectable patterns of motifs and correlated mutations evident from the alignment of the sequences of these complex biological systems. The decoding of these patterns in terms of structural and functional determinants can provide indications about the most likely interfaces of dimerization/oligomerization of GPCRs. We review here the main approaches from bioinformatics, enhanced by computational molecular modeling, that have been used to predict likely interfaces of dimerization/oligomerization of GPCRs, and compare results from their application to rhodopsin-like GPCRs. A compilation of the most frequently predicted GPCR oligomerization interfaces points to specific regions of TMs 4-6.

Computational Biology↗