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At least 109 records · Page 6Linked to original sources

PubMed1993

An augmented computer model of motor unit reorganization in neurogenic diseases of skeletal muscle.

A computer model of denervation and complete reinnervation in skeletal muscle was originally developed for the purpose of furthering an understanding of the underlying mechanisms of motor unit reorganization in neurogenic diseases. We now describe its successor, a computer model for investigating different rates of denervation and reinnervation, as well as incomplete reinnervation. The new model introduces the concept of permanent denervation and features enhanced interactive control over the distribution of motor unit centers and additional measures of dispersion and co-dispersion of muscle fibers. The use of this model for investigating pathophysiologically significant issues in denervating diseases is illustrated with five different sets of parameters. These simulate some of the processes that may be operational in chronic spinal muscular atrophy, amyotrophic lateral sclerosis, and progressive postpolio muscular dystrophy. The enhanced model will allow in-depth analysis of the influence of hypothesized pathophysiological processes on clinical, electrophysiological and pathological outcomes in human disease.

Computer Simulation↗

PubMed1993

The fractional volume available to prolate spheroids in a network of randomly oriented fibers obtained by computer modeling: correlation with the Ogston equation.

Computer modeling was used to measure the fractional volumes available to prolate spheroid objects in a random, inert network of fibers. The data fit the Ogston equation exactly when the object was a sphere (axial ratio = 1). When the axial ratio was increased from 1 to 9, the Ogston equation was still obeyed if the fiber concentration is multiplied by a factor, A, which increases linearly in proportion to the axial ratio. The factor A allows one to adjust the retardation coefficient derived from gel electrophoresis, KR, for spherical objects to that of prolate spheroids with axial ratios from 1 to 9. Potentially, the same adjustment of KR is possible for objects of other shapes.

Algorithms↗

PubMed1990

[Analysis of dynamic changes in glycosylated blood proteins using a computer model].

UNLABELLED: The authors elaborated a computer model of albumin glycosylation based on the irreversible glycosylation reaction with first order kinetics. The dynamics of changes of glycosylated albumin in relation to the glycaemic profile was confirmed with an older model of haemoglobin glycosylation. By means of regression analysis parameters of the model in three groups of patients were calculated. CONCLUSION: 1. Stratification of the red cell pool is the reason why there is a smaller clinical difference between glycosylated protein and haemoglobin than corresponds to their half-times. 2. Glycosylated proteins are probably eliminated more rapidly than non-glycosylated ones. 3. Higher levels of glycosylated proteins sometimes do not correspond to model calculations are probably due to other factors.

Computer Simulation↗

PubMed1983

Predictions of a network thermodynamics computer model relating to the mechanism of methotrexate rescue by 5-formyltetrahydrofolate and to the importance of inhibition of thymidylate synthase by methotrexate-polyglutamates.

Computer modeling has been a valuable tool for clarifying the mechanism of action of antifolates. Some consequences of folyl and antifolyl polyglutamate synthesis can be addressed by adaptation of a network thermodynamic computer model of methotrexate action. Reversal or prevention of methotrexate cytotoxicity by 5-formyltetrahydrofolate has widely been assumed to occur through the delivery of reduced folate in substrate amounts for thymidylate synthesis, by-passing the effects of methotrexate at dihydrofolate reductase. This mechanism is inconsistent with experimental data which shows that "rescue" is a competitive phenomenon and that the transport process is incapable of delivering reduced folate at an adequate rate. Computer modeling studies are presented which predict that expansion of the total folate pool as folylpolyglutamates with "rescue" would reduce the inhibitory effect of MTX on thymidylate synthesis. Dihydrofolate polyglutamates could then accumulate to the high level needed to displace methotrexate from the small fraction of sites on dihydrofolate reductase that are sufficient to sustain tetrahydrofolate synthesis. Experimental studies with Ehrlich ascites tumor cells support this prediction. It is likely that a critical step in the protection of normal host tissues in high dose-rescue treatment regimens is the conversion of exogenously supplied 5-formyltetrahydrofolate to polyglutamyl derivatives and accumulation of total intracellular folate to higher than normal levels. Other computer simulations are presented which examine the potential significance of direct inhibition of thymidylate synthase by polyglutamyl forms of methotrexate. The model predicts that in cells with biochemical properties similar to methotrexate sensitive L1210 cells, inhibition of dihydrofolate reductase would still be the predominant site of action unless the thymidylate synthase Ki for a methotrexate polyglutamate is below about 0.1 microM. However, in methotrexate-resistant cells with elevated dihydrofolate reductase but normal membrane transport and polyglutamylation, thymidylate synthase may be the more important target enzyme.

Computers↗

PubMed1992

Computer modeling of gibberellin-DNA binding.

Computer modeling and molecular mechanics performed on the intercalation complexes of selected gibberellins or biosynthetic precursors with DNA dinucleotides revealed that under appropriate conditions the ligands insert (intercalate) between the base-paired double-stranded dinucleotide, 5'-dTdA-3'. Stabilization of the double-stranded dinucleotide after docking of a gibberellin between base pairs is inferred by the sum negative energy of hydrogen bonding and van der Waals contacts and the entropic changes which accompany the formation of each ligand-dinucleotide complex. In addition, the interactions of the gibberellins and dinucleotides, with the gibberellic acid-dinucleotide complex serving as the prototype, show optimum geometry and stereochemical hydrogen bonding recognition which are dependent upon the complementary chirality and stereochemistry of the individual components. Whether or not the gibberellins directly influence the uncoiling of DNA or gene expression at the transcriptional level via an intercalation mechanism is a matter of conjecture, albeit one that warrants intensive investigation.

Computer Simulation↗

PubMed1999

The dynamics of vortex-like reentry wave filaments in three-dimensional computer models.

Recent studies using computer simulation and biological studies in 2-dimensional excitable media have suggested that spiral wave reentrant activation and its core dynamics are important elements in the mechanism of functional reentrant tachyarrhythmias, such as atrial and ventricular fibrillation. However, vortex-like reentry has been observed in homogeneous 3-dimensional excitable media, and the dynamics of the related "filaments," which have 3-dimensionally connected "cores" in 2 dimensions, have not been clarified. In order to determine whether the filaments of vortex-like reentry waves can be observed in 3-dimensional media using a mathematical ionic current heart model and whether the abnormal ionic currents in myocardium affect the complexity of the filaments, we studied the qualitative features of vortex-like reentry dynamics using mathematical models in computer simulations. We employed the Luo-Rudy Phase I and the FitzHugh-Nagumo models for our heart media, which were cubic and ventricular shaped, and consisted of 8,000,000 and 5,636,654 myocardial units, respectively. Functional reentry, in the form of vortex waves, was induced in the media by the S1-S2 method. The vortex-like reentry waves and their filaments were displayed by computer graphics. Computations were performed on an NEC SX-4 supercomputer (NEC, Tokyo, Japan) using programs written in C language. Computer simulation studies have shown that the filament dynamics of vortex-like reentry in the original Luo-Rudy model is considerably more complex than that in the FitzHugh-Nagumo model. However, when we mathematically modified the L-type calcium current and shortened the action potential duration, just as occurs with sustained rapid ventricular pacing, the dynamics of the vortex-like reentrant wave fronts and the filaments were similar in both models. Our results suggested that the original character of myocardium causes drastic changes in filament shape and location, resulting in intricate functional reentrant waves, and that if the L-type calcium current is depressed, the complexity of the dynamics of the filaments are decreased to some degree.

Calcium↗

PubMed1990

Analysis of glycosylated serum protein changes using a computer model.

UNLABELLED: The authors devised a computer model of albumin glycosylation based on irreversible glycosylation reaction of first-order kinetics. The dynamism of glycosylated albumin changes in relation to glycaemic profiles was compared with an earlier model of haemoglobin glycosylation. A non-linear regression analysis was employed to calculate the parameters of the model in three groups of patients. CONCLUSIONS: 1. Erythrocyte pool stratification accounts for the smaller clinical difference between glycosylated protein and haemoglobin than would correspond to their respective half-life values. 2. Glycosylated proteins are probably eliminated more rapidly than non-glycosylated proteins. 3. Higher levels of glycosylated proteins are occasionally at variance with model calculations, a fact which is probably due to other factors.

Computer Simulation↗

PubMed2000

An evaluation of a computational model of lexical access: comment on Dell et al. (1997).

The computational model of lexical access proposed by G. S. Dell, M. F. Schwartz, N. Martin, E. M. Saffran, and D. A. Gagnon (1997) is evaluated. They argued that fits of their model to naming data obtained from normal and brain-damaged patients support assumptions regarding interactivity in the lexicon, global damage in aphasia, and continuity between normal and aphasic naming behavior. Additional analysis reveals that the model fits the empirical data poorly and that the claims Dell et al. made on the basis of the model's performance would not follow even if the model were accurate. Although use of a novel automatic regression procedure improved the model's fit, it cannot account for 5 of Dell et al.'s 21 patients (24%), and its limitations were found to be inherent in its design. It is argued that claims such as those made by Dell et al. can only be addressed by considering evidence from multiple related tasks and by comparing multiple computational models.

Aphasia↗

PubMed2000

Three-dimensional computational model of left heart diastolic function with fluid-structure interaction.

Aided by advancements in computer speed and modeling techniques, computational modeling of cardiac function has continued to develop over the past twenty years. The goal of the current study was to develop a computational model that provides blood-tissue interaction under physiologic flow conditions, and apply it to a thin-walled model of the left heart. To accomplish this goal, the Immersed Boundary Method was used to study the interaction of the tissue and blood in response to fluid forces and changes in tissue pathophysiology. The fluid mass and momentum conservation equations were solved using Patankar's Semi-Implicit Method for Pressure Linked Equations (SIMPLE). A left heart model was developed to examine diastolic function, and consisted of the left ventricle, left atrium, and pulmonary flow. The input functions for the model included the pulmonary driving pressure and time-dependent relationship for changes in chamber tissue properties during the simulation. The results obtained from the left heart model were compared to clinically observed diastolic flow conditions for validation. The inflow velocities through the mitral valve corresponded with clinical values (E-wave = 74.4 cm/s, A-wave = 43 cm/s, and E/A = 1.73). The pressure traces for the atrium and ventricle, and the appearance of the ventricular flow fields throughout filling, agreed with those observed in the heart. In addition, the atrial flow fields could be observed in this model and showed the conduit and pump functions that current theory suggests. The ability to examine atrial function in the present model is something not described previously in computational simulations of cardiac function.

Biomedical Engineering↗

PubMed1998

Human factors project: development of computer models of anatomy as an aid to risk management.

Behavioral studies and reports in the pediatric medical literature suggest that children, particularly those younger than 4 years, frequently place foreign objects such as toys and small parts of consumer products in their mouths, nasal cavities and ear canals. These actions not infrequently lead to injury or death. Accurate models of the anatomical areas most often severely injured by foreign body impaction (oral cavity, orbit, ear canal and nasal passages) would greatly facilitate assessment of the risks of impaction. Because models of these anatomic regions in children of the ages when they are most at risk are not widely available, Intertek Testing Services, Risk Analysis and Management (ITS RAM), in association with faculty at the University of Pittsburgh and the Pittsburgh Supercomputing Center at Carnegie Mellon University, developed computerized models of these anatomical areas of interest in children at the critical stages of child development. Computer models were also developed of proposed or existing products and of objects represented in the ITS RAM Small Parts Aspiration and Ingestion Database (comprised of data from 17 children's hospitals) and fatality data from the Consumer Product Safety Commission. The computer models of products and computer anatomical models can be used to assess the possible hazards inherent in the product designs and to communicate the risks associated with product designs to manufacturers and marketing groups.

Child, Preschool↗

PubMed1984

Sensitivity and specificity of the computational model for maximal expiratory flow.

The computational model for forced expiratory flow from human lungs of Lambert and associates (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 44-56, 1982) was used to investigate the sensitivity of maximal expiratory flow to lung properties. It was found that maximal flow is very sensitive to recoil pressure and airway areas but not very sensitive to lung volume, airway compliance, and airway length. Linear programming was used to show that a given air flow-pressure curves was compatible with a fairly wide range of airway properties. Additional data for maximal flow with a He-O2 mixture narrowed the range somewhat. It was shown that the flow-pressure curve contains more information about central than peripheral airways and that information about the latter is obtainable only from flows at recoils less than 2 cmH2O. Parameter ranges compatible with individual flow-pressure curves showed differences that demonstrated that such curves give some indication of individual central airway properties.

Airway Resistance↗

PubMed1977

A Monte Carlo computer model to investigate patient scheduling.

A Monte Carlo computer model was developed to investigate various types of patient appointment schedules for a single channel queue. Input parameters included the incidence of no-shows, the rate of unscheduled walk-ins, the frequency distribution of physician examination times, and the string of appointment times. The results included the frequency distributions of physician utilization rates and the total waiting time of all patients. Five hospital clinics were simulated. Even increment schedules yielded the best trade-off between physician utilization and patient waiting.

Appointments and Schedules↗

PubMed1989

Computer model of cardiac repolarization processes and of the recovery sequence.

A computer model simulating both excitation and recovery processes within a block of heart muscle tissue has been developed and implemented on different IBM PC AT compatible computers. The model incorporates blocks of tissue consisting of several thousand elements and introduces phenomena which are completely or partly omitted in other existing cardiac electrophysiology models. These phenomena include the electric anisotropy of the tissue, different durations of repolarization in different layers of tissue, and the different shapes of action potential which correspond to cells excited when not fully recovered. Implementation of the model on small personal computers requires the use of a special data structure management and an effective algorithmic background. The program of the model is written in PASCAL and uses dynamically allocated data structures and the asynchronous simulation technique of event planing. These techniques are described in detail. The model has been used in various experiments. Results of simulation studies are presented in the form of modeled three-lead electrocardiographic records. The experimental series which are described include basic patterns of regular activation sequences, modeling of premature beats, simulation of effects due to fast pacing, models of ischemia and infarction, simulation of reentry mechanisms with a special reference to the initiation of ventricular fibrillation, and models of late potentials. The future development of more realistic models of the cardiac recovery process is also discussed.

Action Potentials↗

PubMed1987

A computer model of hemorrhagic shock in domestic swine.

We used a modified version of the computer model of the circulation developed by C.V. Greenway (Pharmacol Rev 33:213-251, 1982) to study the volume-pressure relationship of the systemic venous circulation during and immediately after massive blood loss. Our theoretical predictions were based on experimental measurements performed in conscious, chronically instrumented swine subjected to massive and rapid loss of a predetermined amount of blood. These animals were subjected to an exponential removal of either 50% of their calculated blood volume in 1 hour or a linear removal of 60% in 15 minutes. Our computer model indicates a hysteresis effect between the volume-pressure curves during and immediately following hemorrhage. The results emphasize the importance of venous capacitance changes as a compensatory response to blood loss.

Animals↗

PubMed1996

Sensory gating in a computer model of the CA3 neural network of the hippocampus.

We have developed a unique computer model of the CA3 region of the hippocampus that simulates the P50 auditory evoked potential response to repeated stimuli in order to study the neuronal circuits involved in a sensory processing deficit associated with schizophrenia. Our computer model of the CA3 hippocampal network includes recurrent activation from within the CA3 region as well as input from the entorhinal cortex and the medial septal nucleus. We used the model to help us determine if the cortical and septal inputs to the CA3 hippocampus alone are responsible for the gating of auditory evoked activity, or if the strong recurrent activity within the CA3 region contributes to this phenomenon. The model suggests that the medial septal input is critical for normal gating; however, to a large extent the activity of the medial septal input can be replaced by simulated stimulation of the hippocampal neurons by a nicotinic agonist. The model is thus consistent with experimental data that show that nicotine restores gating of the N40 evoked potential in fimbria-fornix lesioned rats and of the P50 evoked potential in schizophrenic patients.

Animals↗

PubMed1985

Shell computer model of cardiac electropotential changes.

A discrete process computer model has been developed to simulate the electropotential changes of heart musculature and the operation of the cardiac conduction system. The model is implemented on an ICL-4/72 computer and is oriented to cardiac rhythm studies, allowing practically all rhythm pathologies, including pacemaker applications, to be simulated. The paper describes in detail the principles on which the model is based, compares the model with other models of the same system and shows concisely some results of simulation experiments in the form of computer generated ECG records.

Atrioventricular Node↗

PubMed1986

Computer modeling of actinomycin D interactions with double-helical DNA.

We have performed molecular mechanical calculations on intercalation complexes of actinomycin D with a series of base-paired hexanucleoside pentaphosphates; d(GCGCGC)2, d(GCCGGC)2, d(GCATGC)2, d(GCTAGC)2 and d(ATGCAT)2. Our results are in good agreement with previous experimental work on sequence selectivity. The results provide a rationalization for the strong preference of actinomycin D to intercalate on the 3' side of guanine residues, consistent with previously proposed models. Finally, the computed structures for d(ATGCAT)2-actinomycin D complexes have been compared with two-dimensional nuclear magnetic resonance nuclear Overhauser effect experimental results. To our knowledge, this is the first extensive comparison of molecular mechanical model structures for a drug-DNA complex with experimental solution phase data. We find generally good agreement between our computational models and the experimental solution phase structures.

Computers↗

PubMed1995

Validation of a computer model of haemorrhage and transcapillary refill.

A computer model is described which uses blood volume deficit and its duration to simulate the first two hours of haemorrhage, including an estimation of the blood volume added by Starlings transcapillary refill mechanism. Computer prediction of the haematocrit was compared with published data on haemorrhage in animals. There was close correlation with data on the haemodilution caused by Starling's transcapillary refill mechanism in conscious swine (r = 0.84).

Animals↗