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At least 1,405 records · Page 78Linked to original sources
PubMed1991

A computer model of pancreatic islet glycolysis.

We have modeled an experiment with perifused pancreatic islet cells using our BIOSSIM language. The experiment and the resulting model are concerned with glucose uptake and glycolysis by the beta-cells of pancreatic islets. Although glycolysis appears to be involved in insulin release, we do not have enough information to represent insulin release in detail. The rapid entry of glucose into the beta-cell is promoted by a carrier having a very high tissue capacity. Phosphorylation of glucose by the low affinity enzyme glucokinase appears to be limiting for glycolysis. The effects of several hexose diphosphate activators of phosphofructokinase are modeled. Model behavior is described. The kinetic parameters of the enzyme submodels are given. Because of the difficulties of preparing large amounts of experimental material, information on pancreatic islet metabolism is limited. This model is a plausible explanation of the experimental results. Recent work on the genetically engineered glucose transporter and glucokinase is discussed.

Animals↗
PubMed2003

[Prospects for computer modeling technology of osteosynthesis in fractures of bones of the lower limbs].

To improve the results of treatment of the patients with femur and shin bone fractures the digital processing of video-information and computer simulation of perosseous osteosynthesis were used. The roentgenogram analysis was conducted using the personal computer equipped with the tolls for image input and visualization and software for data processing. 235 patients with femur and shin bone fractures were treated. The method of perosseous osteosynthesis was used in 127 of them. The digital computer simulation of the operation was conducted in 75 patients. The method has allowed to improve the anatomic and functional results, to reduce the treatment duration, to decrease the number of complications and unsatisfactory outcomes, to optimize the method of perosseous osteosynthesis in the whole.

Fractures, Bone↗
PubMed1995

Computational modeling of a putative fetal alcohol syndrome mechanism.

Fetal alcohol syndrome (FAS) refers to a pattern of birth defects occurring in a subpopulation of children born to women who consume alcohol during pregnancy. The significant medical, social, and economic impact of FAS is increasing. Particularly hard-hit are African-American and native-American women and children. Over the past two decades, basic and clinical research produced voluminous data on ethanol effects on developing organisms. In 1991, Duester and Pullarkat proposed that competition of ethanol with retinol at the alcohol dehydrogenase (ADH) binding site formed the basis of the FAS mechanism. This competition adversely affects the developing fetus caused by deregulation of retinoic acid (RA) homeostasis essential for proper fetal tissue development. Stated concisely, the FAS hypothesis is: 1. Class I ADH catalyzes the rate-limiting step in oxidation of retinol (ROH) to RA, and ethanol (ETOH) to acetic acid, thus establishing competition for ADH between ROH and ETOH. 2. RA is required as a signal molecule for cell differentiation critical for normal fetal morphogenesis. 3. ADH binds ingested ETOH, thus deregulating RA homeostasis leading to improper RA signal transduction. Preliminary results from molecular modeling studies of ROH-ADH and ETOH-ADH structures, and physiologic pharmacokinetic modeling confirm the hypothesis with remarkable fidelity.

Alcohol Dehydrogenase↗
PubMed1995

A computer modeling postulated mechanism for angiotensin II receptor activation.

The angiotensin II receptor of the AT1-type has been modeled starting from the experimentally determined three-dimensional structure of bacteriorhodopsin as the template. Intermediate 3D structures of rhodopsin and beta 2-adrenergic receptors were built because no direct sequence alignment is possible between the AT1 receptor and bacteriorhodopsin. Docking calculations were carried out on the complex of the modeled receptor with AII, and the results were used to analyze the binding possibilities of DuP753-type antagonistic non-peptide ligands. We confirm that the positively charged Lys199 on helix 5 is crucial for ligand binding, as in our model; the charged side chain of this amino acid interacts strongly with the C-terminal carboxyl group of peptide agonists or with the acidic group at the 2'-position of the biphenyl moiety of DuP753-type antagonists. Several other receptor residues which are implicated in the binding of ligands and the activation of receptor by agonists are identified, and their functional role is discussed. Therefore, a plausible mechanism of receptor activation is proposed. The three-dimensional docking model integrates most of the available experimental observations and helps to plan pertinent site-directed mutagenesis experiments which in turn may validate or modify the present model and the proposed mechanism of receptor activation.

Amino Acid Sequence↗
PubMed1999

Synthesis, computer modeling and biological evaluation of novel protein kinase C agonists based on a 7-membered lactam moiety.

4-Hydroxymethyl-5a-methyl-1,3,4,5,5a beta,6,7,8,9,9a alpha-decahydro-2H-benz[d]azepin-2-ones (4-12), which were designed to mimic the biologically active conformation of teleocidins and benzolactams, were synthesized and evaluated for the ability to compete with [3H]phorbol 12,13-dibutyrate in a PKC delta binding assay. Among the compounds, 10-12 showed potent binding affinity, with inhibition constants (Ki) of low nanomolar order. Computational docking simulation also indicates that the relative positions of the hydrogen-bonding sites and hydrophobic regions of the compounds are well matched to the PKC delta binding site.

Benzazepines↗
PubMed2003

Development and validation of computational models for mammalian circadian oscillators.

Circadian rhythms are endogenous rhythms with a cycle length of approximately 24 h. Rhythmic production of specific proteins within pacemaker structures is the basis for these physiological and behavioral rhythms. Prior work on mathematical modeling of molecular circadian oscillators has focused on the fruit fly, Drosophila melanogaster. Recently, great advances have been made in our understanding of the molecular basis of circadian rhythms in mammals. Mathematical models of the mammalian circadian oscillator are needed to piece together diverse data, predict experimental results, and help us understand the clock as a whole. Our objectives are to develop mathematical models of the mammalian circadian oscillator, generate and test predictions from these models, gather information on the parameters needed for model development, integrate the molecular model with an existing model of the influence of light and rhythmicity on human performance, and make models available in BioSpice so that they can be easily used by the general community. Two new mammalian models have been developed, and experimental data are summarized. These studies have the potential to lead to new strategies for resetting the circadian clock. Manipulations of the circadian clock can be used to optimize performance by promoting alertness and physiological synchronization.

Animals↗
PubMed2002

ECVAM's activities on computer modelling and integrated testing.

This paper introduces the basic concepts of quantitative structure-activity relationship (QSAR), expert system and integrated testing strategy, and explains how the analogy between QSARs and prediction models leads naturally to criteria for the validation of QSARs. ECVAM's in-house research programme on QSAR modelling and integrated testing is summarised, along with plans for the validation of QSAR models and expert system rulebases at the European Union level.

Animal Testing Alternatives↗
PubMed2000

Computational model of DIC microscopy for reconstructing 3-D specimens.

Differential Interference Contrast (DIC) microscopy is a powerful visualization tool used to study live biological cells. Its use, however, has been limited to qualitative observations. The inherent non-linear relation between the object properties and the image intensity makes quantitative analysis difficult. As a first step towards measuring optical properties of objects from DIC images, we develop a model for the image formation process using methods consistent with energy conservation laws. We verify our model by comparing real image data of manufactured specimens to simulated images of virtual objects. As the next step, we plan to use this model to reconstruct the three-dimensional properties of unknown specimens.

Computer Simulation↗
PubMed1986

A computational model of the error detector of human visual accommodation.

A mathematical model is proposed for the error detector of the human visual accommodative system. The model supposes that the accommodative error detector derives both the direction and the magnitude of the accommodative error from naturally-occurring oscillations of the lens and their effects on retinal-image contrast. Differential operators take the first derivatives of two time varying functions: lens power and retinal-image contrast. Directional information is obtained by comparing the signs of these two derivatives and magnitude information is obtained by comparing their amplitudes.

Accommodation, Ocular↗
PubMed1997

Computer model analysis of the relationship of ST-segment and ST-segment/heart rate slope response to the constituents of the ischemic injury source.

The objective of the study was to investigate a proposed linear relationship between the extent of myocardial ischemic injury and the ST-segment/heart rate (ST/HR) slope by computer simulation of the injury sources arising in exercise electrocardiographic (ECG) tests. The extent and location of the ischemic injury were simulated for both single- and multivessel coronary artery disease by use of an accurate source-volume conductor model which assumes a linear relationship between heart rate and extent of ischemia. The results indicated that in some cases the ST/HR slope in leads II, aVF, and especially V5 may be related to the extent of ischemia. However, the simulations demonstrated that neither the ST-segment deviation nor the ST/HR slope was directly proportional to either the area of the ischemic boundary or the number of vessels occluded. Furthermore, in multivessel coronary artery disease, the temporal and spatial diversity of the generated multiple injury sources distorted the presumed linearity between ST-segment deviation and heart rate. It was concluded that the ST/HR slope and ST-segment deviation of the 12-lead ECG are not able to indicate extent of ischemic injury or number of vessels occluded.

Adult↗
PubMed2000

Computational models of blood flow in the circle of Willis.

A two-dimensional, steady state model of the circle of Willis has been developed. To simulate the peripheral resistance of the cerebrovascular tree, blocks of porous media were used. Their effective resistance was kept constant, disregarding the effects of arterial auto-regulation. The model was then used to simulate different common abnormalities of the circle of Willis while a range of varying boundary conditions was imposed to the right internal carotid artery (ICA). The total flux was tabulated and compared favourably with both clinical measurements and other models of the circle of Willis. Relevant fluid dynamics effects were also observed and analysed. The present model demonstrates that the use of CFD can produce physiological results if the appropriate boundary conditions are used. We can provide clinicians with a priority list of the severity of the flux reduction for the considered abnormalities for different degrees of stenosis of the right ICA. From this study it is apparent that the redistribution of blood via the circle of Willis is mainly driven by changes in the vascular resistance of the brain rather than in the local arterial geometry. The use of valid peripheral resistances allows for a more realistic model of the circle of Willis but also highlights the need for more accurate means to estimate the vascular resistance of a patient.

Animals↗
PubMed1993

Combined evaluation of interaural time and intensity differences: psychoacoustic results and computer modeling.

The physical and the psychophysical relationships between interaural time and intensity differences were studied for 24 frequency bands of critical bandwidth covering the full audio range. For the physical investigations a catalogue of outer ear impulse responses for 122 directions of the upper hemisphere was analyzed according to the combinations of interaural time and level differences found in each critical band. From these data curves of "natural combinations" of the interaural parameter differences were determined by the minimum square error method. In a psychoacoustical study it is shown that signals containing "natural" parameter combinations produce response patterns that differ from those produced when signals with contradictory interaural properties have been used. Finally an extension to the powerful binaural model of Lindemann [J. Acoust. Soc. Am. 80, 1608-1622 (1986)] is introduced, taking into account the results of the previous investigations.

Acoustic Stimulation↗
PubMed1993

A computer model of the interleukin-4/receptor complex.

Interleukin-4 is a member of the cytokine family, a group of related messenger proteins which collectively help to moderate and control the immune response. It is believed that the folding topology of the beta-sheets of the interleukin-4 receptor (IL4R) is the same as that seen in the crystal structure of CD4. Although the sequence identity is low, homology modeling techniques have been used to model the IL4R structure from CD4. Refinement by molecular dynamics leads to a suggested structure which has been docked to interleukin-4 (IL4). Several residues of apparent importance for binding are identified.

Amino Acid Sequence↗