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Results for “computational modelling”

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At least 145 records · Page 8Linked to original sources

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↗

PubMed1989

Three-dimensional computer model of the heart: fibrillation induced by extrastimulation.

We present a three-dimensional (3D) computer model that simulates electrical activity in the heart during fibrillation. A real dog heart is discretized to form 1473 interconnected cubic elements. The model exhibits normal activation and recovery from pacing. Five or more extrastimuli induce a self-sustaining tachyarrhythmia that soon degenerates into a fibrillatory rhythm. The extrastimuli increase the excitability of the myocardial cell population. The result is a rapid re-excitation of cells that allows for only a partial recovery of cell action potential. This suggests that a dispersion of refractory states of the cell population is the cause of fibrillation in this computer model.

Animals↗

PubMed1991

An evaluation of eight computer models of mammalian inner hair-cell function.

Eight computer models of auditory inner hair cells have been evaluated. From an extensive literature on mammalian species, a subset of well-reported auditory-nerve properties in response to tone-burst stimuli were selected and tested for in the models. This subset included tests for: (a) rate-level functions for onset and steady-state responses; (b) two-component adaptation; (c) recovery of spontaneous activity; (d) physiological forward masking; (e) additivity; and (f) frequency-limited phase locking. As models of hair-cell functioning are increasingly used as the front end of speech-recognition devices, the computational efficiency of each model was also considered. The evaluation shows that no single model completely replicates the subset of tests. Reasons are given for our favoring the Meddis model [R. Meddis, J. Acoust. Soc. Am. 83, 1056-1063 (1988)] both in terms of its good agreement with physiological data and its computational efficiency. It is concluded that this model is well suited to provide the primary input to speech recognition devices and models of central auditory processing.

Animals↗

PubMed2001

Computational models of cells and tissues: machines, agents and fungal infection.

Computational models have been of interest in biology for many years and have represented a particular approach to trying to understand biological processes and phenomena from a systems point of view. Much of the early work was rather abstract and high level and probably seemed to many to be of more philosophical than practical value. There have, however, been some advances in the development of more realistic models and the current state of computer science research provides us with new opportunities through both the emergence of models that can model seriously complex systems and also the support that modern software can give to the modelling process. This paper describes a few of the early simple models and then goes on to look at some new ideas in the area with a particular application drawn from the world of mycology. Some general principles relating to how new and emerging computational techniques can help to represent and understand extremely complex models conclude the paper.

Computational Biology↗

PubMed1995

Computer models: killing mosquitoes with information.

This paper looks at the relationship between man and mosquitoes from the perspective of coevolution. From this perspective, the primacy of information processing in vector control programs becomes acutely evident. A composite mosquito control program is developed and illustrated to show the benefits derived from incremental increases in information. The use of computer modeling is seen as the next logical step to be taken by vector control personnel to add the next increment of efficiency and effectiveness. This step could well lead to significant reductions or perhaps the elimination of the need for pesticide use. The author encourages the use of computer modeling in teams as the means to learn across disciplines. The feasibility of this approach has been greatly enhanced by the availability of off-the-shelf modeling programs. The author appeals to university and vector control professionals to support students and staff in learning computer modeling techniques.

Animals↗

PubMed2000

Computational modeling of the baroreflex arc: nucleus tractus solitarius.

In this study, we examine the utility of computational modeling in understanding nervous system function. We start by examining the reasons for, and major approaches to, computational modeling. We then chose a modeling approach and applied different variations to understanding nucleus tractus solitarius (NTS) neuronal responses to various baroreceptive stimuli. We examine the results in light of our objectives and with regard to the known parameters of the system under investigation. Our results demonstrate that modeling can be a useful tool in analysis of (and examination of underlying mechanisms for) NTS behavior on many levels.

Animals↗

PubMed1999

A computational model for visual selection.

We propose a computational model for detecting and localizing instances from an object class in static gray-level images. We divide detection into visual selection and final classification, concentrating on the former: drastically reducing the number of candidate regions that require further, usually more intensive, processing, but with a minimum of computation and missed detections. Bottom-up processing is based on local groupings of edge fragments constrained by loose geometrical relationships. They have no a priori semantic or geometric interpretation. The role of training is to select special groupings that are moderately likely at certain places on the object but rate in the background. We show that the statistics in both populations are stable. The candidate regions are those that contain global arrangements of several local groupings. Whereas our model was not conceived to explain brain functions, it does cohere with evidence about the functions of neurons in V1 and V2, such as responses to coarse or incomplete patterns (e.g., illusory contours) and to scale and translation invariance in IT. Finally, the algorithm is applied to face and symbol detection.

Algorithms↗

PubMed1987

A computational model of reasoning from the clinical literature.

This paper explores the premise that a formalized representation of empirical studies can play a central role in computer-based decision support. The specific motivations underlying this research include the following propositions: Reasoning from experimental evidence contained in the clinical literature is central to the decisions physicians make in patient care. A computational model, based upon a declarative representation for published reports of clinical studies, can drive a computer program that selectively tailors knowledge of the clinical literature as it is applied to a particular case. The development of such a computational model is an important first step toward filling a void in computer-based decision support systems. Furthermore, the model may help us better understand the general principles of reasoning from experimental evidence both in medicine and other domains. Roundsman is a developmental computer system which draws upon structured representations of the clinical literature in order to critique plans for the management of primary breast cancer. Roundsman is able to produce patient-specific analyses of breast cancer management options based on the 24 clinical studies currently encoded in its knowledge base. The Roundsman system is a first step in exploring how the computer can help to bring a critical analysis of the relevant literature to the physician, structured around a particular patient and treatment decision.

Artificial Intelligence↗

PubMed1999

[Study of the posterior cruciate ligament using a 3D computer model: ligament biometry during flexion, application to surgical replacement of the ligament].

We have developed a 3D computed model of the knee joint, constructed from MRI acquisitions in a living individual. We have used this model to perform an anatomic and biometric study of the posterior cruciate ligament (PCL) during flexion, and an assessment of the optimal location for an intraarticular graft. The method used a 3D computed model constructed from MRI acquisitions during knee flexion (0 to 75 degrees). The range of motion was limited by a positioning device. We took 13 acquisitions from 0 to 75 degrees of flexion. Each acquisition consisted of 21 sagittal cross sections of 3 mm slice thickness. We used the Delaunay reconstruction to obtain a 3D geometric model. A matching process to fix one part of the articulation during the movement, allows for the kinematic analysis of the tibia relative to the fixed femur. This model allows to follow the displacement of a bone point during knee flexion. Knowing the relative displacement of the bone insertions of the ligament, it may be possible to determine the length of the PCL and its bands, to evaluate the length variation during movement, and to determine the optimal location for the insertion of an intraarticular graft, that would lead to the least stretch during flexion. It was found that the mean length of the PCL was 30.2 mm, with the posterior band being 30% longer than the anterior band. During flexion the posterior band increases its length by 10% at 50 degrees flexion, and by 20% at 75 degrees flexion. The anterior band stretches more, to reach 40% elongation at 75 degrees flexion. The best position for insertion of a graft seems to be in the posterolateral portion of the anatomic tibial insertion, and posterior to the anatomic femoral insertion. This method confirms the data in the literature, states precisely the length of the different bands of the PCL, and specifies the points of insertion for a graft, which lead to the least variation in length during flexion.

Biometry↗

PubMed1998

Using computer modeling to help identify patient subgroups in clinical data repositories.

OBJECTIVE: The ability to accurately and efficiently identify patient cases of interest in a hospital information system has many important clinical, research, educational and administrative uses. The identification of cases of interest sometimes can be difficult. This paper describes a two-stage method for searching for cases of interest. DESIGN: First, a Boolean search is performed using coded database variables. The user classifies the retrieved cases as being of interest or not. Second, based on the user-classified cases, a computer model of the patient cases of interest is constructed. The model is then used to help locate additional cases. These cases provide an augmented training set for constructing a new computer model of the cases of interest. This cycle of modeling and user classification continues until halted by the user. MEASUREMENTS: This paper describes a pilot study in which this method is used to identify the records of patients who have venous thrombosis. RESULTS: The results indicate that computer modeling enhances the identification of patient cases of interest.

Bayes Theorem↗

PubMed2001

Computational models of normal and abnormal action potential propagation in cardiac tissue: linking experimental and clinical cardiology.

Computational models have the potential to make a huge impact on our understanding of normal and abnormal cardiac function. The aim of this article is to review tools that have been developed to simulate the electrophysiology of cardiac cells and tissue, and to show how computational models have been used to gain insight into normal and abnormal action potential propagation. Some of the practical problems experienced in the development and application of these models are described, and examples are given.

Action Potentials↗

PubMedDate not supplied

Parallel neural systems for classical conditioning: support from computational modeling.

Classical conditioning has been explained by two main types of theories that postulate different learning mechanisms. Rescorla and Wagner (1972) put forth a theory in which conditioning is based on the ability of the US to drive learning through error correction. Alternatively, Mackintosh (1973) put forth a theory in which the ability of the CS to be associated with the unconditioned stimulus is modulated. We have proposed a reconciliation of these two mechanisms as working in parallel within different neural systems: a cerebellar system for US modulation and a hippocampal system for CS modulation. We developed a computational model of cerebellar function in eyeblink conditioning based on the error correction mechanism of the Rescorla-Wagner rule in which learning-related activity from the cerebellum inhibits the inferior olive, which is the US input pathway to the cerebellum (Gluck et al., 1994). We developed a computational model of the hippocampal region that forms altered representations of conditioned stimuli based on their behavioral outcomes (Gluck & Myers, 1993; Myers et al., 1995). Overall, computational modeling and empirical findings support the idea that, at least in the case of eyeblink conditioning, there may be two different neural systems: the cerebellum which mediates US-based error correction and hippocampus which alters representations of CSs.

Animals↗

PubMedDate not supplied

Computational modelling of blood flow through curved stenosed arteries.

A computational model of three-dimensional blood flow in curved arteries with elliptic stenosis was developed. Two groups of models, (a) different angles of curvature and (b) degrees of stenosis, have been studied under typical conditions for stenosed coronary artery. Useful information on the haemodynamics has been obtained. Results of pressure drop show that the presence of the curvature augments the increased flow resistance due to stenotic lesions. The study also demonstrates the significant presence of secondary flow in a curved artery. In addition, the results have shown that the secondary flow in a curved artery brings about elevated shear stress on the vessel wall. These results indicated that both curvature and stenosis should be considered together by cardiologists to assess or quantify the severity of the stenosis. This study employed a powerful computer-aided design (CAD) package to construct the model and a commercial computational fluid dynamics (CFD) code for the analysis of blood flow in stenosed arteries. The long-term application of this form of research promises to be an effective tool for gaining insights into the pathology of arterial diseases.

Arteries↗

PubMed1993

Regularity of cochlear nucleus stellate cells: a computational modeling study.

This article reports on a computational modeling study designed to investigate the generation of the transient chopper response of cochlear nucleus stellate cells. The model is based on a simulation of the auditory periphery which feeds a generic stellate-cell model. Physiological recordings of transient chopper units in response to short, best frequency, tone bursts show a brief initial period (typically < 10 ms) of rapid rate adaptation as evidenced by a rapid rise in mean interspike interval. Associated with this rate adaptation is a significant increase in firing irregularity. The changes in rate and irregularity have recently been attributed to the activation of noisy inhibitory inputs on the cell [e.g., Banks and Sachs, J. Neurophysiol. 65, 606-629 (1991)]. However, the results show that the transient chopper response pattern can be generated without the need for inhibitory inputs. The transience of the initial chopping pattern is sensitive to the following model parameters: (a) the firing threshold of the cell, (b) the number of excitatory inputs that converge on the cell, and (c) the magnitude of the current delivered to the cell for each active input. The response was also found to be relatively insensitive to changes in the degree of dendritic filtering imposed on the auditory-nerve input. The results of each simulation can be explained by considering the pattern of depolarization the cell receives during the course of a tone burst.

Acoustic Stimulation↗

PubMed1990

The use of selective inhibitors and computer modelling to evaluate the role of specific high affinity cyclic AMP phosphodiesterases in the hormonal regulation of hepatocyte intracellular cyclic AMP concentrations.

Using experimentally derived data for the activities and kinetic constants of hepatocyte cyclic AMP phosphodiesterase isoenzymes together with the derived changes in adenylate cyclase activity, due to stimulation and subsequent desensitization by glucagon, a computer model was established to simulate hepatocyte cyclic AMP metabolism. The established ability of glucagon to activate the 'dense-vesicle' cyclic AMP phosphodiesterase by eliciting its cyclic AMP-dependent phosphorylation was shown on the model to be capable of eliciting a profound reduction in the glucagon-stimulated increase in intracellular cyclic AMP. This was consistent with experimentally derived observations using the compound ICI 118233 which was used to inactivate the 'dense-vesicle' enzyme selectively. The non-hydrolysable adenosine agonist N6 (phenylisopropyl)-adenosine (PIA), which prevents glucagon pre-treatment of hepatocytes blocking the ability of insulin to stimulate the peripheral plasma membrane cyclic AMP phosphodiesterase, is shown here to accentuate the ability of insulin to decrease glucagon-elevated intracellular cyclic AMP concentrations. This effect was obliterated using the compound ICI 63197, a selective inhibitor of the peripheral plasma membrane phosphodiesterase. Computer modelling studies, taking into account experimentally derived actions in insulin in activating the peripheral plasma membrane phosphodiesterase, confirmed the potential of this enzyme to decrease intracellular cyclic AMP concentrations. Modelling of the putative effect of an insulin 'mediator' in activating the two cyclic GMP-stimulated cyclic AMP phosphodiesterase isoenzymes was shown to elicit a decrease in intracellular cyclic AMP concentrations which was comparable to that caused by insulin's action on intact hepatocytes. The relative contribution of each phosphodiesterase form to the metabolism of hepatocyte intracellular cyclic AMP, together with an assessment of the potential effect of inhibition and activation of specific species, was evaluated using the computer model. These experimental and stimulation studies indicate that alterations in the phosphodiesterase activity of the 'dense-vesicle' enzyme, the peripheral plasma membrane enzyme, the cyclic GMP-stimulated cyclic AMP isoforms and the IBMX-insensitive PDE-MQ-II can elicit profound effects upon hepatocyte intracellular cyclic AMP concentrations.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2000

A computational model for the prediction of total knee replacement kinematics in the sagittal plane.

A computational model has been developed using a current generation computer-aided engineering (CAE) package to predict total knee replacement (TKR) kinematic in the sagittal plane. The model includes friction and soft tissue restraint varying according to the flexion angle. The model was validated by comparing the outcomes of anterior-posterior (A-P) laxity tests of two contemporary knee replacements against data obtained from a knee simulating machine. It was also validated against predictions from a computer model reported in the literature. Results show good agreement in terms of A-P displacements. Further tests were performed to determined the influence of the soft tissue restraints varying with flexion angle. This work represents the first attempt to use a sophisticated commercial CAE package to predict TKR motions and the advantages of the modelling procedure chosen are discussed.

Biomechanical Phenomena↗

PubMedDate not supplied

A computer model of lung morphology to analyze SPECT images.

Measurement of the spatial distribution of aerosol deposition in human lungs can be performed using single photon emission computed tomography (SPECT). To relate deposition patterns to real lung structures, a computer model of the airway network has been developed. Computer simulations are presented that are compatible with the analysis of SPECT images. Computational techniques that are consistent with clinical procedures are used to analyze airways by type and number within transverse slices of the lung volume. The computer models serve as customized templates, which when analyzed alongside gamma scintigraphy images, can assist in the interpretation of human test data.

Computer Simulation↗