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At least 127 records · Page 7Linked to original sources
PubMed1997

A computer model of uterine contractions based on action potential propagation and intercellular calcium waves.

OBJECTIVE: To simulate a uterine contraction using a novel computer model for uterine communication and to validate the assumptions of the computer model by comparing the simulated contraction with a real uterine contraction. METHODS: The computer model assumed two known mechanisms of intercellular communication: action potential propagation and calcium wave propagation. Simulations were performed on a desktop computer using available programming language. Model validity was assessed by fitting the computer-simulated contraction to a real contraction and comparing the fit values with values measured independently. RESULTS: The simulated contraction demonstrated five characteristics that are also observed in human labor: 1) gradual onset, 2) a linear rising segment, 3) a plateau region, 4) a symmetrical fall, and 5) gradual offset. The fit values agreed well with values determined experimentally and supported the model. CONCLUSIONS: Our results support the model, strongly suggesting that intercellular communication occurs throughout the uterus by action potentials and locally within the tissue by calcium waves.

Action Potentials↗
PubMed1998

GABA(B) modulation improves sequence disambiguation in computational models of hippocampal region CA3.

Computational models of hippocampal region CA3 were used to study the role of theta rhythm in storage and retrieval of temporal sequences of neuronal activity patterns. Retrieval of multiple overlapping temporal sequences requires a mechanism for disambiguation, e.g., for choosing between two sequences with the same starting pattern but different final patterns (forked sequences). Modulatory input to the hippocampus from the medial septum may enhance the disambiguation of pattern sequences by causing phasic changes in the relative strength of afferent input and recurrent excitation. In the models, the strength of recurrent synaptic transmission is modulated by activation of GABA(B) receptors. Theta frequency inputs from the medial septum cause oscillations in the levels of GABA in the model, producing phasic changes in the strength of synaptic potentials during a theta cycle similar to those observed experimentally (Wyble et al., Soc Neurosci Abstr 1997;23: 197.7). These phasic changes in GABA(B) suppression improve sequence disambiguation in the simulations, as previously shown with analysis of a simpler model (Sohal and Hasselmo, Neural Comp 1998;10:889-902). In addition, tonic changes in levels of cholinergic modulation enhance the storage of forked sequences by preventing a strong influence of recurrent synapses during storage.

Animals↗
PubMed2005

Differential binding of VEGF isoforms to VEGF receptor 2 in the presence of neuropilin-1: a computational model.

A comprehensive, biophysically accurate, computational model of vascular endothelial growth factor (VEGF) family member interactions with endothelial cell surface receptors was developed to study angiogenesis. Neuropilin-1 (NRP1) and the signaling VEGF receptor, VEGFR2, do not interact directly but are bridged by one VEGF isoform, VEGF(165). Using the model and published experimental data, we estimated the kinetic rate of this VEGFR2-NRP1 coupling in vitro. With the use of this rate, our model gives predictions in good quantitative agreement with several independent in vitro experiments involving VEGF(121) and VEGF(165) isoforms, confirming that VEGFR2-NRP1 coupling through VEGF(165) can fully explain the observed differences in receptor binding and phosphorylation in response to these isoforms. Model predictions also determine the mechanism of action of a commonly used NRP1 antibody and predict the results of potential future experiments. This is the first model to include VEGF isoforms or NRPs, and it is a necessary step toward a quantitative molecular level description of VEGF that can be extended to in vivo situations. The model has applications for both proangiogenic and antiangiogenic therapies, such as for heart disease and cancer, as well as in tissue engineering.

Kinetics↗
PubMed2004

Development and validation of computational models of cellular interaction.

In this paper we take the view that computational models of biological systems should satisfy two conditions - they should be able to predict function at a systems biology level, and robust techniques of validation against biological models must be available. A modelling paradigm for developing a predictive computational model of cellular interaction is described, and methods of providing robust validation against biological models are explored, followed by a consideration of software issues.

Animals↗
PubMed1989

Paraplegic standing controlled by functional neuromuscular stimulation: Part I--computer model and control-system design.

We have developed a planar computer model to investigate paraplegic standing induced by functional neuromuscular stimulation. The model consists of nonlinear musculotendon dynamics (pulse train activation dynamics and musculotendon actuator dynamics), nonlinear body-segmental dynamics, and a linear output-feedback control law. The model of activation dynamics is an analytic expression that characterizes the relation between the stimulus parameters (pulse width and interpulse interval) and the muscle activation. Hill's classic two-element muscle model was modified into a musculotendon actuator model in order to account for the effects of submaximal activation and tendon elasticity on development of force by the actuator. The three body-segmental, multijoint model accounts for the anterior-posterior movements of the head and trunk, the thigh, and the shank. We modeled arm movement as an external disturbance and imposed the disturbance to the body-segmental dynamics by means of a quasistatic analysis. Linearization, and at times linear approximation of the computer model, enabled us to compute a constant, linear feedback-gain matrix, whose output is the net activation needed by a dynamical joint-torque actuator. Motivated by an assumption that minimization of energy expenditure lessens muscle fatigue, we developed an algorithm that then computes how to distribute the net activation among all the muscles crossing the joint. In part II, the combined feedback control strategy is applied to the nonlinear model of musculotendon and body-segmental dynamics to study how well the body ought to maintain balance should the feedback control strategy be employed.

Biomechanical Phenomena↗
PubMed1989

Computer model for simulation of first transit cardiac radionuclide curves--I.

A discrete-time, lumped-parameter mathematical model of the human cardiopulmonary circulation as it appears during a first-transit radionuclide study is developed. Eleven compartments, four delays, and 26 transfer paths are modeled, including the entire circulation from an input compartment before the vena cava to an output compartment after the aorta. The 26 transfer paths include forward and reverse flow through the heart valves, backflow from the atria into the veins, and five types of shunts. A method of modeling continuously-variable delay segments with only discrete-time sample points is devised to allow more versatility in specifying delays. The model simulates discrete time-activity curves for the various compartments of the cardiopulmonary system. The curves are obtained for end-systole and end-diastole. Simulation of curves indicative of a normal heart and several heart defects is presented. The use of this model for computer analysis of first-transit cardio-radionuclide curves is discussed.

Computer Simulation↗
PubMed1998

Applications of computer modelling for the design of orthopaedic, dental and cardiovascular biomaterials.

Biomaterials do not escape from the general trend present in all contemporary science and technology towards increasing use of computers and information technology. In this paper the use of computer modelling for the design of biomaterials is discussed. The word 'biomaterials' is interpreted in its broadest sense, i.e. referring to any foreign object brought into the body for temporary or permanent use. Computer modelling will first be discussed as a tool to model biological structures (bones, arteries) or to investigate and simulate biological interactions at implant-host interfaces. It will then be illustrated how computer modelling, using insights gained from the modelling of the biological structures themselves, is used in the design process of dental, orthopaedic and cardiovascular prostheses. The area of computer modelling for biomaterials applications has become so vast that an exhaustive overview is impossible in the framework of one paper. Rather, some illustrative case studies will be discussed which are, in the opinion of the authors, representative of general trends in this challenging domain of science on the boundary between engineering and medicine.

Cardiovascular Diseases↗
PubMed2001

Three-dimensional computer modeling of the human upper respiratory tract.

Computer simulations of airflow and particle-transport phenomena within the human respiratory system have important applications to aerosol therapy (e.g., the targeted delivery of inhaled drugs) and inhalation toxicology (e.g., the risk assessment of air pollutants). A detailed description of airway morphology is necessary for these simulations to accurately reflect conditions in vivo. Therefore, a three-dimensional (3D) physiologically realistic computer model of the human upper-respiratory tract (URT) has been developed. The URT morphological model consists of the extrathoracic (ET) region (nasal, oral, pharyngeal, and laryngeal passages) and upper airways (trachea and main bronchi) of the lung. The computer representation evolved from a silicone rubber impression of a medical school teaching model of the human head and throat. A mold of this ET system was sliced into 2-mm serial sections, scanned, and digitized. Numerical grids, for use in future computational fluid dynamics (CFD) simulations, were generated for each slice using commercially available software (CFX-F3D), AEA Technology, Harwell, UK. The meshed sections were subsequently aligned and connected to be consistent with the anatomical model. Finally, a 3D curvilinear grid and a multiblock method were employed to generate the complete computational mesh defined by the cross-sections. The computer reconstruction of the trachea and main bronchi was based on data from the literature (cited herein). The final unified 3D computer model may have significant applications to aerosol medicine and inhalation toxicology, and serve as a cornerstone for computer simulations of air flow and particle-transport processes in the human respiratory system.

Bronchi↗
PubMed1986

Computer modeling of estradiol interactions with the estrogen receptor.

Two computer models for the binding of estradiol to estrogen receptors were constructed, based solely upon the thermodynamic constraints of the most likely equilibria involved and known equilibrium constants. Previous data had suggested that the positive cooperativity of the system was dependent upon a monomer-dimer equilibrium (Notides et al., Proc. natn. Acad. Sci., U.S.A. 78 (1981) 4926-4930). Using computer modeling, we confirmed that the thermodynamic constraints of a monomer-dimer equilibrium system result in convex Scatchard plots in agreement with experimental data, including the progression to linearity at low receptor concentrations. This technique yielded estimates of the equilibrium constant for dimerization (approx. 10(10) to 10(14) M-1). The dose-response characteristics of the monomer-dimer equilibrium system revealed steep dose-response curves that were sensitive to the receptor concentration. In contrast, the dose-response curves that did not undergo a monomer-dimer equilibrium system and had a single step equilibrium process were more gradual.

Computers↗
PubMed2005

The role of computational models of the immune system in designing vaccination strategies.

Mathematical and computational models are designed to improve our understanding of biological phenomena, to confirm/reject hypotheses, and to find points of intervention by altering the behavior of the studied systems. Here we describe the role of mathematical/computational models of the immune system. In particular, we analyze some examples of how mathematical modeling can contribute to finding optimal vaccination strategies. Indeed, computational modeling offers an intriguing opportunity from the theoretical point of view, and it will be of interest for clinically oriented investigators who wish to find optimal therapeutic strategies and for pharmaceutical industries that want to produce effective and successful drugs.

Computational Biology↗
PubMed2006

Biologically based computational models of high-level cognition.

Computer models based on the detailed biology of the brain can help us understand the myriad complexities of human cognition and intelligence. Here, we review models of the higher level aspects of human intelligence, which depend critically on the prefrontal cortex and associated subcortical areas. The picture emerging from a convergence of detailed mechanistic models and more abstract functional models represents a synthesis between analog and digital forms of computation. Specifically, the need for robust active maintenance and rapid updating of information in the prefrontal cortex appears to be satisfied by bistable activation states and dynamic gating mechanisms. These mechanisms are fundamental to digital computers and may be critical for the distinctive aspects of human intelligence.

Brain↗
PubMedDate not supplied

Computer modeling of the abdominal aorta using magnetic resonance images.

An approach is described for creating a 3-D computer model of the abdominal aorta from just two projective images. The aorta is modeled by conical segments connecting circular cross sections. Accuracy of this technique is within 1 mm. From the 3-D computer model, quantitative measurements of vessel diameter, length, and position are available for any subset of the arterial structure. Visualization is enhanced by displaying the computer model rather than a direct set of images obtained from different perspectives. Ambiguities from overlapping branches can be resolved by rotating the model or by eliminating the interfering structures. This approach has been applied in both phantom studies, in which quantitative comparisons were made, and in vivo studies, in which qualitative evaluations were made.

Aorta, Abdominal↗
PubMed2005

Prediction of gastric cancer lymph node status by sentinel lymph node biopsy and the Maruyama computer model.

AIMS: The extent of lymph node dissection in gastric cancer remains controversial. The Maruyama computer model and the sentinel lymph node biopsy (SLNB) are compared for their value to predict the nodal status and lead to stage-adapted surgery. METHODS: Thirty four patients with stage I-IV gastric cancer underwent both staging procedures. For SLNB, 15 patients underwent endoscopic, peri-tumoural injection of (99m)Tc-colloid, and 19 patients were injected of Patent blue V. All 'hot' or blue sentinel lymph nodes (SLNs) were separately excised and histopathologically assessed. If the SLN was negative after routine staining by H&E, it was processed completely and reanalysed after immunohistochemistry. RESULTS: At least, one SLN was detected by means of SLNB in 33/34 of the patients. The sensitivity to identify a positive nodal status was 22/33 and the specificity/positive predictive value was 10/10 and 22/22. Additional micrometastases or isolated tumour cells in the SLN led to 'upstaging' of 5/15, initially classified as nodal negative by H&E-staining. Using the Maruyama computer model, a sensitivity of 22/23 for the correct prediction of the lymph node involvement was associated with a specificity of 2/10 and a positive predictive value of 22/30. CONCLUSIONS: The clinical impact of the Maruyama computer model is limited due to low specificity and a low positive predictive value, rendering the method less useful as an indicator for individualised surgery.

Diagnosis, Computer-Assisted↗
PubMed2005

Computational modelling of a total knee prosthetic loaded in a dynamic knee simulator.

Dynamic knee simulators attempt to reproduce the estimated forces, moments, and motions of both the patello-femoral and tibio-femoral joints during ambulatory activities. As a continuation of work designed to reproduce desired three-dimensional joint loading and motion on a dynamic knee simulator, the goal of this study was to develop a computational model of a prosthetic knee placed within an existing computational model of a dynamic knee simulator. The resulting model was then used to produce inputs to the controllable axes of the simulator for reproduction of desired knee loading and motion. Previously, a three-dimensional computational model of the simulator was developed and verified using a simplified and instrumented analog knee. The work presented here replaced the simplified and constrained geometries of the analog knee with structures representing a prosthetic knee. Three-dimensional geometries were determined based on digitized surface points of a right total knee replacement. Deformable contacts between the articulating surfaces of the tibio-femoral and patello-femoral joints were then defined and model sensitivities were identified. Predicted results from the computational model were compared to experimental results for force profiles applied at the simulator's controllable axes. Within identified limitations, the model was then used to generate inputs to the simulator to reproduce desired patellar tendon load during a squat and desired out-of-sagittal-plane motion during a squat.

Arthroplasty, Replacement, Knee↗
PubMedDate not supplied

A dose computation model for 241Am vaginal applicators including the source-to-source shielding effects.

A dose computation model has been developed for the determination of dose distributions around vaginal plaque applicators containing encapsulated 241Am sources. Encapsulated sources of 241Am emit primarily 60-keV photons which have a half-value layer thickness of 1/8 mm of lead. This makes possible highly effective in vivo shielding of normal tissues at risk, by placing thin lead shields at appropriate places on the applicator. However, self-absorption of photons in the source material itself is intense, requiring bulky sources of about 1 cm diameter. These sources also produce considerable source-to-source shielding which must be taken into account in dose calculations. Our dose computation model for a single source employs three-dimensional integration of dose contributions from volume elements of the source including the effects of absorption and scattering of photons in the source material, titanium encapsulation, and water. An empirical correction to Berger's data on buildup factors of point, isotropic sources is made to account for the effects of anisotropic photon emission by cylindrical 241Am sources. The second part of our dose computation model takes into account source-to-source shielding effects on both primary and scattered photons for the vaginal plaque geometry. The results of the model have been verified for accuracy by comparisons with extensive dosimetry measurements using lithium fluoride thermoluminescent dosimeters.

Americium↗
PubMed1988

Computer modeling of cardiac rhythm disturbances and heart-pacemaker interaction.

Different computer models have been developed in order to study various aspects of cardiac electrophysiological processes. These models can be classified according to many parameters and also in respect to their application areas. One group of the models is devoted to computer simulation of cardiac rhythm disturbances and to reproduction of interactions between the heart and an artificial pulse generator. This report overviews the recent models of arrhythmias and heart-pacemaker interaction. Special attention is paid to (1) functioning of fundamental model elements, (2) structure of the heart model, (3) pacemaker models, and (4) forms of results offered by simulation experiments. Existing models are classified and compared. To illustrate the medical capability of rhythm and pacemaker models, three computational experiments are presented with model atrioventricular reentry tachycardia and reentry tachycardia mediated by a DDD pacemaker. Future development and utilization of arrhythmia and pacemaker models are briefly discussed.

Arrhythmias, Cardiac↗
PubMed2000

Self-organization and competition in the immune response to cancer invasion: a phase-orientated computational model of oncogenesis.

MOTIVATION: Recent studies indicate that fractal dimensions can uncover aspects of cellular dynamics prior to pathological manifestation. In this respect we are interested in building a computational model of oncogenesis able to generate patterns with the same fractal dimension spectrum as the in vivo tumor. RESULTS: A new theoretical model incorporating a systemic view of oncogenesis in a computational model was proposed. The tumor growth is viewed as competition for resources between the two self-organizing subsystems: the neoplastic and the immune. Numerical simulations revealed that tumor escape can be uncovered in some earlier stage of the immune-system-tumor interaction using multifractal measures. The described computational model is able to simulate also the case of immune, surgical, chemical and radiotherapeutical treatment, as well as their effects. AVAILABILITY: T The software used is available on request from the authors. CONTACT: Sorinel Oprisan, University of New Orleans, Department of Psychology, Ne w Orleans, LA 70148, USA. soprisan@uno.edu

Computer Simulation↗
PubMed2005

Computational model for cell migration in three-dimensional matrices.

Although computational models for cell migration on two-dimensional (2D) substrata have described how various molecular and cellular properties and physiochemical processes are integrated to accomplish cell locomotion, the same issues, along with certain new ones, might contribute differently to a model for migration within three-dimensional (3D) matrices. To address this more complicated situation, we have developed a computational model for cell migration in 3D matrices using a force-based dynamics approach. This model determines an overall locomotion velocity vector, comprising speed and direction, for individual cells based on internally generated forces transmitted into external traction forces and considering a timescale during which multiple attachment and detachment events are integrated. Key parameters characterize cell and matrix properties, including cell/matrix adhesion and mechanical and steric properties of the matrix; critical underlying molecular properties are incorporated explicitly or implicitly. Model predictions agree well with experimental results for the limiting case of migration on 2D substrata as well as with recent experiments in 3D natural tissues and synthetic gels. Certain predicted features such as biphasic behavior of speed with density of matrix ligands for 3D migration are qualitatively similar to their 2D counterparts, but new effects generally absent in 2D systems, such as effects due to matrix sterics and mechanics, are now predicted to arise in many 3D situations. As one particular sample manifestation of these effects, the optimal levels of cell receptor expression and matrix ligand density yielding maximal migration are dependent on matrix mechanical compliance.

Animals↗