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Results for “Computer Simulation”

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PubMed1993

Variables affecting pulmonary nodule detection with computed tomography: evaluation with three-dimensional computer simulation.

To meaningfully evaluate factors determining the overall accuracy of computed tomography (CT) for identifying pulmonary nodules, computer-generated nodules were superimposed on normal CT scans and interpreted independently by three experienced chest radiologists. Variables evaluated included nodule size, shape, number, density, location, edge characteristics, and relationship to adjacent vessels, as well as technical factors, including slice thickness and electronic windowing. The overall sensitivity in identifying nodules was 62% and the specificity was 80%. On average, the observers identified 56, 67, and 63% of nodules on 1.5-, 5-, and 10-mm-thick sections, respectively (p = 0.037). Nodules were more difficult to identify on 1.5-mm-thick sections. On average, observers identified 1, 48, 82, and 91% of nodules < 1.5, < 3, < 4.5, and < 7 mm in diameter, respectively (p < 0.001). Other factors that made a significant contribution (p < 0.01) in identifying nodules, as determined by linear discriminant function analysis, included nodule location, angiocentricity, and density. We concluded that computer-generated nodules can be used to assess a large number of imaging variables. We anticipate that this approach will be of considerable utility in assessing the accuracy of interpretation of a wide range of pathologic entities as well as in optimizing three-dimensional scan protocols within the thorax.

Humans↗

PubMed1977

Dialysis continuous process for ammonium-lactate fermentation of whey: mathematical model and computer simulation.

A mathematical model was developed to describe a dialysis process for the continuous fermentation of whey lactose to lactic acid, with neutralization to a constant pH by ammonia. In the process, whey of a relatively high concentration is fed into the fermentor circuit at a relatively low rate so that the residual concentration of lactose is low. The fermentor effluent contains ammonium lactate, bacterial cells, and residual whey solids and could be used as a nitrogen-enriched feedstuff for ruminant animals. Only water is fed into the dialysate circuit at a relatively high rate. The dialysate effluent contains purified ammonium lactate and could be converted to lactic acid and ammonium sulfate for industry. The fermentation was specifically modeled as a set of equations representing material balances and rate relationships in the two circuits. Dialysis continuous fermentations, in general, were modeled by combining these equations and by using dimensionless parameters. The generalized model was then solved for the steady state and used to simulate the specific fermentation on a digital computer. The results showed the effects of various material and operational and kinetic parameters on the process and predicted that it could be operated efficiently.

Journal Article↗

PubMed1994

Comparison of a computer simulation program and a traditional laboratory practical class for teaching the principles of intestinal absorption.

Here we describe an evaluation of the effectiveness, compared with a traditional laboratory, of an interactive computer-assisted learning (CAL) program, which simulates a series of experiments performed using isolated, everted sacs of rat small intestine. The program is aimed at undergraduate students of physiology and is designed to offer an alternative student-centered learning approach to the traditional laboratory-based practical class. The evaluative study compared two groups of second-year undergraduate students studying a module on epithelial transport: one group worked independently using the CAL program and associated learning materials, and the other group followed a conventional practical class approach, working in the laboratory under supervision. Knowledge gain of each group was measured by means of a test consisting of a range of question types (e.g., short-answer factual, calculation, interpretation) given to students before and after the module. Student attitude to both approaches was assessed by questionnaire, and the resource requirements were also compared. It was found that the knowledge gain of both groups of students was the same, that students had a positive attitude toward using CAL programs of this type, and that the cost of the conventional laboratory-based approach was five times greater. The potential for integrating CAL programs into the undergraduate curriculum is discussed.

Animal Testing Alternatives↗

PubMed2000

Computer simulations of protein folding by targeted molecular dynamics.

We have performed 128 folding and 45 unfolding molecular dynamics runs of chymotrypsin inhibitor 2 (CI2) with an implicit solvation model for a total simulation time of 0.4 microseconds. Folding requires that the three-dimensional structure of the native state is known. It was simulated at 300 K by supplementing the force field with a harmonic restraint which acts on the root-mean-square deviation and allows to decrease the distance to the target conformation. High temperature and/or the harmonic restraint were used to induce unfolding. Of the 62 folding simulations started from random conformations, 31 reached the native structure, while the success rate was 83% for the 66 trajectories which began from conformations unfolded by high-temperature dynamics. A funnel-like energy landscape is observed for unfolding at 475 K, while the unfolding runs at 300 K and 375 K as well as most of the folding trajectories have an almost flat energy landscape for conformations with less than about 50% of native contacts formed. The sequence of events, i.e., secondary and tertiary structure formation, is similar in all folding and unfolding simulations, despite the diversity of the pathways. Previous unfolding simulations of CI2 performed with different force fields showed a similar sequence of events. These results suggest that the topology of the native state plays an important role in the folding process.

Computer Simulation↗

PubMed1998

Computer simulations of de novo designed helical proteins.

In the context of reduced protein models, Monte Carlo simulations of three de novo designed helical proteins (four-member helical bundle) were performed. At low temperatures, for all proteins under consideration, protein-like folds having different topologies were obtained from random starting conformations. These simulations are consistent with experimental evidence indicating that these de novo designed proteins have the features of a molten globule state. The results of Monte Carlo simulations suggest that these molecules adopt four-helix bundle topologies. They also give insight into the possible mechanism of folding and association, which occurs in these simulations by on-site assembly of the helices. The low-temperature conformations of all three sequences have the features of a molten globule state.

Amino Acid Sequence↗

PubMed1998

Computer simulation of the measured respiratory impedance in newborn infants and the effect of the measurement equipment.

The forced oscillation technique (FOT) is a non-invasive method to investigate lung mechanics. FOT does not require active cooperation and therefore it seems to be useful for lung function measurements in newborn infants. The aims of this simulation study were to investigate the effects of development and growth of the lung, pulmonary inhomogeneities and the measurement equipment on the respiratory impedance (Zrs). The respiratory impedance was simulated by using four lung models with lumped parameters in the frequency range of 3-50 Hz considering resistive and elastic resistances of the respiratory system and the inertance of breathing air and tissue. The simulation has shown that the maturation of lungs produces only a parallel shifting of the real and imaginary part of the impedance curves whereas respiratory diseases change the course of the curves. Furthermore, a high influence of the measurement equipment (e.g. compliance of the face mask, endotracheal tube leaks) on Zrs was found. In conclusion, the simulation has shown that FOT offers a deeper insight in the structure of the respiratory system. However, the technical requirements for accurate measurements in newborns are very high.

Airway Resistance↗

PubMed2001

How do concentration and dosage of the contrast agent affect the signal change in perfusion-weighted magnetic resonance imaging? A computer simulation.

In this study we investigated the effect of varying both concentration and dosage of an intravenously administered MR contrast agent on the concentration-time curve in brain tissue. Aside from injection time and injection rate, our model considers the distribution of transit-time between injection site and brain but it is independent from pulse rate, heart volume or other circulation parameters. The width of the transit-time distribution and the concentration-time course in the brain were computed according to indicator dilution theory. We found that increasing the dosage of the administered contrast agent raises the maximum concentration of the agent in the brain, particularly if the injection time is short. Increasing the concentration of the agent (at fixed dosage and injection rate) also increases maximum concentration in the brain capillaries, particularly if the injection time is long. This increase, however, is less than that achieved by raising the dosage.

Animals↗

PubMed1988

Computer simulation of fluid resuscitation in thermal injury. A. B. Wallace memorial lecture 1987.

Following thermal injury many subsystems of the human body interact closely. The effects both of the pathological event in one subsystem and the subsequent therapy are masked or compensated by changes in other homeostatic subsystems. Not until the capacity of the homeostatic subsystems and/or the therapy is inadequate will the effects become obvious. The very complex postburn situation explains why there are so many different shock-preventing fluid therapy programmes and such crude and insecure monitoring of the therapy. In these situations when there are too many factors to be grasped by the unaided human mind, a computer-based 'patient-simulator' could be of value in diagnosis, monitoring and therapy of the severely ill patient with trauma. An extensive pathophysiological model has been designed to describe fluid shifts and haemodynamics in connection with fluid therapy of traumatic patients. The model makes it possible to calculate and predict clinically important state variables on the basis of fluid input and fluid losses. Sample runs are presented for illustrations in haemorrhage and fluid and salt loading. The model is also used to simulate treatment of a burn patient and the results are compared with measured physiological and biochemical variables. Furthermore, four different formulae for resuscitation of patients with thermal injuries according to Evans, Brooke, Parkland and a hypertonic fluid programme are simulated. The results illustrate the potential use of the 'patient-simulator' for designing fluid resuscitation programmes and attempt to optimize them with respect to infusion rate of the fluid administered.

Animals↗

PubMed1996

Management of queues in out-patient departments: the use of computer simulation.

Notes that patients attending public outpatient departments in Hong Kong spend a long time waiting for a short consultation, that clinics are congested and that both staff and patients are dissatisfied. Points out that experimentation of management changes in a busy clinical environment can be both expensive and difficult. Demonstrates computerized simulation modelling as a potential tool for clarifying processes occurring within such systems, improving clinic operation by suggesting possible answers to problems identified and evaluating the solutions, without interfering with the clinic routine. Adds that solutions can be implemented after they had proved to be successful on the model. Demonstrates some ways in which managers in health care facilities can benefit from the use of computerized simulation modelling. Specifically, shows the effect of changing the duration of consultation and the effect of the application of an appointment system on patients' waiting time.

Appointments and Schedules↗

PubMed1991

[Computer simulation of the dynamics of the arterial system for various cardiovascular situations].

The simulation model describes the basic characteristics of the pulse in a wide range of arterial vessels. By comparison of simulated stenosis with photoplethysmographic registered curves of patients suffering from stenosis, it could be shown, that also pathologic hemodynamics can be adequately described. A new sight of dicrotic pulse generation was derived by the simulated removal of large arteries. This led to the hypothesis of decoupled, autonomous multiple reflections in the arteries of the arm, the leg and the head.

Arterial Occlusive Diseases↗

PubMed1998

X-ray digital subtraction angiography to magnetic resonance-digital subtraction angiography using three-dimensional TRICKS. Historical perspective and computer simulations: a review.

Seventeen years after the introduction of x-ray digital subtraction angiography (DSA), gadolinium-enhanced magnetic resonance (MR) angiography techniques have become available for the performance of MR-DSA. For the purposes of this article, we will consider this to include two-dimensional and three-dimensional approaches using time-resolved and non-time-resolved applications. Magnetic resonance-DSA is one in a historical progression of techniques which have aimed to produce less invasive forms of angiography. After outlining some historical milestones, several current issues regarding current methods for MR-DSA are discussed.

Angiography, Digital Subtraction↗

PubMed1992

Binding of an antiviral agent to a sensitive and a resistant human rhinovirus. Computer simulation studies with sampling of amino acid side-chain conformation. I. Mapping the rotamers of residue 188 of viral protein 1.

The mutation of valine 188 to leucine in the viral protein 1 of human rhinovirus 14 renders the virus resistant to certain antiviral compounds. Thermodynamic-cycle perturbation theory provides a means of calculating the difference in the binding free energies of an antiviral compound to the wild-type virus and to the mutant virus. In calculating the relevant free-energy differences in molecular dynamics simulations, it is important to sample the multiple rotational isomers of residue 188 correctly. In general, these rotamers will not be fully sampled during a single molecular dynamics simulation. However, the contributions of all the rotamers to the free-energy differences associated with mutation of residue 188 may be considered explicitly once they have been identified and their relative free energies determined. Therefore, we describe here the mapping of the rotamers of residue 188 by steric-bump search and energy minimization techniques, and by the computation of potentials of mean force (p.m.f.s.) using umbrella sampling. The usefulness, validity and efficiency of these methods of examining rotameric states is discussed. Adiabatic mapping by energy minimization was found to be unreliable for this residue due to the small magnitude of its interactions with the surrounding protein atoms. Ambiguities in the adiabatic maps were resolved by computing p.m.f.s. The p.m.f. for valine 188 in the unliganded wild-type virus shows a minimum corresponding to the crystallographically observed conformation of valine 188. The p.m.f.s. for valine 188 in the liganded virus and for leucine 188 in the unliganded mutant virus suggest that the experimentally observed conformations may be interpreted as averages of a number of conformations corresponding to those at the minima in the p.m.f.s. The calculations suggest also that the conformation of leucine 188 may change when the ligand binds. The use of the calculated p.m.f.s. to compute the difference in the free energy of binding of an antiviral compound to the wild-type and mutant rhinoviruses is described in the accompanying article.

Antiviral Agents↗

PubMedDate not supplied

Coupled computational simulation and empirical research into the foraging system of Pharaoh's ant (Monomorium pharaonis).

The Pharaoh's ant (Monomorium pharaonis), a significant pest in many human environments, is phenomenally successful at locating and exploiting available food resources. Several pheromones are utilized in the self-organized foraging of this ant but most aspects of the overall system are poorly characterised. Agent-based modelling of ants as individual complex X-machines facilitates study of the mechanisms underlying the emergence of trails and aids understanding of the process. Conducting simultaneous modelling, and simulation, alongside empirical biological studies is shown to drive the research by formulating hypotheses that must be tested before the model can be verified and extended. Integration of newly characterised behavioural processes into the overall model will enable testing of general theories giving insight into division of labour within insect societies. This study aims to establish a new paradigm in computational modelling applicable to all types of multi-agent biological systems, from tissues to animal societies, as a powerful tool to accelerate basic research.

Animals↗

PubMed2004

Computational simulations of interactions of scorpion toxins with the voltage-gated potassium ion channel.

Based on a homology model of the Kv1.3 potassium channel, the recognitions of the six scorpion toxins, viz. agitoxin2, charybdotoxin, kaliotoxin, margatoxin, noxiustoxin, and Pandinus toxin, to the human Kv1.3 potassium channel have been investigated by using an approach of the Brownian dynamics (BD) simulation integrating molecular dynamics (MD) simulation. Reasonable three-dimensional structures of the toxin-channel complexes have been obtained employing BD simulations and triplet contact analyses. All of the available structures of the six scorpion toxins in the Research Collaboratory for Structural Bioinformatics Protein Data Bank determined by NMR were considered during the simulation, which indicated that the conformations of the toxin significantly affect both the molecular recognition and binding energy between the two proteins. BD simulations predicted that all the six scorpion toxins in this study use their beta-sheets to bind to the extracellular entryway of the Kv1.3 channel, which is in line with the primary clues from the electrostatic interaction calculations and mutagenesis results. Additionally, the electrostatic interaction energies between the toxins and Kv1.3 channel correlate well with the binding affinities (-logK(d)s), R(2) = 0.603, suggesting that the electrostatic interaction is a dominant component for toxin-channel binding specificity. Most importantly, recognition residues and interaction contacts for the binding were identified. Lys-27 or Lys-28, residues Arg-24 or Arg-25 in the separate six toxins, and residues Tyr-400, Asp-402, His-404, Asp-386, and Gly-380 in each subunit of the Kv1.3 potassium channel, are the key residues for the toxin-channel recognitions. This is in agreement with the mutation results. MD simulations lasting 5 ns for the individual proteins and the toxin-channel complexes in a solvated lipid bilayer environment confirmed that the toxins are flexible and the channel is not flexible in the binding. The consistency between the results of the simulations and the experimental data indicated that our three-dimensional models of the toxin-channel complex are reasonable and can be used as a guide for future biological studies, such as the rational design of the blocking agents of the Kv1.3 channel and mutagenesis in both toxins and the Kv1.3 channel. Moreover, the simulation result demonstrates that the electrostatic interaction energies combined with the distribution frequencies from BD simulations might be used as criteria in ranking the binding configuration of a scorpion toxin to the Kv1.3 channel.

Amino Acid Sequence↗

PubMed1996

Structure of a cyclic peptide with a catalytic triad, determined by computer simulation and NMR spectroscopy.

We report the design of a cyclic, eight-residue peptide that possesses the catalytic triad residues of the serine proteases. A manually built model has been relaxed by 0.3 ns of molecular dynamics simulation at room temperature, during which no major changes occurred in the peptide. The molecule has been synthesised and purified. Two-dimensional NMR spectroscopy provided 35 distance and 7 torsion angle constraints, which were used to determine the three-dimensional structure. The experimental conformation agrees with the predicted one at the beta-turn, but deviates in the arrangement of the disulphide bridge that closes the backbone to a ring. A 1.2 ns simulation at 600 K provided extended sampling of conformation space. The disulphide bridge reoriented into the experimental arrangement, producing a minimum backbone rmsd from the experimental conformation of 0.8 A. At a later stage in the simulation, a transition at Ser3 produced more pronounced high-temperature behaviour. The peptide hydrolyses p-nitrophenyl acetate about nine times faster than free histidine.

Amino Acid Sequence↗

PubMed1999

Dynamical properties of phospholipid bilayers from computer simulation.

We present the results of a 10-ns molecular dynamics simulation of a dipalmitoylphosphatidylcholine/water system. The main emphasis of the present study is on the investigation of the stability over a long time and the dynamic properties of the water/membrane system. The motion of the lipid molecules is characterized by the center of mass movement and the displacement of individual atom groups. Because of the slow movement of the headgroup atoms, their contributions to the dipole potential vary slowly and with a large amplitude. Nevertheless, the water molecules compensate the strong fluctuations and maintain an almost constant total dipole potential. From the lateral displacement of the center of masses, we calculate the lateral diffusion coefficient to be Dlat = (3 +/- 0.6) x 10(-7) cm2/s, in agreement with neutron scattering results. The rotational motion is also investigated in our simulations. The calculated value for the rotational diffusion coefficient parallel to the molecular long axis, D = (1.6 +/- 0.1) x 10(8) s-1, is in good agreement with the experiment.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

Following the aggregation of amyloid-forming peptides by computer simulations.

There is experimental evidence suggesting that the toxicity of neurodegenerative diseases such as Alzheimer's disease may result from the soluble intermediate oligomers. It is therefore important to characterize extensively the early steps of oligomer formation at atomic level. As these structures are metastable and short lived, experimental data are difficult to obtain and they must be complemented with numerical simulations. In this work, we use the activation-relaxation technique coupled with a coarse-grained energy model to study in detail the mechanisms of aggregation of four lys-phe-phe-glu (KFFE) peptides. This is the shortest peptide known to form amyloid fibrils in vitro. Our simulations indicate that four KFFE peptides adopt a variety of oligomeric states (tetramers, trimers, and dimers) with various orientations of the chains in rapid equilibrium. This conformational distribution is consistent with all-atom molecular-dynamics simulations in explicit solvent and is sequence dependent; as seen experimentally, the lys-pro-gly-glu (KPGE) peptides adopt disordered structures in solution. Our unbiased simulations also indicate that the assembly process is much more complex than previously thought and point to intermediate structures which likely are kinetic traps for longer chains.

Amyloid beta-Peptides↗

PubMed1991

Computer simulations of activation in an anatomically based model of the human ventricular conduction system.

Simulations of the electrical activity during excitation were performed in an anatomically based model of the human ventricular conduction system. Each of the 33,000 elements of this model represented a unit bundle of Purkinje or atrioventricular nodal tissue. The Ebihara-Johnson model for sodium defined the active membrane characteristics. Using a combination of new and existing modeling techniques, simulations of excitation were completed in approximately 5 min CPU time on an IBM 3090 at the Cornell National Supercomputer Facility. Activation times at sites in the model were compared to experimental measurements for the excitation of the ventricular myocardium on the endocardial surface. These "literature-based" times were estimated from a number of reported human heart mapping studies. Initially, the times fit poorly. The major factor for the discrepancy was the conduction velocities of the elements, which were a result of the physical and electrical parameters derived from a review of histologic and electrical properties studies. In addition, there was a latency between activation of the system in the left ventricle of the model and that in the right ventricle when compared to the experimental work. When the times were scaled to adjust for the conduction velocity and ventricular latency effects, the match between the simulation and literature-based times was much improved. Quantitative comparison between normalized times resulted in correlation coefficients CCF = 0.76 for the right ventricle and CCF = 0.64 for the left ventricle.

Atrial Function↗