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PubMed2000

Computer modeling of occlusal surfaces of posterior teeth with the CICERO CAD/CAM system.

STATEMENT OF PROBLEM: Static and dynamic occlusal interference frequently needs to be corrected by selective grinding of the occlusal surface of conventional cast and ceramic-fused-to-metal restorations. CAD/CAM techniques allow control of the dimensional contours of these restorations. However, parameters responsible for the occlusal form need to be determined. In most articulators, these parameters are set as default values. Which technique is best for minimizing the introduction of occlusal interference in restorations has not been determined. PURPOSE: This study investigated differences in crown structure of a crown designed in static occlusion (STA) with designs adapted for dynamic occlusal interferences. Therefore, values from an optoelectronic registration system (String-Condylocomp, KAVO), an occlusal generated path (OGP) technique and default settings (DEF) were used in the CICERO CAD/CAM system. MATERIAL AND METHODS: Morphology of CON, DEF, and OGP crowns was compared with that of the STA crown with respect to differences in a buccolingual section and frequency of occlusal distances in an interocclusal range of 1 mm, measured from the occlusal surface of the crown. RESULTS: All crown types fulfilled the esthetic and morphologic criteria for restorations in clinical dentistry. Difference in the morphology of the OGP crown, compared with that of the STA crown, was greater than that for the CON and DEF crowns. These differences were seen especially in the distobuccal part of the occlusal surface; however, the number of occlusal contacts was considered sufficient to stabilize occlusion. CONCLUSION: Functional occlusion, adapted to dynamic occlusion in a CICERO crown for the first mandibular molar, can be obtained using data acquired with the String-Condylocomp registration system. The OGP technique was preferred to other techniques because of the simplicity of the technique for eliminating potential problems with opposing teeth during motion. However, this is achieved at the cost of fewer points of contact during occlusion than with the CON crown.

Computer-Aided Design↗

PubMed2001

Computer modelling of the Swedish two county trial of mammographic screening and trade offs between participation and screening interval.

OBJECTIVES: A computerised model of the Swedish two county trial of mammographic screening was built to explore the applicability of deterministic group modelling for health policy analysis and to examine trade offs between screening interval and population coverage on breast cancer mortality. METHODS: Powersim system dynamics modelling software running on a PC was used. Model inputs were published data on the populations and screening regimens used in the trial, a Swedish female population life table, incidence of breast cancer in Sweden, 95% confidence intervals (95% CIs) for mean sojourn time and screening sensitivity, and survival after diagnosis. RESULTS: The model's output--cumulative mortality from breast cancer--agreed closely with trial results. This was robust to uncertainties in key input variables. Furthermore, with hypothetical screening regimes that had a fixed total number of mammograms over a fixed period a positive association was found between more even distribution of mammograms among a population and reduction in breast cancer mortality. For example, screening 50% of a hypothetical population annually produced a 33% reduction in breast cancer mortality, whereas screening 100% of the population every 2 years produced a 48% reduction. CONCLUSIONS: Deterministic group simulation modelling can be used to build reliable, evidence based quantitative models for policy analysis. This opens health policy simulation modelling to epidemiological researchers and will assist them in identifying important information needs--such as breast cancer survival according to sojourn time (the time between cancer being detectable by screening and becoming symptomatic). Scenarios examining reductions in mortality for a given number of mammograms showed that the more equitable the distribution of screening mammograms, the greater the reduction in deaths from breast cancer.

Adult↗

PubMed1988

Use of computer modeling to predict the magnitude of intralaboratory error tolerated by proposed CDC interlaboratory proficiency testing performance criteria.

In December 1987, the Centers for Disease Control (CDC) proposed to the Health Care Financing Administration revised criteria for evaluating participating laboratories' performance in proficiency-testing programs. If these criteria are accepted, they will become the minimum standard for all regulatory proficiency-testing programs. To evaluate a laboratory's performance in a clinical chemistry proficiency-testing program, the CDC proposed a combination of the use of fixed limits, multiples of the interlaboratory group standard deviations, and absolute values. In addition, laboratories would be required to meet 70% of the most recent proficiency-testing challenges. Because the purpose of regulatory proficiency testing is to identify poorly performing laboratories, it is essential that regulators be aware of the relationship between the regulatory criteria and the actual magnitude of intralaboratory error they tolerate. Through computer simulation, we determined for 21 chemistry analytes the amount of intralaboratory error tolerated by the CDC-proposed criteria. We evaluated the effectiveness of the proposed criteria by comparing the levels of total intralaboratory error permitted by a proficiency-testing program by using the CDC criteria with actual currently achievable levels of performance and defined medical usefulness needs. The proposed CDC criteria were too lenient for six analytes, about correct for seven, and too stringent on two; no medical usefulness limits were available for six.

Blood Chemical Analysis↗

PubMed1987

Relationship between the inhibitory potencies of thiorphan and retrothiorphan enantiomers on thermolysin and neutral endopeptidase 24.11 and their interactions with the thermolysin active site by computer modelling.

The inhibitory potency of separate enantiomers of thiorphan and retrothiorphan has shown that several particularities of the active site of thermolysin are also present in the neutral endopeptidase 24.11, "enkephalinase", such as its ability: i) to recognize a retroamide bond as well as a standard amide bond, ii) to interact similarly with residues in P1' position of either R or S configuration in the thiorphan series but contrastingly to discriminate between the R and S isomers in the retrothiorphan series. These four inhibitors were modellized in the thermolysin active site and their spatial arrangement compared with that of a thiol inhibitor co-crystallized with thermolysin. In all cases, the essential interactions involved in the stabilization of the bound inhibitor were conserved. However, the bound (R) retrothiorphan displayed unfavorable intramolecular contacts, accounting for its lower inhibitory potency for the two metallopeptidases.

Amino Acids, Sulfur↗

PubMed2004

Relating neuronal dynamics for auditory object processing to neuroimaging activity: a computational modeling and an fMRI study.

We investigated the neural basis of auditory object processing in the cerebral cortex by combining neural modeling and functional neuroimaging. We developed a large-scale, neurobiologically realistic network model of auditory pattern recognition that relates the neuronal dynamics of cortical auditory processing of frequency modulated (FM) sweeps to functional neuroimaging data of the type obtained using PET and fMRI. Areas included in the model extend from primary auditory to prefrontal cortex. The electrical activities of the neuronal units of the model were constrained to agree with data from the neurophysiological literature regarding the perception of FM sweeps. We also conducted an fMRI experiment using stimuli and tasks similar to those used in our simulations. The integrated synaptic activity of the neuronal units in each region of the model, convolved with a hemodynamic response function, was used as a correlate of the simulated fMRI activity, and generally agreed with the experimentally observed fMRI data in the brain areas corresponding to the regions of the model. Our results demonstrate that the model is capable of exhibiting the salient features of both electrophysiological neuronal activities and fMRI values that are in agreement with empirically observed data. These findings provide support for our hypotheses concerning how auditory objects are processed by primate neocortex.

Adult↗

PubMed2006

The development of a computer model for a fixed bed gasifier and its use for optimization and control.

The development of a mathematical model of a fixed-bed gasifier is described. The model was used for studies of the stationary performance of the gasifier and the results were compared to experimental results. The model was also used in an effort to identify an efficient control strategy for the operation during load changes. The resulting strategy was very simple and has been implemented in an unmanned, automatically controlled, power plant that was operated for over 3000h. The mathematical model was based on conservation of mass and energy in a simple one-dimensional flow, chemical equilibrium in the gas phase, and a Langmuir-Hinshelwood correlation describing the reaction kinetics in the char. The results of the thermo-gravimetric analysis experiments required to determine the reactivity for char of beech as a function of temperature, gas composition and conversion ratio of the char are presented.

Carbon↗

PubMed2005

Simple computer model for calculating and reporting 5-year osteoporotic fracture risk in postmenopausal women.

PURPOSE: To devise, validate, and test a software model that improves how clinicians calculate individual risk for osteoporotic fracture and expected treatment benefit. METHODS: We developed a simple model of seven easily ascertained items plus bone mineral density (BMD) that calculates absolute fracture risk and expected absolute risk reduction after treatment. Baseline clinical variables and longitudinal fracture data from two large osteoporosis cohort studies validated the model's accuracy in predicting fracture risk. We then surveyed 298 clinicians to evaluate the likelihood they would prescribe alendronate in three hypothetical cases, first given the clinical data alone and then with model-derived data on fracture risk and expected treatment benefit. RESULTS: We found a strong linear relationship with the model's predicted fracture risk and observed fracture rates in two large observational cohorts but the model overestimated risk 2-3 fold. The model predicted a 1:200 5-year risk for spinal fracture and a 1:40 risk for nonspinal fracture in an index case of a younger, thin, osteopenic woman. Given this hypothetical history with BMD t-scores, 26% of clinicians were likely to prescribe alendronate; when also given model-calculated 5-year fracture risks with or without treatment, only 13% were likely to prescribe alendronate (p < 0.001). For 2 other osteoporosis patients in whom risk was much higher, further information on fracture risk and expected treatment benefit did not alter prescribing. CONCLUSIONS: Reporting absolute fracture risk with and without treatment promises to be most useful in women with osteopenia, a common clinical dilemma in younger postmenopausal women.

Aged↗

PubMed1999

Superhelical DNA studied by solution scattering and computer models.

We present here recent results on the structure of superhelical DNA and its changes with salt concentration between 0.01 and 1.5 M NaCl. Scattering curves of two different superhelical DNAs were determined by static light scattering. The measured radii of gyration do not change significantly with salt concentration. Small-angle neutron scattering, together with calculations from a Monte Carlo model, allows to determine the superhelix diameter. Measured and simulated scattering curves agreed almost quantitatively. Experimentally we find that the diameter decreases from 16.0 +/- 0.9 nm at 10 mM to 9.0 +/- 0.7 nm at 100 mM NaCl. The superhelix diameter from the simulated conformations decreased from 18.0 +/- 1.5 nm at 10 mM to 9.4 +/- 1.5 nm at 100 mM NaCl. At higher salt concentrations up to 1.5 M NaCl, the diameter stays constant at 9 nm.

Computer Simulation↗

PubMed1998

Visualization of the human larynx: a three-dimensional computer modeling tool.

The larynx is a complex compact organ. A detailed understanding of the anatomical relationships of its various structures is critical to the various workers in the field. To facilitate this goal, a 3-D model of the human larynx has been developed using multiple thin section MRI and CT images taken through a cadaver larynx. A databank of individual laryngeal structures ('units') has been built up. A software package has then been utilized which allows for representation of any of the stored 'units'. In this manner, elements of the larynx can be viewed from any direction, with the larynx static or in motion. Similarities and differences from current CD-ROM packages of the larynx are discussed.

Computer Simulation↗

PubMed1995

Nitrate Effects on Nodule Oxygen Permeability and Leghemoglobin (Nodule Oximetry and Computer Modeling).

Two current hypotheses to explain nitrate inhibition of nodule function both involve decreased O2 supply for respiration in support of N2 fixation. This decrease could result from either (a) decreased O2 permeability (PO) of the nodule cortex, or (b) conversion of leghemoglobin (Lb) to an inactive, nitrosyl form. These hypotheses were tested using alfalfa (Medicago sativa L. cv Weevlchek) and birdsfoot trefoil (Lotus corniculatus L. cv Fergus) plants grown in growth pouches under controlled conditions. Nodulated roots were exposed to 10 mM KNO3 or KCI. Fractional oxygenation of Lb under air (FOLair), relative concentration of functional Lb, apparent PO, and O2-saturated central zone respiration rate were all monitored by nodule oximetry. Apparent PO and FOLair in nitrate-treated nodules decreased to <50% of values for KCI controls within 24 h, but there was no decrease in functional Lb concentration during the first 72 h. In nitrate-treated alfalfa, but not in birdsfoot trefoil, FOLair, apparent PO, and O2-saturated central zone respiration rate decreased during each light period and recovered somewhat during the subsequent dark period. This species difference could be explained by greater reliance on photoreduction of nitrate in alfalfa than in birdsfoot trefoil. Computer simulations extended the experimental results, showing that previously reported decreases in apparent PO of Glycine max nodules with nitrate exposure cannot be explained by hypothetical decreases in the concentration or O2 affinity of Lb.

Journal Article↗

PubMed1990

Comparison of the X-ray structure of baboon alpha-lactalbumin and the tertiary predicted computer models of human alpha-lactalbumin.

The previously predicted structures of human alpha-lactalbumin by homology with hen egg white lysozyme by an automatic method, after the alignment stage, are compared to the X-ray determined structure of baboon alpha-lactalbumin. The root mean square by rotation method (RMSR) deviations for 122 C-alpha atoms between the two models and the X-ray structure are 2.0 A and 2.3 A. The RMSR deviations for all atoms, except for differences in human and baboon sequences, are 2.8 A and 3.1 A. If the flexible C-terminus (residues 112-122) are removed then these RMSR deviations are reduced to 2.4 A and 2.3 A respectively. These results are consistent with the fact that the RMSR deviation between the human and baboon X-ray structures increases from residue 112 onwards and is conformationally flexible.

Amino Acid Sequence↗

PubMed1989

Quinazoline antifolates inhibiting thymidylate synthase: computer modelling of the N10 substituent.

The synthesis and biological properties of N10-(2,2,2-trifluoroethyl)-5, 8-dideazafolic acid are described. It was fivefold less active as an inhibitor of L1210 thymidylate synthase (TS) than its N10-ethyl congener and sevenfold less active as an inhibitor of the growth of L1210 cells in culture. CNDO calculations were performed on the following N10 substituents in a model fragment of 5, 8-dideazafolic acid: propargyl, ethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, cyanomethyl and methyl. The resulting values of partial charge on the distal terminus of the substituent correlated with the TS inhibition induced by the substituent. In particular, the mildly net positive charge on the acetylenic hydrogen in the propargyl substituent (+0.064) was not matched by any other in the series. N10-propargyl-5, 8-dideazafolic acid continues as the best inhibitor in this series.

Animals↗

PubMed1997

Synthetic and model computational studies of molar rotation additivity for interacting chiral centers: a reinvestigation of van't Hoff's principle.

When plane-polarized light impinges on a solution of optically active molecules, the polarization of the light that emerges is rotated. This simple phenomenon arises from the interaction of light with matter and is well understood, in principle, van't Hoff's rule of optical superposition correlates the molar rotation with the individual contributions to optical activity of isolated centers of asymmetry. This straightforward empirical additivity rule is rarely used for structure elucidation nowadays because of its limitations in the assessment of conformationally restricted or interacting chiral centers. However, additivity can be used successfully to assign the configuration of complex natural products such as hennoxazole A if appropriate synthetic partial structures are available. Therefore, van't Hoff's principle is a powerful stereochemical complement to natural products' total synthesis. The quest for reliable quantitative methods to calculate the angle of rotation a priori has been underway for a long time. Both classical and quantum methods for calculating molar rotation have been developed. Of particular practical importance for determining the absolute structure of molecules by calculation is the manner in which interactions between multiple chiral centers in a single molecule are included, leading to additive or non-additive optical rotation angles. This problem is addressed here using semi-empirical electronic structure models and the Rosenfeld equation.

Chemistry, Physical↗

PubMed1996

Identification and analysis of long-range electrostatic effects in proteins by computer modeling:aspartate transcarbamylase.

While ion pairs are readily identified in crystal structures, longer range electrostatic interactions cannot be identified from the three-dimensional structure alone. These interactions are likely to be important in large, multisubunit proteins that are regulated by allosteric interactions. In this paper, we show that these interactions are readily detected by electrostatic modeling, using, as an example, unliganded Escherichia coli aspartate transcarbamylase, a widely studied allosteric enzyme with 12 subunits and a molecular weight of 310 kD. The Born, dipolar, and site-site interaction terms of the free energy of protonation of the 810 titratable sites in the holoenzyme were calculated using the multigrid solution of the nonlinear Poisson-Boltzmann equation. Calculated titration curves are in good agreement with experimental titration curves, and the structural asymmetry observed in the crystal structure is readily apparent in the calculated free energies and pK1/2 values. Most of the residues with pK1/2 values that differ substantially from those of model compounds are buried in the low dielectric medium of the protein, particularly at the intersubunit interfaces. The dependence of the site-site interaction free energies on distance is complex, with a steep dependence at distances less than 5 A and a more shallow dependence at longer distances. Interactions over distances of 6 to 15 A require a bridging residue and are often not apparent in the structure. The network of interactions between ionizable groups extends across and between subunits and provides a potential mechanism for transmitting long-range structural effects and allosteric signals.

Aspartate Carbamoyltransferase↗

PubMedDate not supplied

[Efficacy of radioprotectors and gene mutations following 2-deoxyribosyl damage. Computer modeling].

The fundamental new universal method of evaluation of the interaction between macroradical and radioprotector (the access window method) is presented here. It's based on the modelling phenomenon of molecule penetration to the active centre of macromolecule structure through the functional groups free "window". The steric modelling of the B-DNA structure fragments allowed to measure the conformation parameters of the intermediate stereocomplex between interacting substancies. Using the thesis about molecule InH mask the interaction process of InH (steric hindered phenol 4-oxy-3,5-di-tret-butyl-alpha-metylbenzylamine, mercaptoethanol, MET, and L-cysteine, CYS) with 2-deoxyribosyl five radicals in DNA was studied. It was determined, that the radioprotection maximum effect on single-strand breakage formation in irradiated cell can reach 2/3 of the total sugar radicals yield and for MET and CYS (with minor mask squares) -87.5, and 91%, accordingly (it agrees with experiment in literature data).

Computer Simulation↗

PubMed2000

Computer model analysis of the Swanson and Sutter metacarpophalangeal joint implants.

A representative model which mimics the behaviour of Silastic finger metacarpophalangeal joint implants was constructed using a finite element software package. The modelled implants were moved through a range of flexion, lateral deviation and a combination of both. Pistoning of both implants stems occurred within the modelled medullary cavities. For equivalent flexion angles, the Sutter implant produced a higher stress field than the Swanson implant, and the field was positioned at the central hinge mechanism. In both implants, lateral deviation increased the internal stress concentrations more than when pure flexion was applied. Overall the Swanson style of implant had lower stress magnitudes than the Sutter implant, and it is predicted that the Sutter implant will be more likely to fail than the Swanson. The failure mode for the Sutter implant would be at the central hinge region. The Swanson implant is likely to fail at the central hinge-stem interface regions.

Computer Simulation↗

PubMed1990

Insights into associative long-term potentiation from computational models of NMDA receptor-mediated calcium influx and intracellular calcium concentration changes.

1. Because induction of associative long-term potentiation (LTP) in the dentate gyrus is thought to depend on Ca2+ influx through channels controlled by N-methyl-D-aspartate (NMDA) receptors, quantitative modeling was performed of synaptically mediated Ca2+ influx as a function of synaptic coactivation. The goal was to determine whether Ca2+ influx through NMDA-receptor channels was, by itself, sufficient to explain associative LTP, including control experiments and the temporal requirements of LTP. 2. Ca2+ influx through NMDA-receptor channels was modeled at a synapse on a dendritic spine of a reconstructed hippocampal dentate granule cell when 1-115 synapses on spines at different dendritic locations were activated eight times at frequencies of 10-800 Hz. The resulting change in [Ca2+] in the spine head was estimated from the Ca2+ influx with the use of a model of a dendritic spine that included Ca2+ buffers, pumps, and diffusion. 3. To use a compelling model of synaptic activation, we developed quantitative descriptions of the NMDA and non-NMDA receptor-mediated conductances consistent with available experimental data. The experimental data reported for NMDA and non-NMDA receptor-channel properties and data from other non-LTP experiments that separated the NMDA and non-NMDA receptor-mediated components of synaptic events proved to be limiting for particular synaptic variables. Relative to the non-NMDA glutamate-type receptors, 1) the unbinding of transmitter from NMDA receptors had to be slow, 2) the transition from the bound NMDA receptor-transmitter complex to the open channel state had to be even slower, and 3) the average number of NMDA-receptor channels at a single activated synapse on a single spine head that were open and conducting at a given moment in time had to be very small (usually less than 1). 4. With the use of these quantitative synaptic conductance descriptions. Ca2+ influx through NMDA-receptor channels at a synapse was computed for a variety of conditions. For a constant number of pulses, Ca2+ influx was calculated as a function of input frequency and the number of coactivated synapses. When few synapses were coactivated, Ca2+ influx was small, even for high-frequency activation. However, with larger numbers of coactivated synapses, there was a steep increase in Ca2+ influx with increasing input frequency because of the voltage-dependent nature of the NMDA receptor-mediated conductance. Nevertheless, total Ca2+ influx was never increased more than fourfold by increasing input frequency or the number of coactivated synapses.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed2002

Computational models of MRI characteristics of focal cortical dysplasia improve lesion detection.

In many patients, focal cortical dysplasia (FCD) is characterized by minor structural changes that may go unrecognized by standard radiological analysis. We previously demonstrated that visual analysis of a composite map based on three simple models of MRI features of FCD increased the sensitivity of FCD lesion detection, compared to visual analysis of conventional MRI. Here we report on the use of improved methods for characterizing FCD which improve contrast in the composite maps: a Laplacian-based metric for measuring cortical thickness, a convolutional kernel to model blurring of the GM-WM interface, and an operator to measure hyperintense T1 signal. To validate these methods, we processed the MRIs of 14 FCD patients with our original set of image processing operators and an improved set of image processing operators. Comparison of the composite maps associated with the two sets of operators revealed that contrast between lesional tissue and nonlesional cortex was significantly increased in the composite maps associated with the set of improved operators. Increasing this contrast is an important step toward the goal of automated FCD lesion detection.

Brain Mapping↗