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At least 235 records · Page 13Linked to original sources

PubMed1991

3-D computer model of subcortical structures of human brain.

Three-dimensional computer model of thalamus and adjacent formations of human brain has been elaborated on the basis of sagittal slices from the Schaltenbrand-Bailey stereotactic atlas. The model includes 120 morphologically distinguishable structures and consists of more than 16 million points (volume elements) each of them being associated with the particular structure in the brain. The model is stored in the long-term computer memory. A special software has been developed to facilitate utilizing the model obtained. The software facilitates synthesizing arbitrary cross-sections through the brain and provides the correspondence between the stereotactic coordinates of any point and its position on the screen of monitor. The coordinates of the point in the system of stereotactic atlas and the name of the structure, the point belongs to, are also supplied. It is also possible to get magnified images of cross-sections and to get isometrical images. The system enables the neurosurgeon to improve the planning and execution of stereotactic operations, and will also be helpful for education.

Brain↗

PubMed1991

Three-dimensional model of Escherichia coli ribosomal 5 S RNA as deduced from structure probing in solution and computer modeling.

The conformation of Escherichia coli 5 S rRNA was investigated using chemical and enzymatic probes. The four bases were monitored at one of their Watson-Crick positions with dimethylsulfate (at C(N-3) and A(N-1], with a carbodiimide derivative (at G(N-1) and U(N-3] and with kethoxal (at G(N-1, N-2]. Position N-7 of purine was probed with diethylpyrocarbonate (at A(N-7] and dimethylsulfate (at G(N-7]. Double-stranded or stacked regions were tested with RNase V1 and unpaired guanine residues with RNase T1. We also used lead(II) that has a preferential affinity for interhelical and loop regions and a high sensitivity for flexible regions. Particular care was taken to use uniform conditions of salt, magnesium, pH and temperature for the different enzymatic chemical probes. Derived from these experimental data, a three dimensional model of the 5 S rRNA was built using computer modeling which integrates stereochemical constraints and phylogenetic data. The three domains of 5 S rRNA secondary structure fold into a Y-shaped structure that does not accommodate long-range tertiary interactions between domains. The three domains have distinct structural and dynamic features as revealed by the chemical reactivity and the lead(II)-induced hydrolysis: domain 2 (loop B/helix III/loop C) displays a rather weak structure and possesses dynamic properties while domain 3 (helix V/region E/helix IV/loop D) adopts a highly structured and overall helical conformation. Conserved nucleotides are not crucial for the tertiary folding but maintain an intrinsic structure in the loop regions, especially via non-canonical pairing (A.G, G.U, G.G, A.C, C.C), which can close the loops in a highly specific fashion. In particular, nucleotides in the large external loop C fold into an organized conformation leading to the formation of a five-membered loop motif. Finally, nucleotides at the hinge region of the Y-shape are involved in a precise array of hydrogen bonds based on a triple interaction between U14, G69 and G107 stabilizing the quasi-colinearity of helices II and V. The proposed tertiary model is consistent with the localization of the ribosomal protein binding sites and possesses strong analogy with the model proposed for Xenopus laevis 5 S rRNA, indicating that the Y-shape model can be generalized to all 5 S rRNAs.

Base Sequence↗

PubMed2001

Introduction of computational models to PhysioNet.

PhysioNet is a national research resource that provides experimental data sets and open-source software for their analysis. Computational modeling can complement studies of these experimental data sets so as to facilitate the advancement of physiologic research. Thus, in order to introduce computational models to PhysioNet, we have developed and posted a cardiovascular model designed for research that generates reasonable human pulsatile hemodynamic waveforms, cardiac output and venous return curves, and beat-to-beat variability. Some of the key features of the software include: 1) compatibility with PhysioNet's open-source data analysis software; 2) online viewing and parameter updating as the data are being calculated; 3) off-line viewing after completion of the simulation; 4) pre-compiled Linux binaries; 5) open-source code that may be compiled on other platforms; and 6) an extensive user's manual and software guide.

Cardiac Output↗

PubMed1999

A computational model of neglect dyslexia.

This paper presents a straightforward theory of neglect (a pre-attentive salience system selects objects' centers for the focus of an attentional "spotlight") as a computational model. This construction permits simulations of model "lesions" and allows checking unequivocally the model's implications. The current model can account for some of the common patterns of observations of neglect dyslexia: that errors increase with word length and that short words may be read as "too long". Most importantly, it also accounts for a dissociation between neglect dyslexia and neglect on line bisection tasks. A two stage model can account for the patterns of performance seen in many neglect subjects, but more important is the demonstration that a theory's implementation as a computational model permits unambiguous evaluation of the theory's implications.

Computer Simulation↗

PubMed2007

Computational models of neocortical neuronogenesis and programmed cell death in the developing mouse, monkey, and human.

This paper presents a computational model allowing quantitative simulations of acquisition of neocortical neuronal number across mammalian species. When extrapolating scientific findings from rodents to humans, it is particularly pertinent to acknowledge the importance of the accelerated enlargement of the neocortex during human evolution. Neocortex development is marked by discrete stages of neural progenitor cell proliferation and death, neuronal differentiation, and neuronal programmed cell death. We have developed computational models of human and rhesus monkey neocortical neuronal cell acquisition based on experimentally derived parameters of cell cycle length, commitment to cell cycle exit, and cell death. Our model results agree with independent stereological studies estimating neocortical neuron number in adult and developing rhesus monkey and human. Comparisons of our primate models with previously developed rodent models suggest correlations between the lengthening of the duration of the neuronogenesis period and a lengthening of the cellular processes of cell cycle progression and death can account for the vast increase in size of the primate neocortex. Furthermore, when compared with rodents, we predict that cell death may play a larger role in shaping the primate neocortex. Our mathematical models of the development and evolution of the neocortex provide a quantitative, biologically based construct for extrapolation between rodent and humans. These models can assist in focusing future experimental research on the differing mechanisms of rodent versus human neocortical development.

Aging↗

PubMed1988

Computer modelling antibiotic therapy costs. Impact of therapeutic range.

Computer modelling techniques were used to examine the economic consequences of intravenous chemotherapy of serious infection. Acquisition cost of the drug was found to be a poor predictor of global cost, since inclusion of the preparation and administration costs and projected laboratory and drug complication costs narrow, or even reverse, apparent cost differentials between drugs. Thus, the cost per day for acquisition/total treatment (in US dollars) are: penicillin $5/$30, gentamicin $1/$46, amikacin $26/$63, clindamycin $38/$57, metronidazole $12/$20 and cefotaxime $47/$60. 'Triple therapy' involving gentamicin ($0.40/dose) resulted in higher hospital costs than the equivalent regimen involving cefotaxime ($16/dose). Even when the purchase price is high, humanitarian considerations advocate the use of safe, predictable, efficacious drugs. Fortunately, the present analysis suggests that such drugs frequently result in the lowest total treatment cost. Current cost containment efforts that are based on acquisition costs only are flawed and may result in both suboptimal care and higher actual costs.

Anti-Bacterial Agents↗

PubMed1994

An interactive computer model of propagated activation with analytically defined geometry of ventricles.

A computer model of propagated activation in cardiac ventricles was developed for simulation experiments in an interactive regime on personal computers. In the model, the geometry of ventricles is defined by parts of "compound quasi-ellipsoids". The parameters specifying these ellipsoids as well as their spatial positions are derived from input data characterizing the heart geometry. Because the ventricles are defined analytically, the model renders a wide range of possibilities to vary their shape and gross dimensions. The activation is propagated from predetermined starting elements in agreement with Huygen's principle. Different propagation velocities for the myocardium and the subendocardial mesh of Purkinje fibers also may be simulated. The results of computer simulations may be evaluated both qualitatively, by isochrones of the activation propagation, and quantitatively, by the resulting cardiac vector computer in any moment of activation process.

Computer Simulation↗

PubMedDate not supplied

A computational model of the progression of Alzheimer's disease.

Computational modeling allows analysis of the role of network dynamics in the initiation and progression of neuropathology in Alzheimer's disease. The model focuses on a final common breakdown in function, termed runaway synaptic modification. This phenomenon could account for evidence that neuropathological markers associated with neuronal death in Alzheimer's disease first appear and attain their highest concentration in subregions of the hippocampal formation, and then successively spread into the temporal lobe cortex and the cortex of the frontal and parietal lobes. The model demonstrates how the spread of neuropathology from the hippocampus into neocortical structures could result from the mechanisms of consolidation. Initial sensitivity of the hippocampus and entorhinal cortex to the neuropathological process is proposed to result from an imbalance of variables regulating the influence of synaptic transmission on synaptic modification. Memory deficits are described as due to increased interference effects on recent memory caused by runaway synaptic modification, which ultimately leads to impairments of remote and semantic memory.

Alzheimer Disease↗

PubMed1991

Stereochemical complementarity of progesterone and cavities between base pairs in partially unwound double stranded DNA using computer modeling and energy calculations to determine degree of fit.

Computer modeling was applied for the first time to investigate previously reported complementarity of progesterone and cavities formed between base pairs in partially unwound double stranded DNA. Computer graphics enabled a more objective assessment of complementarity; energy calculations provided a rigorous method to evaluate degree of fit. Graphics confirmed that the complementarity was virtually "lock and key", i.e. close contacts were formed between van der Waals surfaces in the progesterone/DNA complexes and hydrogen bonds were formed between the two carbonyl groups on opposite ends of the steroid and phosphate groups on adjacent strands of DNA. Molecular mechanics calculations revealed that insertion of the steroid resulted in a relatively stable complex i.e. both van der Waals and electrostatic energies were lowered due to favorable steric interactions and stereospecific hydrogen bonds, respectively. Three published X-ray crystal structures of progesterone exhibited similar complementarity. Ent-progesterone which does not occur naturally possessed very poor complementarity. These findings confirm that the structure of progesterone is directly reflected in the stereochemistry of DNA. While no mechanistic explanation for these results is proffered, we hypothesize that such complementarity must have played a decisive role in the evolution of steroid hormone structure and function.

Base Composition↗

PubMed2005

Sensitivity analysis for computer model projections of hurricane losses.

Projecting losses associated with hurricanes is a complex and difficult undertaking that is fraught with uncertainties. Hurricane Charley, which struck southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting damages from these storms. Due to shifts in the track and the rapid intensification of the storm, real-time estimates grew from 2 billion dollars to 3 billion dollars in losses late on the 12th to a peak of 50 billion dollars for a brief time as the storm appeared to be headed for the Tampa Bay area. The storm struck the resort areas of Charlotte Harbor and moved across the densely populated central part of the state, with early poststorm estimates in the 28 dollars to 31 billion dollars range, and final estimates converging at 15 billion dollars as the actual intensity at landfall became apparent. The Florida Commission on Hurricane Loss Projection Methodology (FCHLPM) has a great appreciation for the role of computer models in projecting losses from hurricanes. The FCHLPM contracts with a professional team to perform onsite (confidential) audits of computer models developed by several different companies in the United States that seek to have their models approved for use in insurance rate filings in Florida. The team's members represent the fields of actuarial science, computer science, meteorology, statistics, and wind and structural engineering. An important part of the auditing process requires uncertainty and sensitivity analyses to be performed with the applicant's proprietary model. To influence future such analyses, an uncertainty and sensitivity analysis has been completed for loss projections arising from use of a sophisticated computer model based on the Holland wind field. Sensitivity analyses presented in this article utilize standardized regression coefficients to quantify the contribution of the computer input variables to the magnitude of the wind speed.

Journal Article↗

PubMed2006

Computer model study of electrocardiologic manifestations in asymmetric left ventricular hypertrophy.

Electrocardiologic criteria of left ventricular enlargement do not take into consideration the eventuality of asymmetric hypertrophy. Since experimental techniques for production of this condition are not available, computer modeling was utilized to study its electrocardiologic manifestations. A computer model of human ventricles with analytically defined geometry, consisting of 142,000 elements (1.2 mm spatial resolution), was used to produce models of circumscribed hypertrophies by increasing the wall thickness to 150% in various regions of the free left ventricular wall, the septum and the apex. Gradients of simulated transmembrane action potentials were utilized to compute resultant heart vectors at any instant of ventricular activation and recovery, as well as time courses of their characteristics and planar projections of vectorgraphic loops. Involvement of the septum and/or the anterior wall decreased the maximum QRS vector magnitude, an opposite effect resulted from involvement of the lateral and posterior wall segments. Directional vector changes predicted the diagnostic value of S waves in precordial leads. Asymmetric hypertrophy did not produce abnormal Q waves. The maximum T vector increased in hypertrophy of any part of the free wall along with an increase of the spatial angle between maximum QRS and T vectors. The results of this study may be useful for refinement of electrocardiographic and vectorcardiographic diagnostic criteria of asymmetric left ventricular hypertrophy.

Computer Simulation↗

PubMed2005

Computational modeling of type I collagen fibers to determine the extracellular matrix structure of connective tissues.

A method is presented for generating computer models of biological tissues. The method uses properties of extracellular matrix proteins to predict the structure and physical chemistry of the elements that make up the tissue. The method begins with Protein Data Bank coordinate positions of amino acids as input into TissueLab software. From the amino acid sequence, a type I collagen-like triple helix backbone was computationally constructed and boundary spheres were added based on known chemical and physical properties of the amino acids. Boundary spheres determined the contact surface characteristics of the collagen molecules and intermolecular interactions were then determined by considering the relationships of the contact surfaces and by resolving the energy-minimum state using feasible sequential quadratic programming. From this, the software created fibrils that corresponded exactly to known collagen parameters and were further confirmed by finite element modeling. Computationally derived fibrils were then used to create collagen fibers and three-dimensional collagen matrices. By resolving the energy-minimum state, large complex components of the extracellular space as well as other structures can be determined to provide three-dimensional structure of molecules, molecular interactions and the tissues that they form.

Amino Acid Sequence↗

PubMed1993

Computational modeling of neuronal dynamics for systems analysis: application to neurons of the cardiorespiratory NTS in the rat.

The study constructs computational models of neurons in order to examine the contribution that their response dynamics may make to functional properties at the system level. As described in the accompanying study, neurons in the cardiorespiratory nucleus tractus solitarii (NTS) of the rat were recorded in vitro. When these cells were intracellularly injected with a constant current pulse, spike discharge patterns and subthreshold voltage trajectories were observed that were time- and voltage-dependent. The accompanying manuscript describes these dynamic responses in 4 classes of putative second-order cells that appear to receive direct primary afferent input, and a previous paper described two populations of rhythmically firing interneurons, one of which is intrinsically auto-active. In the present manuscript experimental neuronal voltage response data was collected across a current injection series for the S3 neuron type described in the accompanying study and for the auto-active neuron described previously. Using this data, computational model neurons have been constructed for these two neurons by using membrane ion channels to produce and match the observed neuronal voltage behavior. The channels were those implicated in the dynamic responses observed in the companion study, and include gNafast, gKdr, gKA, gKCa, gKAHP, gKM, gCaT and gCaL. The description of channel kinetics follows the Hodgkin-Huxley form. Different neuronal sources from the literature of channel kinetics were investigated and assembled into a 'channel kinetics library' from which both neuron models were tuned, primarily by adjusting the maximum channel densities, g, and time-dependence of kinetics. Methods are described for tuning the channel kinetics library to match various physiological responses. This approach created neuron models that were able to closely replicate the observed complex voltage and spiking responses of the two very different cardiorespiratory NTS neurons. The interaction of voltage- and calcium-dependent conductances were analyzed for their functional contributions by tuning their kinetics. Specific parameters are given that account for the behavior of each model. Sensitivity analyses by perturbing KCa and KA are shown for both neurons, and I/F curves are presented for the auto-active neuron's stimulated and recorded responses. The potential systems-level functional implications resulting from the different kinetics is demonstrated by driving the S3 model neuron in simulation with the pattern of input produced by model primary baroreceptor afferents. The limitations and significance of this approach are discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1999

An EGS4-ready tomographic computational model of a 14-year-old female torso for calculating organ doses from CT examinations.

Fifty-four consecutive CT scans have been used to construct a tomographic computational model of a 14-year-old female torso suitable for the determination of organ doses from CT. The model, known as ADELAIDE, is in the form of an input file compatible with user codes based on XYZDOS.MOR from the readily available EGS4 Monte Carlo radiation transport code. ADELAIDE's dimensions are close to the Australian averages for her age so the model is representative of a 14-year-old girl. The realistic anatomy in the model differs considerably from that in Cristy's 15-year-old mathematical computational model by having realistically shaped organs that are appropriately located within a real external contour. Average absorbed dose to organs from simulated CT examinations of the chest and abdomen have been calculated for ADELAIDE using EGS4 within a geometry specific to the General Electric Hi-Speed Advantage CT scanner and using an x-ray spectrum calculated using data from the scanner's x-ray tube. The simulations include the scanner's beam shaping filter and patient table. It is suggested that the resulting values have fewer possible sources of uncertainty than organ doses derived from dose coefficients calculated for a MIRD style model with mathematical anatomy and a spectrum that may not match that of the scanner. The organ doses were normalized using the scanner's CTDI measured free-in-air and an EGS4 simulation of the CTDI measurement. Effective dose to the torso from 26-slice chest and 24-slice abdomen examinations (at 120 kV, 200 mAs, 7 mm slices) is 4.6 +/- 0.1 mSv and 4.3 +/- 0.1 mSv respectively.

Adolescent↗

PubMed2005

Using computational modeling to drive the development of targeted therapeutics.

Computational biology is impacting drug design and has the potential to revolutionize the drug development process. Here, we describe how data-driven computational models can optimize the design of targeted therapeutics to yield improved safety and efficacy. We propose that, in the future, this approach will improve drug discovery, clinical development, diagnosis and treatment.

Computational Biology↗

PubMed2000

Analysis of dielectric spectra of eukaryotic cells by computer modeling.

An analysis of dielectric spectra, obtained by computer modeling, of spherical eukaryotic cells (lymphocytes in particular) is presented. The number of fitting parameters required to describe these spectra is determined. The influence of parameter variation on the spectral shape is illustrated.

Animals↗

PubMed2005

Computational modeling of multicellular constructs with the material point method.

Computational modeling of the mechanics of cells and multicellular constructs with standard numerical discretization techniques such as the finite element (FE) method is complicated by the complex geometry, material properties and boundary conditions that are associated with such systems. The objectives of this research were to apply the material point method (MPM), a meshless method, to the modeling of vascularized constructs by adapting the algorithm to accurately handle quasi-static, large deformation mechanics, and to apply the modified MPM algorithm to large-scale simulations using a discretization that was obtained directly from volumetric confocal image data. The standard implicit time integration algorithm for MPM was modified to allow the background computational grid to remain fixed with respect to the spatial distribution of material points during the analysis. This algorithm was used to simulate the 3D mechanics of a vascularized scaffold under tension, consisting of growing microvascular fragments embedded in a collagen gel, by discretizing the construct with over 13.6 million material points. Baseline 3D simulations demonstrated that the modified MPM algorithm was both more accurate and more robust than the standard MPM algorithm. Scaling studies demonstrated the ability of the parallel code to scale to 200 processors. Optimal discretization was established for the simulations of the mechanics of vascularized scaffolds by examining stress distributions and reaction forces. Sensitivity studies demonstrated that the reaction force during simulated extension was highly sensitive to the modulus of the microvessels, despite the fact that they comprised only 10.4% of the volume of the total sample. In contrast, the reaction force was relatively insensitive to the effective Poisson's ratio of the entire sample. These results suggest that the MPM simulations could form the basis for estimating the modulus of the embedded microvessels through a parameter estimation scheme. Because of the generality and robustness of the modified MPM algorithm, the relative ease of generating spatial discretizations from volumetric image data, and the ability of the parallel computational implementation to scale to large processor counts, it is anticipated that this modeling approach may be extended to many other applications, including the analysis of other multicellular constructs and investigations of cell mechanics.

Algorithms↗

PubMed2003

A computer model for the study of breast cancer.

A computer model was designed as a relational database to assess breast cancer screening in a cohort of women where the growth and development of breast cancer originates with the first malignant cell. The concepts of thresholds for growth, axillary spread, and distant sites are integrated. With tumor diagnosis, staging was performed that includes clinical and sub-clinical states. The model was parameterized to have staging characteristics similar to data published by the Surveillance, Epidemiology, and End-Results (SEER) Program. Validation was accomplished by comparing simulated staging results with non-SEER sources, and simulated survival with independent clinical survival data.

Breast Neoplasms↗