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Patient-specific anatomic models. Geometric surface generation from three-dimensional medical images using a specified polygonal budget.

Virtual reality offers the promise of highly interactive, natural control of the visualization process, greatly enhancing the scientific value of the data produced by medical imaging systems. Due to the computational and real time update requirements of virtual reality interfaces, however, the complexity of polygonal surfaces which can be displayed is limited. In this paper, we present a novel method for the production of a polygonal surface containing a pre-specified number of polygons from volumetric data. To preserve surface detail, we extract a set of curvature weights from the volumetric data and use these weights as the input vectors to a 2-D Kohonen network. The adaptation of the network to the input vectors results in a display surface that preserves useful detail relative to the number of polygons used.

Computer Simulation↗

A model for the generation of spontaneous yet predictable ventricular arrhythmias.

Development of an experimental preparation aided to investigate arrhythmogenic and antiarrhythmogenic factors influencing incidence of spontaneous and yet predictable ventricular arrhythmias is described. Using the isolated perfused guinea-pig heart and a system for quantitating rhythm disturbances based on computer-aided statistical analysis of beat-to-beat intervals, a number of factors influencing the incidence of rhythm disturbances were investigated. Manipulation of perfusate composition revealed that, after 'moderate' ischaemia, reperfusion arrhythmias were increased in the presence of noradrenaline and non-glucose fuels. Free fatty acids, unless in the presence of catecholamines, were not particularly arrhythmogenic. In contrast, the presence of pyruvate or lactate, endproduct inhibitors of glycolysis, significantly increased incidence of reflow rhythm disturbances. The dose-dependent arrhythmogenic effects of pyruvate and anti-arrhythmogenic effects of glucose support the thesis that inadequate glycolytic flux could be important in the development of arrhythmias.

Acetates↗

Mathematical models of central pattern generators in locomotion: I. Current problems.

As a background for subsequent studies of mathematical models of central pattern generators in locomotion (Stafford & Barnwell, 1985a, b) relevant aspects of the literature on locomotion are reviewed, concepts of locomotion discussed, and extant models considered. Advantages and disadvantages of present models are discussed, and the need for mathematical models is emphasized. It is shown that realistic models of pattern generation in locomotion must take numerous factors into account, including phases of step cycle, muscle sequencing, gait and interlimb coordination, initiation and cessation of locomotion, and many aspects of neuromuscular control and function.

Journal Article↗

Numerical modelling of the generation and transport of heat in a bottom ash monofill.

Municipal solid waste is incinerated to reduce its volume, toxicity and reactivity. Several studies have shown that the resulting bottom ash has a high exothermic capacity. Temperature measurements in municipal solid waste incineration (MSWI) bottom ash landfills have found temperatures up to 90 degrees C. Such high temperatures may affect the stability of the landfill's flexible polymer membrane liner (FML) and may also lead to an accelerated desiccation of the clay barrier. The purpose of this study was to gain detailed knowledge of temperature development under several disposal conditions in relation to the rate of ash disposal, the variation of layer thickness, and the environmental conditions in a modern landfill. Based on this knowledge, a simulation was developed to predict temperature development. Temperature development was simulated using several storage periods prior to the deposition and several modes of emplacement. Both the storage time and the mode of emplacement have a significant influence on the temperature development at the sensitive base of the landfill. Without a preliminary storage of the fresh quenched bottom ash, high temperatures at the bottom of a landfill cannot be avoided.

Air Movements↗

Determination of copolymer ratios of poly(lactide-co-glycolide) using near-infrared spectroscopy.

The near infrared (NIR) spectroscopic technique was used to determine copolymer ratios of polylactide-co-glycolide samples. Appropriate quantities of DL-polylactic acid and lactic-co-glycolic acid polymers with 86:14, 75:25, 64:36 and 52:48 lactide to glycolide ratios were dissolved in methylene chloride to obtain 5% (w/w) solutions. NIR spectra of the samples were obtained from the solutions using a Polyol Analyzer operated in the transmittance mode. Linear regression calibration models were generated at 2130 and 2288 nm from the second derivative spectral data obtained from the NIR technique. The lowest and highest standard errors of calibration (SEC) at 2130 nm were 1.29 and 1.63%, whereas those obtained from the calibration models generated at 2288 nm were 2.00 and 2.03%, respectively. Partial least squares (PLS) calibration models were also generated from the second derivative spectral data from 1100 to 2500 nm. The lowest and the highest SEC for the models were 1.46 and 1.53%, respectively. The calibration models were then used to predict the lactide contents of the unknown (test) samples. The highest percent error of prediction was 2.56% for samples with 86% lactide content when the linear regression calibration at 2130 nm was used, whereas the highest percent error of prediction was 1.56% for samples with 64% lactide content when the linear regression calibration at 2288 nm was used. The highest percent error of prediction was 1.73% for samples with 75% lactide content when the two-factor PLS calibration model was used.

Calibration↗

Generating synthetic genotypes using diffusion models.

SUMMARY: In this paper, we introduce the first diffusion model designed to generate complete synthetic human genotypes, which, by standard protocols, one can straightforwardly expand into full-length, DNA-level genomes. The synthetic genotypes mimic real human genotypes without just reproducing known genotypes, in terms of approved metrics. When training biomedically relevant classifiers with synthetic genotypes, accuracy is near-identical to the accuracy achieved when training classifiers with real data. We further demonstrate that augmenting small amounts of real with synthetically generated genotypes drastically improves performance rates. This addresses a significant challenge in translational human genetics: real human genotypes, although emerging in large volumes from genome wide association studies, are sensitive private data, which limits their public availability. Therefore, the integration of additional, insensitive data when striving for rapid sharing of biomedical knowledge of public interest appears imperative. AVAILABILITY AND IMPLEMENTATION: All non proprietary data and the code to replicate the experiments is available on Github.

Humans↗

Neural control of interlimb oscillations. II. Biped and quadruped gaits and bifurcations.

Behavioral data concerning animal and human gaits and gait transitions are simulated as emergent properties of a central pattern generator (CPG) model. The CPG model is a version of the Ellias-Grossberg oscillator. Its neurons obey Hodgkin-Huxley type equations whose excitatory signals operate on a faster time scale than their inhibitory signals in a recurrent on-center off-surround anatomy. A descending command or GO signal activates the gaits and triggers gait transitions as its amplitude increases. A single model CPG can generate both in-phase and anti-phase oscillations at different GO amplitudes. Phase transitions from either in-phase to anti-phase oscillations or from anti-phase to in-phase oscillations can occur in different parameter ranges, as the GO signal increases. Quadruped vertebrate gaits, including the amble, the walk, all three pairwise gaits (trot, pace, and gallop), and the pronk are simulated using this property. Rapid gait transitions are simulated in the order--walk, trot, pace, and gallop--that occurs in the cat, along with the observed increase in oscillation frequency. Precise control of quadruped gait switching uses GO-dependent modulation of inhibitory interactions, which generates a different functional anatomy at different arousal levels. The primary human gaits (the walk and the run) and elephant gaits (the amble and the walk) are simulated, without modulation, by oscillations with the same phase relationships but different waveform shapes at different GO signal levels, much as the duty cycles of the feet are longer in the walk than in the run. Relevant neural data from spinal cord, globus pallidus, and motor cortex, among other structures, are discussed.

Animals↗

Membrane position of a basic aromatic peptide that sequesters phosphatidylinositol 4,5 bisphosphate determined by site-directed spin labeling and high-resolution NMR.

The membrane interactions and position of a positively charged and highly aromatic peptide derived from a secretory carrier membrane protein (SCAMP) are examined using magnetic resonance spectroscopy and several biochemical methods. This peptide (SCAMP-E) is shown to bind to membranes containing phosphatidylinositol 4,5-bisphosphate, PI(4,5)P2, and sequester PI(4,5)P2 within the plane of the membrane. Site-directed spin labeling of the SCAMP-E peptide indicates that the position and structure of membrane bound SCAMP-E are not altered by the presence of PI(4,5)P2, and that the peptide backbone is positioned within the lipid interface below the level of the lipid phosphates. A second approach using high-resolution NMR was used to generate a model for SCAMP-E bound to bicelles. This approach combined oxygen enhancements of nuclear relaxation with a computational method to dock the SCAMP-E peptide at the lipid interface. The model for SCAMP generated by NMR is consistent with the results of site-directed spin labeling and places the peptide backbone in the bilayer interfacial region and the aromatic side chains within the lipid hydrocarbon region. The charged side chains of SCAMP-E lie well within the interface with two arginine residues lying deeper than a plane defined by the position of the lipid phosphates. These data suggest that SCAMP-E interacts with PI(4,5)P2 through an electrostatic mechanism that does not involve specific lipid-peptide contacts. This interaction may be facilitated by the position of the positively charged side chains on SCAMP-E within a low-dielectric region of the bilayer interface.

Binding Sites↗

Social support transactions between professional and nonprofessional women and their mothers.

A theoretical model predicting professional and nonprofessional women's perceptions of social support transactions with their mothers was tested. A sample of 210 Professional women and 165 nonprofessional women answered mailed questionnaires. LISREL VI was used to evaluate the quality of the measurement model and generate a revised model. Social support was greatest when employed women were professional, had positive filial responsibility attitudes, lived near their mothers, visited them frequently, and when mothers were not married. These findings provide a beginning theoretical model that can serve as a basis for nursing practice and research when working with intergenerational families.

Adult↗

An animal model for in vivo evaluation of tumor glycolytic rates with positron emission tomography.

We developed a method for evaluating tumor glycolytic rates in vivo with nude mice injected with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) and a dedicated animal positron emission tomography (PET) scanner. Animals were injected with NR-6 mouse fibroblast tumor cell lines. When tumors achieved a large enough size to be macroscopically visible, quantitative measurements of FDG uptake in vivo were obtained, using both standard nonlinear regression with the FDG tracer kinetic model to generate estimates of model parameters, including KNLR, the rate constant for net phosphorylation of FDG. Additionally, we determined the values of KPAT, the rate constant for net phosphorylation of FDG measured with a non-iterative graphical method. Estimates of K were highly correlated (r = 0.95) with both methods, and parametric images of KPAT demonstrate both the tumor location and size, but are also scaled in units of phosphorylation of FDG. The method is suitable for serial studies of tumor glucose metabolism during and after therapeutic interventions, such as chemotherapeutic trials.

Animals↗

Time-resolved synchrotron X-ray "footprinting", a new approach to the study of nucleic acid structure and function: application to protein-DNA interactions and RNA folding.

Hydroxyl radicals (.OH) can cleave the phosphodiester backbone of nucleic acids and are valuable reagents in the study of nucleic acid structure and protein-nucleic acid interactions. Irradiation of solutions by high flux "white light" X-ray beams based on bending magnet beamlines at the National Synchrotron Light Source (NSLS) yields sufficient concentrations of .OH so that quantitative nuclease protection ("footprinting") studies of DNA and RNA can be conducted with a duration of exposure in the range of 50 to 100 ms. The sensitivity of DNA and RNA to X-ray mediated .OH cleavage is equivalent. Both nucleic acids are completely protected from synchrotron X-ray induced cleavage by the presence of thiourea in the sample solution, demonstrating that cleavage is suppressed by a free radical scavenger. The utility of this time-dependent approach to footprinting is demonstrated with a synchrotron X-ray footprint of a protein-DNA complex and by a time-resolved footprinting analysis of the Mg(2+)-dependent folding of the Tetrahymena thermophilia L-21 ScaI ribozyme RNA. Equilibrium titrations reveal differences among the ribozyme domains in the cooperativity of Mg(2+)-dependent .OH protection. RNA .OH protection progress curves were obtained for several regions of the ribozyme over timescales of 30 seconds to several minutes. Progress curves ranging from > or = 3.5 to 0.4 min-1 were obtained for the P4-P6 and P5 sub-domains and the P3-P7 domain, respectively. The .OH protection progress curves have been correlated with the available biochemical, structural and modeling data to generate a model of the ribozyme folding pathway. Rate differences observed for specific regions within domains provide evidence for steps in the folding pathway not previously observed. Synchrotron X-ray footprinting is a new approach of general applicability for the study of time-resolved structural changes of nucleic acid conformation and protein-nucleic acid complexes.

Animals↗

Disruption of PLC-beta 1-mediated signal transduction in mutant mice causes age-dependent hippocampal mossy fiber sprouting and neurodegeneration.

Aberrant reorganization of hippocampal mossy fibers occurs in human temporal lobe epilepsy and rodent epilepsy models. We generated a mouse model showing massive late-onset aberrant mossy fiber sprouting in the adult hippocampus. The mutation in this mouse model derives from an intronic insertion of transgene DNA in the mouse PLC-beta1 gene (PLC-beta 1(-/-)(TC) mutation) leading to a splice mutation of the PLC-beta 1 gene and a complete loss of downstream PLC-beta 1 expression. PLC-beta 1(-/-)(TC) mutants develop a loss of NMDA-receptors in the stratum oriens of region CA1, apoptotic neuronal death, and reduced hippocampal PKC activity. The phenotype of these mice further consists of a late-onset epileptiform hyperexcitability, behavioral modifications in a radial maze and in an open field, female nurturing defect, and male infertility. In the present study, we provide evidence that the arising of the behavioral phenotype in PLC-beta 1(-/-)(TC) mice correlates in time with the development of the aberrant mossy fiber projections and that the disruption of the PLC-beta 1-mediated signal transduction pathway may lead to a functional cholinergic denervation, which could cause hippocampal remodeling and, in consequence, epileptiform hyperexcitability.

Aging↗

A community model of ciliate Tetrahymena and bacteria E. coli: Part I. individual-based models of tetrahymena and E. coli populations.

The dynamics of a microbial community consisting of a eucaryotic ciliate Tetrahymena pyriformis and procaryotic Escherichia coli in a batch culture is explored by employing an individual-based approach. In this portion of the article, Part I, population models are presented. Because both models are individual-based, models of individual organisms are developed prior to construction of the population models. The individual models use an energy budget method in which growth depends on energy gain from feeding and energy sinks such as maintenance and reproduction. These models are not limited by simplifying assumptions about constant yield, constant energy sinks and Monod growth kinetics as are traditional models of microbal organisms. Population models are generated from individual models by creating distinct individual types and assigning to each type the number of real individuals they represent. A population is a compilation of individual types that vary in a phase of cell cycle and physiological parameters such as filtering rate for ciliates and maximum anabolic rate for bacteria. An advantage of the developed models is that they realistically describe the growth of the individual cells feeding on resource which varies in density and composition. Part II, the core of the project, integrates models into a dynamic microbial community and provides model analysis based upon available data.

Animals↗

Homology modeling of tubulin: influence predictions for microtubule's biophysical properties.

Using comparative modeling, we have generated structural models of 475 alpha and beta tubulins. Using these models, we observed a global, structural similarity between the tubulin isotypes. However, a number of subtle differences in the isotypes physical properties, including net electric charges, solvent accessible surface areas, and electric dipole moments were also apparent. In order to examine the roles that these properties may play in microtubule (MT) assembly and stability, we have created a model to evaluate the dipole-dipole interaction energies of varying MT lattice conformations, using human tubulin isotypes as particularly important examples. We conclude that the dipole moments of each tubulin isotype may influence their functional characteristics within the cell, resulting in differences for MT assembly kinetics and stability.

Biophysics↗

Neural control of interlimb oscillations. I. Human bimanual coordination.

How do humans and other animals accomplish coordinated movements? How are novel combinations of limb joints rapidly assembled into new behavioral units that move together in in-phase or anti-phase movement patterns during complex movement tasks? A neural central pattern generator (CPG) model simulates data from human bimanual coordination tasks. As in the data, anti-phase oscillations at low frequencies switch to in-phase oscillations at high frequencies, in-phase oscillations occur at both low and high frequencies, phase fluctuations occur at the anti-phase in-phase transition, a "seagull effect" of larger errors occurs at intermediate phases, and oscillations slip toward in-phase and anti-phase when driven at intermediate phases. These oscillations and bifurcations are emergent properties of the CPG model in response to volitional inputs. The CPG model is a version of the Ellias-Grossberg oscillator. Its neurons obey Hodgkin-Huxley type equations whose excitatory signals operate on a faster time scale than their inhibitory signals in a recurrent on-center off-surround anatomy. When an equal command or GO signal activates both model channels, the model CPG can generate both in-phase and anti-phase oscillations at different GO amplitudes. Phase transitions from either in-phase to anti-phase oscillations, or from anti-phase to in-phase oscillations, can occur in different parameter ranges, as the GO signal increases.

Extremities↗

Atom, atom-type, and total nonstochastic and stochastic quadratic fingerprints: a promising approach for modeling of antibacterial activity.

The TOpological MOlecular COMputer Design (TOMOCOMD-CARDD) approach has been introduced for the classification and design of antimicrobial agents using computer-aided molecular design. For this propose, atom, atom-type, and total quadratic indices have been generalized to codify chemical structure information. In this sense, stochastic quadratic indices have been introduced for the description of the molecular structure. These stochastic fingerprints are based on a simple model for the intramolecular movement of all valence-bond electrons. In this work, a complete data set containing 1006 antimicrobial agents is collected and presented. Two structure-based antibacterial activity classification models have been generated. The models (including nonstochastic and stochastic indices) classify correctly more than 90% of 1525 compounds in training sets. These models permit the correct classification of 92.28% and 89.31% of 505 compounds in an external test sets. The TOMOCOMD-CARDD approach, also, satisfactorily compares with respect to nine of the most useful models for antimicrobial selection reported to date. Finally, a virtual screening of 87 new compounds reported in the antiinfective field with antibacterial activities is developed showing the ability of the TOMOCOMD-CARDD models to identify new leads as antibacterial.

Anti-Bacterial Agents↗