ELF coupling to spherical models of man and animals.
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Animals↗
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Results for “Coupled model”
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Combining strings and necklaces for interactive three-dimensional segmentation of spinal images using an integral deformable spine model.
Segmentation of the spine directly from three-dimensional (3-D) image data is desirable to accurately capture its morphological properties. We describe a method that allows true 3-D spinal image segmentation using a deformable integral spine model. The method learns the appearance of vertebrae from multiple continuous features recorded along vertebra boundaries in a given training set of images. Important summarizing statistics are encoded into a necklace model on which landmarks are differentiated on their free dimensions. The landmarks are used within a priority segmentation scheme to reduce the complexity of the segmentation problem. Necklace models are coupled by string models. The string models describe in detail the biological variability in the appearance of spinal curvatures from multiple continuous features recorded in the training set. In the segmentation phase, the necklace and string models are used to interactively detect vertebral structures in new image data via elastic deformation reminiscent of a marionette with strings allowing for movement between interrelated structures. Strings constrain the deformation of the spine model within feasible solutions. The driving application in this work is analysis of computed tomography scans of the human lumbar spine. An illustration of the segmentation process shows that the method is promising for segmentation of the spine and for assessment of its morphological properties.
Aged↗
A model system of coupled activity of co-immobilized creatine kinase and myosin.
Myosin and creatine kinase were co-immobilized onto Immunodyne films to mimic the behaviour of creatine kinase bound to the M-line of myofilaments. The Mg-ATPase activity of bound myosin was studied by a coupled enzymatic assay, which detects Mg-ADP in the bulk solution by means of pyruvate kinase and lactate dehydrogenase. The competition for Mg-ADP between pyruvate kinase and creatine kinase either free in solution or co-immobilized with myosin was studied at various creatine phosphate concentrations. Bound creatine kinase competed efficiently when present in very low amounts, corresponding to an activity ratio higher than 1:20,000 between creatine kinase and pyruvate kinase and a molar ratio higher than 1:1000 between creatine kinase and myosin. The Mg-ADP produced by myosin ATPase in the vicinity of the film did not diffuse into the bulk solution but, in the presence of creatine phosphate, was recycled into Mg-ATP by the neighbouring creatine kinase. The existence of an unstirred layer near the surface of the film is sufficient to explain the channeling of ADP (or ATP) between co-immobilized myosin and creatine kinase, without direct interaction or 'intimate coupling' between the enzymes. The problem now is to determine the importance of this kind of facilitated diffusion in the myofilaments in vivo.
Animals↗
Engineered yeast cells as model to study coupling between human xenobiotic metabolizing enzymes. Simulation of the two first steps of benzo[a]pyrene activation.
Human microsomal epoxide hydrolase and cytochrome P450 (P450) 1A1 were coexpressed in Saccharomyces cerevisiae from expression cassettes integrated respectively into the host chromosomal DNA and on a multicopy plasmid in a strain already overexpressing yeast NADPH-cytochrome P450 reductase (P450 reductase). A styrene-oxide-hydrolase activity (2 nmol.min-1.mg microsomal protein-1) and a 7-ethoxyresorufin-O-deethylase activity (320 pmol.min-1.mg microsomal protein-1) characteristic respectively of microsomal epoxide hydrolase and P450 1A1 were detected. The conversion of benzo[a]pyrene (B[a]P) to B[a]P-7,8-dihydrodiol both in microsomal preparations and in growing yeast cells was observed, demonstrating an efficient coupling between the two human enzymes. Kinetic analysis indicated that the B[a]P-7,8-oxide produced by the P450-1A1-dependent reaction does not accumulate before hydrolysis by microsomal epoxide hydrolase. This system was also used as a control to evaluate the coupling efficiency of a mixture of microsomes or of yeast cells containing separately the individual enzymes (i.e., human P450 1A1 and microsomal epoxide hydrolase). B[a]P-7,8-oxide was well converted to the corresponding dihydrodiol with a mixture of microsomes. In contrast, when the same experiment was repeated with a mixture of cells expressing independently the two activities, dihydrodiol formation was not observed. Coexpression of human phase I and phase II enzymes in a single yeast cell and microsome mixture thus appear to be complementary tools for the simulation of human-drug-metabolism or carcinogen-metabolism pathways.
Base Sequence↗
Glottal flow through a two-mass model: comparison of Navier-Stokes solutions with simplified models.
A new numerical model of the vocal folds is presented based on the well-known two-mass models of the vocal folds. The two-mass model is coupled to a model of glottal airflow based on the incompressible Navier-Stokes equations. Glottal waves are produced using different initial glottal gaps and different subglottal pressures. Fundamental frequency, glottal peak flow, and closed phase of the glottal waves have been compared with values known from the literature. The phonation threshold pressure was determined for different initial glottal gaps. The phonation threshold pressure obtained using the flow model with Navier-Stokes equations corresponds better to values determined in normal phonation than the phonation threshold pressure obtained using the flow model based on the Bernoulli equation. Using the Navier-Stokes equations, an increase of the subglottal pressure causes the fundamental frequency and the glottal peak flow to increase, whereas the fundamental frequency in the Bernoulli-based model does not change with increasing pressure.
Air Pressure↗
Discontinuous spectral element method modeling of optical coupling by whispering gallery modes between microcylinders.
We introduce a high-order time-domain discontinuous spectral element method for the study of the optical coupling by evanescent whispering gallery modes between two microcylinders, the building blocks of coupled resonator optical waveguide devices. By using the discontinuous spectral element method with a Dubiner orthogonal polynomial basis on triangles and a Legendre nodal orthogonal basis on quadrilaterals, we conduct a systematic study of the optical coupling by whispering gallery modes between two microcylinders and demonstrate the successful coupling between the microcylinders and also the dependence of such a coupling on the separation and the size variation of the microcylinders.
Journal Article↗
Synaptic depression mediates bistability in neuronal networks with recurrent inhibitory connectivity.
When depressing synapses are embedded in a circuit composed of a pacemaker neuron and a neuron with no autorhythmic properties, the network can show two modes of oscillation. In one mode the synapses are mostly depressed, and the oscillations are dominated by the properties of the oscillating neuron. In the other mode, the synapses recover from depression, and the oscillations are primarily controlled by the synapses. We demonstrate the two modes of oscillation in a hybrid circuit consisting of a biological pacemaker and a model neuron, reciprocally coupled via model depressing synapses. We show that across a wide range of parameter values this network shows robust bistability of the oscillation mode and that it is possible to switch the network from one mode to the other by injection of a brief current pulse in either neuron. The underlying mechanism for bistability may be present in many types of circuits with reciprocal connections and synaptic depression.
Animals↗
[Identification of synthesis routes of "Ecstasy" by GC-MS coupled soft independent modeling of class analogies].
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Gas Chromatography-Mass Spectrometry↗
The HIV-1 Rev protein: a model system for coupled RNA transport and translation.
The impact of the Rev protein of the human immunodeficiency virus type 1 (HIV-1) on RNA transport, intranuclear RNA distribution, and gene expression was examined for two Rev-dependent expression systems by means of fluorescence in situ hybridization, immunofluorescence, S1 nuclease protection, and functional assays. In the pgTat expression system, which utilizes authentic HIV-1 splice signals, unspliced mRNA remained entrapped in the nucleus in the absence of Rev and was exported to the cytoplasm in its presence, consistent with published findings. In the pSVAR expression system, significant levels of mRNA were found in the nucleus and cytoplasm in both the presence and absence of Rev, but only in the presence of Rev was mRNA translated into protein. The presence of cytoplasmic untranslated mRNA in the absence of Rev was demonstrated by in situ hybridization analysis of individual cells as well as by S1 nuclease analysis of cell populations. The results indicate that Rev has the potential to affect translation as well as transport, suggesting the possibility that cellular mechanisms exist whereby the translational efficiency of an mRNA may be affected by the manner in which it is transported from the nucleus. Fluorescence hybridization also provided high-resolution visualization of the intranuclear distribution of RNAs containing the Rev response element. This demonstrated for both expression systems that mRNA was not highly localized in tracks or around the nucleolus in the presence or absence of Rev, a nucleolar protein, but was more widely distributed throughout the nucleus. In pgTat transfectants, HIV-1 RNA often became localized in 5 to 20 discrete large intranuclear clusters in the presence of Rev, the potential significance of which is discussed.
Biological Transport↗
Application of the coupled harmonic oscillators model to the description of beta-cells of the pancreatic langerhans islets.
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Animals↗
A coupled pacemaker-slave model for the insect photoperiodic clock: interpretation of ovarian diapause data in Drosophila melanogaster.
A coupled circadian oscillator model for the insect photoperiodic clock is described which consists of a hierarchically arranged pacemaker and slave. The pacemaker is self-sustained, temperature compensated, and entrainable by the light cycle; the slave is a damping oscillation receiving entrainment from two sources, from the pacemaker via a coupling factor, and also directly from the light. The damping slave oscillation is seen as the "photoperiodic oscillator", equivalent to that proposed earlier by Lewis and Saunders (1987). The present simulations describe the effect of the strength of the coupling factor between hypothetical short- and long-period pacemaker oscillations (modelled on the "clock" mutants perS and perL2 in Drosophila melanogaster) and a slave oscillation with a period of about 24 hours. The output is presented in terms of photoperiodic response curves and Nanda-Hamner, or resonance, plots. With a high coupling strength, the pacemakers strongly entrain the slave, but with a low coupling strength the slave's properties are more evident. The model is presented as a possible explanation for recent ovarian diapause data in D. melanogaster "clock" mutants (Saunders 1990), but also as a more general model for the role of the insect circadian system in seasonal time measurement.
Animals↗
Three dimensional electromechanical model of porcine heart with penetrating wound injury.
The aim of this study is development a prototype computational model of the pig heart that can be used to predict physiological responses to a penetrating wound injury. The pig has been chosen for this model studies because it shares many anatomical similarities with humans. Three-dimensional cubic Hermite finite element meshes based on detailed measurements of porcine anatomy combined into an integrated anatomic model. The pig ventricular model includes detailed left and right ventricular geometry and myofiber and laminar sheet orientations throughout the mesh. The cardiac mesh was refined and monodomain equations for action potential propagation solved using well-established collocation-Galerkin finite element methods. The membrane kinetic equations for the action potential model was based on detailed cellular models of transmembrane ionic fluxes and intracellular calcium fluxes in canine ventricular myocytes and human atrial myocytes. We modified the anisotropic myocardial conductivity tensor on the endocardial surface of the ventricles by making use of a surface model fitted to measured of Purkinje fiber network anatomy. The mechanical model compute regional three-dimensional stress and strain distributions using anisotropic constitutive laws referred to local material coordinate axes defined by local myofiber and laminar sheet orientations. Passive myocardial mechanics modeled using exponential orthotropic strain energy functions. Active systolic myocardial stresses computed from a multi-scale model that uses crossbridge theory to predict calcium-activated sarcomere length- and velocity-dependent tension filament tension. Since the electrical and mechanical models use a common finite element mesh as the parent parametric framework and both models are solved within our custom finite element package, it is straightforward to couple these models, as we have recently done for a model of coupled ventricular electromechanics. We apply the coupled electromechanical model to predict alterations in regional diastolic and systolic wall mechanics associated with rhythm disturbances and possible arrhythmias with decreased blood volume, tamponade, myocardial injury, and regional ischemia caused by a penetrating wound.
Animals↗
The use of physiologically-based pharmacokinetic/pharmacodynamic dosimetry models for chemical mixtures.
Human exposure to chemicals is rarely, if ever, limited to a single chemical. Therefore, it is essential that we consider multiple chemical effects and interactions in our risk assessment process. However, with the almost infinitely large number of chemical mixtures in the environment, systematic studies of the toxicology of these chemical mixtures with conventional methodologies and approaches are impossible because of the immense resources and unrealistically long durations required. Thus, the development of 'Predictive and Alternative Toxicology' is imperative. At Colorado State University (CSU), our research effort is entirely devoted to this challenge. In order to have a reasonable chance to deal with the complex issue of toxicology of chemical mixtures, we believe that the following concepts must be considered: (1) the utilization of computer, (2) the exploitation of mathematical/statistical methodologies; (3) developing very focused, mechanistically based, and short-term toxicology studies; (4) coupling computer/mathematical modeling with mechanistically-based toxicology. Our strategy therefore the utilization of physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, coupled with very focused, model-directed toxicology experiments as well as other statistical/mathematical methodologies such as Monte Carlo simulation, isobolographic analysis, and response surface methodology. We believe that 'Predictive and Alternative Toxicology' in terms of tissue dosimetry at the pharmacokinetic and pharmacodynamic levels is achievable with simple and complex but chemically defined mixtures. In this presentation, we describe two ongoing research projects as an illustration of our 'Bottom-Up' and 'Top-Down' approaches for handling the chemical mixtures: (1) PBPK/PD modeling of toxicologic interactions between Kepone and carbon tetrachloride (CCl4) and the coupling of Monte Carlo simulation for the prediction of acute toxicity; (2) the conceptual development of PBPK/PD modeling for a more complex chemical mixture of seven groundwater contaminants from hazardous waste sites and the consideration of subfractionation of this chemical mixture.
Animals↗
Coupled modified baker's transformations for the Ising model.
An invertible coupled map lattice is proposed for the Ising model. Each elemental map is a modified baker's transformation, which is a two-dimensional map of X and Y. The time evolution of the spin variable is memorized in the binary representation of the Y variable. The temporal entropy and time correlation of the spin variable are calculated from the snapshot configuration of the Y variables.
Journal Article↗
[Minimal mathematical model of the energetic coupling of cotransport and anion-exchange mechanisms for transport in biological membranes].
A minimal model for the coupling of fluxes of two different anions was constructed, in which one anion Y, is transferred by both the cotransport and anion-exchange pathways, whereas the other anion, Z, only by the anion-exchange mechanism. The possibilities of the model for describing the cooperativity of cotransport and anion-exchange pathways are demonstrated by using the computer simulation approach. It is shown that the energetic coupling of Y and Z anion fluxes becomes possible when the following conditions are fulfilled: (1) The inward-directed flux of Y by the cotransport pathway exceeds its anion-exchange flux directed outward; (2) the reorientation probability of the Y-loaded anion-exchanger is higher than that of the unloaded exchanger.
Anions↗
Automated modelling of the transmembrane region of G-protein coupled receptor by Swiss-model.
Molecular modelling of the transmembrane helices of G-protein coupled receptors is an increasingly used method to identify the possible three-dimensional environment of key residues. Thereby site-directed mutagenesis experiments, aimed at the understanding of the receptor-ligand interactions, can be designed in a rational way. The modelling methods are however not generally available to experimentalists, and often require expensive software and hardware. To overcome these limitations, we have constructed a World Wide Web server for the automated protein modelling of user-defined transmembrane helices. The service is freely available at this address: http:/(/)expasy.hcuge.ch/swissmod/SWISS-MODEL.++ +html.
Animals↗
A coupled ecosystem-climate model for predicting the methane concentration in the Archean atmosphere.
A simple coupled ecosystem-climate model is described that can predict levels of atmospheric CH4, CO2, and H2 during the Late Archean, given observed constraints on Earth's surface temperature. We find that methanogenic bacteria should have converted most of the available atmospheric H2 into CH4, and that CH4 may have been equal in importance to CO2 as a greenhouse gas. Photolysis of this CH4 may have produced a hydrocarbon smog layer that would have shielded the surface from solar UV radiation. Methanotrophic bacteria would have consumed some of the atmospheric CH4, but they would have been incapable of reducing CH4 to modern levels. The rise of O2 around 2.3 Ga would have drastically reduced the atmospheric CH4 concentration and may thereby have triggered the Huronian glaciation.
Aerobiosis↗
Introduction to the integrated model: medical, surgical and psychological therapies for the couple.
The integrated model is the interplay of behavioural, cognitive, medical, and surgical approach to sexual problems. Research demonstrates that prognosis and outcome of patients with sexual diseases dramatically improve when medical solutions are proposed along with the evaluation of the therapies' sexual impact on the couple's dynamics. Current classification of treatments for erectile dysfunction (here used as a paradigm of sexual disorder therapies) distinguishes between central and peripheral "initiators" and "conditioners" of erection. However, such a taxonomy does not take into account the impact on the couple, the final recipient of the treatment. For this reason, we propose here a new, couple-based sexological taxonomy which divides therapies into "harmonious" and "inharmonious". Pilot data are also presented on the use of a carnitine analogue as a model of an etiological, harmonious therapy for impotence. The integrated model suggests a strict collaboration between sexologists of different areas. Considering the growing complexity of therapies for sexual symptoms and diseases, there seems to be a need for the new professional figure of the medical sexologist.
Couples Therapy↗