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Computational Modelling (computational + modelling)
Selected AbstractsBücher: Computational Modelling of Concrete Structures.BAUTECHNIK, Issue 2 2009By G. Meschke, H. Mang, N. Bicanic, R. de Borst No abstract is available for this article. [source] Computational modelling of amino acid transfer interactions in the placentaEXPERIMENTAL PHYSIOLOGY, Issue 7 2010B. G. Sengers Amino acid transfer from mother to fetus via the placenta plays a critical role in normal development, and restricted transfer is associated with fetal growth restriction. Placental amino acid transfer involves the interaction of 15 or more transporters and 20 amino acids. This complexity means that knowing which transporters are present is not sufficient to predict how they operate together as a system. Therefore, in order to investigate how placental amino acid transfer occurs as a system, an integrated mathematical/computational modelling framework was developed to represent the simultaneous transport of multiple amino acids. The approach was based on a compartmental model, in which separate maternal, syncytiotrophoblast and fetal volumes were distinguished, and transporters were modelled on the maternal- and fetal-facing membranes of the syncytiotrophoblast using Michaelis,Menten-type kinetics. The model was tested in comparison with placental perfusion experiments studying serine,alanine exchange and found to correspond well. The results demonstrated how the different transporters can work together as an integrated system and allowed their relative importance to be assessed. Placental,fetal serine exchange was found to be most sensitive to basal membrane transporter characteristics, but a range of secondary, less intuitive effects were also revealed. While this work only addressed a relatively simple three amino acid system, it demonstrates the feasibility of the approach and could be extended to incorporate additional experimental parameters. Ultimately, this approach will allow physiological simulations of amino acid transfer. This will enhance our understanding of these complex systems and placental function in health and disease. [source] Computational modelling of the surface fatigue crack growth on gear teeth flanksINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 8 2001S. Glode Abstract The paper describes a 2-dimensional computational model for simulation of the surface initiated fatigue crack growth in the contact area of gear teeth flanks that leads to surface pitting. The discretized model of a gear tooth with the assumed initial crack is subjected to normal contact pressure, which takes into account the EHD-lubrication conditions and tangential loading due to friction between gear teeth flanks. The model accounts also for the influence of a fluid driven into the crack by hydraulic mechanism on crack propagation. The J -integral method in the framework of the finite element analysis is used for simulation of the fatigue crack propagation from the initial to the critical crack length, when the surface material layer breaks away and pit appears on the surface. The model is applied to a real pitting problem of a gear and corresponding computational results in terms of pit sizes correlate well to the development of micropits observed in experimental testing. Copyright © 2001 John Wiley & Sons, Ltd. [source] Bivalent phenethylamines as novel dopamine transporter inhibitors: evidence for multiple substrate-binding sites in a single transporterJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Kyle C. Schmitt J. Neurochem. (2010) 112, 1605,1618. Abstract Bivalent ligands , compounds incorporating two receptor-interacting moieties linked by a flexible chain , often exhibit profoundly enhanced binding affinity compared with their monovalent components, implying concurrent binding to multiple sites on the target protein. It is generally assumed that neurotransmitter sodium symporter (NSS) proteins, such as the dopamine transporter (DAT), contain a single domain responsible for recognition of substrate molecules. In this report, we show that molecules possessing two substrate-like phenylalkylamine moieties linked by a progressively longer aliphatic spacer act as progressively more potent DAT inhibitors (rather than substrates). One compound bearing two dopamine (DA)-like pharmacophoric ,heads' separated by an 8-carbon linker achieved an 82-fold gain in inhibition of [3H] 2,-carbomethoxy-3,-(4-fluorophenyl)-tropane (CFT) binding compared with DA itself; bivalent compounds with a 6-carbon linker and heterologous combinations of DA-, amphetamine- and ,-phenethylamine-like heads all resulted in considerable and comparable gains in DAT affinity. A series of short-chain bivalent-like compounds with a single N -linkage was also identified, the most potent of which displayed a 74-fold gain in binding affinity. Computational modelling of the DAT protein and docking of the two most potent bivalent (-like) ligands suggested simultaneous occupancy of two discrete substrate-binding domains. Assays with the DAT mutants W84L and D313N , previously employed by our laboratory to probe conformation-specific binding of different structural classes of DAT inhibitors , indicated a bias of the bivalent ligands for inward-facing transporters. Our results strongly indicate the existence of multiple DAT substrate-interaction sites, implying that it is possible to design novel types of DAT inhibitors based upon the ,multivalent ligand' strategy. [source] Multiple causality in developmental disorders: methodological implications from computational modellingDEVELOPMENTAL SCIENCE, Issue 5 2003Michael S.C. Thomas When developmental disorders are defined on the basis of behavioural impairments alone, there is a risk that individuals with different underlying cognitive deficits will be grouped together on the basis that they happen to share a certain impairment. This phenomenon is labelled multiple causality. In contrast, a developmental disorder generated by a single underlying cognitive deficit may nevertheless show variable patterns of impairments due to individual differences. Connectionist computational models of development are used to investigate whether there may be ways to distinguish disorder groups with a single underlying cause (homogeneous disorder groups) from disorder groups with multiple underlying causes (heterogeneous disorder groups) on the basis of behavioural measures alone. A heuristic is proposed to assess the underlying causal homogeneity of the disorder group based on the variability of different behavioural measures from the target domain. Heterogeneous disorder groups are likely to show smaller variability on the measure used to define the disorder than on subsequent behavioural measures, while homogeneous groups should show approximately equivalent variability. Homogeneous disorder groups should show reductions in the variability of behavioural measures over time, while heterogeneous groups may not. It is demonstrated how these predictions arise from computational assumptions, and their use is illustrated with reference to behavioural data on naming skills from two developmental disorder groups, Williams syndrome and children with Word Finding Difficulties. [source] Towards predictive modelling of the electrophysiology of the heartEXPERIMENTAL PHYSIOLOGY, Issue 5 2009Edward Vigmond The simulation of cardiac electrical function is an example of a successful integrative multiscale modelling approach that is directly relevant to human disease. Today we stand at the threshold of a new era, in which anatomically detailed, tomographically reconstructed models are being developed that integrate from the ion channel to the electromechanical interactions in the intact heart. Such models hold high promise for interpretation of clinical and physiological measurements, for improving the basic understanding of the mechanisms of dysfunction in disease, such as arrhythmias, myocardial ischaemia and heart failure, and for the development and performance optimization of medical devices. The goal of this article is to present an overview of current state-of-art advances towards predictive computational modelling of the heart as developed recently by the authors of this article. We first outline the methodology for constructing electrophysiological models of the heart. We then provide three examples that demonstrate the use of these models, focusing specifically on the mechanisms for arrhythmogenesis and defibrillation in the heart. These include: (1) uncovering the role of ventricular structure in defibrillation; (2) examining the contribution of Purkinje fibres to the failure of the shock; and (3) using magnetic resonance imaging reconstructed heart models to investigate the re-entrant circuits formed in the presence of an infarct scar. [source] Stochastic computational modelling of highly heterogeneous poroelastic media with long-range correlationsINTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 1 2004Diego G. Frias Abstract The compaction of highly heterogeneous poroelastic reservoirs with the geology characterized by long-range correlations displaying fractal character is investigated within the framework of the stochastic computational modelling. The influence of reservoir heterogeneity upon the magnitude of the stresses induced in the porous matrix during fluid withdrawal and rock consolidation is analysed by performing ensemble averages over realizations of a log-normally distributed stationary random hydraulic conductivity field. Considering the statistical distribution of this parameter characterized by a coefficient of variation governing the magnitude of heterogeneity and a correlation function which decays with a power-law scaling behaviour we show that the combination of these two effects result in an increase in the magnitude of effective stresses of the rock during reservoir depletion. Further, within the framework of a perturbation analysis we show that the randomness in the hydraulic conductivity gives rise to non-linear corrections in the upscaled poroelastic equations. These corrections are illustrated by a self-consistent recursive hierarchy of solutions of the stochastic poroelastic equations parametrized by a scale parameter representing the fluctuating log-conductivity standard deviation. A classical example of land subsidence caused by fluid extraction of a weak reservoir is numerically simulated by performing Monte Carlo simulations in conjunction with finite elements discretizations of the poroelastic equations associated with an ensemble of geologies. Numerical results illustrate the effects of the spatial variability and fractal character of the permeability distribution upon the evolution of the Mohr,Coulomb function of the rock. Copyright © 2004 John Wiley & Sons, Ltd. [source] Special issue on patient-specific computational modellingINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 1 2010P. Nithiarasu Guest Editor Abstract A total of eight papers in the area of patient-specific computational modelling are collated and presented in this special issue. Copyright © 2009 John Wiley & Sons, Ltd. [source] Numerical prediction of the hydrodynamic performance of a centrifugal pump in cavitating flowsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 5 2007Jun Li Abstract A computational modelling for the prediction of the hydrodynamic performance of a centrifugal pump in cavitating flows is presented in this paper. The cavitation model is implemented in a viscous Reynolds-averaged Navier,Stokes solver. The cavity interface and shape are determined using an iterative procedure matching the cavity surface to a constant pressure boundary. The pressure distribution, as well as its gradient on the wall, is taken into account in updating the cavity shape iteratively. Numerical validation of the present cavitation model and algorithms is performed on different headform/cylinder bodies for a range of cavitation numbers through comparing with the experimental data. Flow characteristics trends associated with off-design flow and twin cavities in the blade channel are observed using the presented cavitation prediction. The rapid drop in head coefficient at low cavitation number is captured for two different flow coefficients. Local flow field solution illustrates the principle physical mechanisms associated with the onset of breakdown. Copyright © 2006 John Wiley & Sons, Ltd. [source] A hybrid discontinuous Galerkin/interface method for the computational modelling of failureINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 7 2004J. Mergheim Abstract The present contribution is concerned with the computational modelling of failure along well-defined surfaces, which occur for example in the case of light-weight composite materials. A hybrid method will be introduced which makes use of the discontinuous Galerkin method in combination with a finite element interface approach. As a natural choice interface elements are introduced along the known failure surface. The discontinuous Galerkin method is applied in the pre-failure regime to avoid the unphysical use of penalty terms and instead to enforce the continuity of the solution along the interface weakly. Once a particular failure criterion is fulfilled, the behaviour of the interface is determined constitutively, depending on the displacement jump. The applicability of the proposed method is illustrated by means of two computational model problems. Copyright © 2004 John Wiley & Sons, Ltd. [source] Surface wavelets: a multiresolution signal processing tool for 3D computational modellingINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 3 2001Kevin Amaratunga Abstract In this paper, we provide an introduction to wavelet representations for complex surfaces (surface wavelets), with the goal of demonstrating their potential for 3D scientific and engineering computing applications. Surface wavelets were originally developed for representing geometric objects in a multiresolution format in computer graphics. These wavelets share all of the major advantages of conventional wavelets, in that they provide an analysis tool for studying data, functions and operators at different scales. However, unlike conventional wavelets, which are restricted to uniform grids, surface wavelets have the power to perform signal processing operations on complex meshes, such as those encountered in finite element modelling. This motivates the study of surface wavelets as an efficient representation for the modelling and simulation of physical processes. We show how surface wavelets can be applied to partial differential equations, stated either in integral form or in differential form. We analyse and implement the wavelet approach for a model 3D potential problem using a surface wavelet basis with linear interpolating properties. We show both theoretically and experimentally that an O(h) convergence rate, hn being the mesh size, can be obtained by retaining only O((logN) 7/2N) entries in the discrete operator matrix, where N is the number of unknowns. The principles described here may also be extended to volumetric discretizations. Copyright © 2001 John Wiley & Sons, Ltd. [source] Investigation of structure and dynamics in the sodium metallocenes CpNa and CpNa·THF via solid-state NMR, X-ray diffraction and computational modellingMAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2007Cory M. Widdifield Abstract Solid-state 23Na NMR spectra of two organometallic complexes, cyclopentadienylsodium (CpNa) and the tetrahydrofuran (THF) solvate of CpNa (CpNa·THF), are presented. Analytical simulations of experimental spectra and calculated 23Na electric-field gradient (EFG) tensors confirm that both complexes are present in microcrystalline samples of CpNa recrystallized from THF. For the solvate, 23Na NMR experiments at 9.4 T and 11.7 T elucidate sodium chemical shielding (CS) tensor parameters, and establish that the EFG and CS tensor frames are non-coincident. Single-crystal X-ray diffraction (XRD) experiments are used to determine the crystal structure of CpNa·THF: Cmca (a = 9.3242(15) Å, b = 20.611(3) Å, c = 9.8236(14) Å, , = , = , = 90° , V = 1887.9(5)Å3, Z = 8). For CpNa, 23Na NMR data acquired at multiple field strengths establish sodium CS tensor parameters more precisely than in previous reports. Variable-temperature (VT) powder XRD (pXRD) experiments determine the temperature dependence of the CpNa unit cell parameters. The combination of 23Na quadrupolar NMR parameters, pXRD data and calculations of 23Na EFG tensors is used to examine various models of dynamic motion in the solid state. It is proposed that the sodium atom in CpNa undergoes an anisotropic, temperature-dependent, low frequency motion within the ab crystallographic plane, in contrast with previous models. Copyright © 2007 John Wiley & Sons, Ltd. [source] Physiological properties of rod photoreceptor electrical coupling in the tiger salamander retinaTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Jian Zhang Using dual whole-cell voltage and current clamp recording techniques, we investigated the gap junctional conductance and the coupling coefficient between neighbouring rods in live salamander retinal slices. The application of sinusoidal stimuli over a wide range of temporal frequencies allowed us to characterize the band-pass filtering properties of the rod network. We found that the electrical coupling of all neighbouring rods exhibited reciprocal and symmetrical conductivities. On average, the junctional conductance between paired rods was 500 pS and the coupling coefficient (the ratio of voltage responses of the follower cell to those of the driver cell), or K -value, was 0.07. Our experimental results also demonstrated that the rod network behaved like a band-pass filter with a peak frequency of about 2,5 Hz. However, the gap junctions between adjacent rods exhibited linearity and voltage independency within the physiological range of rods. These gap junctions did not contribute to the filtering mechanisms of the rod network. Combined with the computational modelling, our data suggest that the filtering of higher frequency rod signals by the network is largely mediated by the passive resistive and capacitive (RC) properties of rod plasma membranes. Furthermore, we found several attributes of rod electrical coupling resembling the physiological properties of gene-encoded Cx35/36 gap junctions examined in other in vitro studies. This indicates that the previously found Cx35/36 expression in the salamander rod network may be functionally involved in rod,rod electrical coupling. [source] Living with an active starASTRONOMY & GEOPHYSICS, Issue 3 2001Andy Breen Observations have shown that the Sun is far from being a stable, unchanging object. Rather, we live within the outer atmosphere of a variable star. Andy Breen presents a summary of a meeting that drew together new results from observations and computational modelling of the Sun, interplanetary space and the upper atmosphere of the Earth. [source] Trianglamines,Readily Prepared, Conformationally Flexible Inclusion-Forming Chiral HexaminesCHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2006Jacek Gawronski Prof. Dr. Abstract Trianglamines, macrocyclic heteraphanes, were readily synthesised through a [3+3] cyclocondensation of (R,R)-1,2-diaminocyclohexane with terephthalaldehyde, followed by NaBH4 reduction and N-alkylation. The macrocyclic ring shows a remarkable ability to change its conformation, as a consequence of rotation about the CN bonds or nitrogen inversion due to protonation or N-alkylation, as revealed by circular dichroism spectra, computational modelling and X-ray diffraction analysis. The flexible natures of the trianglamine macrocycles allow ready accommodation of a variety of guest molecules to form crystalline inclusion complexes of highly diversified interpenetrating structures. [source] SPATIAL AND TEMPORAL ASPECTS OF cAMP SIGNALLING IN CARDIAC MYOCYTESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2008Radu V Iancu SUMMARY 1,1 -Adrenoceptor and M2 muscarinic receptor regulation of cAMP production plays a pivotal role in autonomic regulation of cardiac myocyte function. However, not all responses are easily explained by a uniform increase or decrease in cAMP activity throughout the entire cell. 2Adenovirus expression of fluorescence resonance energy transfer (FRET)-based biosensors can be used to monitor cAMP activity in protein kinase A (PKA) signalling domains, as well as the bulk cytoplasmic domain of intact adult cardiac myocytes. 3Data obtained using FRET-based biosensors expressed in different cellular microdomains have been used to develop a computational model of compartmentalized cAMP signalling. 4A systems biology approach that uses quantitative computational modelling together with experimental data obtained using FRET-based biosensors has been used to provide evidence for the idea that compartmentation of cAMP signalling is necessary to explain the stimulatory responses to ,1 -adrenoceptor activation as well as the complex temporal responses to M2 muscarinic receptor activation. [source] | |||||||||||||||||||