MODELING OF PROTEIN INTERACTIONS INVOLVED IN CARDIAC TENSION DEVELOPMENT

2003 ◽  
Vol 13 (12) ◽  
pp. 3561-3578 ◽  
Author(s):  
F. B. SACHSE ◽  
K. G. GLÄNZEL ◽  
G. SEEMANN
Keyword(s):  
Steady State ◽  
Numerical Simulations ◽  
Intracellular Calcium ◽  
Hybrid Model ◽  
Protein Interactions ◽  
Experimental Studies ◽  
Quantitative Agreement ◽  
Tension Development ◽  
Cross Bridge ◽  
Configuration Changes

Modeling of protein interactions responsible for cardiac tension development can enhance the understanding of physiological and pathophysiological phenomena of the heart. Principal components of muscular tension development are the proteins actin, myosin, troponin and tropomyosin. The tension is produced by cross-bridge cycling of actin and myosin using adenosine triphosphate as energy source. The cross-bridge cycling is initiated by binding of intracellular calcium to troponin, resulting in configuration changes of tropomyosin. In this work a hybrid model of protein interactions in cardiac tension development is derived on basis of recent measurements and descriptions on protein level. Dependencies on intracellular calcium concentration, sarcomere stretch and stretch velocity as well as cooperativity mechanisms are incorporated. The model quantifies the tension development by states associated to configurations of the involved proteins. The model enables in conjunction with electrophysiological models of cardiac myocytes the reconstruction of electro-mechanical phenomena. Numerical simulations with the hybrid model were performed, which illustrated the reconstruction of steady state and length switches experiments. The steady state experiments describe the force-cytosolic [ Ca 2+] relationship in intact rat cardiac trabeculae. The length switch experiments provide data on the redevelopment of force after sudden stretch in rabbit right ventricular papillary muscles. Results of the numerical simulations show quantitative agreement with experimental studies. The hybrid model of cardiac tension development offers interfaces to further models of cardiac electro-mechanics. The hybrid model can be coupled with models of cellular electrophysiology and passive mechanics of myocardium allowing the inclusion of mechano-electrical feedback mechanisms. The hybrid model can be applied to elucidate cooperativity mechanisms, pathophysiological changes and metabolism of tension development.

A Consistent Implementation of Inelastic Material Models into Steady State Rolling

2016 ◽  
Vol 44 (3) ◽  
pp. 174-190 ◽  
Author(s):  
Mario A. Garcia ◽  
Michael Kaliske ◽  
Jin Wang ◽  
Grama Bhashyam
Keyword(s):  
Steady State ◽  
Numerical Simulations ◽  
Viscoelastic Material ◽  
Rolling Contact ◽  
Arbitrary Lagrangian Eulerian ◽  
Ale Formulation ◽  
Inelastic Material ◽  
Material Formulation ◽  
Steady State Rolling ◽  
Efficient Alternative

ABSTRACT Rolling contact is an important aspect in tire design, and reliable numerical simulations are required in order to improve the tire layout, performance, and safety. This includes the consideration of as many significant characteristics of the materials as possible. An example is found in the nonlinear and inelastic properties of the rubber compounds. For numerical simulations of tires, steady state rolling is an efficient alternative to standard transient analyses, and this work makes use of an Arbitrary Lagrangian Eulerian (ALE) formulation for the computation of the inertia contribution. Since the reference configuration is neither attached to the material nor fixed in space, handling history variables of inelastic materials becomes a complex task. A standard viscoelastic material approach is implemented. In the inelastic steady state rolling case, one location in the cross-section depends on all material locations on its circumferential ring. A consistent linearization is formulated taking into account the contribution of all finite elements connected in the hoop direction. As an outcome of this approach, the number of nonzero values in the general stiffness matrix increases, producing a more populated matrix that has to be solved. This implementation is done in the commercial finite element code ANSYS. Numerical results confirm the reliability and capabilities of the linearization for the steady state viscoelastic material formulation. A discussion on the results obtained, important remarks, and an outlook on further research conclude this work.

Mapping of Protein-Protein Interactions: Web-Based Resources for Revealing Interactomes

2019 ◽  
Vol 26 (21) ◽  
pp. 3890-3910 ◽  
Author(s):  
Branislava Gemovic ◽  
Neven Sumonja ◽  
Radoslav Davidovic ◽  
Vladimir Perovic ◽  
Nevena Veljkovic
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Experimental Studies ◽  
Protein Protein Interactions ◽  
Web Based ◽  
Prediction Tools ◽  
Physiological Processes ◽  
Modern Drug ◽  
Ppi Prediction

Background: The significant number of protein-protein interactions (PPIs) discovered by harnessing concomitant advances in the fields of sequencing, crystallography, spectrometry and two-hybrid screening suggests astonishing prospects for remodelling drug discovery. The PPI space which includes up to 650 000 entities is a remarkable reservoir of potential therapeutic targets for every human disease. In order to allow modern drug discovery programs to leverage this, we should be able to discern complete PPI maps associated with a specific disorder and corresponding normal physiology. Objective: Here, we will review community available computational programs for predicting PPIs and web-based resources for storing experimentally annotated interactions. Methods: We compared the capacities of prediction tools: iLoops, Struck2Net, HOMCOS, COTH, PrePPI, InterPreTS and PRISM to predict recently discovered protein interactions. Results: We described sequence-based and structure-based PPI prediction tools and addressed their peculiarities. Additionally, since the usefulness of prediction algorithms critically depends on the quality and quantity of the experimental data they are built on; we extensively discussed community resources for protein interactions. We focused on the active and recently updated primary and secondary PPI databases, repositories specialized to the subject or species, as well as databases that include both experimental and predicted PPIs. Conclusion: PPI complexes are the basis of important physiological processes and therefore, possible targets for cell-penetrating ligands. Reliable computational PPI predictions can speed up new target discoveries through prioritization of therapeutically relevant protein–protein complexes for experimental studies.

Prediction of Disease Comorbidity Using HeteSim Scores based on Multiple Heterogeneous Networks

2019 ◽  
Vol 19 (4) ◽  
pp. 232-241 ◽  
Author(s):  
Xuegong Chen ◽  
Wanwan Shi ◽  
Lei Deng
Keyword(s):  
Protein Interactions ◽  
Experimental Studies ◽  
Treatment Strategies ◽  
Computational Method ◽  
Biological Information ◽  
Support Vector ◽  
Protein Protein Interactions ◽  
Efficient Treatment ◽  
Disease Associations ◽  
Previous State

Background: Accumulating experimental studies have indicated that disease comorbidity causes additional pain to patients and leads to the failure of standard treatments compared to patients who have a single disease. Therefore, accurate prediction of potential comorbidity is essential to design more efficient treatment strategies. However, only a few disease comorbidities have been discovered in the clinic. Objective: In this work, we propose PCHS, an effective computational method for predicting disease comorbidity. Materials and Methods: We utilized the HeteSim measure to calculate the relatedness score for different disease pairs in the global heterogeneous network, which integrates six networks based on biological information, including disease-disease associations, drug-drug interactions, protein-protein interactions and associations among them. We built the prediction model using the Support Vector Machine (SVM) based on the HeteSim scores. Results and Conclusion: The results showed that PCHS performed significantly better than previous state-of-the-art approaches and achieved an AUC score of 0.90 in 10-fold cross-validation. Furthermore, some of our predictions have been verified in literatures, indicating the effectiveness of our method.

scholarly journals Spatiotemporal Patterns Formed by a Discrete Nutrient-Phytoplankton Model with Time Delay

Complexity ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Feifan Zhang ◽  
Wenjiao Zhou ◽  
Lei Yao ◽  
Xuanwen Wu ◽  
Huayong Zhang
Keyword(s):  
Steady State ◽  
Time Delay ◽  
Numerical Simulations ◽  
Functional Response ◽  
Bifurcation Analysis ◽  
Discrete Model ◽  
Continuous Model ◽  
Spatiotemporal Patterns ◽  
Homogeneous Steady State ◽  
Simulation Results

In this research, a continuous nutrient-phytoplankton model with time delay and Michaelis–Menten functional response is discretized to a spatiotemporal discrete model. Around the homogeneous steady state of the discrete model, Neimark–Sacker bifurcation and Turing bifurcation analysis are investigated. Based on the bifurcation analysis, numerical simulations are carried out on the formation of spatiotemporal patterns. Simulation results show that the diffusion of phytoplankton and nutrients can induce the formation of Turing-like patterns, while time delay can also induce the formation of cloud-like pattern by Neimark–Sacker bifurcation. Compared with the results generated by the continuous model, more types of patterns are obtained and are compared with real observed patterns.

scholarly journals Magnetoactive elastomers for magnetically tunable vibrating sensor systems

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tatiana I. Becker ◽  
Yuriy L. Raikher ◽  
Oleg V. Stolbov ◽  
Valter Böhm ◽  
Klaus Zimmermann
Keyword(s):  
Magnetic Field ◽  
Steady State ◽  
Smart Materials ◽  
Excitation Frequency ◽  
Experimental Studies ◽  
Uniform Field ◽  
Sensor Systems ◽  
Ongoing Research ◽  
Amplification Ratio ◽  
Field Distortion

Abstract Magnetoactive elastomers (MAEs) are a special type of smart materials consisting of an elastic matrix with embedded microsized particles that are made of ferromagnetic materials with high or low coercivity. Due to their composition, such elastomers possess unique magnetic field-dependent material properties. The present paper compiles the results of investigations on MAEs towards an approach of their potential application as vibrating sensor elements with adaptable sensitivity. Starting with the model-based and experimental studies of the free vibrational behavior displayed by cantilevers made of MAEs, it is shown that the first bending eigenfrequency of the cantilevers depends strongly on the strength of an applied uniform magnetic field. The investigations of the forced vibration response of MAE beams subjected to in-plane kinematic excitation confirm the possibility of active magnetic control of the amplitude-frequency characteristics. With change of the uniform field strength, the MAE beam reveals different steady-state responses for the same excitation, and the resonance may occur at various ranges of the excitation frequency. Nonlinear dependencies of the amplification ratio on the excitation frequency are obtained for different magnitudes of the applied field. Furthermore, it is shown that the steady-state vibrations of MAE beams can be detected based on the magnetic field distortion. The field difference, which is measured simultaneously on the sides of a vibrating MAE beam, provides a signal with the same frequency as the excitation and an amplitude proportional to the amplitude of resulting vibrations. The presented prototype of the MAE-based vibrating unit with the field-controlled “configuration” can be implemented for realization of acceleration sensor systems with adaptable sensitivity. The ongoing research on MAEs is oriented to the use of other geometrical forms along with beams, e.g. two-dimensional structures such as membranes.

Vortex-Induced Vibrations of a Cylinder at Subcritical Reynolds Number

2011 ◽  
Author(s):  
Yoann Jus ◽  
Elisabeth Longatte ◽  
Jean-Camille Chassaing ◽  
Pierre Sagaut
Keyword(s):  
Reynolds Number ◽  
Numerical Simulations ◽  
Numerical Study ◽  
Damping Ratio ◽  
Experimental Studies ◽  
Cross Flow ◽  
Physical Analysis ◽  
Arbitrary Lagrangian Eulerian ◽  
Vortex Induced Vibrations ◽  
Low Mass

The present work focusses on the numerical study of Vortex-Induced Vibrations (VIV) of an elastically mounted cylinder in a cross flow at moderate Reynolds numbers. Low mass-damping experimental studies show that the dynamic behavior of the cylinder exhibits a three-branch response model, depending on the range of the reduced velocity. However, few numerical simulations deal with accurate computations of the VIV amplitudes at the lock-in upper branch of the bifurcation diagram. In this work, the dynamic response of the cylinder is investigated by means of three-dimensional Large Eddy Simulation (LES). An Arbitrary Lagrangian Eulerian framework is employed to account for fluid solid interface boundary motion and grid deformation. Numerous numerical simulations are performed at a Reynolds number of 3900 for both no damping and low-mass damping ratio and various reduced velocities. A detailed physical analysis is conducted to show how the present methodology is able to capture the different VIV responses.

Crashworthiness Performance of Mass-Efficient Extruded Structures

2002 ◽  
Author(s):  
Robert R. Mayer ◽  
Weigang Chen ◽  
Anil Sachdev
Keyword(s):  
Numerical Simulations ◽  
Single Cell ◽  
Experimental Testing ◽  
Experimental Studies ◽  
Nonlinear Material ◽  
Dynamic Strain ◽  
Cell Design ◽  
Explicit Finite Element ◽  
The One ◽  
Crushing Behavior

Theoretical, numerical and experimental studies were conducted on the axial crushing behavior of traditional single-cell and innovative four-cell extrusions. Two commercial aluminum alloys, 6061 and 6063, both with two tempers (T4 and T6), were considered in the study. Testing coupons taken from the extrusions assessed the nonlinear material properties. A theoretical solution was available for the one-cell design, and was developed for the mean crushing force of the four-cell section. Numerical simulations were carried out using the explicit finite element code LS-DYNA. The aluminum alloy 6063T4 was found to absorb less energy than 6061T4, for both the one-cell and four-cell configurations. Both 6061 and 6063 in the T6 temper were found to have significant fracture in the experimental testing. Theoretical analysis and numerical simulations predicted a greater number of folds for the four-cell design, as compared to the one-cell design, and this was confirmed in the experiments. The theoretical improvement in energy absorption of 57% for the four-cell in comparison with the one-cell design was confirmed by experiment. The good agreement between the theoretical, numerical and experimental results allows confidence in the application of the theoretical and numerical tools for both single-cell and innovative four-cell extrusions. It was also demonstrated that these materials have very little dynamic strain rate effect.

EFFECT OF WATER CURRENT ON UNDERWATER GLIDER VELOCITY AND RANGE

2016 ◽  
Vol 78 (10-4) ◽  
Author(s):  
Muhammad Yasar Javaid ◽  
Mark Ovinis ◽  
Fakhruldin Mohd Hashim ◽  
Adi Maimun ◽  
Yasser M. Ahmed ◽  
...  
Keyword(s):  
Steady State ◽  
Numerical Simulations ◽  
Relative Motion ◽  
Water Current ◽  
Underwater Glider ◽  
Water Currents ◽  
Effect Of Water ◽  
Actuation System ◽  
Autonomous Underwater Glider

An autonomous underwater glider speed and range is influenced by water currents. This is compounded by a weak actuation system for controlling its movement. In this work, the effects of water currents on the speed and range of an underwater glider at steady state glide conditions are investigated. Extensive numerical simulations have been performed to determine the speed and range of a glider with and without water current at different net buoyancies. The results show that the effect of water current on the glider speed and range depends on the current relative motion and direction. In the presence of water current, for a given glide angle, glide speed can be increased by increasing the net buoyancy of the glider.

scholarly journals Identification of the genomic mutation in Epha4rb-2J/rb-2J mice

Genome ◽  
2016 ◽  
Vol 59 (7) ◽  
pp. 439-448 ◽  
Author(s):  
Siti W. Mohd-Zin ◽  
Nor-Linda Abdullah ◽  
Aminah Abdullah ◽  
Nicholas D.E. Greene ◽  
Pike-See Cheah ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Tyrosine Kinases ◽  
Stop Codon ◽  
Cell Signalling ◽  
Experimental Studies ◽  
Premature Stop Codon ◽  
Mouse Mutant ◽  
Functional Studies ◽  
Base Pair Deletion ◽  
Numerous Cell

The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4rb-2J/rb-2J, is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or “hopping gait” phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4rb-2J corresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile α motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4rb-2J allele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein–protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype.

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