Differential voltage-dependent modulation of the ACh-gated K+ current by adenosine and acetylcholine

Inhibitory regulation of the heart is determined by both cholinergic M2 receptors (M2R) and adenosine A1 receptors (A1R) that activate the same signaling pathway, the ACh-gated inward rectifier K+ (KACh) channels via Gi/o proteins. Previously, we have shown that the agonist-specific voltage sensitivity of M2R underlies several voltage-dependent features of IKACh, including the ‘relaxation’ property, which is characterized by a gradual increase or decrease of the current when cardiomyocytes are stepped to hyperpolarized or depolarized voltages, respectively. However, it is unknown whether membrane potential also affects A1R and how this could impact IKACh. Upon recording whole-cell currents of guinea-pig cardiomyocytes, we found that stimulation of the A1R-Gi/o-IKACh pathway with adenosine only caused a very slight voltage dependence in concentration-response relationships (~1.2-fold EC50 increase with depolarization) that was not manifested in the relative affinity, as estimated by the current deactivation kinetics (τ = 4074 ± 214 ms at -100 mV and τ = 4331 ± 341 ms at +30 mV; P = 0.31). Moreover, IKACh did not exhibit relaxation. Contrarily, activation of the M2R-Gi/o-IKACh pathway with acetylcholine induced the typical relaxation of the current, which correlated with the clear voltage-dependent effect observed in the concentration-response curves (~2.8-fold EC50 increase with depolarization) and in the IKACh deactivation kinetics (τ = 1762 ± 119 ms at -100 mV and τ = 1503 ± 160 ms at +30 mV; P = 0.01). Our findings further substantiate the hypothesis of the agonist-specific voltage dependence of GPCRs and that the IKACh relaxation is consequence of this property.

An analytic signal based accurate time-domain visco-acoustic wave equation from the Constant-Q theory

We present a concise time-domain wave equation to accurately simulate wave propagation in visco-acoustic media. The central idea behind this work is to dismiss the negative frequency components from a time-domain signal by converting the signal to its analytic format. The negative frequency components of any analytic signal are always zero, meaning we can construct the visco-acoustic wave equation to honor the relaxation property of the media for positive frequencies only. The newly proposed complex-valued wave equation (CWE) represents the wavefield with its analytic signal, whose real part is the desired physical wavefield, while the imaginary part is the Hilbert transform of the real component. Specifically, this CWE is accurate for both weak and strong attenuating media in terms of both dissipation and dispersion and the attenuation is precisely linear with respect to the frequencies. Besides, the CWE is easy and flexible to model dispersion-only, dissipation-only or dispersion-plus-dissipation seismic waves. We have verified these CWEs by comparing the results with analytical solutions, and achieved nearly perfect matching. Except for the homogeneous Q media, we have also extended the CWEs to heterogeneous media. The results of the CWEs for heterogeneous Q media are consistent with those computed from the nonstationary operator based Fourier Integral method and from the Standard Linear Solid (SLS) equations.

Modeling and Verification of Stress Relaxation Behavior of Ti-6Al-4V

The phenomenon of gradual decrease of internal stress with the deformation of material maintained under the precondition of certain temperature and initial stress or pre-strain is called stress relaxation. Due to that, the flow stress of the metal material falls rapidly when the hot forming process pauses, and then the required forming load. In this paper, the experiment was carried out to study the stress relaxation property of Ti-6Al-4V, in the temperature range of 1023K~1123K and with the pre-tension strain 0.7%, 4% and 10%. The quartic delay function was used to describe the stress relaxation behavior. The predicted value of stress relaxation equation is in good agreement with the experimental data, and the correlation coefficient is above 0.99. Arrhenius creep constitutive equation embedded in CAE software was derived. The finite element model of stress relaxation process of test bar was builded, and the tensile-relaxation experiment was performed under the loading condition of 1:1 part forming process. The forming force results agree well, and the validity and accuracy of the constitutive model are verified, laying a foundation for the subsequent process simulation and optimization.

Left ventricular vortex and intraventricular pressure difference in dogs under various loading conditions

Restrictions on the conventional evaluation of diastolic function have been recognized, especially under various loading conditions. Recently, new noninvasive ventricular vortex indexes have been introduced and are expected to reflect the cardiac function. Physiologically, there is a hypothesis that the intraventricular pressure difference (IVPD) is related to the formation of vortexes. IVPD and vortex indexes were simultaneously measured, and the relationship between the two was investigated. To verify the possibility of diastolic vorticity as an index of diastolic relaxation, a correlation between diastolic vorticity and the load dependency of vorticity [time constant (τ)] was examined. Six healthy dogs were studied using transthoracic echocardiography, pressure, and a conductance catheter. Vorticity was analyzed using vector flow mapping (VFM). IVPD was determined using Euler’s equation with color M-mode Doppler images. Data were obtained at baseline, at balloon dilatation in the thoracic aorta to alter afterload, at hydroxyethyl starch infusion to alter preload, and at milrinone administration to alter ventricular relaxation. Peak vorticity at early diastole (E-Vor) and IVPD of the midventricle (MIVPD) decreased under pressure loading, were unchanged under volume loading, and increased during milrinone administration. In multivariate analysis, the independent predictors of τ were global longitudinal strain, strain rate at early diastole, and E-Vor. MIVPD was strongly correlated with E-Vor ( r = 0.84). VFM-derived peak E vorticity was strongly related to IVPD, especially MIVPD, under various loading conditions. Both of these novel indexes are promising as reliable indexes of ventricular relaxation, independent from preload. NEW & NOTEWORTHY We showed the close relationship of vortex and intraventricular pressure difference and showed that both of them can become new markers of the left ventricular relaxation property. Our present study creates a paradigm for future studies in the field of intraventircular flow physiology and clinical diastology.

Frequency-dependent dielectric properties of sodium silicate

The dielectric properties of sodium silicate (Na2SiO3) (SS) have been investigated in a wide range of frequencies and temperatures. A strong dielectric dispersion is found to exist in low-frequency region. The frequency-dependent dielectric properties of SS follow the universal dynamic response proposed by Jonscher. The measured dielectric data strongly depends on dielectric dispersion and controls the basic relaxation property. However, the parameters that control the frequency-dependent dielectric properties such as coupling of ions or polarizability are found to have peak values at the frozen out condition or critical point.