Transduction Coefficients Research Articles

Predicted structure and cell signaling of TAS2R14 reveal receptor hyper-flexibility for detecting diverse bitter tastes

The 25 human bitter taste receptors (TAS2Rs) are expressed on taste and extra-oral cells representing an integrated chemosensory system. The archetypal TAS2R14 is activated by>150 topographically diverse agonists, raising the question of how this uncharacteristic accommodation is achieved for these GPCRs. We report the computationally derived structure of TAS2R14 with binding sites and energies for five highly diverse agonists. Remarkably, the binding pocket is the same for all five agonists. The energies derived from molecular dynamics are consistent with experiments determining signal transduction coefficients in livecells. TAS2R14 accommodates agonists through the breaking of a TMD3 H-bond instead of the prototypic strong salt bridge, a TMD1,2,7 interaction different from Class A GPCRs, and agonist-promoted TMD3 salt bridges for high affinity (which we confirmed by receptor mutagenesis). Thus, the broadly tuned TAS2Rs accommodate diverse agonists via a single (vs multiple) binding pocket through unique TM interactions for sensing disparate micro-environments.

Structure with thin SiOx/SiNx bilayer and Al electrodes for high-frequency, large-coupling, and low-cost surface acoustic wave devices

With the development of fifth-generation wireless systems, the Internet of Things, and health services, surface acoustic wave (SAW)-based filters and sensors have attracted considerable interest. This study presents a new structure for high-frequency, large-coupling, and low-cost SAW devices that helps implement high-frequency and wideband filters and enhances the sensitivity of sensors. The structure is based on 15°Y-X LiNbO3, thin SiOx/SiNx bilayer overlay, and Al electrodes. Furthermore, a low-cost fabrication process for SAW devices based on this structure was designed. Simulation and experimental results show that the bilayer substantially weakens the leaky nature of shear-horizontal-type SAWs with a phase velocity higher than that of a slow-shear bulk wave in LiNbO3. Thus, the limitation related to the velocity of 4029 m/s was overcome, and the phase velocity reached approximately 4500 m/s, which means an increase of 50% compared with that of conventional Cu/15°Y-X LiNbO3 devices. Consequently, the frequency dramatically increases, and the quality of the SAW response is ensured. Simultaneously, a large electromechanical coupling factor close to 20% can be achieved, which is still suitable for wideband filters and sensors with high energy transduction coefficients. This new structure is expected to become a major candidate for SAW devices in the future.

Scaling laws of electromagnetic and piezoelectric seismic vibration energy harvesters built from discrete components

This paper presents a theoretical study on the scaling laws of electromagnetic and piezoelectric seismic vibration energy harvesters, which are assembled from discrete components. The scaling laws are therefore derived for the so called meso-scale range, which is typical of devices built from distinct elements. Isotropic scaling is considered for both harvesters such that the shape of the components and of the whole transducers do not change with scaling. The scaling analyses are restricted to the case of linearly elastic seismic transducers subject to tonal ambient vibrations at their fundamental natural frequency, where the energy harvesting is particularly effective. Both resistive-reactive and resistive optimal electric harvesting loads are considered. The study is based on equivalent formulations for the response and power harvesting of the two transducers, which employ the so called electromagnetic and piezoelectric power transduction factors, Πcm2 and Πpe2. The scaling laws of the transduction coefficients and electrical and mechanical parameters for the two transducers are first provided. A comprehensive comparative scaling analysis is then presented for the harvested power, for the power harvesting efficiency and for the stroke of the two harvesters. Particular attention is dedicated to the scaling laws for the dissipative effects in the two harvesters, that is the Couette air losses and eddy currents losses that develop in the electromagnetic harvester and the material, air and dielectric losses that arise in the piezoelectric harvester. The scaling laws emerged from the study, are thoroughly examined and interpreted with respect to equivalent mechanical effects produced by the harvesting loads.

A composite approach boosts transduction coefficients of piezoceramics for energy harvesting

Piezoelectric energy harvesting is a hotspot in the field of new energy, the core goal of which is to prepare piezoceramics with a high transduction coefficient (d33×g33). The traditional solid–solution design strategy usually causes the same variation trend of d33 and εr, resulting in a low d33×g33 value. In this work, a composite design strategy was proposed that uses PZN–PZT/ZnAl2O4 as an example. By introducing ZnAl2O4, which is nonferroelectric with low εr, to the PZN–PZT piezoelectric matrix, εr decreased rapidly while d33 remained relatively stable. This behavior was ascribed to the increase of Q33 caused by an interfacial effect facilitating the formation of micro-domain structure.

A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses

Compelling data in the literature from the recent years leave no doubt about the pluridimensional nature of G protein-coupled receptor function and the fact that some ligands can couple with different efficacies to the multiple pathways that a receptor can signal through, a phenomenon most commonly known as functional selectivity or biased agonism. Nowadays, transduction coefficients (log(τ/KA)), based on the Black and Leff operational model of agonism, are widely used to calculate bias. Nevertheless, combining both affinity and efficacy in a single parameter can result in compounds showing a defined calculated bias of one pathway over other though displaying varying experimental bias preferences. In this paper, we present a novel scale (log(τ)), that attempts to give extra substance to different compound profiles in order to better classify compounds and quantify their bias. The efficacy-driven log(τ) scale is not proposed as an alternative to the affinity&efficacy-driven log(τ/KA) scale but as a complement in those situations where partial agonism is present. Both theoretical and practical approaches using μ-opioid receptor agonists are presented.

Reciprocity of linear systems with smart materials utilized for precise measurement techniques

In electromechanical measurement techniques, passive transducers and passive electrical networks often interact. In some applications, continua are considered as part of the system, where fields are formed and waves are propagated. In this article, networks, continua, and electromechanical transducers feature sufficient amplitude linear behavior in their environment (e.g. for operation around a bias) and are reciprocal. In addition, all elements of the system have constant parameters during the measurement. Then, the skillful application of the inherent reciprocity of these systems can lead to surprisingly useful benefits. This is shown by actual examples from metrology. The examples include the precise determination of transduction coefficients. It is also shown how the linearity of a system is checked by utilizing reciprocity relations. Although the facts of the matter are well known, its potential is often overlooked or disregarded in measurement techniques.

Gaddum Memorial Lecture 2014: receptors as an evolving concept: from switches to biased microprocessors.

This review is based on the JR Vane Medal Lecture presented at the BPS Winter Meeting in December 2014 by T. Kenakin. A recording of the lecture is included as supporting information and can also be viewed online here: https://www.youtube.com/watch?v=xrP81AQ8l-8. Pharmacological models used to describe drug agonism and antagonism have evolved over the past 20 years from a parsimonious model describing single active and inactive receptor states to models of multiconformational receptor systems modified by ligand conformational selection. These latter models describe the observed, presently underexploited, pharmacological mechanism of ligand-directed biased signalling. Biased signals can be quantified with transduction coefficients (ΔΔLog(τ/KA) values), a scale grounded in the Black/Leff operational model; this enables the optimization of biased profiles through medicinal chemistry. The past decades have also brought the availability of new technologies to measure multiple functional effects mediated by seven transmembrane receptors. These have confirmed that drugs can have many efficacies, which may be collaterally linked, that is there is no linear sequence of activities required. In addition, new functional screening assays have introduced increasing numbers of allosteric ligands into drug discovery. These molecules are permissive (they do not necessarily preclude endogenous signalling in vivo); therefore, they may allow better fine tuning of pathological physiology. The permissive quality of allosteric ligands can also change the quality of endogenous signalling efficacy ('induced bias') as well as the quantity of signal; in this regard, indices related to ΔΔLog(τ/KA) values (namely ΔLog(αβ) values) can be used to quantify these effects for optimization in the drug discovery process. All of these added scales of drug activity will, hopefully, allow better targeting of candidate molecules towards therapies.

Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor.

Comprehensive studies that consolidate selective ligands, quantitative comparisons of G protein versus arrestin-2/3 coupling, together with structure-activity relationship models for G protein-coupled receptor (GPCR) systems are less commonly employed. Here we examine biased signaling at the nociceptin/orphanin FQ opioid receptor (NOPR), the most recently identified member of the opioid receptor family. Using real-time, live-cell assays, we identified the signaling profiles of several NOPR-selective ligands in upstream GPCR signaling (G protein and arrestin pathways) to determine their relative transduction coefficients and signaling bias. Complementing this analysis, we designed novel ligands on the basis of NOPR antagonist J-113,397 [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] to explore structure-activity relationships. Our study shows that NOPR is capable of biased signaling, and further, the NOPR selective ligands MCOPPB [1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-(3R)-3-piperidinyl-1H-benzimidazole trihydrochloride] and NNC 63-0532 [8-(1-naphthalenylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-3-acetic acid, methyl ester] are G protein-biased agonists. Additionally, minor structural modification of J-113,397 can dramatically shift signaling from antagonist to partial agonist activity. We explore these findings with in silico modeling of binding poses. This work is the first to demonstrate functional selectivity and identification of biased ligands at the nociceptin opioid receptor.

Theoretical modeling and equivalent electric circuit of a bimorph piezoelectric micromachined ultrasonic transducer

An electric circuit model for a circular bimorph piezoelectric micromachined ultrasonic transducer (PMUT) was developed for the first time. The model was made up of an electric mesh, which was coupled to a mechanical mesh via a transformer element. The bimorph PMUT consisted of two piezoelectric layers of the same material, having equal thicknesses, and sandwiched between three thin electrodes. The piezoelectric layers, having the same poling axis, were biased with electric potentials of the same magnitude but opposite polarity. The strain mismatches between the two layers created by the converse piezoelectric effect caused the membrane to vibrate and, hence, transmit a pressure wave. Upon receiving the echo of the acoustic wave, the membrane deformation led to the generation of electric charges as a result of the direct piezoelectric phenomenon. The membrane angular velocity and electric current were related to the applied electric field, the impinging acoustic pressure, and the moment at the edge of the membrane using two canonical equations. The transduction coefficients from the electrical to the mechanical domain and vice-versa were shown to be bilateral and the system was shown to be reversible. The circuit parameters of the derived model were extracted, including the transformer ratio, the clamped electric impedance, the spring-softening impedance, and the open-circuit mechanical impedance. The theoretical model was fully examined by generating the electrical input impedance and average plate displacement curves versus frequency under both air and water loading conditions. A PMUT composed of piezoelectric material with a lossy dielectric was also investigated and the maximum possible electroacoustical conversion efficiency was calculated.

Acoustic meta-materials in MEMS BAW resonators

This paper presents a meta-material-based design method for bulk acoustic wave (BAW) resonators with enhanced characteristics compared to those obtained with the typical bulk material implementation. We demonstrate the novel use of empty inclusions (i.e., ‘holes’) in bulk materials for engineering their acoustic (mechanical) properties (e.g. Young’s modulus E, Poisson’s ratio ν and mass density ρ) to tune and achieve optimal acoustical performance/characteristics. Inclusions have been demonstrated before to produce phononic band gaps for wave trapping. We focus on the propagation characteristics of the meta-materials brought into being by these inclusions. We implement patterns of holes with different sizes and distributions, to effectively scatter acoustic waves in bar-type BAW resonators and to devise the desired resonator properties, e.g., the resonant frequency. While the available bulk material is homogeneous and isotropic, the bar consists of an equivalent non-homogeneous material that can for example be distributed by design in order to shrink the overall resonator size, enhance electromechanical transduction coefficients or reject spurious modes. Our paper compares two extraction methods for the equivalent material properties of a periodically hole-punched material: the steady-state mechanical simulation of a unit cell and its ‘phase delay’ counterpart. We discuss their validity and practical use for the design of bar resonators.

Acoustic waves guided by a fluid layer on a piezoelectric substrate

This paper theoretically studies the propagation and the generation of leaky acoustic waves in a fluid layer enclosed between the half-infinite YZ-LiNbO3 (lithium niobate) substrate coated with a thin SiO2 (silicone dioxide) layer and the half-infinite domain occupied by silicone rubber. The plane wave spectrum in the structure is computed, and the specific features of the behavior of the real and imaginary parts of the leaky wave velocity depending on the fluid layer thickness and the electric boundary conditions are analyzed. Besides, the numerical estimations are made of the coupling-of-mode (COM) parameters describing a periodic grating deposited on the LiNbO3 substrate under the SiO2 layer. The dependence of the COM parameters is investigated on characteristics and conditions specifying the structure, such as the fluid layer thickness, the SiO2 coating thickness, and the presence or the absence of projections on the SiO2 coating face in contact with the fluid. In particular, it is found that the reflection and the transduction coefficients remain high enough even when the fluid layer is several wavelengths thick provided that the frequency is close to the value f0=vl0′∕2p, where vl0′ is the real leaky wave velocity at the zeroth thickness of the fluid layer and p is the grating period. It is also found that projections on the SiO2-fluid interface significantly increase the reflection coefficient.

Extraction of all coefficients of coupled-mode equations for natural, single-phase, unidirectional SAW transducers from dispersion characteristics computed by hybrid finite element method.

A numerical method is presented for determining all of the coefficients of coupled-mode equations for natural, single-phase, unidirectional SAW transducers (NSP-UDTs). Substituting numerical results computed by the hybrid finite element method for infinite NSPUDTs with shorted and open electric ports into several relations derived from the coupled-mode theory, we can determine all of the coefficients. Specifically, the edge frequencies of a stop-band and the static capacitances yield the self-coupling coefficients and the amplitudes of mutual-coupling and transduction coefficients, and the electric potential standing wave on the substrate surface, which can be derived from the projection of the standing wave distributions of particle displacements and electric potential in the whole substrate onto the set of those predicted by the coupled-mode theory, yields the phases of mutual-coupling and transduction coefficients. NSPUDTs on ST-25 degrees X quartz, Y-51.25 degrees Z LiTaO3, and 50 degrees Y-25 degrees X La3Ga5SiO14 substrates are investigated. Our results agree well with the earlier experimental ones.

Analysis of an Electrode-Width-Difference-Reversal-of-Directivity Transducer on a La3Ga5.5Nb0.5O14 Substrate

The parameters included in coupling-of-modes equations such as coupling coefficients, transduction coefficients and electrostatic capacitances are theoretically determined for an electrode-width-difference-reversal-of-directivity transducer (EWD-RDT) on a La3Ga5.5Nb0.5O14 substrate with Euler angles of (108°, 148°, 144°). In the hybrid finite-element method (HFEM), used for determining these parameters, all the effects of anisotropy of the substrate, piezoelectric perturbation, mechanical perturbation and energy storage are taken into account. Numerical results for the frequency characteristics of insertion loss and for the directivity are compared to the experimental data, and the validity and usefulness of the present method are demonstrated. Furthermore, the electrode height dependence of the parameters and the directivity of EWD-RDT are investigated in detail.

Parameters of Coupling-of-Modes Equations for a Natural Single-Phase-Unidirectional Transducer on a La3Ga5.5Nb0.5O14 Substrate

Parameters included in coupling-of-modes equations such as coupling coefficients, transduction coefficients and electrostatic capacitances are theoretically determined for a natural single-phase unidirectional transducer (NSPUDT) on a La3Ga5.5Nb0.5O14 substrate with Euler angles of (110°, 145°, 145°) and an electromechanical coupling coefficient larger than quartz. In the hybrid finite-element method (HFEM), used for determining these parameters, all the effects of anisotropy of the substrate, piezoelectric perturbation, mechanical perturbation and energy storage are taken into account. The electrode thickness and width dependence of the parameters and the excitation characteristics of NSPUDT are investigated in detail. The parameters obtained by the present method are compared with those obtained by the perturbation method. Furthermore, numerical results for the frequency characteristics of NSPUDT are compared to the experimental data, and the validity and usefulness of the present method are demonstrated.

A Design of Surface Acoustic Wave Wideband Single-Phase-Unidirectional Transducers Using Coupling-of-Modes Theory

To realize wideband surface acoustic wave (SAW) filters, a weighted single-phase-unidirectional transducer (SPUDT) has been analyzed by direct numerical analysis of the coupling-of-modes equations. It was found that the directivity was obtained over a wide frequency range when the reflection coefficient of the SPUDT was weighted using a sinc function in order to distribute the positive and negative reflection elements into the SPUDT; this was called a wideband SPUDT. This paper also describes a high-performance wideband SPUDT, with both the reflection and transduction coefficients weighted on 128°Y-X LiNbO3 substrates, and a new wideband natural-SPUDT (NSPUDT) on 50°Y-23°X La3Ga5SiO14 substrates, which has recently attracted much attention for intermediate frequency (IF) SAW filters.

An Analysis of Surface-Acoustic-Wave Devices Using Coupling-of-Mode Theory and Finite-Element Method

A coupling-of-mode theory is described for the analysis of excitation characteristics of interdigital transducers (IDT) for surface acoustic waves (SAW) and of reflection characteristics of SAW gratings. Coupling and transduction coefficients of coupled mode equations can be theoretically determined by applying the finite-element method (FEM) to an infinite array corresponding to an electrically shorted or open IDT. The FEM is also used to calculate the static capacitance for one pair of IDTs. Examples are computed for various types of IDTs and metallic gratings on a 128° Y-X LiNbO3 substrate.

An Analysis of Excitation Characteristics of Interdigital Transducers for Surface Acoustic Waves

An equivalent network theory and a coupled mode theory are described for the analysis of excitation characteristics of interdigital transducers (IDT) for surface acoustic waves. Circuit parameters of equivalent circuits and coupling and transduction coefficients of coupled mode equations can be theoretically determined by applying the finite-element method to an infinite array corresponding to an electrically shorted or open IDT. Examples are computed for two types of IDTs fabricated on a 128° Y-X LiNbO3 substrate. One is a uniform type of IDT and the other is a single-phase unidirectional transducer utilizing internal floating electrodes.

Symmetry in the Equations for Electromechanical Coupling

The conventional forms of the electromechanical coupling equations exhibit symmetry for electrostatic coupling and antisymmetry for electromagnetic coupling, or vice versa. Both types of coupling can be represented in symmetrical form, however, if the transduction coefficient for electromagnetic coupling includes a space-operator k that embodies the sign convention associated with axial vectors. The same kind of conventional electric network representations can then be used for either type of coupling. There is a sound physical basis for the appearance of a space-operator k in the transduction coefficients for electromagnetic systems in a manner completely symmetrical with the appearance of the time-phase operator j in electrostatic coupling. Violations of reciprocity in interconnected systems, as discussed by MacMillan and others, can be dealt with analytically in a straightforward way by observing that the operators k and j do not commute, i.e., kj = − jk. Antisymmetrical coupling terms arise in the equations for all-mechanical systems involving gyroscopes, just as in the electromagnetic case, but symmetry can be restored in these cases also by using the same kind of quaternionlike space-operator.