Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors

Rogue waves in opposing currents: an experimental study on deterministic and stochastic wave trains

Interaction with an opposing current amplifies wave modulation and accelerates nonlinear wave focusing in regular wavepackets. This results in large-amplitude waves, usually known as rogue waves, even if the wave conditions are less prone to extremes. Laboratory experiments in three independent facilities are presented here to assess the role of opposing currents in changing the statistical properties of unidirectional and directional mechanically generated random wavefields. The results demonstrate in a consistent and robust manner that opposing currents induce a sharp and rapid transition from weakly to strongly non-Gaussian properties. This is associated with a substantial increase in the probability of occurrence of rogue waves for unidirectional and directional sea states, for which the occurrence of extreme and rogue waves is normally the least expected

Wave Response of a Monocolumn Platform with a Skirt Using CFD and Experimental Approaches

This paper aims to investigate the nonlinear motion characteristics of a monocolumn type floater with skirts numerically and experimentally. Wave calibration, free decay, and regular wave tests were simulated using a computational fluid dynamics (CFD) code OpenFOAM. The experiments were carried out in a wave tank to validate the CFD results. First, wave calibration tests were performed to investigate wave generation, development, propagation, and absorption in the numerical wave tank. Second, the simulation input parameters were calibrated to reproduce the waves generated in the tank experiment. Third, free decay tests of heave and pitch were conducted to examine the natural period and the linear and quadratic damping of the floater. A verification and validation study was performed using experimental data for free decay tests. Finally, regular wave tests were performed to investigate the motion characteristics of the floater. The results were processed to obtain the response amplitude operator (RAO) for the heave and pitch motions. The RAOs of the floater was compared with the experimental data and numerical simulations based on the linear potential theory code WAMIT to investigate the performance of the CFD simulations. The comparisons made in this work showed the potential of the CFD method to reproduce the motion characteristics of a shallow-draft floating object with a skirt in waves and to visualize the nonlinear phenomena behind the oscillation of the floating object

Wave Response of a Monocolumn Platform with a Skirt Using CFD and Experimental Approaches

This paper aims to investigate the nonlinear motion characteristics of a monocolumn type floater with skirts numerically and experimentally. Wave calibration, free decay, and regular wave tests were simulated using a computational fluid dynamics (CFD) code OpenFOAM. The experiments were carried out in a wave tank to validate the CFD results. First, wave calibration tests were performed to investigate wave generation, development, propagation, and absorption in the numerical wave tank. Second, the simulation input parameters were calibrated to reproduce the waves generated in the tank experiment. Third, free decay tests of heave and pitch were conducted to examine the natural period and the linear and quadratic damping of the floater. A verification and validation study was performed using experimental data for free decay tests. Finally, regular wave tests were performed to investigate the motion characteristics of the floater. The results were processed to obtain the response amplitude operator (RAO) for the heave and pitch motions. The RAOs of the floater was compared with the experimental data and numerical simulations based on the linear potential theory code WAMIT to investigate the performance of the CFD simulations. The comparisons made in this work showed the potential of the CFD method to reproduce the motion characteristics of a shallow-draft floating object with a skirt in waves and to visualize the nonlinear phenomena behind the oscillation of the floating object

Stereo Reconstruction Method for 3D Surface Wave Fields around a Floating Body Using a Marker Net in a Wave Tank

Spatial wave fields around floating bodies are important for the understanding of hydrodynamics, and particularly the wave drift forces, of floating bodies in waves; however, experimental measurement of these fields is challenging. This paper presents a stereo reconstruction method for three-dimensional (3D) surface wave fields around floating bodies in a wave tank. Styrofoam markers were attached to a flexible net in a regular grid, called a marker net, and were placed on the water surface to be used as targets for stereo cameras (SCs). A thin plate spline was applied to the markers detected by the SCs to reconstruct the 3D surface wave profile around a floating body model. The proposed method was validated by measuring the wave field around a cylindrical floating body with a footing at its bottom. These experiments were conducted under regular wave incidence conditions. A wave elevation time series measured using a servo-controlled wave gauge was used as the benchmark data. The 3D surface wave field reconstruction method was applied under three different conditions: without the model, with a fixed model, and with a freely oscillating model. The results showed reliable reconstructions of the scattering and radiation waves. The marker net’s effects on the floating body’s motion and the surrounding wave fields were shown to be negligible by comparing the results acquired with and without the marker net

Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor.

In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is constituted of the three distinct opioid receptors (namely delta-, mu- and kappa-subtypes) and the receptor for nociceptin (also designated orphaninFQ). The members of the opioid receptor subfamily were known to mediate a variety of cellular inhibitory effects. The three opioid receptors are known to play central roles in mediating analgesia and many other physiological activities; however, the nociceptin receptor was identified recently and less is known about its physiological roles. Here we report the generation and characterization of mice lacking the nociceptin receptor. The knockout mice showed no significant differences in nociceptive threshold and locomotor activity compared with control mice, but they lost nociceptin-induced behavioral responses. These results indicate that the nociceptin system is not essential for regulation of nociception or locomotor activity. On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system

Excitation of rogue waves in a variable medium:An experimental study on the interaction of water waves and currents

We show experimentally that a stable wave propagating into a region characterized by an opposite current may become modulationally unstable. Experiments have been performed in two independent wave tank facilities; both of them are equipped with a wavemaker and a pump for generating a current propagating in the opposite direction with respect to the waves. The experimental results support a recent conjecture based on a current-modified nonlinear Schrödinger equation which establishes that rogue waves can be triggered by a nonhomogeneous current characterized by a negative horizontal velocity gradient