Dynein regulates Kv7.4 channel trafficking from the cell membrane.

The dynein motor protein transports proteins away from the cell membrane along the microtubule network. Recently, we found the microtubule network was important for regulating the membrane abundance of voltage-gated Kv7.4 potassium channels in vascular smooth muscle. Here, we aimed to investigate the influence of dynein on the microtubule-dependent internalization of the Kv7.4 channel. Patch-clamp recordings from HEK293B cells showed Kv7.4 currents were increased after inhibiting dynein function with ciliobrevin D or by coexpressing p50/dynamitin, which specifically interferes with dynein motor function. Mutation of a dynein-binding site in the Kv7.4 C terminus increased the Kv7.4 current and prevented p50 interference. Structured illumination microscopy, proximity ligation assays, and coimmunoprecipitation showed colocalization of Kv7.4 and dynein in mesenteric artery myocytes. Ciliobrevin D enhanced mesenteric artery relaxation to activators of Kv7.2-Kv7.5 channels and increased membrane abundance of Kv7.4 protein in isolated smooth muscle cells and HEK293B cells. Ciliobrevin D failed to enhance the negligible S-1-mediated relaxations after morpholino-mediated knockdown of Kv7.4. Mass spectrometry revealed an interaction of dynein with caveolin-1, confirmed using proximity ligation and coimmunoprecipitation assays, which also provided evidence for interaction of caveolin-1 with Kv7.4, confirming that Kv7.4 channels are localized to caveolae in mesenteric artery myocytes. Lastly, cholesterol depletion reduced the interaction of Kv7.4 with caveolin-1 and dynein while increasing the overall membrane expression of Kv7.4, although it attenuated the Kv7.4 current in oocytes and interfered with the action of ciliobrevin D and channel activators in arterial segments. Overall, this study shows that dynein can traffic Kv7.4 channels in vascular smooth muscle in a mechanism dependent on cholesterol-rich caveolae

Kinematic Indices of rotation-floating space robots for on-orbit servicing

There is a growing need for space and in-orbit operations that would require use of advance robotic systems. The robotics systems could be used in debris removal from orbits, as well as, in on-orbit servicing activities. This paper is addressing design and control problems related to autonomous spacecraft-manipulator system for space operation. The dynamics equations for rotation floating manipulator were introduced using Lagrange approach with additional states representing the kinetic moment exchange actuators. In this paper, a serial-link manipulator with multi degree of freedoms mounted on the satellite platform was used. For detailed analysis of base motion and manipulability of the end effector, the special indices were introduced. Simulation examples to illustrate kinematic indices were shown with physical parameters for a microsatellite from Myriade series equipped with a robotic arm

Creatinine- versus cystatine C-based equations in assessing the renal function of candidates for liver transplantation with cirrhosis

International audienceRenal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR-predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score \textless/= or \textgreater15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR \textless60 mL/min/1.73 m(2)). CONCLUSION: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging

Towards Industry 4.0: The Future Automated Aircraft Assembly Demonstrator

Part 4: Digital Technologies and Industry 4.0 ApplicationsInternational audienceAs part of the Future Automated Aircraft Assembly Demonstrator developed by the University of Nottingham, this paper presents a new flexible production environment for the complete manufacturing of high-accuracy high-complexity low-volume aerospace products. The aim is to design a product-independent manufacturing and assembly system that can react to fluctuating product specifications and demands through self-reconfiguration. This environment features a flexible, holistic, and context-aware solution that includes automated positioning, drilling and fastening processes, and is suitable for different aircraft structures with scope to address other manufacturing domains in the future (e.g. automotive, naval and energy). The assembly cell features industrial robots for the handling of aircraft components, while intelligent metrology and control systems monitor the cell to ensure that the assembly process is safe and the target tolerances are met. These three modules are integrated into a single standardized interface, requiring only one operator to control the cell. Performance analyses have shown that, using the reconfigurable production environment described hereafter, a positioning accuracy better than ±0.1 mm can be achieved for large airframe components

Configuration-dependent modal analysis of a Cartesian parallel kinematics manipulator: numerical modeling and experimental validation

In the design optimization of a robot the configuration-dependent modal analysis can be a powerful tool to be exploited when high stiffness and high dynamic performances are concurrently required. In this paper the elastodynamics of a lower-mobility Parallel Kinematic Machine for pure translational motions is analyzed. The vibrational modes and the natural frequencies of the robot are evaluated as functions of the end effector position inside the workspace. A finite element model including kinematic joints is used to perform a series of modal analyses in a grid of points inside the workspace. A polynomial regression gives continuous volume maps of the natural frequencies distributions. The numerical model is validated by comparison with experiments: a modal analysis is conducted on a set of inertance Frequency Response Functions acquired on several points of the machine components as a result of an excitation given by an instrumented hammer. A Natural Frequency Difference analysis validates the model under certain conditions and highlights some critical issues to be focused on in future works. �� 2013 Springer Science+Business Media Dordrecht