12 research outputs found
Aeronautics Application of Direct-Detection Doppler Wind Lidar: Alleviation of Airframe Structural Loads Caused by Turbulence and Gusts
How Future Aircraft Shall Lose Weight Thanks to Doppler Wind Lidar Technology - the UP Wing Project of the EC Clean Aviation Joint Undertaking
How Future Aircraft Shall Lose Weight Thanks to Doppler Wind Lidar Technology - the UP Wing Project of the EC Clean Aviation Joint Undertaking
Human beta3-adrenoreceptors couple to the KvLQT1/ minK potassium channels via protein kinase A - protein kinase C cross-talk
Bertosamil blocks HERG potassium channels in their open and inactivated states
1. Bertosamil is chemically related to the class-III anti-arrhythmic drug tedisamil and has been developed as a bradycardic, anti-ischemic and anti-arrhythmic drug. Its anti-arrhythmic properties might in part be attributed to its block of voltage-dependent potassium channels Kv(1.2), Kv(1.4). and Kv(1.5). However, HERG-potassium channel block as an important target for class-III drugs has not yet been investigated. 2. We investigated the effect of bertosamil on the HERG potassium channel heterologously expressed in Xenopus oocytes with the two-electrode voltage-clamp technique. 3. Bertosamil (70 μM) inhibited HERG tail currrent after a test pulse to 30 mV by 49.3±8.4% (n=5) and the IC(50) was 62.7 μM. Onset of block was fast, i.e. 90% of inhibition developed within 180±8.22 s (n=5), and block was totally reversible upon washout within 294±38.7 s (n=5). 4. Bertosamil-induced block of HERG potassium channels was state-dependent with block mainly to open- and inactivated channels. Half-maximal activation voltage was slightly shifted towards more negative potentials. 5. Steady-state inactivation of HERG was not influenced by bertosamil. Bertosamil block elicited voltage–but no frequency-dependent effects. 6. In summary, bertosamil blocked the HERG potassium channel. These blocking properties may contribute to the anti-arrhythmic effects of bertosamil in the treatment of atrial and particular ventricular arrhythmias
Aeronautics lidar revisited - Towards lidar-based gust and turbulence measurement for aircraft load alleviation control
We give an overview of the authors' and their institutions' latest R&D activities regarding Direct-Detection Doppler-Wind-Lidar (DD-DWL) for the usage as remote flow sensor on civil aircraft. The purpose of such a lidar, when flying through Clear Air Turbulence (CAT) at cruise altitudes, is delivering sufficient turbulent wind information for feeding a chain of gust reconstruction, control and command modules. Hence, aerodynamic effects on the aircraft structure shall be mitigated.
The long-standing record of the ONERA and DLR lidar groups in aeronautics' application lidar allowed us recently to team up in the European Clean Aviation Joint Undertaking (CAJU) co-financed project UP Wing with the agenda of maturing the critical technologies (like laser, Doppler spectrometric receiver, etc.) and validating these at component and system level with extensive ground and also airborne tests.
Here, we present the main bricks of this technology suite, an overview of some prior and actual achievements and some perspective
Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action
1. The topoisomerase II inhibitor amsacrine is used in the treatment of acute myelogenous leukemia. Although most anticancer drugs are believed not to cause acquired long QT syndrome (LQTS), concerns have been raised by reports of QT interval prolongation, ventricular fibrillation and death associated with amsacrine treatment. Since blockade of cardiac human ether-a-go-go-related gene (HERG) potassium currents is an important cause of acquired LQTS, we investigated the acute effects of amsacrine on cloned HERG channels to determine the electrophysiological basis for its proarrhythmic potential. 2. HERG channels were heterologously expressed in human HEK 293 cells and Xenopus laevis oocytes, and the respective potassium currents were recorded using patch-clamp and two-microelectrode voltage-clamp electrophysiology. 3. Amsacrine blocked HERG currents in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner, with IC(50) values of 209.4 nM and 2.0 μM, respectively. 4. HERG channels were primarily blocked in the open and inactivated states, and no additional voltage dependence was observed. Amsacrine caused a negative shift in the voltage dependence of both activation (−7.6 mV) and inactivation (−7.6 mV). HERG current block by amsacrine was not frequency dependent. 5. The S6 domain mutations Y652A and F656A attenuated (Y652A) or abolished (F656A, Y652A/F656A) HERG current blockade, indicating that amsacrine binding requires a common drug receptor within the pore-S6 region. 6. In conclusion, these data demonstrate that the anticancer drug amsacrine is an antagonist of cloned HERG potassium channels, providing a molecular mechanism for the previously reported QTc interval prolongation during clinical administration of amsacrine