A titrant for the SARS-CoV-2 main protease(M^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active M^(pro) by active-site titration.The covalent b...A titrant for the SARS-CoV-2 main protease(M^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active M^(pro) by active-site titration.The covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant complex.Four fluorogenic substrates of M^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay conditions.By exploiting the new titrant,key kinetic parameters for the M^(pro)-catalyzed cleavage of these substrates were determined.展开更多
An adaptive command filter control strategy was proposed to realize the asymptotic tracking of the roll speed,which successfully suppressed torsional vibration for the main drive system of the rolling mill with nonlin...An adaptive command filter control strategy was proposed to realize the asymptotic tracking of the roll speed,which successfully suppressed torsional vibration for the main drive system of the rolling mill with nonlinear friction,nonlinear damping,current harmonic,time-varying stiffness and unknown disturbance.A finite time predetermined performance method was proposed,so that the speed tracking error of the main transmission system was always constrained in the performance function and converged to its minimum boundary within the specified time.Based on the adaptive estimation of harmonic amplitude,the torque control law of the motor was obtained by using the filter backstepping method,which prevented the torsional vibration of the system caused by the input fluctuation and avoided the complexity explosion of the controller design,and the stability of the closed-loop system was strictly proved by the Lyapunov theory.The actual numerical simulation verified the effectiveness of the proposed control strategy.展开更多
基金The authors acknowledge support by Dr.Carina Lemke and Marion Schneider.Christa E.Müller and Michael Gütschow were supported by the Volkswagen Foundation(9A894)Rabea Voget,Christian Steinebach,Christa E.Müller and Michael Gütschow by the German Research Foundation(RTG 2873)Norbert Sträter by the Volkswagen Foundation(9A850).We acknowledge DESY(Hamburg,Germany),a member of the Helmholtz Association HGF,and the EMBL for the provision of experimental facilities at synchrotron beamlines P13 and P14 and the MX Laboratory at the Helmholtz Zentrum Berlin(BESSY II)for beam time.We would like to thank Selina Storm for assistance in using the EMBL beamlines.
文摘A titrant for the SARS-CoV-2 main protease(M^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active M^(pro) by active-site titration.The covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant complex.Four fluorogenic substrates of M^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay conditions.By exploiting the new titrant,key kinetic parameters for the M^(pro)-catalyzed cleavage of these substrates were determined.
基金This work was supported by the Natural Science Foundation of China(Grant No.U20A20187).
文摘An adaptive command filter control strategy was proposed to realize the asymptotic tracking of the roll speed,which successfully suppressed torsional vibration for the main drive system of the rolling mill with nonlinear friction,nonlinear damping,current harmonic,time-varying stiffness and unknown disturbance.A finite time predetermined performance method was proposed,so that the speed tracking error of the main transmission system was always constrained in the performance function and converged to its minimum boundary within the specified time.Based on the adaptive estimation of harmonic amplitude,the torque control law of the motor was obtained by using the filter backstepping method,which prevented the torsional vibration of the system caused by the input fluctuation and avoided the complexity explosion of the controller design,and the stability of the closed-loop system was strictly proved by the Lyapunov theory.The actual numerical simulation verified the effectiveness of the proposed control strategy.