Computer-assisted structure analysis indicated (+)-discodermolide, a polyhydroxylated alkatetraene lactone marine natural product, was an antimitotic compound, and we confirmed this prediction. Previous work had shown an accumulation of discodermolide-treated cells in the G2/M portion of the cell cycle, and we have now found that discodermolide arrests Burkitt lymphoma cells in mitosis. Discodermolide-treated breast carcinoma cells displayed spectacular rearrangement of the microtubule cytoskeleton, including extensive microtubule bundling. Microtubule rearrangement that occurred with 10 nM discodermolide required 1 microM taxol. Discodermolide had equally impressive effects on tubulin assembly in vitro. Near-total polymerization occurred at 0 degree C with tubulin plus microtubule-associated proteins (MAPs) under conditions in which taxol at an identical concentration was inactive. Without MAPs and/or without GTP, tubulin assembly was also more vigorous with discodermolide than with taxol under every reaction condition examined. Discodermolide-induced polymer differed from taxol-induced polymer in that it was completely stable at 0 degree C in the presence of high concentrations of Ca2+. In a quantitative assay designed to select for agents more effective than taxol in inducing assembly, discodermolide had an EC50 value of 3.2 microM versus 23 microM for taxol.
Wing rock is a highly nonlinear phenomenon in which an aircraft undergoes limit cycle roll oscillations at high angles of attack. In this paper, a supervisory recurrent fuzzy neural network control (SRFNNC) system is developed to control the wing rock system. This SRFNNC system is comprised of a recurrent fuzzy neural network (RFNN) controller and a supervisory controller. The RFNN controller is investigated to mimic an ideal controller and the supervisory controller is designed to compensate for the approximation error between the RFNN controller and the ideal controller. The RFNN is inherently a recurrent multilayered neural network for realizing fuzzy inference using dynamic fuzzy rules. Moreover, an on-line parameter training methodology, using the gradient descent method and the Lyapunov stability theorem, is proposed to increase the learning capability. Finally, a comparison between the sliding-mode control, the fuzzy sliding control and the proposed SRFNNC of a wing rock system is presented to illustrate the effectiveness of the SRFNNC system. Simulation results demonstrate that the proposed design method can achieve favorable control performance for the wing rock system without the knowledge of system dynamic functions.
In this study, an adaptive fuzzy sliding-mode control (AFSMC) system with an integral-operation switching surface is adopted to control the position of an electrical servo drive. The AFSMC system is comprised of a fuzzy control design and a hitting control design. In the fuzzy control design a fuzzy controller is designed to mimic a feedback linearization (FL) control law. In the hitting control design a hitting controller is designed to compensate the approximation error between the FL control law and the fuzzy controller. The tuning algorithms are derived in the sense of the Lyapunov stability theorem, thus the stability of the system can be guaranteed. Moreover, to relax the requirement for the bound of approximation error, an error estimation mechanism is investigated to observe the bound of approximation error real-time. Experimental results verify that the proposed control systems can achieve favorable tracking performance and robust with regard to parameter variations and external load disturbance.
The anticancer drug paclitaxel (Taxol) has been converted to a large number of 2-debenzoyl-2-aroyl derivatives by three different methods. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with enhanced activity as compared with paclitaxel were discovered. Correlation of cytotoxicity in three cell lines with tubulin polymerization activity showed reasonable agreement. Among the cell lines examined, the closest correlation with antitubulin activity was observed with a human ovarian carcinoma cell line.
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