L∞-gain adaptive fuzzy fault accommodation control design for nonlinear time-delay systems.

In this paper, an adaptive fuzzy fault accommodation (FA) control design with a guaranteed L(∞)-gain performance is developed for a class of nonlinear time-delay systems with persistent bounded disturbances. Using the Lyapunov technique and the Razumikhin-type lemma, the existence condition of the L(∞) -gain adaptive fuzzy FA controllers is provided in terms of linear matrix inequalities (LMIs). In the proposed FA scheme, a fuzzy logic system is employed to approximate the unknown term in the derivative of the Lyapunov function due to the unknown fault function; a continuous-state feedback control strategy is adopted for the control design to avoid the undesirable chattering phenomenon. The resulting FA controllers can ensure that every response of the closed-loop system is uniformly ultimately bounded with a guaranteed L(∞)-gain performance in the presence of a fault. Moreover, by the existing LMI optimization technique, a suboptimal controller is obtained in the sense of minimizing an upper bound of the L(∞)-gain. Finally, the achieved simulation results on the FA control of a continuous stirred tank reactor (CSTR) show the effectiveness of the proposed design procedure.

Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro.

AIM: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. METHODS: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPE-LC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-(127)I iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC(50)) of sifuvirtide on cell fusion was determined by co-cultivation assay. RESULTS: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 microg/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10 626+/-2886 microg/L and 528+/-191 microg/L, and the terminal elimination half-lives (T(1/2)) were 6.3+/-0.9 h and 5.5+/-1.0 h, respectively. After sc, T(max) was 0.25-2 h, and the absolute bioavailability was 49%+/-13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC(50) of 0.33 microg/L. CONCLUSION: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T(1/2) of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC(50) in vitro.