Fault-tolerant attitude tracking control of combined spacecraft with reaction wheels under prescribed performance.

Capture and control of a failed spacecraft can be achieved by a space manipulator installed in a service spacecraft. After this target has been captured, the combined spacecraft must be controlled in a prescribed way. The attitude attacking control of the combined spacecraft system is one major challenge since the mass properties of the whole spacecraft system and configuration matrix of the reaction wheels change, especially when actuator fault occurs. In this paper, a nonlinear disturbance-observer-based fault-tolerant attitude control scheme is developed for the combined spacecraft with prescribed performance. Firstly, an approach is given to reconstruct the attitude tracking dynamics of the combined spacecraft with reaction wheels. Then, a fault-tolerant controller, based on dynamic surface method and nonlinear extended state observer, is developed whereby performance in the light of convergence time, stability and accuracy with inertia uncertainty, actuator saturation and external disturbance can be prescribed. Finally, comparative simulations in both actuator faults and actuator fault-free cases are conducted to show the superiority of the developed attitude tracking control method.

Association of Plasma 7-Ketocholesterol With Cardiovascular Outcomes and Total Mortality in Patients With Coronary Artery Disease.

RATIONALE: 7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. OBJECTIVE: We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease. METHODS AND RESULTS: We measured the plasma 7-KC levels by high-performance liquid chromatography in a prospective cohort study of 1016 patients (mean age, 63.2 years; male 61.1%) with stable coronary artery disease who were recruited from December 2008 to December 2011 and followed up for a median of 4.6 years. We adjudicated myocardial infarction, hospitalization of heart failure, cardiovascular death, all-cause death, and composite end points of myocardial infarction/heart failure/death by review of medical records and death certificates. We used multivariable Cox proportional hazards analysis to compare the incidence rate of cardiovascular events and all-cause death according to the quartile of the plasma 7-KC. During the median 4.6 years follow-up, totally 221 participants (21.8%) experienced a cardiovascular event or death. The adjusted risk of the composite end points was higher in the highest 7-KC quartile than in the lowest quartile (hazard ratio, 1.76; 95% confidence interval, 1.42-2.21; P<0.001). After adjustment for demographic and clinical variables and other biomarkers, including high-sensitivity C-reactive protein and NT-proBNP (N-terminal pro-B-type natriuretic peptide), 1 SD increase in the 7-KC level remained associated with a 36% higher rate of composite outcomes (hazard ratio, 1.36; 95% confidence interval, 1.22-1.48; P=0.007). Plasma 7-KC clearly improved various model performance measures, including C statistics, integrated discrimination, and category-free net reclassification. CONCLUSIONS: High 7-KC levels are associated with increased risk of cardiovascular events, total death, and composite outcomes in patients with stable coronary artery disease.

7-Ketocholesterol inhibits isocitrate dehydrogenase 2 expression and impairs endothelial function via microRNA-144.

Oxysterol is associated with the induction of endothelial oxidative stress and impaired endothelial function. Mitochondria play a central role in oxidative energy metabolism and the maintenance of proper redox status. The purpose of this study was to determine the effects and mechanisms of 7-ketocholesterol (7-KC) on isocitrate dehydrogenase 2 (IDH2) and its impact on endothelial function in both human aortic endothelial cells (HAECs) and C57BL/6J mice. HAECs treated with 7-KC showed significant reductions of IDH2 mRNA and protein levels and enzyme activity, leading to decreased NADPH concentration and an increased ratio of reduced-to-oxidized glutathione in the mitochondria. 7-KC induced the expression of a specific microRNA, miR-144, which in turn targets and downregulates IDH2. In silico analysis predicted that miR-144 could bind to the 3'-untranslated region of IDH2 mRNA. Overexpression of miR-144 decreased the expression of IDH2 and the levels of NADPH. A complementary finding is that a miR-144 inhibitor increased the mRNA and protein expression levels of IDH2. Furthermore, miR-144 level was elevated in HAECs in response to 7-KC. Anti-Ago1/2 immunoprecipitation coupled with a real-time polymerase chain reaction assay revealed that 7-KC increased the functional targeting of miR-144/IDH2 mRNA in HAECs. Infusion of 7-KC in vivo decreased vascular IDH2 expression and impaired vascular reactivity via miR-144. 7-KC controls miR-144 expression, which in turn decreases IDH2 expression and attenuates NO bioavailability to impair endothelial homeostasis. The newly identified 7-KC-miR-144-IDH2 pathway may contribute to atherosclerosis progression and provides new insight into 7-KC function and microRNA biology in cardiovascular disease.

Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia.

CONTEXT AND OBJECTIVE: Paraoxonase 1 (PON1), an enzyme associated with high-density lipoprotein (HDL-PON1), is reported to have antioxidant and cardioprotective properties. The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects. DESIGN AND PARTICIPANTS: A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo (n = 61 of each group) for 24 weeks in a double-blind, randomized, placebo-controlled trial. Participants and investigators were masked to treatment allocation. RESULTS: Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo (P < .018 and P < .001, respectively). Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo (P < .001). Furthermore, cholesterol efflux capacity was increased more in the anthocyanin group (20.0% increase) than in the placebo group (0.2% increase) (P < .001). The negative correlations established between HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins. Furthermore, a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects (both P < .001). Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group. CONCLUSIONS: Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects.