Tentatively Identified (UPLC/T-TOF–MS/MS) Compounds in the Extract of Saussurea costus Roots Exhibit In Vivo Hepatoprotection via Modulation of HNF-1α, Sirtuin-1, C/ebpα, miRNA-34a and miRNA-223

Saussurea costus is a plant traditionally used for the treatment of several ailments. Our study accomplished the UPLC/T-TOF–MS/MS analysis of a methanol extract of Saussurea costus roots (MESC), in addition to lipoidal matter determination and assessment of its in vivo hepatoprotective activity. In this study, we were able to identify the major metabolites in MESC rather than the previously known isolated compounds, improving our knowledge of its chemical constituents. The flavones apigenin, acacetin, baicalein, luteolin, and diosmetin, and the flavonol aglycones quercetin, kaempferol, isorhamnetin, gossypetin, and myricetin and/or their glycosides and glucuronic derivatives were the major identified compounds. The hepatoprotective activity of MESC was evaluated by measuring catalase activity using UV spectrophotometry, inflammatory cytokines and apoptotic markers using ELISA techniques, and genetic markers using PCR. Paracetamol toxicity caused a significant increase in plasma caspase 2, cytokeratin 18 (CK18), liver tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miRNA-34a, and miRNA-223, as well as a significant decrease in liver catalase (CAT) activity and in the levels of liver nuclear factor 1α (HNF-1α), sirtuin-1, and C/ebpα. Oral pretreatment with MESC (200 mg/kg) showed a significant decrease in caspase 2, CK18, TNF-α, IL-6 and a significant increase in liver CAT activity. MESC decreased the levels of liver miRNA-34a and miRNA-223 and induced HNF-1α, sirtuin-1, and C/ebpα gene expression. The histological examination showed a significant normalization in rats pretreated with MESC. Our findings showed that Saussurea costus may exert a potent hepatoprotective activity through the modulation of the expression of cellular cytokines, miRNA-34a, and miRNA-223.     

Stable fuzzy logic design of point-to-point control for mechanical systems

An approach for the development of fuzzy point-to-point control laws for second-order mechanical systems is presented. Asymptotic stability of the resulting closed-loop system is proved using Lyapunov stability theory. Closed-loop performance and robustness are quantified in terms of the parameters of membership functions. As opposed to most existing fuzzy control laws, the closed-loop stability of the proposed controller does not depend on the knowledge of the entire dynamics. Moreover, the approach does not require the plant to be open-loop stable. The proposed approach is demonstrated on design and simulation study of a fuzzy controller for a two-link robotic arm.     

A new bound for the ratio between the 2-matching problem and its linear programming relaxation

Consider the 2-matching problem defined on the complete graph, with edge costs which satisfy the triangle inequality. We prove that the value of a minimum cost 2-matching is bounded above by 4/3 times the value of its linear programming relaxation, the fractional 2-matching problem. This lends credibility to a long-standing conjecture that the optimal value for the traveling salesman problem is bounded above by 4/3 times the value of its linear programming relaxation, the subtour elimination problem. Received August 26, 1996 / Revised version received July 6, 1999? Published online September 15, 1999     

Stable Configurations in Superconductivity: Uniqueness, Multiplicity, and Vortex‐Nucleation

. We find new stable solutions of the Ginzburg‐Landau equation for high κ superconductors with exterior magnetic field h _ex. First, we prove the uniqueness of the Meissner‐type solution. Then, we prove, in the case of a disc domain, the coexistence of branches of solutions with n vortices of degree one, for any n not too high and for a certain range of h _ex; and describe these branches. Finally, we give an estimate on the nucleation energy barrier, to pass continuously from a vortexless configuration to a configuration with a centered vortex. (Accepted October 29, 1998)     

Structural Characteristics and Permeability of Ethyl Cellulose Films Containing Different Plasticizers

The effect of different type of plasticizers was investigated in ethyl cellulose as coating polymer for manufacturing coated pellets of modified release containing a water soluble model drug. Scanning electron microscopic image analysis (SEM), differential scanning calorimetry (DSC), X-ray photoelectron spectroscopic chemical surface analysis (XPS) were used to study the films, and the dissolution profiles of coated pellets were evaluated. The effect of the different plasticizers and coating levels on the first order dissolution rate constant is determined by statistical experimental design. Correlation was found between the dissolution rate constant and the structural characteristics of the coating layer containing different plasticizers. Partial segregation of the plasticizers was detected especially on the surface of the films, which is in correlation with the differences in the glass transition temperatures. PEG 400 is found to be compatible enough to form continuous, durable EC coating at 5% concentration level, which gave the slowest dissolution.