关于BL-代数的模糊滤子与模糊理想

在BL-代数中引入模糊超滤子和模糊固执滤子的概念,证明了如下条件对于BL-代数的非常数模糊滤子f来说是等价的:(1)f是布尔的和素的,(2)f是蕴涵的和素的,(3)f是超的,(4)f是固执的。应用模糊正蕴涵滤子给出G-代数的若干特征性质。提出BL-代数模糊理想的概念,给出一些重要例子,并通过例子说明在BL-代数中模糊理想一般不能由模糊滤子导出。同时,从模糊理想出发构造了商BL-代数,并建立了相应的同态基本定理。最后,研究了BL-代数的几类模糊理想及其相互关系,给出模糊布尔理想、模糊素理想、模糊超理想的特征性质。     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

Issue Information

An integrated finite element method (FEM) is proposed to simulate incompressible two‐phase flows with surface tension effects, and three different surface tension models are applied to the FEM to investigate spurious currents and temporal stability. A Q2Q1 element is adopted to solve the continuity and Navier–Stokes equations and a Q2‐iso‐Q1 to solve the level set equation. The integrated FEM solves pressure and velocity simultaneously in a strongly coupled manner; the level set function is reinitialized by adopting a direct approach using interfacial geometry information instead of solving a conventional hyperbolic‐type equation. In addition, a consistent continuum surface force (consistent CSF) model is utilized by employing the same basis function for both surface tension and pressure variables to damp out spurious currents and to estimate the accurate pressure distribution. The model is further represented as a semi‐implicit manner to improve temporal stability with an increased time step. In order to verify the accuracy and robustness of the code, the present method is applied to a few benchmark problems of the static bubble and rising bubble with large density and viscosity ratios. The Q2Q1‐integrated FEM coupled with the semi‐implicit consistent CSF demonstrates the significantly reduced spurious currents and improved temporal stability. The numerical results are in good qualitative and quantitative agreements with those of the existing studies. Copyright © 2015 John Wiley & Sons, Ltd.     

On $$\epsilon $$ ϵ -solutions for robust semi-infinite optimization problems

Positivity - In this paper, we consider semi-infinite optimization problems involving a convex objective function and infinitely many convex constraint functions with data uncertainty, and give its...     

Pd nanoparticles immobilized on PNIPAM–halloysite: highly active and reusable catalyst for Suzuki–Miyaura coupling reactions in water

Poly(N‐isopropylacrylamide)–halloysite (PNIPAM‐HNT) nanocomposites exhibited inverse temperature solubility with a lower critical solution temperature (LCST) in water. Palladium (Pd) nanoparticles were anchored on PNIPAM‐HNT nanocomposites with various amounts of HNT from 5 to 30 wt%. These Pd catalysts exhibited excellent reactivities for Suzuki–Miyaura coupling reactions at 50–70 °C in water. In particular, Pd anchored PNIPAM/HNT (95:5 w/w ratio) nanocomposites showed excellent recyclability up to 10 times in 96% average yield by simple filtration. Copyright © 2014 John Wiley & Sons, Ltd.     

Liquid chromatographic resolution of racemic rasagiline and its analogues on a chiral stationary phase based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

A liquid chromatographic chiral stationary phase based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid was applied to the resolution of 15 analytes, including racemic rasagiline, a chiral drug for the treatment of Parkinson's disease, and its analogues. The composition of mobile phase was optimized to be ethanol/acetonitrile/acetic acid/triethylamine (80:20:0.2:0.3, v/v/v/v) by evaluating the chromatographic results for the resolution of five selected analytes under various mobile phase conditions. Under the optimized mobile phase conditions, racemic rasagiline was resolved quite well with a separation factor of 1.48 and resolution of 2.71 and its 14 analogues were also resolved reasonably well with separation factors of 1.06–1.54 and resolutions of 0.54–2.11. Among 15 analytes, racemic rasagiline was resolved best except for just one analyte. The analyte structure–enantioselectivity relationship indicated that racemic rasagiline has the most appropriate structural characteristics for resolution on the chiral stationary phase.