Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation

Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from Artemisia capillaris were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in db/db mice without elevation of insulin levels.     

Characterization of the calcination process of yttria

A complete characterization of the calcination of precipitates obtained from a continuous operation was carried out in this study. The precipitate was obtained by reacting yttrium nitrate and ammonia solutions in a MSMPR reactor. It precipitated out as yttrium hydroxide nitrate hydrate, which has the general form Y₂(OH)_6-x(NO₃)_x·y H₂O. This compound decomposed in consecutive steps with the last reaction occurring at 525°C.The calcination process was characterized by chemical analysis, X-ray diffraction analysis, DTA and TG. In addition, the physical characteristics of calcined powders, such as specific surface area, particle size distribution, pore volume distribution, X-ray crystallite size and conversion were measured as a function of calcination temperature and time. Finally, the kinetics of the reduction of surface area, the growth of crystallite size and conversion were also examined.     

青蒿素及其一类物结构和合成的研究——Ⅸ.全合成青蒿素中若干关键化合物的合成

青蒿素是一个含有过氧基团的新型倍半萜内酯~([1]),它具有突出的抗疟作用~([2])。本文报道     

A note on circulant transition matrices in Markov chains

Let g and n be positive integers and gcd(g,n)=1. Let C=(c_ij) be a g-circulant transition matrix of order n of Markov chain. We are interested in studying and lim_k→∞C^k.     

五阶势MKdV方程的一个不变性

§1Introduction Asweknow,Backlundtransformation[1-3]isaverypowerfulwayforfindingnonline evolutionequations.Inrecentdecades,Painlevéanalysis[4]hasbecomeaverypopu methodtoobtainBacklundtransformation.Inreference[5],fordevelopingthetheory Painlevéanalysis,AndrewPickeringintroduceanewexpansionvariableZwhichsatisf thefollowingRicattiSystem:Zx=1-AZ-BZ2,Zt=-C+(AC+Cx)Z-(D-BC)Z2.(1.Astheapplicationofthenewexpansionvaraible,thepotentialfifth-orderMKd equation(PMKdV5)-vxt+(vxxxxx-10k2v2…     

An Engel condition with skew derivations

Let R be a prime ring and set [x, y]₁ = [x, y] = xy ? yx for ${x,y\in R}$ and inductively [x, y] _k = [[x, y] _k-1, y] for k > 1. We apply the theory of generalized polynomial identities with automorphisms and skew derivations to obtain the following result: If δ is a nonzero σ-derivation of R and L is a noncommutative Lie ideal of R so that [δ(x), x] _k  = 0 for all ${x \in L}$ , where k is a fixed positive integer, then charR = 2 and ${R\subseteq M_{2}(F)}$ for some field F. This result generalizes the case of derivations by Lanski and also the case of automorphisms by Mayne.     

Local elastodynamic stresses in the unit cell of a woven fabric composite

Summary A theoretical study of the local elastodynamic stresses of woven fabric composites under dynamic loadings is presented in this article. The analysis focuses on the unit cell of an orthogonal woven fabric composite, which is composed of two sets of mutually orthogonal yarns of either the same fiber (nonhybrid fabric) or different fibers (hybrid fabric) in a matrix material. Using the mosaic model for simplifying woven fabric composites and a shear lag approach to account for the inter-yarn deformation, a one-dimensional analysis has been developed to predict the local elastodynamic and elastostatic behavior. The initial and boundary value problems are formulated and then solved using Laplace transforms. Closed form solutions of the dynamic displacements and stresses in each yarn and the bond shearing stresses at the interfaces between adjacent yarns are obtained in the time domain for any type of in-plane impact loadings. When time tends to infinity, the dynamic solutions approach to their corresponding static solutions, which are also developed in this article. Solutions of certain special cases are identical to those reported in the literature. Lastly, the dynamic stresses and bond shearing stresses of plain weave composites subjected to step uniform impacts are presented and discussed as an example of the general analytical model. Received 3 May 1999; accepted for publication 22 September 1999     

An agent-based model of organizational ambidexterity decisions and strategies in new product development

Organizational ambidexterity, defined as the pursuit of both exploitation and exploration, has become an important topic in the study of organizations, especially in innovation management theory. Previous literature has not focused on the strategic (game-theoretic) aspects of organizational ambidexterity or on its decision-making aspects. Little is known about how or even whether the decision to adopt ambidexterity is competitively advantageous in the presence of diverse strategies that competitors may adopt. This facet of the subject is inherently game-theoretic; the value of a decision by one firm depends in part on decisions made by other firms. This paper initiates systematic investigation of these strategic aspects, including the overall performance of available strategies. Specifically, this study examines questions of ambidexterity-related strategy performance in the context of new product development. The main contributions are (1) to introduce and make available to the research community an agent-based model and decision support system that captures many of the key aspects and tradeoffs, which have been identified in the literature, of the exploration–exploitation dilemma faced by firms in the new product development process, with a focus on organizations’ product investment decisions and (2) to report on results obtained from the model, calibrated with available data from the literature, augmented by new data collected from interviews with practitioners.     

A general mixed covolume framework for constructing conservative schemes for elliptic problems

We present a general framework for the finite volume or covolume schemes developed for second order elliptic problems in mixed form, i.e., written as first order systems. We connect these schemes to standard mixed finite element methods via a one-to-one transfer operator between trial and test spaces. In the nonsymmetric case (convection-diffusion equation) we show one-half order convergence rate for the flux variable which is approximated either by the lowest order Raviart-Thomas space or by its image in the space of discontinuous piecewise constants. In the symmetric case (diffusion equation) a first order convergence rate is obtained for both the state variable (e.g., concentration) and its flux. Numerical experiments are included.

     

A logarithmic Gauss curvature flow and the Minkowski problem

Let X₀ be a smooth uniformly convex hypersurface and f a postive smooth function in Sⁿ. We study the motion of convex hypersurfaces X(·,t) with initial X(·,0)=θX₀ along its inner normal at a rate equal to log(K/f) where K is the Gauss curvature of X(·,t). We show that the hypersurfaces remain smooth and uniformly convex, and there exists θ^*>0 such that if θ<θ^*, they shrink to a point in finite time and, if θ>θ^*, they expand to an asymptotic sphere. Finally, when θ=θ^*, they converge to a convex hypersurface of which Gauss curvature is given explicitly by a function depending on f(x).