Het(aryl)isatin to het(aryl)aminoindoline scaffold hopping: A route to selective inhibitors of matrix metalloproteinases

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, ?8 and ?13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37–39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC₅₀ of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design.     

Formal proofs of operator identities by a single formal computation

A formal computation proving a new operator identity from known ones is, in principle, restricted by domains and codomains of linear operators involved, since not any two operators can be added or composed. Algebraically, identities can be modelled by noncommutative polynomials and such a formal computation proves that the polynomial corresponding to the new identity lies in the ideal generated by the polynomials corresponding to the known identities. In order to prove an operator identity, however, just proving membership of the polynomial in the ideal is not enough, since the ring of noncommutative polynomials ignores domains and codomains. We show that it suffices to additionally verify compatibility of this polynomial and of the generators of the ideal with the labelled quiver that encodes which polynomials can be realized as linear operators. Then, for every consistent representation of such a quiver in a linear category, there exists a computation in the category that proves the corresponding instance of the identity. Moreover, by assigning the same label to several edges of the quiver, the algebraic framework developed allows to model different versions of an operator by the same indeterminate in the noncommutative polynomials.     

Real time estimation of CO2 laser weld quality for automotive industry

Laser welding is one of the most precise welding processes in joining sheet metals. In laser welding, performing real time evaluation of the welding quality is very important to enhance the efficiency of the welding process. In this study, the plasma and spatter, which are generated during laser welding, are measured using UV and IR photodiodes. The factors that influence weld quality are classified into five categories; optimal heat input, slightly low heat input, low heat input, partial joining due to gap mismatch, and nozzle deviation. The data number deviated from reference signals and their standard deviations were also considered to evaluate the qualities. A system was also formulated to perform real time evaluations of the weld quality using a fuzzy multi-feature pattern recognition with the measured signals.     

矩阵方程A^TXB=C的正定和半正定解

给出了矩阵方程Ａ＾ＴＸＢ＝Ｃ在正定和半正定矩阵类中有解的充要条件及解的一般表达式。     

模糊线性回归模型的约束最小二乘估计

自Tanaka等1982年提出模糊回归概念以来,该问题已得到广泛的研究。作为主要估计方法之一的模糊最小二乘估计以其与统计最小二乘估计的密切联系更受到人们的重视。本文依据适当定义的两个模糊数之间的距离,提出了模糊线性回归模型的一个约束最小二乘估计方法,该方法不仅能使估计的模糊参数的宽度具有非负性而且估计的模糊参数的中心线与传统的最小二乘估计相一致。最后,通过数值例子说明了所提方法的具体应用。     

Interlaboratory comparisons and improvements of methods for acid number determination in used motor oils

The results of two interlaboratory comparisons of acid number determinations in used motor oils are discussed. It is shown that the comparability of the measurement results is not as good as that required by known standards for petroleum products. The problem is motor oil contaminants which accumulated during use, and which are the source of a matrix effect in the acid number determination. The standard methods’ drawbacks are analyzed and some improvements are proposed. Repeatability and accuracy of the improved methods are evaluated. Received: 11 December 2001 Accepted: 15 February 2002     

基于模糊集相容性的模糊控制规则优化方法

在简要介绍模糊模型的完备性和相容性的基础上 ,根据模糊集贴近度 ,提出模糊集相容性的概念 ;通过对模糊控制规则表特征的分析 ,进一步完善规则相容性概念及其定量评价方法 ;最后给出模糊控制规则模型自寻优优化方法。仿真结果表明 ,该方法可以大大提高控制系统的控制性能。     

一阶形式系统K~*及其完备性

模糊命题演算的形式系统L＊已经在模糊逻辑与模糊推理的结合研究中得到了成功的应用.本文考虑与系统L＊相应的一阶逻辑理论,建立了一阶形式系统K＊,并证明了这个系统的完备性.     

Hypernormal form theory: foundations and algorithms

Hypernormal forms (unique normal forms, simplest normal forms) are investigated both from the standpoint of foundational theory and algorithms suitable for use with computer algebra. The Baider theory of the Campbell-Hausdorff group is refined, by a study of its subgroups, to determine the smallest substages into which the hypernormalization process can be divided. This leads to a linear algebra algorithm to compute the generators needed for each substage with the least amount of work. A concrete interpretation of Jan Sanders’ spectral sequence for hypernormal forms is presented. Examples are given, and a proof is given for a little-known theorem of Belitskii expressing the hypernormal form space (in the inner product style) as the kernel of a higher-order differential operator.     

Cochran's statistical theorem for outer inverses of matrices and matrix quadratic forms

We extend the matrix version of Cochran's statistical theorem to outer inverses of a matrix. As applications, we investigate the Wishartness and independence of matrix quadratic forms for Kronecker product covariance structures.