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.     

Human-to-metal electrostatic discharge current measurements – Notes on the ESD current waveform

The Electrostatic Discharge (ESD) phenomenon has been described through the IEC 61000-4-2. ESD current parameters' values, have been set in this Standard. The theoretical ESD current waveform defined in this standard, describing the conventional Contact discharge mode, needs to be re-evaluated on the basis of accurate experimental data. Even though the standard deals with commercial ESD generators, its goal is to simulate the natural phenomenon as good as possible. More and accurate data may contribute to the better simulation of the natural phenomenon. New values and better comprehension of the phenomenon demand new measurements based on high end measuring equipment. Such works and publications have been carried out the past years. Yet, the need to systematize and integrate this work remains. Larger and trust-worthy series of measurements need to be carried out and presented clearly.This paper deals with new ESD-current data, taken with broadband equipment. New and more detailed measurements like these, were never before taken at such a large number of individuals. The goal of this work is that the data acquired can serve as a basis for re-evaluating the conventional approach of the scientific community to the ESD event.In this paper, using a broadband measuring system, new parameters' values are measured and relations are presented, following standard statistical procedures. The results, which occur from measurements carried out on tenths of human individuals, are questioning the Standard in many points. A new way of approaching the standardization of the ESD current is proposed, as the excuse of the poor measuring equipment that sets barriers on the measuring accuracy, does not apply any more. The charging voltages of 500 V and 1000 V were also examined since such range of voltages are often met at ESD events and they are considered very harmful.     

用等厚干涉测定液体折射率

介绍一种采用等厚干涉原理测定液体折射率的简单可靠的方法。     

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。     

计算全息检测非球面干涉场的理论分析与实验结果

本文应用光学全息术及傅里叶光学的理论对计算全息图干涉检测非球面面形的光路及干涉场进行了理论分析,提出了其干涉场为不定域干涉的观点,并在实验中予以证实.     

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     

迈克尔逊干涉仪中补偿板与干涉条纹

通过分析缺失补偿板的迈克尔逊干涉仪中的附加光程差,推出干涉条纹满足的方程式,并用计算机模拟了动镜移动过程中变化的干涉条纹,与实验结果相一致.     

激光二极管反馈干涉的实验观测

利用LabView软件虚拟示波器和信号源,观测了激光二极管反馈干涉实验现象．实验证明反馈回激光二极管的光的入射方向和入射光强以及信号处理电路的带宽,对反馈干涉信号有很大的影响．     

Experimental observation of quantum corrections to electrical resistivity in nanocrystalline soft magnetic alloys

X-ray diffraction patterns of nanocrystalline Fe-Cu-Nb-Si-B (FINEMET) alloys reveal that bcc α-Fe/α-FeSi crystallites with the average grain size of 20(5) nm are dispersed in amorphous matrix. Enhanced electron—electron interaction (EEI) and quantum interference (QI) effects as well as electron-magnon (and/or electron-spin fluctuation) scattering turn out to be the main mechanisms that govern the temperature dependence of resistivity. Of all the inelastic scattering processes, inelastic electron-phonon scattering is the most effective mechanism to destroy phase coherence of electron wave functions. The diffusion constant, density of states at the Fermi level and the inelastic scattering time have been estimated, for the first time, for the alloys in question Article presented at the International Symposium on Advances in Superconductivity and Magnetism: Materials, Mechanisms and Devices, ASMM2D-2001, 25–28 September 2001, Mangalore, India.