Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.     

Dispersion effects in unreplicated factorial designs

Methods for estimation of dispersion effects in two‐level unreplicated factorial designs are studied. The consequences of non‐constant variance are discussed. A natural assumption concerning the form of the covariance of location effects leads to a particular normal model. Some linear combinations of the response variables are constructed in order to make a simple structure for inference. The precision of point estimators of dispersion effects, where one is based on experiments with replicates, are compared. A numerical example is given as an illustration of a test. Finally, estimations in fractional designs are described and discussed. Copyright © 2002 John Wiley & Sons, Ltd.     

Sufficiency and fuzziness in random experiments

In previous papers, the consequences of the “presence of fuzziness” in the experimental information on which statistical inferences are based were discussed. Thus, the intuitive assertion «fuzziness entails a loss of information» was formalized, by comparing the information in the “exact case” with that in the “fuzzy case”. This comparison was carried out through different criteria to compare experiments (in particular, that based on the “pattern” one, Blackwell's sufficiency criterion). Our purpose now is slightly different, in the sense that we try to compare two “fuzzy cases”. More precisely, the question we are interested in is the following: how will different “degrees of fuzziness” in the experimental information affect the sufficiency? In this paper, a study of this question is carried out by constructing an alternative criterion (equivalent to sufficiency under comparability conditions), but whose interpretation is more intuitive in the fuzzy case. The study is first developed for Bernoulli experiments, and the coherence with the axiomatic requirements for measures of fuzziness is also analyzed in such a situation. Then it is generalized to other random experiments and a simple example is examined.     

综合性、设计性实验教学的探讨

综合性、设计性实验是培养学生的创新意识、创新精神和创新能力的有效措施;本文就开设综合性、设计性实验的意义、内涵、与基础实验的关系以及如何设计项目内容进行了初步的探讨。     

Parameter identification for viscoelastic materials

Starting from the general stress-strain relation for a linear Boltzmann-Volterra material, which is in agreement with the principle of inertia, a new identification procedure is proposed. Instead of running one long-range relaxation experiment, following asingle suitably specified deformation history, material characterization is done using the data ofn short relaxation experiments followingn different deformation histories. To interpret these data a direct non-iterative algorithm has been developed. Compared with other methods, for example curve fitting by using Gauss' method, this direct method is numerically stable and allows a simple direct evaluation of the error due to the scattering of experimental data. The method has been applied to the determination of the relaxation times of an unsaturated polyester material.     

A fractional order hyperchaotic system derived from Liu system and its circuit realization

In this paper we propose a novel four-dimensional fractional order hyperchaotic system derived from Liu system. Electronics workbench (EWB) and Matlab simulations show the dynamical behavior of the proposed four-dimensional fractional order hyperchaotic system. Finally, after separately using EWB and Matlab, an electronic circuit is designed to realize the novel four-dimensional fractional order hyperchaotic system and the experimental circuit results are obtained which are identical to software simulations.     

基于贝叶斯序贯方法的微波效应实验设计

提出了一种基于贝叶斯验后概率的序贯检验方法,建立了检验的判别准则,给出了判别准则临界值的计算方法。在给定截尾实验次数的条件下,提出了一种截尾方案,建立了截尾判断方法。将其用于解决验证效应物在微波作用下失效概率达到给定水平的微波效应实验设计问题,给出了相应的实验方案和所需样本量的估计。最后,通过实例对上述方法的应用过程进行了说明,并和现有方法进行了分析比较。     

对超重、失重演示实验的改进

对传统的超重、失重演示实验进行了改进,使弹簧秤的指针能静止在超重(或失重)的位置上,从而能准确地读出读数,提高演示效果.     

金属薄膜制备及物性测量系列实验

介绍了由模拟真空实验和“金属薄膜的制备”、“金属薄膜厚度的测量”、“金属薄膜电阻率的测量”,以及“金属薄膜生长过程的动态监测”等4个实验组成的金属薄膜制备与物性测量系列实验.这组实验与现代科学技术发展联系紧密,仪器设备可靠,操作简单,适合于普通物理实验阶段的研究性教学.     

工科物理实验课程改革与实践

针对21世纪实验教学的要求,介绍了开展工科物理实验教学体系与教学内容改革的经验。