Nucleic acid reactivity: Challenges for next‐generation semiempirical quantum models

Semiempirical quantum models are routinely used to study mechanisms of RNA catalysis and phosphoryl transfer reactions using combined quantum mechanical (QM)/molecular mechanical methods. Herein, we provide a broad assessment of the performance of existing semiempirical quantum models to describe nucleic acid structure and reactivity to quantify their limitations and guide the development of next‐generation quantum models with improved accuracy. Neglect of diatomic differential overlap and self‐consistent density‐functional tight‐binding semiempirical models are evaluated against high‐level QM benchmark calculations for seven biologically important datasets. The datasets include: proton affinities, polarizabilities, nucleobase dimer interactions, dimethyl phosphate anion, nucleoside sugar and glycosidic torsion conformations, and RNA phosphoryl transfer model reactions. As an additional baseline, comparisons are made with several commonly used density‐functional models, including M062X and B3LYP (in some cases with dispersion corrections). The results show that, among the semiempirical models examined, the AM1/d‐PhoT model is the most robust at predicting proton affinities. AM1/d‐PhoT and DFTB3‐3ob/OPhyd reproduce the MP2 potential energy surfaces of 6 associative RNA phosphoryl transfer model reactions reasonably well. Further, a recently developed linear‐scaling “modified divide‐and‐conquer” model exhibits the most accurate results for binding energies of both hydrogen bonded and stacked nucleobase dimers. The semiempirical models considered here are shown to underestimate the isotropic polarizabilities of neutral molecules by approximately 30%. The semiempirical models also fail to adequately describe torsion profiles for the dimethyl phosphate anion, the nucleoside sugar ring puckers, and the rotations about the nucleoside glycosidic bond. The modeling of pentavalent phosphorus, particularly with thio substitutions often used experimentally as mechanistic probes, was problematic for all of the models considered. Analysis of the strengths and weakness of the models suggests that the creation of robust next‐generation models should emphasize the improvement of relative conformational energies and barriers, and nonbonded interactions. © 2015 Wiley Periodicals, Inc.     

不同的灰熔点调控方式对煤灰熔融特性的影响

对两种原始煤灰进行混合,并分别搭配不同的添加剂,得到3种元素组成相同的煤灰,灰熔点测试结果显示,三者的灰熔点存在较大差异。结合X射线衍射技术和SEM-EDX(扫描电子显微镜与能谱联用)分析了3种煤灰(>800 ℃)在高温时的矿物质转化过程。结果表明,不同的灰熔点调控手段对不同煤的影响是不同的。原因是高温时矿物质组成不仅与煤灰化学元素组成相关,更与元素在矿物质中的赋存状态有关。两者共同决定了煤灰的熔融特性。     

新烟碱类杀虫剂生物活性的理论研究和结构修饰*

在B3LYP/6-311G基组水平下,运用密度泛函理论(DFT)的量子化学方法,对20种重氮乙烷新烟碱类杀虫剂分子的电子结构特征进行了研究,获得了它们的前线轨道能(EHOMO、ENHOMO、ELUMO、ENLUMO等)、原子电荷(Qi)、摩尔熵(Sm)、偶极矩(μ)等量化参数与物理性质。经最佳变量子集回归研究发现,重氮乙烷新烟碱类杀虫剂分子对果蝇n AChRs、哺乳动物α4β2亚型的亲和力常数(p KD、p KA)分别与ELUMO、QW、QF、QN等参数具有良好的线性关系。逐一或逐四剔除交互验证以及VIF、tα/2检验,所建2个QSAR模型具有良好的稳健性及预测能力。根据2个QSAR模型推断了重氮乙烷新烟碱类分子可能的杀虫机理。进一步研究发现,在重氮乙烷新烟碱类分子的吡啶环上的合适部位,选用不含复键的吸电子能力较强的取代基团对其进行结构修饰,有利于提高修饰后分子的生物活性。基于分子17,设计出4种经结构修饰后对果蝇n AChRs亲和力显著提高的重氮乙烷新烟碱类分子(分别是分子27,28,30和31),希望能得到实验的证实。     

Ill-posed problems in rheology

Experimental data are always noisy and often incomplete. This leads to ambiguities if one wants to infer from the data some functions, which are related to the measured quantity through an integral equation of the first kind. In rheology many of such so-called ill-posed problems appear. Two techniques to treat such problems, the regularization method and the maximum entropy method, are applied to the determination of the relaxation spectrum from data of small oscillatory shear flow. With simulated data from a reference spectrum it is discussed how the inferred spectrum depends on the region, in which data are available. It turns out that information about the asymptotic behavior of the measured quantity can be of great help in determining the full spectrum also from incomplete data.Dedicated to Prof. Dr. J. Meissner on the occasion of his 60th birthday.     

A numerical approach to spherical indentation techniques for material property evaluation

In this work, some inaccuracies and limitations of prior indentation theories, which are based on experimental observations and the deformation theory of plasticity, are investigated. Effects of major material properties on the indentation load-deflection curve are examined via finite element (FE) analyses based on incremental plasticity theory. It is confirmed that subindenter deformation and stress-strain distribution from deformation plasticity theory are quite dissimilar to those obtained from incremental plasticity theory. We suggest an optimal data acquisition location, where the strain gradient is the least and the effect of friction is negligible. A new numerical approach to indentation techniques is then proposed by examining the FE solutions at the optimal point. Numerical regressions of obtained data exhibit that the strain-hardening exponent and yield strain are the two key parameters which govern the subindenter deformation characteristics. The new indentation theory successfully provides a stress-strain curve and material properties with an average error of less than 3%.     

In search of physical parameters influenced by flow patterns in a heterogeneous two-phase mixture in microchannels using concomitant measurements

Space transportation systems require high-performance thermal protection and fluid management for systems ranging from cryogenic fluid devices to primary structures, and for propulsion systems exposed to extremely high temperatures, and other space systems, e.g., integrated circuits and cooling/environment control devices for advanced space suits. Although considerable developmental effort is underway to bring promising technologies to a readiness level for practical use, new and innovative methods are still needed. One such method is the Advanced Micro Cooling Module (AMCM), essentially a compact two-phase heat exchanger constructed of microchannels and designed to rapidly remove large quantities of heat from critical systems by incorporating phase transition. This paper describes the results of experimental research in two-phase flow phenomena, encompassing both an experimental and an analytical approach to the incorporation of flow patterns for air–water mixtures flowing in microchannels. Specifically addressed are: (1) design and construction of a sensitive two-phase experimental system which measures both ac and dc components of in situ physical mixture parameters including spatial concentration, using concomitant methods; (2) data acquisition and analysis in the amplitude, time, and frequency domains; and (3) analysis of results including evaluation of in situ physical parameters, and assessment of their validity for application in flow pattern determination.     

基于变形场测量数据主元压缩的模型参量反求方法

利用主元分析法对数字图像相关技术所测结构变形信息进行数据压缩,并进一步用于力学模型未知参量的反求计算。首先,为降低数字图像相关技术所测庞大数据的应用成本,提出利用主元分析法对结构表面变形场数据进行压缩,实现在保留结构表面变形信息主要特征的前提下显著降低数据量的目的;其次,针对压缩后的数据建立了基于最小二乘法的力学模型参量反求模型,并利用高斯牛顿法进行求解;最后,以具体算例从计算精度、收敛速度和抗噪性等方面验证了数据压缩对模型参量反求的效果。研究结果表明,所提方法在显著降低使用数据量的前提下,能够有效提高力学模型参量反求计算的收敛速度,特别是对于包含多个模型参数的反求问题,具有较高的精度和较好的稳定性。     

异质传感器数据的最优线性融合

研究了异质传感器对参数矢量进行的测量，测量数据基于线性均方估计的最优融合算法。提出和证明了异质传感器数据的最优线性融合定理，并得出“精度再差的传感器参与数据融合后都有利于提高系统的测量精度”这一结论。     

一种用于分散化滤波的融合算法及其在组合导航系统中的应用

提出了一种局部估计相关时的最优融合算法，其特点是加权矩阵是对角阵，即全局估计中的各分量分别是局部估计中相应分量的线性组合，在此融合算法中局部估计是最优的，并且不存在由主滤波器向子滤波器的信息反馈，因此具有较好的客措性。给出了最优加权矩阵的存在性和唯一性的证明，并通过与现有类似融合算法的对比，表明该算法具有计算量小的优点。最后，以组合导航系统为例作了仿真计算，结果表明该融合算法是可行的。     

大数据时代下的化学经验2.0：基于键能的大规模反应途径预测

报道了一个基于键能数据预测反应途径的可编程算法．运用该算法,成功预测了F₂+CH₃Cl气相反应的最优产物(CF₄)和对应的反应途径．提供了一个启示性的化学经验2.0 的例子,并可能开启大数据时代下的大规模反应途径预测的大门．