Anticancer SAR establishment and novel accruing signal transduction model of drug action using biscoumarin scaffold

In this paper, we have established methylenebis (4-hydroxy-2H-chromen-2-one) as a promising anticancer scaffold with kinesin spindle protein (KSP) inhibitory activity under malignant condition. A series of biscoumarin derivatives (MN1 to MN30) with different substituent were synthesized, and their anticancer activity was explored. Six biscoumarin derivatives that were found active were further selected to formulate organic nanoparticles (ONPs). Anticancer activity of both the forms (viz conventional and ONPs) was compared. MN30 was found most potent whereby MN10 showed good anticancer activity in both, i.e., conventional and ONP form; the structural activity relationship (SAR) study has been established. Computational investigation revealed biscoumarin scaffold as a suitable pharmacophore to bind against KSP protein. Molecular dynamics simulation studies revealed protein-ligand stability and dynamic behavior of biscoumarin-KSP complex. Finally, accruing signal transduction model was formulated to explain the observed MTT trend of conventional and ONP form. The model seems useful towards solving population specific varied results of chemotherapeutic agents. According to the model, MN10 and MN30 derivatives have good pharmacodynamics inertia and therefore, both the molecules were able to provide dose-dependent cytotoxic results.     

How does the ambiguity of the electronic stress tensor influence its ability to serve as bonding indicator

The electronic stress tensor is not uniquely defined. Possible bonding indicators originating from the quantum stress tensor may inherit this ambiguity. Based on a general formula of the stress tensor this ambiguity can be described by an external parameter λ for indicators derived from the scaled trace of the stress tensor (whereby the scaling function is proportional to the Thomas–Fermi kinetic energy density). The influence of λ is analyzed and the consequences for the representation of chemical bonding are discussed in detail. It is found that the scaled trace of the stress tensor may serve as suitable bonding indicator over a wide range of λ values, excluding the value range between ?0.15 and ?0.48. Focusing on the eigenvalues of the stress tensor, it is found that the sign of the eigenvalues heavily depends on the chosen representation of the stress tensor. Therefore, chemical bonding analyses which are based on the interpretation of the eigenvalue sign (e.g., the spindle structure) are strongly dependent on the chosen form of the stress tensor. © 2014 Wiley Periodicals, Inc.     

微液滴在仿蛛丝结构TiO2纤维表面的定向运动与粘附

制备了具有响应性的仿蛛丝周期纺锤节TiO₂纤维。通过改变纤维表面微观结构、紫外光照和超声波等手段,仿蛛丝结构TiO₂纤维表面浸润性会发生响应性变化。纤维表面的这种浸润性变化,不仅实现了水滴从纺锤节两端到中心处的定向运动,而且可以使得水滴被纤维纺锤节粘附。当仿蛛丝结构TiO₂纤维表面为亲水状态时,无论纺锤节光滑还是粗糙,水都是从纺锤节两端向中心方向运动;当仿蛛丝TiO₂纤维表面疏水时,水滴会被具有粗糙表面的纺锤节两端粘附。     

薄壁件加工系统动态响应分析

薄壁件在铣削加工中容易产生共振或变形,直接影响加工稳定性及加工精度。采用主轴-刀具-工件整体铣削系统连续梁模型,系统研究在动态铣削力作用下,刀具端部与工件端部的动态响应之间的相互影响关系以及对整体系统动态响应影响较大的薄壁件尺寸。结果表明,工件横截面高度对系统共振的影响较为明显,当高度尺寸较小时,工件的低频共振会通过动态铣削力直接反映到刀具端部的振动频响上。工件横截面底边宽度尺寸的增大虽然对共振频率的改变不太明显,但会导致激发出来的刀具共振幅度出现明显降低。研究成果可以为薄壁件铣削加工系统的稳定性控制提供理论基础。     

Dimethylarsinic acid targets tubulin in mitotic cells to induce abnormal spindles

Dimethylarsinic acid (DMA) is the most effective inducer of cell‐cycle disruption among the arsenic compounds and their metabolites. The present study was conducted to gain further insight into cell‐cycle disruption induced by DMA. The inhibition of cell proliferation and the mitotic arrest induced by DMA were significant and dose‐dependent in Chinese hamster V79 cells and the two seemed to be closely related. At less than 140 µM the DMA did not inhibit the proliferation of cells, but it significantly induced mitotic arrest. An indirect immunofluorescence assay using anti‐α‐tubulin antibodies revealed that DMA induced the formation of abnormal spindles in the metaphase cells even at 350 µM with 5 h of treatment. At 1.4 mM DMA no metaphase cells could form a definite spindle structure. The spindle figures were similar to those induced by colchicine (125 nM ) or vinblastine (110 nM ), major antimitotic agents. In DMA‐treated interphase cells, the microtubule networks were indistinguishable from those of normal cells. With the tubulin‐assembly assay estimated by turbidity, DMA at less than 200 µM suppressed tubulin assembly in a dose‐dependent manner, whereas at more than 700 µM it enhanced tubulin polymerization remarkably with or without addition of excess guanosine‐5′‐triphosphate. According to the above findings, we discussed the possibility that DMA, a primary metabolite of inorganic arsenic in mammals, is related to arsenic carcinogenicity. Copyright © 2001 John Wiley & Sons, Ltd.     

Effects of inorganic and organic lead compounds on chromosomal length in human lymphocytes

In vitro exposure of human lymphocyte cultures to spindle inhibitors reduce the average chromosome length^1,2. In this report chromosome length measurements were used for indirect but quantitative evaluation of the effects of inorganic and organic lead compounds on spindle function. The data indicate that organic compounds are much more powerful spindle inhibitors than inorganic lead compounds, almost as potent as colchicine. Occupational exposure to organic lead compounds may result in partial spindle inhibition, leading to a high probability of nondisjunction.     

基于电力线载波与TCP/IP协议的刚体转动惯量实验系统的设计

介绍了一种新的测量刚体转动惯量的实验方法与实验装置,在实验中,通过增加标准刚体试件,把细线拉力对转轴摩擦力矩的影响考虑进去,大幅度地提高了实验测试精度,另外,利用电力线载波通讯网络,将转动惯量测量仪采集的时间数据传输到PC机中,再经过PC机端数据处理软件,快速准确地将待测刚体的转动惯量以及其它与刚体有关的物理量计算、显...     

Muscle spindles are concentrated in the superior vocalis subcompartment of the human thyroarytenoid muscle

It is hypothesized that different parts of the thyroarytenoid muscle (TA) are functionally specialized. Specifically, the TA is divided into a lateral muscularis compartment and a medial vocalis compartment. This study examined the distribution of muscle spindles throughout the human TA as an indicator of these functional differences. Histological cross-sections from the anterior, middle, and posterior regions of five human membranous vocal folds were examined for the number and location of muscle spindles. There was an average of 6.1 muscle spindles in sections from each region with no significant variation between the different regions (p < .05). However, in sections from all three regions, the muscle spindles were always found to be concentrated in the superior medial quadrant of the TA (mean 85.9%, p < .01). The inferior medial, superior lateral, and inferior lateral quadrants of the TA contained 11.96%, 2.17%, and 0%, respectively, of the total muscle spindles. Within the superior medial quadrant, most of the muscle spindles were localized in the most superficial part of the muscle.The results of this study demonstrate that the majority of TA muscle spindlesare concentrated in its superior medial quadrant, an area we have termed the superior vocalis subcompartment (SC. This finding suggests that the superior vocalis SC is functionally distinct from the remainder of the TA. It is hypothesized that tension in the superior vocalis SC can be controlled independently from the remainder of the TA, and this capability is used to effect the biomechanics of vocal fold vibration during phonation.     

滚珠花键支撑斯特林制冷机研制

针对整体式斯特林制冷机"侧向力"的问题,提出一种滚珠花键支撑结构,并设计加工了样机。对采用滚珠花键支撑结构斯特林制冷机结构设计的要点进行了详尽的分析,指出采用滚珠花键支撑结构改善了整体式斯特林制冷机的可靠性。文中还对样机性能调试的相关情况进行了介绍。     

硅酸盐对Ferrihydrite相转化为α-Fe2O3微粒形貌的调控作用

以Ferrihydrite(又称水合氧化铁hydrous iron oxide)为反应前驱物, Fe(II)为催化剂, 在微量Na₂SiO₃存在下, 控制pH＝6～9范围内合成出了亚微米级纺锤形和准立方形α-Fe₂O₃微粒. 研究了初始pH, Na₂SiO₃浓度, Ferrihydrite老化方式对相转化时间和产物形貌的影响, 利用XRD, SEM等手段对产物进行了表征. 结果表明, Na₂SiO₃对Ferriihydrite催化相转化有一定的抑制作用, 是影响其相转化过程及产物形貌的关键. 在弱碱性条件下, [Si]/[Fe^3＋]为0.01时可直接获得纺锤形(轴比≥2)或准立方形(300～400 nm) α-Fe₂O₃粒子, 并对形成机理进行了初步讨论.