Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells

Originally purified as a major lipid component of a strain of the cyanobacterium Lyngbya majuscula isolated in Cura?ao, curacin A is a potent inhibitor of cell growth and mitosis, binding rapidly and tightly at the colchicine site of tubulin. Because its molecular structure differs so greatly from that of colchicine and other colchicine site inhibitors, we prepared a series of curacin A analogs to determine the important structural features of the molecule. These modifications include reduction and E-to-Z transitions of the olefinic bonds in the 14-carbon side chain of the molecule; disruption of and configurational changes in the cyclopropyl moiety; disruption, oxidation, and configurational reversal in the thiazoline moiety; configurational reversal and substituent modifications at C13; and demethylation at C10. Inhibitory effects on tubulin assembly, the binding of colchicine to tubulin, and the growth of MCF-7 human breast carcinoma cells were examined. The most important portions of curacin A required for its interaction with tubulin seem to be the thiazoline ring and the side chain at least through C4, the portion of the side chain including the C9-C10 olefinic bond, and the C10 methyl group. Only two modifications totally eliminated the tubulin-drug interaction. The inactive compounds were a segment containing most of the side chain, including its two substituents, and analogs in which the methyl group at the C13 oxygen atom was replaced by a benzoate residue. Antiproliferative activity comparable with that observed with curacin A was only reproduced in compounds that were potent inhibitors of the binding of colchicine to tubulin. Molecular modeling and quantitative structure-activity relationship studies demonstrated that most active analogs overlapped extensively with curacin A but failed to provide an explanation for the apparent structural analogy between curacin A and colchicine.     

An economic discrete replacement policy for a shock damage model with minimal repairs

A discrete replacement model for a repairable system which is subject to shocks and minimal repairs is discussed. Such shocks can be classified, depending on its effect to the system, into two types: Type I and Type II shocks. Whenever a type II shock occurs causes the system to go into failure, such a failure is called type II failure and can be corrected by a minimal repair. A type I shock does damage to the system in the sense that it increases the failure rate by a certain amount and the failure rate also increases with age due to aging process without external shocks; furthermore, the failure occurred in this condition is called type I failure. The system is replaced at the time of the first type I failure or the n-th type Il failure, whichever occurs first. Introducing costs due to replacement and mininal repairs, the long-run expected cost per unit time is derived as a criterion of optimality and the optimal number n∗ found by minimizing that cost. It is shown that, under certain conditions, there exists a finite and unique optimal number n∗.     

短时间、大功率磁流体发电

介绍了正在发展中的、以炸药或燃烧驱动的等离子体为工质的短时间、大功率磁流体（MHD）发电系统。这是一种脉冲发电系统，可提供几百兆瓦或更高的脉冲功率；也是一种利用电能的新概念火炮的合适能源，具有广阔的军事应用前景。文中还介绍了磁流体发电的基本原理；结合国外的发展现状、动态和我们做过的有关工作，对研制这种脉冲发电系统将会碰到的部分问题作出了评述。     

灯饰横梁压形整形复合模设计与工艺分析

介绍了灯饰横梁零件成形工作过程及工艺过程,对灯饰横梁零件压形整形复合模作了较详细介绍,对生产类似产品的厂家有一定的参考应用价值。     

合成油酸丁酯用TiSiW_(12)O_(40)/TiO_2-SnO_2催化剂的制备与性能研究

制备出以混合氧化物为载体的固载杂多酸盐催化剂TiSiW1 2 O4 0 /TiO2 -SnO2 ,以油酸和正丁醇为原料 ,系统研究了催化合成油酸丁酯的影响因素 ,确定了该反应的优化条件 :醇酸摩尔比为 2∶1,催化剂用量为反应物总质量的 1 5 % ,反应时间 60min ,反应温度 13 0～ 14 0℃。在此反应条件下 ,油酸丁酯的收率达到 90 8%。     

Fiber Bragg grating dispersion compensator by single-period overlap-step-scan exposure

We theoretically demonstrate that a high-quality fiber Bragg grating dispersion compensator can be fabricated by a properly designed single-period overlap-step-scan exposure method. A practical design example and a detailed tolerance analysis of this new fabrication method are given.     

Improved ESD protection by combining InGaN-GaN MQW LEDs with GaN Schottky diodes

GaN Schottky diodes were built internally inside the GaN green LEDs by using etching and redeposition techniques. By properly selecting the etching areas underneath the bonding pads, one can minimize the optical loss due to the etching process. Although the reverse current and the forward turn-on voltage were both higher for the GaN LED with a Schottky diode, it was found that the internal Schottky diode could significantly increase the electrostatic discharge threshold from 450 to 1300 V.     

Electrothermal coupling analysis of current crowding and Joule heating in flip-chip packages

Solder bumps serve as electrical paths as well as structural support in a flip-chip package assembly. Owing to the differences of feature sizes and electric resistivities between a solder bump and its adjacent traces, current densities around the regions where traces connect the solder bump increase in a significant amount. This current crowding effect along with the induced Joule heating would accelerate fatigue failure due to electromigration. In this paper we apply the three-dimensional electrothermal coupling analysis to investigate current crowding and Joule heating in a flip-chip package assembly carrying different constant electric currents under different ambient temperatures. Experiments are conducted to calibrate temperature-dependent electric resistivities of solder alloy, Al trace, and Cu trace, and to verify the numerical model by comparing calculated and measured maximum temperatures on the die surface. Through the electrothermal coupling analysis, effects of current crowding and Joule heating induced by different solder bump structures are examined and compared.