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Mitotic Kinesin motors, Eg5 and Kif15, have recently emerged as good targets for cancer as they play an inevitable role during mitosis. But, most of the Eg5 inhibitors were found ineffective when the cancer cells develop resistance to them by escalating the expression of Kif15 as alternative to Eg5. Therefore, the drugs that target Kif15 became necessary to be used either as a single or in combination with Eg5 inhibitors. The present study used 39 dihydropyrazole and 13 dihydropyrrole derivatives that were having in vitro inhibitory potential against kinesin motors to develop a common pharmacophore hypothesis AHRR and atom-based QSAR model. The model was used for virtual screening of ZINC database and the resultant hits were docked against Kif15. The four drug candidates with high docking score were examined for their activity and pharmacokinetic behaviour. Based on the results these drugs could be considered as lead candidates in further drug development for cancer. 相似文献
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巴力登 《新疆大学学报(理工版)》2006,23(1):93-97,101
以交流电机统一的双轴理论为基础,建立异步电动机的线性化控制模型,并对线性化控制系统的动态结构进行数值分析,所获仿真结果说明采用上述方法的有效性. 相似文献
115.
Dmitri Pavlov Svetla Slavova Richard J. Kryscio 《Methodology and Computing in Applied Probability》2009,11(2):249-265
This paper considers a non-parametric method for identifying intervals on the line where the relative risk of cases to controls
exceeds a pre-specified level. The method is based on the kth nearest neighbor (kNN) approach for density estimation. An asymptotic result is presented that yields an explicit formula
for constructing a confidence interval for the relative risk at a given point. Numerical simulations are used to compare this
approach with a kernel density estimation procedure. An application is made to a case-control study in which the relative
risk of motor vehicle crashes caused by female drivers is compared to male drivers in the state of Kentucky as a function
of age and then by time of day.
相似文献
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This article draws a bow from the fundamentals of the flame chemistry to combustion in engines. Aspects of radical chemistry, pollutant formation and combustion are highlighted. Concepts of current and future internal combustion engines are presented. A main focus lies on pollutant formation and reduction (CO2, CO, NOx, HC and soot). Finally, a vision of the future role of the internal combustion engine with respect to fuel cell and electrical engine is outlined. 相似文献
119.
THE ROLE OF FRONTAL NEURONS IN PAIN AND ACUPUNCTURE ANALGESIA 总被引:1,自引:0,他引:1
To study the role of frontal neurons in pain and acupuncture analgesia, experiments were carried out on 4 monkeys (Macaca mulatta) during performing two tasks, the Heat Discrimination Response GO/NO-GO Task (Task Ⅰ) and the Heat Delayed Discrimination GO/NO-GO Task (Task Ⅱ). After a criterion of 90% of correct performances over three successive days had been reached, activity of single neurons was recorded from the frontal cortex. Of 276 Task Ⅰ-related neurons, 211 responded to noxious and/or innocuous heat stimuli. Of 73 Task Ⅱ-related neurons, 59 responded to noxious and/or innocuous heat stimuli. During acupuncture, the nociceptive reaction time for lever release to avoid painful stimuli was increased, the percentage of correct performances was lowered, and the neuronal responses to noxious and/or innocuous stimuli were suppressed. These neurons were mainly located in a circumscribed area medial to the superior ramus of the arcuate sulcus in frontal cortex, including the prefrontal and premotor a 相似文献
120.
Quantification of paeonol, the principal bioactive component of Moutan cortex, in rat plasma following oral administration of Moutan cortex decoction was achieved by using a simple and sensitive high-performance liquid chromatographic method. The calibration curves for paeonol were linear in both the low (25-200 ng/mL) and the high concentration range (200-4000 ng/mL) with r(2) values of 0.9928 and 0.9993, respectively. The coefficients of variation of intra- and inter-day assays were 14.36, 6.52, 1.76, 1.25, 5.36, 3.30 and 1.42% and 12.70, 1.19, 2.98, 1.91, 1.75, 1.78 and 0.96% at concentrations of 25, 50, 100, 200, 500, 1000 and 2000 ng/mL, respectively. The recoveries of paeonol from rat plasma were found to be 101.9, 104.5, 105.4 and 101.2% for concentrations of 50, 500, 1000 and 2000 ng/mL, respectively. The paeonol plasma concentrations were fitted to two-compartment model with fi rst order absorption. The mean terminal half-lives (t(1/2)) of paeonol was 80.9 min. 相似文献