Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

一种高效的硬布线控制CPU的设计方法

文章提出了一种硬布线逻辑CPU的设计流程，即以CPU设计工具软件LDF为核心的设计方法，其主要目的的提高硬布线逻辑CPU的设计效率。定义了一种用于描述硬布线控制逻辑的语言-MCDL，对总线优化问题进行了研究，并且给出了解决总线优化问题的近似算法。     

三峡地下电站变顶高尾水洞水动力特性

在国内首次应用模型水轮发电机组对三峡地下电站变顶高尾水洞方案进行水力过渡过程试验研究。对水轮机导叶实行分段关闭 ,并求出了二段关闭的最佳拐点 ,试验证实了二段关闭对减小尾水管进口的负压和机组转速上升有明显的作用。通过有关水力参数的测试 ,认为变顶高尾水洞可以满足各项技术要求 ,是一个减少山体开挖、节省投资的新型设计方案。在地下电站中具有广泛的应用前景     

Note on ‘Construction of Double Sampling s‐Control Charts for Agile Manufacturing’

He and Grigoryan (Quality and Reliability Engineering International 2002; 18 :343–355) formulated the design of a double‐sampling (DS) s control chart as an optimization problem and solved it with a genetic algorithm. They concluded that the DS s control charts can be a more economically preferable alternative in detecting small shifts than traditional s control charts. We explain that, since they only considered the average sample size when the process is in control, their conclusion is questionable. Copyright © 2006 John Wiley & Sons, Ltd.     

分置式牛津型斯特林制冷机的数值分析与实验验证

对分置式牛津型斯特林制冷机进行了数值计算 ,介绍了计算模型考虑到的众多不可逆因素。通过对计算结果与实验结果的对比 ,验证了本文数值计算的准确性 ,说明本文计算模型与数值处理方法是切实可行的     

COMMENTS ON THE DETERMINATION OF FRIABILITY AND UNMODIFIED GRAINS

The Analysis Committee of the European Brewery Convention is aware that the Friabilimeter sometimes is used on samples that do not comply with the field of application. The precision of the method is also overlooked by some users. The field of application, precision of the method as well as the need for frequent testing of the instrument is therefore stressed in more detail than in the earlier published method by the EBC Analysis Committee.