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We show herein that human DNA topoisomerase II beta is functional in yeast. It can complement a yeast temperature-sensitive mutation in topoisomerase II. The effect on human topoisomerase II beta of a number of topoisomerase II inhibitors was analysed in a yeast in vivo system and compared with that of human topoisomerase II alpha and wild-type yeast topoisomerase II. A drug permeable yeast strain (JN394 top2-4) was used to analyse the in vivo effects of known anti-topoisomerase II agents on human topoisomerase II beta transformants. A parallel analysis on human topoisomerase II alpha transformants provides the first in vivo analysis of the responses of yeast bearing the individual isoforms to these drugs. The strain was analysed at 35 degrees C, a non-permissive temperature at which only plasmid-borne topoisomerase II is active. A shuttle vector with either human topoisomerase II beta, human topoisomerase II alpha or yeast topoisomerase II under the control of a GAL1 promoter was used. The key findings were that amsacrine produced comparable levels of cell killing with both alpha and beta, whilst etoposide, doxorubicin and mitoxantrone produced higher degrees of cell killing with alpha than with beta or yeast topoisomerase II. Merbarone had the greatest effect on the yeast strain bearing plasmid-borne yeast topoisomerase II. Suramin, quercetin and genistein showed little cell killing in this system. This yeast in vivo system provides a powerful way to analyse the effects of anti-topoisomerase II agents on transformants bearing the individual human isoforms. This system also provides a means of analysing putative drug-resistance mutations in human topoisomerase II beta or to select for drug-resistance mutations in human topoisomerase II beta. 相似文献
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M. I. McManus 《Computers & Operations Research》1977,4(4):271-278
This paper notes that the workload of a sorting office varies from day to day, that scheduled duties are fixed in the short run, and that some overtime is usually available to deal with the excess. Without specific assumptions about the distribution of workload, it gives a means of saying what the optimum staffing level is, and how it depends on the cost of overtime, overheads associated with employing a man, and on any “penalty” for failure to sort the mail on time. For a simplified assumption about the workload distribution, it then considers some specific overtime rules and illustrates how costs and average pay per man depend on the staffing level and the manner of allocation of overtime. It suggests a sense in which the financial interests of the employer do not necessarily conflict with those of the employees. 相似文献
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The reversed-phase, ion-pairing approach to high-pressure liquid chromatography was applied to the simultaneous analysis of hydrocortisone and its phosphate ester in laboratory-prepared samples and injectable solutions. Results of this technique were evaluated and compared with results of the official procedure. 相似文献
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