PCF1-1 is a dominant suppressor of a tRNA gene A block promoter mutation (A19) in Saccharomyces cerevisiae. Transcriptional activation by PCF1-1 was examined in vitro using whole-cell extracts and purified factors derived from mutant and wild-type strains. These experiments show that PCF1 is a general activator of RNA polymerase III (pol III) gene transcription. The transcription of all pol III genes analyzed to date, including type I and numerous type II genes, is increased 3-7 fold in mutant cell extracts. Single round transcription assays indicate that the PCF1-1 mutation increases the number of functional preinitiation complexes and suggest that this is achieved by increasing the intrinsic activity of the encoded product rather than its amount. Point mutations throughout the A block of the sup3-e gene and numerous B block mutations fail to abolish transcriptional activation suggesting that interactions between TFIIIC and the internal promoter are unaffected by PCF1-1. Moreover, TFIIIC purified from the mutant strain is incapable of conferring PCF1-1 transcriptional activity to a reaction in which the remaining components are wild-type. In contrast, the activity of the TFIIIB fraction is increased in PCF1-1 extracts and can reconstitute mutant levels of transcription when added to wild-type TFIIIC and polymerase. We conclude that PCF1 is a component or regulator of TFIIIB.
Risk involves identifying several options that the decision-maker can opt for while making a choice either in the direction of risk or reliability. In this approach, risk is defined as the action of the subject which will lead to the loss or guaranteed safety of what has been achieved. As the uncertainty of the external business environment increases for companies, the task of managing risks both individually and as a set of risks becomes more and more relevant. The purpose of this study is to solve the problem of managing multifactorial risks using mathematical methods for determining the optimal risk management trajectories separately for each factor. To determine the optimal risk management trajectories for each factor, a numerical method is used based on the choice of the most effective direction, which is defined as the ratio of risk change to cost change. An information system prototype has been created that can support the management of a set of risks. Approbation of the information system was carried out on an example containing two conceptual risk factors. The proposed prototype builds a three-dimensional risk map by interpolating the risk matrix entered by the risk manager using an additive–multiplicative aggregation procedure, as well as optimal risk management trajectories for all entered risk factors.
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