PARP inhibitors have recently been approved as monotherapies for the treatment of recurrent ovarian cancer and metastatic -associated breast cancer, and ongoing studies are exploring additional indications and combinations with other agents. PARP inhibitors trap PARP onto damaged chromatin when combined with temozolomide and methyl methanesulfonate, but the clinical relevance of these findings remains unknown. PARP trapping has thus far been undetectable in cancer cells treated with PARP inhibitors alone.
View Article and Find Full Text PDFThe evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p-Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains.
View Article and Find Full Text PDFMonitoring promoter response to environmental changes using reporter systems has provided invaluable information regarding cellular state. With the development of in vivo luciferase reporter systems, inexpensive, sensitive and accurate promoter assays have been developed without the variability reported between in vitro samplings. Current luciferase reporter systems, however, are largely inflexible to modifications to the promoter of interest.
View Article and Find Full Text PDFIn this paper, the perceptual effects of vowel-to-vowel transitions determined by different temporal variations of model parameters which specify the shapes of the vocal tract area function are investigated. It is shown that, (a) the method of deformation of the vocal tract area function between two targets can be perceptually important and (b) conversely, within certain limits, the time course of parameters from one state to another, and the precise synchronization of two parameters is not important for the correct identification of a vowel series. These characteristics are necessary but not sufficient to prove the existence of a phonetic gesture percept.
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