Ritter Behrens (lawyersharon64)

Fractional killing, which is a significant impediment to successful chemotherapy, is observed even in a population of genetically identical cancer cells exposed to apoptosis-inducing agents. This phenomenon arises not from genetic mutation but from cell-to-cell variation in the activation timing and level of the proteins that regulates apoptosis. To understand the mechanism behind the phenomenon, we formulate complex fractional killing processes as a first-passage time (FPT) problem with a stochastically fluctuating boundary. Analytical calculations are performed for the FPT distribution in a toy model of stochastic p53 gene expression, where the cancer cell is killed only when the p53 expression level crosses an active apoptotic threshold. Counterintuitively, we find that threshold fluctuations can effectively enhance cellular killing by significantly decreasing the mean time that the p53 protein reaches the threshold level for the first time. Moreover, faster fluctuations lead to the killing of more cells. These qualitative results imply that fluctuations in threshold are a non-negligible stochastic source, and can be taken as a strategy for combating fractional killing of cancer cells. © 2020 The Authors.Bilinguals purportedly outperform monolinguals in non-verbal tasks of cognitive control (the 'bilingual advantage'). The most common explanation is that managing two languages during language production constantly draws upon, and thus strengthens, domain-general inhibitory mechanisms (Green 1998 Biling. Lang. Cogn. 1, 67-81. (doi10.1017/S1366728998000133)). However, this theory cannot explain why a bilingual advantage has been found in preverbal infants (Kovacs & Mehler 2009 Proc. Natl Acad. Sci. USA 106, 6556-6560. (doi10.1073/pnas.0811323106)). An alternative explanation is needed. We propose that exposure to more varied, less predictable (language) environments drive infants to sample more by placing less weight on consolidating familiar information in order to orient sooner to (and explore) new stimuli. To confirm the bilingual advantage in infants and test our proposal, we administered four gaze-contingent eye-tracking tasks to seven- to nine-month-old infants who were being raised in either bilingual (n = 51) or monolingual (n = 51) homes. We could not replicate the finding by Kovacs and Mehler that bilingual but not monolingual infants inhibit learned behaviour (experiment 1). However, we found that infants exposed to bilingual environments do indeed explore more than those exposed to monolingual environments, by potentially disengaging attention faster from one stimulus in order to shift attention to another (experiment 3) and by switching attention more frequently between stimuli (experiment 4). These data suggest that experience-driven adaptations may indeed result in infants exposed to bilingual environments switching attention more frequently than infants exposed to a monolingual environment. © 2020 The Authors.[This corrects the article DOI 10.1093/workar/waw038.][This corrects the article DOI 10.1093/workar/waw038.]. © The Author(s) 2019. Published by Oxford University Press. For permissions please e-mail journals.permissions@oup.com.We encountered a patient with mitochondrial trifunctional protein deficiency in whom the corresponding mutations were not identified by a DNA panel for newborn screening for targeted diseases. After diagnosis confirmation by an enzyme assay and immunoblotting using the autopsied liver, the re-evaluation of the panel data indicated a heterozygous deletion of exons 6-9 that was later confirmed at the genomic level. cDNA analysis also identified exonization of the 5' region of intron 9 caused by a deep intronic mutation, c.811 + 82A>G. © The Author(s) 2020.We report a 7-year-old boy with infantile spasms caused by a novel mutation in the Aristaless-related homeobox (ARX) gene. He showed infantile spasms and hypsarrhythmia on electroencephalogram from early infancy. Brain MRI