Adenoviral Vector Driven by a Minimal Rad51 Promoter Is Selective for p53-Deficient Tumor Cells

Background: The full length Rad51 promoter is highly active in cancer cells but not in normal cells. We therefore set out to assess whether we could confer this tumor-selectivity to an adenovirus vector. Methodology/Principal Findings: Expression of an adenovirally-vectored luciferase reporter gene from the Rad51 promoter was up to 50 fold higher in cancer cells than in normal cells. Further evaluations of a panel of truncated promoter mutants identified a 447 bp minimal core promoter element that retained the full tumor selectivity and transcriptional activity of the original promoter, in the context of an adenovirus vector. This core Rad51 promoter was highly active in cancer cells that lack functional p53, but less active in normal cells and in cancer cell lines with intact p53 function. Exogenous expression of p53 in a p53 null cell line strongly suppressed activity of the Rad51 core promoter, underscoring the selectivity of this promoter for p53-deficient cells. Follow-up experiments showed that the p53-dependent suppression of the Rad51 core promoter was mediated via an indirect, p300 coactivator dependent mechanism. Finally, transduction of target cells with an adenovirus vector encoding the thymidine kinase gene under transcriptional control of the Rad51 core promoter resulted in efficient killing of p53 defective cancer cells, but not of normal cells, upon addition of ganciclovir. Conclusions/Significance: Overall, these experiments demonstrated that a small core domain of the Rad51 promoter ca

Recognition, remember-know, and confidence judgments: no evidence of cross-contamination here!

We report three experiments designed to reveal the mechanisms that underlie subjective experiences of recognition by examining effects of how those experiences are measured. Prior research has explored the potential influences of collecting metacognitive measures on memory performance. Building on this work, here we systematically evaluated whether cross-measure contamination occurs when remember-know (RK) and/or confidence (C) judgments are made after old/new recognition decisions. In Experiment 1, making either RK or C judgments did not significantly influence recognition relative to a standard no-judgment condition. In Experiment 2, making RK judgments in addition to C judgments did not significantly affect recognition or confidence. In Experiment 3, making C judgments in addition to RK judgments did not significantly affect recognition or patterns of RK responses. Cross-contamination was not apparent regardless of whether items were studied using a shallow or deep levels-of-processing task – a manipulation that yielded robust effects on recognition, RK judgments, and C. Our results indicate that under some conditions, participants can independently evaluate their recognition, subjective recognition experience, and confidence. Though contamination across measures of metamemory and memory is always possible, it may not be inevitable. This has implications for the mechanisms that underlie subjective experiences that accompany recognition judgments

Direct-drive laser fusion: Status and prospects

Techniques have been developed to improve the uniformity of the laser focal profile, to reduce the ablative Rayleigh-Taylor instability, and to suppress the various laser-plasma instabilities. There are now three direct-drive ignition target designs that utilize these techniques. Evaluation of these designs is still ongoing. Some of them may achieve the gains above 100 that are necessary for a fusion reactor. Two laser systems have been proposed that may meet all of the requirements for a fusion reactor