The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.     

Continental runoff: a quality-controlled global runoff data set

Gedney et al. attribute an increase in the twentieth-century continental runoff to the suppression of plant transpiration by CO2-induced stomatal closure, by replicating a continental runoff data set. However, we have concerns about this data set and the methods used to construct it, in addition to those already raised, which we believe may undermine their conclusions.     

Testing time-predictable earthquake recurrence by direct measurement of strain accumulation and release

Probabilistic estimates of earthquake hazard use various models for the temporal distribution of earthquakes, including the 'time-predictable' recurrence model formulated by Shimazaki and Nakata (which incorporates the concept of elastic rebound described as early as 1910 by H. F. Reid). This model states that an earthquake occurs when the fault recovers the stress relieved in the most recent earthquake. Unlike time-independent models (for example, Poisson probability), the time-predictable model is thought to encompass some of the physics behind the earthquake cycle, in that earthquake probability increases with time. The time-predictable model is therefore often preferred when adequate data are available, and it is incorporated in hazard predictions for many earthquake-prone regions, including northern California, southern California, New Zealand and Japan. Here we show that the model fails in what should be an ideal locale for its application -- Parkfield, California. We estimate rigorous bounds on the predicted recurrence time of the magnitude approximately 6 1966 Parkfield earthquake through inversion of geodetic measurements and we show that, according to the time-predictable model, another earthquake should have occurred by 1987. The model's poor performance in a relatively simple tectonic setting does not bode well for its successful application to the many areas of the world characterized by complex fault interactions.     

Cyclin synthesis drives the early embryonic cell cycle

We have produced extracts of frog eggs that can perform multiple cell cycles in vitro. Destruction of the endogenous messenger RNA arrests the extracts in interphase. The addition of exogenous cyclin mRNA is sufficient to produce multiple cell cycles. The newly synthesized cyclin protein accumulates during each interphase and is degraded at the end of each mitosis.     

Shock effects onEuglena gracilis: The effect of the pressure duration

Résumé Les cultures d'Euglena gracilis ont été soumises à des chocs de 20 et 40 (1.21 et 2.41 kg/cm²). La pression engendrée par une pulsation durait de 25µsec, 4 et 10 sec. La durée de la pression servit de critère pour évaluer les effets des niveaux élevés du choc atmosphérique sur le photo-thermotropisme d'Euglena gracilis.

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This work was supported in part by funds from Advanced Research Projects Agency, Department of Defense, through the U.S. Geological Survey, under A.R.P.A. Order No, 938. Special thanks are expressed to Dr. C. L.Newcombe of San Francisco State College, and Dr. T.Sh. Hansford of the Geological Survey for making this study possible.     

Electron-microscopic mapping of the hinge region of myosin

Summary The trypsin-sensitive sites in the labile hinge region of the myosin molecule are located with heightened accuracy (±2 nm) by electron microscopy as lying at 70, 85, 95, and 103 nm from the C-terminus of the rod section of the molecule.I thank Dr.Michael Young for valuable advice and encouragement, Drs.Jerome Gross andRomaine R. Bruns for use of their electron microscope, and Mrs.Muriel H. Blanchard for excellent technical assistance. This work was supported by the American Heart Association, The John A. Hartford Foundation, Inc., and the National Institutes of Health.