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DiscussionWe congratulate the authors for their thought-provoking and fascinating work on a fundamental yet challenging topic in variable selection. Driven by the pressing need of high dimensional data analysis in many fields, the problem of dimension reduction without losing relevant information becomes increasingly important. Fan and Lv successfully tackled the extremely challenging case, where log(p) = O(n ξ ), ξ > 0. The proposed Sure Independence Screening (SIS) is a state of the art method for high dimensional variable screening: simple, powerful, and having optimal properties. This work is a substantial contribution to the area of variable selection and will also make a significant impact in other scientific fields.. Extension to nonparametric modelsIn linear models, marginal correlation coefficients between linear predictors and the response are effective measures to capture strength of their linear relationship. However, correlation coefficients generally do not work for ranking nonlinear effects. Consider the additive model, where f j takes an arbitrary nonlinear function form. Motivated by the ranking idea of the SIS, one could first fit a univariate smoother for each predictor and then use some marginal statistics to rank the covariates. Many interesting questions arise in this approach. Firstly, what are good measures to characterize the strength of the nonlinear relationship fully? Possible choices include nonparametric test statistics, p-values, and goodness-of-fit statistics like R 2 . But which is best? Also, how do we develop the consistent selection theory for the procedure of screening nonlinear effects? All of these questions are challenging because of the complicated estimation that is involved in nonparametric modeling. It would be interesting to explore whether and how the SIS can be extended to this context. Connection to multiple hypotheses testing and false discovery rate controlThe variable selection problem can be regarded as the problem of testing multiple hypotheses: H 1 : β 1 = 0, …, H p : β p = 0. Screening important variables is hence equivalent to identifying the hypotheses to be rejected. The false discovery rate (Benjamini and Hochberg, 1995) has been developed to control the proportion of false rejections. Some consistent procedures based on individual tests of each parameter have been developed (Potscher 1983;Bauer et al. 1988). Recently, Bunea et al., (2006) considered the case when p increases with n, and showed the false discover rate or Bernoulli adjustment can lead to consistent selection of variables under certain conditions. Their method is based on the ordered p-values of individual t-statistics NIH Public Access

Autophagy is a catabolic pathway used by cells to support metabolism in response to starvation and to clear damaged proteins and organelles in response to stress. We report here that expression of a H-ras V12 or K-ras V12 oncogene up-regulates basal autophagy, which is required for tumor cell survival in starvation and in tumorigenesis.In Ras-expressing cells, defective autophagosome formation or cargo delivery causes accumulation of abnormal mitochondria and reduced oxygen consumption. Autophagy defects also lead to tricarboxylic acid (TCA) cycle metabolite and energy depletion in starvation. As mitochondria sustain viability of Ras-expressing cells in starvation, autophagy is required to maintain the pool of functional mitochondria necessary to support growth of Ras-driven tumors. Human cancer cell lines bearing activating mutations in Ras commonly have high levels of basal autophagy, and, in a subset of these, down-regulating the expression of essential autophagy proteins impaired cell growth. As cancers with Ras mutations have a poor prognosis, this ''autophagy addiction'' suggests that targeting autophagy and mitochondrial metabolism are valuable new approaches to treat these aggressive cancers.