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, 2013; Miyazaki et?al., 2012; Nakano and Kornblum, 2009). Animals were monitored until the development of neuropathological symptoms. Statistical Analysis For analysis of FACS data, measurements with less than 2,000 cell counts were excluded. Measurements were standardized by the average of the non-target shRNA measurements separately for each plate. Ratios were log2 transformed to more closely follow a normal distribution. Relevant kinase directed shRNAs were identified using the empirical Bayes approach (Smyth, 2004) based on moderated t statistics as implemented in the Bioconductor Lapatinib chemical structure package limma (Smyth, 2005). All p values were adjusted for multiple testing using Benjamini-Hochberg correction in order to control the false discovery rate. Adjusted p values below 0.05 were considered statistically significant. All analyses were carried out using software R 3.0.1. (RDC Team, 2011). A detailed method is described in the Supplemental Information. Functional data were analyzed using Graphpad prism 6 and presented as mean �� SD. Statistical significance of Kaplan-Meier survival plot was determined by log-rank test; p?PI3K inhibitor and P.L. wrote the manuscript. I.N. designed experiments, analyzed data, and wrote manuscript. V.G. designed experiments, performed experiments, analyzed data, and wrote the manuscript. Acknowledgments We would like to thank David Jones for fruitful discussion and suggestions. P.C. was supported by The First Hospital of China Medical University. E.P. was supported by the Helmholtz International Graduate School for Cancer Research. This work was supported by a fund of the Bundesministerium f��r Bildung und Forschung, BMBF (NGFNplus, #01GS0883) to V.G. and CA163205-01A1, NS083767-01, CA175875-01A1, S6 Kinase and NS087913-01 to I.N. and P30 CA016058 to the Comparative Pathology and Mouse Phenotyping Shared Resource of Ohio State University. Footnotes This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Supplemental Information Document S1. Supplemental Experimental Procedures and Figures S1�CS5: Click here to view.(3.6M, pdf) Document S2. Article plus Supplemental Information: Click here to view.(6.9M, pdf)""With the first reports on generating human induced pluripotent stem cells (hiPSCs) from human cells (Takahashi et?al., 2007; Yu et?al., 2007), the controversy regarding the ethics of research involving human embryonic stem cells (hESCs) (Thomson et?al., 1998) has arisen once again (Holm, 2008).