Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation. We developed a bootstrap likelihood ratio test for the interpretation of the effects of multiple shRNAs over multiple cell line passages. Our analysis identified 44 genes whose depletion preferentially inhibited the growth of cancer cells. Among these genes ribosomal protein RPL35A, putative RNA helicase DDX24, and coatomer complex I (COPI) subunit ARCN1 most significantly inhibited growth of multiple cancer cell lines without affecting normal cell growth and survival. Further investigation revealed that the growth inhibition caused by DDX24 depletion is independent of p53 status underlining its value as a drug target. Overall, our study establishes a new approach for the analysis of proliferation-based shRNA selection strategies and identifies new targets for the development of cancer therapeutics.

By making use of Langlands functoriality between GSp(4) and GL(4), we show that the images of the Galois representations attached to "genuine" globally generic automorphic representations of GSp(4) are "large" for a set of primes of density one. Moreover, by using the notion of (n, p)-groups (introduced by Khare, Larsen and Savin) and generic Langlands functoriality from SO(5) to GL(4) we construct automorphic representations of GSp(4) such that the compatible system attached to them has large image for all primes.

In this paper we construct families of Hilbert modular newforms without exceptional primes. This is achieved by generalizing the notion of good-dihedral primes, introduced by Khare and Wintenberger in their proof of Serre's modularity conjecture, to totally real fields.

In the 80's Aschbacher classified the maximal subgroups of almost all of the finite almost simple classical groups. Essentially, this classification divide these subgroups into two types. The first of these consist roughly of subgroups that preserve some kind of geometric structure, so they are commonly called subgroups of geometric type. In this paper we will prove the existence of infinitely many compatible systems {ρ ℓ