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Mice in which lung epithelial cells can be induced to express an oncogenic KrasG12D develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non-coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of KrasG12D tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase-related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide polymorphisms revealed not only a change in expression of Cd22 but also that its expression became allele specific in tumors. The most salient finding, however, came from small RNA sequencing of the tumor samples, which revealed that a cluster of ∼53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome 12qF1 was markedly and consistently increased in tumors. Activation of this locus occurred specifically in sorted tumor-originating cancer cells. Interestingly, the 12qF1 RNAs were repressed in cultured KrasG12D tumor cells but reactivated when transplanted in vivo. These microRNAs have been implicated in stem cell pleuripotency and proteins targeted by these microRNAs are involved in key pathways in cancer as well as embryogenesis. Taken together, our results strongly imply that these microRNAs represent key targets in unraveling the mechanism of lung oncogenesis. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper, passive and active approaches for the design of fault-tolerant controllers (FTCs) are presented. The FTCs are used to improve the damping of inter-area oscillations in a power grid. The effectiveness of using a combination of local and remote (wide area) feedback signals is first demonstrated. The challenge is then to guarantee a minimum level of dynamic performance following a loss of remote signals. The designs are based on regional pole placement using linear matrix inequalities. First, a passive FTC is proposed. It is shown that the computation of the controller reduces to the solution of bilinear matrix inequalities. An iterative procedure is then used to design the controller. Next, as an alternative to active, time-varying controllers, one for each fault scenario, we propose an approach for the design of a 'minimal switching' FTC in which only one controller is designed, but where a simple switch is incorporated into the controller structure. A case study in a linear and nonlinear Nordic equivalent system is presented to show that the closed-loop response using a conventional control design could deteriorate the performance or even destabilize the system if the remote signals are lost and to demonstrate the effectiveness of the proposed FTC designs. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]