Activation of mammalian innate and acquired immune responses must be tightly regulated by elaborate mechanisms to control their onset and termination. MicroRNAs have been implicated as negative regulators controlling diverse biological processes at the level of posttranscriptional repression. Expression profiling of 200 microRNAs in human monocytes revealed that several of them (miR-146a͞b, miR-132, and miR-155) are endotoxin-responsive genes. Analysis of miR-146a and miR-146b gene expression unveiled a pattern of induction in response to a variety of microbial components and proinflammatory cytokines. By means of promoter analysis, miR-146a was found to be a NF-B-dependent gene. Importantly, miR-146a͞b were predicted to base-pair with sequences in the 3 UTRs of the TNF receptor-associated factor 6 and IL-1 receptor-associated kinase 1 genes, and we found that these UTRs inhibit expression of a linked reporter gene. These genes encode two key adapter molecules downstream of Toll-like and cytokine receptors. Thus, we propose a role for miR-146 in control of Toll-like receptor and cytokine signaling through a negative feedback regulation loop involving down-regulation of IL-1 receptor-associated kinase 1 and TNF receptor-associated factor 6 protein levels.immunity ͉ microRNA ͉ LPS ͉ Toll-like receptor

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Reachability analysis is a fundamental technique in the synthesis, verification of VLSI circuits. This paper presents a novel semi-formal approach which combines the advantages of simulation and formal methods to traverse the state space of the FSMs. We conduct the experiments on a set of ISCAS'89 benchmarks. Compared with a previous work which relies on biased random technique, our approach reaches more states with less CPU time.978-1-4244-5271-2/10/$26.00 ©2010 IEEE