Role of MicroRNA-26b in Glioma Development and Its Mediated Regulation on EphA2

BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Deregulation of miRNAs is common in human tumorigenesis. Low level expression of miR-26b has been found in glioma cells. However, its underlying mechanism of action has not been determined. METHODOLOGY/PRINCIPAL FINDINGS: Real-time PCR was employed to measure the expression level of miR-26b in glioma patients and cells. The level of miR-26b was inversely correlated with the grade of glioma. Ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells. A binding site for miR-26b was identified in the 3'UTR of EphA2. Over-expression of miR-26b in glioma cells repressed the endogenous level of EphA2 protein. Vasculogenic mimicry (VM) experiments were performed to further confirm the effects of miR-26b on the regulation of EphA2, and the results showed that miR-26b inhibited the VM processes which regulated by EphA2. SIGNIFICANCE: This study demonstrated that miR-26b may act as a tumor suppressor in glioma and it directly regulates EphA2 expression. EphA2 is a direct target of miR-26b, and the down-regulation of EphA2 mediated by miR-26b is dependent on the binding of miR-26b to a specific response element of microRNA in the 3'UTR region of EphA2 mRNA

A non-uniform multi-rate control strategy for a Markov chain-driven Networked Control System

[EN] In this work, a non-uniform multi-rate control strategy is applied to a kind of Networked Control System (NCS) where a wireless path tracking control for an Unmanned Ground Vehicle (UGV) is carried out. The main aims of the proposed strategy are to face time-varying network-induced delays and to avoid packet disorder. A Markov chain-driven NCS scenario will be considered, where different network load situations, and consequently, different probability density functions for the network delay are assumed. In order to assure mean-square stability for the considered NCS, a decay-rate based sufficient condition is enunciated in terms of probabilistic Linear Matrix Inequalities (LMIs). Simulation results show better control performance, and more accurate path tracking, for the scheduled (delay-dependent) controller than for the non-scheduled one (i.e. the nominal controller when delays appear). Finally, the control strategy is validated on an experimental test-bed.This work was supported in part by Grants TEC2012-31506 from the Spanish Ministry of Education, DPI2011-28507-C02-01 by the Spanish Ministry of Economy, and PAID-00-12 from Technical University of Valencia (Spain). In addition, this research work has been developed as a result of a mobility stay funded by the Erasmus Mundus Programme of the European Commission under the Transatlantic Partnership for Excellence in Engineering (TEE Project).Cuenca Lacruz, ÁM.; Ojha, U.; Salt Llobregat, JJ.; Chow, M. (2015). A non-uniform multi-rate control strategy for a Markov chain-driven Networked Control System. Information Sciences. 321:31-47. https://doi.org/10.1016/J.INS.2015.05.035S314732

Fault Diagnosis of Complex Industrial Process Using KICA and Sparse SVM

New approaches are proposed for complex industrial process monitoring and fault diagnosis based on kernel independent component analysis (KICA) and sparse support vector machine (SVM). The KICA method is a two-phase algorithm: whitened kernel principal component analysis (KPCA). The data are firstly mapped into high-dimensional feature subspace. Then, the ICA algorithm seeks the projection directions in the KPCA whitened space. Performance monitoring is implemented through constructing the statistical index and control limit in the feature space. If the statistical indexes exceed the predefined control limit, a fault may have occurred. Then, the nonlinear score vectors are calculated and fed into the sparse SVM to identify the faults. The proposed method is applied to the simulation of Tennessee Eastman (TE) chemical process. The simulation results show that the proposed method can identify various types of faults accurately and rapidly

Antitumor Activity of FL118, a Survivin, Mcl-1, XIAP, and cIAP2 Selective Inhibitor, Is Highly Dependent on Its Primary Structure and Steric Configuration

We recently reported the identification and characterization of a novel small chemical molecule designated FL118. FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal models (Ling et al., <i>PLoS One</i> <b>2012</b>, <i>7</i>, e45571). Here, we report a follow-up study on the structure–activity relationship (SAR) of the hydroxyl group in the lactone ring of FL118. We found that the superior antitumor efficacy of FL118 heavily depends on its steric configuration through comparing the antitumor activity of FL118 with FL113 (the racemic mixture of FL118). Consistently, FL118 proved much more effective in inhibiting the expression of survivin, Mcl-1, and cIAP2, both <i>in vitro</i> and <i>in vivo</i>, compared to FL113. Additionally, Tet-on controlled induction of survivin or forced expression of Mcl-1 protects cancer cells from FL118-mediated growth inhibition and cell death. To further explore the SAR, we synthesized seven position 20-esterifiable FL118 and FL113 derivatives. Studies on these seven new compounds revealed that keeping a free hydroxyl group of FL118 is also important for high antitumor efficacy. Together, these studies confirm the superior anticancer activity of FL118 and narrow the window for further SAR studies to generate novel analogues based on FL118 core structure on its other potential chemical positions