Engineered external guide sequences are highly effective in inducing RNase P for inhibition of gene expression and replication of human cytomegalovirus

External guide sequences (EGSs), which are RNA molecules derived from natural tRNAs, bind to a target mRNA and render the mRNA susceptible to hydrolysis by RNase P, a tRNA processing enzyme. Using an in vitro selection procedure, we have previously generated EGS variants that efficiently direct human RNase P to cleave a target mRNA in vitro. In this study, a variant was used to target the overlapping region of the mRNAs encoding human cytomegalovirus (HCMV) essential transcription regulatory factors IE1 and IE2. The EGS variant was ∼25-fold more active in inducing human RNase P to cleave the mRNA in vitro than the EGS derived from a natural tRNA. Moreover, a reduction of 93% in IE1/IE2 gene expression and a reduction of 3000-fold in viral growth were observed in HCMV-infected cells that expressed the variant, while cells expressing the tRNA-derived EGS exhibited a reduction of 80% in IE1/IE2 expression and an inhibition of 150-fold in viral growth. Our results provide the first direct evidence that EGS variant is highly effective in blocking HCMV gene expression and growth and furthermore, demonstrate the feasibility of developing effective EGS RNA variants for anti-HCMV applications by using in vitro selection procedures

Transcriptional Regulation and Biological Functions of Selenium-Binding Protein 1 in Colorectal Cancer In Vitro and in Nude Mouse Xenografts

It has been shown that selenium-binding protein 1 (SBP1) is significantly downregulated in different human cancers. Its regulation and function have not yet been established.We show that the SBP1 promoter is hypermethylated in colon cancer tissues and human colon cancer cells. Treatment with 5'-Aza-2'-deoxycytidine leads to demethylation of the SBP1 promoter and to an increase of SBP1 promoter activity, rescues SBP1 mRNA and protein expression in human colon cancer cells. Additionally, overexpression of SBP1 sensitizes colon cancer cells to H2O2-induced apoptosis, inhibits cancer cell migration in vitro and inhibits tumor growth in nude mice.These data demonstrate that SBP1 has tumor suppressor functions that are inhibited in colorectal cancer through epigenetic silencing

Development of magnetorheological elastomers-based tuned mass damper for building protection from seismic events

This study investigated and evaluated a semi-active tuned mass damper which incorporated four multi-layered structures fabricated using magnetorheological elastomers. The four magnetorheological elastomer structures formed a square and provided the tuned mass damper variable stiffness used to track the excitation frequencies. This design not only increases the stability of the tuned mass damper but more importantly eliminates the magnetic circuit gap in a design which we used in the past because all four of the magnetic circuits used to control the magnetorheological elastomer isolators are closed circuits. In order to verify the capability of the magnetorheological elastomer-based tuned mass damper to protect a building from earthquake, extensive simulation and experimental testing were conducted. The swept sinusoidal signal and the scaled 1940 El Centro earthquake record were used to excite a scaled three-story building. Both simulation and experiment have verified that the magnetorheological elastomer-based tuned mass damper outperformed all other passive tuned mass dampers under either swept sinusoidal or seismic conditions

A New Approach of Waveform Interpretation Applied in Nondestructive Testing of Defects in Rock Bolts Based on Mode Identification

Due to the characteristics of dispersion of guided waves, the waveforms recorded in ultrasonic nondestructive testing (NDT) of rock bolts are complicated to interpret. With a goal to increase the inspection sensitivity and accuracy in NDT of rock bolts, an approach of waveform interpretation based on wave modes identification is developed. The numerical simulation of full rock bolt and rock bolts with grout defect by Finite Element Method (FEM) is applied to illustrate the approach; it is found that the sensitive and low attenuation wave modes exist. Laboratory tests on full rock bolt and rock bolt with grout loss using NDT are conducted to evaluate the efficacy of the approach of waveform interpretation. In addition to that, a parametric study was conducted on rock bolt models with different sectional defect size. Based on the waveform interpretation, the mode-based reflection coefficient R is proposed to evaluate the sensitivity of wave modes to the defect size of sectional area. It is found that the sensitivity of the wave mode does not change with the defect sectional area, and the amplitude depends on the size of the defect

Autonomous Navigation Based on SEIF with Consistency Constraint for C-Ranger AUV

An autonomous underwater vehicle (AUV) has to solve two essential problems in underwater environment, namely, localization and mapping. SLAM is one novel solution to estimate locations and maps simultaneously based on motion models and sensor measurements. Sparse extended information filter (SEIF) is an effective algorithm to reduce storage and computational costs of large-scale maps in the SLAM problem. However, there exists the inconsistency in the SEIF since the rank of the observability matrix of linearized error-state model in SLAM system is higher than that of the nonlinear SLAM system. By analyzing the consistency of the SEIF-based SLAM from the perspective of observability, a SLAM based on SEIF with consistency constraint (SEIF-CC SLAM) is developed to improve the estimator’s consistency. The proposed algorithm uses the first-ever available estimates to calculate SEIF Jacobians for each of the state variables, called the First Estimates Jacobian (FEJ). Then, the linearized error-state model can keep the same observability as the underlying nonlinear SLAM system. The capability of autonomous navigation with the proposed algorithm is validated through simulations experiments and sea trials for a C-Ranger AUV. Experimental results show that the proposed SEIF-CC SLAM algorithm yields more consistent and accurate estimates compared with the SEIF-based SLAM