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Abnormal activation of the IGF1R signaling pathway accelerates melanoma development and metastases. RNAi systems with complex cloning procedures and unsatisfactory efficiency in suppressing gene expression have become the technical difficulties that hinder their utility when studying gene knockdown. Here we established a simplified adenovirus-mediated gene knockdown system by which a single adenoviral vector carries multiple siRNA fragments that can effectively suppress IGF1R expression in melanoma cells. We first generated the adenovirus that simultaneously expresses three human or mouse siRNAs targeting IGF1R (AdRIGF1R-OK). qRT-PCR and immunofluorescence staining revealed that IGF1R expression was significantly decreased in the melanoma cells that were infected with AdRIGF1R-OK. Bioluminescence imaging showed that the size of the tumor formed by the xenografts infected with AdRIGF1R-OK was significantly smaller than that of the controls. Annexin V-FITC flow cytometry assay, immunofluorescence staining for cleaved caspase-3, and Hoechst staining showed that more cells underwent apoptosis after infection with AdRIGF1R-OK. Luciferase reporter assay, crystal violet cell viability assay, and cell-cycle analysis showed that the proliferation of melanoma cells infected with AdRIGF1R-OK was significantly decreased compared to the controls. This study demonstrates that the OK system is effective in silencing gene expression, with promising potential to treat melanoma and other diseases. Keywords: RNAi technology, gene therapy, melanoma, IGF1R, one-step knockdown system, adenovirus

One of the major track issues in urban rail transit is the rail side wear, especially at the high rail on sharp curves. The mechanism of rail side wear is very complex and has not been fully understood. This study attempts to characterize the progressive development of high rail side wear in a transit track with heavy traffic. A numerical vehicle-track model is developed based on multi-body dynamics and the modified Archard wear formula and is used to perform a parametric analysis. The side wear development trend observed in the field is in good agreement with the results calculated from the numerical mode. According to the results obtained from this study, the side wear during the life-cycle of the high rail can be approximately characterized into three stages: 1) Stage I, rail wear initiates at the gauge side corner; 2) Stage II, side wear propagates linearly; 3) Stage III, side wear propagates exponentially. The parametric analysis suggests that three maintenance activities may ease the development rate of the high rail side wear in Stage III. These include increasing the rail inclination, adjusting the track gauge on time, and restoring the rail profile of the low rail.

For the passive detection of azimuth and frequency of azimuths and frequencies of line-spectrum signals radiated from underwater weak targets, a space-frequency joint detection and tracking method based on track-before-detect (TBD) technology is proposed. This method works directly with the time sequence of frequency-azimuth (FRAZ) spectra to estimate the frequency and azimuth of line-spectrum signals. And the change of the frequency and azimuth states of a line-spectrum signal is modeled as a first-order hidden Markov process. The distribution of the FRAZ spectra of linear array received signal are derived in this paper to set the parameters of Hidden Markov Models (HMM). The FRAZ spectra at different times is joint process using Viterbi algorithm to obtain the maximum a posteriori estimation of the azimuth and frequency of line-spectrum signal. A dynamic searching method based on region segmentation and merging similar line-spectrum is designed to solve the problem of large computation of Viterbi algorithm in the detection of line-spectrum. The proposed method can make full use of the correlation between the target's information in the multi-frame FRAZ spectra to distinguish the target from the background noise. The processing results of simulation data and actual data show that the method has excellent line-spectrum detection performance at low SNR and can adapt to the complex situation such as there are multiple targets and multiple line-spectrum signals.