DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1.

Let-7 miRNAs act as tumour suppressors by directly binding to the 3\u27UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback relationship is Dicer, a central regulator of miRNA expression through sequence-specific silencing. We first identified that DICER1 is the key downstream gene for cyclin D1-induced let-7 expression. In addition, we found that let-7 miRNAs expression decreased because of the p53-induced cell death response, with deregulated cyclin D1. Our results also showed that cyclin D1 is required for Nutlin-3 and TAX-induced let-7 expression in cancer repression and the cell death response. For the first time, we provide evidence that let-7 and cyclin D1 form a feedback loop in regulating therapy response of cancer cells and cancer stem cells, and importantly, that alteration of let-7 expression, mainly caused by cyclin D1, is a sensitive indicator for better chemotherapies response

A stochastic process approach for modeling arrival delay in train operations

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Effects of Au and Ge Additions on the Microstructures and Properties of Ag-1.5Cu-0.1Y Alloys

The application of silver is seriously affected by its tendency to oxidize and corrode. Therefore, the addition of proper alloying elements to silver-based alloys to achieve better properties has become a hot topic at present. In this current study, the effects of the addition of the two elements Au and Ge on the microstructures and properties of Ag-1.5Cu-0.1Y alloys were investigated. The results showed that the microstructures were refined and the second dendrite was shortened in the Ag-1.5Cu-0.1Y alloys with the addition of Au and Ge. Adding Au enhanced the corrosion resistance of the Ag-1.5Cu-0.1Y alloys. Furthermore, the corrosion resistance of the Ag-1.5Cu-0.1Y alloys with the addition of both Ge and Au was better than that of the alloy samples with Au added alone. The best corrosion resistance of the Ag-1.5Cu-0.1Y alloys was achieved by adding 1.0 wt.% Au and 1.0 wt.% Ge. The microhardness was enhanced by the addition of Au and Ge, and was strongly correlated with the secondary dendrite arm spacing (&lambda;2) of the Ag-1.5Cu-0.1Y alloys. In addition, the Au addition could improve the conductivity of the Ag-1.5Cu-0.1Y alloy; however, Ge had little effect on the conductivity of the alloy samples. This work provides an experimental basis for the design of better performing silver-based alloys

Two-year safety evaluation of a biodegradable polymer sirolimus-eluting stent with increased drug elution and polymer absorption kinetics in complex patient and lesion cohort

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