Risk Analysis via Generalized Pareto Distributions.

We compute the value-at-risk of financial losses by fitting a generalized Pareto distribution to exceedances over a threshold. Following the common practice of setting the threshold as high sample quantiles, we show that, for both independent observations and time-series data, the asymptotic variance for the maximum likelihood estimation depends on the choice of threshold, unlike the existing study of using a divergent threshold. We also propose a random weighted bootstrap method for the interval estimation of VaR, with critical values computed by the empirical distribution of the absolute differences between the bootstrapped estimators and the maximum likelihood estimator. While our asymptotic results unify the inference with non-divergent and divergent thresholds, the finite sample studies via simulation and application to real data show that the derived confidence intervals well cover the true VaR in insurance and finance.

MiR-212-3p inhibits cell proliferation and promotes apoptosis by targeting nuclear factor IA in bladder cancer.

Accumulating evidence suggest that microRNAs play crucial roles in the development and progression of bladder cancer (BC). Here, we found that miR-212-3p was significantly down-regulated and negatively correlated with nuclear factor IA (NFIA) in human BC tissues. Bioinformatics analysis predicted that NFIA was a target gene of miR-212-3p. Then BC cell lines, T24 and J82 cells were transfected with miR-212-3p mimics or siNFIA to obtain miR-212-3p overexpression or NFIA knockdown cell lines, respectively. Quantitative real-time PCR was used to determine the expression of miR-212-3p and NFIA. Western blot analysis was utilized to detect NFIA expression. MTT assay showed either miR-212-3 overexpression or NFIA knockdown significantly inhibited the BC cell proliferation. Double staining with Annexin V-APC and 7-AAD showed the total number of apoptotic BC cells were remarkably increased after miR-212-3p overexpression or NFIA knockdown. Collectively, our results indicated that miR-212-3p targeting NFIA might serve as a promising target for BC.

Scutellaria barbata D. Don polysaccharides inhibit the growth of Calu-3 xenograft tumors via suppression of the HER2 pathway and angiogenesis.

Scutellaria barbata D. Don, a perennial herb belonging to the family Lamiaceae, is widely distributed throughout China and the Republic of Korea, and has been traditionally used in folk medicine as an antitumor and anti-inflammatory agent. Polysaccharides isolated from Scutellaria barbata D. Don (PSB), have been reported to possess antitumor effects. However, the detailed antitumor mechanisms behind the effects of PSB remain unclear. In the present study, a non-small cell lung cancer cell line harboring the HER2 gene mutation Calu-3, the Calu-3 cell line, was used to investigate the underlying mechanisms of the antitumor effects of PSB. The results revealed that PSB potently inhibited cell proliferation and human epidermal growth factor receptor (HER)2 phosphorylation in vitro, and also downregulated the expression of the downstream signaling molecules, including phosphorylated (phospho-)Akt and phospho-extracellular signal-related kinase. In vivo, PSB demonstrated efficacy at well-tolerated doses, including significant antitumor activity in a Calu-3 subcutaneous xenograft model. Immunohistochemistry (IHC) analysis revealed a PSB dose-dependent reduction of microvessel density, demonstrated by cluster of differentiation 31 staining. The present findings suggest that inhibition of tumor angiogenesis via suppression of the HER2 pathway may be one of the mechanisms by which PSB can be effective in the treatment of cancers.