Nampt is involved in DNA double-strand break repair

DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer.Nicotinamide phosphoribosyltransferase(Nampt),which is involved in nicotinamide adenine dinucleotide metabolism,is overexpressed in a variety of tumors.In this report,we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80,which are key factors in HR and NHEJ,respectively.Depletion of Nampt by small interfering RNA(siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair.Furthermore,the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining,indicating a delay in the onset of cellular senescence in normal human fibroblasts.Taken together,our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair,contributing to the acceleration of cellular senescence.

Adaptive nonlinear Kalman filters based on credibility theory with noise correlation

To solve the divergence problem and overcome the difficulty in guaranteeing filtering accuracy during estimation of the process noise covariance or the measurement noise covariance with traditional new information-based nonlinear filtering methods,we design a new method for estimating noise statistical characteristics of nonlinear systems based on the credibility Kalman Filter(KF)theory considering noise correlation.This method first extends credibility to the Unscented Kalman Filter(UKF)and Extended Kalman Filter(EKF)based on the credibility theory.Further,an optimization model for nonlinear credibility under noise related conditions is established considering noise correlation.A combination of filtering smoothing and credibility iteration formula is used to improve the real-time performance of the nonlinear adaptive credibility KF algorithm,further expanding its application scenarios,and the derivation process of the formula theory is provided.Finally,the performance of the nonlinear credibility filtering algorithm is simulated and analyzed from multiple perspectives,and a comparative analysis conducted on specific experimental data.The simulation and experimental results show that the proposed credibility EKF and credibility UKF algorithms can estimate the noise covariance more accurately and effectively with lower average estimation time than traditional methods,indicating that the proposed algorithm has stable estimation performance and good real-time performance.