Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication

Early tumorigenesis is associated with the engagement of the DNA-damage checkpoint response (DDR). Cell proliferation and transformation induced by oncogene activation are restrained by cellular senescence. It is unclear whether DDR activation and oncogene-induced senescence (OIS) are causally linked. Here we show that senescence, triggered by the expression of an activated oncogene (H-RasV12) in normal human cells, is a consequence of the activation of a robust DDR. Experimental inactivation of DDR abrogates OIS and promotes cell transformation. DDR and OIS are established after a hyper-replicative phase occurring immediately after oncogene expression. Senescent cells arrest with partly replicated DNA and with DNA replication origins having fired multiple times. In vivo DNA labelling and molecular DNA combing reveal that oncogene activation leads to augmented numbers of active replicons and to alterations in DNA replication fork progression. We also show that oncogene expression does not trigger a DDR in the absence of DNA replication. Last, we show that oncogene activation is associated with DDR activation in a mouse model in vivo. We propose that OIS results from the enforcement of a DDR triggered by oncogene-induced DNA hyper-replication.     

一类带临界非线性项的p-Laplace方程正解的存在性

讨论了一类奇异p-Laplace方程的Dirichlet问题,通过山路引理选取适当的试验函数验证局部PS条件,得到了此类方程正解的存在性.     

Impulsive Control and Synchronization of a Critical Chaotic System

This paper investigates the impulsive control and synchronization of a chaotic system, which is a particular case of the so-called generalized Lorenz canonical form （GLCF） with r τ -1 Based on the impulsive control method, some new criteria are obtained to guarantee the impulsively controlled chaotic system and error system to be globally asymptotically stable at origin. Moreover, to be some simulation results are included to visualize the effectiveness and feasibility of the proposed method.