Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect

The histone deacetylase inhibitors (HDACi) have demonstrated anticancer efficacy across a range of malignancies, most impressively in the hematological cancers. It is uncertain whether this clinical efficacy is attributable predominantly to their ability to induce apoptosis and differentiation in the cancer cell, or to their ability to prime the cell to other pro-death stimuli such as those from the immune system. HDACi-induced apoptosis occurs through altered expression of genes encoding proteins in both intrinsic and extrinsic apoptotic pathways; through effects on the proteasome/aggresome systems; through the production of reactive oxygen species, possibly by directly inducing DNA damage; and through alterations in the tumor microenvironment. In addition HDACi increase the immunogenicity of tumor cells and modulate cytokine signaling and potentially T-cell polarization in ways that may contribute the anti-cancer effect in vivo. Here, we provide an overview of current thinking on the mechanisms of HDACi activity, with attention given to the hematological malignancies as well as scientific observations arising from the clinical trials. We also focus on the immune effects of these agents

Designing a recurrent neural network-based controller for gyro-mirror line-of-sight stabilization system using an artificial immune algorithm

10.1007/978-3-540-72377-6_8Studies in Computational Intelligence66189-20

Sliding mode load frequency control for multi‐area time‐delay power system with wind power integration

The interconnected time-delay power system has become an important issue for the open communication network. Meanwhile, due to the output power fluctuation of integrated wind energy, load frequency control (LFC) for power system with variable sources and loads has become more complicated. The novel decentralised sliding mode (SM) LFC strategy is proposed for multi-area time-delay power system with significant wind power penetration. The appropriate switching surface gain is selected to assure the stability of power system with mismatched uncertainties. The SM controller is constructed to satisfy the hitting condition. At last, the SM controller is proved by using the real-time digital simulator device under different case of time delay, wind penetration, load disturbance and operating point. The test results show that the proposed SM LFC can reduce frequency deviation and tie-line power fluctuation effectively