Metformin inhibits polyphosphate-induced hyper-permeability and inflammation

Circulating inflammatory factor inorganic polyphosphate (polyP) released from activated platelets could enhance factor XII and bradykinin resulted in increased capillary leakage and vascular permeability. PolyP induce inflammatory responses through mTOR pathway in endothelial cells, which is being reported in several diseases including atherosclerosis, thrombosis, sepsis, and cancer. Systems and molecular biology approaches were used to explore the regulatory role of the AMPK activator, metformin, on polyP-induced hyper-permeability in different organs in three different models of polyP-induced hyper-permeability including local, systemic shortand systemic long-term approaches in murine models. Our results showed that polyP disrupts endothelial barrier integrity in skin, liver, kidney, brain, heart, and lung in all three study models and metformin abrogates the disruptive effect of polyP. We also showed that activation of AMPK signaling pathway, regulation of oxidant/ anti-oxidant balance, as well as decrease in inflammatory cell infiltration constitute a set of molecular mechanisms through which metformin elicits it's protective responses against polyP-induced hyper-permeability. These results support the clinical values of AMPK activators including the FDA-approved metformin in attenuating vascular damage in polyP-associated inflammatory diseases.Peer reviewe

A novel neural network approach to dynamic state estimation of generators subjected to ageing in complex power systems

Emami, K ORCiD: 0000-0001-5614-4861In this paper, a neural network based technique for estimating dynamic states of generators in highly complex power systems is presented. The proposed method is independent to the mathematical model of the generators and uses a nonlinear autoregressive neural network with exogenous inputs to estimate dynamic states of the generators. The proposed technique has been compared to particle filter and unscented Kalman filter based schemes previously reported in the literature. The simulation results show superiority of the proposed technique over the two other schemes when parameters of the generators alter. Parameter alterations in generators are practically occur due to environment impacts, ageing of the equipment and so on. The proposed scheme is capable of keeping its accuracy and precision even in the presence of unobservable variances in generator parameters. © 2019 IEEE