No abstract

Alzheimer's disease (AD) and type 2 diabetes appear to share similar pathogenic mechanisms. dsRNA-dependent protein kinase (PKR) underlies peripheral insulin resistance in metabolic disorders. PKR phosphorylates eukaryotic translation initiation factor 2α (eIF2α-P), and AD brains exhibit elevated phospho-PKR and eIF2α-P levels. Whether and how PKR and eIF2α-P participate in defective brain insulin signaling and cognitive impairment in AD are unknown. We report that β-amyloid oligomers, AD-associated toxins, activate PKR in a tumor necrosis factor α (TNF-α)-dependent manner, resulting in eIF2α-P, neuronal insulin receptor substrate (IRS-1) inhibition, synapse loss, and memory impairment. Brain phospho-PKR and eIF2α-P were elevated in AD animal models, including monkeys given intracerebroventricular oligomer infusions. Oligomers failed to trigger eIF2α-P and cognitive impairment in PKR(-/-) and TNFR1(-/-) mice. Bolstering insulin signaling rescued phospho-PKR and eIF2α-P. Results reveal pathogenic mechanisms shared by AD and diabetes and establish that proinflammatory signaling mediates oligomer-induced IRS-1 inhibition and PKR-dependent synapse and memory loss.

No abstract

No abstract

Abstract-Low-voltage ride-through (LVRT) requirements demand wind-power plants to remain connected to the network in presence of grid-voltage dips. Most dips present positive-, negative-, and zero-sequence components. Hence, regulators based on symmetrical components are well suited to control gridconnected converters. A neutral-point-clamped topology has been considered as an active front end of a distributed power-generation system, following the trend of increasing power and voltage levels in wind-power systems. Three different current controllers based on symmetrical components and linear quadratic regulator have been considered. The performance of each controller is evaluated on LVRT requirement fulfillment, grid-current balancing, maximum grid-current value control, and oscillating power flow. Simulation and experimental results show that all three controllers meet LVRT requirements, although different system performance is found for each control approach. Therefore, controller selection depends on the system constraints and the type of preferred performance features.Index Terms-Distributed power generation, grid interface, multilevel conversion, three-level inverter, wind-power system.