A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.

Simulation of OWES with five-Level converter linked to the grid: Harmonic assessment

This paper deals with a computing simulation for an offshore wind energy system taking into account the influence of the marine waves action throughout the floating platform. The wind energy system has a variable-speed turbine equipped with a permanent magnet synchronous generator and a full-power five level converter, injecting energy into the electric grid through a high voltage alternate current link. A reduction on the unbalance of the voltage in the DC-link capacitors of the five-level converter is proposed by a strategic selection of the output voltage vectors. The model for the drive train of the wind energy system is a two mass model, including the dynamics of the floating platform. A case study is presented and the assessment of the quality of the energy injected into the electric grid is discussed.

Introduction [to Contact force models for multibody dynamics]

"Series: Solid mechanics and its applications, vol. 226"