Electric fields in plasmas under pulsed currents

Electric fields in a plasma that conducts a high-current pulse are measured as a function of time and space. The experiment is performed using a coaxial configuration, in which a current rising to 160 kA in 100 ns is conducted through a plasma that prefills the region between two coaxial electrodes. The electric field is determined using laser spectroscopy and line-shape analysis. Plasma doping allows for 3D spatially resolved measurements. The measured peak magnitude and propagation velocity of the electric field is found to match those of the Hall electric field, inferred from the magnetic-field front propagation measured previously.Comment: 13 pages, 13 figures, submitted to PR

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p