Potential Benefits of Sequential Inhibitor-Mutagen Treatments of RNA Virus Infections

Lethal mutagenesis is an antiviral strategy consisting of virus extinction associated with enhanced mutagenesis. The use of non-mutagenic antiviral inhibitors has faced the problem of selection of inhibitor-resistant virus mutants. Quasispecies dynamics predicts, and clinical results have confirmed, that combination therapy has an advantage over monotherapy to delay or prevent selection of inhibitor-escape mutants. Using ribavirin-mediated mutagenesis of foot-and-mouth disease virus (FMDV), here we show that, contrary to expectations, sequential administration of the antiviral inhibitor guanidine (GU) first, followed by ribavirin, is more effective than combination therapy with the two drugs, or than either drug used individually. Coelectroporation experiments suggest that limited inhibition of replication of interfering mutants by GU may contribute to the benefits of the sequential treatment. In lethal mutagenesis, a sequential inhibitor-mutagen treatment can be more effective than the corresponding combination treatment to drive a virus towards extinction. Such an advantage is also supported by a theoretical model for the evolution of a viral population under the action of increased mutagenesis in the presence of an inhibitor of viral replication. The model suggests that benefits of the sequential treatment are due to the involvement of a mutagenic agent, and to competition for susceptible cells exerted by the mutant spectrum. The results may impact lethal mutagenesis-based protocols, as well as current antiviral therapies involving ribavirin

Oxide scale formation of stainless steels with different heating methods:effect of hydrogen as fuel

Abstract The evolution from natural gas usage to new technologies, such as the use of hydrogen as fuel or electricity-based heating, strongly influences the oxidation of the stainless steel surface in the reheating furnace. Thermogravimetric tests using different simulated combustion and induction reheating conditions are performed for austenitic AISI 301, AISI 304, and ferritic AISI 444 steel grades. Simulated furnace atmospheres in combustion methods are based on methane–air, methane–oxygen, hydrogen–oxygen, and methane–hydrogen–oxygen combinations. For induction simulations, air and nitrogen are used as furnace atmospheres. The results indicate that changes in heating conditions to H2-fueled combustion or induction only have a minor influence on the oxidation of the ferritic grade; whereas, their effects on the austenitic grades are more pronounced. The transition from a methane–air to H2–oxyfuel combustion increases the total oxidation by 1.7 and 4 times for steel grades 304 and 301, respectively; therefore, grade 304 can be considered better suited for transition for H2–oxyfuel use. The shorter induction heating considerably decreases the amount of oxide scale for austenitic grades, but the nitrogen atmosphere produces a subscale inside the steel matrix, which can hinder the descaling process

Oxide scale formation of EN 1.4622 and EN 1.4828 stainless steels during annealing and descaling behavior in neutral electrolytic pickling

Abstract Oxide scale formation during short-term annealing and electrolytic pickling behavior of ferritic EN 1.4622 and austenitic EN 1.4828 stainless steels are investigated. The annealing is performed at temperatures between 1000 and 1100 °C for ferritic and 1100 and 1200 °C for austenitic steel grade under humid atmospheres in simulated industrial process. Neutral electrolytic pickling, also referred to as neutral electrochemical pickling or the Ruthner Neolyte Process, is performed in Na₂SO₄ electrolyte, and pickling efficiency is evaluated visually and by image analysis of pickled surfaces. The results show that annealing conditions have a more impactful effect on the structure and the composition of the resulting oxide in the austenitic grade within the studied condition range. The thicknesses of the ferritic scales are mainly less than 0.4 μm, while almost all austenitic scales are thicker than it. In addition, the amount of silicon oxide formation inside the steel matrix of the austenitic and ferritic grades is highly different. Longer exposure times and higher temperatures promote scale growth during annealing, resulting in inefficient electrolytic pickling for the ferritic grade. For the austenitic grade, almost all steel surfaces are still covered with oxide scale after electrolytic pickling

Effect of simulated annealing conditions on scale formation and neutral electrolytic pickling

Abstract Scale formation of AISI 304 stainless steel during annealing at temperatures between 1100 and 1200 °C under a water vapor‐containing atmosphere is studied. Characterization of the oxide scale is performed with field‐emission scanning electron microscopy–energy dispersive spectroscopy (FESEM–EDS) and glow discharge optical emission spectroscopy (GDOES) and removal of oxide scale is done via neutral electrolyte pickling. The pickling conditions are kept constant and the effect of the annealing conditions and scale properties on the pickling result are examined. The effectiveness of pickling is evaluated using analysis FESEM images taken on polished sections of pickled surfaces. Research shows that the thickness, morphology, and composition of the oxide scale are dependent on annealing temperature and time. The thicknesses of the scale formed under the established conditions vary from 0.2 to over 30 μm, and morphologies between the chromium rich oxide layer and layered scale structure formed by breakaway oxidation. The pickling response of oxide scales remains good at all annealing temperatures with the shortest exposure time