New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3‐deazaneplanocin A, galidesivir, GS‐6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS‐6620, remdesivir and pyrazofurin) are C‐nucleosides, and two of them (GS‐6620, remdesivir) also contain a phosphoramidate part. The C‐nucleoside and phosphoramidate (and for the adenine analogues the 1′‐cyano group as well) may be considered as essential attributes for their antiviral activity.     

Asymptotically safe gravitons in electroweak precision physics

Asymptotic safety offers a field theory based UV completion to gravity. For low Planck scales, gravitational effects on low-energy precision observables cannot be neglected. We compute the contribution to the ρ parameter from asymptotically safe gravitons and find that in contrast to effective theory, constraints on models with more than three extra dimensions are significantly weakened. The relative size of the trans-Planckian contribution increases proportional to the number of extra dimensions.     

The roles of added chlorine and sulfur on ash deposition mechanisms during solid fuel combustion

The focus of this paper is on effects of chlorine and sulfur on coal ash deposition rates, under practically relevant but systematically controlled combustion conditions. This problem is important, not so much for coal, but to understand and predict deposition rates for biomass combustion where chlorine contents can be high. To this end, ash deposition rates on a controlled temperature surface were measured for controlled amounts of chlorine and sulfur added to a pulverized coal, doped with potassium and burned in a 100 kW rated combustion rig. Previous work with 35 tests on 11 coal, biomass and petroleum coke fuels burned under a range of operating conditions had strongly suggested that the deposition rate of the tightly bound inside deposits was independent of the ash aerosol composition, and depended only on PM₁ in the flue gas. The loosely bound outside deposition rate was dependent primarily on the total alkali content in the flue gas. The new results using chlorine added to the fuel (in the form of ammonium chloride) required these previous conclusions to be drastically revised. They showed that chlorine, not alkali alone, had large effects on the deposition rate of the inside deposits, which now were orders of magnitude higher than without chlorine addition, and did not fit previous (multi-fuel) correlations with PM₁. Sulfur addition, together with chlorine, did not affect deposition rates much, although it did lower the chlorine content of the deposit. These results are interpreted in terms of the ash aerosol size segregated composition, which was also measured, and potential sulfation reactions within the deposit.     

A Quick and Reproducible Silanization Method by Using Plasma Activation for Hydrophobicity-Based Kinesin Single Molecule Fluorescence–Microscopy Assays

Single-molecule assays often require functionalized surfaces. One approach for microtubule assays renders surfaces hydrophobic and uses amphiphilic blocking agents. However, the optimal hydrophobicity is unclear, protocols take long, produce toxic waste, and are susceptible to failure. Our method uses plasma activation with hydrocarbons for hexamethyldisilazane (HMDS) silanization in the gas phase. We measured the surface hydrophobicity, its effect on how well microtubule filaments were bound to the surface, and the number of nonspecific interactions with kinesin motor proteins. Additionally, we tested and discuss the use of different silanes and activation methods. We found that even weakly hydrophobic surfaces were optimal. Our environmentally friendly method significanty reduced the overall preparation effort and resulted in reproducible, high-quality surfaces with low variability. We expect the method to be applicable to a wide range of other single-molecule assays.     

NanoSIMS50 — a powerful tool to elucidate cellular localization of halogenated organic compounds

Persistent organic pollutants are widely distributed in the environment and lots of toxicological data are available. However, little is known on the intracellular fate of such compounds. Here a method applying secondary ion mass spectrometry is described that can be used to visualize cellular localization of halogenated compounds and to semi-quantitatively calculate concentrations of such compounds. Of the model compounds tested, TBBPA was homogenously distributed in the cell membrane of the H295R cells while PFOS accumulated in very distinct locations in the cell membrane. Relative intracellular concentrations of 4-OH-BDE69 and 4-OH-BDE121 in GH3.TRE were 61?% and 18?%, respectively, compared to the parent compounds. These differences may partly explain that observed effect concentrations for 4-OH-BDEs in in vitro experiments are usually lower than what would be expected based on receptor binding studies. NanoSIMS50 proved to be a powerful tool to describe the cellular distribution of halogenated compounds. The semi-quantitative data that can be obtained may help to further explain results from in vitro or in vivo experiments.     

Detecting exponential dichotomy on the real line: SVD and QR algorithms

In this paper we propose and implement numerical methods to detect exponential dichotomy on the real line. Our algorithms are based on the singular value decomposition and the QR factorization of a fundamental matrix solution. The theoretical justification for our methods was laid down in the companion paper: “Exponential Dichotomy on the real line: SVD and QR methods.”     

On a conjecture by Blocki and Zwonek

This paper gives a counterexample to a conjecture by Blocki and Zwonek on the area of sublevel sets of the Green’s function.