Effects of inhibiting antioxidant pathways on cellular hydrogen sulfide and polysulfide metabolism

Elaborate antioxidant pathways have evolved to minimize the threat of excessive reactive oxygen species (ROS) and to regulate ROS as signaling entities. ROS are chemically and functionally similar to reactive sulfur species (RSS) and both ROS and RSS have been shown to be metabolized by the antioxidant enzymes, superoxide dismutase and catalase. Here we use fluorophores to examine the effects of a variety of inhibitors of antioxidant pathways on metabolism of two important RSS, hydrogen sulfide (H2S with AzMC) and polysulfides (H2Sn, where n = 2–7, with SSP4) in HEK293 cells. Cells were exposed to inhibitors for up to 5 days in normoxia (21% O2) and hypoxia (5% O2), conditions also known to affect ROS production. Decreasing intracellular glutathione (GSH) with l-buthionine-sulfoximine (BSO) or diethyl maleate (DEM) decreased H2S production for 5 days but did not affect H2Sn. The glutathione reductase inhibitor, auranofin, initially decreased H2S and H2Sn but after two days H2Sn increased over controls. Inhibition of peroxiredoxins with conoidin A decreased H2S and increased H2Sn, whereas the glutathione peroxidase inhibitor, tiopronin, increased H2S. Aminoadipic acid, an inhibitor of cystine uptake did not affect either H2S or H2Sn. In buffer, the glutathione reductase and thioredoxin reductase inhibitor, 2-AAPA, the glutathione peroxidase mimetic, ebselen, and tiopronin variously reacted directly with AzMC and SSP4, reacted with H2S and H2S2, or optically interfered with AzMC or SSP4 fluorescence. Collectively these results show that antioxidant inhibitors, generally known for their ability to increase cellular ROS, have various effects on cellular RSS. These findings suggest that the inhibitors may affect cellular sulfur metabolism pathways that are not related to ROS production and in some instances they may directly affect RSS or the methods used to measure them. They also illustrate the importance of carefully evaluating RSS metabolism when biologically or pharmacologically attempting to manipulate ROS

Geodesics on Calabi-Yau manifolds and winding states in nonlinear sigma models

We conjecture that a non-flat $D$-real-dimensional compact Calabi-Yau manifold, such as a quintic hypersurface with D=6, or a K3 manifold with D=4, has locally length minimizing closed geodesics, and that the number of these with length less than L grows asymptotically as L^{D}. We also outline the physical arguments behind this conjecture, which involve the claim that all states in a nonlinear sigma model can be identified as "momentum" and "winding" states in the large volume limit.Comment: minor corrections, 43 pages, to appear in frontiers in mathematical physics. Frontiers in Physics, Dec 16, 201

How proofs are prepared at Camelot

We study a design framework for robust, independently verifiable, and workload-balanced distributed algorithms working on a common input. An algorithm based on the framework is essentially a distributed encoding procedure for a Reed--Solomon code, which enables (a) robustness against byzantine failures with intrinsic error-correction and identification of failed nodes, and (b) independent randomized verification to check the entire computation for correctness, which takes essentially no more resources than each node individually contributes to the computation. The framework builds on recent Merlin--Arthur proofs of batch evaluation of Williams~[{\em Electron.\ Colloq.\ Comput.\ Complexity}, Report TR16-002, January 2016] with the observation that {\em Merlin's magic is not needed} for batch evaluation---mere Knights can prepare the proof, in parallel, and with intrinsic error-correction. The contribution of this paper is to show that in many cases the verifiable batch evaluation framework admits algorithms that match in total resource consumption the best known sequential algorithm for solving the problem. As our main result, we show that the $k$-cliques in an $n$-vertex graph can be counted {\em and} verified in per-node $O(n^{(\omega+\epsilon)k/6})$ time and space on $O(n^{(\omega+\epsilon)k/6})$ compute nodes, for any constant $\epsilon>0$ and positive integer $k$ divisible by $6$, where $2\leq\omega<2.3728639$ is the exponent of matrix multiplication. This matches in total running time the best known sequential algorithm, due to Ne{\v{s}}et{\v{r}}il and Poljak [{\em Comment.~Math.~Univ.~Carolin.}~26 (1985) 415--419], and considerably improves its space usage and parallelizability. Further results include novel algorithms for counting triangles in sparse graphs, computing the chromatic polynomial of a graph, and computing the Tutte polynomial of a graph.Comment: 42 p

Pressure effects on bimolecular recombination and unimolecular dissociation reactions

The treatment of pressure effects on bimolecular recombinations and unimolecular dissociations is discussed. The analysis of recombination and dissociation reactions is made by showing how the nonequilibrium energy (E) and angular momentum (J)-dependent steady-state population distribution functions for the two reactions are related to each other and to the equilibrium population distribution function at the given E and J. As a special case a strong collision model is then used for the collisional rotational angular momentum transfer, and a ladder model for the collisional energy transfer. An analytical result is obtained for states below the dissociation threshold. The extension to recombinations with two exit channels is described, for application to ozone formation and isotopic effects

Application of the z-transform to composite materials

Applications of the z-transform were made earlier to interfacial electron transfer involving semi-infinite solids, e.g., semiconductor/liquid and metal/liquid interfaces and scanning tunneling microscopy. It is shown how the method is readily adapted to treat composite materials, such as solid/solid interfaces or "molecular wire"/solid interfaces

On the theory of electron transfer reactions at semiconductor/liquid interfaces. II. A free electron model

Electron transfer reactions at semiconductor/liquid interfaces are studied using the Fermi Golden rule and a free electron model for the semiconductor and the redox molecule. Bardeen's method is adapted to calculate the coupling matrix element between the molecular and semiconductor electronic states where the effective electron mass in the semiconductor need not equal the actual electron mass. The calculated maximum electron transfer rate constants are compared with the experimental results as well as with the theoretical results obtained in Part I using tight-binding calculations. The results, which are analytic for an s-electron in the redox agent and reduced to a quadrature for pz- and dz2-electrons, add to the insight of the earlier calculations

An approximate theory of the ozone isotopic effects: Rate constant ratios and pressure dependence

The isotopic effects in ozone recombination reactions at low pressures are studied using an approximate theory which yields simple analytic expressions for the individual rate constant ratios, observed under “unscrambled” conditions. It is shown that the rate constant ratio between the two competing channels XYZ-->X+YZ and XYZ-->XY+Z is mainly determined by the difference of the zero-point energies of diatomic molecules YZ and XY and by the efficiency of the deactivation of the newly formed excited ozone molecules, whereas the mass-independent fractionation depends on a “nonstatistical” symmetry factor eta and the collisional deactivation efficiency. Formulas for the pressure effects on the enrichment and on the rate constant ratios are obtained, and the calculated results are compared with experiments and more exact calculations. In all cases, ratios of isotope rates and the pressure dependence of enrichments, the agreement is good. While the initial focus was on isotope effects in the formation of O3, predictions are made for isotope effects on ratios of rate constants in other reactions such as O+CO-->CO2, O+NO-->NO2, and O+SO-->SO2

Can gravitational dynamics be obtained by diffeomorphism invariance of action?

It has recently been suggested that the gravitational dynamics could be obtained by requiring the action to be invariant under diffeomorphism transformations. We argue that the action constructed in usual way is automatically diffeomorphism invariant in nature, which thus invalidates this alternative perspective to obtain gravitational dynamics. Especially, we also show what is wrong with the technical derivation of gravitational dynamics in the alternative approach.Comment: version published in PR