Differential effects of various trivalent and pentavalent organic and inorganic arsenic species on glucose metabolism in isolated kidney cells

We have compared the acute toxicities of the trivalent arsenic species arsenite, oxophenylarsine (PhAsO), 2-chlorovinyloxoarsine (ClvinAsO), methyloxoarsine (MeAsO), and of the pentavalent arsenic species arsenate, methyl- and phenyl-arsonic acid in rat kidney tubules (RKT) and Madin-Darby canine kidney (MDCK) cells. In RKT, PhAsO (1 μmol I⁻¹, 60 min) almost completely (>90%) blocked gluconeogenesis without affecting cell viability as assessed by dye exclusion. In MDCK cells, PhAsO (2 μmol I⁻¹) markedly inhibited glucose uptake (60% of controls) within 30 min, while cell viability, as assessed by formazan formation, was not affected within 180 min. MeAsO and CIvinAsO were similarly effective to PhAsO in both RKT and MDCK cells. Estimated IC₅₀ values for the inhibition of gluconeogenesis were 0.55 (PhAsO), 0.69 (CIvinAsO) and 0.99 μmol I⁻¹ (MeAsO) and for the inhibition of glucose uptake 1.23 (PhAsO). 2.62 (CIvinAsO) and 6.99 μmol I⁻¹ (MeAsO). At longer storage times, aqueous solutions of MeAsO and of CIvinAsO, but not of PhAsO, gradually lost toxic activity in RKT and MDCK cells, especially at alkaline pH. Concomitantly, a gradual decrease in content as assessed by HPLC was detected. Roughly 10-fold higher concentrations of arsenite than of PhAsO were required for comparable effects on gluconeogenesis in RKT, whereas in MDCK cells about 100-fold higher concentrations were needed for similar inhibition of glucose uptake. Pentavalent arsenate and phenylarsonate were two orders of magnitude less effective than PhAsO in RKT, while methylarsonate had virtually no influence on gluconeogenic activity. In MDCK cells the pentavalent arsenic species showed effects only in the millimolar range. It is concluded (1) that different mechanisms are involved in the acute toxicity of oxoarsines and inorganic arsenic and (2) that PhAsO offers advantages as a model substance for mono-substituted trivalent arsenicals, because it is more stable and more readily detectable.     

Influence of organic and inorganic arsenicals on glucose uptake in Madin-Darby canine kidney (MDCK) cells.

The effect of organic (oxophenylarsine; PhAsO) and inorganic (arsenite) arsenicals on the availability of glucose to Madin-Darby canine kidney (MDCK) cells was investigated. The MDCK cells revealed stereospecific D-glucose uptake which was inhibited by both arsenicals in a time- and concentration-dependent manner. After 10 min (37 degrees C), the effects on D-glucose and 2-deoxy-D-glucose accumulation were analogous, suggesting an impaired hexose uptake. With arsenite, 0.5-1 mmol dm-3 were required for half-maximum inhibition (IC50), whereas PhAsO inhibited glucose uptake in the micromolar range (IC50 5-30 mumol dm-3). Under these conditions neither cell morphology nor cellular viability was affected. After 60 min, however, the inhibition of glucose utilization was paralleled by the formation of blebs, detachment of the monolayer and a loss of cellular viability as confirmed by dye exclusion, lactate dehydrogenase and potassium release. It is concluded that inhibition of glucose uptake may contribute to the acute toxicity, especially of organic arsenicals, by further aggravating the depletion of intracellular carbohydrates.     

Active control of the depletion boundary layers in microfluidic electrochemical reactors

In this paper, we describe three methods to improve the performance of pressure-driven laminar flow-based microreactors by manipulating reaction-depletion boundary layers to overcome mass transfer limitations at reactive surfaces on the walls, such as electrodes. The transport rate of the reactants to the reactive surfaces is enhanced by (i) removing the depleted zone through multiple periodically-placed outlets; (ii) adding fresh reactants through multiple periodically-placed inlets along the reactive surface; or (iii) producing a spiraling, transverse flow through the integration of herringbone ridges along the channel walls. For approaches (i) and (ii), the network of microfluidic channels needs to be designed such that under the operating conditions used the right amount of boundary layer at each outlet or inlet is removed or replenished, respectively. Here, we report a set of design rules, derived with the help of a fluidic resistance circuit model, to aid in the design of appropriate microfluidic networks. Also, the actual enhancement of the performance of the electrochemical microreactor, i.e. chemical conversion efficiency, using multiple inlets, multiple outlets, or herringbone ridges is reported.     

Counting of Oxygen Defects versus Metal Surface Sites in Methanol Synthesis Catalysts by Different Probe Molecules

Different surface sites of solid catalysts are usually quantified by dedicated chemisorption techniques from the adsorption capacity of probe molecules, assuming they specifically react with unique sites. In case of methanol synthesis catalysts, the Cu surface area is one of the crucial parameters in catalyst design and was for over 25 years commonly determined using diluted N₂O. To disentangle the influence of the catalyst components, different model catalysts were prepared and characterized using N₂O, temperature programmed desorption of H₂, and kinetic experiments. The presence of ZnO dramatically influences the N₂O measurements. This effect can be explained by the presence of oxygen defect sites that are generated at the Cu‐ZnO interface and can be used to easily quantify the intensity of Cu‐Zn interaction. N₂O in fact probes the Cu surface plus the oxygen vacancies, whereas the exposed Cu surface area can be accurately determined by H₂.     

ChemInform Abstract: μ‐Oxido‐bis(pentammine Iron(III))‐chloride‐ammonia(1/8), [Fe2(μ—O)(NH3)10] Cl4·8NH3.

The title compound is synthesized by reaction of FeCl₃·6H₂O with liquid NH₃ and characterized by single crystal XRD.     

Orbital freezing and orbital glass state in FeCr2S4

Low-temperature specific heat measurements and dielectric spectroscopy have been performed on polycrystalline and single-crystalline FeCr2S4, the single crystals showing a transition into a low-temperature orbital glass phase. The freezing of the orbital moments is revealed by a glasslike specific heat anomaly and by a clear relaxational behavior of the dielectric permittivity, exhibiting several hallmark features of glassy dynamics. The orbital relaxation dynamics continuously slows down over six decades in time, before at the lowest temperatures the glass transition becomes suppressed by quantum tunneling.     

The stochastic collocation method for radiation transport in random media

Stochastic spectral expansions are used to represent random input parameters and the random unknown solution to describe radiation transport in random media. The total macroscopic cross section is taken to be a spatially continuous log-normal random process with known covariance function and expressed as a memoryless transformation of a Gaussian random process. The Karhunen-Loève expansion is applied to represent the spatially continuous random cross section in terms of a finite number of discrete Gaussian random variables. The angular flux is then expanded in terms of Hermite polynomials and, using a quadrature-based stochastic collocation method, the expansion coefficients are shown to satisfy uncoupled deterministic transport equations. Sparse grid Gauss quadrature rules are investigated to establish the efficacy of the polynomial chaos-collocation scheme. Numerical results for the mean and standard deviation of the scalar flux as well as probability density functions of the scalar flux and transmission function are obtained for a deterministic incident source, contrasting between absorbing and diffusive media.     

Statistical analysis of the intermediate filament network in cells of mesenchymal lineage by greyvalue-oriented image segmentation

Intermediate filament networks are part of the cytoskeleton and protect cellular integrity during large deformations. In cells from mesenchymal lineage the cytoskeleton is centrally involved in signal transduction, thereby influencing differentiation. We study the ultrastructure of IF networks in three human mesenchymal cell types, namely undifferentiated mesenchymal stem cells, chondrocytes, and osteoblasts. In order to capture the high morphological variability of IF networks we apply techniques from image analysis to extract the network graph from 2D scanning electron microscopy (SEM) images in a fully automatic way, which allows for a high-throughput analysis of SEM data. The extracted network graphs are analyzed by techniques from spatial statistics to detect differences in network morphology between different cell types and infer strategies of network remodeling used by the cells to adapt their mechanical properties during migration and differentiation.     

Krylov iterative methods and synthetic acceleration for transport in binary statistical media

In particle transport applications there are numerous physical constructs in which heterogeneities are randomly distributed. The quantity of interest in these problems is the ensemble average of the flux, or the average of the flux over all possible material ‘realizations.’ The Levermore–Pomraning closure assumes Markovian mixing statistics and allows a closed, coupled system of equations to be written for the ensemble averages of the flux in each material. Generally, binary statistical mixtures are considered in which there are two (homogeneous) materials and corresponding coupled equations. The solution process is iterative, but convergence may be slow as either or both materials approach the diffusion and/or atomic mix limits. A three-part acceleration scheme is devised to expedite convergence, particularly in the atomic mix-diffusion limit where computation is extremely slow. The iteration is first divided into a series of ‘inner’ material and source iterations to attenuate the diffusion and atomic mix error modes separately. Secondly, atomic mix synthetic acceleration is applied to the inner material iteration and S₂${\mathrm{S}}_2$ synthetic acceleration to the inner source iterations to offset the cost of doing several inner iterations per outer iteration. Finally, a Krylov iterative solver is wrapped around each iteration, inner and outer, to further expedite convergence. A spectral analysis is conducted and iteration counts and computing cost for the new two-step scheme are compared against those for a simple one-step iteration, to which a Krylov iterative method can also be applied.     

Large-scale molecular dynamics simulations of dense plasmas: The Cimarron Project

We describe the status of a new time-dependent simulation capability for dense plasmas. The backbone of this multi-institutional effort – the Cimarron Project – is the massively parallel molecular dynamics (MD) code “ddcMD,” developed at Lawrence Livermore National Laboratory. The project’s focus is material conditions such as exist in inertial confinement fusion experiments, and in many stellar interiors: high temperatures, high densities, significant electromagnetic fields, mixtures of high- and low-Z elements, and non-Maxwellian particle distributions. Of particular importance is our ability to incorporate into this classical MD code key atomic, radiative, and nuclear processes, so that their interacting effects under non-ideal plasma conditions can be investigated. This paper summarizes progress in computational methodology, discusses strengths and weaknesses of quantum statistical potentials as effective interactions for MD, explains the model used for quantum events possibly occurring in a collision, describes two new experimental efforts that play a central role in our validation work, highlights some significant results obtained to date, outlines concepts now being explored to deal more efficiently with the very disparate dynamical timescales that arise in fusion plasmas, and provides a careful comparison of quantum effects on electron trajectories predicted by more elaborate dynamical methods.