Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex

This study considers whether the current standard toxicokinetic methods are an accurate and applicable assessment of xenobiotic exposure in an aquatic freshwater invertebrate. An in vivo exposure examined the uptake and elimination kinetics for eight pharmaceutical compounds in the amphipod crustacean, Gammarus pulex by measuring their concentrations in both biological material and in the exposure medium over a 96 h period. Selected pharmaceuticals included two anti-inflammatories (diclofenac and ibuprofen), two beta-blockers (propranolol and metoprolol), an anti-depressant (imipramine), an anti-histamine (ranitidine) and two beta-agonists (formoterol and terbutaline). Kinetic bioconcentration factors (BCFs) for the selected pharmaceuticals were derived from a first-order one-compartment model using either the simultaneous or sequential modelling methods. Using the simultaneous method for parameter estimation, BCF values ranged from 12 to 212. In contrast, the sequential method for parameter estimation resulted in bioconcentration factors ranging from 19 to 4533. Observed toxicokinetic plots showed statistically significant lack-of-fits and further interrogation of the models revealed a decreasing trend in the uptake rate constant over time for rantidine, diclofenac, imipramine, metoprolol, formoterol and terbutaline. Previous published toxicokinetic data for 14 organic micro-pollutants were also assessed and similar trends were identified to those observed in this study. The decreasing trend of the uptake rate constant over time highlights the need to interpret modelled data more comprehensively to ensure uncertainties associated with uptake and elimination parameters for determining bioconcentration factors are minimised

Oxygen adsorption on the Ru (10 bar 1 0) surface: Anomalous coverage dependence

Oxygen adsorption onto Ru (10 bar 1 0) results in the formation of two ordered overlayers, i.e. a c(2 times 4)-2O and a (2 times 1)pg-2O phase, which were analyzed by low-energy electron diffraction (LEED) and density functional theory (DFT) calculation. In addition, the vibrational properties of these overlayers were studied by high-resolution electron loss spectroscopy. In both phases, oxygen occupies the threefold coordinated hcp site along the densely packed rows on an otherwise unreconstructed surface, i.e. the O atoms are attached to two atoms in the first Ru layer Ru(1) and to one Ru atom in the second layer Ru(2), forming zigzag chains along the troughs. While in the low-coverage c(2 times 4)-O phase, the bond lengths of O to Ru(1) and Ru(2) are 2.08 A and 2.03 A, respectively, corresponding bond lengths in the high-coverage (2 times 1)-2O phase are 2.01 A and 2.04 A (LEED). Although the adsorption energy decreases by 220 meV with O coverage (DFT calculations), we observe experimentally a shortening of the Ru(1)-O bond length with O coverage. This effect could not be reconciled with the present DFT-GGA calculations. The nu(Ru-O) stretch mode is found at 67 meV [c(2 times 4)-2O] and 64 meV [(2 times 1)pg-2O].Comment: 10 pages, figures are available as hardcopies on request by mailing [email protected], submitted to Phys. Rev. B (8. Aug. 97), other related publications can be found at http://www.rz-berlin.mpg.de/th/paper.htm

Accumulation of Self-Reactive Naive and Memory B Cell Reveals Sequential Defects in B Cell Tolerance Checkpoints in Sjogren's Syndrome

This work was funded by grants number 18237 and 20089 from Arthritis Research UK (http://www.arthritisresearchuk.org) to MB and the William Harvey Research Foundation. EC was recipient of short-term travel fellowships from EMBO (ASTF 318-2010) and EFIS-IL

On Smooth Orthogonal and Octilinear Drawings: Relations, Complexity and Kandinsky Drawings

We study two variants of the well-known orthogonal drawing model: (i) the smooth orthogonal, and (ii) the octilinear. Both models form an extension of the orthogonal, by supporting one additional type of edge segments (circular arcs and diagonal segments, respectively). For planar graphs of max-degree 4, we analyze relationships between the graph classes that can be drawn bendless in the two models and we also prove NP-hardness for a restricted version of the bendless drawing problem for both models. For planar graphs of higher degree, we present an algorithm that produces bi-monotone smooth orthogonal drawings with at most two segments per edge, which also guarantees a linear number of edges with exactly one segment.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis

Objectives: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. Methods: A systematic search was performed for studies of rifampicin PK published in the English language up to May 2017. Data describing the Cmax and AUC were extracted. Meta-analysis provided summary estimates for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the I 2 statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were compared graphically and contextualized using preclinical pharmacodynamic (PD) data. Results: Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment duration had a significant impact on the summary estimates for rifampicin PK parameters, with Cmax 8.98 mg/L (SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mgh/L (SEM 2.60) and 38.73 mgh/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies. Conclusions: Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages as efforts to explore higher dosing strategies continue in this field

Dynamical properties of liquid Al near melting. An orbital-free molecular dynamics study

The static and dynamic structure of liquid Al is studied using the orbital free ab-initio molecular dynamics method. Two thermodynamic states along the coexistence line are considered, namely T = 943 K and 1323 K for which X-ray and neutron scattering data are available. A new kinetic energy functional, which fulfills a number of physically relevant conditions is employed, along with a local first principles pseudopotential. In addition to a comparison with experiment, we also compare our ab-initio results with those obtained from conventional molecular dynamics simulations using effective interionic pair potentials derived from second order pseudopotential perturbation theory.Comment: 15 pages, 12 figures, 2 tables, submitted to PR

An Introduction to Gas Accretion onto Galaxies

Evidence for gas accretion onto galaxies can be found throughout the universe. In this chapter, I summarize the direct and indirect signatures of this process and discuss the primary sources. The evidence for gas accretion includes the star formation rates and metallicities of galaxies, the evolution of the cold gas content of the universe with time, numerous indirect indicators for individual galaxies, and a few direct detections of inflow. The primary sources of gas accretion are the intergalactic medium, satellite gas and feedback material. There is support for each of these sources from observations and simulations, but the methods with which the fuel ultimately settles in to form stars remain murky.Comment: 14 pages, 5 figures, Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

Layer-by-layer deposition of open-pore mesoporous TiO 2- Nafion® film electrodes

The formation of variable thickness TiO2 nanoparticle-Nafion® composite films with open pores is demonstrated via a layer-by-layer deposition process. Films of about 6 nm diameter TiO2 nanoparticles grow in the presence of Nafion® by “clustering” of nanoparticles into bigger aggregates, and the resulting hierarchical structure thickens with about 25 nm per deposition cycle. Film growth is characterized by electron microscopy, atomic force microscopy, and quartz crystal microbalance techniques. Simultaneous small-angle X-ray scattering and wide-angle X-ray scattering measurements for films before and after calcination demonstrate the effect of Nafion® binder causing aggregation. Electrochemical methods are employed to characterize the electrical conductivity and diffusivity of charge through the TiO2-Nafion® composite films. Characteristic electrochemical responses are observed for cationic redox systems (diheptylviologen2+/+, Ru(NH3)3+/2+6, and ferrocenylmethyl-trimethylammonium2+/+) immobilized into the TiO2-Nafion® nanocomposite material. Charge conduction is dependent on the type of redox system and is proposed to occur either via direct conduction through the TiO2 backbone (at sufficiently negative potentials) or via redox-center-based diffusion/electron hopping (at more positive potentials)

To wet or not to wet: that is the question

Wetting transitions have been predicted and observed to occur for various combinations of fluids and surfaces. This paper describes the origin of such transitions, for liquid films on solid surfaces, in terms of the gas-surface interaction potentials V(r), which depend on the specific adsorption system. The transitions of light inert gases and H2 molecules on alkali metal surfaces have been explored extensively and are relatively well understood in terms of the least attractive adsorption interactions in nature. Much less thoroughly investigated are wetting transitions of Hg, water, heavy inert gases and other molecular films. The basic idea is that nonwetting occurs, for energetic reasons, if the adsorption potential's well-depth D is smaller than, or comparable to, the well-depth of the adsorbate-adsorbate mutual interaction. At the wetting temperature, Tw, the transition to wetting occurs, for entropic reasons, when the liquid's surface tension is sufficiently small that the free energy cost in forming a thick film is sufficiently compensated by the fluid- surface interaction energy. Guidelines useful for exploring wetting transitions of other systems are analyzed, in terms of generic criteria involving the "simple model", which yields results in terms of gas-surface interaction parameters and thermodynamic properties of the bulk adsorbate.Comment: Article accepted for publication in J. Low Temp. Phy

Gas Accretion and Star Formation Rates

Cosmological numerical simulations of galaxy evolution show that accretion of metal-poor gas from the cosmic web drives the star formation in galaxy disks. Unfortunately, the observational support for this theoretical prediction is still indirect, and modeling and analysis are required to identify hints as actual signs of star-formation feeding from metal-poor gas accretion. Thus, a meticulous interpretation of the observations is crucial, and this observational review begins with a simple theoretical description of the physical process and the key ingredients it involves, including the properties of the accreted gas and of the star-formation that it induces. A number of observations pointing out the connection between metal-poor gas accretion and star-formation are analyzed, specifically, the short gas consumption time-scale compared to the age of the stellar populations, the fundamental metallicity relationship, the relationship between disk morphology and gas metallicity, the existence of metallicity drops in starbursts of star-forming galaxies, the so-called G dwarf problem, the existence of a minimum metallicity for the star-forming gas in the local universe, the origin of the alpha-enhanced gas forming stars in the local universe, the metallicity of the quiescent BCDs, and the direct measurements of gas accretion onto galaxies. A final section discusses intrinsic difficulties to obtain direct observational evidence, and points out alternative observational pathways to further consolidate the current ideas.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe