Optimization and Dose Estimation of Aerosol Delivery to Non-Human Primates

Background: In pre-clinical animal studies, the uniformity of dosing across subjects and routes of administration is a crucial requirement. In preparation for a study in which aerosolized live-attenuated measles virus vaccine was administered to cynomolgus monkeys (Macaca fascicularis) by inhalation, we assessed the percentage of a nebulized dose inhaled under varying conditions. Methods: Drug delivery varies with breathing parameters. Therefore we determined macaque breathing patterns (tidal volume, breathing frequency, and inspiratory to expiratory (I:E) ratio) across a range of 3.3-6.5 kg body weight, using a pediatric pneumotachometer interfaced either with an endotracheal tube or a facemask. Subsequently, these breathing patterns were reproduced using a breathing simulator attached to a filter to collect the inhaled dose. Albuterol was nebulized using a vibrating mesh nebulizer and the percentage inhaled dose was determined by extraction of drug from the filter and subsequent quantification. Results: Tidal volumes ranged from 24 to 46 mL, breathing frequencies from 19 to 31 breaths per minute and I:E ratios from 0.7 to 1.6. A small pediatric resuscitation mask was identified as the best fitting interface between animal and pneumotachometer. The average efficiency of inhaled dose delivery was 32.1% (standard deviation 7.5, range 24%-48%), with variation in tidal volumes as the most important determinant. Conclusions: Studies in non-human primates aimed at comparing aerosol delivery with other routes of administration should take both the inter-subject variation and relatively low efficiency of delivery to these low body weight mammals into account

Relating inclusive e+e- annihilation to electroproduction sum rules in Quantum Chromodynamics

The Broadhurst-Kataev conjecture, that the ``discrepancy'' in the connection with the $\pi^0 \to \gamma\gamma$ anomaly equals the beta function $\beta(\bar{\alpha})$ times a power series in the effective coupling $\bar{\alpha}$, is proven to all orders of perturbative quantum chromodynamics. The use of nested short-distance expansions is justified via Weinberg's power-counting theorem.Comment: 10 pages, LaTeX 2e with packages cite, multicol, and curves, 2 figures in LaTe

On the formation process of silicon carbide nanophases via hydrogenated thermally induced templated synthesis

A thermally induced templated synthesis for SiC nanotubes and nanofibers using ammonia or nitrogen as a carrier gas, single wall carbon nanotubes (SWCNT) as templates as well as gaseous Si is presented. The bundles of SWCNT act as both the carbon source and as a nanoframe from which SiC structuctures form. Depending on the duration of the thermally induced templated reaction, for a fixed temperature, carrier gas, and gas pressure, various SiC nanostructures are obtained. These structures include SiC nanorods coated in C, SiC nanorods, SiC nanotubes, and SiC nanocrytals. From our analysis using transmission electron microscopy (TEM) and scanning electron microscopy (SEM), electron energy-loss spectroscopy (EELS), electron diffraction (EDX), optical absorption spectroscopy and Raman spectroscopy as probes we prove that H has a key role on the morphology and stochiometry of the different SiC nanostructures.Comment: 9 pages, 2 Figure

Nernst Effect of stripe ordering La1.8−x_{1.8-x}Eu0.2_{0.2}Srx_xCuO4_4

We investigate the transport properties of La$_{1.8-x}$Eu$_{0.2}$Sr$_x$CuO$_4$ ($x=0.04$, 0.08, 0.125, 0.15, 0.2) with a special focus on the Nernst effect in the normal state. Various anomalous features are present in the data. For $x=0.125$ and 0.15 a kink-like anomaly is present in the vicinity of the onset of charge stripe order in the LTT phase, suggestive of enhanced positive quasiparticle Nernst response in the stripe ordered phase. At higher temperature, all doping levels except $x=0.2$ exhibit a further kink anomaly in the LTO phase which cannot unambiguously be related to stripe order. Moreover, a direct comparison between the Nernst coefficients of stripe ordering La$_{1.8-x}$Eu$_{0.2}$Sr$_x$CuO$_4$ and superconducting La$_{2-x}$Sr$_x$CuO$_4$ at the doping levels $x=0.125$ and $x=0.15$ reveals only weak differences. Our findings make high demands on any scenario interpreting the Nernst response in hole-doped cuprates

Models for Type Ia supernovae and related astrophysical transients

We give an overview of recent efforts to model Type Ia supernovae and related astrophysical transients resulting from thermonuclear explosions in white dwarfs. In particular we point out the challenges resulting from the multi-physics multi-scale nature of the problem and discuss possible numerical approaches to meet them in hydrodynamical explosion simulations and radiative transfer modeling. We give examples of how these methods are applied to several explosion scenarios that have been proposed to explain distinct subsets or, in some cases, the majority of the observed events. In case we comment on some of the successes and shortcoming of these scenarios and highlight important outstanding issues.Comment: 20 pages, 2 figures, review published in Space Science Reviews as part of the topical collection on supernovae, replacement corrects typos in the conclusions sectio

Excitatory effect of ATP on rat area postrema neurons

ATP-induced inward currents and increases in the cytosolic Ca2+ concentration ([Ca]in) were investigated in neurons acutely dissociated from rat area postrema using whole-cell patch-clamp recordings and fura-2 microfluorometry, respectively. The ATP-induced current (IATP) and [Ca]in increases were mimicked by 2-methylthio-ATP and ATP-γS, and were inhibited by P2X receptor (P2XR) antagonists. The current–voltage relationship of the IATP exhibited a strong inward rectification, and the amplitude of the IATP was concentration-dependent. The IATP was markedly reduced in the absence of external Na+, and the addition of Ca2+ to Na+-free saline increased the IATP. ATP did not increase [Ca]in in the absence of external Ca2+, and Ca2+ channel antagonists partially inhibited the ATP-induced [Ca]in increase, indicating that ATP increases [Ca]in by Ca2+ influx through both P2XR channels and voltage-dependent Ca2+ channels. There was a negative interaction between P2XR- and nicotinic ACh receptor (nAChR)-channels, which depended on the amplitude and direction of current flow through either channel. Current occlusion was observed at Vhs between −70 and −10 mV when the IATP and ACh-induced current (IACh) were inward, but no occlusion was observed when these currents were outward at a Vh of +40 mV. The IATP was not inhibited by co-application of ACh when the IACh was markedly decreased either by removal of permeant cations, by setting Vh close to the equilibrium potential of IACh, or by the addition of d-tubocurarine or serotonin. These results suggest that the inhibitory interaction is attributable to inward current flow of cations through the activated P2XR- and nAChR-channels