Metabolism of Butoxyethanol in excised human skin in vitro

Glycol ethers are widely used in industrial and household applications because their chemical and physical properties make them versatile solvents, miscible with both water and organic media. Due to the ease with which the glycol ethers are absorbed through the skin and the potential for development of adverse health effects it is important to understand the extent to which local metabolism can contribute to local and systemic toxicity. Sections of previously frozen, full thickness excised human skin samples were placed on transwell supports and placed with the underside of the skin in contact with receptor fluid. The skin surface was dosed with 115.2 mg of neat butoxyethanol and the absorption and metabolism of butoxyethanol to butoxyacetic acid monitored over time. In total 64.94 ± 0.04 mg of butoxyethanol or its metabolites were removed from the surface of the skin at 24 hours, representing the equivalent of 56% of the applied dose, the equivalent of 17.5% of the applied dose was recovered from the receiver fluid, 3% from within the skin and the remaining 23.5% of the dose was lost to the atmosphere through evaporation. After 24 hours a total of 31.5 μg of butoxyacetic acid had been produced representing approximately 0.03% of the applied dose. Therefore approximately 0.16% (31.5 μg as a percentage of the total amount of butoxyethanol reaching the receiver fluid (20.17 mg) of the absorbed butoxyethanol was metabolised to butoxyacetic acid during its passage through the skin. This suggested that, although enzyme activities capable of converting butoxyethanol to butoxyacetic acid are present in skin, metabolic conversion during percutaneous absorption was small and systemic exposure to the parent compound rather than the metabolite would occur following dermal exposure to butoxyethanol. This experiment demonstrates that it is possible to maintain metabolic activity in skin samples in an in vitro set up for short, but experimentally useful, period.Peer reviewe

The influence of water mixtures on the dermal absorption of glycol ethers

Original article can be found at: http://www.sciencedirect.com/science/journal/0041008X Copyright Elsevier Inc. DOI: 10.1016/j.taap.2006.09.019Glycol ethers are solvents widely used alone and as mixtures in industrial and household products. Some glycol ethers have been shown to have a range of toxic effects in humans following absorption and metabolism to their aldehyde and acid metabolites. This study assessed the influence of water mixtures on the dermal absorption of butoxyethanol and ethoxyethanol in vitro through human skin. Butoxyethanol penetrated human skin up to sixfold more rapidly from aqueous solution (50%, 450 mg/ml) than from the neat solvent. Similarly penetration of ethoxyethanol was increased threefold in the presence of water (50%, 697 mg/ml). There was a corresponding increase in apparent permeability coefficient as the glycol ether concentration in water decreased. The maximum penetration rate of water also increased in the presence of both glycol ethers. Absorption through a synthetic membrane obeyed Fick's Law and absorption through rat skin showed a similar profile to human skin but with a lesser effect. The mechanisms for this phenomenon involves disruption of the stratum corneum lipid bilayer by desiccation by neat glycol ether micelles, hydration with water mixtures and the physicochemical properties of the glycol ether–water mixtures. Full elucidation of the profile of absorption of glycol ethers from mixtures is required for risk assessment of dermal exposure. This work supports the view that risk assessments for dermal contact scenarios should ideally be based on absorption data obtained for the relevant formulation or mixture and exposure scenario and that absorption derived from permeability coefficients may be inappropriate for water-miscible solvents.Peer reviewe

To Blink or Not to Blink: Fine Cognitive Tuning of the Defensive Peripersonal Space

The blink reflex elicited by the electrical stimulation of the median nerve at the wrist (hand blink reflex, HBR) is a subcortical, defensive response that is enhanced when the stimulated hand is inside the peripersonal space of the face. Such enhancement results from a tonic, topdown modulation of the excitability of the brainstem interneurons mediating the HBR. Here we aim to (1) characterize the somatotopical specificity of this top down modulation and (2) investigate the effect of cognitive expectations on such modulation. Experiment 1 showed that the somatotopical specificity of the HBR enhancement is not only heterosegmental, but also partially homosegmental, i.e. the enhancement is greater for the HBR elicited by stimulation of the hand located inside the peripersonal space of the face, as compared to the HBR elicited by the stimulation of the other hand, always kept far from the face. Experiment 2 showed that the top-down modulation of the HBR is triggered only when the participants expect to receive stimuli on the hand placed inside the peripersonal space of the face, and is thus strongly dependent on cognitive expectations. Taken together, these findings indicate a fine somatotopical and cognitive tuning of the excitability of brainstem circuits subserving the HBR, whose strength is adjusted depending on the context in a purposeful manner

Plutonium and cesium radionuclides in the Hudson River Estuary. Annual technical progress report, December 1, 1974--November 30, 1975

We have obtained a large set of gravity cores from the Hudson Estuary through much of the ambient salinity range. A number of core sections have been analyzed for $sup 137$Cs, $sup 134$Cs, $sup 60$Co, and $sup 40$K by direct gamma counting, and for $sup 239$,$sup 240$Pu by alpha-spectrometry. The distribution of both $sup 137$Cs and $sup 239$,$sup 240$Pu indicates rapid accumulation in marginal cove areas and in the harbor region adjacent to New York City. The distribution of both $sup 137$Cs and $sup 239$,$sup 240$Pu in the sediments is quite similar in surface sediments, and the trends with depth in cores are also similar. The ratio of sediment $sup 239$,$sup 240$Pu to $sup 137$Cs throughout the sampled salinity range (0-20 $sup 0$/$sub 00$) approximates that in fallout, except near the nuclear reactor at Indian Point where releases of $sup 137$Cs result in a ratio lower (0.004 to 0.008) than typical of fallout (0.015). Measurement amounts of reactor-derived $sup 134$Cs, $sup 60$Co, and $sup 54$Mn are found in nearly all of the samples containing appreciable $sup 137$Cs. These samples were between 15 km upstream of Indian Point reactor site and the downstream extent of our sampling, 70 km south of the reactor. (auth

Exploiting monitoring data in environmental exposure modelling and risk assessment of pharmaceuticals

In order to establish the environmental impact of an active pharmaceutical ingredient (API), good information on the level of exposure in surface waters is needed. Exposure concentrations are typically estimated using information on the usage of an API as well as removal rates in the patient, the wastewater system and in surface waters. These input data are often highly variable and difficult to obtain, so model estimates often do not agree with measurements made in the field. In this paper we present an approach which uses inverse modelling to estimate overall removal rates of pharmaceuticals at the catchment scale using a hydrological model as well as prescription and monitoring data for a few representative sites for a country or region. These overall removal rates are then used to model exposure across the broader landscape. Evaluation of this approach for APIs in surface waters across England and Wales showed good agreement between modelled exposure distributions and available monitoring data. Use of the approach, alongside estimates of predicted no-effect concentrations for the 12 study compounds, to assess risk of the APIs across the UK landscape, indicated that, for most of the compounds, risks to aquatic life were low. However, ibuprofen was predicted to pose an unacceptable risk in 49.5% of the river reaches studied. For diclofenac, predicted exposure concentrations were also compared to the Environmental Quality Standard previously proposed by the European Commission and 4.5% of river reaches were predicted to exceed this concentration. While the current study focused on pharmaceuticals, the approach could also be valuable in assessing the risks of other ‘down the drain’ chemicals and could help inform our understanding of the important dissipation processes for pharmaceuticals in the pathway from the patient to ecological receptors

Entanglement Dynamics in 1D Quantum Cellular Automata

Several proposed schemes for the physical realization of a quantum computer consist of qubits arranged in a cellular array. In the quantum circuit model of quantum computation, an often complex series of two-qubit gate operations is required between arbitrarily distant pairs of lattice qubits. An alternative model of quantum computation based on quantum cellular automata (QCA) requires only homogeneous local interactions that can be implemented in parallel. This would be a huge simplification in an actual experiment. We find some minimal physical requirements for the construction of unitary QCA in a 1 dimensional Ising spin chain and demonstrate optimal pulse sequences for information transport and entanglement distribution. We also introduce the theory of non-unitary QCA and show by example that non-unitary rules can generate environment assisted entanglement.Comment: 12 pages, 8 figures, submitted to Physical Review

Are subjectively scored linear type traits suitable predictors of the genetic merit for feed intake in grazing Holstein-Friesian dairy cows?

peer-reviewedMeasuring dry matter intake (DMI) in grazing dairy cows using currently available techniques is invasive, time consuming, and expensive. An alternative to directly measuring DMI for use in genetic evaluations is to identify a set of readily available animal features that can be used in a multitrait genetic evaluation for DMI. The objectives of the present study were thus to estimate the genetic correlations between readily available body-related linear type traits and DMI in grazing lactating Holstein-Friesian cows, but importantly also estimate the partial genetic correlations between these linear traits and DMI, after adjusting for differences in genetic merit for body weight. Also of interest was whether the predictive ability derived from the estimated genetic correlations materialized upon validation. After edits, a total of 8,055 test-day records of DMI, body weight, and milk yield from 1,331 Holstein-Friesian cows were available, as were chest width, body depth, and stature from 47,141 first lactation Holstein-Friesian cows. In addition to considering the routinely recorded linear type traits individually, novel composite traits were defined as the product of the linear type traits as an approximation of rumen volume. All linear type traits were moderately heritable, with heritability estimates ranging from 0.27 (standard error = 0.14) to 0.49 (standard error = 0.15); furthermore, all linear type traits were genetically correlated (0.29 to 0.63, standard error 0.14 to 0.12) with DMI. The genetic correlations between the individual linear type traits and DMI, when adjusted for genetic differences in body weight, varied from −0.51 (stature) to 0.48 (chest width). These genetic correlations between DMI and linear type traits suggest linear type traits may be useful predictors of DMI, even when body weight information is available. Nonetheless, estimated genetic merit of DMI derived from a multitrait genetic evaluation of linear type traits did not correlate strongly with actual DMI in a set of validation animals; the benefit was even less if body weight data were also available

Electronic structure, exchange interactions and Curie temperature in diluted III-V magnetic semiconductors: (GaCr)As, (GaMn)As, (GaFe)As

We complete our earlier (Phys. Rev. B, {\bf 66}, 134435 (2002)) study of the electronic structure, exchange interactions and Curie temperature in (GaMn)As and extend the study to two other diluted magnetic semiconductors (GaCr)As and (GaFe)As. Four concentrations of the 3d impurities are studied: 25%, 12.5%, 6.25%, 3.125%. (GaCr)As and (GaMn)As are found to possess a number of similar features. Both are semi-metallic and ferromagnetic, with similar properties of the interatomic exchange interactions and the same scale of the Curie temperature. In both systems the presence of the charge carriers is crucial for establishing the ferromagnetic order. An important difference between two systems is in the character of the dependence on the variation of the number of carriers. The ferromagnetism in (GaMn)As is found to be very sensitive to the presence of the donor defects, like As$_{\rm Ga}$ antisites. On the other hand, the Curie temperature of (GaCr)As depends rather weakly on the presence of this type of defects but decreases strongly with decreasing number of electrons. We find the exchange interactions between 3d atoms that make a major contribution into the ferromagnetism of (GaCr)As and (GaMn)As and propose an exchange path responsible for these interactions. The properties of (GaFe)As are found to differ crucially from the properties of (GaCr)As and (GaMn)As. (GaFe)As does not show a trend to ferromagnetism and is not half-metallic that makes this system unsuitable for the use in spintronic semiconductor devices

H2 in the interstitial channels of nanotube bundles

The equation of state of H2 adsorbed in the interstitial channels of a carbon nanotube bundle has been calculated using the diffusion Monte Carlo method. The possibility of a lattice dilation, induced by H2 adsorption, has been analyzed by modeling the cohesion energy of the bundle. The influence of factors like the interatomic potentials, the nanotube radius and the geometry of the channel on the bundle swelling is systematically analyzed. The most critical input is proved to be the C-H2 potential. Using the same model than in planar graphite, which is expected to be also accurate in nanotubes, the dilation is observed to be smaller than in previous estimations or even inexistent. H2 is highly unidimensional near the equilibrium density, the radial degree of freedom appearing progressively at higher densities.Comment: Accepted for publication in PR

User-Centered Evaluation of a Discovery Layer System with Google Scholar

Discovery layer systems allow library users to obtain search results from multiple library resources and view results in a consistent format. The implementation of a discovery layer is expected to simplify users’ workflow of searching for scholarly information. Previous studies on discovery layer systems focused on functionality and content, but not quality of search results from the user’s perspective. The objective of this study was to obtain users’ assessment of search results of a discovery layer system (Ex Libris Primo®) and compare that with a widely used scholarly search tool (Google Scholar). Results showed that Primo’s search results relevancy is comparable to Google Scholar, but it received significantly lower usability and preference ratings. A number of usability issues of Primo were also identified from the study. Results of the study are used to improve the interface of Primo and adjust relevancy ranking options. The empirical method of search results assessment and feedback collection used in this study can be extended to similar user-centered system implementation and evaluation efforts