The Phenion (R) Full-Thickness Skin Model for Percutaneous Absorption Testing

In recent years many efforts have been made to replace dermal toxicity testing of chemicals in the animal by in vitro assays. As a member of a German research consortium, we have previously contributed to the validation of an in vitro test protocol for percutaneous absorption studies on the basis of reconstructed human epidermis and both human and pig skin ex vivo. Aiming to assess the barrier properties of a newly developed reconstructed skin model, this protocol has now been transferred to the Phenion (R) Full-Thickness Skin Model (FT model). The permeation of testosterone and caffeine was quantified in parallel to that of pig skin using Franz-type diffusion cells. In addition, the permeation of benzoic acid and nicotine was studied. As expected, the FT model is more permeable than pig skin, yet its barrier properties are well in accordance with those of reconstructed human epidermis when compared to previous data. In fact, the FT model most efficiently retards testosterone as the compound of highest lipophilicity, which can be explained by an additional uptake by a reservoir formed by the dermis equivalent. Thus, the structure closely parallels human skin. In consequence, the Phenion FT model appears to be suitable for percutaneous absorption studies in hazard analysis and should be subjected to a catch-up validation study. Copyright (C) 2009 S. Karger AG, Base

Design of a high-intensity RFQ for a possible LHC laser ion source

We have designed a 100 MHz RFQ to accelerate Pb25+ ions from 9.6 keV/u to 250 keV/u for the LHC ion program. We assume an input beam from a laser ion source with a total beam current of 90 mA, out of which 9 mA is Pb25+. The main challenge of the design is to match the tight longitudinal acceptance of the downstream Interdigital H structure while dealing with a high intensity beam composed of a variety of charge states. In this paper, we present a baseline setup optimized for nominal conditions, and show the sensitivity of the RFQ performance to varying input beam characteristics and rf parameters. Further studies will cover the compatibility of this design with an upgraded ECR source under investigation at CERN

Deep H-band Galaxy Counts and Half-light Radii from HST/NICMOS Parallel Observations

We present deep galaxy counts and half-light radii from F160W ($\lambda_c=1.6\mu$) images obtained with NICMOS on HST. Nearly 9 arcmin$^2$ have been imaged with camera 3, with $3\sigma$ depths ranging from H = 24.3 to 25.5 in a 0.6$''$ diameter aperture. The slope of the counts fainter than H~$= 20$ is 0.31, and the integrated surface density to H$\leq 24.75$ is $4 \times 10^5$ galaxies per square degree. The half-light radii of the galaxies declines steeply with apparent magnitude. At H~$=24$ we are limited by both the delivered FWHM and the detection threshold of the images.Comment: 8 pages. Accepted for publication in ApJ Letter

Origin of Heart Rate Variability and Turbulence: An Appraisal of Autonomic Modulation of Cardiovascular Function

Heart period constantly changes on a beat to beat basis, due to autonomic influences on the sinoatrial node, and changes can be quantified as heart rate variability (HRV). In addition, after a premature ventricular beat, there are reproducible variations in RR interval, also due to baroreflex mediated autonomic influences on the sinoatrial node, that can be measured as heart rate turbulence (HRT). Impaired autonomic function as measured by HRV and HRT has proven to predict adverse outcomes in clinical settings. The ability of reduced HRV and HRT to predict adverse outcomes has been explained by their dependency on vagal mechanisms that could reflect an increased sympathetic and a reduced vagal modulation of sinus node, thus favoring cardiac electrical instability. Analysis of non-linear dynamics of HRV has also been utilized to describe the fractal like characteristic of the variability signal and proven effective in identify patients at risk for sudden cardiac death. Despite the clinical validity of these measures, it has also been evident that the relationship between neural input and sinus node responsiveness is extremely complex and variable in different clinical conditions. Thus, abnormal HRV or HRT on a clinical Holter recordings may reflect non-neural as well as autonomic mechanisms, and this also needs to be taken into account when interpreting any findings. However, under controlled conditions, the computation of the low and high frequency components of HRV and of their normalized powers or ratio seems capable of providing valid information on sympatho-vagal balance in normal subjects, as well as in most patients with a preserved left ventricular function. Thus, analysis of HRV does provide a unique tool to specifically assess autonomic control mechanisms in association with various perturbations. In conclusion, HRV measures are of substantial utility to identify patients with an increased cardiac mortality and to evaluate autonomic control mechanisms, but their ability to capture specific levels of autonomic control may be limited to controlled laboratory studies in relatively healthy subjects

LIBERAL EGALITARIANISM AND THE HARM PRINCIPLE

We analyse the implications of classical liberal and libertarian approaches for distributive justice in the context of social welfare orderings. We study an axiom capturing a liberal non-interfering view of society, Weak Harm Principle, whose roots can be traced back to John Stuart Mill. We show that liberal views of individual autonomy and freedom can provide consistent foundations for welfare judgements. In particular, a liberal non-interfering approach can help to adjudicate some fundamental distributive issues relative to intergenerational justice. However, a strong relation is established between liberal views of individual autonomy and non-interference, and egalitarian principles in the Rawlsian tradition

The C IV Mass Density of the Universe at Redshift 5

In order to search for metals in the Lyman alpha forest at redshifts z > 4, we have obtained spectra of high S/N and resolution of three QSOs at z > 5.4 discovered by the Sloan Digital Sky Survey. These data allow us to probe to metal enrichment of the intergalactic medium at early times with higher sensitivity than previous studies. We find 16 C IV absorption systems with column densities log N(C IV) = 12.50 - 13.98 over a total redshift path Delta X = 3.29. In the redshift interval z = 4.5-5.0, where our statistics are most reliable, we deduce a comoving mass density of C IV ions Omega(C IV) = (4.3 +/- 2.5) x 10(-8) (90% confidence limits) for absorption systems with log N(C IV) > 13.0 (for an Einstein-de Sitter cosmology with h = 0.65). This value of Omega(C IV) is entirely consistent with those measured at z < 4; we confirm the earlier finding by Songaila (2001) that neither the column density distribution of C IV absorbers nor its integral show significant redshift evolution over a period of time which stretches from 1.25 to 4.5 Gyr after the big bang. This somewhat surprising conclusion may be an indication that the intergalactic medium was enriched in metals at redshifts much greater than 5, perhaps by the sources responsible for its reionization. Alternatively, the C IV systems we see may be associated with outflows from massive star-forming galaxies at later times, while the truly intergalactic metals may reside in regions of the Lyman alpha forest of lower density than those probed up to now.Comment: 24 pages including 5 figures. Accepted for publication in the Astrophysical Journal (September 10, 2003 issue