Modern therapies in atopic dermatitis: biologics and small molecule drugs

Atopic dermatitis (AD) is a frequent, chronic remittent skin disease. The pathophysiology of AD has been increasingly understood within the last years, which may help to identify different endotypes suitable for defined therapies in the future. A patient-oriented therapy considers phenotypical features in addition to genetic and biological markers. The most recent developments in biologics and small-molecule drugs for AD treatment are presented in this article. These molecules, if approved, could change the perspectives for future therapies. Dupilumab is the first approved biologic for the treatment of moderate to severe atopic dermatitis in adolescence and adulthood and has led to a significant improvement in the treatment of this chronic disease. In the present article we present real-life data on the efficacy of dupilumab in adult dermatitis patients. We also discuss other data relevant to the use of dupilumab, and address open questions important for the standard care of atopic dermatitis patients

Radiation Hardness Studies in a CCD with High-Speed Column Parallel Readout

Charge Coupled Devices (CCDs) have been successfully used in several high energy physics experiments over the past two decades. Their high spatial resolution and thin sensitive layers make them an excellent tool for studying short-lived particles. The Linear Collider Flavour Identification (LCFI) collaboration is developing Column-Parallel CCDs (CPCCDs) for the vertex detector of the International Linear Collider (ILC). The CPCCDs can be read out many times faster than standard CCDs, significantly increasing their operating speed. The results of detailed simulations of the charge transfer inefficiency (CTI) of a prototype CPCCD are reported and studies of the influence of gate voltage on the CTI described. The effects of bulk radiation damage on the CTI of a CPCCD are studied by simulating the effects of two electron trap levels, 0.17 and 0.44 eV, at different concentrations and operating temperatures. The dependence of the CTI on different occupancy levels (percentage of hit pixels) and readout frequencies is also studied. The optimal operating temperature for the CPCCD, where the effects of the charge trapping are at a minimum, is found to be about 230 K for the range of readout speeds proposed for the ILC. The results of the full simulation have been compared with a simple analytic model.Comment: 3 pages, 6 figures; presented at IEEE'07, ALCPG'07, ICATPP'0

The Influence of Radiation Damage on the Deflection of High-Energy Beams in Bent Silicon Crystals

Experimental results obtained for deflection of 450 GeV/c protons channeling along the {111} planes in a bent, strongly irradiated silicon crystal are presented. A comparison between the deflection efficiencies in irradiated areas and non-irradiated areas in the crystal shows that irradiation by 2.4 · 1020 protons/cm2 leads to a reduction of around 30 % in deflection efficiency. As a consequence, beam-splitting and extraction from an accelerator by means of a bent crystal are feasible solutions at high energies even for intense beams and during long periods

Record deflection efficiencies measured for high energy protons in a bent germanium crystal

New experimental results on the deflection of high energy protons in a bent germanium crystal are presented. At 450 GeV/c, the 50 mm long crystal gave record deflection efficiencies up to 60% for small angles (1 mrad), while at angles as large as 12 mrad, the efficiency is about 25 times larger than for a silicon crystal of the same size. The experimental results are in good agreement with a model for channeling and deflection developed by Ellison and give - together with a similar comparison for a 200 GeV/c beam - confidence in extrapolations to higher energies (e.g. to LHC), other crystal materials or different deflection angles

A genomic view on syntrophic versus non-syntrophic lifestyle of anaerobic fatty acid-degrading bacteria

In sulfate-reducing and methanogenic environments complex biopolymers are degraded by fermentative micro-organisms that produce hydrogen, carbon dioxide and short chain fatty acids. Degradation of short chain fatty acids can be coupled to methanogenesis or to sulfate reduction. We applied a genomic approach to understand why some bacteria are able to grow in syntrophy with methanogens and others are not. Bacterial strains were selected based on genome availability and upon their ability to grow on short chain fatty acids alone or in syntrophic association with methanogens. Systematic functional domain profiling allowed us to shed light on this fundamental and ecologically important question. Extra-cytoplasmic formate dehydrogenases, including their maturation protein are a typical difference between syntrophic and non-syntrophic butyrate and propionate degraders. Furthermore, two domains with a currently unknown function seem to be associated with the ability of syntrophic growth. One is putatively involved in capsule or biofilm production and a second in cell division, shape-determination or sporulation. Some sulfate reducing bacteria have never been tested for syntrophic growth, but as all crucial domains were found in their genomes, it is possible that these are able to grow in syntrophic association with methanogens. In addition, profiling domains involved in electron transfer mechanisms revealed the important role of the Rnfcomplex and the formate transporter in syntrophy, and indicates that DUF224 may have a role in electron transfer in bacteria that show syntrophic growth