Filaggrin Genotype Determines Functional and Molecular Alterations in Skin of Patients with Atopic Dermatitis and Ichthyosis Vulgaris

BACKGROUND: Several common genetic and environmental disease mechanisms are important for the pathophysiology behind atopic dermatitis (AD). Filaggrin (FLG) loss-of-function is of great significance for barrier impairment in AD and ichthyosis vulgaris (IV), which is commonly associated with AD. The molecular background is, however, complex and various clusters of genes are altered, including inflammatory and epidermal-differentiation genes. OBJECTIVE: The objective was to study whether the functional and molecular alterations in AD and IV skin depend directly on FLG loss-of-function, and whether FLG genotype determines the type of downstream molecular pathway affected. METHODS AND FINDINGS: Patients with AD/IV (n = 43) and controls (n = 15) were recruited from two Swedish outpatient clinics and a Swedish AD family material with known FLG genotype. They were clinically examined and their medical history recorded using a standardized questionnaire. Blood samples and punch biopsies were taken and trans-epidermal water loss (TEWL) and skin pH was assessed with standard techniques. In addition to FLG genotyping, the STS gene was analyzed to exclude X-linked recessive ichthyosis (XLI). Microarrays and quantitative real-time PCR were used to compare differences in gene expression depending on FLG genotype. Several different signalling pathways were altered depending on FLG genotype in patients suffering from AD or AD/IV. Disease severity, TEWL and pH follow FLG deficiency in the skin; and the number of altered genes and pathways are correlated to FLG mRNA expression. CONCLUSIONS: We emphasize further the role of FLG in skin-barrier integrity and the complex compensatory activation of signalling pathways. This involves inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion in response to FLG-dependent skin-barrier dysfunction

A probability-conserving cross-section biasing mechanism for variance reduction in Monte Carlo particle transport calculations

In Monte Carlo particle transport codes, it is often important to adjust reaction cross sections to reduce the variance of calculations of relatively rare events, in a technique known as non-analogous Monte Carlo. We present the theory and sample code for a Geant4 process which allows the cross section of a G4VDiscreteProcess to be scaled, while adjusting track weights so as to mitigate the effects of altered primary beam depletion induced by the cross section change. This makes it possible to increase the cross section of nuclear reactions by factors exceeding 10^4 (in appropriate cases), without distorting the results of energy deposition calculations or coincidence rates. The procedure is also valid for bias factors less than unity, which is useful, for example, in problems that involve computation of particle penetration deep into a target, such as occurs in atmospheric showers or in shielding

Effects of some emollients on the transmission of ultraviolet

Background/purpose: Various topical agents which can be used in combination with phototherapy may have blocking or enhancing effects. In this in vivo study, the effects of topical petrolatum, basis cream, glycerine and olive oil on the transmission of ultraviolet B (UVB) were investigated

Evaluation of the CloudSat surface snowfall product over Antarctica using ground-based precipitation radars

© 2018 Author(s). In situ observations of snowfall over the Antarctic Ice Sheet are scarce. Currently, continent-wide assessments of snowfall are limited to information from the Cloud Profiling Radar on board the CloudSat satellite, which has not been evaluated up to now. In this study, snowfall derived from CloudSat is evaluated using three ground-based vertically profiling 24 GHz precipitation radars (Micro Rain Radars: MRRs). Firstly, using the MRR long-term measurement records, an assessment of the uncertainty caused by the low temporal sampling rate of CloudSat (one revisit per 2.1 to 4.5 days) is performed. The 10-90th-percentile temporal sampling uncertainty in the snowfall climatology varies between 30% and 40% depending on the latitudinal location and revisit time of CloudSat. Secondly, an evaluation of the snowfall climatology indicates that the CloudSat product, derived at a resolution of 1° latitude by 2° longitude, is able to accurately represent the snowfall climatology at the three MRR sites (biases<15 %), outperforming ERA-Interim. For coarser and finer resolutions, the performance drops as a result of higher omission errors by CloudSat. Moreover, the CloudSat product does not perform well in simulating individual snowfall events. Since the difference between the MRRs and the CloudSat climatology are limited and the temporal uncertainty is lower than current Climate Model Intercomparison Project Phase 5 (CMIP5) snowfall variability, our results imply that the CloudSat product is valuable for climate model evaluation purposes.status: publishe