IgE autoantibodies in serum and skin of non-bullous and bullous pemphigoid patients

Background Non-bullous pemphigoid (NBP) is a pemphigoid variant which frequently resembles other pruritic skin diseases. In contrast with bullous pemphigoid (BP), blisters are absent. In BP, previous studies showed that IgE autoantibodies may be involved in its pathogenesis. IgE-activated mast cells, basophils and eosinophils may participate in BP by inducing pruritus and possibly blister formation, although the differential role of IgE in NBP compared with BP has not yet been described. Objective To assess IgE in serum and skin of NBP and BP patients. Methods We examined total IgE and pemphigoid-specific IgE in the serum of 68 NBP and 50 BP patients by enzyme-linked immunosorbent assay (ELISA). Sera of 25 pemphigus patients and 25 elderly patients with pruritus were included as controls. Skin biopsies of 14 NBP and 14 BP patients with the highest IgE titres to NC16A were stained for IgE by immunofluorescence techniques. Results Total IgE was elevated in 63% of NBP and 60% of BP patients, and in 20% of pemphigus controls, as well as 60% of elderly controls. IgE ELISAs were more frequently positive in BP than in NBP (NC16A 18% vs. 9%, P = 0.139; BP230 34% vs. 22%, P = 0.149). IgE ELISAs for NC16A and BP230 were positive in 8% and 20% of elderly controls, respectively, while all pemphigus controls were negative. Two of 28 biopsies (7%; one NBP, one BP) showed linear IgE along the basement membrane zone, while in most biopsies (71% NBP; 86% BP) IgE was bound to dermal cells. Conclusion Since IgE was present in the serum and skin of both NBP and BP patients, this supports IgE-dependent mechanisms common to both diseases, such as pruritus. However, it remains to be elucidated whether IgE contributes to blister formation in BP

Challenges in Rotor Aerodynamic Modeling for Non-Uniform Inflow Conditions

Within an international collaboration framework, the accuracy of rotor aerodynamic models used for design load calculations of wind turbines is being assessed. Where the use of high-fidelity computation fluid dynamics (CFD) and mid-fidelity free-vortex wake (FVW) models has become commonplace within the wind energy community, these still fail to meet the requirements in terms of execution time and computational cost needed for design load calculations. The fast but engineering fidelity blade-element/momentum (BEM) method can therefore still be considered the industry workhorse for design load simulations. At the same time, upscaling of wind turbine rotors makes inflow non-uniformities (e.g. shear, veer, turbulence) more important. The objective of this work is to assess model accuracy in non-uniform inflow conditions, which violate several BEM assumptions. Thereto a comparison in turbulent inflow has been executed including a wide variety of codes, focusing on the DanAero field measurements, where a 2.3-MW turbine was equipped with, among other sensors, a pressure measurement apparatus. The results indicate that, although average load patterns are in good agreement, this does not hold for the unsteady loads that drive fatigue damage and aeroelastic stability. A simplified comparison round in vertical shear was initiated to investigate the observed differences in a more controlled manner. A consistent offset in load amplitude was observed between CFD and free-vortex codes on the one hand and BEM-type codes on the other hand. To shed more light on the observations, dedicated efforts are ongoing to pinpoint the cause for these differences, in the end leading to guidelines for an improved BEM implementation

A review of ransomware families and detection methods

Ransomware has become a significant problem and its impact is getting worse. It has now become a lucrative business as it is being offered as a service. Unlike other security issues, the effect of ransomware is irreversible and difficult to stop. This research has analysed existing ransomware classifications and its detection and prevention methods. Due to the difficulty in categorizing the steps none of the existing methods can stop ransomware. Ransomware families are identified and classified from the year 1989 to 2017 and surprisingly there are not much difference in the pattern. This paper concludes with a brief discussion about the findings and future work of this research

Nanotomie van huid en mucosa van pemfiguspatiënten

Pemphigus is an auto-immune blistering skin and/or mucosal disease caused by antibodies against proteins of desmosomes. Desmosomes are cell-cell adhesion structures that interconnect intermediate filament networks of neighboring cells. The transmembrane desmosomal proteins that are the targets of pemphigus autoantibodies, desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3), are specific for the stratified epithelia of the skin and mucosal membranes and are not present in the simple epithelia. Therefore, loss of cell-cell adhesion (acantholysis) induced by pemphigus autoantibodies and clinically presented as blistering occurs only in these tissues. Two main forms of pemphigus are known: pemphigus vulgaris (PV) and pemphigus foliaceus (PF) with a different clinical picture and a different autoantibody profile. How pemphigus autoantibodies induce loss of cell-cell adhesion is our main question. Large scale electron microscopy ("nanotomy") was applied to study pemphigus patients skin and mucosa. This non-biased technique allows easy exploration of large tissue areas which is not possible by conventional EM. We examined both skin and mucosa of PF and PV patients, focusing on ultrastructural details: localization of blister, presence of half desmosomes and localization of keratin filament network in the cells surrounding the blister and desmosomes and intercellular space in nonlesional layers. In spontaneous lesional PF patient skin no desmosomes were present round the blister, while in Nikolsky positive PF patient skin half desmosomes were observed round the blister. In all lesional pemphigus samples and to a lesser extend in non-lesional samples newly described structures named interdigitations composed out of two neighboring cell membranes were present. These structures were abundant in lesional pemphigus skin, which provides a clue to blister pathogenesis.Open source electron-microscopic maps of pemphigus tissue are freely accessible at www.nanotomy.org

Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa

Contains fulltext : 214010.pdf (publisher's version ) (Open Access

Cardiomyopathy in patients with epidermolysis bullosa simplex with mutations in KLHL24

Dominant mutations in the KLHL24 gene, encoding for kelch-like protein 24, have been implicated in the pathogenesis of epidermolysis bullosa simplex (EBS). So far, 26 patients from different ethnicities have been reported and all of them harboured a heterozygous KLHL24 start-codon mutation, with c.1A>G;p.Met1? being the most prevalent.1-3 Through this report, we aimed to expand the phenotypic spectrum by incorporating additional findings, in particular, dilated cardiomyopathy, seen in a Dutch family. This article is protected by copyright. All rights reserved

Theory of carrier phase ambiguity resolution

Carrier phase ambiguity resolution is the key to high precision Global Navigation Satellite System (GNSS) positioning and navigation. It applies to a great variety of current and future models of GPS, modernized GPS and Galileo. A proper handling of carrier phase ambiguity resolution requires a proper understanding of the underlying theory of integer inference. In this contribution a brief review is given of the probabilistic theory of integer ambiguity estimation. We describe the concept of ambiguity pull-in regions, introduce the class of admissible integer estimators, determine their probability mass functions and show how their variability affect the uncertainty in the so-called ‘fixed’ baseline solution. The theory is worked out in more detail for integer least-squares and integer bootstrapping. It is shown that the integer least-squares principle maximizes the probability of correct integer estimation. Sharp and easy-to-compute bounds are given for both the ambiguity success rate and the baseline’s probability of concentration. Finally the probability density function of the ambiguity residuals is determined. This allows one for the first time to formulate rigorous tests for the integerness of the parameters

Dirac electrons in graphene-based quantum wires and quantum dots

In this paper we analyse the electronic properties of Dirac electrons in finite-size ribbons and in circular and hexagonal quantum dots made of graphene.Comment: Contribution for J. Phys.: Cond. Mat. special issue on graphene physic