Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

CTCF induces histone variant incorporation, erases the H3K27me3 histone mark and opens chromatin

Insulators functionally separate active chromatin domains frominactive ones. The insulator factor, CTCF, has been found to bind to boundaries and to mediate insulator function. CTCF binding sites are depleted for the histone modification H3K27me3 and are enriched for the histone variant H3.3. In order to determine whether demethylation of H3K27me3 and H3.3 incorporation are a requirement for CTCF binding at domain boundaries or whether CTCF causes these changes, we made use of the LacI DNA binding domain to control CTCF binding by the Lac inducer IPTG. Here we show that, in contrast to the related factor CTCFL, the N-terminus plus zinc finger domain of CTCF is sufficient to open compact chromatin rapidly. This is preceded by incorporation of the histone variant H3.3, which thereby removes the H3K27me3 mark. This demonstrates the causal role for CTCF in generating the chromatin features found at insulators. Thereby, spreading of a histone modification from one domain through the insulator into the neighbouring domain is inhibited

Choice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference

The two paralogous zinc finger factors CTCF and CTCFL differ in expression such that CTCF is ubiquitously expressed, whereas CTCFL is found during spermatogenesis and in some cancer types in addition to other cell types. Both factors share the highly conserved DNA binding domain and are bound to DNA sequences with an identical consensus. In contrast, both factors differ substantially in the number of bound sites in the genome. Here, we addressed the molecular features for this binding specificity. In contrast to CTCF we found CTCFL highly enriched at 'open' chromatin marked by H3K27 acetylation, H3K4 di- and trimethylation, H3K79 dimethylation and H3K9 acetylation plus the histone variant H2A.Z. CTCFL is enriched at transcriptional start sites and regions bound by transcription factors. Consequently, genes deregulated by CTCFL are highly cell specific. In addition to a chromatin-driven choice of binding sites, we determined nucleotide positions critical for DNA binding by CTCFL, but not by CTCF

Prediction of inter-particle adhesion force from surface energy and surface roughness

Fine powder flow is a topic of great interest to industry, in particular for the pharmaceutical industry; a major concern being their poor flow behavior due to high cohesion. In this study, cohesion reduction, produced via surface modification, at the particle scale as well as bulk scale is addressed. The adhesion force model of Derjaguin-Muller-Toporov (DMT) was utilized to quantify the inter-particle adhesion force of both pure and surface modified fine aluminum powders (∼8 μm in size). Inverse Gas Chromatography was utilized for the determination of surface energy of the samples, and Atomic Force Microscopy was utilized to evaluate surface roughness of the powders. Surface modification of the original aluminum powders was done for the purpose of reduction in cohesiveness and improvement in flowability, employing either silane surface treatment or dry mechanical coating of nano-particles on the surface of original powders. For selected samples, the AFM was utilized for direct evaluation of the particle pull-off force. The results indicated that surface modification reduced the surface energy and altered the surface nano-roughness, resulting in drastic reduction of the inter-particle adhesion force. The particle bond number values were computed based on either the inter-particle adhesion force from the DMT model or the inter-particle pull-off force obtained from direct AFM measurements. Surface modification resulted in two to three fold reductions in the Bond number. In order to examine the influence of the particle scale property such as the Bond number on the bulk-scale flow characterization, Angle of Repose measurements were done and showed good qualitative agreements with the Bond number and acid/base surface characteristics of the powders. The results indicate a promising method that may be used to predict flow behavior of original (cohesive) and surface modified (previously cohesive) powders utilizing very small samples

A guide to the Choquard equation

We survey old and recent results dealing with the existence and properties of solutions to the Choquard type equations $$-\Delta u + V(x)u = \bigl(|x|^{-(N-\alpha)} * |u|^p\bigr)|u|^{p - 2} u \qquad \text{in $\mathbb{R}^N$},$$ and some of its variants and extensions.Comment: 39 page

Randomized clinical trial of the effect of semi-occlusive dressings on the microflora and clinical outcome of acute facial wounds

This study investigated whether treatment with occlusive, hydroactive polyurethane dressings affects the microflora and clinical outcome of acute wounds. A randomized, controlled trial was performed on 60 patients with acute facial lacerations. Following primary closure, patients were provided with either a dry-gauze dressing or a hydroactive polyurethane dressing (Cutinova® Thin). The wounds were assessed clinically and microbiologically prior to closure, then after 5, 28 and 56 days. The dressing, which was removed at day 5, was also sent for microbiological culture. Wounds treated with the polyurethane dressing showed improved comfort and contour (p 0.05). A total of 518 isolates were recovered from the patients during the study. Mean number of isolates and bacterial growth density were calculated in both groups. A similar range of microorganisms were obtained from both treatment groups with no clear difference in organism colonization. This study shows the potential usefulness of facial wounds as a human model for studying acute wound healing responses and anti-scarring therapy. While short-term, clinical benefits of occlusive dressings were evident in the management of acute wounds, these data clearly show that all studies of scarring following acute wounding should extend over at least 3 months post-injury to allow for spontaneous improvement to occur

Design update and mock-up test strategy for the validation of the eu-hcpb-tbm concept

In the frame of the activities of the EU Breeder Blanket Programme and of the Test Blanket Working Group of ITER, the Helium Cooled Pebble Bed Test Blanket Module (HCPB-TBM) is developed to investigate DEMO relevant concepts for blanket modules. The main functions of a blanket module (heat removal, tritium breeding and sensitive components shielding) will be tested in DEMO relevant conditions during four different test campaigns in ITER. One TBM of the HCPB concept will be installed into the vacuum vessel connected to one equatorial port designed for vertical TBM orientation during each of the four test campaigns. This paper describes the FZK activities in order to verify the design of the HCPB TBM with regard to operational conditions in ITER and to prove the feasibility of the manufacturing techniques proposed. As the studies performed in FZK up to 2006 concerned a horizontal orientation of the HCPB, a review of the design was necessary to match with the new ITER specifications. Even if the general architecture of the horizontal TBM is maintained, nevertheless the change of configuration has significant impact on the design of the TBM sub-components. An overview of the new vertical HCPB design is presented, detailing the strategy adopted to assess the design and the thermal and fluid dynamic analyses performed for the TBM First Wall. In parallel to the TBM design and analysis, a large mock-up programme addresses the main issues of manufacturing and performances for single components and systems. The three medium-size mock-ups foreseen in FZK to validate the fabrication and mounting processes are presented detailing their purposes