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We consider the quasi-static energy of a drop on a textured hydrophilic surface, with taking the contact angle hysteresis (CAH) into account. We demonstrate how energy varies as the contact state ...changes from the Cassie state (in which air is trapped at the drop bottom) to the Wenzel state (in which liquid fills the texture at the drop bottom) assuming that the latter state nucleates from the center of the drop bottom. When the textured substrate is hydrophilic enough to allow spontaneous penetration of liquid film of the texture thickness, the present theory asserts that the drop develops into an experimentally observed state in which a drop looks like an egg fried without flipped over (sunny-side up) with a well-defined radius of “the egg yolk.” Otherwise, the final contact state of the drop becomes like a Wenzel state, but with the contact circle smaller than the original Wenzel state due to the CAH. We provide simple analytical estimations for the yolk radius of the “sunny-side-up” state and for the final radius of the contact circle of the pseudo-Wenzel state.
We present a giant molecular cloud (GMC) catalog of M33, containing 71 GMCs in total, based on wide-field and high-sensitivity CO(J = 3-2) observations with a spatial resolution of 100 pc using the ...ASTE 10 m telescope. Employing archival optical data, we identify 75 young stellar groups (YSGs) from the excess of the surface stellar density, and estimate their ages by comparing with stellar evolution models. A spatial comparison among the GMCs, YSGs, and H II regions enable us to classify GMCs into four categories: Type A, showing no sign of massive star formation (SF); Type B, being associated only with H II regions; Type C, with both H II regions and <10 Myr old YSGs; and Type D, with both H II regions and 10-30 Myr YSGs. Out of 65 GMCs (discarding those at the edges of the observed fields), 1 (1%), 13 (20%), 29 (45%), and 22 (34%) are Types A, B, C, and D, respectively. We interpret these categories as stages in a GMC evolutionary sequence. Assuming that the timescale for each evolutionary stage is proportional to the number of GMCs, the lifetime of a GMC with a mass >10 super(5) M sub(middot in circle) is estimated to be 20-40 Myr. In addition, we find that the dense gas fraction as traced by the CO(J = 3-2)/CO(J = 1-0) ratio is enhanced around SF regions. This confirms a scenario where dense gas is preferentially formed around previously generated stars, and will be the fuel for the next stellar generation. In this way, massive SF gradually propagates in a GMC until gas is exhausted.
Summary
Background
S100A7/psoriasin is a member of the S100 protein family and is encoded in the epidermal differentiation complex, which contains genes for markers of epidermal differentiation. ...S100A7/psoriasin is overexpressed in hyperproliferative skin diseases, where it is believed not only to exhibit antimicrobial functions, but also to induce immunomodulatory activities, including chemotaxis and cytokine/chemokine production.
Objectives
To evaluate the effect of S100A7/psoriasin on keratinocyte differentiation and regulation of the tight junction (TJ) barrier.
Methods
Expression of differentiation markers and TJ proteins in human keratinocytes was determined by real‐time polymerase chain reaction and Western blot. The changes in TJ barrier function were assessed by transepithelial electrical resistance and paracellular permeability assays. Glycogen synthase kinase‐3 (GSK‐3) and mitogen‐activated protein kinase (MAPK) activation was analysed by Western blot, whereas β‐catenin and E‐cadherin activation was evaluated by Western blot and immunofluorescence.
Results
S100A7/psoriasin enhanced the expression of several differentiation markers and selectively increased the expression of TJ proteins (e.g. claudins and occludin), which are known to strengthen the TJ barrier. Furthermore, S100A7/psoriasin increased β‐catenin and E‐cadherin accumulation at cell–cell contact, and enhanced transepithelial electrical resistance while reducing the paracellular permeability of keratinocyte layers. The data suggest that S100A7/psoriasin‐mediated regulation of the TJ barrier was via both the GSK‐3 and MAPK pathways, as evidenced by the inhibitory effects of inhibitors for GSK‐3 and MAPKs.
Conclusions
Our finding that S100A7/psoriasin regulates differentiation and strengthens TJ barrier function provides novel evidence that, in addition to antimicrobial and immunoregulatory activities, S100A7/psoriasin is involved in skin innate immunity.
What's already known about this topic?
S100A7/psoriasin is a component of the epidermal differentiation complex; however, its direct role in keratinocyte differentiation and the tight junction (TJ) barrier is not known.
What does this study add?
S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and TJ components, and strengthens the TJ barrier, providing novel evidence that S100A7/psoriasin contributes to cutaneous innate immunity by enhancing the skin barrier, as well as having antimicrobial properties.
Abstract
Background
In patients with atrial fibrillation (AF) receiving anticoagulant therapy, bleeding events are associated with reduced survival. Previous studies showed that bleeding events ...during anticoagulant therapy were more frequent in elderly AF patients than in younger patients. HAS-BLED score has been used to assess the risk of bleeding in AF patients. In patients at high bleeding risk (HAS-BLED score ≥3), we sought to identify other risk factors associated with major bleeding not included in HAS-BLED score in elderly non-valvular AF (NVAF) patients.
Purpose
The All Nippon Atrial Fibrillation In the Elderly (ANAFIE) Registry is a prospective, multicenter, observational study to collect real-world data on clinical status and prognosis in more than 30,000 Japanese patients (aged ≥75 y) with NVAF. This sub-analysis of the ANAFIE Registry assessed the 2-year outcomes and identified predictors for major bleeding in elderly NVAF patients with a high bleeding risk.
Methods
A total of 32,275 patients from the ANAFIE Registry were divided into 2 groups according to HAS-BLED score (≥3 high-risk group and ≤2 reference group). The annualized incidence rate, hazard ratio (HR) for clinical outcomes, and independent predictors for major bleeding were analyzed using Kaplan-Meier analysis and the Cox proportional-hazards model.
Results
A total of 6,826 patients constituted the high-risk group: mean age, 81.8 years old (75–80 years, 37.8%; 81–84 years, 33.9%; ≥85 years, 28.3%); male ratio, 72.2%; mean creatinine clearance (CrCL), 42.7 mL/min; history of major bleeding, 14.2%; presence of non-paroxysmal AF, 62.2%; mean total number of medicines used, 7.8. Anticoagulants were used in 91.2% (warfarin WF, 29.9%; direct oral anticoagulants DOACs, 61.2%). Proton-pump inhibitors (PPI) were administered in 46.5%. Compared to the reference group, the high-risk group had higher annualized incidence rates (/100 patient-year) of major bleeding (1.49 vs 0.97), intracranial hemorrhage (0.95 vs 0.70), gastrointestinal (GI) bleeding (2.63 vs 1.73), and all-cause mortality (5.50 vs 3.24). All-cause mortality more frequently occurred in patients aged ≥85 years compared to 75–79 years and those with CrCL <50 mL/min compared to CrCL ≥50 mL/min. In the high-risk group, DOAC subgroup had lower incidences of the above-mentioned outcomes other than GI bleeding than WF subgroup. The following relevant factors for major bleeding not included in HAS-BLED score were identified in the high-risk group: Body mass index (BMI) ≥25.0 kg/m2 (HR, 0.40), heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HR, 1.38), a fall within 1 year (HR, 2.29), and use of PPI (HR, 0.65).
Conclusions
Among elderly (≥75 years) Japanese NVAF patients in the high bleeding risk group (HAS-BLED score ≥3), HF with reduced LVEF, and a fall within 1 year were identified as independent predictors of major bleeding. BMI ≥25.0 kg/m2 and PPI use were protective for major bleeding.
Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.
We present an overview of the HERschel Inventory of The Agents of Galaxy Evolution (HERITAGE) in the Magellanic Clouds project, which is a Herschel Space Observatory open time key program. We ...describe in detail the data processing, particularly for the PACS data, which required some custom steps because of the large angular extent of a single observational unit and overall the large amount of data to be processed as an ensemble. We report total global fluxes for the LMC and SMC and demonstrate their agreement with measurements by prior missions. We describe the point source extraction processing and the criteria used to establish a catalog for each waveband for the HERITAGE program. The 250 mu m band is the most sensitive and the source catalogs for this band have ~25,000 objects for the LMC and ~5500 objects for the SMC.
Used for both proton decay searches and neutrino physics, large water Cherenkov (WC) detectors have been very successful tools in particle physics. They are notable for their large masses and charged ...particle detection capabilities. While current WC detectors reconstruct charged particle tracks over a wide energy range, they cannot efficiently detect neutrons. Gadolinium (Gd) has the largest thermal neutron capture cross section of all stable nuclei and produces an 8 MeV gamma cascade that can be detected with high efficiency. Because of the many new physics opportunities that neutron tagging with a Gd salt dissolved in water would open up, a large-scale R&D program called EGADS was established to demonstrate this technique’s feasibility. EGADS features all the components of a WC detector, chiefly a 200-ton stainless steel water tank furnished with 240 photo-detectors, DAQ, and a water system that removes all impurities from water while keeping Gd in solution. In this paper we discuss the milestones towards demonstrating the feasibility of this novel technique, and the features of EGADS in detail.
House dust mites produce serine and cysteine proteases. Mite-derived proteases have been suggested to be involved in the pathogenesis of allergies; however, whether mite-derived serine protease ...activity can stimulate keratinocytes remains unknown. We examined the activation of primary human keratinocytes by serine protease-rich extract of whole mite culture and compared with that by recombinant group 1 allergens (rDer f 1 and rDer p 1), which exclusively exhibit cysteine protease activity. Protease activity of whole mite culture extract (WCE), rDer f 1 and rDer p 1 induced the release of IL-8 and granulocyte-macrophage colony-stimulating factor. Protease activity of WCEs induced a significant upregulation of their mRNA expression but rDer f 1 had much less effect. Protease activity of the WCE stimulated intracellular Ca²⁺ mobilization but rDer f 1 and rDer p 1 did not. The mobilization induced by agonists for the human protease-activated receptor (PAR)-2, an agonist peptide or trypsin, was diminished by pre-incubation of keratinocytes with WCE. rDer f 1 inefficiently cleaved a synthetic N-terminal peptide of PAR-2 at different sites from trypsin, but the resultant peptides did not stimulate the release of interleukin-8. The results suggest that mite-derived serine protease activity may contribute to the pathogenesis of atopic dermatitis by activating keratinocytes via PAR-2 activation but cysteine protease activity of Der f 1 and Der p 1 acts via another mechanism.
It remains poorly understood how symptoms in allergic rhinitis are most severe during overnight or early in the morning. The circadian clock consisting of a network of several ‘clock genes’ including ...Clock drives daily rhythms in physiology. This study showed that allergen‐induced surface CD203c expression on basophils in seasonal allergic rhinitis caused by Japanese cedar pollen exhibited a time‐of‐day‐dependent variation associated with temporal variations in canonical circadian clock gene expression. We also found that bone‐marrow‐derived basophils (BM basophils) generated from wild‐type mice exhibited a time‐of‐day‐dependent variation in IgE‐mediated IL‐4 and histamine production, which was not observed in BM basophils generated from Clock‐mutated mice. Therefore, allergen‐specific basophil reactivity shows daily variations depending on the circadian clock activity in basophils, which could partly explain temporal symptomatic variations in allergic rhinitis. Additionally, circadian variations in CD203c expression should be considered for interpretation of this biomarker in clinical research.
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