ABSTRACT
Tidal features in the outskirts of galaxies yield unique information about their past interactions and are a key prediction of the hierarchical structure formation paradigm. The Vera C. ...Rubin Observatory is poised to deliver deep observations for potentially millions of objects with visible tidal features, but the inference of galaxy interaction histories from such features is not straightforward. Utilizing automated techniques and human visual classification in conjunction with realistic mock images produced using the NewHorizon cosmological simulation, we investigate the nature, frequency, and visibility of tidal features and debris across a range of environments and stellar masses. In our simulated sample, around 80 per cent of the flux in the tidal features around Milky Way or greater mass galaxies is detected at the 10-yr depth of the Legacy Survey of Space and Time (30–31 mag arcsec−2), falling to 60 per cent assuming a shallower final depth of 29.5 mag arcsec−2. The fraction of total flux found in tidal features increases towards higher masses, rising to 10 per cent for the most massive objects in our sample (M⋆ ∼ 1011.5 M⊙). When observed at sufficient depth, such objects frequently exhibit many distinct tidal features with complex shapes. The interpretation and characterization of such features varies significantly with image depth and object orientation, introducing significant biases in their classification. Assuming the data reduction pipeline is properly optimized, we expect the Rubin Observatory to be capable of recovering much of the flux found in the outskirts of Milky Way mass galaxies, even at intermediate redshifts (z < 0.2).
ABSTRACT
Over the last few decades, weather and climate extremes have become a major focus of researchers, the media and general public due to their damaging effects on human society and ...infrastructure. Trends in indices of climate extremes are studied for the South Asian region using high‐quality records of daily temperature and precipitation observations. Data records from 210 (265) temperature (precipitation) observation stations are analysed over the period 1971–2000 (1961–2000). Spatial maps of station trends, time series of regional averages and frequency distribution analysis form the basis of this study. Due to the highly diverse geography of the South Asian region, the results are also described for some specific regions, such as the island of Sri Lanka; the tropical region (excluding Sri Lanka); the Greater Himalayas above 35°N, the Eastern Himalayas (Nepal) and the Thar Desert. Generally, changes in the frequency of temperature extremes over South Asia are what one would expect in a warming world; warm extremes have become more common and cold extremes less common. The warming influence is greater in the Eastern Himalayas compared with that in the Greater Himalayas. The Thar Desert also shows enhanced warming, but increases are mostly less than in the Eastern Himalayas. Changes in the indices of extreme precipitation are more mixed than those of temperature, with spatially coherent changes evident only at relatively small scales. Nevertheless, most extreme precipitation indices show increases in the South Asia average, consistent with globally averaged results. The indices trends are further studied in the context of Atmospheric Brown Clouds (ABCs) over the region. Countries falling within the ABC hotspot namely Indo‐Gangetic Plain (IGP) have shown a different behaviour on the trends of extreme indices compared with the parts outside this hotspot. IGP has increased temperature and decreased rainfall and tally closely with the actual trends.
Eosinophilic oesophagitis (EO) is an emerging yet increasingly prevalent disorder characterised by a dense and selective eosinophilic infiltration of the oesophageal wall. While EO is considered an ...atopic disease primarily triggered by food antigens, disparities between standard allergen testing and clinical responses to exclusion diets suggest the participation of distinct antigen-specific immunoglobulin E (IgE) in the pathophysiology of EO.
To find evidence for a local IgE response.
Endoscopic biopsies of the distal oesophagus of atopic and non-atopic EO and control individuals (CTL) were processed for immunohistochemistry and immunofluorescence to assess the presence of B cells, mast cells, and IgE-bearing cells. Oesophageal RNA was analysed for the expression of genes involved in B cell activation, class switch recombination to IgE and IgE production, including germline transcripts (GLTs), activation-induced cytidine deaminase (AID), IgE heavy chain (Cepsilon) and mature IgE mRNA using polymerase chain reaction and microarray analysis.
Regardless of atopy, EO showed increased density of B cells (p<0.05) and of IgE-bounded mast cells compared to CTL. Both EO and CTL expressed muGLT, epsilonGLT, gamma4GLT, AID, Cepsilon and IgE mRNA. However, the frequency of expression of total GLTs (p = 0.002), epsilonGLT (p = 0.024), and Cepsilon (p = 0.0003) was significantly higher in EO than in CTL, independent of the atopic status.
These results support the heretofore unproven occurrence of both local immunoglobulin class switching to IgE and IgE production in the oesophageal mucosa of EO patients. Sensitisation and activation of mast cells involving local IgE may therefore critically contribute to disease pathogenesis.
The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug ...interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions.
Satellite-based passive microwave remote sensing typically involves a scanning antenna that makes measurements at irregularly spaced locations. These locations can change on a day to day basis. Soil ...moisture products derived from satellite-based passive microwave remote sensing are usually resampled to a fixed Earth grid that facilitates their use in applications. In many cases the grid size is finer than the actual spatial resolution of the observation, and often this difference is not well understood by the user. Here, this issue was examined for the Soil Moisture Active Passive (SMAP) enhanced version of the passive-based soil moisture product, which has a grid size of 9-km and a nominal spatial resolution of 33-km. In situ observations from core validation sites were used to compute comparison metrics. For sites that satisfied the established reliability and scaling criteria, the impact of validating the 9-km grid product with in situ data collected over a 9-km versus a 33-km domain was very small for the sites studied (0.039 m3/m3 unbiased root mean square difference for the 9-km case versus 0.037 m3/m3 for the 33-km case). This result does not mean that the resolution of the product is 9-km but that for the conditions studied here the soil moisture estimated from in situ observations over 9-km is a close approximation of the soil moisture estimated from in situ observations over the 33-km resolution. The implication is that using the enhanced SMAP product at its grid resolution of 9-km should not introduce large errors in most applications.
•Comparison of SMAP soil moisture validation at 9-km and 33-km spatial scales.•In situ soil moisture at 9-km scale correlates well with soil moisture at 33-km.•Validation metrics similar at 9-km and 33-km scales for the SMAP product.•The SMAP product can be used at 9-km scale with most applications.
Leukocyte Activation by Triglyceride-Rich Lipoproteins Alipour, Arash; van Oostrom, Antonie J.H.H.M; Izraeljan, Alisa ...
Arteriosclerosis, thrombosis, and vascular biology,
2008-April, Letnik:
28, Številka:
4
Journal Article
Recenzirano
Odprti dostop
OBJECTIVE—Postprandial lipemia has been linked to atherosclerosis and inflammation. Because leukocyte activation is obligatory for atherogenesis, leukocyte activation by triglyceride-rich ...lipoproteins (TRLs) was investigated.
METHODS AND RESULTS—The expression of CD11b and CD66b after incubation with glucose and native and artificial TRLs (NTRL and ATRL) in vivo and in vitro was evaluated by flowcytometry. Oral fat loading tests showed an increased expression of CD11b on monocytes and neutrophils and CD66b on neutrophils. In 11 volunteers, postprandial leukocytes became enriched with meal-derived fatty acids (1-C16:0) suggesting uptake of exogenous fat. ApoB binding on leukocytes measured by flowcytometry in 65 subjects was highest on neutrophils and monocytes suggesting adherence of apoB-containing lipoproteins. Physiological concentrations of TRLs showed 62% increased neutrophil CD11b and a dose-dependent increased monocyte CD11b up to 84% in vitro. Incubations with lipid emulsions in the hypertriglyceridemic range showed a 5-fold increased monocyte CD11b expression, which was higher than the positive control (fMLP), and a dose-dependent 2- to 3-fold increased neutrophil CD11b and CD66b. The oxidative scavenger DMTU decreased the neutrophil CD66b expression by 36%.
CONCLUSION—Acute hypertriglyceridemia is a leukocyte activator most likely by direct interaction between TRLs and leukocytes and uptake of fatty acids. TG-mediated leukocyte activation is an alternative proinflammatory and proatherogenic mechanism of hypertriglyceridemia in part associated to the generation of oxidative stress.
Background
Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels ...and to determine functional correlations as assessed by histologic and transcriptome analyses.
Methods
This case‐control study included pediatric subjects with EoE (≥15 eosinophils/HPF) and non‐EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1‐IgG4 using the Luminex 100 system; IgE was quantified by ELISA. Esophageal biopsies were scored using the EoE histology scoring system. Transcripts were probed by the EoE diagnostic panel, designed to examine the expression of 96 esophageal transcripts.
Results
Esophageal IgG subclasses, IgA, and IgM, but not IgE, were increased in subjects with EoE relative to controls. The greatest change between groups was seen in IgG4 (4.2 mg/g protein interquartile range: 1.0‐13.1 mg/g protein vs 0.2 mg/g protein 0.1‐0.9; P < .0001). Tissue IgG4 levels correlated with esophageal eosinophil counts (P = .0006); histologic grade (P = .0011) and stage (P = .0112) scores; and IL4, IL10, IL13, but not TGFB1, expression and had strong associations with a subset of the EoE transcriptome. Esophageal IgG4 transcript expression was increased and correlated with IgG4 protein levels and IL10 expression.
Conclusion
These findings extend prior studies on IgG4 in adult EoE to the pediatric population and provide deeper understanding of the potential significance and regulation of IgG4, demonstrating that IgG4 is a relevant feature of the disease; is closely related to esophageal eosinophil levels, type 2 immunity and T regulatory cytokines; and is likely produced locally.
Esophageal IgG4 levels are increased in patients with EoE compared with control individuals and strongly correlate with esophageal eosinophil numbers and multiple features of histologic grade and stage scores. Esophageal IgG4 protein levels correlate with multiple components of the disease as assessed by transcriptome profiling, including IL4, IL13 and IL10 mRNA expression levels. IgG4 heavy chain mRNA expression is proportional to IgG4 protein levels and IL10 mRNA expression levels in the esophagus of patients with EoE.
Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory ...Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope.
The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field.
A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02, "Rehabilitation and Chronic Care," determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed on by all members.
An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease, and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed.
The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas without effective therapeutics. Bioinformatics was used to identify potential therapeutic targets. Paired Box (PAX), Eyes ...Absent (EYA), Dachsund (DACH) and Sine Oculis (SIX) genes, which form a regulatory interactive network in Drosophila, were found to be dysregulated in human MPNST cell lines and solid tumors. We identified a decrease in DACH1 expression, and increases in the expressions of PAX6, EYA1, EYA2, EYA4, and SIX1-4 genes. Consistent with the observation that half of MPNSTs develop in neurofibromatosis type 1 (NF1) patients, subsequent to NF1 mutation, we found that exogenous expression of the NF1-GTPase activating protein-related domain normalized DACH1 expression. EYA4 mRNA was elevated more than 100-fold as estimated by quantitative real-time PCR in most MPNST cell lines. In vitro, suppression of EYA4 expression using short hairpin RNA reduced cell adhesion and migration and caused cellular necrosis without affecting cell proliferation or apoptotic cell death. MPNST cells expressing shEYA4 either failed to form tumors in nude mice or formed very small tumors, with extensive necrosis but similar levels of proliferation and apoptosis as control cells. Our findings identify a role of EYA4 and possibly interacting SIX and DACH proteins in MPNSTs and suggest the EYA4 pathway as a rational therapeutic target.
Summary Objective Meniscal tears occur frequently in patients with knee osteoarthritis (OA). The aim of our study was to determine whether meniscal damage identified on magnetic resonance imaging ...(MRI) is associated with the severity of knee pain or the frequency of meniscal symptoms in patients with knee OA. Methods We performed a cross-sectional study using data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial. We characterized meniscal damage hierarchically as: root tear; maceration; long and short complex or horizontal tears; and simple tears. Subjects completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scale and a survey of frequency of meniscal symptoms. We used multivariable general linear models to assess the relationships between meniscal damage and 1) pain severity; and 2) meniscal symptoms, after adjusting for demographic and radiographic features. In further analysis root tear was considered as a binary variable. Results Analysis included 227 knees. Root tears were present in 19%, maceration in 14%, long complex or horizontal tears in 22%, short complex or horizontal tears in 30%, and simple tears in 14%. Root tears were associated with higher WOMAC pain scores. The adjusted mean WOMAC pain score was 45.2 (standard error (SE) 2.7) for those with root tear and 38.7 (SE 1.2) for subjects without root tear ( P = 0.03). We did not find statistically significant associations between meniscal morphology and frequency of meniscal symptoms. Conclusion Root tears were associated with greater pain than meniscal tears or maceration. We did not find a relationship between meniscal damage and meniscal symptoms.
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