In this paper, the prediction skills of five ensemble methods for temperature and precipitation are discussed by considering 20 yr of simulation results (from 1989 to 2008) for four regional climate ...models (RCMs) driven by NCEP–Department of Energy and ECMWF Interim Re-Analysis (ERA-Interim) boundary conditions. The simulation domain is the Coordinated Regional Downscaling Experiment (CORDEX) for East Asia, and the number of grid points is 197 × 233 with a 50-km horizontal resolution. Three new performance-based ensemble averaging (PEA) methods are developed in this study using 1) bias, root-mean-square errors (RMSEs) and absolute correlation (PEA_BRC), RMSE and absolute correlation (PEA_RAC), and RMSE and original correlation (PEA_ROC). The other two ensemble methods are equal-weighted averaging (EWA) and multivariate linear regression (Mul_Reg). To derive the weighting coefficients and cross validate the prediction skills of the five ensemble methods, the authors considered 15-yr and 5-yr data, respectively, from the 20-yr simulation data. Among the five ensemble methods, the Mul_Reg (EWA) method shows the best (worst) skill during the training period. The PEA_RAC and PEA_ROC methods show skills that are similar to those of Mul_Reg during the training period. However, the skills and stabilities of Mul_Reg were drastically reduced when this method was applied to the prediction period. But, the skills and stabilities of PEA_RAC were only slightly reduced in this case. As a result, PEA_RAC shows the best skill, irrespective of the seasons and variables, during the prediction period. This result confirms that the new ensemble method developed in this study, PEA_RAC, can be used for the prediction of regional climate.
Although capsule endoscopy has become a central diagnostic tool for small-bowel evaluation, retention of a capsule remains a major concern. This study attempted to investigate the incidence and ...clinical outcomes of capsule retention, and to determine the factors predictive of spontaneous capsule passage after retention.
Through a nationwide multicenter survey, we retrospectively reviewed the records of 1291 patients who had a capsule endoscopy between February 2002 and July 2006 in Korea. Clinical and procedural characteristics and postprocedural outcomes were analyzed for the cases with capsule retention.
Capsule retention occurred in 2.5 % of total cases (32/1291). The major diseases accompanying capsule retention were Crohn's disease, malignant tumors, and tuberculous enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early surgical or endoscopic interventions were instituted for diagnosis or treatment of diseases before retention symptoms developed. The remaining 21 (65.6 %) patients initially received medical treatments. Of these, 10 (31.3 %) ultimately underwent surgical intervention due to the development of symptoms of intestinal obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed the capsule. The presence of a larger lumen diameter (greater than two-thirds of the capsule diameter) at the stricture site was associated with spontaneous passage.
Our large-scale study suggests that retention occurs infrequently during capsule endoscopy. Moreover, a retained capsule might indicate the best intervention for the offending pathology, or it may spontaneously pass in the long run, particularly in patients with less small bowel stricture.
Inflammation in the central nervous system (CNS) and disruption of its immune privilege are major contributors to the pathogenesis of multiple sclerosis (MS) and of its rodent counterpart, ...experimental autoimmune encephalomyelitis (EAE). We have previously identified developmental endothelial locus-1 (Del-1) as an endogenous anti-inflammatory factor, which inhibits integrin-dependent leukocyte adhesion. Here we show that Del-1 contributes to the immune privilege status of the CNS. Intriguingly, Del-1 expression decreased in chronic-active MS lesions and in the inflamed CNS in the course of EAE. Del-1-deficiency was associated with increased EAE severity, accompanied by increased demyelination and axonal loss. As compared with control mice, Del-1(-/-) mice displayed enhanced disruption of the blood-brain barrier and increased infiltration of neutrophil granulocytes in the spinal cord in the course of EAE, accompanied by elevated levels of inflammatory cytokines, including interleukin-17 (IL-17). The augmented levels of IL-17 in Del-1-deficiency derived predominantly from infiltrated CD8(+) T cells. Increased EAE severity and neutrophil infiltration because of Del-1-deficiency was reversed in mice lacking both Del-1 and IL-17 receptor, indicating a crucial role for the IL-17/neutrophil inflammatory axis in EAE pathogenesis in Del-1(-/-) mice. Strikingly, systemic administration of Del-1-Fc ameliorated clinical relapse in relapsing-remitting EAE. Therefore, Del-1 is an endogenous homeostatic factor in the CNS protecting from neuroinflammation and demyelination. Our findings provide mechanistic underpinnings for the previous implication of Del-1 as a candidate MS susceptibility gene and suggest that Del-1-centered therapeutic approaches may be beneficial in neuroinflammatory and demyelinating disorders.
Summary
Background
Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify ...the pathogenesis of asthma by systemic review.
Objective
We applied a 1H‐NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers.
Method
A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using 1H‐NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target‐profiling procedure.
Results
Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O‐phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV1%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects).
Conclusion & Clinical Relevance
These data showed that 1H‐NMR‐based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.
Background
Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu.
Objective
To evaluate whether inhalation ...of S. aureus‐derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseases.
Methods
Staphylococcus aureus EV were prepared by sequential ultrafiltration and ultracentrifugation. The innate immune response was evaluated in vitro after the application of EV to airway epithelial cells and alveolar macrophages. In vivo innate and adaptive immune responses were evaluated after airway exposure to EV. Adjuvant effects of EV on the development of hypersensitivity to inhaled allergens were also evaluated after airway sensitization with S. aureus EV and ovalbumin (OVA).
Results
Staphylococcus aureus and S. aureus EV were detected in house dust. Alveolar macrophages produced both tumor necrosis α (TNF‐α) and interleukin 6 (IL‐6) after in vitro stimulation with S. aureus EV, whereas airway epithelial cells produced only IL‐6. Repeated airway exposure to S. aureus EV induced both Th1 and Th17 cell responses and neutrophilic pulmonary inflammation, mainly via a Toll‐like receptor 2 (TLR2)‐dependent mechanism. In terms of adjuvant effects, airway sensitization with S. aureus EV and OVA resulted in neutrophilic pulmonary inflammation after OVA challenge alone. This phenotype was partly reversed by the absence of interferon γ (IFN‐γ) or IL‐17.
Conclusion
Staphylococcus aureus EV can induce Th1 and Th17 neutrophilic pulmonary inflammation, mainly in a TLR2‐dependent manner. Additionally, S. aureus EV enhance the development of airway hypersensitivity to inhaled allergens.
Prediction of the
(IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our ...aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
Ninety-three patients with World Health Organization grade II gliomas with known
mutation and 1p/19q-codeletion status (18
wild-type, 45
mutant and no 1p/19q codeletion, 30
mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the
-mutation and 1p/19q-codeletion status. The predictive powers of imaging features for
wild-type tumors and 1p/19q-codeletion status in
-mutant subgroups were evaluated using the least absolute shrinkage and selection operator.
Various histogram and texture parameters differed significantly according to
-mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an
wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in
-mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807.
Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
The Kilo-Degree Survey is an optical wide-field survey designed to map the matter distribution in the Universe using weak gravitational lensing. In this paper, we use these data to measure the ...density profiles and masses of a sample of ∼1400 spectroscopically identified galaxy groups and clusters from the Galaxy And Mass Assembly survey. We detect a highly significant signal (signal-to-noise-ratio ∼120), allowing us to study the properties of dark matter haloes over one and a half order of magnitude in mass, from M ∼ 1013–1014.5 h
−1 M⊙. We interpret the results for various subsamples of groups using a halo model framework which accounts for the mis-centring of the brightest cluster galaxy (used as the tracer of the group centre) with respect to the centre of the group's dark matter halo. We find that the density profiles of the haloes are well described by an NFW profile with concentrations that agree with predictions from numerical simulations. In addition, we constrain scaling relations between the mass and a number of observable group properties. We find that the mass scales with the total r-band luminosity as a power law with slope 1.16 ± 0.13 (1σ) and with the group velocity dispersion as a power law with slope 1.89 ± 0.27 (1σ). Finally, we demonstrate the potential of weak lensing studies of groups to discriminate between models of baryonic feedback at group scales by comparing our results with the predictions from the Cosmo-OverWhelmingly Large Simulations project, ruling out models without AGN feedback.
•Protein-protein interaction (PPI) mapping at proteome-scale provides a global view of cellular organization and function.•Of the various methods for identifying PPIs, only three techniques can be ...easily scaled to survey the entire proteome.•Computational efforts allow for the prediction of PPIs, as well as finer mapping by modeling PPIs.•The collection and integration of proteome-scale PPI data has many applications, including exploration of disease mechanisms and evolution.•Future mapping efforts will move beyond static or simplified maps by incorporating quantitative and dynamic features.
Proteins effect a number of biological functions, from cellular signaling, organization, mobility, and transport to catalyzing biochemical reactions and coordinating an immune response. These varied functions are often dependent upon macromolecular interactions, particularly with other proteins. Small-scale studies in the scientific literature report protein–protein interactions (PPIs), but slowly and with bias towards well-studied proteins. In an era where genomic sequence is readily available, deducing genotype–phenotype relationships requires an understanding of protein connectivity at proteome-scale. A proteome-scale map of the protein–protein interaction network provides a global view of cellular organization and function. Here, we discuss a summary of methods for building proteome-scale interactome maps and the current status and implications of mapping achievements. Not only do interactome maps serve as a reference, detailing global cellular function and organization patterns, but they can also reveal the mechanisms altered by disease alleles, highlight the patterns of interaction rewiring across evolution, and help pinpoint biologically and therapeutically relevant proteins. Despite the considerable strides made in proteome-wide mapping, several technical challenges persist. Therefore, future considerations that impact current mapping efforts are also discussed.
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