Assessment of airway inflammation using sputum, BAL, and endobronchial biopsies in current and ex-smokers with established COPD

Rationale: Smoking effects on physiological and gross pathology in chronic obstructive pulmonary disease (COPD) are relatively well described. However, there is little known in COPD about the detailed interrelationships between lung function and inflammatory profiles in different airway compartments from the same individual and whether airway inflammation in these different compartments differs in ex- and current smokers with established COPD. Objectives: We compared sputum, bronchoalveolar (BAL), and airway wall inflammatory profiles in current versus ex-smokers and related this to smoking intensity and lung function in 17 current and 17 ex-smokers with mild to moderate COPD. Results: Current smokers had more sputum mast cells (% differential and absolute numbers), whereas ex-smokers had increased sputum neutrophils. In BAL, there was a significant increase in eosinophils in current smokers, but ex-smokers had significantly increased neutrophils, lymphocytes, and epithelial cells. There were no cell profile differences observed in airway biopsies between current and ex-smokers and there were no correlations between the individual inflammatory cell populations in any of the airway compartments. In current smokers only, smoking intensity was negatively correlated with lung function, and associated with a reduction in overall cellularity of both sputum and BAL. Conclusion: Airway inflammation persists in ex-smokers with COPD, but differs from COPD current smokers. The impact of smoking appears to vary in different airway compartments and any direct relationships between cellularity and lung function tended to be negative, ie, worse lung function indicated the presence of fewer cells

Efficient Secure Multiparty Computation Protocol for Sequencing Problem over Insecure Channel

As a powerful tool in solving privacy preserving cooperative problems, secure multiparty computation is more and more popular in electronic bidding, anonymous voting, and online auction. Privacy preserving sequencing problem which is an essential link is regarded as the core issue in these applications. However, due to the difficulties of solving multiparty privacy preserving sequencing problem, related secure protocol is extremely rare. In order to break this deadlock, this paper first presents an efficient secure multiparty computation protocol for the general privacy-preserving sequencing problem based on symmetric homomorphic encryption. The result is of value not only in theory, but also in practice

Marked methylation changes in intestinal genes during the perinatal period of preterm neonates

BACKGROUND: The serious feeding- and microbiota-associated intestinal disease, necrotizing enterocolitis (NEC), occurs mainly in infants born prematurely (5-10% of all newborns) and most frequently after formula-feeding. We hypothesized that changes in gene methylation is involved in the prenatal maturation of the intestine and its response to the first days of formula feeding, potentially leading to NEC in preterm pigs used as models for preterm infants. RESULTS: Reduced Representation Bisulfite Sequencing (RRBS) was used to assess if changes in intestinal DNA methylation are associated with formula-induced NEC outbreak and advancing age from 10 days before birth to 4 days after birth. Selected key genes with differentially methylated gene regions (DMRs) between groups were further validated by HiSeq-based bisulfite sequencing PCR and RT-qPCR to assess methylation and expression levels. Consistent with the maturation of many intestinal functions in the perinatal period, methylation level of most genes decreased with advancing pre- and postnatal age. The highest number of DMRs was identified between the newborn and 4 d-old preterm pigs. There were few intestinal DMR differences between unaffected pigs and pigs with initial evidence of NEC. In the 4 d-old formula-fed preterm pigs, four genes associated with intestinal metabolism (CYP2W1, GPR146, TOP1MT, CEND1) showed significant hyper-methylation in their promoter CGIs, and thus, down-regulated transcription. Methylation-driven down-regulation of such genes may predispose the immature intestine to later metabolic dysfunctions and severe NEC lesions. CONCLUSIONS: Pre- and postnatal changes in intestinal DNA methylation may contribute to high NEC sensitivity in preterm neonates. Optimizing gene methylation changes via environmental stimuli (e.g. diet, nutrition, gut microbiota), may help to make immature newborn infants more resistant to gut dysfunctions, both short and long term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-716) contains supplementary material, which is available to authorized users

First Evaluation of the Climatological Calibration Algorithm in the Real-time TMPA Precipitation Estimates over Two Basins at High and Low Latitudes

The TRMM Multi-satellite Precipitation Analysis (TMPA) system underwent a crucial upgrade in early 2009 to include a climatological calibration algorithm (CCA) to its realtime product 3B42RT, and this algorithm will continue to be applied in the future Global Precipitation Measurement era constellation precipitation products. In this study, efforts are focused on the comparison and validation of the Version 6 3B42RT estimates before and after the climatological calibration is applied. The evaluation is accomplished using independent rain gauge networks located within the high-latitude Laohahe basin and the low-latitude Mishui basin, both in China. The analyses indicate the CCA can effectively reduce the systematic errors over the low-latitude Mishui basin but misrepresent the intensity distribution pattern of medium-high rain rates. This behavior could adversely affect TMPA's hydrological applications, especially for extreme events (e.g., floods and landslides). Results also show that the CCA tends to perform slightly worse, in particular, during summer and winter, over the high-latitude Laohahe basin. This is possibly due to the simplified calibration-processing scheme in the CCA that directly applies the climatological calibrators developed within 40 degrees latitude to the latitude belts of 40 degrees N-50 degrees N. Caution should therefore be exercised when using the calibrated 3B42RT for heavy rainfall-related flood forecasting (or landslide warning) over high-latitude regions, as the employment of the smooth-fill scheme in the CCA bias correction could homogenize the varying rainstorm characteristics. Finally, this study highlights that accurate detection and estimation of snow at high latitudes is still a challenging task for the future development of satellite precipitation retrievals

Is Fermi 1544-0649 a misaligned blazar? discovering the jet structure with VLBI

Fermi J1544-0649 is a transient GeV source first detected during its GeV flares in 2017. Multi-wavelength observations during the flaring time demonstrate variability and spectral energy distribution(SED) that are typical of a blazar. Other than the flare time, Fermi J1544-0649 is quiet in the GeV band and looks rather like a quiet galaxy (2MASX J15441967-0649156) for a decade. Together with the broad absorption lines feature we further explore the "misaligned blazar scenario". We analyzed the Very Long Baseline Array (VLBA) and East Asian VLBI Network (EAVN) data from 2018 to 2020 and discovered the four jet components from Fermi J1544-0649. We found a viewing angle around 3.7{\deg} to 7.4{\deg}. The lower limit of the viewing angle indicates a blazar with an extremely low duty cycle of the gamma-ray emission, the upper limit of it supports the "misaligned blazar scenario". Follow-up multi-wavelength observations after 2018 show Fermi J1544-0649 remains quiet in GeV, X-ray, and optical bands. Multi-messenger search of neutrinos is also performed, and an excess of 3.1 {\sigma} significance is found for this source.Comment: Accepted for publication in ApJ. 13 pages, 7 figure

Analysis of the Interference Effects in CMOS Image Sensors Caused by Strong Electromagnetic Pulses

With the electromagnetic environment becoming increasingly complex, it is crucial to address the risk posed by electromagnetic pulse, which critically impairs the performance and reliability of electronic systems based on complementary metal oxide semiconductor (CMOS) image sensors. In this context, research on the failure types of CMOS image sensors in a high-power electromagnetic environment, caused by strong electromagnetic pulses and the rapid evaluation method of interference immunity, has garnered significant interest. This paper conducts electromagnetic pulse simulation experiments on CMOS image sensors to first study their failure types, such as image abnormalities and functional interruption, and then identify the corresponding failure criteria. Furthermore, this study builds on the small sample test evaluation method to investigate the interference threshold of functional interruptions in CMOS image sensors by calculating the failure probability at different field strengths. The obtained data were combined with the Weibull distribution function for fitting, the results of which found the interference threshold to be at 40.4 kV/m. The findings of this study provide a basis for evaluating the survivability of CMOS image sensors and their associated reinforcement technology in high-power electromagnetic environments

Ancient Genomes Reveal the Evolutionary History and Origin of Cashmere-Producing Goats in China

Goats are one of the most widespread farmed animals across the world; however, their migration route to East Asia and local evolutionary history remain poorly understood. Here, we sequenced 27 ancient Chinese goat genomes dating from the Late Neolithic period to the Iron Age. We found close genetic affinities between ancient and modern Chinese goats, demonstrating their genetic continuity. We found that Chinese goats originated from the eastern regions around the Fertile Crescent, and we estimated that the ancestors of Chinese goats diverged from this population in the Chalcolithic period. Modern Chinese goats were divided into a northern and a southern group, coinciding with the most prominent climatic division in China, and two genes related to hair follicle development, FGF5 and EDA2R, were highly divergent between these populations. We identified a likely causal de novo deletion near FGF5 in northern Chinese goats that increased to high frequency over time, whereas EDA2R harbored standing variation dating to the Neolithic. Our findings add to our understanding of the genetic composition and local evolutionary process of Chinese goats

Robust Detection of Hierarchical Communities from Escherichia coli Gene Expression Data

Determining the functional structure of biological networks is a central goal of systems biology. One approach is to analyze gene expression data to infer a network of gene interactions on the basis of their correlated responses to environmental and genetic perturbations. The inferred network can then be analyzed to identify functional communities. However, commonly used algorithms can yield unreliable results due to experimental noise, algorithmic stochasticity, and the influence of arbitrarily chosen parameter values. Furthermore, the results obtained typically provide only a simplistic view of the network partitioned into disjoint communities and provide no information of the relationship between communities. Here, we present methods to robustly detect coregulated and functionally enriched gene communities and demonstrate their application and validity for Escherichia coli gene expression data. Applying a recently developed community detection algorithm to the network of interactions identified with the context likelihood of relatedness (CLR) method, we show that a hierarchy of network communities can be identified. These communities significantly enrich for gene ontology (GO) terms, consistent with them representing biologically meaningful groups. Further, analysis of the most significantly enriched communities identified several candidate new regulatory interactions. The robustness of our methods is demonstrated by showing that a core set of functional communities is reliably found when artificial noise, modeling experimental noise, is added to the data. We find that noise mainly acts conservatively, increasing the relatedness required for a network link to be reliably assigned and decreasing the size of the core communities, rather than causing association of genes into new communities.Comment: Due to appear in PLoS Computational Biology. Supplementary Figure S1 was not uploaded but is available by contacting the author. 27 pages, 5 figures, 15 supplementary file