Integrative construction of regulatory region networks in 127 human reference epigenomes by matrix factorization

© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. Despite large experimental and computational efforts aiming to dissect the mechanisms underlying disease risk, mapping cis-regulatory elements to target genes remains a challenge. Here, we introduce a matrix factorization framework to integrate physical and functional interaction data of genomic segments. The framework was used to predict a regulatory network of chromatin interaction edges linking more than 20 000 promoters and 1.8 million enhancers across 127 human reference epigenomes, including edges that are present in any of the input datasets. Our network integrates functional evidence of correlated activity patterns from epigenomic data and physical evidence of chromatin interactions. An important contribution of this work is the representation of heterogeneous data with different qualities as networks. We show that the unbiased integration of independent data sources suggestive of regulatory interactions produces meaningful associations supported by existing functional and physical evidence, correlating with expected independent biological features

Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIAPET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells

Spatial Distribution and Relationship between Slope Micro-Topography Changes and Soil Aggregate Stability under Rainfall Conditions

Natural rainfall affects the stability of soil aggregates by the kinetic energy of the rain changing the morphological characteristics of slope micro-topographic factors. Although the relationship between the stability of soil aggregates and micro-topography is not very significant at the slope scale, there are also rules to be found. This study aims to explore the relationship between slope micro-topography and aggregate stability, and to observe the spatial distribution of aggregate stability after water erosion. In this study, a digital elevation model of slope micro-topography was established by using a three-dimensional laser scanner to observe the slope erosion changes after rainfall events and clarify the spatial changes of soil aggregate stability and its relationship with slope micro-topography by combining geostatistics and generalized additive model (GAM). The results showed that the area of serious water erosion in the lower part of the slope accounted for 38.67% of the slope, and the micro-topography index of the slope changed obviously after rainfall, with the slope increasing by 3.1%, the surface roughness increasing by 5.34%, the surface cutting degree increasing by 26.67%, and the plane curvature decreasing by 61.7%. In addition, the GAM model was used to fit the multivariate variables. The results revealed that the slope and surface roughness were the key factors affecting the stability of water-stable aggregate. The slope and surface roughness were negatively correlated with the stability of water-stable aggregates

Research on Chinese Question-Answering for Gaokao Based on Graph

Reading comprehension Question-Answering (QA) for College Entrance Examination (Gaokao in Chinese) is a challenging AI task because it requires effective representation to capture complicated semantic relations between the question and answers. In this paper, a novel method of Chinese Automatic Question-Answering based on a graph is proposed. The method first uses the Chinese FrameNet and discourse topic (paragraph topic sentence and author’s opinion sentence) to construct the affinity matrix between the question and candidate sentences and then employs the algorithm based on the graph to iteratively calculate the importance of each sentence. At last, the top 6 candidate answer sentences are selected based on the ranking scores. The recall on Beijing College Entrance Examination in the recent twelve years is 67.86%, which verifies the effectiveness of the method

The Role of Fibular Fixation in Distal Tibia-Fibula Fractures: A Meta-Analysis

Objectives. The necessity of fibular fixation in distal tibia-fibula fractures remains controversial. This study aimed to assess its impact on radiographic outcomes as well as rates of nonunion and infection. Methods. A systematic search of the electronic databases of PubMed, Embase, and Cochrane library was performed to identify studies comparing the outcomes of reduction and internal fixation of the tibia with or without fibular fixation. Radiographic outcomes included malalignment and malrotation of the tibial shaft. Data regarding varus/valgus angulation, anterior/posterior angulation, internal/external rotation deformity, and the rates of nonunion and infection were extracted and then polled. A meta-analysis was performed using the random-effects model for heterogeneity. Results. Additional fibular fixation was statistically associated with a decreased rate of rotation deformity (OR = 0.13; 95% CI 0.02–0.82, p=0.03). However, there was no difference in the rate of malreduction between the trial group and the control group (OR = 0.86; 95% CI 0.27–2.74, p=0.80). There was also no difference in radiographic outcomes of varus-valgus deformity rate (OR = 0.17; 95% CI 0.03–1.00, p=0.05) or anterior-posterior deformity rate (OR = 0.76; 95% CI 0.02–36.91, p=0.89) between the two groups. Meanwhile, statistical analysis showed no significant difference in the nonunion rate (OR = 0.62; 95% CI 0.37–1.02, p=0.06) or the infection rate (OR = 0.81; 95% CI 0.18–3.67, p=0.78) between the two groups. Conclusions. Additional fibular fixation does not appear to reduce the rate of varus-valgus deformity, anterior-posterior deformity, or malreduction. Meanwhile, it does not appear to impair the union process or increase the odds of infection. However, additional fibular fixation was associated with decreased odds of rotation deformity compared to controls

Effects of Zn on Corrosion Properties of Homogenized Mg-3Sn-1Ca-1Cu Alloy

The effects of 1% Zn on the corrosion properties of homogenized Mg-3Sn-1Ca-1Cu alloys were investigated. The corrosion behavior of homogeneous TXC311 and TXCZ3111 alloys in 3.5% NaCl solution was studied by using a hydrogen evolution test, polarization curve and impedance spectrum, and the corrosion properties of the alloys were discussed with considerations relative to microstructure. The results show that the second phases of TXC311 alloy consist of CaMgSn and Mg2Cu. The corrosion rate is 132 mm·year−1. After the addition of 1% Zn element, the grains are significantly refined, the number of Mg2Cu phases is reduced and the MgZnCu phases are formed. The corrosion rate of Mg-3Sn-1Ca-1Cu alloy decreased to 80 mm·year−1. TXCZ3111 alloy presents fine grains and a reduced number of Mg2Cu phases, which improve the stability of the corrosion film and reduce the corrosion rate of the alloy. Therefore, the corrosion resistance of TXCZ3111 alloy is much higher than that of TXC311 alloy

A Polymorphic Type System in Logic Programming

Conference Name:3rd International Conference on Intelligent System and Knowledge Engineering. Conference Address: Xiamen, PEOPLES R CHINA. Time:NOV 17-19, 2008.This paper is concerned with the design of type systems for logic programming so as to satisfy the requirements of modern logic programming. The design of type systems is based on the language Godel which has a strongly type system based on many-sorted logic with parametric polymorphism. The definitions of the basic logic programming concepts of terms, atoms, programs are given in the setting of polymorphic many-sorted logic. In particular, an unification algorithm for typed predicates is proposed for the compiler construction of Godel

Effectiveness of Focused Shockwave Therapy versus Radial Shockwave Therapy for Noncalcific Rotator Cuff Tendinopathies: A Randomized Clinical Trial

Background. The superiority of focused shockwave therapy (F-SWT) versus radial shockwave therapy (R-SWT) for treating noncalcific rotator cuff tendinopathies remains controversial. This study is aimed at comparing the effectiveness of F-SWT versus R-SWT for the management of noncalcific rotator cuff tendinopathies. Methods. A total of 46 patients affected by noncalcific rotator cuff tendinopathies were randomly divided into 2 groups of 23 individuals. Patients in group A received 4 sessions of F-SWT, while patients in group B were treated by 4 sessions of R-SWT. In each session, mean energy flux density (EFD) for F-SW 3000 shots was 0.09±0.018 mJ/mm2 with 5.1±0.5 Hz, while average pressure for R-SW 3000 shots was 4.0±0.35 bar with 3.2±0.0 Hz. Pain level and shoulder function were assessed with the numerical rating scale (NRS) and Constant-Murley Scale (CMS). The primary endpoint was the change in the mean NRS pain score from baseline to 24 weeks after the intervention. Secondary endpoints were changes in the mean NRS pain scores at all other follow-up points, changes in the mean CMS scores, and radiographic findings. Results. There were no significant differences between the two groups regarding NRS pain score and CMS score within 24 weeks after intervention (all p>0.05). However, F-SWT resulted in significantly lower NRS compared with R-SWT at 24 weeks and 48 weeks after treatment (2.7±1.0 vs. 4.5±1.2 and 1.4±1.0 vs. 3.0±0.8, respectively, all p<0.001). Similar results were found in CMS changes and radiographic findings. Conclusions. Both F-SWT and R-SWT are effective in patients with noncalcific rotator cuff tendinopathy. F-SWT proved to be significantly superior to R-SWT at long-term follow-up (more than 24 weeks). This trial is registered with ChiCTR1900022932

Alpha-Defensin versus Leukocyte Esterase in Periprosthetic Joint Infection: An Updated Meta-Analysis

Periprosthetic joint infection (PJI) is a devastating complication after arthroplasty. Prompt establishment of an infection diagnosis is critical but can be very challenging at present. In order to evaluate the diagnostic accuracy of alpha-defensin or leukocyte esterase for PJI, we performed systematic research in PubMed, Embase, and Cochrane Library to retrieve relevant studies. Data extraction and quality assessment were performed by two reviewers independently. A total of thirty-one eligible studies were finally included in the quantitative analysis. The pooled sensitivity and specificity of alpha-defensin (21 studies) for the diagnosis of PJI were 0.89 (95% confidence interval (CI), 0.83 to 0.93) and 0.96 (95% CI, 0.95 to 0.97), respectively. The value of the pooled diagnostic odds ratios (DOR) of alpha-defensin for PJI was 209.14 (95% CI, 97.31 to 449.50), and the area under the curve (AUC) was 0.98 (95% CI, 0.96 to 0.99). The pooled sensitivity and specificity of leukocyte esterase (17 studies) for the diagnosis of PJI were 0.90 (95% CI, 0.84 to 0.95) and 0.96 (95% CI, 0.93 to 0.97), respectively. The value of the DOR of leukocyte esterase for PJI was 203.23 (95% CI, 96.14 to 429.61), and the AUC was 0.98 (95% CI, 0.96 to 0.99). Based on the results of our meta-analysis, we can conclude that alpha-defensin and leukocyte esterase are valuable synovial fluid markers for identifying PJI with comparable high diagnostic accuracy