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

A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms.

Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in stroke research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-consuming, subjective, and requires neuroanatomical expertise. We previously released an open-source dataset of stroke T1w MRIs and manually-segmented lesion masks (ATLAS v1.2, N = 304) to encourage the development of better algorithms. However, many methods developed with ATLAS v1.2 report low accuracy, are not publicly accessible or are improperly validated, limiting their utility to the field. Here we present ATLAS v2.0 (N = 1271), a larger dataset of T1w MRIs and manually segmented lesion masks that includes training (n = 655), test (hidden masks, n = 300), and generalizability (hidden MRIs and masks, n = 316) datasets. Algorithm development using this larger sample should lead to more robust solutions; the hidden datasets allow for unbiased performance evaluation via segmentation challenges. We anticipate that ATLAS v2.0 will lead to improved algorithms, facilitating large-scale stroke research

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

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β = 0.21; 95% CI 0.04-0.38, DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets

Accurate Calibration of a Large Field of View Camera with Coplanar Constraint for Large-Scale Specular Three-Dimensional Profile Measurement

In the vision-based inspection of specular or shiny surfaces, we often compute the camera pose with respect to a reference plane by analyzing images of calibration grids, reflected in such a surface. To obtain high precision in camera calibration, the calibration target should be large enough to cover the whole field of view (FOV). For a camera with a large FOV, using a small target can only obtain a locally optimal solution. However, using a large target causes many difficulties in making, carrying, and employing the large target. To solve this problem, an improved calibration method based on coplanar constraint is proposed for a camera with a large FOV. Firstly, with an auxiliary plane mirror provided, the positions of the calibration grid and the tilt angles of the plane mirror are changed several times to capture several mirrored calibration images. Secondly, the initial parameters of the camera are calculated based on each group of mirrored calibration images. Finally, adding with the coplanar constraint between each group of calibration grid, the external parameters between the camera and the reference plane are optimized via the Levenberg-Marquardt algorithm (LM). The experimental results show that the proposed camera calibration method has good robustness and accuracy

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

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

Evaluation of Regional Water Resources Management Performance and Analysis of the Influencing Factors: A Case Study in China

Water resources management (WRM) is a global strategic issue. Effectively evaluating WRM performance and analyzing its influencing factors have strong practical significance for improving regional WRM performance. Data envelopment analysis (DEA) is one of the most popular models to measure the efficiency of decision-making units (DMUs). Taking regional WRM performance as efficiency DMUs, this paper proposes the indicator system to quantify WRM performance from the perspectives of resource endowments, economic and technological development, and ecosystem protection. The WRM performance of 31 provincial administrative regions in mainland China from 2013 to 2019 are measured, and the temporal and spatial changes are explored using the window DEA model and the Malmquist index model. Finally, the Tobit model is used to quantitatively analyze the affecting factors. The results indicate that: (1) in 2015 and 2019, WRM performance of Sichuan, Shaanxi, Xinjiang, Inner Mongolia, and Guangxi were slightly higher than that in other years, and the areas with more room for WRM performance improvements were areas with abundant water resources; (2) from 2013 to 2019, China’s overall WRM performance showed a slow rise, and there were obvious fluctuations in 2018; (3) the improvement in WRM performance was primarily the result of an improvement to comprehensive technical efficiency changes (EC), whereas technological progress changes (TC) have largely restricted China’s WRM performance; (4) the main influencing factors of WRM performance in China were as follows: industrial development level, water resources utilization rate, and urban sewage discharge per capita

An Improved Rapidly-Exploring Random Trees Algorithm Combining Parent Point Priority Determination Strategy and Real-Time Optimization Strategy for Path Planning

In order to solve the problems of long path planning time and large number of redundant points in the rapidly-exploring random trees algorithm, this paper proposed an improved algorithm based on the parent point priority determination strategy and the real-time optimization strategy to optimize the rapidly-exploring random trees algorithm. First, in order to shorten the path-planning time, the parent point is determined before generating a new point, which eliminates the complicated process of traversing the random tree to search the parent point when generating a new point. Second, a real-time optimization strategy is combined, whose core idea is to compare the distance of a new point, its parent point, and two ancestor points to the target point when a new point is generated, choosing the new point that is helpful for the growth of the random tree to reduce the number of redundant points. Simulation results of 3-dimensional path planning showed that the success rate of the proposed algorithm, which combines the strategy of parent point priority determination and the strategy of real-time optimization, was close to 100%. Compared with the rapidly-exploring random trees algorithm, the number of points was reduced by more than 93.25%, the path planning time was reduced by more than 91.49%, and the path length was reduced by more than 7.88%. The IRB1410 manipulator was used to build a test platform in a laboratory environment. The path obtained by the proposed algorithm enables the manipulator to safely avoid obstacles to reach the target point. The conclusion can be made that the proposed strategy has a better performance on optimizing the success rate, the number of points, the planning time, and the path length