Predominant contribution of cis-regulatory divergence in the evolution of mouse alternative splicing

Divergence of alternative splicing represents one of the major driving forces to shape phenotypic diversity during evolution. However, the extent to which these divergences could be explained by the evolving cis-regulatory versus trans-acting factors remains unresolved. To globally investigate the relative contributions of the two factors for the first time in mammals, we measured splicing difference between C57BL/6J and SPRET/EiJ mouse strains and allele-specific splicing pattern in their F1 hybrid. Out of 11,818 alternative splicing events expressed in the cultured fibroblast cells, we identified 796 with significant difference between the parental strains. After integrating allele-specific data from F1 hybrid, we demonstrated that these events could be predominately attributed to cis-regulatory variants, including those residing at and beyond canonical splicing sites. Contrary to previous observations in Drosophila, such predominant contribution was consistently observed across different types of alternative splicing. Further analysis of liver tissues from the same mouse strains and reanalysis of published datasets on other strains showed similar trends, implying in general the predominant contribution of cis-regulatory changes in the evolution of mouse alternative splicing

RobustSTL: A Robust Seasonal-Trend Decomposition Algorithm for Long Time Series

Decomposing complex time series into trend, seasonality, and remainder components is an important task to facilitate time series anomaly detection and forecasting. Although numerous methods have been proposed, there are still many time series characteristics exhibiting in real-world data which are not addressed properly, including 1) ability to handle seasonality fluctuation and shift, and abrupt change in trend and reminder; 2) robustness on data with anomalies; 3) applicability on time series with long seasonality period. In the paper, we propose a novel and generic time series decomposition algorithm to address these challenges. Specifically, we extract the trend component robustly by solving a regression problem using the least absolute deviations loss with sparse regularization. Based on the extracted trend, we apply the the non-local seasonal filtering to extract the seasonality component. This process is repeated until accurate decomposition is obtained. Experiments on different synthetic and real-world time series datasets demonstrate that our method outperforms existing solutions.Comment: Accepted to the thirty-third AAAI Conference on Artificial Intelligence (AAAI 2019), 9 pages, 5 figure

Removal of 17α-ethynylestradiol from aqueous solutions by a hybrid PAC/UF process

This study investigated the removal of 17α-ethynylestradiol (EE2) from water using activated carbon adsorption and powdered activated carbon/ultrafiltration (PAC/UF). EE2 was easily adsorbed by PAC. The adsorption of EE2 fitted the Freundlich model well. The influences of initial EE2 concentration, filtration rate, PAC dose, natural organic matter (NOM), and sodium dodecyl benzene sulfonate (SDBS) were investigated. The EE2 concentration and filtration rate had no significant effect on EE2 removal, whereas the addition of PAC had a significant effect on EE2 removal. The removal rate of EE2 increased dramatically from 7.01% to 80.03% as the PAC dose was increased from 0 to 10 mg/L. Both SDBS and NOM decreased the EE2 removal efficiency. The removal efficiency of EE2 in the PAC/UF process decreased from 86.77% to 42.64% as the SDBS concentration was increased from 0 to 50 mg/L. It was concluded that activated carbon adsorption and PAC/UF can be used for the effective removal of EE2 from water.Keywords: 17-α-ethynylestradiol, adsorption, ultrafiltration, PAC/UF process, removal efficienc

FlexDelta: A flexure-based fully decoupled parallel xyzxyz positioning stage with long stroke

Decoupled parallel $xyz$ positioning stages with large stroke have been desired in high-speed and precise positioning fields. However, currently such stages are either short in stroke or unqualified in parasitic motion and coupling rate. This paper proposes a novel flexure-based decoupled parallel $xyz$ positioning stage (FlexDelta) and conducts its conceptual design, modeling, and experimental study. Firstly, the working principle of FlexDelta is introduced, followed by its mechanism design with flexure. Secondly, the stiffness model of flexure is established via matrix-based Castigliano's second theorem, and the influence of its lateral stiffness on the stiffness model of FlexDelta is comprehensively investigated and then optimally designed. Finally, experimental study was carried out based on the prototype fabricated. The results reveal that the positioning stage features centimeter-stroke in three axes, with coupling rate less than 0.53%, parasitic motion less than 1.72 mrad over full range. And its natural frequencies are 20.8 Hz, 20.8 Hz, and 22.4 Hz for $x$, $y$, and $z$ axis respectively. Multi-axis path tracking tests were also carried out, which validates its dynamic performance with micrometer error

Gene- or region-based association study via kernel principal component analysis.

BACKGROUND: In genetic association study, especially in GWAS, gene- or region-based methods have been more popular to detect the association between multiple SNPs and diseases (or traits). Kernel principal component analysis combined with logistic regression test (KPCA-LRT) has been successfully used in classifying gene expression data. Nevertheless, the purpose of association study is to detect the correlation between genetic variations and disease rather than to classify the sample, and the genomic data is categorical rather than numerical. Recently, although the kernel-based logistic regression model in association study has been proposed by projecting the nonlinear original SNPs data into a linear feature space, it is still impacted by multicolinearity between the projections, which may lead to loss of power. We, therefore, proposed a KPCA-LRT model to avoid the multicolinearity. RESULTS: Simulation results showed that KPCA-LRT was always more powerful than principal component analysis combined with logistic regression test (PCA-LRT) at different sample sizes, different significant levels and different relative risks, especially at the genewide level (1E-5) and lower relative risks (RR = 1.2, 1.3). Application to the four gene regions of rheumatoid arthritis (RA) data from Genetic Analysis Workshop16 (GAW16) indicated that KPCA-LRT had better performance than single-locus test and PCA-LRT. CONCLUSIONS: KPCA-LRT is a valid and powerful gene- or region-based method for the analysis of GWAS data set, especially under lower relative risks and lower significant levels.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Make Transformer Great Again for Time Series Forecasting: Channel Aligned Robust Dual Transformer

Recent studies have demonstrated the great power of deep learning methods, particularly Transformer and MLP, for time series forecasting. Despite its success in NLP and CV, many studies found that Transformer is less effective than MLP for time series forecasting. In this work, we design a special Transformer, i.e., channel-aligned robust dual Transformer (CARD for short), that addresses key shortcomings of Transformer in time series forecasting. First, CARD introduces a dual Transformer structure that allows it to capture both temporal correlations among signals and dynamical dependence among multiple variables over time. Second, we introduce a robust loss function for time series forecasting to alleviate the potential overfitting issue. This new loss function weights the importance of forecasting over a finite horizon based on prediction uncertainties. Our evaluation of multiple long-term and short-term forecasting datasets demonstrates that CARD significantly outperforms state-of-the-art time series forecasting methods, including both Transformer and MLP-based models