With advances in next-generation sequencing technologies, numerous novel transcripts in a large number of organisms have been identified. With the goal of fast, accurate assessment of the coding ...ability of RNA transcripts, we upgraded the coding potential calculator CPC1 to CPC2. CPC2 runs ∼1000 times faster than CPC1 and exhibits superior accuracy compared with CPC1, especially for long non-coding transcripts. Moreover, the model of CPC2 is species-neutral, making it feasible for ever-growing non-model organism transcriptomes. A mobile-friendly web server, as well as a downloadable standalone package, is freely available at http://cpc2.cbi.pku.edu.cn.
Abstract
The complex system of gene expression is regulated by the cell type-specific binding of transcription factors (TFs) to regulatory elements. Identifying variants that disrupt TF binding and ...lead to human diseases remains a great challenge. To address this, we implement sequence-based deep learning models that accurately predict the TF binding intensities to given DNA sequences. In addition to accurately classifying TF-DNA binding or unbinding, our models are capable of accurately predicting real-valued TF binding intensities by leveraging large-scale TF ChIP-seq data. The changes in the TF binding intensities between the altered sequence and the reference sequence reflect the degree of functional impact for the variant. This enables us to develop the tool DeFine (Deep learning based Functional impact of non-coding variants evaluator, http://define.cbi.pku.edu.cn) with improved performance for assessing the functional impact of non-coding variants including SNPs and indels. DeFine accurately identifies the causal functional non-coding variants from disease-associated variants in GWAS. DeFine is an effective and easy-to-use tool that facilities systematic prioritization of functional non-coding variants.
High-throughput experimental technologies often identify dozens to hundreds of genes related to, or changed in, a biological or pathological process. From these genes one wants to identify biological ...pathways that may be involved and diseases that may be implicated. Here, we report a web server, KOBAS 2.0, which annotates an input set of genes with putative pathways and disease relationships based on mapping to genes with known annotations. It allows for both ID mapping and cross-species sequence similarity mapping. It then performs statistical tests to identify statistically significantly enriched pathways and diseases. KOBAS 2.0 incorporates knowledge across 1327 species from 5 pathway databases (KEGG PATHWAY, PID, BioCyc, Reactome and Panther) and 5 human disease databases (OMIM, KEGG DISEASE, FunDO, GAD and NHGRI GWAS Catalog). KOBAS 2.0 can be accessed at http://kobas.cbi.pku.edu.cn.
The global atmospheric nitrogen (N) deposition has intensified in recent years, resulting in a complex impact on forest ecosystems. This study investigated the effects of canopy (CAN) and understory ...additions of N (UAN) on leaf carbon (C) and N assimilations, as well as growth parameters of representative woody plant species in an evergreen broad-leaved forest, i.e. Castanea henryi, Schefflera heptaphylla, Blastus cochinchinensis, and Lasianthus chinensis. The results showed that leaf N assimilation key enzyme nitrate reductase (NR) activities of B. cochinchinensis and S. heptaphylla were significantly decreased by UAN, and were significantly decreased by CAN for C. henryi. CAN significantly decreased the nitrite reductase activity of C. henryi, while significantly increased that of L. chinensis. However, the Amax values of each woody species were not significantly different among control (CK), CAN, and UAN. Community surveys demonstrated that CAN and UAN inhibited the growth (diameter at breast height, height, or crown width) of the representative large tree, C. henryi, while promoting the growths of understory woody species (B. cochinchinensis and L. chinensis). Overall, N addition was found to change the physiological processes of N and C metabolisms of the dominant woody species in an evergreen broad-leaved forest. The community of subtropical evergreen broad-leaved forests may further decline and its C fixation capacity may be detrimentally changed under N deposition in the future.
•N addition changed Amax, NR and NiR activities of dominant woody plant in a forest.•DBH, height and crown width of plants were differentially changed by N addition.•Growth of large tree was inhibited while understory woody species were promoted.•Subtropical forest may decline and its C fixation may change under N deposition.
The unprecedented use of English as a means of international and intercultural communication around the world has made it increasingly unrealistic and inappropriate to hold to the native speaker ...norms. This paper examines preservice teachers' perceptions of teaching English as an International Language (EIL), employing qualitative methods. The participants were 31 teacher candidates enrolled in an undergraduate course "Teaching English as a Second Language" in the teacher education program of a public university in a Southwestern State of the U.S. The data sources included online postings, interview transcripts, and synthesis papers. This study revealed that although the participants were all aware of the heterogeneity of the English language and were willing to promote multilingualism, the majority of them still clung to the notion that "Standard" English is the only variety of English that should be taught in the classroom. This paper maintains that in order to raise classroom teachers' awareness of teaching EIL, teacher educators should demolish American or British English as the orthodox and establish a new pedagogic model that de-emphasizes the native speaker norms and embraces all varieties of the English language. Keywords: paradigm shift; teaching English as an International Language; preservice teachers; perceptions.
Upstream open reading frames (uORFs) play important roles in regulating the main coding DNA sequences (CDSs) via translational repression. Despite their prevalence in the genomes, uORFs are overall ...discriminated against by natural selection. However, it remains unclear why in the genomes there are so many uORFs more conserved than expected under the assumption of neutral evolution. Here, we generated genome-wide maps of translational efficiency (TE) at the codon level throughout the life cycle of Drosophila melanogaster. We identified 35,735 uORFs that were expressed, and 32,224 (90.2%) of them showed evidence of ribosome occupancy during Drosophila development. The ribosome occupancy of uORFs is determined by genomic features, such as optimized sequence contexts around their start codons, a shorter distance to CDSs, and higher coding potentials. Our population genomic analysis suggests the segregating mutations that create or disrupt uORFs are overall deleterious in D. melanogaster. However, we found for the first time that many (68.3% of) newly fixed uORFs that are associated with ribosomes in D. melanogaster are driven by positive Darwinian selection. Our findings also suggest that uORFs play a vital role in controlling the translational program in Drosophila. Moreover, we found that many uORFs are transcribed or translated in a developmental stage-, sex-, or tissue-specific manner, suggesting that selective transcription or translation of uORFs could potentially modulate the TE of the downstream CDSs during Drosophila development.
The fluidization behaviors of Geldart-A and B particles in high pressure, sub-critical and supercritical water were investigated experimentally with the conditions of pressure up to 27.2MPa and ...temperature up to 482°C. Minimum fluidization velocity was determined by measuring pressure drop. Minimum bubbling velocity was obtained not only by analysis of the experimental differential pressure fluctuation signals, also by the relationship between bed voidage and superficial velocity. Correlations for the minimum fluidization velocity, homogeneous bed expansion rate and the minimum bubbling velocity were proposed. Transitions of fluidization regimes: fixed–homogeneous (F-H), fixed-homogeneous-bubbling (F-H-B) and fixed-bubbling (F-B) were uncovered at temperature from ambient to supercritical. The fluidization of F-H was found when discrimination number Dn is below 1.2×104, and the fluidization of F-H-B was found when discrimination number Dn is between 1.2×104 and 6×104, the fluidization of F-B was found when discrimination number Dn is above 6×104. These results are very useful for the design of the high pressure, sub-critical and supercritical water fluidized bed.
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•Fluidization of solid with water were conducted from ambient to supercritical zone.•A correlation for minimum fluidization velocity was obtained based on experiments.•A correlation for minimum bubbling velocity was obtained for supercritical zone.•A correlation of bed expansion rate covering supercritical zone was provided.•Fluidization regimes from ambient to supercritical zone were discriminated.
Particle distribution and residence time distribution (RTD) in supercritical water fluidized bed reactor (SCWFBR) greatly affect the hydrogen yield through determining the two phase mixing and ...reaction time. A Eulerian model incorporating the kinetic theory for solid particles was applied to simulate the solid distribution and RTD of feeding materials. The effect of four types of feeding methods and feeding rates on solid distribution and RTD were evaluated based on the simulation results. Results showed that double symmetrical feeding pipe with an feeding mouth angle of 45° provides more uniform solid distribution and longer residence time compared with those of other three types. A nonlinear relationship between feeding rate and RTD was observed, and an optimum feeding rate was found to be related to the best solid-fluid mixing in the study.
► Four types of feeding methods are designed and simulated to study solid distribution and RTD. ► Feeding pipe with an angle of 45° provides the most uniform solid distribution. ► There is an optimum feeding rate relating to the best mixing between feeding materials and particles.
Methylation of histone lysine residues plays important roles in gene expression regulation as well as cancer initiation. Lysine specific demethylase 1 (LSD1) is responsible for maintaining balanced ...methylation levels at histone H3 lysine 4 (H3K4). LSD1 is a drug target for certain cancers, due to important functions of methylated H3K4 or LSD1 overexpression. We report the design, synthesis, and structure-activity relationships of 3-(piperidin-4-ylmethoxy)pyridine containing compounds as potent LSD1 inhibitors with Ki values as low as 29 nM. These compounds exhibited high selectivity (>160×) against related monoamine oxidase A and B. Enzyme kinetics and docking studies suggested they are competitive inhibitors against a dimethylated H3K4 substrate and provided a possible binding mode. The potent LSD1 inhibitors can increase cellular H3K4 methylation and strongly inhibit proliferation of several leukemia and solid tumor cells with EC50 values as low as 280 nM, while they had negligible effects on normal cells.
In this article, we prove the existence of eigenvalues for the problem
under hypotheses that
, and
is a nonnegative measurable function on
, which may be singular at 0 and/or 1. For the result, we ...establish the existence of connected components of positive solutions for the following problem:
where
is a real parameter,
,
satisfies
and
for some
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