Transcription is a chromatin mark that can be used effectively to identify the location of active enhancers and promoters, collectively known as transcriptional regulatory elements (TREs). We recently introduced dREG, a tool for the identification of TREs using run‐on and sequencing (RO‐seq) assays, including global run‐on and sequencing (GRO‐seq), precision run‐on and sequencing (PRO‐seq), and chromatin run‐on and sequencing (ChRO‐seq). In this protocol, we present step‐by‐step instructions for running dREG on an arbitrary run‐on and sequencing dataset. Users provide dREG with bigWig files (in which each read is represented by a single base) representing the location of RNA polymerase in a cell or tissue sample of interest, and dREG returns a list of genomic regions that are predicted to be active TREs. Finally, we demonstrate the use of dREG regions in discovering transcription factors controlling response to a stimulus and predicting their target genes. Together, this protocol provides detailed instructions for running dREG on arbitrary run‐on and sequencing data. © 2018 by John Wiley & Sons, Inc.
On the basis of these concepts, modular pharmacology (MP) has emerged as a method that can balance multiple outcomes by regulating the response of property modules on the basis of the benefits and risks of diversified modules and drugs, thereby allowing novel approaches for drug discovery. Further research of pharmacological mechanisms underlying diversity interactions between multiple modules is necessary for a better understanding of the basic therapeutic processes.
In most regions of China, Electronic Medical Record (EMR) systems in hospitals are developed in an uncoordinated manner. Medical Insurance and Healthcare Administration are localised and organizations gather data from a functional management viewpoint without consideration of wider information sharing. Discontinuity of data resources is serious. Despite the government’s repeated emphasis on EMR data integration, little progress has been made, causing inconvenience to patients, but also significantly hindering data mining. This exploratory investigation used a case study to identify bottlenecks of data integration and proposes countermeasures. Interviews were carried out with 27 practitioners from central and provincial governments, hospitals, and related enterprises in China. This research shows that EMR data collection without patients’ authorization poses a major hazard to data integration. In addition, non-uniform information standards and hospitals’ unwillingness to share data are also significant obstacles to integration. Moreover, friction caused by the administrative decentralization, as well as unsustainability of public finance investment, also hinders the integration of data resources. To solve these problems, first, a protocol should be adopted for multi-stakeholder participation in data collection. Administrative authorities should then co-establish information standards and a data audit mechanism. Finally, measures are proposed for expanding data integration for multiplying effectiveness and adopting the Public-Private Partnerships model.
The reason why evolutions have been studied as a special science is that there exist reversal and transitional changes – blown‐ups – in the objective reality. However, the first‐push dynamical system has not been able to provide a mechanical explanation for these dramatic changes. Provides an exploratory explanation on how to understand “time and space” and some fundamental problems of evolutions, based on a discussion of problems existing in the first‐push system. In addition, points out the fact that the essence of the evolution science is that the concept of spinning materials is not an extrapolation or continuation of the first‐push system. What needs to be emphasized is that the presented work was originally based on first‐hand scientific practice and has been successfully evidenced by practical applications.
Previous research on the INTRODUCTORY IT PATTERN unveiled various lexical and grammatical aspects of its use as a grammatical stance device, including the range of the most frequently used adjectival and verbal stance lexemes, associated stance meanings, the most frequent sub-patterns, and the distinct uses in various contextual settings of the pattern. However, the stance meanings of the pattern, which are deeply rooted in the associated lexical resources, are still understudied. This study explores the meanings of the INTRODUCTORY IT PATTERN by referring to the stance meanings of the pattern associated with the adjectival and verbal lexemes that are statistically attracted to the pattern. The research samples were extracted from the British component of the International Corpus of English (ICE-GB). The samples were manually annotated for different stance types and a collexeme analysis was performed to identify the full range of stance lexemes statistically associated with the INTRODUCTORY IT PATTERN (collexemes). The results show that both adjectival and verbal collexemes are statistically and functionally significant for the delivery of discrete stance types/subtypes. Adjectival collexemes are frequently deployed for all four stance types: Epistemic stance, Evaluation stance, Dynamic stance, and Deontic stance, while verbal collexemes are valuable lexical resources for the Epistemic stance, as their use entails modalized evidentiality, pointing to epistemic judgment of the writer-speaker toward events/propositions. Close examination of the use of adjectival and verbal collexemes identified three fundamental meanings of the INTRODUCTORY IT PATTERN. First, the pattern is inherently evaluative as it tends to attract more lexemes with evaluative meanings and associates evaluative meanings with superficially non-evaluative lexemes. Second, it features a scalarized expression of diversified stance types/subtypes, thus, especially reflective of the scalarized semantic feature of stance expression. Third, it connotates an overwhelmingly positive likelihood judgment. The article concludes by discussing the limitations of this study.
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