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关键词： antidiabetic drug   insulin therapy   pharmaco-economics   type 2 diabetes   weight control  

摘要： Aims To study the association of body mass index (BMI) and insulin use with type 2 diabetes-related healthcare expenditures (T2D-HE). Materials and methods Retrospective study using de-identified electronic health records linked to insurance claims data. Study included a prevalence-based sample of overweight or obese patients with antihyperglycaemic-treated T2D. Patients had >= 1 A1c measurement in 2014 (last observed = index A1c), >= 1 BMI measurement within +/- 90 days of index (average BMI = baseline BMI), and continuous enrolment for 180 days before (baseline) through 395 days after index (day 30-395 = follow-up). BMI was categorized as: 25 to 29.9 kg/m(2) = overweight;30 to 34.9 kg/m(2) = obese class I (OCI);35 to 39.9 kg/m(2) = OCII;>= 40 kg/m(2) = OCIII. Multivariable regressions were used to examine one-year follow-up T2D-HE as a function of BMI, insulin use, an interaction term between BMI and insulin use, and patient demographics. Results Study included 13 026 patients (mean age = 63.6 years;48.1% female;29.5% overweight, 31.6% OCI, 20.3% OCII, 18.6% OCIII;25.3% insulin users). Baseline insulin use rates monotonically ranged from 19.7% in overweight patients to 33.0% in OCIII patients (P < 0.001). Together, BMI and insulin use were jointly associated with one-year follow-up T2D-HE, which monotonically ranged from $5842 in overweight patients with no insulin to $17 700 OCIII insulin users, P < 0.001. Within each BMI category, insulin users' one-year T2D-HE was at least double that of non-users. Additional analyses of all-cause healthcare expenditures yielded consistent results. Conclusions BMI and insulin use represent simple stratifiers for identifying high-cost patients. OCIII insulin users incurred the greatest annual healthcare expenditures;these patients may be an ideal group for targeted interventions.

关键词： mutagenesis   directed evolution   protein engineering   synthetic biology   biocatalysis  

摘要： Directed evolution requires the creation of genetic diversity and subsequent screening or selection for improved variants. For DNA mutagenesis, conventional site-directed methods implicitly utilize the Boolean AND operator (creating all mutations simultaneously), producing a combinatorial explosion in the number of genetic variants as the number of mutations increases. We introduce GeneORator, a novel strategy for creating DNA libraries based on the Boolean logical OR operator. Here, a single library is divided into many subsets, each containing different combinations of the desired mutations. Consequently, the effect of adding more mutations on the number of genetic combinations is additive (Boolean OR logic) and not exponential (AND logic). We demonstrate this strategy with large-scale mutagenesis studies, using monoamine oxidase-N (Aspergillus niger) as the exemplar target. First, we mutated every residue in the secondary structure-containing regions (276 out of a total 495 amino acids) to screen for improvements in k(cat). Second, combinatorial OR-type libraries permitted screening of diverse mutation combinations in the enzyme active site to detect activity toward novel substrates. In both examples, OR-type libraries effectively reduced the number of variants searched up to 10(10)-fold, dramatically reducing the screening effort required to discover variants with improved and/or novel activity. Importantly, this approach enables the screening of a greater diversity of mutation combinations, accessing a larger area of a proteins sequence space. OR-type libraries can be applied to any biological engineering objective requiring DNA mutagenesis, and the approach has wide ranging applications in, for example, enzyme engineering, antibody engineering, and synthetic biology.

关键词： Discrete Global Grid System (DGGS)   Inverse Snyder Equal-Area Projection (ISEA)   ISEA Aperture 3 Hexagon Discrete Global Grid System (ISEA3H)   grid   indexing   identifier   performance  

摘要： Geospatial data is often spatially aggregated by the use of Discrete Global Grid Systems. References to grid cells are needed for the communication of such data, and different identifier schemes have accordingly been introduced in literature. These schemes suffer, however, from being hard to understand for non-experts, and the geometry of a cell cannot be inferred from its identifier without complex computations. In this article, a novel identifier scheme that encodes the geographic coordinates of the centroid of a cell is proposed, which comes at the cost of potentially being ambiguous in case of a very fine-grained grid. We reason and computationally demonstrate that ambiguity does though not occur for real-world applications. The novel identifier scheme minimizes the amount of data to be communicated, for example, between a server and a client application, and it allows to infer approximate geometries of the cells only by their identifiers.

关键词： 标识符   出版物   光盘   数字信息   标识   条形码   书刊  

摘要： 数字对象唯一标识符(digital object identifier,DOI)是对包括互联网信息在内的数字信息进行标识的一种工具。在传统的出版物中,书刊、磁带、光盘都有国际标准编号(ISBN、ISSN、ISCN)及其条形码,作为出版物的唯一标识。这些标识使出版物得到有效的管理,便于读者查找和利用。而网上的文档一旦变更了网址便无从追索。数字信息标注DOI如同出版物的条形码,是一个永久和唯一的标识号。

关键词： 船舶自动识别系统   标识符   图标  

摘要： 当前船舶海图体系缺乏对实时沉船信息进行可靠标识的手段,特别是电子海图显示规范中没有支持沉船边界标识的显示符号,影响了其对碍航物的指示效果。该文针对船载显示终端实时沉船信息的显示需求,对现有的沉船标识符的显示体系进行了研究,分析了现有体系与实时沉船标识符显示要求的差距,并提出了实时沉船标识符显示图标设计的建议。

关键词： 构造函数   复制构造函数   赋值运算符  

摘要： C++中,类中存在常数据成员情况下,需要对赋值运算符函数进行重新定义,不能用系统提供的默认赋值运算符函数,否则使用赋值时存在语法错误。在类数据成员中存在指针的情况下,需要对复制构造函数和赋值运算符函数进行重新定义,否则在进行复制和赋值时,对象之间的指针指向同一个内存,对象数据之间会存在关联。

摘要： Motivation: Low-frequency DNA mutations are often confounded with technical artifacts from sample preparation and sequencing. With unique molecular identifiers (UMIs), most of the sequencing errors can be corrected. However, errors before UMI tagging, such as DNA polymerase errors during end repair and the first PCR cycle, cannot be corrected with single-strand UMIs and impose fundamental limits to UMI-based variant calling. Results: We developed smCounter2, a UMI-based variant caller for targeted sequencing data and an upgrade from the current version of smCounter. Compared to smCounter, smCounter2 features lower detection limit that decreases from 1 to 0.5%, better overall accuracy (particularly in non-coding regions), a consistent threshold that can be applied to both deep and shallow sequencing runs, and easier use via a Docker image and code for read pre-processing. We benchmarked smCounter2 against several state-of-the-art UMI-based variant calling methods using multiple datasets and demonstrated smCounter2's superior performance in detecting somatic variants. At the core of smCounter2 is a statistical test to determine whether the allele frequency of the putative variant is significantly above the background error rate, which was carefully modeled using an independent dataset. The improved accuracy in non-coding regions was mainly achieved using novel repetitive region filters that were specifically designed for UMI data. Availability and implementation: The entire pipeline is available at https://***/qiaseq/qiaseq-dna under MIT license.

关键词： Boolean model   Type 2 diabetes mellitus   Insulin resistance   -cell apoptosis  

摘要： BackgroundMajor alteration in lifestyle of human population has promoted Type 2 diabetes mellitus (T2DM) to the level of an epidemic. This metabolic disorder is characterized by insulin resistance and pancreatic -cell dysfunction and apoptosis, triggered by endoplasmic reticulum (ER) stress, oxidative stress and cytokines. Computational modeling is necessary to consolidate information from various sources in order to obtain a comprehensive understanding of the pathogenesis of T2DM and to investigate possible interventions by performing in silico *** this paper, we propose a Boolean network model integrating the insulin resistance pathway with pancreatic -cell apoptosis pathway which are responsible for T2DM. The model has five input signals, i.e. ER stress, oxidative stress, tumor necrosis factor (TNF ), Fas ligand (FasL), and interleukin-6 (IL-6). We performed dynamical simulations using random order asynchronous update and with different combinations of the input signals. From the results, we observed that the proposed model made predictions that closely resemble the expression levels of genes in T2DM as reported in the *** proposed model can make predictions about expression levels of genes in T2DM that are in concordance with literature. Although experimental validation of the model is beyond the scope of this study, the model can be useful for understanding the aetiology of T2DM and discovery of therapeutic intervention for this prevalent complex disease. The files of our model and results are available at https://***/JieZheng-ShanghaiTech/boolean-t2dm.

关键词： author identifiers   authority files   institutional repositories   linked data   name authority control  

摘要： Linked data solutions for name authority control in digital libraries are an area of growing interest, particularly among institutional repositories (IRs). This article first considers the shift from traditional authority files to author identifiers, highlighting some of the challenges and possibilities. An analysis of author name strings in Duke University's open access repository, DukeSpace, is conducted to identify a suitable source of author URIs for Duke's newly launched repository for research data. Does one of the three prominent international authority sources—Library of Congress Name Authority File (LCNAF), Virtual International Authority File (VIAF), and Open Researcher and Contributor Identifier (ORCID)—demonstrate the most comprehensive uptake? Finally, recommendations surrounding a technical approach to leveraging author Uniform Resource Identifiers (URIs) at Duke are briefly considered. ©, Published with license by Taylor & Francis Group, LLC. ©, © Moira Downey.

关键词： 数字对象唯一标识符   DOI  

摘要： 数字对象唯一标识符(digital object identifier,DOI)是对包括互联网信息在内的数字信息进行标识的一种工具。在传统的出版物中,书刊、磁带、光盘都有国际标准编号(ISBN、ISSN、ISCN)及其条形码,作为出版物的唯一标识。这些标识使出版物得到有效的管理,便于读者查找和利用。