A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Smart firefighting construction in China: Status,problems, and reflections

“Smart firefighting” construction as a part of the “smart city” has been a concern of the public security and fire agencies at all levels. In this study, the status, problems, and reflections of “smart firefighting” construction in China are discussed. A recent survey indicates that China has launched its smart firefighting construction and initially created a new perspective on its regional smart firefighting work based on three main aspects: intelligent disaster perception by Internet of Things (IoT) construction, intelligent disaster prevention by big data construction, and intelligent disaster disposal by emergency rescue platform construction. However, the current smart firefighting construction in China still has some prominent problems such as the data interconnectivity and normalized management of various platforms, the extensibility of smart firefighting platforms, and the intelligent level of smart firefighting researches, which need to be solved urgently. Therefore, we argue that smart firefighting construction in China should establish data interconnectivity, industrial normalized management, 2D/3D geographic information interaction and extension, high-integration fire protection theory, and many other aspects in the near future and truly realize firefighting visualization and efficient data applications for 4D time space. This study could provide valuable reference for smart firefighting and smart city construction.     

基于低碳排放的城市空间规划策略研究

面对现代城市污染加剧的问题,做好城市规划对减少城市的碳排放具有决定性的作用。本文以低碳排放作为城市规划的出发点,从现代节能减排技术入手,构建城市空间规划立体网络,为低碳城市建设提供参考。     

锦纶长丝染色均匀度判色新方法

锦纶长丝的染色均匀度测试方法一直是采用人工判色方法,其判色结果会因人眼目光的不同导致经常会存在一定的误差,对企业节约成本和实际生产应用相当不利。本文提出了一种利用测试锦纶DTY长丝热收缩应力的方法,用热应力测试结果对锦纶染色性能进行预判,不需要进行织袜染色,为企业节约大量的人工成本。     

Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.     

Decoder side information generation techniques in Wyner-Ziv video coding: a review

Multimedia Tools and Applications - In Wyner-Ziv (WZ) video coding, decoder side information (SI) takes a key role in a WZ video codec among other building blocks. In this paper, we review the...     

液压支架立柱拆装机构设计

拆柱机由电动机匹配乳化液泵将电能转化为泵的液压能,带动液压马达回转作为拆装柱的动力。     

基于门控联合池化自编码器的通用性文本表征

为了学习文本的语义表征,以往的研究者主要依赖于复杂的循环神经网络(recurrent neural networks, RNNs)和监督式学习方法。该文提出了一种门控联合池化自编码器(gated mean-max AAE)用于学习中英文的文本语义表征。该文的自编码器完全通过多头自注意力机制(multi-head self-attention mechanism)来构建编码器和解码器网络。在编码阶段,提出了均值—最大化(mean-max)联合表征策略,即同时运用平均池化(mean pooling)和最大池化(max pooling)操作来捕获输入文本中多样性的语义信息。为促使联合池化表征可以全面地指导重构过程,解码器采用门控操作进行动态关注。通过在大规模中英文未标注语料上训练模型,获得了高质量的句子编码器。在重构文本段落的实验中,该文模型在实验效果和计算效率上均超越了传统的RNNs模型。将公开训练好的文本编码器,使其可以方便地运用于后续的研究。     

非常规蛋白基木材胶黏剂研究现状及发展前景

介绍了动物和植物型非常规蛋白资源的种类及其制备蛋白基木材胶黏剂的研究现状和存在的问题,展望了非常规蛋白胶黏剂的发展前景。