Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value.     

Exploration of GH94 Sequence Space for Enzyme Discovery Reveals a Novel Glucosylgalactose Phosphorylase Specificity

The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis.     

2种侧围加强内框总成检具结构对比分析

概述了侧围加强内框总成与周边零件的匹配关系,从检具操作的人机工程出发,描述了侧围加强内框总成检具的2种定位方式和结构设计,对比了2种定位方式对于检测结果的影响,总结了其优点和弊端,结果表明侧围加强内框总成检具采用车内方向朝下的定位方式效果更好。     

Image sequence-based risk behavior detection of power operation inspection personnel

A novel image sequence-based risk behavior detection method to achieve high-precision risk behavior detection for power maintenance personnel is proposed in this paper. In this method, the original image sequence data is first separated from the foreground and background. Then, the free anchor frame detection method is used in the foreground image to detect the personnel and correct their direction. Finally, human posture nodes are extracted from each frame of the image sequence, which are then used to identify the abnormal behavior of the human. Simulation experiment results demonstrate that the proposed algorithm has significant advantages in terms of the accuracy of human posture node detection and risk behavior identification.     

Structure-sensitive semantic matching for aggregate question answering over knowledge base

Aggregate question answering essentially returns answers for given questions by obtaining query graphs with unique dependencies between values and corresponding objects. Word order dependency, as the key to uniquely identify dependency of the query graph, reflects the dependencies between the words in the question. However, due to the semantic gap caused by the expression difference between questions encoded with word vectors and query graphs represented with logical formal elements, it is not trivial to match the correct query graph for the question. Most existing approaches design more expressive query graphs for complex questions and rank them just by directly calculating their similarities, ignoring the semantic gap between them. In this paper, we propose a novel Structure-sensitive Semantic Matching(SSM) approach that learns aligned representations of dependencies in questions and query graphs to eliminate their gap. First, we propose a cross-structure matching module to bridge the gap between two modalities(i.e., textual question and query graph). Then, we propose an entropy-based gated AQG filter to remove the structural noise caused by the uncertainty of dependencies. Finally, we present a two-channel query graph representation that fuses the semantics of abstract structure and grounding content of the query graph explicitly. Experimental results show that SSM could learn aligned representations of questions and query graphs to eliminate the gaps between their dependencies, and improves up to 12% (F1 score) on aggregation questions of two benchmark datasets.     

基于PolyWorks虚拟装配间隙面差计算分析研究

随着当今社会汽车制造业的迅猛发展,高标准和高需求已经是消费者对汽车制造凯歌的主旋律。而这其中,汽车钣金件的间隙面差就是其中一个重要因素。快速检测间隙面差是否满足设计要求直接关系到汽车白车身的生产精度和企业的工作效率。传统计算间隙面差大多利用量具,易划伤被测物且在零件实际装配后才可测量,降低生产效率,而非接触测量造价昂贵。本课题基于实物的汽车钣金件虚拟装配,对间隙面差的计算方法进行分类与参数调整,提出一种高效率、高标准的间隙面差计算流程。     

Copy Move Forgery Detection based on double matching

Copy Move is a technique widespreadly used in digital image tampering, meaning Copy Move Forgery Detection (CMFD) is still a significant research. In this paper, a novel CMFD method is proposed, including double matching process and region localizing process. In double matching process, the first matching is conducted on Delaunay triangles consisting of Local Intensity Order Pattern (LIOP) keypoints, to find the approximate location of suspicious regions. In order to find sufficient keypoint pairs, the existing set of matching triangles is expanded by adding their neighbors iteratively, covering the whole tampered regions, and the second matching with a looser threshold is conducted on the vertices. In the region localizing process, considering the case of multiple copies, Density-Based Spatial Clustering of Applications with Noise (DBSCAN) is used to classify the keypoint pairs described in a new model. Experimental results indicate that the proposed method, with good robustness, outperforms some state-of-the-art methods.     

基于“炉机对应”原则的连浇优化方案

国内某炼钢厂为保证浇注周期较短的2号连铸机连浇，多座转炉需同时向该连铸机供应钢水，导致炉 机对应关系不明确，生产组织难度较大。通过对该厂炼钢 连铸过程的工序作业周期与生产运行模式进行解析，在保证连铸机连浇的基础上，探究合理的炉 机对应关系，改善该厂的生产顺行。结果表明，在“一一对应”运行模式下，2号连铸机最大连浇炉数仅为6炉；而在“定炉对定机”运行模式下，若适时接受3号转炉冶炼的钢水，2号连铸机最大连浇炉数可延长至19炉。在此基础上，通过对连铸机“柔性”的优化和钢水供应的合理调配，2号连铸机可满足实际生产的连浇要求。此外，运用“炉→机”匹配度进行评价，计算结果表明优化后的炉 机对应关系得到显著改善。     

物联网中基于Multi-Agent的物间动态关系发现

物联网中存在大量异构关系的实体，其信息间的交互造成了物联网的内在矛盾。针对这一问题，提出将物联网中实体抽象化为对应的Agent，并以个体人为中心，利用本体的语义匹配及改进的物间动态关系计算方法，计算出针对个体人的物间动态关系；将原本异构的实体关系转化为Agent间基于动态关系紧密度排序的网络关系。经实验验证，该方法构建的关系网络可明显改善异构实体间交互的矛盾，而且相比原有类似方法，该方法解决问题的准确率和误差率均有改善，说明了该方法的准确性和可行性。