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1.
Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9
LIUCHENG WU YI WANG LILI DU GUIQING JI RUI ZHOU ZEYI ZHAO JUN CHEN SHUNXING ZHU 《Biocell》2021,45(6):1501-1507
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. 相似文献
2.
Marc De Doncker Chloé De Graeve Dr. Jorick Franceus Dr. Koen Beerens Prof. Vladimír Křen Dr. Helena Pelantová Dr. Ronny Vercauteren Prof. Dr. Tom Desmet 《Chembiochem : a European journal of chemical biology》2021,22(23):3319-3325
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. 相似文献
3.
《全球能源互联网(英文)》2022,5(6):618-626
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. 相似文献
4.
The deterministic and probabilistic prediction of ship motion is important for safe navigation and stable real-time operational control of ships at sea. However, the volatility and randomness of ship motion, the non-adaptive nature of single predictors and the poor coverage of quantile regression pose serious challenges to uncertainty prediction, making research in this field limited. In this paper, a multi-predictor integration model based on hybrid data preprocessing, reinforcement learning and improved quantile regression neural network (QRNN) is proposed to explore the deterministic and probabilistic prediction of ship pitch motion. To validate the performance of the proposed multi-predictor integrated prediction model, an experimental study is conducted with three sets of actual ship longitudinal motions during sea trials in the South China Sea. The experimental results indicate that the root mean square errors (RMSEs) of the proposed model of deterministic prediction are 0.0254°, 0.0359°, and 0.0188°, respectively. Taking series #2 as an example, the prediction interval coverage probabilities (PICPs) of the proposed model of probability predictions at 90%, 95%, and 99% confidence levels (CLs) are 0.9400, 0.9800, and 1.0000, respectively. This study signifies that the proposed model can provide trusted deterministic predictions and can effectively quantify the uncertainty of ship pitch motion, which has the potential to provide practical support for ship early warning systems. 相似文献
5.
摘 要:为了提高码索引调制(code index modulation,CIM)系统的传输效率,提出了一种具有更低复杂度的单输入单输出(single input single output,SISO)的广义正交码索引调制(generalized orthogonal code index modulation,GQCIM)系统。CIM 系统使用扩频码和星座符号传输信息,但只能激活两个扩频码索引和一个调制符号。而 GQCIM 系统以一种新颖的方式克服了只激活一个调制符号的限制,同时充分利用了调制符号的正交性,增加扩频码索引以传输更多的额外信息位,提高了系统的传输效率。此外,分析了GQCIM系统的理论性能,推导了误码率性能的上界。通过蒙特卡罗仿真验证了GQCIM系统的性能,对比发现GQCIM系统的理论和仿真性能一致。而且在相同的传输效率下,结果显示GQCIM系统的性能优于同样具有正交性的调制系统,如广义码索引调制(generalized code index modulation,GCIM)系统、CIM系统、码索引调制-正交空间调制(code index modulation aided quadrature spatial modulation,CIM-QSM)系统、码索引调制-正交空间调制(code index modulation aided spatial modulation,CIM-SM)系统、脉冲索引调制(pulse index modulation,PIM)系统。 相似文献
6.
The Pythagorean fuzzy set (PFS) is characterized by two functions expressing the degree of membership and the degree of nonmembership, which square sum of them is equal or less than 1. It was proposed as a generalization of a fuzzy set to deal with indeterminate and inconsistent information. In this study, we shall present some novel Dice similarity measures of PFSs and the generalized Dice similarity measures of PFSs and indicates that the Dice similarity measures and asymmetric measures (projection measures) are the special cases of the generalized Dice similarity measures in some parameter values. Then, we propose the generalized Dice similarity measures-based multiple attribute group decision-making models with Pythagorean fuzzy information. Then, we apply the generalized Dice similarity measures between PFSs to multiple attribute group decision making. Finally, an illustrative example is given to demonstrate the efficiency of the similarity measures for selecting the desirable ERP system. 相似文献
7.
Paul-Baptiste Rubio François Louf Ludovic Chamoin 《International journal for numerical methods in engineering》2019,120(4):447-472
The motivation of this work is to address real-time sequential inference of parameters with a full Bayesian formulation. First, the proper generalized decomposition (PGD) is used to reduce the computational evaluation of the posterior density in the online phase. Second, Transport Map sampling is used to build a deterministic coupling between a reference measure and the posterior measure. The determination of the transport maps involves the solution of a minimization problem. As the PGD model is quasi-analytical and under a variable separation form, the use of gradient and Hessian information speeds up the minimization algorithm. Eventually, uncertainty quantification on outputs of interest of the model can be easily performed due to the global feature of the PGD solution over all coordinate domains. Numerical examples highlight the performance of the method. 相似文献
8.
Facial Expression Recognition (FER) is an important subject of human–computer interaction and has long been a research area of great interest. Accurate Facial Expression Sequence Interception (FESI) and discriminative expression feature extraction are two enormous challenges for the video-based FER. This paper proposes a framework of FER for the intercepted video sequences by using feature point movement trend and feature block texture variation. Firstly, the feature points are marked by Active Appearance Model (AAM) and the most representative 24 of them are selected. Secondly, facial expression sequence is intercepted from the face video by determining two key frames whose emotional intensities are minimum and maximum, respectively. Thirdly, the trend curve which represents the Euclidean distance variations between any two selected feature points is fitted, and the slopes of specific points on the trend curve are calculated. Finally, combining Slope Set which is composed by the calculated slopes with the proposed Feature Block Texture Difference (FBTD) which refers to the texture variation of facial patch, the final expressional feature are formed and inputted to One-dimensional Convolution Neural Network (1DCNN) for FER. Five experiments are conducted in this research, and three average FER rates 95.2%, 96.5%, and 97% for Beihang University (BHU) facial expression database, MMI facial expression database, and the combination of two databases, respectively, have shown the significant advantages of the proposed method over the existing ones. 相似文献
9.
Mohammed Heyouni Farid Saberi-Movahed Azita Tajaddini 《Computers & Mathematics with Applications》2019,77(1):77-92
In the first part of this paper, we investigate the use of Hessenberg-based methods for solving the Sylvester matrix equation . To achieve this goal, the Sylvester form of the global generalized Hessenberg process is presented. Using this process, different methods based on a Petrov–Galerkin or on a minimal norm condition are derived. In the second part, we focus on the SGl-CMRH method which is based on the Sylvester form of the Hessenberg process with pivoting strategy combined with a minimal norm condition. In order to accelerate the SGl-CMRH method, a preconditioned framework of this method is also considered. It includes both fixed and flexible variants of the SGl-CMRH method. Moreover, the connection between the flexible preconditioned SGl-CMRH method and the fixed one is studied and some upper bounds for the residual norm are obtained. In particular, application of the obtained theoretical results is investigated for the special case of solving linear systems of equations with several right-hand sides. Finally, some numerical experiments are given in order to evaluate the effectiveness of the proposed methods. 相似文献
10.
吐哈盆地葡北地区“两宽一高”地震勘探技术及应用效果 总被引:1,自引:0,他引:1
吐哈盆地台北凹陷圈闭落实的准确度和储层分布预测的精度一直是制约该区油气发现的关键因素。通过可控震源“两宽一高”地震采集、OVT域时间偏移、地质导向深度偏移初始模型建立及各向异性深度偏移迭代处理,在地震资料的信噪比、频带宽度和分辨率等方面明显提高的基础上,以高精度层序地层学为指导,基于高分辨率地震资料与钻井、测井资料的综合分析,识别出侏罗系6个三级层序,在三级层序格架内将研究区七克台组底部和三间房组顶部砂体识别为两个连续上升半旋回四级层序;通过构造几何属性分析及精细构造分析,揭示了本区“四带、两凹”的构造格局及形成机制;以宽频带多种反演技术为手段,对含油气层段的七克台组和三间房组砂体分布进行了预测;在综合构造分析、储层分析和油藏成藏规律分析的基础上,提出本区油气沿构造带脊线聚集,断裂系统是油气运移的优势路径,七克台组、三间房组储层在葡北构造带发育,向玉果构造带和胜北次凹减薄尖灭,葡北构造带与玉果构造带结合部位的,具有鼻状构造背景的岩性圈闭是获得油气突破的有利地区。 相似文献