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.     

两种混合单元混合机理的数值模拟

为了研究SV型和SX型混合单元在全静态乳化器的混合机理,使用群体平衡模型对乳化器内部流场进行模拟分析。结果表明,SV型与SX型混合单元的混合机理是油相与水相材料通过混合单元时其空间流动方向改变,在流场内形成大量的漩涡,从而达到乳化的目的;通过比较流体在经过SV型和SX型混合单元后的水相索特平均直径(d_(32)),得出SV型混合单元的乳化效果更强,但同时消耗更多的能量,压降更大。     

Adaptive finite-time tracking control for parameterized nonlinear systems with full state constraints

In this article, the issue of adaptive finite-time dynamic surface control (DSC) is discussed for a class of parameterized nonlinear systems with full state constraints. Using the property of logarithmic function, a one-to-one nonlinear mapping is constructed to transform a constrained system into an unconstrained system with the same structure. The nonlinear filter is constructed to replace the first-order linear filter in the traditional DSC, and the demand on the filter time constant is reduced. Based on finite-time stable theory and using modified DSC, the finite-time controller is designed via DSC. Theoretical analysis shows that all the signals in the closed-loop system are semiglobal practical finite-time stable. Furthermore, none of the states are outside the defined open set. In the end, simulation results are presented to demonstrate the effectiveness of the proposed control schemes with both linear filters and nonlinear filters.     

New modified-majority voter-based efficient QCA digital logic design

ABSTRACT

Quantum-dot cellular automata (QCA) is an emerging nanotechnology and a possible alternative solution to the limitation of complementary metal oxide semiconductor (CMOS) technology. One of the most attractive fields in QCA is the implementation of configurable digital systems. This article presents a novel multifunctional gate called the modified-majority voter (MMV). The proposed gate works on the explicit interaction of the cell characteristic property for the implementation of digital circuits. This prominent feature of the proposed gate reduces the maximum hardware cost and implements highly efficient QCA structures. To verify the functionality of the proposed gate, some physical proofs, truth table and computational simulation results are performed. These results assured the validity of the existence of the proposed gate. It also dissipates less energy which has been calculated under three separate tunnelling energy levels using the QCAPro tool. To prove the effectiveness of the proposed MMV gate, several optimal irreversible arithmetic circuits such as three-input XOR, half-adder and full-adder are proposed. The modular layouts are verified with the freely available QCADesigner tool version 2.0.3.     

杨泗港快速通道武昌青菱段芦湾湖立交的选型研究

杨泗港快速通道青菱段是杨泗港过江通道江南岸重要的快速疏解道路,既承担快速通过性交通,又承担地方性服务功能。芦湾湖立交为青菱段与城市放射线珞狮南路的重要交通转换枢纽,在节点流量分析基础上,从功能定位方面进行阐述。芦湾湖立交由部分互通立交提升为全互通立交,并根据立交用地等限制因素进行全互通的方案比选,满足现状并适合整体需求和建设标准的立交方案,达到保证交通安全,适应城市发展和交通需求的目的。     

多分量数据全波形反演在气藏检测中的关键问题——以苏里格气田为例

苏里格气田是中国典型的致密砂岩气藏，构造简单、平缓，横向非均质性强，有效储层与围岩声学特征差别小，地震响应不明显，常规地震监测方法预测难度大，但气田含气砂岩泊松比低，是地震气藏检测的有效参数。利用弹性全波形反演精度高和能处理复杂非均质介质的优势，反演地层拉梅常数、剪切模量和密度，并计算泊松比，从而进行气藏预测。重点阐述了苏里格气田多分量数据全波形反演初始模型建模、先验模型建模和地震数据预处理3个关键问题的处理方法。二维三分量数据反演和"甜点"预测结果表明：①对于具有强非均质性的苏里格气田，利用全波形反演获得精度较高的地层弹性参数能显著提高气藏预测的准确度；②苏里格地区构造简单、平缓，利用常规叠加速度并结合构造解释可以建立比较好的初始模型，从而有效地解决了周波跳跃和局部极小的难题；③先验知识的约束和地震数据的预处理是全波形反演成功应用于苏里格气田气藏检测的关键。     

超级计算机网络引导技术研究与分析

针对超级计算机系统中网络引导时间开销大的问题，提出网络引导分布算法是影响网络引导性能的主要因素之一，是优化网络引导性能的主要方向的观点。首先，分析了影响大规模网络引导性能的主要因素；其次，结合一种典型超级计算机系统，分析了超节点循环分布算法（SCDA）和插件循环分布算法（BCDA）的网络引导数据流拓扑结构；最后，量化分析了这两种算法对各个网络路径段的压力和可获得的网络性能，发现BCDA性能是SCDA性能的1~20倍。通过理论分析和模型推导发现，在计算节点和引导服务器之间使用更细粒度的映射算法可以在引导部分资源时使用尽量多的引导服务器，减少对局部网络资源的过早竞争，提升网络引导性能。     

上游泵送机械密封多目标多工况优化研究

为了获得具有较强适应工况变化能力的上游泵送机械密封,以微间隙内流场的CFD计算为基础,建立涉及多工况的多目标优化数学模型,综合分析相关研究成果和密封特性确定了优化变量及其取值范围、工况参数取值范围和优化目标。应用模糊集理论确定不同工况下的液膜刚度和泄漏量的权重因子,并研究人工神经网络模型对优化结果的影响。基于穷尽搜索法和遗传算法对密封进行优化设计,对比分析2种优化方法得到的优化结果,并对优化前后的密封润滑膜流场特性进行BVF诊断分析。优化研究表明:人工神经网络模型很好地拟合了液膜刚度、泄漏量随槽型参数变化的函数关系;2种优化方法都能提高密封性能,但遗传算法优化比穷尽搜索法优化能获得更好的优化结果。     

瞬变电磁井间勘探的全空间几何因子

井间是剩余油的主要分布区域,为探测井间剩余油,提高采收率,提出了基于全空间几何因子的瞬变电磁井间勘探方法。在本井使用线圈发射、邻井使用线圈接收,根据瞬变电磁场理论,在阶跃信号的激励下发射线圈在地层中激发出沿圆周方向的闭合瞬变电场,该电场在导电地层中产生与地层电导率呈正比的涡流。由Doll地层环模型可知,地层中的涡流在空间任意点激发得到与地层电导率成正比的二次场响应信号(有用信号),并可表示为空间各点电导率的加权平均值,其权重即为井间瞬变电磁勘探的全空间几何因子;全空间几何因子集中分布在发射线圈和接收线圈附近,其它区域分布较少,在发射线圈和接收线圈两侧呈现不同的极性;对瞬变电磁响应与地层电导率、井间距和源距的变化规律研究可知,瞬变电磁井间勘探有用信号随着地层电导率的增大而增大,随着井间距的增加单调减小,在发射线圈和接收线圈处于同一深度时该响应信号幅度最大。     

复杂膨胀性围岩条件下交岔点支护技术研究

针对复杂膨胀性围岩条件下交岔点高应力集中区围岩稳定性控制和支护技术难题，通过对交岔点围岩变形表现形式、交岔点围岩变形机理的研究分析，提出了交岔点支护难点及重点。基于围岩控制理论分析，提出了“有限让压的柔性支护+全断面封闭抗压的刚性支护技术”，前期柔性支护采用“高强、高预应力锚杆+锚索+喷浆”联合支护有限度控制围岩变形，允许围岩在可控范围内释放围岩应力|后期通过架设异形支架与支撑架组成的联合支护体并喷射混凝土对交岔点围岩进行全断面封闭抗压支护，有效控制巷道交岔点围岩的变形。确保了交岔点围岩变形的整体可控性、稳定性，达到了预期支护效果。