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.     

荷花山铅锌矿与铜陵地区其它矿床成矿控制因素的对比研究

为了探讨荷花山铅锌矿控矿因素上与铜陵地区其它矿床异同，运用宏、微观相结合，地质观察研究同位素地球化学以及流体包裹体分析相结合的方法，通过地层岩性、地质构造、特定地质体及成矿流体的来源和性质等几个方面与成矿关系的比较，揭示了这种新类型矿床的控矿因素的特点是与岩浆关系不密切的低温热液、角砾岩控矿。得出了这种新类型矿床既具有铜陵地区其它矿床的控矿因素，同时也具有自己独特的控矿因素的结论。     

Nature of heterophase inclusions in high-purity optical fiber materials as studied with 3D laser ultramicroscopy

3D laser ultramicroscopy (3D LUM) is intended specially for determining the concentration and size distribution of submicron inclusions in the bulk samples of high-purity materials for visible and IR fiber optics. In this work the 3D LUM technique is shown to be able to identify the nature of individual inclusions detected. The measurement of the light scattered by an inclusion at a varied probe beam wavelength and polarization and at a varied scattered light collection angle makes it possible to determine the inclusion refractive index. The 3D LUM possibilities are illustrated by the example of studying the inclusion nature in the As₂S₃ glass samples prepared by the direct synthesis from elements in a quartz container at elevated temperatures.     

薄带连铸低碳钢中低熔点夹杂物控制研究

介绍了利用非水溶液电解法提取薄带连铸低碳钢中氧化物夹杂的方法,采用带有EDS系统的扫描电镜(SEM)研究了氧化物夹杂的三维形貌和化学成分,并通过热力学计算获得控制低熔点夹杂物生成所需成分范围。结果表明:低熔点Al2O3-Si O2-Mn O类夹杂物三维形貌为球形;随着钢液中酸溶铝含量的增加,夹杂物中Al2O3含量相应地增加,当钢液中[%C]=0.10、[%Si]=0.35、[%Mn]=0.90、夹杂物的熔点控制在1 200℃范围时,要求钢液中的酸溶铝含量很低,需控制在(1~5)×10-6。     

Technology-driven growth and inclusive growth- implications for sustainable development in Africa

The 21st century industrial and digital age has been largely driven by technological dynamics and advancement. The Neo-classical argued that beyond the classical notion of investments and capital accumulation, technology growth, which is driven by innovation and development is a major driver for growth and development. Africa economies, which has been largely described as technologically dependent, has over the years through technological diffusion engaged modern processes in driving its economic activities, which has informed economic and even social outcomes. Therefore, using the generalised methods of moments for selected sub-Saharan African economies, this study intends to assess the extent to which the presence of technology has informed economic activities in Africa as well as its impact in addressing developmental issues of poverty and unemployment. Also, given the current drive towards sustainability, this study takes the neo-classical growth theory a step higher by examining the modulating effects of technology-driven growth (through mobile densities and ICTs) in setting the pace for sustainable development in Africa. The study shows that the expected long-run impact of a technology-induced growth in reshaping developmental outcomes is seen from the estimates.     

On the transformation of symmetric sparse matrices to the triple diagonal form

The problem of minimizing the number of zero elements that become non-zero during the computation when a sparse symmetric matrix is reduced to a triple diagonal form, either by Givens' or Householder's method, is discussed. Algorithms for minimizing the growth of such non-zero elements are given.     

Inclusion problem of a two-dimensional finite domain: The shape effect of matrix

With the advance in composite mechanics and micromechanics, there are increasing demands for analytical solutions of inclusion problems in a bounded domain. To echo this need, this study is focused on establishing explicit expressions of elastic fields for a 2D elastic domain containing a circular inclusion at center. Unlike the configuration in the classical Eshelby formulation, the elastic domain in this study is bounded and has shapes other than a circle. To circumvent the mathematical difficulty in solving Green’s function in a finite domain, an approach powered by complex potential method, which has been successfully employed to formulate the elastic fields for inclusion problems where matrix is unbounded or bounded by a circle, is extended to finite domains displaying complicated shapes, particularly, a Pascal’s limaçon and a curved square (an approximation of perfect square) in this study. In order to take advantage of the mathematical simplicity inherent in expressing a circular geometry, conformal mapping is used to transform the complex geometry of the finite domain of interest to a unit circle. The governing complex potentials, which capture the discontinuity on the inclusion–matrix interface due to the uniform eigenstrain within the inclusion, are formulated with the aid of Cauchy integral and then explicitly identified by satisfying the prescribed boundary conditions. In this study, the displacement fields for finite domains bounded by a Pascal’s limaçon and a curved square are obtained based on Dirichlet (displacement) boundary conditions imposed by the far field strain. In addition to asymptotical behaviors, firm agreement is also achieved when the analytical solutions based on complex potentials are compared with the FEM results. Furthermore, inverse of the conformal mapping is discussed here in order to get the explicit expression for elastic fields.     

Formulation of Eshelby’s inclusion problem by BIEM (boundary integral equation method) and PDD (parametric dislocation dynamics)

Eshelby’s inclusion problem is implemented by boundary integral equation method (BIEM) and parametric dislocation dynamics (PDD), which are surface- and line-discretization approaches based on Green’s function method. In BIEM calculations, unknown constraint displacements at the inclusion boundary are deduced from surface integration associated with eigenstrain, and then unknown tractions are solved by a linear system of equations. Field quantities and strain energy are readily calculated by using the boundary tractions and displacements. In the meantime, inclusion stress by PDD is directly calculated by line integration over the dislocation elements, where the burgers vector satisfies geometrical argument of eigenstrain of inclusion. In particular, double line integral formula associated with dislocation interaction is utilized for elastic energy calculation. Computation efficiency of BIEM and PDD is mutually compared as a function of the number of Gauss integration points. Accuracy of field quantities and strain-energy of inclusion are verified by comparison of numerical results to analytical solutions.     

Ofloxacin/β-Cyclodextrin Complexation

Ofloxacin (OFX) is a fluorquinolone characterized by photochemical instability. With the goal to improve its photostability in aqueous solutions, the complexation of ofloxacin with β-cyclodextrin was investigated. The complexes showed a water solubility enhancement of approximately 2.6 times; nevertheless, the photodegradation of ofloxacin was not reduced. The complexes obtained were characterized by thermal and ¹H nuclear magnetic resonance (NMR) analysis, which revealed an interaction between ofloxacin and β-cyclodextrin. The last analysis indicated that only partial inclusion of the N-methylpiperazinyl moiety occurred, which can explain the fact that photostabilization was not improved. This partial inclusion phenomenon could be explained also by computer-aided molecular modeling.     

Critical oxidation behavior of Ta-containing ZrB2 composites in the 1500–1650 °C temperature range

The microstructure evolution of ZrB₂ hot pressed with 15 vol% TaSi₂ was studied in the as-sintered state and after oxidation for 15 min at 1500 and 1650 °C in stagnant air. In the pristine material, the original ZrB₂ nuclei are surrounded by a mixed (Zr,Ta)B₂ solid solution. Refractory Ta-compounds are located at triple junctions and wetted grain boundaries are distinctive of this ceramic. After oxidation, the solid solution evolves into ZrO₂ grains encasing intragranular nano-structured TaB₂ particles. Here we show that the operating limit temperature of this composite is related to the critical oxidation of TaB₂ to Ta₂O₅ above 1600 °C, accompanied by large volume expansion and local liquid formation, which ruptures the ZrO₂ grains and structure.