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.     

我国水-能源-粮食耦合关系及影响因素

为缓解我国水、能源和粮食资源紧张问题，促进资源可持续利用，构建水-能源-粮食系统，利用耦合协调度模型对我国的30个省（自治区、直辖市）进行测算,并利用空间杜宾模型分析主要影响因素。结果表明：2003—2017年，我国能源、粮食评价[JP]指数高于水资源评价指数，系统综合评价指数逐年递增；大部分省份耦合协调度处于初级协调水平且呈现逐年上升的态势，个别省份耦合协调度濒临失调；耦合协调度空间自相关性较强，虽有明显波动，但是呈现逐年加强的态势；影响耦合协调度的主要因素有从业人口数、固定资产投资额、人均生产总值、人口总数、[JP]文盲人口占比、工业污染排放、城镇化。     

Effects of alkali metal ion on imprinting GRIN microstructure in GeS2-Ga2S3-MCl (M=Na,K, Cs) glasses for visible to mid-infrared microgratings

Gradient refractive index (GRIN) micro-optics present unique opportunities for control of the chromatic properties, new degrees of freedom for optical design as well as the potential for use in new optical system applications. GRIN microgratings were imprinted in GeS₂-Ga₂S₃-MCl (M = Na, K, Cs) chalcohalide glasses by microthermal poling, and the effects of the type and concentration of alkali cations on their performance were investigated. Two effective imprinting formation regions of the GRIN microstructure based on the poling saturation voltage (U_s) and glass composition are observed at fixed poling time and temperature. The U_s increases from 140 to 750 and 2600 V in accordance with the activation energy (E_a) of alkali ions (Na⁺ to K⁺ and Cs⁺) increasing from 45.15 to 58.62 and 92.58 kJ/mol for studied samples. The saturated numbers of diffraction order (N_s) of the gratings in these samples are 7, 9 and 6, respectively, the highest number being provided by the K⁺-containing sample. This is in accordance with imprinting-induced phase differences (0.14λ, 0.19λ and 0.09λ) measured in the fabricated samples containing Na⁺, K⁺ and Cs⁺ ions. Furthermore, the U_s of samples decreases from 1500 to 300 V with four concentrations of K⁺ from 10 to 30%, associated with their E_a of K⁺ decreasing from 69.62 to 53.46 kJ/mol, while N_s increases from 8 to 14, which is attributed to the increase of the phase difference in the GRIN structures. The controllable GRIN microstructures are realized by adjusting the type and concentration of alkali cations in chalcohalide glasses, which is expected to drive the design of broadband GRIN microgratings.     

Deterministic and probabilistic ship pitch prediction using a multi-predictor integration model based on hybrid data preprocessing,reinforcement learning and improved QRNN

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.     

Glycaemic response of pseudocereal-based gluten-free food products: a review

Rapid digestion and absorption of carbohydrates have become a health issue (high glycaemic index, GI), which can be a matter of greater concern when consumed in large quantities. Depending upon the influence of carbohydrates on the blood sugar levels, GI classifies carbohydrates (on a scale of 100) as low (<55), medium (55–70) and high (>70) GI foods. Among the pseudocereals, chia seed possesses relatively lower GI (28.53), as compared to buckwheat (52.35), amaranth (47.65) and quinoa (61.50). Consumers now prefer foods with a high GI over the ones with low GI to prevent various metabolic alterations. Celiac disease is a lifelong disorder prevalent worldwide and can only be controlled by following a strict lifelong gluten-free diet. Therefore, pseudocereals could be a potential alternate for low GI food and developing gluten-free food products, including bread, cookies, noodles and pasta. This review synthesises the recently published literatures on pseudocereals as a lowering GI and healthy food option. This review also gives insights into developing pseudocereals as a potential and novel ingredient for gluten-free food applications and the latest research conducted worldwide.     

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。     

Thermal destratification of cryogenic liquid storage tanks by continuous bubbling of gases

This paper focuses on thermal destratification and pressurisation inside thermally stratified storage tanks by continuous gas bubbling. The primary purpose of doing these studies is to better understand the effect of bubble dynamics on thermal destratification and quantify the extent of destratification. The volume of fluid and interface compression method of OpenFOAM CFD code is utilised for the present analysis. Different values of inlet gas velocities (V_g), orifice diameters (d_o), and arrangement of the orifices in triangular and square fashion with different pitches (p/d_o) are considered. In addition, the effect of gravitational forces (g/g_e) on thermal destratification is also reported. For all these cases, the effectiveness of thermal destratification is quantified in terms of a newly defined parameter, the destratification index (I_d). For V_g = 1 m/s, the I_d value is maximum compared to lower V_g values. It is seen that when the gas velocity increased from 0.3 m/s to 1.0 m/s, the average effectiveness in thermal destratification (I_davg) and pressure at the ullage increased by 44.38% and by 64.81%, respectively. The I_davg and pressure at ullage increased by 96.29% and 14.91%, respectively, when the g/g_e ratio changed from 0.3 to 3. Compared to the triangular arrangement with p/d_o = 10, the calculated I_davg increased by 30.67% when gas inlets were arranged with a square pitch of 10. For p/d_o = 4, 6 and 8, the increments in I_davg are of the order of 12.86%, 19.43% and 21.92%, respectively, for gas inlets arranged in a square fashion as compared to the triangular arrangement. It is found that continuous bubbling with gas inlets arranged in square pitch p/d_o = 10 gives higher effectiveness in thermal destratification. Thus, by these studies, one can develop a thermal destratification mechanism with continuous bubbling for optimum performance. Also, these studies give an overall idea of sparger design for getting the correct gas flow rate for thermal destratification within the cryogenic liquid storage tanks.     

Natural hydrogen emanations in Namibia: Field acquisition and vegetation indexes from multispectral satellite image analysis

Natural hydrogen exploration is now active in various places of the world. Onshore, correlation between natural H₂ generation and the presence of iron rich rocks especially from Archean and Neoproterozoic cratons have been observed. Emanations and accumulations of H₂ have already been confirmed in such geological settings in Australia, South Africa and Brazil. The geological similitude and the presence of numerous sub circular depressions that are a good proxy for hydrogen emanations suggest that hydrogen resources may also exist in Namibia. We present here the results of a data acquisition campaign which allowed us to confirm the presence of natural hydrogen in this country in the vicinity of Neoproterozoic Banded Iron Formation. The H₂ content in the soil, as in Brazil, is variable within the depressions in time and space and is particularly time sensitive across the day. Comparison of the H₂ signal versus time within these two regions shows a similar behavior of the soils with an increase of the H₂ flow at the middle of the day. In addition, these new data allow us to better constrain the morphological characteristics of such H₂-emiting depressions. By using satellite images and digital elevation model we propose a new proxy to differentiate potentially H₂-emiting features from other type of depressions such as Salt Pan. The Landsat multispectral images and their processing through NDVI and SAVI indexes, that highlight a ring of healthy vegetation around the sub circular area with scarce vegetation already observed appear able to discriminate between H₂ emitting structures and other soft depressions.     

Importance of optical homogeneity for high-quality transparent ceramics

Two types of transparent Y₂O₃ ceramics without including large scattering sources such as residual pores, one with very high optical homogeneity (type A) and another one with slightly insufficient optical homogeneity (type B), are purposely prepared, and their optical properties are investigated and compared qualitatively and quantitatively. Type A ceramic exhibits transmittance characteristics with very low internal loss in the visible to infrared wavelength region, while type B ceramic is inferior in various optical performances especially in the short (visible) wavelength region. In type B ceramic, birefringence occurs due to optical inhomogeneity in the visible region, resulting in a decrease in the extinction ratio. Non-uniform refractive index distribution is also observed in the Schlieren image of type B ceramic, hence the laser beam quality through that material is degraded. This study proved the importance of optical homogeneity of transparent ceramics and clarified the problems in actual applications.     

广义正交码索引调制系统的性能分析

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。