Truncated gRNA reduces CRISPR/Cas9-mediated off-target rate for MSTN gene knockout in bovines

The CRISPR/Cas9 mediates efficient gene editing but has off-target effects inconducive to animal breeding. In this study, the efficacy of CRISPR/Cas9 vectors containing different lengths of g RNA in reduction of the off-target phenomenon in the bovine MSTN gene knockout fibroblast cell lines was assessed, providing insight into improved methods for livestock breeding. A 20-bp g RNA was designed for the second exon of the bovine MSTN gene, and CRISPR/Cas9-B was constructed to guide the Cas9 protein to the AGAACCAGGAGAAGATGGACTGG site. The alternative CRISPR/Cas9-19, CRISPR/Cas9-18, CRISPR/Cas9-17 and CRISPR/Cas9-15 vectors were constructed using g RNAs truncated by 1, 2, 3 and 5 bp, respectively. These vectors were then introduced into bovine fetal fibroblasts by the electroporation method, and single cells were obtained by flow cytometry sorting. PCR was performed for each off-target site. All samples were sequenced and analyzed, and finally the efficiency of each vector in target and off-target sites was compared. The CRISPR/Cas9-B vector successfully knocked out the MSTN gene, but the off-target phenomenon was observed. The efficiencies of CRISPR/Cas-B, CRISPR/Cas9-19, CRISPR/Cas9-18, CRISPR/Cas9-17 and CRISPR/Cas9-15 in triggering gene mutations at MSTN targeting sites were 62.16, 17.39, 7.69, 74.29 and 3.85%, respectively;rates of each at the Off-MSTN-1 locus were 52.86, 0, 0, 8.82 and 0%, respectively;all were 0% at the Off-MSTN-2 locus;rates at the Off-MSTN-3 site were 44.87, 51.72, 86.36, 0 and 50%, respectively. The efficiency of the CRISPR/Cas9-17 plasmid in the MSTN site was higher than that in the CRISPR/Cas9-B plasmid, and the effect at the three off-target sites was significantly lower. This study demonstrated that the CRISPR/Cas9-17 plasmid constructed by truncating 3 bp g RNA can effectively reduce the off-target effect without reducing the efficiency of bovine MSTN gene targeting. This finding will provide more effective gene editing strategy for use of CRISPR/Cas9 technology.

Fusion Reaction Rate Coefficient for Different Beam and Target Scenarios

Fusion power output is proportional not only to the fuel particle number densities participating in reaction but also to the fusion reaction rate coefficient （or reactivity）, which is dependent on reactant velocity distribution functions. They are usuMly assumed to be dual Maxwellian distribution functions with the same temperature for thermal nuclear fusion circumstances. However, if high power neutral beam injection and minority ion species ICRF plasma heating, or multi-pinched plasma beam head-on collision, in a converging region are required and investigated in future large scale fusion reactors, then the fractions of the injected energetic fast ion tail resulting from ionization or charge exchange will be large enough and their contribution to the non-Maxwellian distribution functions is not negligible, hence to the fusion reaction rate coefficient or calculation of fusion power. In such cases, beam-target, and beam-beam reaction enhancement effect contributions should play very important roles. In this paper, several useful formulae to calculate the fusion reaction rate coefticient for different beam and target combination scenarios are derived in detail

Target rotation parameter estimation for ISAR imaging via frame processing

Frame processing method offers a model-based approach to Inverse Synthetic Aperture Radar(ISAR) imaging. It also provides a way to estimate the rotation rate of a non-cooperative target from radar returns via the frame operator properties. In this paper, the relationship between the best achievable ISAR image and the reconstructed image from radar returns was derived in the framework of Finite Frame Processing theory. We show that image defocusing caused by the use of an incorrect target rotation rate is interpreted under the FP method as a frame operator mismatch problem which causes energy dispersion. The unknown target rotation rate may be computed by optimizing the frame operator via a prominent point. Consequently, a prominent intensity maximization method in FP framework was proposed to estimate the underlying target rotation rate from radar returns. In addition, an image filtering technique was implemented to assist searching for a prominent point in practice. The proposed method is justified via a simulation analysis on the performance of FP imaging versus target rotation rate error.Effectiveness of the proposed method is also confirmed from real ISAR data experiments.

Analysis on the Option of RMB Exchange Rate Regime

This paper analyses four effects of pegging exchange rate regime： effects on government policymaking, nominal anchor, domestic currency appreciation expectation, and currericy speculative attacks. Based on this, the paper concludes that China should give up RMB pegging exchange rate regime at present, carry out RMB floating exchange rate regime in the long term and RMB exchange rate target zone regime in the mid and short term.

New CFAR target detector for SAR images based on kernel density estimation and mean square error distance

A new constant false alarm rate （CFAR） target detector for synthetic aperture radar （SAR） images is developed. For each pixel under test, both the local probability density function （PDF） of the pixel and the clutter PDF in the reference window are estimated by the non-parametric density estimation. The target detector is defined as the mean square error （MSE） distance between the two PDFs. The CFAR detection in SAR images having multiplicative noise is achieved by adaptive kernel bandwidth proportional to the clutter level. In addition, for obtaining a threshold with respect to a given probability of false alarm （PFA）, an unsupervised null distribution fitting method with outlier rejection is proposed. The effectiveness of the proposed target detector is demonstrated by the experiment result using the RADATSAT-2 SAR image.

Novel Rate-Control Algorithm Based on TM5 Framework

Rate control is a key technology in the fields of video coding and transmission, and it has attracted a great attention and has been studied extensively. The TM5 framework of MPEG-2 is a classical rate control algo-rithm and has being widely used. However, it has some underlying drawbacks during practical applications such as the poor rate control precision and high computational complexity. Hence, in this paper, a novel rate-control algorithm based on the TM5 framework is proposed. The drawback of the target bit allocation method of the original TM5 algorithm is firstly analyzed and improved. Then, a new rate-distortion model is incorporated into the rate control algorithm to implement rate prediction to enhance the rate-control precision. Meanwhile, the macro-block (MB) level rate control is adapted to be frame level to reduce the computational complexity. Experiments are conducted and some results are given. Compared with the original TM5 algo-rithm, the improved novel algorithm not only can enhance the rate-control precision but also can reduce the complexity and the fluctuation of decoded image quality.

靶盏预处理技术在双镜联合治疗完全型鹿角形结石中的应用价值

目的探讨采用输尿管软镜靶盏预处理技术行一期输尿管软镜联合经皮肾镜钬激光碎石治疗完全型鹿角形结石的安全性和有效性。方法回顾性分析2019年10月~2021年9月采用输尿管软镜联合经皮肾镜手术治疗21例完全型鹿角形结石的临床资料,结石位于左侧8例,右侧12例,双侧结石一期处理右肾结石1例。结石密度(1101±185)HU。手术采用双人双镜操作,全身麻醉,斜仰卧截石位,结合术前影像学检查设计肾穿刺靶盏,输尿管软镜将靶盏内结石击碎,暴露乳头穹隆位置,经皮对靶盏穹隆精准穿刺扩张,直视下建立F_(18)或F_(20)经皮肾通道,双镜联合完成手术。结果本组21例手术均一期顺利完成,手术时间85~158(121.8±21.2)min,术后血红蛋白降低值(9.38±4.36)g/L,术后住院时间3~7(4.4±1.4)d,一期结石清除率85.7%(18/21)。并发症6例,包括术中出血需输血1例,发热3例,胸腔积液1例,术后术区疼痛需要镇痛治疗1例。结论对于完全型鹿角形结石,利用输尿管软镜将靶盏结石预处理后再穿刺建立经皮肾工作通道,手术成功率及一期结石清除率高,经皮肾通道数量少,提高手术安全性。

目标体温管理对体外心肺复苏患者神经功能结局和出院生存率影响的系统评价

目的系统评价目标体温管理对体外心肺复苏(extracorporeal cardiopulmonary resuscitation,ECPR)患者神经功能结局和出院生存率的影响。方法计算机检索PubMed、Cochrane Library、Elsevier、Web of Science、Ovid、中国知网、万方、SinoMed、中华医学期刊全文数据库中关于目标体温管理对ECPR患者结局指标影响的文献,检索时限均从建库至2023年6月1日。严格按照纳入排除标准进行筛选,提取资料,评价文献质量,采用RevMan 5.3软件对纳入研究进行Meta分析。结果共纳入8篇研究,包括3687例ECPR患者。与非目标体温管理组比较,目标体温管理未能显著改善患者神经功能结局(OR=1.37,95%CI 0.89~2.13,P=0.16)和出院生存率(OR=0.98,95%CI 0.82~1.15,P=0.77),且两组出血、下肢缺血、肾损伤和感染等ECMO相关并发症发生率差异无统计学意义(OR=1.24,95%CI 0.91~1.68,P=0.17)。结论目标体温管理对ECPR患者的神经结局和出院生存率无显著改善作用,但不会加重ECMO相关并发症的发生。

Efficacy and Safety of Low Target Pressure Trabeculectomy: 2-Year Clinical Results

Purpose: To compare the success and complication rates of low target pressure trabeculectomy (LTT) and conventional trabeculectomy (CT). Methods: A retrospective study was conducted with consecutive patients undergoing trabeculectomy. Twelve eyes of 12 patients underwent LTT, and 17 eyes of 17 patients underwent CT. Surgical success was defined as meeting each target intraocular pressure (IOP) without additional medication or further glaucoma surgery. A Kaplan-Meier survival analysis was used to estimate survival rate. Incidences of surgical complications were also assessed. Results: The median postoperative IOP 2 years after surgery were 10.0 mmHg (interquartile range [IQR] 8.5 - 12.0 mmHg) in the LTT group and 16.0 mmHg (IQR, 14.0 - 18.5 mmHg) in the CT group (P = 0.000). Estimated survival rates for patients who underwent the two types of trabeculectomy were significantly different with all IOP criteria of 10, 12 and 14 mmHg (P Conclusion: LTT provided more chances to maintain low postoperative IOP and had no more vision-threatening complication than those of CT.

Energy Efficient Power Allocation Scheme for Distributed Antenna Systems with Target BER Constraint

The energy efficiency(EE) of distributed antenna system with quality of service(Qo S) requirement is investigated over composite Rayleigh fading channel,where the shadow fading,path loss and Rayleigh fading are all considered. Our aim is to maximize the EE which is defined as the ratio of the transmission rate to the total consumed power subject to the maximum transmit power of each remote antenna constraint and Qo S(target BER) requirement. According to the definition of EE and using the upper bound of average EE,the optimized objective function is provided. Based on this,utilizing Karush-KuhnTucker conditions and numerical calculation,a suboptimal energy efficient power allocation(PA) scheme is developed,and the closedform expression of PA coefficients is derived. The scheme may obtain the EE performance close to the existing optimal scheme. Moreover,it has relatively lower complexity than the existing scheme because only the statistic channel information and less iteration are required. Simulation results show the presented scheme is valid and can meet the target BER requirement,and the EE can be increased as target BER requirement decreases.

直流磁控溅射系统研究及其维护

通过介绍磁控溅射镀膜系统的原理,分析了磁控溅射系统在溅射镀膜的过程中遇到的沉积速率、沉积均匀性、常见故障等方面的问题,对沉积速率和沉积均匀性的影响因素进行了具体地研究;同时描述了设备在使用过程中经常遇到的一些故障,对这些故障发生的原因进行了详细地分析,根据原因分析给出了故障的具体解决方法;最后,对磁控溅射系统在日常使用过程中的保养和维护方面提出了一些建议。注重日常的保养和维护可大大降低设备的故障率。

Neutron distribution and yield produced by 50 MeV/u^(18)O-ion on thick targets

Neutron energy, fluence rate, angular distributions and dose equivalent rate distributions around the thick Be, Cu, An targets bombarded by 50 MeV/u 18O-ion were measured using a threshold detector activation method. At the same time,the neutron yields of 18O-ion and the neutron emission rates in the forward direction were obtained approximately.

围产期全程针对性营养指导对初产妇分娩的影响

目的:探讨围产期全程针对性营养指导对初产妇分娩的影响。方法:纳入2020年4月-2023年6月本院收治初产妇103例,随机数字表法分为对照组(51例)和观察组(52例),两组均常规围产期产科护理,观察组同时实施围产期全程针对性营养指导干预,干预过程中对照组和观察组各脱落1例,观察各组总产程、产后2h出血量、自然分娩、产妇并发症、新生儿并发症、分娩时产妇疼痛程度(VAS评分)、产后3d产妇爱丁堡产后抑郁量表(EPDS)评分与康纳-戴维森弹性量表(CD-RISC)评分、孕妇营养情况及产妇干预满意率。结果:观察组产妇总产程(431.49±24.19 min)短于对照组(508.18±22.17 min),产后2h出血量(123±10 ml)少于对照组(204±11 ml),自然分娩率(80.4%)高于对照组(60.0%),产妇并发症率(0)、新生儿并发症率(3.9%)均低于对照组(8.0%、16.0%);分娩时观察组VAS评分(4.85±0.94分)低于对照组(6.23±0.56分),产后3d的EPDS评分(7.29±0.69分)与CD-RISC评分(81.27±4.27分)均优于对照组(9.13±0.77分、77.62±2.65分),孕妇营养不良发生率(0)低于对照组(8.0%),产妇干预满意率(94.1%)高于对照组(78.0%)(均P<0.05)。结论:围产期全程针对性营养指导可较好改善初产妇营养状况,降低营养不良发生率,缩短总产程、减少产后出血,减轻了分娩疼痛,提高自然分娩率,降低并发症发生,产妇产后心理状态好、满意度高。

经直肠实时组织弹性成像引导靶向穿刺在前列腺癌诊断中的应用研究

目的 探讨经直肠实时组织弹性成像(transrectal real-time tissue elastography,TRTE)引导靶向穿刺诊断前列腺癌的临床应用价值。方法 选取2020年1月至2022年12月于郑州市第一人民医院就诊的可疑前列腺癌患者52例为研究对象,术前均行经直肠常规超声及TRTE检查评估前列腺病变的良恶性,对TRTE发现可疑病灶的28例患者行TRTE引导靶向穿刺(2针)+系统穿刺(8针),对TRTE未发现可疑病灶的24例患者行直肠常规超声引导系统穿刺(12针),分析TRTE诊断前列腺癌的效能及对比分析靶向穿刺与系统穿刺的穿刺阳性率。结果 本研究最终病理确诊前列腺癌25例,良性病变27例;TRTE诊断前列腺癌28例,良性病变24例,诊断的阳性预测值、阴性预测值分别为75.0%(21/28)、83.3%(20/24)。TRTE发现可疑病灶的28例患者,靶向穿刺共56针,诊断前列腺癌36针,阳性率64.29%(36/56),系统穿刺共224针,诊断前列腺癌89针,阳性率39.73%(89/224);靶向穿刺的前列腺癌穿刺阳性率显著高于系统穿刺(P<0.05)。结论 TRTE可较好地诊断前列腺癌,其引导靶向穿刺诊断前列腺癌的阳性率更高,可在减少穿刺针数的基础上最大限度提高穿刺阳性率。

基于WGAN-GP-CNN的海面小目标检测

针对传统基于统计理论的海面小目标检测方法在复杂海面环境中性能不高的问题,该文提出了一种改进的检测方法。首先通过分析海杂波和目标回波的特征,将检测问题转化为特征空间的分类任务。鉴于海面小目标样本数量有限,存在样本不平衡的问题,该文引入了一种基于梯度惩罚的沃瑟斯坦生成对抗网络(Wasserstein Generative Adversarial Network with Gradient Penalty,WGAN-GP)来增强目标数据,从而在数量上平衡目标样本与海杂波样本。同时,对原始WGAN-GP网络的损失函数进行了改进,引入相位损失以确保生成数据能够反映真实数据的相位信息。基于这些数据,进一步提取了生成目标和海杂波的高维特征,并将其送入卷积神经网络(Convolutional Neural Network,CNN)进行训练。为了应对高维特征空间中虚警概率难以控制的问题,对CNN算法进行了改进,通过设置Softmax分类器的阈值,实现了虚警概率可控。最后,借助公开的IPIX雷达数据集进行实验验证,所提的WGAN-GP-CNN检测器在积累时间为1.024 s,虚警概率为0.001时,平均检测概率达到0.8683,具有良好的检测效果。

CoFe/NiFe复合自由层对自旋阀磁电阻变化率的影响

研究CoFe/NiFe复合自由层对自旋阀磁电阻变化率的影响。在实验中通过固定溅射功率、时间和气流,调节靶基距(TSD)得到不同厚度及均匀性的复合自由层CoFe/NiFe薄膜,进而达到优化自旋阀结构提高其磁电阻率的目的。实验结果表明:在TSD分别为8.382 cm、8.890 cm时,制备的CoFe和NiFe单层膜性能最优,电阻标准偏差分别为1.33%、0.98%。通过磁性能综合测试平台对优化后的CoFe/NiFe复合自由层的自旋阀结构进行了测试,磁电阻变化率(MR)较优化前提高了约0.84%。该研究可为高性能自旋阀结构的制备提供参考。

鳖甲煎丸对肝癌大鼠黏着斑激酶/雷帕霉素靶蛋白通路的影响

目的:探讨鳖甲煎丸对肝癌模型大鼠肝组织病理特征及FAK/mTORC1通路的影响。方法:HepG2(1×10^(7))细胞注射于大鼠右腋皮下,建立肝癌模型,分为模型组、5-氟尿嘧啶组、鳖甲煎丸低剂量组、鳖甲煎丸高剂量组,另设正常组。各药物组给予相应药物灌胃,持续给药4周,正常组、模型组给予等体积的0.9%氯化钠溶液。实验结束后,测定肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、肝癌FAK、mTORC1水平、肝癌VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白水平。结果:与正常组比较,模型组肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白、肝癌FAK、mTORC1 mRNA和蛋白表达升高(均P<0.05)。与模型组比较,5-氟尿嘧啶组、鳖甲煎丸低剂量组、鳖甲煎丸高剂量组肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白、肝癌FAK、mTORC1 mRNA和蛋白表达降低(均P<0.05)。鳖甲煎丸高剂量组肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白、肝癌FAK、mTORC1 mRNA和蛋白表达低于鳖甲煎丸低剂量组(均P<0.05)。结论:鳖甲煎丸对大鼠肝癌具有明显抑制作用,能减轻大鼠肝癌所致的病理损伤,其机制可能与鳖甲煎丸抑制肝癌FAK、mTORC1表达,诱导肝癌细胞凋亡,降低炎症反应有关。

二维片状相对论电子束到靶规律研究

相对论电子束在理想顺磁环境下能够以较高的注量率击中靶目标,但实际情况中由于受环境的影响,相对论电子束的传输方向可能会与地磁场呈小角度偏差,因此会受到地磁场的作用产生拉莫尔进动,影响电子束的到靶瞄准以及到靶注量。基于二维片状相对论电子束,分别对相对论电子束顺磁和偏离磁场3°角两种传输情况进行仿真模拟,通过模拟束团的传输过程,分析研究了顺磁环境下不同传输距离束团到靶率的变化规律,以及偏离磁场3°角时传输过程中注量率的变化规律,为相对论电子束到靶率的预估和靶目标的瞄准提供数据参考。

基于多维空间离散基准的目标检测网络设计

针对目标检测网络中检测头的设计缺少依据,不能对不同数据集进行相应优化的问题,用一至四维的空间离散基准和正样本点(组)分配冲突率模型,提出了相应的设计依据。即基于位置的分配原则中,针对特定数据集的正样本点在4个回归量所组成的空间维度中的分布特点,在不高于指定的分配冲突率的条件下,以减少正负样本不均衡度和系统计算资源为目的,设计出具有最少点数检测头的规律。其本质是一个回归基准编码和正负样本分配设计的过程,进而实现检测性能与资源消耗之间的平衡。得出基于卷积目标检测网络检测头的回归基准可以采用4个回归中的任意组合,但需结合样本分配策略与数据集的正样本分配冲突率进行综合设计的结论。

Discovery and validation of potential drug targets based on the phylogenetic evolution of GPCRs

Target identification is a critical step following the discovery of small molecules that elicit a biological phenotype. G-protein coupled recaptors (GPCRs) are among the most important drug targets for the pharmaceutical industry. The present work seeks to provide an in silico model of known GPCR protein fishing technologies in order to rapidly fish out potential drug targets on the basis of amino acid sequences and seven transmembrane regions (TMs) of GPCRs. Some scoring matrices were trained on 22 groups of GPCRs in the GPCRDB database. These models were employed to predict the GPCR proteins in two groups of test sets. On average, the mean correct rate of each TM of 38 GPCRs from two test sets (ST23 and ST24) was found 62% and 57.5%, respectively, using training set 18 (SLD18);the mean hit rate of each TM of 38 GPCRs from ST23 and ST24 was found 68.1% and 64.7%, respectively. Based on the scoring matrices of PreMod, the mean correct rate of each TM of GPCRs from ST23 and ST24 was found 62% and 62.04%, respectively;the mean hit rate of each TM of GPCRs from ST23 and ST24 was found 67.7% and 68.0%, respecttively. The means of GPCRs in ST23 based on SLD18 is close to those based on PreMod;whereas the means of GPCRs in ST24 based on?SLD18 is less than those based on PreMod. Moreover, the accuracy (“2”) and validity (“2 + 1”) rates of prediction all seven TMs of 38 GPCRs by the scoring matrices of PreMod are more than those by SLD18, SLA14 and SLA3;whereas the hit rates (94.74% and 97.37%) by PreMod are less than those of?SLA3 but bigger than those of?SLD18 and SLA14, respectively. This is the reason that we choose PreMod to predict some potential drug targets. 22 GPCR proteins in the sense chain of chromosome 19 constructing validation set were predicted and validated by PreMod whose hit rate is up to 90.91%. Further evaluation is under investigation.