Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease- causing mutations in patients. However, problems such as mosaic...Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease- causing mutations in patients. However, problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical applicaUon of such approaches. Recently, a base editor （BE） system built on cytidine （C） deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine （T） efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified high- fidelity version of base editor 2 （HF2-BE2）, and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.展开更多
Acoustic holograms can recover wavefront stored acoustic field information and produce high-fidelity complex acoustic fields. Benefiting from the huge spatial information that traditional acoustic elements cannot matc...Acoustic holograms can recover wavefront stored acoustic field information and produce high-fidelity complex acoustic fields. Benefiting from the huge spatial information that traditional acoustic elements cannot match, acoustic holograms pursue the realization of high-resolution complex acoustic fields and gradually tend to high-frequency ultrasound applications. However, conventional continuous phase holograms are limited by three-dimensional(3D) printing size, and the presence of unavoidable small printing errors makes it difficult to achieve acoustic field reconstruction at high frequency accuracy. Here, we present an optimized discrete multi-step phase hologram. It can ensure the reconstruction quality of image with high robustness, and properly lower the requirement for the 3D printing accuracy. Meanwhile, the concept of reconstruction similarity is proposed to refine a measure of acoustic field quality. In addition, the realized complex acoustic field at 20 MHz promotes the application of acoustic holograms at high frequencies and provides a new way to generate high-fidelity acoustic fields.展开更多
Reversible data hiding is a confidential communication technique that takes advantage of image file characteristics,which allows us to hide sensitive data in image files.In this paper,we propose a novel high-fidelity ...Reversible data hiding is a confidential communication technique that takes advantage of image file characteristics,which allows us to hide sensitive data in image files.In this paper,we propose a novel high-fidelity reversible data hiding scheme.Based on the advantage of the multipredictor mechanism,we combine two effective prediction schemes to improve prediction accuracy.In addition,the multihistogram technique is utilized to further improve the image quality of the stego image.Moreover,a model of the grouped knapsack problem is used to speed up the search for the suitable embedding bin in each sub-histogram.Experimental results show that the quality of the stego image of our scheme outperforms state-of-the-art schemes in most cases.展开更多
The pneumatic probe is widely used for contact measurements in turbomachinery flow field research.However,it inevitably interferes with the original flow field,leading to additional errors,particularly in wake flow fi...The pneumatic probe is widely used for contact measurements in turbomachinery flow field research.However,it inevitably interferes with the original flow field,leading to additional errors,particularly in wake flow fields or transonic regions with significant pressure gradients.This study employed Reynolds-Averaged Navier-Stokes delete and high-fidelity numerical simulation to investigate the impact of an inserted pneumatic probe on the wake flow field of a transonic turbine blade and compared it to the baseline flow field.Results indicate that the probe causes the shock waves premature occurrence in the high subsonic wake region near the turbine blade trailing edge.These shock waves affect vortex shedding by thickening the boundary layer near the trailing edge and changing the shedding pattern from high-frequency-low-energy to low-frequencyhigh-energy.In addition,the extra flow loss is incurred,and the blade's heat transfer characteristic is changed.This research provides a reference for testing experiments in complex transonic flow fields,guiding experimental researchers to minimize instrument interference with the original flow field.展开更多
Next-generation sequencing(NGS),represented by Illumina platforms,has been an essential cornerstone of basic and applied research.However,the sequencing error rate of 1 per 1000 bp(10^(−3))represents a serious hurdle ...Next-generation sequencing(NGS),represented by Illumina platforms,has been an essential cornerstone of basic and applied research.However,the sequencing error rate of 1 per 1000 bp(10^(−3))represents a serious hurdle for research areas focusing on rare mutations,such as somatic mosaicism or microbe heterogeneity.By examining the high-fidelity sequencing methods developed in the past decade,we summarized three major factors underlying errors and the corresponding 12 strategies mitigating these errors.We then proposed a novel framework to classify 11 preexisting representative methods according to the corresponding combinatory strategies and identified three trends that emerged during methodological developments.We further extended this analysis to eight long-read sequencing methods,emphasizing error reduction strategies.Finally,we suggest two promising future directions that could achieve comparable or even higher accuracy with lower costs in both NGS and long-read sequencing.展开更多
Engineering design is undergoing a paradigm shift from design for performance to design for affordability, operability, and durability, seeking multi-objective optimization. To facilitate this transformation, signific...Engineering design is undergoing a paradigm shift from design for performance to design for affordability, operability, and durability, seeking multi-objective optimization. To facilitate this transformation, significantly extended design freedom and knowledge must be available in the early design stages. This paper presents a high-fidelity framework for design and optimization of the liquid swirl injectors that are widely used in aerospace propulsion and power-generation systems. The framework assembles a set of techniques, including Design Of Experiment(DOE), high-fidelity Large Eddy Simulations(LES), machine learning, Proper Orthogonal Decomposition(POD)-based Kriging surrogate modeling(emulation), inverse problem optimization, and uncertainty quantification. LES-based simulations can reveal detailed spatiotemporal evolution of flow structures and flame dynamics in a high-fidelity manner, and identify important injector design parameters according to their effects on propellant mixing, flame stabilization, and thermal protection.For a given a space of design parameters, DOE determines the number of design points to perform LES-based simulations. POD-based emulations, trained by the LES database, can effectively explore the design space and deduce an optimal group of design parameters in a turn-around time that is reduced by three orders of magnitude. The accuracy of the emulated results is validated, and the uncertainty of prediction is quantified. The proposed design methodology is expected to profoundly extend the knowledge base and reduce the cost for initial design stages.展开更多
基金This work was supported by the National Natural Science Foundation of China （Grant Nos. 91640119, 31601196, 81330055, 31371508, and 31671540）, the Natural Science Foundation of Guangdong Province （2016A030310206 and 2014A030312011）, the Science and Technology Planning Project of Guangdong Province （2015B020228002 and 2015A020212005）, the Guangzhou Science and Technology Project （201605030012 and 201707010085）, and the Fundamental Research Funds for the Central Universities （161gzd13 and 161gpy31）. We would also like to acknowledge the support of CA211653, CPRIT RP160462, the Welch Foundation Q-1673, and the C-BASS Shared Resource at the Dan L. Duncan Cancer Center （DLDCC） of Baylor College of Medicine （P30CA125123）.
文摘Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease- causing mutations in patients. However, problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical applicaUon of such approaches. Recently, a base editor （BE） system built on cytidine （C） deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine （T） efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified high- fidelity version of base editor 2 （HF2-BE2）, and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.
文摘为实现波浪传播的高保真数值模拟,采用包含单元均值和点值(volume-average/point-value method,VPM)的有限体积法求解纳维-斯托克斯方程和具有二次曲面性质和高斯积分的双曲正切函数(THINC method with quadratic surface representation and Gaussian quadrature,THINC/QQ)方法来重构自由面,建立以开源求解库OpenFOAM底层函数库为基础的VPM-THINC/QQ模型.在本模型中添加推板造波法实现波浪的产生功能,采用松弛法实现消波功能,构建高精度黏性流数值波浪水槽.分别采用VPM-THINC/QQ模型和InterFoam求解器(OpenFOAM软件包中广泛使用的多相流求解器)开展规则波的数值模拟,重点探究网格大小和时间步长等因素对波浪传播过程的影响,定量地分析波高衰减程度;为验证本模型的适应性,对长短波进行模拟.结果表明,在相同网格大小或时间步长条件下,VPM-THINC/QQ模型的预测结果与参考值吻合较好,波高衰减较少,且无相位差,在波浪传播过程的模拟中呈现出良好的保真性.本文工作为波浪传播的模拟研究提供了一种高精度的黏性数值波浪水槽模型.
基金国家高技术研究发展计划(863)(the National High-Tech Research and Development Plan of China under Grant No.2004AA1Z2410)国家发改委基金项目(the Foundation of National Development and Reform Commission No.发改高技 20042040)
基金Project supported by the China Postdoctoral Science Foundation (Grant No.2023M732745)the National Natural Science Foundations of China (Grant Nos.61974110 and 62104177)+1 种基金the Fundamental Research Funds for the Central Universities,China (Grant Nos.QTZX23022 and JBF211103)the Cooperation Program of XDU– Chongqing IC Innovation Research Institute (Grant No.CQ IRI-2022CXY-Z07)。
文摘Acoustic holograms can recover wavefront stored acoustic field information and produce high-fidelity complex acoustic fields. Benefiting from the huge spatial information that traditional acoustic elements cannot match, acoustic holograms pursue the realization of high-resolution complex acoustic fields and gradually tend to high-frequency ultrasound applications. However, conventional continuous phase holograms are limited by three-dimensional(3D) printing size, and the presence of unavoidable small printing errors makes it difficult to achieve acoustic field reconstruction at high frequency accuracy. Here, we present an optimized discrete multi-step phase hologram. It can ensure the reconstruction quality of image with high robustness, and properly lower the requirement for the 3D printing accuracy. Meanwhile, the concept of reconstruction similarity is proposed to refine a measure of acoustic field quality. In addition, the realized complex acoustic field at 20 MHz promotes the application of acoustic holograms at high frequencies and provides a new way to generate high-fidelity acoustic fields.
基金funded by National Science Council,Taiwan,the Grant Number is NSC 111-2410-H-167-005-MY2.
文摘Reversible data hiding is a confidential communication technique that takes advantage of image file characteristics,which allows us to hide sensitive data in image files.In this paper,we propose a novel high-fidelity reversible data hiding scheme.Based on the advantage of the multipredictor mechanism,we combine two effective prediction schemes to improve prediction accuracy.In addition,the multihistogram technique is utilized to further improve the image quality of the stego image.Moreover,a model of the grouped knapsack problem is used to speed up the search for the suitable embedding bin in each sub-histogram.Experimental results show that the quality of the stego image of our scheme outperforms state-of-the-art schemes in most cases.
基金supported by the National Science and Technology Major Project(Grant Nos.2017-V-0016-0068,and J2019-V-0017-0112)the National Natural Science Foundation of China(Grant No.51776011).
文摘The pneumatic probe is widely used for contact measurements in turbomachinery flow field research.However,it inevitably interferes with the original flow field,leading to additional errors,particularly in wake flow fields or transonic regions with significant pressure gradients.This study employed Reynolds-Averaged Navier-Stokes delete and high-fidelity numerical simulation to investigate the impact of an inserted pneumatic probe on the wake flow field of a transonic turbine blade and compared it to the baseline flow field.Results indicate that the probe causes the shock waves premature occurrence in the high subsonic wake region near the turbine blade trailing edge.These shock waves affect vortex shedding by thickening the boundary layer near the trailing edge and changing the shedding pattern from high-frequency-low-energy to low-frequencyhigh-energy.In addition,the extra flow loss is incurred,and the blade's heat transfer characteristic is changed.This research provides a reference for testing experiments in complex transonic flow fields,guiding experimental researchers to minimize instrument interference with the original flow field.
基金supported by the Ministry of Agriculture and Rural Affairs of China,the National Key R&D Program of China(Grant No.2019YFA0802600)the Chinese Academy of Sciences(Grant Nos.ZDBS-LY-SM005 and XDPB17)the National Natural Science Foundation of China(Grant No.31970565).
文摘Next-generation sequencing(NGS),represented by Illumina platforms,has been an essential cornerstone of basic and applied research.However,the sequencing error rate of 1 per 1000 bp(10^(−3))represents a serious hurdle for research areas focusing on rare mutations,such as somatic mosaicism or microbe heterogeneity.By examining the high-fidelity sequencing methods developed in the past decade,we summarized three major factors underlying errors and the corresponding 12 strategies mitigating these errors.We then proposed a novel framework to classify 11 preexisting representative methods according to the corresponding combinatory strategies and identified three trends that emerged during methodological developments.We further extended this analysis to eight long-read sequencing methods,emphasizing error reduction strategies.Finally,we suggest two promising future directions that could achieve comparable or even higher accuracy with lower costs in both NGS and long-read sequencing.
基金sponsored by the William RT Oakes Endowment of the Georgia Institute of Technology
文摘Engineering design is undergoing a paradigm shift from design for performance to design for affordability, operability, and durability, seeking multi-objective optimization. To facilitate this transformation, significantly extended design freedom and knowledge must be available in the early design stages. This paper presents a high-fidelity framework for design and optimization of the liquid swirl injectors that are widely used in aerospace propulsion and power-generation systems. The framework assembles a set of techniques, including Design Of Experiment(DOE), high-fidelity Large Eddy Simulations(LES), machine learning, Proper Orthogonal Decomposition(POD)-based Kriging surrogate modeling(emulation), inverse problem optimization, and uncertainty quantification. LES-based simulations can reveal detailed spatiotemporal evolution of flow structures and flame dynamics in a high-fidelity manner, and identify important injector design parameters according to their effects on propellant mixing, flame stabilization, and thermal protection.For a given a space of design parameters, DOE determines the number of design points to perform LES-based simulations. POD-based emulations, trained by the LES database, can effectively explore the design space and deduce an optimal group of design parameters in a turn-around time that is reduced by three orders of magnitude. The accuracy of the emulated results is validated, and the uncertainty of prediction is quantified. The proposed design methodology is expected to profoundly extend the knowledge base and reduce the cost for initial design stages.
