The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base edit...The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base editor(ABE) allow generating precise and irreversible base mutations in a programmable manner and have been used in many different types of cells and organisms. However, their applications are limited by low editing efficiency at certain genomic target sites or at specific target cytosine(C) or adenine(A) residues. Using a strategy of combining optimized synergistic core components, we developed a new multiplex super-assembled ABE(sABE) in rice that showed higher base-editing efficiency than previously developed ABEs. We also designed a new type of nuclear localization signal(NLS) comprising a FLAG epitope tag with four copies of a codon-optimized NLS(F4NLS^(r2)) to generate another ABE named F4NLS-sABE. This new NLS increased editing efficiency or edited additional A at several target sites. A new multiplex super-assembled CBE(sCBE) and F4NLS^(r2) involved F4NLS-sCBE were also created using the same strategy. F4NLS-sCBE was proven to be much more efficient than sCBE in rice. These optimized base editors will serve as powerful genome-editing tools for basic research or molecular breeding in rice and will provide a reference for the development of superior editing tools for other plants or animals.展开更多
Purpose-The purpose of this paper is to eliminate the fluctuations in train arrival and departure times caused by skewed distributions in interval operation times.These fluctuations arise from random origin and proces...Purpose-The purpose of this paper is to eliminate the fluctuations in train arrival and departure times caused by skewed distributions in interval operation times.These fluctuations arise from random origin and process factors during interval operations and can accumulate over multiple intervals.The aim is to enhance the robustness of high-speed rail station arrival and departure track utilization schemes.Design/methodologylapproach-To achieve this objective,the paper simulates actual train operations,incorporating the fluctuations in interval operation times into the utilization of arrival and departure tracks at the station.The Monte Carlo simulation method is adopted to solve this problem.This approach transforms a nonlinear model,which includes constraints from probability distribution functions and is difficult to solve directly,into a linear programming model that is easier to handle.The method then linearly weights two objectives to optimize the solution.Findings-Through the application of Monte Carlo simulation,the study successfully converts the complex nonlinear model with probability distribution function constraints into a manageable linear programming model.By continuously adjusting the weighting coefficients of the linear objectives,the method is able to optimize the Pareto solution.Notably,this approach does not require extensive scene data to obtain a satisfactory Pareto solution set.Originality/value-The paper contributes to the field by introducing a novel method for optimizing high-speed rail station arrival and departure track utilization in the presence of fluctuations in interval operation times.The use of Monte Carlo simulation to transform the problem into a tractable linear programming model represents a significant advancement.Furthermore,the method's ability to produce satisfactory Pareto solutions without relying on extensive data sets adds to its practical value and applicability in real-world scenarios.展开更多
A second harmonic generation system with two type II KDP crystals in quadrature is optimized for the nanosecond chirp pulse. The acceptance bandwidth of this optimizing scheme is close to 10 nm by using two crystals w...A second harmonic generation system with two type II KDP crystals in quadrature is optimized for the nanosecond chirp pulse. The acceptance bandwidth of this optimizing scheme is close to 10 nm by using two crystals with slightly opposite angular detuning from phase matching and the conversion efficiency can reach 70% for top-hat chirp pulse at -2 GW/cm^2 in theory. The preliminary experimental results are obtained on the 9th beam of Shen Guang Ⅱ SGⅡ laser system, and the performance of optimization is partially verified.展开更多
By differentiating four different types of output, the paperargues that their roles are also different. And learners of differ-ent language proficiency levels should be guided to produce dif-ferent types of output. Th...By differentiating four different types of output, the paperargues that their roles are also different. And learners of differ-ent language proficiency levels should be guided to produce dif-ferent types of output. Thus the paper introduces a new concept,namely "optimal output". Blindly making the learner produceoutput which is far beyond his current English level will only doharm to his interlanguage development, making it fossilize at anearly stage.展开更多
基金supported by the Beijing Scholars Program[BSP041]。
文摘The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base editor(ABE) allow generating precise and irreversible base mutations in a programmable manner and have been used in many different types of cells and organisms. However, their applications are limited by low editing efficiency at certain genomic target sites or at specific target cytosine(C) or adenine(A) residues. Using a strategy of combining optimized synergistic core components, we developed a new multiplex super-assembled ABE(sABE) in rice that showed higher base-editing efficiency than previously developed ABEs. We also designed a new type of nuclear localization signal(NLS) comprising a FLAG epitope tag with four copies of a codon-optimized NLS(F4NLS^(r2)) to generate another ABE named F4NLS-sABE. This new NLS increased editing efficiency or edited additional A at several target sites. A new multiplex super-assembled CBE(sCBE) and F4NLS^(r2) involved F4NLS-sCBE were also created using the same strategy. F4NLS-sCBE was proven to be much more efficient than sCBE in rice. These optimized base editors will serve as powerful genome-editing tools for basic research or molecular breeding in rice and will provide a reference for the development of superior editing tools for other plants or animals.
文摘Purpose-The purpose of this paper is to eliminate the fluctuations in train arrival and departure times caused by skewed distributions in interval operation times.These fluctuations arise from random origin and process factors during interval operations and can accumulate over multiple intervals.The aim is to enhance the robustness of high-speed rail station arrival and departure track utilization schemes.Design/methodologylapproach-To achieve this objective,the paper simulates actual train operations,incorporating the fluctuations in interval operation times into the utilization of arrival and departure tracks at the station.The Monte Carlo simulation method is adopted to solve this problem.This approach transforms a nonlinear model,which includes constraints from probability distribution functions and is difficult to solve directly,into a linear programming model that is easier to handle.The method then linearly weights two objectives to optimize the solution.Findings-Through the application of Monte Carlo simulation,the study successfully converts the complex nonlinear model with probability distribution function constraints into a manageable linear programming model.By continuously adjusting the weighting coefficients of the linear objectives,the method is able to optimize the Pareto solution.Notably,this approach does not require extensive scene data to obtain a satisfactory Pareto solution set.Originality/value-The paper contributes to the field by introducing a novel method for optimizing high-speed rail station arrival and departure track utilization in the presence of fluctuations in interval operation times.The use of Monte Carlo simulation to transform the problem into a tractable linear programming model represents a significant advancement.Furthermore,the method's ability to produce satisfactory Pareto solutions without relying on extensive data sets adds to its practical value and applicability in real-world scenarios.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China under Grant No.1229241A00
文摘A second harmonic generation system with two type II KDP crystals in quadrature is optimized for the nanosecond chirp pulse. The acceptance bandwidth of this optimizing scheme is close to 10 nm by using two crystals with slightly opposite angular detuning from phase matching and the conversion efficiency can reach 70% for top-hat chirp pulse at -2 GW/cm^2 in theory. The preliminary experimental results are obtained on the 9th beam of Shen Guang Ⅱ SGⅡ laser system, and the performance of optimization is partially verified.
文摘By differentiating four different types of output, the paperargues that their roles are also different. And learners of differ-ent language proficiency levels should be guided to produce dif-ferent types of output. Thus the paper introduces a new concept,namely "optimal output". Blindly making the learner produceoutput which is far beyond his current English level will only doharm to his interlanguage development, making it fossilize at anearly stage.
