Constellations design for regional terrestrial-satellite network can strengthen the coverage for incomplete terrestrial cellular network. In this paper, a regional satellite constellation design scheme with multiple f...Constellations design for regional terrestrial-satellite network can strengthen the coverage for incomplete terrestrial cellular network. In this paper, a regional satellite constellation design scheme with multiple feature points and multiple optimization indicators is proposed by comprehensively considering multi-objective optimization and genetic algorithm, and "the Belt and Road" model is presented in the way of dividing over 70 nations into three regular target areas. Following this, we formulate the optimization model and devise a multi-objective genetic algorithm suited for the regional area with the coverage rate under simulating, computing and determining. Meanwhile, the total number of satellites in the constellation is reduced by calculating the ratio of actual coverage of a single-orbit constellation and the area of targets. Moreover, the constellations' performances of the proposed scheme are investigated with the connection of C++ and Satellite Tool Kit(STK). Simulation results show that the designed satellite constellations can achieve a good coverage of the target areas.展开更多
Methanol,produced from carbon dioxide,natural gas,and biomass,has drawn increasing attention as a promising green carbon feedstock for biomanufacturing due to its sustainable and energy-rich properties.Nicotinamide ad...Methanol,produced from carbon dioxide,natural gas,and biomass,has drawn increasing attention as a promising green carbon feedstock for biomanufacturing due to its sustainable and energy-rich properties.Nicotinamide adenine dinucleotide(NAD^(+))-dependent methanol dehydrogenase(MDH)catalyzes the oxidation of methanol to formaldehyde via NADH generation,providing a highly active C1 intermediate and reducing power for subsequent biosynthesis.However,the unsatisfactory catalytic efficiency and cofactor bias of MDH significantly impede methanol valorization,especially in nicotinamide adenine dinucleotide phosphate(NADP^(+))-dependent biosynthesis.Herein,we employed synthetic NADH and NADPH auxotrophic Escherichia coli strains as growth-coupled selection platforms for the directed evolution of MDH from Bacillus stearothermophilus DSM 2334.NADH or NADPH generated by MDH-catalyzed methanol oxidation enabled the growth of synthetic cofactor auxotrophs,establishing a positive correlation between the cell growth rate and MDH activity.Using this principle,MDH mutants exhibiting a 20-fold improvement in catalytic efficiency(k_(cat)/K_(m))and a 90-fold cofactor specificity switch from NAD^(+)to NADP+without a decrease in specific enzyme activity,were efficiently screened from random and semi-rationally designed libraries.We envision that these mutants will advance methanol valorization and that the synthetic cofactor auxotrophs will serve as versatile selection platforms for the evolution of NAD(P)^(+)-dependent enzymes.展开更多
Methanol is a promising one-carbon feedstock for biomanufacturing,which can be sustainably produced from carbon dioxide and natural gas.However,the efficiency of methanol bioconversion is limited by the poor catalytic...Methanol is a promising one-carbon feedstock for biomanufacturing,which can be sustainably produced from carbon dioxide and natural gas.However,the efficiency of methanol bioconversion is limited by the poor catalytic properties of nicotinamide adenine dinucleotide(NAD^(+))-dependent methanol dehydrogenase(Mdh)that oxidizes methanol to formaldehyde.Herein,the neutrophilic and mesophilic NAD^(+)-dependent Mdh from Bacillus stearothermophilus DSM 2334(Mdh_(Bs))was subjected to directed evolution for enhancing the catalytic activity.The combination of formaldehyde biosensor and Nash assay allowed high-throughput and accurate measurement of formaldehyde and facilitated efficient selection of desired variants.Mdh_(Bs)variants with up to 6.5-fold higher K_(cat)/K_(M)value for methanol were screened from random mutation libraries.The T153 residue that is spatially proximal to the substrate binding pocket has significant influence on enzyme activity.The beneficial T153P mutation changes the interaction network of this residue and breaks theα-helix important for substrate binding into two shortα-helices.Reconstructing the interaction network of T153 with surrounding residues may represent a promising strategy to further improve Mdh_(Bs),and this study provides an efficient strategy for directed evolution of Mdh.展开更多
目的系统评价青少年自杀未遂患者的心理体验。方法计算机检索PubMed、CINAHL、PsychInfo、Embase、Web of Science、Cochrane Library、中国知网、万方数据库、维普数据库、中国生物医学文献数据库,筛选有关青少年自杀未遂患者的心理体...目的系统评价青少年自杀未遂患者的心理体验。方法计算机检索PubMed、CINAHL、PsychInfo、Embase、Web of Science、Cochrane Library、中国知网、万方数据库、维普数据库、中国生物医学文献数据库,筛选有关青少年自杀未遂患者的心理体验的质性研究,检索时限为建库至2022年7月。采用澳大利亚乔安娜布里格斯研究所循证卫生保健中心制订的质性研究质量评价标准(2016版)进行文献质量评价,采用Meta整合方法对结果进行整合分析。结果共纳入11篇文献,包括4篇现象学研究、6篇描述性质性研究、1篇扎根理论研究。提炼出61个研究结果,归纳成9个新类别,综合成4个整合结果:①思想与情感风暴,包括精神与情绪崩溃、感受爱意并重拾信心;②生活与学业受阻,包括生活目标缺失、学业压力繁重;③冲突的亲密关系,包括家庭摩擦、爱情失利、友情受挫;④调适与应对,包括多元的外部支持、自我调适与感悟。结论护理人员应关注青少年自杀未遂患者的心理体验,引导其缓解生活与学业压力,缓和家庭矛盾,协助患者树立正确的友情观及爱情观,并联合多学科制订长效的干预方案,预防患者再次自杀。展开更多
A novel crystal nucleus-based cement-hardening accelerator was evaluated using various mortar and segment concrete experiments.The mechanism of hardening acceleration was investigated via hydration temperature variati...A novel crystal nucleus-based cement-hardening accelerator was evaluated using various mortar and segment concrete experiments.The mechanism of hardening acceleration was investigated via hydration temperature variation analysis,hydration degree analysis,X-ray diffraction(XRD)and scanning electron microscopy(SEM).In the presence of accelerator,the fluidity loss of mortar was increased after 30 minuites,and a coagulation was also observed.Moreover,based on the image of SEM,the formation of C-S-H gels was enhanced in the early hydration.As a result,the hardening accelerator could significantly boost the early strength of concrete,especially within one day of pouring,and shorten steam curing time to meet the demolding strength.展开更多
Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA me...Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative method.Methods:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding strategy.In the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best performance.Using an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual scores.Furthermore,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and controls.Results:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family history.The overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family history.Conclusions:We developed and validated a new PRS which may improve the utility in predicting the risk of developing PCa.Our innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.展开更多
基金jointly supported by the National Natural Science Foundation in China (No.61601075)the Natural Science Foundation Project of CQ CSTC (No.cstc2016jcyj A0174)
文摘Constellations design for regional terrestrial-satellite network can strengthen the coverage for incomplete terrestrial cellular network. In this paper, a regional satellite constellation design scheme with multiple feature points and multiple optimization indicators is proposed by comprehensively considering multi-objective optimization and genetic algorithm, and "the Belt and Road" model is presented in the way of dividing over 70 nations into three regular target areas. Following this, we formulate the optimization model and devise a multi-objective genetic algorithm suited for the regional area with the coverage rate under simulating, computing and determining. Meanwhile, the total number of satellites in the constellation is reduced by calculating the ratio of actual coverage of a single-orbit constellation and the area of targets. Moreover, the constellations' performances of the proposed scheme are investigated with the connection of C++ and Satellite Tool Kit(STK). Simulation results show that the designed satellite constellations can achieve a good coverage of the target areas.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDC0110201)the National Key R&D Program of China(2018YFA0901500)+3 种基金the National Natural Science Foundation of China(32070083 and 32222004)the Innovation Fund of Haihe Laboratory of Synthetic Biology(22HHSWSS00017)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2021177)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-008).
文摘Methanol,produced from carbon dioxide,natural gas,and biomass,has drawn increasing attention as a promising green carbon feedstock for biomanufacturing due to its sustainable and energy-rich properties.Nicotinamide adenine dinucleotide(NAD^(+))-dependent methanol dehydrogenase(MDH)catalyzes the oxidation of methanol to formaldehyde via NADH generation,providing a highly active C1 intermediate and reducing power for subsequent biosynthesis.However,the unsatisfactory catalytic efficiency and cofactor bias of MDH significantly impede methanol valorization,especially in nicotinamide adenine dinucleotide phosphate(NADP^(+))-dependent biosynthesis.Herein,we employed synthetic NADH and NADPH auxotrophic Escherichia coli strains as growth-coupled selection platforms for the directed evolution of MDH from Bacillus stearothermophilus DSM 2334.NADH or NADPH generated by MDH-catalyzed methanol oxidation enabled the growth of synthetic cofactor auxotrophs,establishing a positive correlation between the cell growth rate and MDH activity.Using this principle,MDH mutants exhibiting a 20-fold improvement in catalytic efficiency(k_(cat)/K_(m))and a 90-fold cofactor specificity switch from NAD^(+)to NADP+without a decrease in specific enzyme activity,were efficiently screened from random and semi-rationally designed libraries.We envision that these mutants will advance methanol valorization and that the synthetic cofactor auxotrophs will serve as versatile selection platforms for the evolution of NAD(P)^(+)-dependent enzymes.
基金the National Key Research and Development Program of China(2018YFA0901500)the National Natural Science Foundation of China(32070083 and 32222004)+2 种基金the Youth Innovation Promotion Association of Chinese Academy of Sciences(2021177)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-008)the Innovation Fund of Haihe Laboratory of Synthetic Biology.
文摘Methanol is a promising one-carbon feedstock for biomanufacturing,which can be sustainably produced from carbon dioxide and natural gas.However,the efficiency of methanol bioconversion is limited by the poor catalytic properties of nicotinamide adenine dinucleotide(NAD^(+))-dependent methanol dehydrogenase(Mdh)that oxidizes methanol to formaldehyde.Herein,the neutrophilic and mesophilic NAD^(+)-dependent Mdh from Bacillus stearothermophilus DSM 2334(Mdh_(Bs))was subjected to directed evolution for enhancing the catalytic activity.The combination of formaldehyde biosensor and Nash assay allowed high-throughput and accurate measurement of formaldehyde and facilitated efficient selection of desired variants.Mdh_(Bs)variants with up to 6.5-fold higher K_(cat)/K_(M)value for methanol were screened from random mutation libraries.The T153 residue that is spatially proximal to the substrate binding pocket has significant influence on enzyme activity.The beneficial T153P mutation changes the interaction network of this residue and breaks theα-helix important for substrate binding into two shortα-helices.Reconstructing the interaction network of T153 with surrounding residues may represent a promising strategy to further improve Mdh_(Bs),and this study provides an efficient strategy for directed evolution of Mdh.
文摘目的系统评价青少年自杀未遂患者的心理体验。方法计算机检索PubMed、CINAHL、PsychInfo、Embase、Web of Science、Cochrane Library、中国知网、万方数据库、维普数据库、中国生物医学文献数据库,筛选有关青少年自杀未遂患者的心理体验的质性研究,检索时限为建库至2022年7月。采用澳大利亚乔安娜布里格斯研究所循证卫生保健中心制订的质性研究质量评价标准(2016版)进行文献质量评价,采用Meta整合方法对结果进行整合分析。结果共纳入11篇文献,包括4篇现象学研究、6篇描述性质性研究、1篇扎根理论研究。提炼出61个研究结果,归纳成9个新类别,综合成4个整合结果:①思想与情感风暴,包括精神与情绪崩溃、感受爱意并重拾信心;②生活与学业受阻,包括生活目标缺失、学业压力繁重;③冲突的亲密关系,包括家庭摩擦、爱情失利、友情受挫;④调适与应对,包括多元的外部支持、自我调适与感悟。结论护理人员应关注青少年自杀未遂患者的心理体验,引导其缓解生活与学业压力,缓和家庭矛盾,协助患者树立正确的友情观及爱情观,并联合多学科制订长效的干预方案,预防患者再次自杀。
基金Funded by Star Program(No.1804QB1403200)from Science and Technology Commission of Shanghai Municipality。
文摘A novel crystal nucleus-based cement-hardening accelerator was evaluated using various mortar and segment concrete experiments.The mechanism of hardening acceleration was investigated via hydration temperature variation analysis,hydration degree analysis,X-ray diffraction(XRD)and scanning electron microscopy(SEM).In the presence of accelerator,the fluidity loss of mortar was increased after 30 minuites,and a coagulation was also observed.Moreover,based on the image of SEM,the formation of C-S-H gels was enhanced in the early hydration.As a result,the hardening accelerator could significantly boost the early strength of concrete,especially within one day of pouring,and shorten steam curing time to meet the demolding strength.
基金NIH,Grant/Award Number:R03 AG070669Canadian Institutes of Health Research,European Commission’s Seventh Framework Programme grant agreement,Grant/Award Number:HEALTH-F2-2009-223175+11 种基金Cancer Research UK,Grant/Award Numbers:C5047/A7357,C1287/A10118,C1287/A16563,C5047/A3354,C5047/A10692,C16913/A6135The National Institute of Health(NIH)Cancer Post-Cancer GWAS,Grant/Award Number:1 U19 CA 148537-01The National Health and Medical Research Council,Australia,Grant/Award Numbers:126402,209057,251533,396414,450104,504700,504702,504715,623204,940394,614296US National Institutes of Health(NIH),Grant/Award Number:U19 CA 148537Prostate cancer SuscEptibility(ELLIPSE),Grant/Award Number:X01HG007492Center for Inherited Disease Research(CIDR),Grant/Award Number:HHSN268201200008INIH NCI,Grant/Award Number:U01 CA188392European Community’s Seventh Framework Programme,Grant/Award Number:223175Post-Cancer GWAS initiative,Grant/Award Numbers:1U19 CA148537,1U19 CA148065,1U19 CA148112U.S.National Institutes of Health,National Cancer Institute,Grant/Award Numbers:U01-CA98233,U01-CA98710,U01-CA98216,U01-CA98758Swedish Cancer Foundation,Grant/Award Numbers:09-0677,11-484,12-823Swedish Research Council,Swedish Research Council,Grant/Award Numbers:K2010-70X-20430-04-3,2014-2269。
文摘Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative method.Methods:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding strategy.In the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best performance.Using an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual scores.Furthermore,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and controls.Results:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family history.The overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family history.Conclusions:We developed and validated a new PRS which may improve the utility in predicting the risk of developing PCa.Our innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.
