The construction of complex synthetic gene circuits with predetermined and reliable output depends on orthogonal regulatory parts that do not inadvertently interfere with the host machinery or with other circuit compo...The construction of complex synthetic gene circuits with predetermined and reliable output depends on orthogonal regulatory parts that do not inadvertently interfere with the host machinery or with other circuit components.Previously,extracytoplasmic function sigma factors(ECFs),a diverse group of alternative sigma factors with distinct promoter specificities,were shown to have great potential as context-independent regulators,but so far,they have only been used in a few model species.Here,we show that the alphaproteobacterium Sinorhizobium meliloti,which has been proposed as a plant-associated bacterial chassis for synthetic biology,has a similar phylogenetic ECF acceptance range as the gammaproteobacterium Escherichia coli.A common set of orthogonal ECF-based regulators that can be used in both bacterial hosts was identified and used to create 2-step delay circuits.The genetic circuits were implemented in single copy in E.coli by chromosomal integration using an established method that utilizes bacteriophage integrases.In S.meliloti,we demonstrated the usability of single-copy pABC plasmids as equivalent carriers of the synthetic circuits.The circuits were either implemented on a single pABC or modularly distributed on 3 such plasmids.In addition,we provide a toolbox containing pABC plasmids compatible with the Golden Gate(MoClo)cloning standard and a library of basic parts that enable the construction of ECF-based circuits in S.meliloti and in E.coli.This work contributes to building a context-independent and species-overarching ECF-based toolbox for synthetic biology applications.展开更多
Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vit...Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).展开更多
The deep integration of digital technology and the real economy is a vital engine for boosting high-quality growth of the real economy.As a result,it is necessary to investigate the effects of this integration on the ...The deep integration of digital technology and the real economy is a vital engine for boosting high-quality growth of the real economy.As a result,it is necessary to investigate the effects of this integration on the real economy.This paper develops a two-sector model that incorporates the production sector and the technology research and development sector,taking into account both the factor attribute and the technical attribute of digital technology.Digital capital,general capital,skilled labor,and unskilled labor are considered as intermediate inputs in the model.Furthermore,this paper examines the effects of two integration modes,i.e.,factor-based integration and technology-based integration,on the development of the real economy and the biased technical change from a theoretical perspective.Empirical tests are conducted to support the analysis.The findings indicate that both factor-based integration and technology-based integration contribute positively to the development of the real economy,although technology-based integration exhibits diminishing marginal effects.Heterogeneity analysis reveals that factor-based integration plays a more significant role in promoting the development of the real economy in regions with geographical advantages,low levels of human resources,high marketization levels,or low market segmentation.On the other hand,technology-based integration assumes a greater role in facilitating the development of the real economy in regions with geographical disadvantages,low costs on human resources,low marketization levels,or high market segmentation.Further analysis demonstrates that the integration of digital technology and the real economy leads to digital capital-biased technical change and skilled labor-biased technical change.Therefore,it is imperative for the public sector to encourage the expansion of both factor-based integration and technology-based integration in the real economy.Additionally,it is also important to develop a reasonable industry layout plan and enhance the skill level of workers to address the rising demand for relevant factors resulting from changes in the biased technical change.展开更多
Hedge funds have recently become popular because of their low correlation with traditional investments and their ability to generate positive returns with a relatively low volatility.However,a close look at those high...Hedge funds have recently become popular because of their low correlation with traditional investments and their ability to generate positive returns with a relatively low volatility.However,a close look at those high-performing hedge funds raises the questions on whether their performance is truly superior and whether the high management fees are justified.Incurring no alpha costs,passive hedge fund replication strategies raise the question on whether they can similarly perform by improving efficiency at reduced costs.Therefore,this study investigates two different model approaches for the equity long/short strategy,where weighted segmented linear regression models are employed and combined with two-state Markov switching models.The main finding proves a short put option structure,i.e.,short equity market volatility,with the put structure present in all market states.We obtain an evidence that the hedge fund managers decrease their short-volatility profile during turbulent markets.展开更多
基金supported by the ERASynBio program of the Federal Ministry of Education and Research(Germany,grant 031L0010B)the LOEWE program of the State of Hesse(Germany)through funding of the Center for Synthetic Microbiology(SYNMIKRO).
文摘The construction of complex synthetic gene circuits with predetermined and reliable output depends on orthogonal regulatory parts that do not inadvertently interfere with the host machinery or with other circuit components.Previously,extracytoplasmic function sigma factors(ECFs),a diverse group of alternative sigma factors with distinct promoter specificities,were shown to have great potential as context-independent regulators,but so far,they have only been used in a few model species.Here,we show that the alphaproteobacterium Sinorhizobium meliloti,which has been proposed as a plant-associated bacterial chassis for synthetic biology,has a similar phylogenetic ECF acceptance range as the gammaproteobacterium Escherichia coli.A common set of orthogonal ECF-based regulators that can be used in both bacterial hosts was identified and used to create 2-step delay circuits.The genetic circuits were implemented in single copy in E.coli by chromosomal integration using an established method that utilizes bacteriophage integrases.In S.meliloti,we demonstrated the usability of single-copy pABC plasmids as equivalent carriers of the synthetic circuits.The circuits were either implemented on a single pABC or modularly distributed on 3 such plasmids.In addition,we provide a toolbox containing pABC plasmids compatible with the Golden Gate(MoClo)cloning standard and a library of basic parts that enable the construction of ECF-based circuits in S.meliloti and in E.coli.This work contributes to building a context-independent and species-overarching ECF-based toolbox for synthetic biology applications.
文摘Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).
基金the“Study on Appropriate Technological Selection and Driving Force Change in the Transformation and Upgrading of China's Manufacturing Industry under High-Quality Development Orientation,”a program from the National Natural Science Foundation of China(No.71973083)the“Study on Appropriate Technology Selection,New and Old Kinetic Energy Conversion and Dynamic Mechanism of Manufacturing Industry Transformation and Upgrading,”a general humanities and social sciences research program from the Ministry of Education(No.19YJA790016)the“Study on Appropriate Technology Selection and New and Old Kinetic Energy Conversion in Manufacturing Industry Transformation and Upgrading,”a general program from Shandong Provincial Natural Science Foundation(No.ZR2019MG018).
文摘The deep integration of digital technology and the real economy is a vital engine for boosting high-quality growth of the real economy.As a result,it is necessary to investigate the effects of this integration on the real economy.This paper develops a two-sector model that incorporates the production sector and the technology research and development sector,taking into account both the factor attribute and the technical attribute of digital technology.Digital capital,general capital,skilled labor,and unskilled labor are considered as intermediate inputs in the model.Furthermore,this paper examines the effects of two integration modes,i.e.,factor-based integration and technology-based integration,on the development of the real economy and the biased technical change from a theoretical perspective.Empirical tests are conducted to support the analysis.The findings indicate that both factor-based integration and technology-based integration contribute positively to the development of the real economy,although technology-based integration exhibits diminishing marginal effects.Heterogeneity analysis reveals that factor-based integration plays a more significant role in promoting the development of the real economy in regions with geographical advantages,low levels of human resources,high marketization levels,or low market segmentation.On the other hand,technology-based integration assumes a greater role in facilitating the development of the real economy in regions with geographical disadvantages,low costs on human resources,low marketization levels,or high market segmentation.Further analysis demonstrates that the integration of digital technology and the real economy leads to digital capital-biased technical change and skilled labor-biased technical change.Therefore,it is imperative for the public sector to encourage the expansion of both factor-based integration and technology-based integration in the real economy.Additionally,it is also important to develop a reasonable industry layout plan and enhance the skill level of workers to address the rising demand for relevant factors resulting from changes in the biased technical change.
文摘Hedge funds have recently become popular because of their low correlation with traditional investments and their ability to generate positive returns with a relatively low volatility.However,a close look at those high-performing hedge funds raises the questions on whether their performance is truly superior and whether the high management fees are justified.Incurring no alpha costs,passive hedge fund replication strategies raise the question on whether they can similarly perform by improving efficiency at reduced costs.Therefore,this study investigates two different model approaches for the equity long/short strategy,where weighted segmented linear regression models are employed and combined with two-state Markov switching models.The main finding proves a short put option structure,i.e.,short equity market volatility,with the put structure present in all market states.We obtain an evidence that the hedge fund managers decrease their short-volatility profile during turbulent markets.