For the incompressible Navier Stokes equations, a new artificial diffusion factor is put forward in the Streamline Upwind/Petrov Galerkin formulation. The corresponding formulae of finite element methods are derived ...For the incompressible Navier Stokes equations, a new artificial diffusion factor is put forward in the Streamline Upwind/Petrov Galerkin formulation. The corresponding formulae of finite element methods are derived in Newton Raphson form, in which velocity and pressure are iterated synchronously. An element with nine nodes satisfying inf sup condition is established, which has a parabolic velocity interpolation and linear pressure distribution. Four numerical examples are presented, and solutions obtained demonstrate the effectivity of the method proposed.展开更多
The production of androst-4-ene-3,17-dione(AD)by the steroidal microbial cell factory requires transcription factors(TFs)to participate in metabolic regulation.However,microbial cell factory lacks effective TFs that c...The production of androst-4-ene-3,17-dione(AD)by the steroidal microbial cell factory requires transcription factors(TFs)to participate in metabolic regulation.However,microbial cell factory lacks effective TFs that can respond to AD in its metabolic pathway.Additionally,finding and obtaining natural TFs that specifically respond to AD is a complex and onerous task.In this study,we devised an artificial TF that responds to AD,termed AdT,based on structure-guided molecular dynamics(MD)simulation.According to MD analysis of the conformational changes of AdT after binding to AD,an LBD in which the N-and C-termini exhibited convergence tendencies was used as a microswitch to guide the assembly of a DNA-binding domain lexA,a linker(GGGGS)2,and a transcription activation domain B42 into an artificial TF.As a proof of design,a AD biosensor was designed and constructed in yeast on the basis of the ligand-binding domain(LBD)of hormone receptor.In addition,the transcription factor activity of AdT was increased by 1.44-fold for its variant F320Y.Overall,we created non-natural TF elements for AD microbial cell factory,and expected that the design TF strategy will be applied to running in parallel to the signaling machinery of the host cell.展开更多
Dear Editor,DCaLC2CO Artificial transcription factors(ATFs),which are composed of programmable DNA-binding proteins and transcription activation domains(TADs),have revolutionized the synthetic transcriptional control ...Dear Editor,DCaLC2CO Artificial transcription factors(ATFs),which are composed of programmable DNA-binding proteins and transcription activation domains(TADs),have revolutionized the synthetic transcriptional control of genes(Sang et al.,2024).The clustered,regularly interspaced short palindromic repeats(CRiSPR)systems have been repurposed as ATFs(Tanenbaum et al.,2014).展开更多
文摘For the incompressible Navier Stokes equations, a new artificial diffusion factor is put forward in the Streamline Upwind/Petrov Galerkin formulation. The corresponding formulae of finite element methods are derived in Newton Raphson form, in which velocity and pressure are iterated synchronously. An element with nine nodes satisfying inf sup condition is established, which has a parabolic velocity interpolation and linear pressure distribution. Four numerical examples are presented, and solutions obtained demonstrate the effectivity of the method proposed.
基金supported by the Scientific Research Foundation of the Higher Education Institutions of Anhui Province,China(Grant No.2022AH050971)Key R&D and Achievement Transformation Projects(2023yf096)the Scientific Research Start-up Fund for Talents of Anhui Polytechnic University(2022YQQ064).
文摘The production of androst-4-ene-3,17-dione(AD)by the steroidal microbial cell factory requires transcription factors(TFs)to participate in metabolic regulation.However,microbial cell factory lacks effective TFs that can respond to AD in its metabolic pathway.Additionally,finding and obtaining natural TFs that specifically respond to AD is a complex and onerous task.In this study,we devised an artificial TF that responds to AD,termed AdT,based on structure-guided molecular dynamics(MD)simulation.According to MD analysis of the conformational changes of AdT after binding to AD,an LBD in which the N-and C-termini exhibited convergence tendencies was used as a microswitch to guide the assembly of a DNA-binding domain lexA,a linker(GGGGS)2,and a transcription activation domain B42 into an artificial TF.As a proof of design,a AD biosensor was designed and constructed in yeast on the basis of the ligand-binding domain(LBD)of hormone receptor.In addition,the transcription factor activity of AdT was increased by 1.44-fold for its variant F320Y.Overall,we created non-natural TF elements for AD microbial cell factory,and expected that the design TF strategy will be applied to running in parallel to the signaling machinery of the host cell.
基金supported by the National Key R&D Program of China(Grant No.2023YFF1204500 to ZB)the National Natural Science Foundation of China(grant No.22308316 to ZB)Fundamental Research Funds for the Central Universities(Grant Nos.226-2025-00043 and 226-2022-00214 to ZB).
文摘Dear Editor,DCaLC2CO Artificial transcription factors(ATFs),which are composed of programmable DNA-binding proteins and transcription activation domains(TADs),have revolutionized the synthetic transcriptional control of genes(Sang et al.,2024).The clustered,regularly interspaced short palindromic repeats(CRiSPR)systems have been repurposed as ATFs(Tanenbaum et al.,2014).
