The surrounding geological conditions and supporting structures of underground engineering are often updated during construction,and these updates require repeated numerical modeling.To improve the numerical modeling ...The surrounding geological conditions and supporting structures of underground engineering are often updated during construction,and these updates require repeated numerical modeling.To improve the numerical modeling efficiency of underground engineering,a modularized and parametric modeling cloud server is developed by using Python codes.The basic framework of the cloud server is as follows:input the modeling parameters into the web platform,implement Rhino software and FLAC3D software to model and run simulations in the cloud server,and return the simulation results to the web platform.The modeling program can automatically generate instructions that can run the modeling process in Rhino based on the input modeling parameters.The main modules of the modeling program include modeling the 3D geological structures,the underground engineering structures,and the supporting structures as well as meshing the geometric models.In particular,various cross-sections of underground caverns are crafted as parametricmodules in themodeling program.Themodularized and parametric modeling program is used for a finite element simulation of the underground powerhouse of the Shuangjiangkou Hydropower Station.This complicatedmodel is rapidly generated for the simulation,and the simulation results are reasonable.Thus,this modularized and parametric modeling program is applicable for three-dimensional finite element simulations and analyses.展开更多
The new economy,featuring new technology,new industry,new business models,and new patterns,has necessitated the development of new requirements for higher engineering education.This paper analyzes the general quality ...The new economy,featuring new technology,new industry,new business models,and new patterns,has necessitated the development of new requirements for higher engineering education.This paper analyzes the general quality standards of engineering specialists and the way typical universities are responding to new economy worldwide.It also examines how to develop an appropriate curriculum for engineering undergraduates in new economy in terms of curriculum system,organizational teaching,curriculum content,teaching methods,and curriculum evaluation.展开更多
Vitamin B_(12)is a complex compound synthesized by microorganisms.The industrial production of vitamin B_(12)relies on specific microbial fermentation processes.E.coli has been utilized as a host for the de novo biosy...Vitamin B_(12)is a complex compound synthesized by microorganisms.The industrial production of vitamin B_(12)relies on specific microbial fermentation processes.E.coli has been utilized as a host for the de novo biosynthesis of vitamin B_(12),incorporating approximately 30 heterologous genes.However,a metabolic imbalance in the intricate pathway significantly limits vitamin B_(12)production.In this study,we employed multivariate modular metabolic engineering to enhance vitamin B_(12)production in E.coli by manipulating two modules comprising a total of 10 genes within the vitamin B_(12)biosynthetic pathway.These two modules were integrated into the chromosome of a chassis cell,regulated by T7,J23119,and J23106 promoters to achieve combinatorial pathway optimization.The highest vitamin B_(12)titer was attained by engineering the two modules controlled by J23119 and T7 promoters.The inclusion of yeast powder to the fermentation medium increased the vitamin B_(12)titer to 1.52 mg/L.This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain’s isopropyl-β-D-1-thiogalactopyranoside(IPTG)tolerance.Ultimately,vitamin B_(12)titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter.The strategies reported herein will expedite the development of industry-scale vitamin B_(12)production utilizing E.coli.展开更多
Recently the integrated modular avionics （IMA） architecture which introduces the concept of resource partitioning becomes popular as an alternative to the traditional federated architecture. A novel hierarchical app...Recently the integrated modular avionics （IMA） architecture which introduces the concept of resource partitioning becomes popular as an alternative to the traditional federated architecture. A novel hierarchical approach is proposed to solve the resource allocation problem for IMA systems in distributed environments. Firstly, the worst case response time of tasks with arbitrary deadlines is analyzed for the two-level scheduler. Then, the hierarchical resource allocation approach is presented in two levels. At the platform level, a task assignment algorithm based on genetic simulated annealing （GSA） is proposed to assign a set of pre-defined tasks to different processing nodes in the form of task groups, so that resources can be allocated as partitions and mapped to task groups. While yielding to all the resource con- straints, the algorithm tries to find an optimal task assignment with minimized communication costs and balanced work load. At the node level, partition parameters are optimized, so that the computational resource can be allocated further. An example is shown to illustrate the hierarchal resource allocation approach and manifest the validity. Simulation results comparing the performance of the proposed GSA with that of traditional genetic algorithms are presented in the context of task assignment in IMA systems.展开更多
Co-culture engineering is an emerging approach for microbial biosynthesis of a variety of biochemicals.In this study,E.coli-E.coli co-cultures were developed for heterologous biosynthesis of the natural product naring...Co-culture engineering is an emerging approach for microbial biosynthesis of a variety of biochemicals.In this study,E.coli-E.coli co-cultures were developed for heterologous biosynthesis of the natural product naringenin.The co-cultures were composed of two independent E.coli strains dedicated to functional expression of different portions of the biosynthetic pathway,respectively.The co-culture biosynthesis was optimized by investigating the effect of carbon source,E.coli strain selection,timing of IPTG induction and the inoculation ratio between the co-culture strains.Compared with the monoculture strategy,the utilization of the designed co-cultures significantly improved the naringenin production,largely due to the reduction of metabolic stress,employment of proper hosts for improving pathway enzyme activities,and flexible adjustment of the relative biosynthetic strength between the coculture strains.The findings of this study extend the applicability of co-culture engineering in complex natural product biosynthesis.展开更多
Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally ...Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally unfriendly chemical synthesis processes,these compounds are not readily accessible.Herein,one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes.Three types of efficiently postmodifying modular strains were engineered by employing methyltransferases,prenyltransferase,and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules.Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes.Especially,a prenylated bibenzyl derivative(12)was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke.RNA-seq,quantitative RT-PCR,and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor,mitochondria associated 3(Aifm3),suggesting that Aifm3 might be a new target in ischemic stroke therapy.This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.展开更多
基金The Construction S&T Project of the Department of Transportation of Sichuan Province(Grant No.2023A02)the National Natural Science Foundation of China(No.52109135).
文摘The surrounding geological conditions and supporting structures of underground engineering are often updated during construction,and these updates require repeated numerical modeling.To improve the numerical modeling efficiency of underground engineering,a modularized and parametric modeling cloud server is developed by using Python codes.The basic framework of the cloud server is as follows:input the modeling parameters into the web platform,implement Rhino software and FLAC3D software to model and run simulations in the cloud server,and return the simulation results to the web platform.The modeling program can automatically generate instructions that can run the modeling process in Rhino based on the input modeling parameters.The main modules of the modeling program include modeling the 3D geological structures,the underground engineering structures,and the supporting structures as well as meshing the geometric models.In particular,various cross-sections of underground caverns are crafted as parametricmodules in themodeling program.Themodularized and parametric modeling program is used for a finite element simulation of the underground powerhouse of the Shuangjiangkou Hydropower Station.This complicatedmodel is rapidly generated for the simulation,and the simulation results are reasonable.Thus,this modularized and parametric modeling program is applicable for three-dimensional finite element simulations and analyses.
基金This research was supported by Exploration and practice of specialty structure adjustment under the background of integration of science and education,Teaching and research project of Qilu University of Technology(Shandong Academy of Sciences)in 2018,Reform and practice of collaborative education mode of mechanical specialty in local colleges and universities under the background of integration of science and education,Teaching and research project of Shandong Province in 2018.
文摘The new economy,featuring new technology,new industry,new business models,and new patterns,has necessitated the development of new requirements for higher engineering education.This paper analyzes the general quality standards of engineering specialists and the way typical universities are responding to new economy worldwide.It also examines how to develop an appropriate curriculum for engineering undergraduates in new economy in terms of curriculum system,organizational teaching,curriculum content,teaching methods,and curriculum evaluation.
基金supported by the National Key R&D Program of China(2018YFA0903700)the National Natural Science Foundation of China(22178372,22208367)+2 种基金National Science Fund for Distinguished Young Scholars(22325807)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-011,TSBICIP-CXRC-055,TSBICIP-PTJJ-007)Youth Innovation Promotion Association,Chinese Academy of Sciences(2020182).
文摘Vitamin B_(12)is a complex compound synthesized by microorganisms.The industrial production of vitamin B_(12)relies on specific microbial fermentation processes.E.coli has been utilized as a host for the de novo biosynthesis of vitamin B_(12),incorporating approximately 30 heterologous genes.However,a metabolic imbalance in the intricate pathway significantly limits vitamin B_(12)production.In this study,we employed multivariate modular metabolic engineering to enhance vitamin B_(12)production in E.coli by manipulating two modules comprising a total of 10 genes within the vitamin B_(12)biosynthetic pathway.These two modules were integrated into the chromosome of a chassis cell,regulated by T7,J23119,and J23106 promoters to achieve combinatorial pathway optimization.The highest vitamin B_(12)titer was attained by engineering the two modules controlled by J23119 and T7 promoters.The inclusion of yeast powder to the fermentation medium increased the vitamin B_(12)titer to 1.52 mg/L.This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain’s isopropyl-β-D-1-thiogalactopyranoside(IPTG)tolerance.Ultimately,vitamin B_(12)titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter.The strategies reported herein will expedite the development of industry-scale vitamin B_(12)production utilizing E.coli.
基金supported by the National Natural Science Foundation of China (60879024)
文摘Recently the integrated modular avionics （IMA） architecture which introduces the concept of resource partitioning becomes popular as an alternative to the traditional federated architecture. A novel hierarchical approach is proposed to solve the resource allocation problem for IMA systems in distributed environments. Firstly, the worst case response time of tasks with arbitrary deadlines is analyzed for the two-level scheduler. Then, the hierarchical resource allocation approach is presented in two levels. At the platform level, a task assignment algorithm based on genetic simulated annealing （GSA） is proposed to assign a set of pre-defined tasks to different processing nodes in the form of task groups, so that resources can be allocated as partitions and mapped to task groups. While yielding to all the resource con- straints, the algorithm tries to find an optimal task assignment with minimized communication costs and balanced work load. At the node level, partition parameters are optimized, so that the computational resource can be allocated further. An example is shown to illustrate the hierarchal resource allocation approach and manifest the validity. Simulation results comparing the performance of the proposed GSA with that of traditional genetic algorithms are presented in the context of task assignment in IMA systems.
基金The authors gratefully acknowledge Professor Matthews Koffas(Rensselaer Polytechnic Institute)and Professor Gregory Stephanopoulos(Massachusetts Institute of Technology)for the generous gift of plasmids pOM-PhCHS-MsCHI,pCDF-trc-RgTAL^syn-Pc4CL^syn and pCA1 in support of this study.This work is supported by startup research funds from Rutgers,The State University of New Jersey.Zhenghong Li is grateful for the Ph.D.fellowship from the China Scholarship Council.
文摘Co-culture engineering is an emerging approach for microbial biosynthesis of a variety of biochemicals.In this study,E.coli-E.coli co-cultures were developed for heterologous biosynthesis of the natural product naringenin.The co-cultures were composed of two independent E.coli strains dedicated to functional expression of different portions of the biosynthetic pathway,respectively.The co-culture biosynthesis was optimized by investigating the effect of carbon source,E.coli strain selection,timing of IPTG induction and the inoculation ratio between the co-culture strains.Compared with the monoculture strategy,the utilization of the designed co-cultures significantly improved the naringenin production,largely due to the reduction of metabolic stress,employment of proper hosts for improving pathway enzyme activities,and flexible adjustment of the relative biosynthetic strength between the coculture strains.The findings of this study extend the applicability of co-culture engineering in complex natural product biosynthesis.
基金supported by the National Key Research and Development Program of China(2020YFA0908000)CAMS Innovation fund for Medical Sciences(CIFMS-2021-I2M1-028 and CIFMS-2021-I2M-1-029,China)Beijing Key Laboratory of non-Clinical Drug Metabolism and PK/PD Study(Z141102004414062,China)。
文摘Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally unfriendly chemical synthesis processes,these compounds are not readily accessible.Herein,one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes.Three types of efficiently postmodifying modular strains were engineered by employing methyltransferases,prenyltransferase,and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules.Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes.Especially,a prenylated bibenzyl derivative(12)was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke.RNA-seq,quantitative RT-PCR,and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor,mitochondria associated 3(Aifm3),suggesting that Aifm3 might be a new target in ischemic stroke therapy.This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.
