系统复杂性主要体现在种类和数量众多的组分和极其复杂的相互作用关系。结合目前人工智能的发展趋势,分析思考了对于仿真学科研究带来的思维方式变化,形成了对于仿真智能内涵和研究范畴的理解。提出一种复杂系统仿真研究的新模式:“以...系统复杂性主要体现在种类和数量众多的组分和极其复杂的相互作用关系。结合目前人工智能的发展趋势,分析思考了对于仿真学科研究带来的思维方式变化,形成了对于仿真智能内涵和研究范畴的理解。提出一种复杂系统仿真研究的新模式:“以决策为愿景的仿真智能(simulation intelligence based generating decisions,SIGD)”。在SIGD研究模式中,仿真学科中的相似性原理、建模方式以及决策引导模式都与传统仿真中的定位有一定的区别。在这种理念指导下,面向连接的仿真世界观成为一种刻画复杂系统的底层逻辑。以主体、连接和结构为基本元素,采用先自顶向下和自底向上相融合的方式编织以神经网络模型为计算单元的“网真”系统。在该系统中,采用代理建模的方式实现从机理模型到神经网络模型的模型变换,并且基于物理信息神经网络(PINN)和图信息神经网络(GINN)表达整个系统。给出了SIGD的技术实现框架:网真神CE平台作为复杂系统仿真新模式的解决方案,以人流仿真为例,探索了“网真”系统的构建过程。展开更多
Corynebacterium glutamicum is widely used in the production of amino acids.C.glutamicum possesses seven sigma factors,among which SigD is responsible for the transcription of genes involved in the synthesis of mycolic...Corynebacterium glutamicum is widely used in the production of amino acids.C.glutamicum possesses seven sigma factors,among which SigD is responsible for the transcription of genes involved in the synthesis of mycolic acid(MA)and its derivatives,the unique cell envelope of C.glutamicum.To understand the influence of MA synthesis on amino acid production and membrane phenotype of C.glutamicum,the expression of sigD gene and some mycolyltransferase genes,i.e.,cmt1,cop1 and cmt2,were regulated by several growth-regulated promoters in this study.Except for 2 mutant strains of P_(cg3096)-sigD and P_(cg1633)-cop1,the growth and 4-hydroxyisoleucine(4-HIL)titer of most modified strains did not change significantly.But the 4-HIL titer of P_(odhI)-sigD strain increased by 20.73%(142.45±3.69 mM)compared to that of control strain(117.99±0.34 mM).After it was cultivated in bioreactor,4-HIL titer reached 372.56 mM.This may be caused by the increase of MA content,and 17%decrease of cell hydrophobicity and 12%increase of membrane permeability were observed at the exponential phase.In conclusion,we proved that rearrangements in regulation of sigD expression contributed to the improved fermentation performance of C.glutamicum and promoted 4-HIL production.展开更多
Mutation of mevalonate kinase （MVK） is thought to account for most cases of hyperimmunoglobulinemia D syndrome （HIDS） with recurrent fever. However, its mechanism and the relationship between elevated serum immuno...Mutation of mevalonate kinase （MVK） is thought to account for most cases of hyperimmunoglobulinemia D syndrome （HIDS） with recurrent fever. However, its mechanism and the relationship between elevated serum immunoglobulin D （IgD） and the clinical features of HIDS are unclear. In this study, we generated by fusion PCR a vector to express high levels of chimeric secretory IgD （cslgD） specifically in the liver. We then generated seven founder lines of transgenic mice by co-microinjection, and verified them using genomic PCR and Southern blotting. We detected the expression of csIgD by reverse transcription PCR, quantitative PCR, western blotting, and enzyme-linked immunosorbent assays. We demonstrated that csIgD could be specifically and stably expressed in the liver. We used flow cytometry to show that overexpression of csIgD in the bone marrow and spleen cells had no effect on B cell development. Morphologic and anatomical observation of the transgenic mice revealed skin damage, hepatosplenomegaly, and nephromegaly in some transgenic mice; in these mice, pathological sections showed high levels of cell necrosis and protein-like sediments in the liver, spleen, and kidney. We demonstrated that the genomic insertion sites of the transgeues did not disrupt the MVK gene on mouse chromosome 5. This transgenic mouse will be useful to explore the pathogenesis of HIDS.展开更多
文摘系统复杂性主要体现在种类和数量众多的组分和极其复杂的相互作用关系。结合目前人工智能的发展趋势,分析思考了对于仿真学科研究带来的思维方式变化,形成了对于仿真智能内涵和研究范畴的理解。提出一种复杂系统仿真研究的新模式:“以决策为愿景的仿真智能(simulation intelligence based generating decisions,SIGD)”。在SIGD研究模式中,仿真学科中的相似性原理、建模方式以及决策引导模式都与传统仿真中的定位有一定的区别。在这种理念指导下,面向连接的仿真世界观成为一种刻画复杂系统的底层逻辑。以主体、连接和结构为基本元素,采用先自顶向下和自底向上相融合的方式编织以神经网络模型为计算单元的“网真”系统。在该系统中,采用代理建模的方式实现从机理模型到神经网络模型的模型变换,并且基于物理信息神经网络(PINN)和图信息神经网络(GINN)表达整个系统。给出了SIGD的技术实现框架:网真神CE平台作为复杂系统仿真新模式的解决方案,以人流仿真为例,探索了“网真”系统的构建过程。
基金supported by the program of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201904).
文摘Corynebacterium glutamicum is widely used in the production of amino acids.C.glutamicum possesses seven sigma factors,among which SigD is responsible for the transcription of genes involved in the synthesis of mycolic acid(MA)and its derivatives,the unique cell envelope of C.glutamicum.To understand the influence of MA synthesis on amino acid production and membrane phenotype of C.glutamicum,the expression of sigD gene and some mycolyltransferase genes,i.e.,cmt1,cop1 and cmt2,were regulated by several growth-regulated promoters in this study.Except for 2 mutant strains of P_(cg3096)-sigD and P_(cg1633)-cop1,the growth and 4-hydroxyisoleucine(4-HIL)titer of most modified strains did not change significantly.But the 4-HIL titer of P_(odhI)-sigD strain increased by 20.73%(142.45±3.69 mM)compared to that of control strain(117.99±0.34 mM).After it was cultivated in bioreactor,4-HIL titer reached 372.56 mM.This may be caused by the increase of MA content,and 17%decrease of cell hydrophobicity and 12%increase of membrane permeability were observed at the exponential phase.In conclusion,we proved that rearrangements in regulation of sigD expression contributed to the improved fermentation performance of C.glutamicum and promoted 4-HIL production.
基金supported by the National Basic Research Program of China(Grant No.2010CB945300)
文摘Mutation of mevalonate kinase （MVK） is thought to account for most cases of hyperimmunoglobulinemia D syndrome （HIDS） with recurrent fever. However, its mechanism and the relationship between elevated serum immunoglobulin D （IgD） and the clinical features of HIDS are unclear. In this study, we generated by fusion PCR a vector to express high levels of chimeric secretory IgD （cslgD） specifically in the liver. We then generated seven founder lines of transgenic mice by co-microinjection, and verified them using genomic PCR and Southern blotting. We detected the expression of csIgD by reverse transcription PCR, quantitative PCR, western blotting, and enzyme-linked immunosorbent assays. We demonstrated that csIgD could be specifically and stably expressed in the liver. We used flow cytometry to show that overexpression of csIgD in the bone marrow and spleen cells had no effect on B cell development. Morphologic and anatomical observation of the transgenic mice revealed skin damage, hepatosplenomegaly, and nephromegaly in some transgenic mice; in these mice, pathological sections showed high levels of cell necrosis and protein-like sediments in the liver, spleen, and kidney. We demonstrated that the genomic insertion sites of the transgeues did not disrupt the MVK gene on mouse chromosome 5. This transgenic mouse will be useful to explore the pathogenesis of HIDS.
