The existing query expansion(QE) methods cannot find the most users-requested source code version at times due to the over-expansion resulting from noises. To solve this problem, we propose a QE method based on evolvi...The existing query expansion(QE) methods cannot find the most users-requested source code version at times due to the over-expansion resulting from noises. To solve this problem, we propose a QE method based on evolving contexts(EC) that are added/deleted terms and their dependent terms during code evolution. On expanding a query, we appended the added terms as relevant terms, and excluded the deleted terms as noisy terms. We also developed a QE-integrating framework based on the Support Vector Machine(SVM) Ranking, called QESR, to simultaneously integrate multiple QE methods. Our experiment shows that QESR outperforms the state-of-the-art QE methods CodeHow and Query Expansion based on Crowd Knowledge(QECK) by 13%-16% in terms of precision when the first query result is inspected.展开更多
The injection of a high pressure gas into a stagnant liquid pool is the characteristic phenomenon during the expansion phase of a hypothetical core disruptive accident in liquid metal cooled fast reactors. In order to...The injection of a high pressure gas into a stagnant liquid pool is the characteristic phenomenon during the expansion phase of a hypothetical core disruptive accident in liquid metal cooled fast reactors. In order to investigate lots of mechanisms involved in this phase of the accident＇s evolution, an experimental campaign called S GI was performed in 1994 in Forschungszentrum Karlsruhe, now KIT. This campaign consists of nine experiments which have been dedicated to assess the effects of different pressure injection, the nozzle＇s size and the presence of inner confinement in the formation of the rising bubble. Three of these experiments, which were focused on the pressure effects, have now been simulated with SIMMER III code and with FLUENT 6.3, a commercial CFD code. Both codes, despite their different features, have showed a good agreement with the experimental results. In particular, time trend evolutions of pressures and bubble volumes have been well reproduced by simulation. Furthermore, both codes agree on the shape of the bubble, even though they have evidenced same discrepancies with the experimental shape.展开更多
Cysteine chemistry provides a low cost and convenient way for site-specific protein modification.However,recombinant expression of disulfide bonding containing protein with unpaired cysteine is technically challenging...Cysteine chemistry provides a low cost and convenient way for site-specific protein modification.However,recombinant expression of disulfide bonding containing protein with unpaired cysteine is technically challenging and the resulting protein often suffers from significantly reduced yield and activity.Here we used genetic code expansion technique to introduce a surface exposed self-paired dithiol functional group into proteins,which can be selectively reduced to afford active thiols.Two compounds containing self-paired disulfides were synthesized,and their genetic incorporations were validated using green fluorescent proteins(GFP).The compatibility of these self-paired di-thiols with natural disulfide bond was demonstrated using antibody fragment to afford site-specifically labeled antibody.This work provides another valuable building block into the chemical tool-box for site-specific labeling of proteins containing internal disulfides.展开更多
In nature,a limited,conservative set of amino acids are utilized to synthesize proteins.Genetic code expansion technique reassigns codons and incorporates noncanonical amino acids(ncAAs)through orthogonal aminoacyltRN...In nature,a limited,conservative set of amino acids are utilized to synthesize proteins.Genetic code expansion technique reassigns codons and incorporates noncanonical amino acids(ncAAs)through orthogonal aminoacyltRNA synthetase(aaRS)/tRNA pairs.The past decade has witnessed the rapid growth in diversity and scope for therapeutic applications of this technology.Here,we provided an update on the recent progress using genetic code expansion in the following areas:antibody-drug conjugates(ADCs),bispecific antibodies(BsAb),immunotherapies,long-lasting protein therapeutics,biosynthesized peptides,engineered viruses and cells,as well as other therapeutic related applications,where the technique was used to elucidate the mechanisms of biotherapeutics and drug targets.展开更多
Unnatural amino acids(UAAs)have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to proteins.In eukaryotes,genetic code expansio...Unnatural amino acids(UAAs)have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to proteins.In eukaryotes,genetic code expansion(GCE)enables the incorporation of UAAs and facilitates posttranscriptional modification(PTM),which is not feasible in prokaryotic systems.GCE is also a powerful tool for cell or animal imaging,the monitoring of protein interactions in target cells,drug development,and switch regulation.Therefore,there is keen interest in utilizing GCE in eukaryotic systems.This review provides an overview of the application of GCE in eukaryotic systems and discusses current challenges that need to be addressed.展开更多
基金Supported by the Science and Technology Project of Jiangxi Education Department(GJJ161151)the School-Level Team Building Project(JXTD1404)
文摘The existing query expansion(QE) methods cannot find the most users-requested source code version at times due to the over-expansion resulting from noises. To solve this problem, we propose a QE method based on evolving contexts(EC) that are added/deleted terms and their dependent terms during code evolution. On expanding a query, we appended the added terms as relevant terms, and excluded the deleted terms as noisy terms. We also developed a QE-integrating framework based on the Support Vector Machine(SVM) Ranking, called QESR, to simultaneously integrate multiple QE methods. Our experiment shows that QESR outperforms the state-of-the-art QE methods CodeHow and Query Expansion based on Crowd Knowledge(QECK) by 13%-16% in terms of precision when the first query result is inspected.
文摘The injection of a high pressure gas into a stagnant liquid pool is the characteristic phenomenon during the expansion phase of a hypothetical core disruptive accident in liquid metal cooled fast reactors. In order to investigate lots of mechanisms involved in this phase of the accident＇s evolution, an experimental campaign called S GI was performed in 1994 in Forschungszentrum Karlsruhe, now KIT. This campaign consists of nine experiments which have been dedicated to assess the effects of different pressure injection, the nozzle＇s size and the presence of inner confinement in the formation of the rising bubble. Three of these experiments, which were focused on the pressure effects, have now been simulated with SIMMER III code and with FLUENT 6.3, a commercial CFD code. Both codes, despite their different features, have showed a good agreement with the experimental results. In particular, time trend evolutions of pressures and bubble volumes have been well reproduced by simulation. Furthermore, both codes agree on the shape of the bubble, even though they have evidenced same discrepancies with the experimental shape.
基金financially supported by National Key Research and Development Program of China (No.2016YFA0201400)the National Natural Science Foundation of China (No.21778005)+1 种基金Peking University Health Science Center (Nos.BMU20160537 andBMU2017QQ006)the Youth Thousand-Talents Program of China for support
文摘Cysteine chemistry provides a low cost and convenient way for site-specific protein modification.However,recombinant expression of disulfide bonding containing protein with unpaired cysteine is technically challenging and the resulting protein often suffers from significantly reduced yield and activity.Here we used genetic code expansion technique to introduce a surface exposed self-paired dithiol functional group into proteins,which can be selectively reduced to afford active thiols.Two compounds containing self-paired disulfides were synthesized,and their genetic incorporations were validated using green fluorescent proteins(GFP).The compatibility of these self-paired di-thiols with natural disulfide bond was demonstrated using antibody fragment to afford site-specifically labeled antibody.This work provides another valuable building block into the chemical tool-box for site-specific labeling of proteins containing internal disulfides.
基金We thank the following agencies for financial support on related ongoing projects in our lab:National Key Research and Development Program of China(No.2016YFA0201400)the National Natural Science Foundation of China(21778005)+1 种基金Peking University Health Science Center(BMU20160537 and BMU2017QQ006)Youth Thousand-Talents Program of China。
文摘In nature,a limited,conservative set of amino acids are utilized to synthesize proteins.Genetic code expansion technique reassigns codons and incorporates noncanonical amino acids(ncAAs)through orthogonal aminoacyltRNA synthetase(aaRS)/tRNA pairs.The past decade has witnessed the rapid growth in diversity and scope for therapeutic applications of this technology.Here,we provided an update on the recent progress using genetic code expansion in the following areas:antibody-drug conjugates(ADCs),bispecific antibodies(BsAb),immunotherapies,long-lasting protein therapeutics,biosynthesized peptides,engineered viruses and cells,as well as other therapeutic related applications,where the technique was used to elucidate the mechanisms of biotherapeutics and drug targets.
基金This work was supported by the National Key R&D Program of China(Nos.2019YFA0904200 and 2019YFA0906100)the National Natural Science Foundation of China(No.32171464)Shenzhen Science and Technology Innovation Program(JCYJ20180504165501371).
文摘Unnatural amino acids(UAAs)have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to proteins.In eukaryotes,genetic code expansion(GCE)enables the incorporation of UAAs and facilitates posttranscriptional modification(PTM),which is not feasible in prokaryotic systems.GCE is also a powerful tool for cell or animal imaging,the monitoring of protein interactions in target cells,drug development,and switch regulation.Therefore,there is keen interest in utilizing GCE in eukaryotic systems.This review provides an overview of the application of GCE in eukaryotic systems and discusses current challenges that need to be addressed.
