Purpose-In order to solve the problem of inaccurate calculation of index weights,subjectivity and uncertainty of index assessment in the risk assessment process,this study aims to propose a scientific and reasonable c...Purpose-In order to solve the problem of inaccurate calculation of index weights,subjectivity and uncertainty of index assessment in the risk assessment process,this study aims to propose a scientific and reasonable centralized traffic control(CTC)system risk assessment method.Design/methodologylapproach-First,system-theoretic process analysis(STPA)is used to conduct risk analysis on the CTC system and constructs risk assessment indexes based on this analysis.Then,to enhance the accuracy of weight calculation,the fuzzy analytical hierarchy process(FAHP),fuzzy decision-making trial and evaluation laboratory(FDEMATEL)and entropy weight method are employed to calculate the subjective weight,relative weight and objective weight of each index.These three types of weights are combined using game theory to obtain the combined weight for each index.To reduce subjectivity and uncertainty in the assessment process,the backward cloud generator method is utilized to obtain the numerical character(NC)of the cloud model for each index.The NCs of the indexes are then weighted to derive the comprehensive cloud for risk assessment of the CTC system.This cloud model is used to obtain the CTC system's comprehensive risk assessment.The model's similarity measurement method gauges the likeness between the comprehensive risk assessment cloud and the risk standard cloud.Finally,this process yields the risk assessment results for the CTC system.Findings-The cloud model can handle the subjectivity and fuzziness in the risk assessment process well.The cloud model-based risk assessment method was applied to the CTC system risk assessment of a railway group and achieved good results.Originality/value-This study provides a cloud model-based method for risk assessment of CTC systems,which accurately calculates the weight of risk indexes and uses cloud models to reduce uncertainty and subjectivity in the assessment,achieving effective risk assessment of CTC systems.It can provide a reference and theoretical basis for risk management of the CTC system.展开更多
Ebola virus （EBOV） and Marburg virus （MARV） are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics. T...Ebola virus （EBOV） and Marburg virus （MARV） are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics. To date, there is no specific laboratory diagnostic test in China, while there is a national need to provide differential diagnosis during outbreaks and for instituting acceptable quarantine procedures. In this study, the TaqMan RT-PCR assays targeting the nucleoprotein genes of the Zaire Ebolavirus （ZEBOV） and MARV were developed and their sensitivities and specificities were investigated. Our results indicated that the assays were able to make reliable diagnosis over a wide range of virus copies from 103 to 109, corresponding to the threshold of a standard RNA transcript. The results showed that there were about 101 RNA copies per milliliter of virus culture supernatant, equivalent to 10,000 RNA molecules per infectious virion, suggesting the presence of many non-infectious particles. These data indicated that the TaqMan RT-PCR assays developed in this study will be suitable展开更多
Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for t...Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.展开更多
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus closely related to the human pathogens including yellow fever virus, dengue virus and West Nile virus. There are currently no effective antiviral therap...Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus closely related to the human pathogens including yellow fever virus, dengue virus and West Nile virus. There are currently no effective antiviral therapies for all of the flavivirus and only a few highly effective vaccines are licensed for human use. In this paper, the E protein domain III (DIII) of six heterologous flaviviruses (DENV1-4, WNV and JEV) was expressed in Escherichia coli successfully. The proteins were purified after a solubilization and refolding procedure, characterized by SDS-PAGE and Western blotting. Competitive inhibition showed that all recombinant flavivirus DIII proteins blocked the entry of JEV into BHK-21 cells. Further studies indicated that antibodies induced by the soluble recombinant flavivirus DIII partially protected mice against lethal JEV challenge. These results demonstrated that recombinant flavivirus DIII proteins could inhibit JEV infection competitively, and immunization with proper folding flavivirus DIII induced cross-protection against JEV infection in mice, implying a possible role of DIII for the cross-protection among flavivirus as well as its use in antigens for immunization in animal models.展开更多
Flaviviral NS2B is a required cofactor for NS3 serine protease activity and plays an important role in promoting functional NS2B-NS3 protease configuration and maintaining critical interactions with protease catalysis...Flaviviral NS2B is a required cofactor for NS3 serine protease activity and plays an important role in promoting functional NS2B-NS3 protease configuration and maintaining critical interactions with protease catalysis substrates. The residues D80DDG in West Nile virus (WNV) NS2B are important for protease activity. To investigate the effects of D80DDG in NS2B on protease activity and viral replication, the negatively charged region D80DD and the conserved residue G83 of NS2B were mutated (D80DD/E80EE, D80DD/K80KK, D80DD/A80AA, G83F, G83S, G83D, G83K, and G83A), and NS3 D75A was designated as the negative control. The effects of the mutations on NS2B-NS3 activity, viral translation, and viral RNA replication were analyzed using kinetic analysis of site-directed enzymes and a transient replicon assay. All substitutions resulted in significantly decreased enzyme activity and blocked RNA replication. The negative charge of D80DD is not important for maintaining NS2B function, but side chain changes in G83 have dramatic effects on protease activity and RNA replication. These results demonstrate that NS2B is important for viral replication and that D80DD and G83 substitutions prevent replication; they will be useful for understanding the relationship between NS2B and NS3.展开更多
Dengue virus(DENV) nonstructural protein 1(NS1) is a highly conserved 46-kDa protein that contains 2 glycosylation sites(Asn-130 and Asn-207) and 12 conserved cysteine(Cys) residues. Here, we performed site-directed m...Dengue virus(DENV) nonstructural protein 1(NS1) is a highly conserved 46-kDa protein that contains 2 glycosylation sites(Asn-130 and Asn-207) and 12 conserved cysteine(Cys) residues. Here, we performed site-directed mutagenesis to generate systematic mutants of viral strain TSV01. The results of the subsequent analysis showed that an alanine substitution at the second N-linked glycan Asn-207 in NS1 delayed viral RNA synthesis, reduced virus plaque size, and weakened the cytopathic effect. Three mutants at Cys sites(Cys-4, Cys-55, Cys-291) and a C-terminal deletion(ΔC) mutant significantly impaired RNA synthesis, and consequently abolished viral growth, whereas alanine mutations at Asn-130 and Glu-173 resulted in phenotypes that were similar to the wild-type(WT) virus. Further analysis showed that the Asn-207 mutation slightly delayed viral replication. These results suggest that the three conserved disulfide bonds and the second N-linked glycan in NS1 are required for DENV-2 replication.展开更多
Unexpected delays in train operations can cause a cascade of negative consequences in a high-speed railway system.In such cases,train timetables need to be rescheduled.However,timely and efficient train timetable resc...Unexpected delays in train operations can cause a cascade of negative consequences in a high-speed railway system.In such cases,train timetables need to be rescheduled.However,timely and efficient train timetable rescheduling is still a challenging problem due to its modeling difficulties and low optimization efficiency.This paper presents a Transformer-based macroscopic regulation approach which consists of two stages including Transformer-based modeling and policy-based decisionmaking.Firstly,the relationship between various train schedules and operations is described by creating a macroscopic model with the Transformer,providing the better understanding of overall operation in the high-speed railway system.Then,a policy-based approach is used to solve a continuous decision problem after macro-modeling for fast convergence.Extensive experiments on various delay scenarios are conducted.The results demonstrate the effectiveness of the proposed method in comparison to other popular methods.展开更多
We developed a Gaussia luciferase (Gluc) reporter replicon of West Nile virus (WNV) and used it to quantify viral translation and RNA replication. The advantage of the Gluc replicon is that Gaussia luciferase is secre...We developed a Gaussia luciferase (Gluc) reporter replicon of West Nile virus (WNV) and used it to quantify viral translation and RNA replication. The advantage of the Gluc replicon is that Gaussia luciferase is secreted into the culture medium from cells transfected with Gluc replicon RNA, and the medium can be assayed directly for luciferase activity. Using a known Flavivirus inhibitor (NITD008), we demonstrated that the Gluc-WNV replicon could be used for antiviral screening. The Gluc-WNV-Rep will be useful for research in antiviral drug development programs, as well as for studying viral replication and pathogenesis of WNV.展开更多
Purpose–The intelligent Central Traffic Control(CTC)system plays a vital role in establishing an intelligent high-speed railway(HSR)system.As the core of HSR transportation command,the intelligent CTC system is a new...Purpose–The intelligent Central Traffic Control(CTC)system plays a vital role in establishing an intelligent high-speed railway(HSR)system.As the core of HSR transportation command,the intelligent CTC system is a new HSR dispatching command system that integrates the widely used CTC in China with the practical service requirements of intelligent dispatching.This paper aims to propose key technologies and applications for intelligent dispatching command in HSR in China.Design/methodology/approach–This paper first briefly introduces the functions and configuration of the intelligent CTC system.Some new servers,terminals and interfaces are introduced,which are plan adjustment server/terminal,interface for automatic train operation(ATO),interface for Dynamic Monitoring System of Train Control Equipment(DMS),interface for Power Supervisory Control and Data Acquisition(PSCADA),interface for Disaster Monitoring,etc.Findings–The key technologies applied in the intelligent CTC system include automatic adjustment of train operation plans,safety control of train routes and commands,traffic information data platform,integrated simulation of traffic dispatching and ATO function.These technologies have been applied in the Beijing-Zhangjiakou HSR,which commenced operations at the end of 2019.Implementing these key intelligent functions has improved the train dispatching command capacity,ensured the safe operation of intelligent HSR,reduced the labor intensity of dispatching operators and enhanced the intelligence level of China’s dispatching system.Originality/value–This paper provides further challenges and research directions for the intelligent dispatching command of HSR.To achieve the objectives,new measures need to be conducted,including the development of advanced technologies for intelligent dispatching command,coping with new requirements with the development of China’s railway signaling system,the integration of traffic dispatching and train control and the application of AI and data-driven modeling and methods.展开更多
Purpose–This paper aims to propose a train timetable rescheduling(TTR)approach from the perspective of multi-train tracking optimization based on the mutual spatiotemporal information in the high-speed railway signal...Purpose–This paper aims to propose a train timetable rescheduling(TTR)approach from the perspective of multi-train tracking optimization based on the mutual spatiotemporal information in the high-speed railway signaling system.Design/methodology/approach–Firstly,a single-train trajectory optimization(STTO)model is constructed based on train dynamics and operating conditions.The train kinematics parameters,including acceleration,speed and time at each position,are calculated to predict the arrival times in the train timetable.A STTO algorithm is developed to optimize a single-train time-efficient driving strategy.Then,a TTR approach based on multi-train tracking optimization(TTR-MTTO)is proposed with mutual information.The constraints of temporary speed restriction(TSR)and end of authority are decoupled to calculate the tracking trajectory of the backward tracking train.The multi-train trajectories at each position are optimized to generate a timeefficient train timetable.Findings–The numerical experiment is performed on the Beijing-Tianjin high-speed railway line and CR400AF.The STTO algorithm predicts the train’s planned arrival time to calculate the total train delay(TTD).As for the TSR scenario,the proposed TTR-MTTO can reduce TTD by 60.60%compared with the traditional TTR approach with dispatchers’experience.Moreover,TTR-MTTO can optimize a time-efficient train timetable to help dispatchers reschedule trains more reasonably.Originality/value–With the cooperative relationship and mutual information between train rescheduling and control,the proposed TTR-MTTO approach can automatically generate a time-efficient train timetable to reduce the total train delay and the work intensity of dispatchers.展开更多
The sharing of pathogens is of great significance for the continuous and comprehensive testing and monitoring of viral samples,vaccine and drug development,and the study of drug resistance and mutability of viral samp...The sharing of pathogens is of great significance for the continuous and comprehensive testing and monitoring of viral samples,vaccine and drug development,and the study of drug resistance and mutability of viral samples.This paper reviews the current legal framework in the field of pathogen sharing,analyzes existing issues,and proposes recommendations to improve the legal framework of pathogen sharing.展开更多
Mosquitoes are classified into approximately 3500 species and further grouped into 41 genera.Epidemiologically,they are considered to be among the most important disease vectors in the world and they can harbor a wide...Mosquitoes are classified into approximately 3500 species and further grouped into 41 genera.Epidemiologically,they are considered to be among the most important disease vectors in the world and they can harbor a wide variety of viruses.Several mosquito viruses are considered to be of significant medical importance and can cause serious public health issues throughout the world.Such viruses are Japanese encephalitis virus(JEV),dengue virus(DENV),chikungunya virus(CHIKV),and Zika virus(ZIKV).Others are the newly recognized mosquito viruses such as Banna virus(BAV)and Yunnan orbivirus(YNOV)with unclear medical significance.The remaining mosquito viruses are those that naturally infect mosquitoes but do not appear to infect humans or other vertebrates.With the continuous development and improvement of mosquito and mosquito-associated virus surveillance systems in China,many novel mosquito-associated viruses have been discovered in recent years.This review aims to systematically outline the history,characteristics,distribution,and/or current epidemic status of mosquito-associated viruses in China.展开更多
In this study, a perforated pontoon floating breakwater（FB） consisting of an impermeable plate and a perforated plate was designed to untangle the effect of a perforated plate on wave transmission and hydrodynamic p...In this study, a perforated pontoon floating breakwater（FB） consisting of an impermeable plate and a perforated plate was designed to untangle the effect of a perforated plate on wave transmission and hydrodynamic performance of floating breakwater. A series of 2-D physical model experiments were conducted to measure the wave transmission coefficient, tension acting on the mooring line, and motion response of FB under a regular wave. The experimental results of the motion responses and mooring lines indicated that the new perforated plate was evidently effective. Furthermore, the study also discussed and analyzed the influence of the perforated plate on transmission coefficients. The experimental results showed that the new perforated plate did not lead to obvious improvement in the transmission performance展开更多
Wastewater-based epidemiology(WBE)has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community.Congruently,SARS-Co V-2,the etiologic agent of COVID-19,has...Wastewater-based epidemiology(WBE)has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community.Congruently,SARS-Co V-2,the etiologic agent of COVID-19,has been demonstrated to infect the gastrointestinal tissues,and be shed in feces.In the present study,SARS-Co V-2 RNA was concentrated from wastewater,sludge,surface water,ground water,sediment,and soil samples of municipal and hospital wastewater systems and related environments in Wuhan during the COVID-19 middle and low risk periods,and the viral RNA copies quantified using reverse transcription quantitative polymerase chain reaction(RT-q PCR).From the findings of this study,during the middle risk period,one influent sample and three secondary effluents collected from waste water treatment plant 2,as well as two samples from Jinyintan Hospital wastewater system influent were SARS-Co V-2 RNA positive.One sludge sample collected from Guanggu Branch of Tongji Hospital,which was obtained during the low risk period,was also positive for SARS-Co V-2 RNA.These study findings demonstrate the significance of WBE in continuous surveillance of SARS-Co V-2 at the community level,even when the COVID-19 prevalence is low.Overall,this study can be used as an important reference for contingency management of wastewater treatment plants and COVID-19 prevention and control departments of Wuhan.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2), the etiologic agent of COVID-19, is an enveloped,positive-sense single-stranded RNA virus that first discovered in December 2019 from a seafood m...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2), the etiologic agent of COVID-19, is an enveloped,positive-sense single-stranded RNA virus that first discovered in December 2019 from a seafood market in Wuhan, China(Zhou et al. 2020).展开更多
Vast viruses are thought to be associated with mosquitoes.Anopheles sinensis,Armigeres subalbatus,Culex quinquefasciatus,and Culex tritaeniorhynchus are very common mosquito species in China,and whether the virome str...Vast viruses are thought to be associated with mosquitoes.Anopheles sinensis,Armigeres subalbatus,Culex quinquefasciatus,and Culex tritaeniorhynchus are very common mosquito species in China,and whether the virome structure in each species is species-specific has not been evaluated.In this study,a total of 2222 mosquitoes were collected from the same geographic location,and RNAs were sequenced using the Illumina Miseq platform.After querying to the Refseq database,a total of 3,435,781,2,223,509,5,727,523,and 6,387,867 paired-end reads were classified under viral sequences from An.sinensis,Ar.subalbatus,Cx.quinquefasciatus,and Cx.tritaeniorhynchus,respectively,with the highest prevalence of virus-associated reads being observed in Cx.quinquefasciatus.The metagenomic comparison analysis showed that the virus-related reads were distributed across 26 virus families,together with an unclassified group of viruses.Anelloviridae,Circoviridae,Genomoviridae,Iridoviridae,Mesoniviridae,Microviridae,Myoviridae,Parvoviridae,Phenuiviridae,and Podoviridae were the top ten significantly different viral families among the four species.Further analysis reveals that the virome is species-specific in four mosquito samples,and several viral sequences which maybe belong to novel viruses are discovered for the first time in those mosquitoes.This investigation provides a basis for a comprehensive knowledge on the mosquito virome status in China.展开更多
基金National Natural Science Foundation of China under Grant 62203468Technological Research and Development Program of China State Railway Group Co.,Ltd.under Grant J2023G007+2 种基金Young Elite Scientist Sponsorship Program by China Association for Science and Technology(CAST)under Grant 2022QNRC001Youth Talent Program Supported by China Railway SocietyResearch Program of Beijing Hua-Tie Information Technology Corporation Limited under Grant 2023HT02.
文摘Purpose-In order to solve the problem of inaccurate calculation of index weights,subjectivity and uncertainty of index assessment in the risk assessment process,this study aims to propose a scientific and reasonable centralized traffic control(CTC)system risk assessment method.Design/methodologylapproach-First,system-theoretic process analysis(STPA)is used to conduct risk analysis on the CTC system and constructs risk assessment indexes based on this analysis.Then,to enhance the accuracy of weight calculation,the fuzzy analytical hierarchy process(FAHP),fuzzy decision-making trial and evaluation laboratory(FDEMATEL)and entropy weight method are employed to calculate the subjective weight,relative weight and objective weight of each index.These three types of weights are combined using game theory to obtain the combined weight for each index.To reduce subjectivity and uncertainty in the assessment process,the backward cloud generator method is utilized to obtain the numerical character(NC)of the cloud model for each index.The NCs of the indexes are then weighted to derive the comprehensive cloud for risk assessment of the CTC system.This cloud model is used to obtain the CTC system's comprehensive risk assessment.The model's similarity measurement method gauges the likeness between the comprehensive risk assessment cloud and the risk standard cloud.Finally,this process yields the risk assessment results for the CTC system.Findings-The cloud model can handle the subjectivity and fuzziness in the risk assessment process well.The cloud model-based risk assessment method was applied to the CTC system risk assessment of a railway group and achieved good results.Originality/value-This study provides a cloud model-based method for risk assessment of CTC systems,which accurately calculates the weight of risk indexes and uses cloud models to reduce uncertainty and subjectivity in the assessment,achieving effective risk assessment of CTC systems.It can provide a reference and theoretical basis for risk management of the CTC system.
基金Supported by Important National Science&Technology Specific Projects(2009ZX10004-504,2009ZX09301-014)National Natural Science Foundation of China(81072675)
文摘Ebola virus （EBOV） and Marburg virus （MARV） are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates and there is currently no licensed vaccine or therapeutics. To date, there is no specific laboratory diagnostic test in China, while there is a national need to provide differential diagnosis during outbreaks and for instituting acceptable quarantine procedures. In this study, the TaqMan RT-PCR assays targeting the nucleoprotein genes of the Zaire Ebolavirus （ZEBOV） and MARV were developed and their sensitivities and specificities were investigated. Our results indicated that the assays were able to make reliable diagnosis over a wide range of virus copies from 103 to 109, corresponding to the threshold of a standard RNA transcript. The results showed that there were about 101 RNA copies per milliliter of virus culture supernatant, equivalent to 10,000 RNA molecules per infectious virion, suggesting the presence of many non-infectious particles. These data indicated that the TaqMan RT-PCR assays developed in this study will be suitable
基金supported by Important National Science & Technology Specific Projects (2012ZX10004403)
文摘Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.
基金supported by Important National Science & Technology Specific Projects (2012ZX10004403, 2012ZX10004219)National Natural Scientific Fund of China (81072675)
文摘Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus closely related to the human pathogens including yellow fever virus, dengue virus and West Nile virus. There are currently no effective antiviral therapies for all of the flavivirus and only a few highly effective vaccines are licensed for human use. In this paper, the E protein domain III (DIII) of six heterologous flaviviruses (DENV1-4, WNV and JEV) was expressed in Escherichia coli successfully. The proteins were purified after a solubilization and refolding procedure, characterized by SDS-PAGE and Western blotting. Competitive inhibition showed that all recombinant flavivirus DIII proteins blocked the entry of JEV into BHK-21 cells. Further studies indicated that antibodies induced by the soluble recombinant flavivirus DIII partially protected mice against lethal JEV challenge. These results demonstrated that recombinant flavivirus DIII proteins could inhibit JEV infection competitively, and immunization with proper folding flavivirus DIII induced cross-protection against JEV infection in mice, implying a possible role of DIII for the cross-protection among flavivirus as well as its use in antigens for immunization in animal models.
基金Supported by Important National Science& Technology Specific Projects (2012ZX10004403,2012ZX10004219)
文摘Flaviviral NS2B is a required cofactor for NS3 serine protease activity and plays an important role in promoting functional NS2B-NS3 protease configuration and maintaining critical interactions with protease catalysis substrates. The residues D80DDG in West Nile virus (WNV) NS2B are important for protease activity. To investigate the effects of D80DDG in NS2B on protease activity and viral replication, the negatively charged region D80DD and the conserved residue G83 of NS2B were mutated (D80DD/E80EE, D80DD/K80KK, D80DD/A80AA, G83F, G83S, G83D, G83K, and G83A), and NS3 D75A was designated as the negative control. The effects of the mutations on NS2B-NS3 activity, viral translation, and viral RNA replication were analyzed using kinetic analysis of site-directed enzymes and a transient replicon assay. All substitutions resulted in significantly decreased enzyme activity and blocked RNA replication. The negative charge of D80DD is not important for maintaining NS2B function, but side chain changes in G83 have dramatic effects on protease activity and RNA replication. These results demonstrate that NS2B is important for viral replication and that D80DD and G83 substitutions prevent replication; they will be useful for understanding the relationship between NS2B and NS3.
基金supported by Important National Science & Technology Specific Projects (2012ZX10004219, 2012ZX10004403)the National Natural Scientific Fund of China (81072675)the Wuhan Key Laboratory on Emerging Infectious Diseases and Biosafety
文摘Dengue virus(DENV) nonstructural protein 1(NS1) is a highly conserved 46-kDa protein that contains 2 glycosylation sites(Asn-130 and Asn-207) and 12 conserved cysteine(Cys) residues. Here, we performed site-directed mutagenesis to generate systematic mutants of viral strain TSV01. The results of the subsequent analysis showed that an alanine substitution at the second N-linked glycan Asn-207 in NS1 delayed viral RNA synthesis, reduced virus plaque size, and weakened the cytopathic effect. Three mutants at Cys sites(Cys-4, Cys-55, Cys-291) and a C-terminal deletion(ΔC) mutant significantly impaired RNA synthesis, and consequently abolished viral growth, whereas alanine mutations at Asn-130 and Glu-173 resulted in phenotypes that were similar to the wild-type(WT) virus. Further analysis showed that the Asn-207 mutation slightly delayed viral replication. These results suggest that the three conserved disulfide bonds and the second N-linked glycan in NS1 are required for DENV-2 replication.
基金supported partially by the National Natural Science Foundation of China(61790573,61790575)the Center of National Railway Intelligent Transportation System Engineering and Technology(RITS2019KF03)+3 种基金China Academy of Railway Sciences Corporation LimitedChina Railway Project(N2019G020)China Railway Project(L2022X002)the Key Project of Science and Technology Research Plan of China Academy of Railway Sciences Group Co.Ltd.(2022YJ326)。
文摘Unexpected delays in train operations can cause a cascade of negative consequences in a high-speed railway system.In such cases,train timetables need to be rescheduled.However,timely and efficient train timetable rescheduling is still a challenging problem due to its modeling difficulties and low optimization efficiency.This paper presents a Transformer-based macroscopic regulation approach which consists of two stages including Transformer-based modeling and policy-based decisionmaking.Firstly,the relationship between various train schedules and operations is described by creating a macroscopic model with the Transformer,providing the better understanding of overall operation in the high-speed railway system.Then,a policy-based approach is used to solve a continuous decision problem after macro-modeling for fast convergence.Extensive experiments on various delay scenarios are conducted.The results demonstrate the effectiveness of the proposed method in comparison to other popular methods.
基金supported by the National Natural Science Foundation of China (grant No. 31170158 and 31000090)the '100 Talents Project' of Chinese Academy of Sciences, China (grant No. Y002171YC1)
文摘We developed a Gaussia luciferase (Gluc) reporter replicon of West Nile virus (WNV) and used it to quantify viral translation and RNA replication. The advantage of the Gluc replicon is that Gaussia luciferase is secreted into the culture medium from cells transfected with Gluc replicon RNA, and the medium can be assayed directly for luciferase activity. Using a known Flavivirus inhibitor (NITD008), we demonstrated that the Gluc-WNV replicon could be used for antiviral screening. The Gluc-WNV-Rep will be useful for research in antiviral drug development programs, as well as for studying viral replication and pathogenesis of WNV.
基金This work was supported in part by the National Natural Science Foundation of China under Grant 62203468Young Elite Scientist Sponsorship Program by CAST under Grant 2022QNRC001+1 种基金Foundation of China State Railway Group Co.,Ltd.under Grant K2021X001Foundation of China Academy of Railway Sciences Corporation Limited under Grant 2021YJ315.
文摘Purpose–The intelligent Central Traffic Control(CTC)system plays a vital role in establishing an intelligent high-speed railway(HSR)system.As the core of HSR transportation command,the intelligent CTC system is a new HSR dispatching command system that integrates the widely used CTC in China with the practical service requirements of intelligent dispatching.This paper aims to propose key technologies and applications for intelligent dispatching command in HSR in China.Design/methodology/approach–This paper first briefly introduces the functions and configuration of the intelligent CTC system.Some new servers,terminals and interfaces are introduced,which are plan adjustment server/terminal,interface for automatic train operation(ATO),interface for Dynamic Monitoring System of Train Control Equipment(DMS),interface for Power Supervisory Control and Data Acquisition(PSCADA),interface for Disaster Monitoring,etc.Findings–The key technologies applied in the intelligent CTC system include automatic adjustment of train operation plans,safety control of train routes and commands,traffic information data platform,integrated simulation of traffic dispatching and ATO function.These technologies have been applied in the Beijing-Zhangjiakou HSR,which commenced operations at the end of 2019.Implementing these key intelligent functions has improved the train dispatching command capacity,ensured the safe operation of intelligent HSR,reduced the labor intensity of dispatching operators and enhanced the intelligence level of China’s dispatching system.Originality/value–This paper provides further challenges and research directions for the intelligent dispatching command of HSR.To achieve the objectives,new measures need to be conducted,including the development of advanced technologies for intelligent dispatching command,coping with new requirements with the development of China’s railway signaling system,the integration of traffic dispatching and train control and the application of AI and data-driven modeling and methods.
基金This research was jointly supported by the National Natural Science Foundation of China[Grant 62203468]the Young Elite Scientist Sponsorship Program by China Association for Science and Technology(CAST)[Grant 2022QNRC001]+1 种基金the Technological Research and Development Program of China Railway Corporation Limited[Grant K2021X001]by the Foundation of China Academy of Railway Sciences Corporation Limited[Grant 2021YJ043].On behalf all authors,the corresponding author states that there is no conflict of interest.
文摘Purpose–This paper aims to propose a train timetable rescheduling(TTR)approach from the perspective of multi-train tracking optimization based on the mutual spatiotemporal information in the high-speed railway signaling system.Design/methodology/approach–Firstly,a single-train trajectory optimization(STTO)model is constructed based on train dynamics and operating conditions.The train kinematics parameters,including acceleration,speed and time at each position,are calculated to predict the arrival times in the train timetable.A STTO algorithm is developed to optimize a single-train time-efficient driving strategy.Then,a TTR approach based on multi-train tracking optimization(TTR-MTTO)is proposed with mutual information.The constraints of temporary speed restriction(TSR)and end of authority are decoupled to calculate the tracking trajectory of the backward tracking train.The multi-train trajectories at each position are optimized to generate a timeefficient train timetable.Findings–The numerical experiment is performed on the Beijing-Tianjin high-speed railway line and CR400AF.The STTO algorithm predicts the train’s planned arrival time to calculate the total train delay(TTD).As for the TSR scenario,the proposed TTR-MTTO can reduce TTD by 60.60%compared with the traditional TTR approach with dispatchers’experience.Moreover,TTR-MTTO can optimize a time-efficient train timetable to help dispatchers reschedule trains more reasonably.Originality/value–With the cooperative relationship and mutual information between train rescheduling and control,the proposed TTR-MTTO approach can automatically generate a time-efficient train timetable to reduce the total train delay and the work intensity of dispatchers.
基金supported by the National Key Research and Development Program of China(Grant no.2020YFA0908603).
文摘The sharing of pathogens is of great significance for the continuous and comprehensive testing and monitoring of viral samples,vaccine and drug development,and the study of drug resistance and mutability of viral samples.This paper reviews the current legal framework in the field of pathogen sharing,analyzes existing issues,and proposes recommendations to improve the legal framework of pathogen sharing.
基金supported by the Ministry of Science and Technology of China (Science and Technology Basic Work Program 2013FY113500)
文摘Mosquitoes are classified into approximately 3500 species and further grouped into 41 genera.Epidemiologically,they are considered to be among the most important disease vectors in the world and they can harbor a wide variety of viruses.Several mosquito viruses are considered to be of significant medical importance and can cause serious public health issues throughout the world.Such viruses are Japanese encephalitis virus(JEV),dengue virus(DENV),chikungunya virus(CHIKV),and Zika virus(ZIKV).Others are the newly recognized mosquito viruses such as Banna virus(BAV)and Yunnan orbivirus(YNOV)with unclear medical significance.The remaining mosquito viruses are those that naturally infect mosquitoes but do not appear to infect humans or other vertebrates.With the continuous development and improvement of mosquito and mosquito-associated virus surveillance systems in China,many novel mosquito-associated viruses have been discovered in recent years.This review aims to systematically outline the history,characteristics,distribution,and/or current epidemic status of mosquito-associated viruses in China.
基金supported by Hehai University Special Funds for COVID-19the National Natural Science Foundation of China(32130063)+4 种基金the National Key Research and Development Program of China(2021YFE0201900 and 2021YFC2301700)China Postdoctoral Science Foundation(2020T130017ZX)the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University(SN-ZJU-SIAS-009)the STS Regional Key Project(KFJSTS-QYZD-2021-12-001)from Chinese Academy of SciencesHubei Science and Technology Major Project(2021ACB0004)。
基金Project supported by the National Natural Science Foun-dation of China(Grant Nos.51309124,51679113 and 51379095)
文摘In this study, a perforated pontoon floating breakwater（FB） consisting of an impermeable plate and a perforated plate was designed to untangle the effect of a perforated plate on wave transmission and hydrodynamic performance of floating breakwater. A series of 2-D physical model experiments were conducted to measure the wave transmission coefficient, tension acting on the mooring line, and motion response of FB under a regular wave. The experimental results of the motion responses and mooring lines indicated that the new perforated plate was evidently effective. Furthermore, the study also discussed and analyzed the influence of the perforated plate on transmission coefficients. The experimental results showed that the new perforated plate did not lead to obvious improvement in the transmission performance
基金supported by the Wuhan Bureau of Science and Technology(No.202002020101010022)China Geological Survey(No.DD20190282)the support team from the National Biosafety Laboratory in Wuhan,China,for the support they extended to us。
文摘Wastewater-based epidemiology(WBE)has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community.Congruently,SARS-Co V-2,the etiologic agent of COVID-19,has been demonstrated to infect the gastrointestinal tissues,and be shed in feces.In the present study,SARS-Co V-2 RNA was concentrated from wastewater,sludge,surface water,ground water,sediment,and soil samples of municipal and hospital wastewater systems and related environments in Wuhan during the COVID-19 middle and low risk periods,and the viral RNA copies quantified using reverse transcription quantitative polymerase chain reaction(RT-q PCR).From the findings of this study,during the middle risk period,one influent sample and three secondary effluents collected from waste water treatment plant 2,as well as two samples from Jinyintan Hospital wastewater system influent were SARS-Co V-2 RNA positive.One sludge sample collected from Guanggu Branch of Tongji Hospital,which was obtained during the low risk period,was also positive for SARS-Co V-2 RNA.These study findings demonstrate the significance of WBE in continuous surveillance of SARS-Co V-2 at the community level,even when the COVID-19 prevalence is low.Overall,this study can be used as an important reference for contingency management of wastewater treatment plants and COVID-19 prevention and control departments of Wuhan.
基金supported by the Ministry of Science and Technology of the People’s Republic of China (2020YFC08845600)the National Health Commission of the People’s Republic of China (2018ZX10711001-006)。
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2), the etiologic agent of COVID-19, is an enveloped,positive-sense single-stranded RNA virus that first discovered in December 2019 from a seafood market in Wuhan, China(Zhou et al. 2020).
基金supported by the Ministry of Science and Technology of China (Science and Technology Basic Work Program 2013FY113500)
文摘Vast viruses are thought to be associated with mosquitoes.Anopheles sinensis,Armigeres subalbatus,Culex quinquefasciatus,and Culex tritaeniorhynchus are very common mosquito species in China,and whether the virome structure in each species is species-specific has not been evaluated.In this study,a total of 2222 mosquitoes were collected from the same geographic location,and RNAs were sequenced using the Illumina Miseq platform.After querying to the Refseq database,a total of 3,435,781,2,223,509,5,727,523,and 6,387,867 paired-end reads were classified under viral sequences from An.sinensis,Ar.subalbatus,Cx.quinquefasciatus,and Cx.tritaeniorhynchus,respectively,with the highest prevalence of virus-associated reads being observed in Cx.quinquefasciatus.The metagenomic comparison analysis showed that the virus-related reads were distributed across 26 virus families,together with an unclassified group of viruses.Anelloviridae,Circoviridae,Genomoviridae,Iridoviridae,Mesoniviridae,Microviridae,Myoviridae,Parvoviridae,Phenuiviridae,and Podoviridae were the top ten significantly different viral families among the four species.Further analysis reveals that the virome is species-specific in four mosquito samples,and several viral sequences which maybe belong to novel viruses are discovered for the first time in those mosquitoes.This investigation provides a basis for a comprehensive knowledge on the mosquito virome status in China.
