【目的】在城市地下空间综合化高速开发的同时,极端降雨所引发的城市内涝灾害频繁发生,洪水倒灌入侵地铁车站事故导致了严重的人员伤亡和财产损失。洪水经由车站流入隧道对运营中的车辆设备及乘客人员造成重大威胁,为预防和应对多种工...【目的】在城市地下空间综合化高速开发的同时,极端降雨所引发的城市内涝灾害频繁发生,洪水倒灌入侵地铁车站事故导致了严重的人员伤亡和财产损失。洪水经由车站流入隧道对运营中的车辆设备及乘客人员造成重大威胁,为预防和应对多种工况下洪水侵入地铁系统灾害,通过数值分析方法,模拟不同工况洪水入侵和淹没复杂地铁车站的全过程,并预测计算流入隧道的洪水量。【方法】以南宁市地铁换乘车站明秀路站为原型,构建三维数值仿真模型。研究防淹门不同启闭条件下,百年一遇入侵洪水高度、50 cm和30 cm入侵洪水高度水位洪水入侵复杂地铁车站的全过程。基于Volume of Fluid(VOF)模型方法,模拟分析了不同工况下洪水在地铁车站内的淹没区域范围与积聚深度,探讨洪水激增规律以及危险区域分布情况。针对百年一遇洪水入侵工况,分析了物业开发层的水深分布规律,并通过计算得到该区域的人员疏散路径。【结果】结果显示:在洪水入侵灾害中,明秀路站被淹没速度和淹没高度随入侵洪水高度的提升而加快和增加;关闭防淹门可以防止大量洪水流入隧道,但是将会严重加剧站内积水;与地铁车站相连的物业开发层可能导致洪水更快更多地入侵淹没明秀路站,分布密集且狭小的通道口处积水较深。【结论】结果表明:数值模拟的方法可以较为容易地计算得到洪水入侵灾害中地铁车站的淹没过程和范围,通过改变出入口条件可以得到例如防淹门启闭措施对不同入侵洪水高度洪水入侵的影响,可为灾前预防隐患和灾时应急措施提供参考。展开更多
Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DN...Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DNA.In our work,by full-atom molecular dynamic simulation, the effects of the Mg^2+ ion on the cyclic adenosine monophosphate(cAMP)response element binding protein(CREB)/cAMP response elements(CRE) complex are investigated.It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg^2+ ion is added.Hence, an obvious change in the structure of the DNA is observed.Then the DNA base groove and base pair parameters are analyzed.We find that, due to the introduction of the Mg2+ ion, the DNA base major groove becomes narrower.A potential mechanism for this observation is proposed.It is confirmed that the Mg^2+ ion can enhance the stability of the DNA–protein complex.展开更多
In a reliability comparative test, the joint censoring model is usually adopted to evaluate the performances of units with the same facility. However, most researchers ignore the pos- sibility that there is more than ...In a reliability comparative test, the joint censoring model is usually adopted to evaluate the performances of units with the same facility. However, most researchers ignore the pos- sibility that there is more than one factor for the failure when a test unit fails. To solve this problem, we consider a joint Type-II hybrid censoring model for the analysis of exponential competing failure data. Based on the maximum likelihood theory, we compute the maximum likelihood estimators （MLEs） of parameters and then obtain the condition ensuring MLEs existence for every unknown parameter. Then we derive the conditional exact distributions and corresponding moment properties for parameters by the moment generating function （MGF）. A Monte-Carlo simulation is conducted to compare the performances of different ways. And finally, we conduct a numerical example to illustrate the proposed method.展开更多
We calculate the complete next-to-leading order(NLO)QCD corrections to J/ψ+W associated production within the factorization formalism of nonrelativistic QCD at the 7 TeV Large Hadron Collider.We provide the numerical...We calculate the complete next-to-leading order(NLO)QCD corrections to J/ψ+W associated production within the factorization formalism of nonrelativistic QCD at the 7 TeV Large Hadron Collider.We provide the numerical results for the leading-order(LO),NLO QCD corrected differential cross sections of the J/ψtransverse momentum by adopting the event selection criteria requested by the ATLAS experiment.It is found that the differential cross section at the LO is significantly enhanced by the NLO QCD corrections.展开更多
Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as ...Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.展开更多
Mouse embryonic stem cells(mESCs)cycle in and out of a transient 2-cell(2C)-like totipotent state,driven by a com-plex genetic circuit involves both the coding and repetitive sections of the genome.While a vast array ...Mouse embryonic stem cells(mESCs)cycle in and out of a transient 2-cell(2C)-like totipotent state,driven by a com-plex genetic circuit involves both the coding and repetitive sections of the genome.While a vast array of regulators,including the multi-functional protein Rif1,has been reported to influence the switch of fate potential,how they act in concert to achieve this cellular plasticity remains elusive.Here,by modularizing the known totipotency regulatory factors,we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repres-sive complex PRC1.6.Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs.The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6,bolstering the intactness of the PRC1.6 complex.Chromatin immunoprecipitation followed by sequencing(ChIP-seq)analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state.Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352,but also derepresses a group of the endogenous retroviral element MERVL,a key marker for totipotency.Collectively,our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential,shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.展开更多
Assuming that the failure time under different risk factors follows the independent exponential distribution, a joint model under Type-I hybrid censoring is addressed in detail. Based on the Maximum likelihood estimat...Assuming that the failure time under different risk factors follows the independent exponential distribution, a joint model under Type-I hybrid censoring is addressed in detail. Based on the Maximum likelihood estimates （MLEs） of unknown parameters, we obtain exact distributions of MLEs by using the moment generating function （MGF）. Confidence intervals （CIs） of parameters are constructed through both the exact method and the parametric bootstrap method. Then we compare the performances of different methods by Monte Carlo simulations. Finally, the validity of the proposed models and methods are demonstrated by a numerical example.展开更多
This paper investigates a simple step-stress accelerated lifetime test(SSALT)model for the inferential analysis of exponential competing risks data.A generalized type-I hybrid censoring scheme is employed to improve t...This paper investigates a simple step-stress accelerated lifetime test(SSALT)model for the inferential analysis of exponential competing risks data.A generalized type-I hybrid censoring scheme is employed to improve the efficiency and controllability of the test.Firstly,the MLEs for parameters are established based on the cumulative exposure model(CEM).Then the conditional moment generating function(MGF)for unknown parameters is set up using conditional expectation and multiple integral techniques.Thirdly,confidence intervals(CIs)are constructed by the exact MGF-based method,the approximate normality-based method,and the bias-corrected and accelerated(BCa)percentile bootstrap method.Finally,we present simulation studies and an illustrative example to compare the performances of different methods.展开更多
文摘【目的】在城市地下空间综合化高速开发的同时,极端降雨所引发的城市内涝灾害频繁发生,洪水倒灌入侵地铁车站事故导致了严重的人员伤亡和财产损失。洪水经由车站流入隧道对运营中的车辆设备及乘客人员造成重大威胁,为预防和应对多种工况下洪水侵入地铁系统灾害,通过数值分析方法,模拟不同工况洪水入侵和淹没复杂地铁车站的全过程,并预测计算流入隧道的洪水量。【方法】以南宁市地铁换乘车站明秀路站为原型,构建三维数值仿真模型。研究防淹门不同启闭条件下,百年一遇入侵洪水高度、50 cm和30 cm入侵洪水高度水位洪水入侵复杂地铁车站的全过程。基于Volume of Fluid(VOF)模型方法,模拟分析了不同工况下洪水在地铁车站内的淹没区域范围与积聚深度,探讨洪水激增规律以及危险区域分布情况。针对百年一遇洪水入侵工况,分析了物业开发层的水深分布规律,并通过计算得到该区域的人员疏散路径。【结果】结果显示:在洪水入侵灾害中,明秀路站被淹没速度和淹没高度随入侵洪水高度的提升而加快和增加;关闭防淹门可以防止大量洪水流入隧道,但是将会严重加剧站内积水;与地铁车站相连的物业开发层可能导致洪水更快更多地入侵淹没明秀路站,分布密集且狭小的通道口处积水较深。【结论】结果表明:数值模拟的方法可以较为容易地计算得到洪水入侵灾害中地铁车站的淹没过程和范围,通过改变出入口条件可以得到例如防淹门启闭措施对不同入侵洪水高度洪水入侵的影响,可为灾前预防隐患和灾时应急措施提供参考。
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11705064,11675060,and 91730301)the Fundamental Research Funds for the Central Universities,China(Grant Nos.2662016QD005 and 26622018JC017)the Huazhong Agricultural University Scientific and Technological Self-Innovation Foundation Program,China(Grant No.2015RC021)
文摘Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DNA.In our work,by full-atom molecular dynamic simulation, the effects of the Mg^2+ ion on the cyclic adenosine monophosphate(cAMP)response element binding protein(CREB)/cAMP response elements(CRE) complex are investigated.It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg^2+ ion is added.Hence, an obvious change in the structure of the DNA is observed.Then the DNA base groove and base pair parameters are analyzed.We find that, due to the introduction of the Mg2+ ion, the DNA base major groove becomes narrower.A potential mechanism for this observation is proposed.It is confirmed that the Mg^2+ ion can enhance the stability of the DNA–protein complex.
基金supported by the National Natural Science Foundation of China(71171164)
文摘In a reliability comparative test, the joint censoring model is usually adopted to evaluate the performances of units with the same facility. However, most researchers ignore the pos- sibility that there is more than one factor for the failure when a test unit fails. To solve this problem, we consider a joint Type-II hybrid censoring model for the analysis of exponential competing failure data. Based on the maximum likelihood theory, we compute the maximum likelihood estimators （MLEs） of parameters and then obtain the condition ensuring MLEs existence for every unknown parameter. Then we derive the conditional exact distributions and corresponding moment properties for parameters by the moment generating function （MGF）. A Monte-Carlo simulation is conducted to compare the performances of different ways. And finally, we conduct a numerical example to illustrate the proposed method.
基金Supported by the National Natural Science Foundation of China under Grant Nos 11205003,11275190,11075150,11005101,and 11175001the Key Research Foundation of Education Ministry of Anhui Province(No KJ2012A021)+1 种基金the Youth Foundation of Anhui Province(No 1308085QA07)the 211 Project of Anhui University(No 02303319).
文摘We calculate the complete next-to-leading order(NLO)QCD corrections to J/ψ+W associated production within the factorization formalism of nonrelativistic QCD at the 7 TeV Large Hadron Collider.We provide the numerical results for the leading-order(LO),NLO QCD corrected differential cross sections of the J/ψtransverse momentum by adopting the event selection criteria requested by the ATLAS experiment.It is found that the differential cross section at the LO is significantly enhanced by the NLO QCD corrections.
基金supported by the National Natural Science Foundation of China,Nos.81800919(to YX),82171140(to PW)the International Cooperation and Exchange of the National Natural Science Foundation of China,Nos.82020108008(to HS),81720108010(to SY).
文摘Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.
基金This project has been supported by the National Natural Science Foundation of China(32170821,31771589 to K.Y)Ministry of Science and Technology of the People’s Republic of China(2021YFC2701202)+1 种基金Department of Science&Technology of Hunan Province(2021JJ10054,2019SK1012,2018DK2015,2017RS3013,2017XK2011 to K.Y,2019JJ40478 to P.L,and the innovative team program 2019RS1010)Central South University(2018CX032 to K.Y,and the innovation-driven team project 2020CX016)。
文摘Mouse embryonic stem cells(mESCs)cycle in and out of a transient 2-cell(2C)-like totipotent state,driven by a com-plex genetic circuit involves both the coding and repetitive sections of the genome.While a vast array of regulators,including the multi-functional protein Rif1,has been reported to influence the switch of fate potential,how they act in concert to achieve this cellular plasticity remains elusive.Here,by modularizing the known totipotency regulatory factors,we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repres-sive complex PRC1.6.Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs.The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6,bolstering the intactness of the PRC1.6 complex.Chromatin immunoprecipitation followed by sequencing(ChIP-seq)analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state.Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352,but also derepresses a group of the endogenous retroviral element MERVL,a key marker for totipotency.Collectively,our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential,shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.
基金Supported by the National Natural Science Foundation of China(No.71571144)Natural Science Basic Research Program of Shaanxi Province(2015JM1003)+1 种基金the Program of International Cooperation and Exchanges in Science and Technology Funded by Shanxi Province(2016KW-033)Shanxi Scholarship Council of China(2016-015)
文摘Assuming that the failure time under different risk factors follows the independent exponential distribution, a joint model under Type-I hybrid censoring is addressed in detail. Based on the Maximum likelihood estimates （MLEs） of unknown parameters, we obtain exact distributions of MLEs by using the moment generating function （MGF）. Confidence intervals （CIs） of parameters are constructed through both the exact method and the parametric bootstrap method. Then we compare the performances of different methods by Monte Carlo simulations. Finally, the validity of the proposed models and methods are demonstrated by a numerical example.
基金Humanities and Social Sciences Fund in Ministry of Education in China(18YJC910009)the National Natural Science Foundation of China(12061091)Program for the Philosophy and Social Sciences Research of Higher Learning Institutions of Shanxi(201803050)。
文摘This paper investigates a simple step-stress accelerated lifetime test(SSALT)model for the inferential analysis of exponential competing risks data.A generalized type-I hybrid censoring scheme is employed to improve the efficiency and controllability of the test.Firstly,the MLEs for parameters are established based on the cumulative exposure model(CEM).Then the conditional moment generating function(MGF)for unknown parameters is set up using conditional expectation and multiple integral techniques.Thirdly,confidence intervals(CIs)are constructed by the exact MGF-based method,the approximate normality-based method,and the bias-corrected and accelerated(BCa)percentile bootstrap method.Finally,we present simulation studies and an illustrative example to compare the performances of different methods.
