Acoustic emission(AE)localization algorithms based on homogeneous media or single-velocity are less accurate when applied to the triaxial localization experiments.To the end,a robust triaxial localization method of AE...Acoustic emission(AE)localization algorithms based on homogeneous media or single-velocity are less accurate when applied to the triaxial localization experiments.To the end,a robust triaxial localization method of AE source using refraction path is proposed.Firstly,the control equation of the refraction path is established according to the sensor coordinates and arrival times.Secondly,considering the influence of time-difference-of-arrival(TDOA)errors,the residual of the governing equation is calculated to estimate the equation weight.Thirdly,the refraction points in different directions are solved using Snell’s law and orthogonal constraints.Finally,the source coordinates are iteratively solved by weighted correction terms.The feasibility and accuracy of the proposed method are verified by pencil-lead breaking experiments.The simulation results show that the new method is almost unaffected by the refraction ratio,and always holds more stable and accurate positioning performance than the traditional method under different ratios and scales of TDOA outliers.展开更多
Rock failure phenomena,such as rockburst,slabbing(or spalling) and zonal disintegration,related to deep underground excavation of hard rocks are frequently reported and pose a great threat to deep mining.Currently,the...Rock failure phenomena,such as rockburst,slabbing(or spalling) and zonal disintegration,related to deep underground excavation of hard rocks are frequently reported and pose a great threat to deep mining.Currently,the explanation for these failure phenomena using existing dynamic or static rock mechanics theory is not straightforward.In this study,new theory and testing method for deep underground rock mass under coupled static-dynamic loading are introduced.Two types of coupled loading modes,i.e.'critical static stress + slight disturbance' and 'elastic static stress + impact disturbance',are proposed,and associated test devices are developed.Rockburst phenomena of hard rocks under coupled static-dynamic loading are successfully reproduced in the laboratory,and the rockburst mechanism and related criteria are demonstrated.The results of true triaxial unloading compression tests on granite and red sandstone indicate that the unloading can induce slabbing when the confining pressure exceeds a certain threshold,and the slabbing failure strength is lower than the shear failure strength according to the conventional Mohr-Column criterion.Numerical results indicate that the rock unloading failure response under different in situ stresses and unloading rates can be characterized by an equivalent strain energy density.In addition,we present a new microseismic source location method without premeasuring the sound wave velocity in rock mass,which can efficiently and accurately locate the rock failure in hard rock mines.Also,a new idea for deep hard rock mining using a non-explosive continuous mining method is briefly introduced.展开更多
Rock drilling machine,INSTRON testing system,and SHPB device are updated to investigate the characteristics of rocks at great depth,with high loads from overburden,tectonic stresses and dynamic impacts due to blasting...Rock drilling machine,INSTRON testing system,and SHPB device are updated to investigate the characteristics of rocks at great depth,with high loads from overburden,tectonic stresses and dynamic impacts due to blasting and boring.It is verified that these testing systems can be used to study the mechanical properties of rock material under coupled static and dynamic loading condition and give useful guidance for the deep mining and underground cavern excavation.Various tests to determine the rock strength,fragmentation behavior,and energy absorption were conducted using the updated testing systems.It is shown that under coupled static-dynamic loads,if the axial prestress is lower than its elastic limit,the rock strength is higher than the individual static or dynamic strength.At the same axial prestress,rock strength under coupled loads rises with the increasing strain rates.Under coupled static and dynamic loads,rock is observed to fail with tensile mode.While shear failure may exist if axial prestress is high enough.In addition,it is shown that the percentage of small particles increases with the increasing axial prestress and impact load based on the analysis of the particle-size distribution of fragments.It is also suggested that the energy absorption ratio of a specimen varies with coupled loads,and the maximum energy absorption ratio for a rock can be obtained with an appropriate combination of static and dynamic loads.展开更多
Due to the significant effect of abnormal arrivals on localization accuracy,a novel acoustic emission(AE)source localization method using clustering detection to eliminate abnormal arrivals is proposed in the paper.Fi...Due to the significant effect of abnormal arrivals on localization accuracy,a novel acoustic emission(AE)source localization method using clustering detection to eliminate abnormal arrivals is proposed in the paper.Firstly,iterative weight estimation is utilized to obtain accurate equation residuals.Secondly,according to the distribution of equation residuals,clustering detection is used to identify and exclude abnormal arrivals.Thirdly,the AE source coordinate is recalculated with remaining normal arrivals.Experimental results of pencil-lead breaks indicate that the proposed method can achieve a better localization result with and without abnormal arrivals.The results of simulation tests further demonstrate that the proposed method possesses higher localization accuracy and robustness under different anomaly ratios and scales;even with abnormal arrivals as high as 30%,the proposed localization method still holds a correct detection rate of 91.85%.展开更多
Due to the complexity of the real engineering environment, the arrival measurement inevitably contains outliers and leads to serious location errors. In order to eliminate the influence of the outliers effectively,thi...Due to the complexity of the real engineering environment, the arrival measurement inevitably contains outliers and leads to serious location errors. In order to eliminate the influence of the outliers effectively,this paper proposes a novel robust AE/MS source localization method using optimized M-estimate consensus sample. First, a sample subset is selected from the entire arrival set to obtain fitting model and its parameters. Second, consensus set is determined by checking the arrivals with the fitting model instantiated by the estimated model parameters. Third, optimization process is performed to further optimize the consensus set. The above steps are iterated, and the final source coordinates are obtained by using all the elements in the optimal consensus set. The novel method is validated by a pencil-lead breaks experiment. The results indicate that the novel method has better location accuracy of less than 5 mm compared to existing methods, regardless of the presence or absence of outliers. With the increase of outlier scale and outlier ratio, the location result of the proposed method is always more stable and accurate than that of the existing methods. Mine blasting experiments further demonstrate that the new method holds good prospects for engineering applications.展开更多
Gas fracturing,which overcomes the limitation of hydraulic fracturing,is a potential alternative technology for the development of unconventional gas and oil resources.However,the mechanical principle of gas fracturin...Gas fracturing,which overcomes the limitation of hydraulic fracturing,is a potential alternative technology for the development of unconventional gas and oil resources.However,the mechanical principle of gas fracturing has not been learned comprehensively when the fluid is injected into the borehole.In this paper,a damage-based model of coupled thermal-flowing-mechanical effects was adopted to illustrate the mechanical principle of gas fracturing.Numerical simulation tools Comsol Multiphysics and Matlab were integrated to simulate the coupled process during the gas fracturing.Besides,the damage evolution of drilling areas under several conditions was fully analyzed.Simulation results indicate that the maximum tensile stress,which occurs in the upper and lower of the injection hole,decreases with the increase of the tectonic stress coefficient(TSC).As the TSC increases,shear fractures increase,a crushed area is gradually formed and the seepage area increases rapidly.The influence of TSC on fracture expansion is concluded as follows:with the decrease of TSC,the relative width of fractures decreases whilst the depth increases.It indicates that thermal stress and pore pressure promote the expansion of tensile fractures but restrain the expansion of shear fractures.Therefore,a relatively lower injection gas pressure is required to obtain the same degree of fracturing with a coupled thermal gradient.展开更多
Metformin is currently a strong candidate anti-tumor agent in multiple cancers.However,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor heterogeneity.It thus rema...Metformin is currently a strong candidate anti-tumor agent in multiple cancers.However,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor heterogeneity.It thus remains unclear which hepatocellular carcinoma(HCC)patient subpopulation(s)can benefit from met-formin treatment.Here,through a genome-wide CRISPR-Cas9-based knockout screen,we find that DOCK1 levels determine the anti-tumor effects of met-formin and that DOCK1 is a synthetic lethal target of metformin in HCC.Mechanistically,metformin promotes DOCK1 phosphorylation,which activates RAC1 to facilitate cell survival,leading to metformin resistance.The DOCK1-selective inhibitor,TBOPP,potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids,and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models.Notably,metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression.This study shows that metformin effective-ness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for met-formin-resistant HCC patients.展开更多
Background:Histone deacetylases(HDACs)engage in the regulation of various cellular processes by controlling global gene expression.The dysregulation of HDACs leads to carcinogenesis,making HDACs ideal targets for canc...Background:Histone deacetylases(HDACs)engage in the regulation of various cellular processes by controlling global gene expression.The dysregulation of HDACs leads to carcinogenesis,making HDACs ideal targets for cancer therapy.However,the use of HDAC inhibitors(HDACi)as single agents has been shown to have limited success in treating solid tumors in clinical studies.This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy.Methods:Transcriptome sequencing and bioinformatics analysis were performed to screen for genes responsive toHDACi in breast cancer cells.The effects of HDACi on cell viability were detected using the MTT assay.The mRNA and protein levels of genes were determined by quantitative reverse transcription-PCR(qRT-PCR)andWestern blotting.Cell cycle distribution and apoptosis were analyzed by flow cytometry.The binding of CREB1(cAMP-response element binding protein 1)to the promoter of the KDELR(The KDEL(Lys-Asp-Glu-Leu)receptor)gene was validated by the ChIP(chromatin immunoprecipitation assay).The association between KDELR2 and protein of centriole 5(POC5)was detected by immunoprecipitation.A breast cancer-bearing mouse model was employed to analyze the effect of the HDAC3-KDELR2 axis on tumor growth.Results:KDELR2 was identified as a novel target of HDAC3,and its aberrant expression indicated the poor prognosis of breast cancer patients.We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients.The results of the ChIP assay and qRT-PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1.The HDAC3-KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation.Moreover,the HDAC3-KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo.Conclusion:Our results uncovered a previously unappreciated function of KDELR2 in tumorigenesis,linking a critical Golgi-the endoplasmic reticulum traffic transport protein to HDAC-controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.展开更多
基金the National Natural Science Foundation of China (Nos.52304123 and 52104077)the Postdoctoral Fellowship Program of CPSF (No.GZB20230914)+1 种基金the China Postdoctoral Science Foundation (No.2023M730412)the National Key Research and Development Program for Young Scientists (No.2021YFC2900400)。
文摘Acoustic emission(AE)localization algorithms based on homogeneous media or single-velocity are less accurate when applied to the triaxial localization experiments.To the end,a robust triaxial localization method of AE source using refraction path is proposed.Firstly,the control equation of the refraction path is established according to the sensor coordinates and arrival times.Secondly,considering the influence of time-difference-of-arrival(TDOA)errors,the residual of the governing equation is calculated to estimate the equation weight.Thirdly,the refraction points in different directions are solved using Snell’s law and orthogonal constraints.Finally,the source coordinates are iteratively solved by weighted correction terms.The feasibility and accuracy of the proposed method are verified by pencil-lead breaking experiments.The simulation results show that the new method is almost unaffected by the refraction ratio,and always holds more stable and accurate positioning performance than the traditional method under different ratios and scales of TDOA outliers.
基金jointly supported by the State Key Research Development Program of China (Grant No.2016YFC0600706)the National Natural Science Foundation of China (Grant Nos.41630642 and 11472311)
文摘Rock failure phenomena,such as rockburst,slabbing(or spalling) and zonal disintegration,related to deep underground excavation of hard rocks are frequently reported and pose a great threat to deep mining.Currently,the explanation for these failure phenomena using existing dynamic or static rock mechanics theory is not straightforward.In this study,new theory and testing method for deep underground rock mass under coupled static-dynamic loading are introduced.Two types of coupled loading modes,i.e.'critical static stress + slight disturbance' and 'elastic static stress + impact disturbance',are proposed,and associated test devices are developed.Rockburst phenomena of hard rocks under coupled static-dynamic loading are successfully reproduced in the laboratory,and the rockburst mechanism and related criteria are demonstrated.The results of true triaxial unloading compression tests on granite and red sandstone indicate that the unloading can induce slabbing when the confining pressure exceeds a certain threshold,and the slabbing failure strength is lower than the shear failure strength according to the conventional Mohr-Column criterion.Numerical results indicate that the rock unloading failure response under different in situ stresses and unloading rates can be characterized by an equivalent strain energy density.In addition,we present a new microseismic source location method without premeasuring the sound wave velocity in rock mass,which can efficiently and accurately locate the rock failure in hard rock mines.Also,a new idea for deep hard rock mining using a non-explosive continuous mining method is briefly introduced.
基金Supported by the National Natural Science Foundation of China (10872218,50934006,50534030)Research Foundation for the Doctoral Program of Higher Education of China (200805331143)
文摘Rock drilling machine,INSTRON testing system,and SHPB device are updated to investigate the characteristics of rocks at great depth,with high loads from overburden,tectonic stresses and dynamic impacts due to blasting and boring.It is verified that these testing systems can be used to study the mechanical properties of rock material under coupled static and dynamic loading condition and give useful guidance for the deep mining and underground cavern excavation.Various tests to determine the rock strength,fragmentation behavior,and energy absorption were conducted using the updated testing systems.It is shown that under coupled static-dynamic loads,if the axial prestress is lower than its elastic limit,the rock strength is higher than the individual static or dynamic strength.At the same axial prestress,rock strength under coupled loads rises with the increasing strain rates.Under coupled static and dynamic loads,rock is observed to fail with tensile mode.While shear failure may exist if axial prestress is high enough.In addition,it is shown that the percentage of small particles increases with the increasing axial prestress and impact load based on the analysis of the particle-size distribution of fragments.It is also suggested that the energy absorption ratio of a specimen varies with coupled loads,and the maximum energy absorption ratio for a rock can be obtained with an appropriate combination of static and dynamic loads.
基金financial support provided by the National Natural Science Foundation of China(Grant No.41772313)Hunan Science and Technology Planning Project(Grant No.2019RS3001).
文摘Due to the significant effect of abnormal arrivals on localization accuracy,a novel acoustic emission(AE)source localization method using clustering detection to eliminate abnormal arrivals is proposed in the paper.Firstly,iterative weight estimation is utilized to obtain accurate equation residuals.Secondly,according to the distribution of equation residuals,clustering detection is used to identify and exclude abnormal arrivals.Thirdly,the AE source coordinate is recalculated with remaining normal arrivals.Experimental results of pencil-lead breaks indicate that the proposed method can achieve a better localization result with and without abnormal arrivals.The results of simulation tests further demonstrate that the proposed method possesses higher localization accuracy and robustness under different anomaly ratios and scales;even with abnormal arrivals as high as 30%,the proposed localization method still holds a correct detection rate of 91.85%.
基金the financial support provided by the National Natural Science Foundation of China (No. 41772313)Hunan Science and Technology Planning Project (No. 2019RS3001)+3 种基金the Science and Technology Innovation Program of Hunan Province (No. 2021RC1001)the National Natural Science Foundation for Young Scientists of China (No. 52104111)the Natural Science Foundation of Hunan (No. 2021JJ30819)Key Science and Technology Project of Guangxi Transportation Industry (Research on fine blasting and disaster control technology of mountain expressway tunnel)。
文摘Due to the complexity of the real engineering environment, the arrival measurement inevitably contains outliers and leads to serious location errors. In order to eliminate the influence of the outliers effectively,this paper proposes a novel robust AE/MS source localization method using optimized M-estimate consensus sample. First, a sample subset is selected from the entire arrival set to obtain fitting model and its parameters. Second, consensus set is determined by checking the arrivals with the fitting model instantiated by the estimated model parameters. Third, optimization process is performed to further optimize the consensus set. The above steps are iterated, and the final source coordinates are obtained by using all the elements in the optimal consensus set. The novel method is validated by a pencil-lead breaks experiment. The results indicate that the novel method has better location accuracy of less than 5 mm compared to existing methods, regardless of the presence or absence of outliers. With the increase of outlier scale and outlier ratio, the location result of the proposed method is always more stable and accurate than that of the existing methods. Mine blasting experiments further demonstrate that the new method holds good prospects for engineering applications.
基金supported by the National Natural Science Foundation of China(41977238 and 51804339)the Young Elite Scientists Sponsorship by CAST,the Special Fund for the Construction of Innovative Provinces in Hunan(2019RS2007)+2 种基金the China Postdoctoral Science Foundation(2019T120715 and 2018M640760)the Open Project Fund for State Key Laboratory of Mining Disaster Prevention and Control(MDPC201901)the Fundamental Research Fund for the Central Universities of CSU(2019zzts675).
文摘Gas fracturing,which overcomes the limitation of hydraulic fracturing,is a potential alternative technology for the development of unconventional gas and oil resources.However,the mechanical principle of gas fracturing has not been learned comprehensively when the fluid is injected into the borehole.In this paper,a damage-based model of coupled thermal-flowing-mechanical effects was adopted to illustrate the mechanical principle of gas fracturing.Numerical simulation tools Comsol Multiphysics and Matlab were integrated to simulate the coupled process during the gas fracturing.Besides,the damage evolution of drilling areas under several conditions was fully analyzed.Simulation results indicate that the maximum tensile stress,which occurs in the upper and lower of the injection hole,decreases with the increase of the tectonic stress coefficient(TSC).As the TSC increases,shear fractures increase,a crushed area is gradually formed and the seepage area increases rapidly.The influence of TSC on fracture expansion is concluded as follows:with the decrease of TSC,the relative width of fractures decreases whilst the depth increases.It indicates that thermal stress and pore pressure promote the expansion of tensile fractures but restrain the expansion of shear fractures.Therefore,a relatively lower injection gas pressure is required to obtain the same degree of fracturing with a coupled thermal gradient.
基金supported in part by National Key R&D Program of China(2018YFA0107103,2018YFA0800300)the Chinese Academy of Sciences(XDB39000000)+3 种基金National Natural Science Foundation of China(81930083,91957203,81821001,81525022)Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110102001)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2017ZT07S054)the Fundamental Research Funds for the Central Universities(YD2070002008,2020ZYGXZR038).
文摘Metformin is currently a strong candidate anti-tumor agent in multiple cancers.However,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor heterogeneity.It thus remains unclear which hepatocellular carcinoma(HCC)patient subpopulation(s)can benefit from met-formin treatment.Here,through a genome-wide CRISPR-Cas9-based knockout screen,we find that DOCK1 levels determine the anti-tumor effects of met-formin and that DOCK1 is a synthetic lethal target of metformin in HCC.Mechanistically,metformin promotes DOCK1 phosphorylation,which activates RAC1 to facilitate cell survival,leading to metformin resistance.The DOCK1-selective inhibitor,TBOPP,potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids,and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models.Notably,metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression.This study shows that metformin effective-ness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for met-formin-resistant HCC patients.
基金National Key R&D Program of China,Grant/Award Numbers:2018YFA0800300,2018YFA0107103National Natural Science Foundation of China,Grant/Award Numbers:82072656,91957203+1 种基金Program for Guangdong Introducing Innovative and Entrepreneurial Teams,Grant/Award Number:2017ZT07S054Fundamental Research Funds for the Central Universities,Grant/Award Number:2019MS133。
文摘Background:Histone deacetylases(HDACs)engage in the regulation of various cellular processes by controlling global gene expression.The dysregulation of HDACs leads to carcinogenesis,making HDACs ideal targets for cancer therapy.However,the use of HDAC inhibitors(HDACi)as single agents has been shown to have limited success in treating solid tumors in clinical studies.This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy.Methods:Transcriptome sequencing and bioinformatics analysis were performed to screen for genes responsive toHDACi in breast cancer cells.The effects of HDACi on cell viability were detected using the MTT assay.The mRNA and protein levels of genes were determined by quantitative reverse transcription-PCR(qRT-PCR)andWestern blotting.Cell cycle distribution and apoptosis were analyzed by flow cytometry.The binding of CREB1(cAMP-response element binding protein 1)to the promoter of the KDELR(The KDEL(Lys-Asp-Glu-Leu)receptor)gene was validated by the ChIP(chromatin immunoprecipitation assay).The association between KDELR2 and protein of centriole 5(POC5)was detected by immunoprecipitation.A breast cancer-bearing mouse model was employed to analyze the effect of the HDAC3-KDELR2 axis on tumor growth.Results:KDELR2 was identified as a novel target of HDAC3,and its aberrant expression indicated the poor prognosis of breast cancer patients.We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients.The results of the ChIP assay and qRT-PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1.The HDAC3-KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation.Moreover,the HDAC3-KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo.Conclusion:Our results uncovered a previously unappreciated function of KDELR2 in tumorigenesis,linking a critical Golgi-the endoplasmic reticulum traffic transport protein to HDAC-controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.
