背景与目的m6A RNA甲基化修饰在肺癌的发生与进展中起着重要作用,可以调节肿瘤免疫进而影响疾病预后。目前很多集中在某些特定的m6A效应器的差异表达及对肿瘤免疫细胞浸润的影响,但单个效应器表达的变化远远不足以反映m6A修饰特征的全貌...背景与目的m6A RNA甲基化修饰在肺癌的发生与进展中起着重要作用,可以调节肿瘤免疫进而影响疾病预后。目前很多集中在某些特定的m6A效应器的差异表达及对肿瘤免疫细胞浸润的影响,但单个效应器表达的变化远远不足以反映m6A修饰特征的全貌,且关于m6A修饰对肺腺癌免疫微环境影响的研究仍较少。本研究拟探讨不同m6A修饰模式对肺腺癌中免疫微环境的影响。方法从癌症基因组图谱数据库(e Cancer Genome Atlas,TCGA)、加州大学圣克鲁兹分校泛癌全基因数据分析工具数据库(University of California Santa Cruz Xena,UCSC Xena)、基因表达综合数据库(Gene Expression Omnibus,GEO)获取肺腺癌相关数据信息。使用Maftools R分析肺腺癌队列中24个m6A效应器的基因突变,比较肺腺癌组织和正常组织中m6A效应器的表达差异,并通过Cox回归分析进行生存分析。通过Consensus Cluster Plus R非监督聚类的方法构建m6A修饰模式,进行m6A聚类生存分析、GSVA通路富集分析、免疫评分及免疫细胞浸润分析。在68例肺腺癌组织中,通过免疫组化分析LRPPRC蛋白表达水平与CD8、CD68的表达水平,验证LRPPRC与CD8;细胞毒性T细胞及巨噬细胞浸润的关系。结果在567例肺腺癌样本中有150例发生了m6A效应器突变,频率为26.46%。与正常组织相比,肺腺癌组织中共有6个读取器和3个写入器的表达明显上调。IGF2BP1和HNRNPC是影响肺腺癌患者预后的独立危险因素,且各效应器之间也存在大量的相互作用。构建了3种具有不同免疫细胞浸润特征和临床预后的m6A修饰模式。发现LRPPRC的表达与包括杀伤性T细胞和巨噬细胞在内的多种免疫细胞的浸润呈负相关,并在68例肺腺癌组织中得到验证。结论m6A修饰对肺腺癌免疫微环境的调节起着重要作用,LRPPRC有可能作为预测抗PD1免疫治疗效果的潜在生物标记物。展开更多
Adopting the classical theory of hydrocodes,the constitutive relations of concretes are separated into an equation of state(EoS)which describes the volumetric behavior of concrete material and a strength model which d...Adopting the classical theory of hydrocodes,the constitutive relations of concretes are separated into an equation of state(EoS)which describes the volumetric behavior of concrete material and a strength model which depicts the shear properties of concrete.The experiments on the EoS of concrete is always challenging due to the technical difficulties and equipment limitations,especially for the specimen size effect on the EoS.Although some researchers investigate the shock properties of concretes by fly-plate impact tests,the specimens used in their tests are usually in one size.In this paper,the fly-plate impact tests on concrete specimens with different sizes are performed to investigate the size effect on the shock properties of concrete materials.The mechanical background of the size effect on the shock properties are revealed,which is related to the lateral rarefaction effect and the deviatoric stress produced in the specimen.According to the tests results,the modified EoS considering the size effect on the shock properties of concrete are proposed,which the bulk modulus of concrete is unpredicted by up to 20% if size effects are not accounted for.展开更多
As a green environmentally-friendly material,rubberised concrete(Ru C),which has the characteristics of low elastic modulus,large deformation capacity,high damping,good energy dissipation and good crack resistance,has...As a green environmentally-friendly material,rubberised concrete(Ru C),which has the characteristics of low elastic modulus,large deformation capacity,high damping,good energy dissipation and good crack resistance,has attracted extensive attention and research in the civil engineering discipline.However,most of existing studies are based on experimental tests on Ru C material properties,and there has been no numerical study based on meso-scale modelling of Ru C yet.To more comprehensively investigate the Ru C dynamic material properties without conducting intensive experimental tests,this study developed a high-fidelity meso-scale model considering coarse and fine aggregates and rubber crumbs to numerically investigate the mechanical properties of rubberised concrete under different strain rates.The meso-scale model was verified against both quasi-static compressive testing data and Split Hopkinson Pressure Bar(SHPB)dynamic testing data.Using the verified numerical model,the dynamic properties of rubberised concrete with various rubber content(0%-30%)under different strain rates were studied.The numerical results show that the developed meso-scale model can use to predict the static and dynamic properties of rubberised concrete with high accuracy.The dynamic compressive strength of the rubberised concrete increases with the increment of the strain rate,and the strain rate sensitivity increases with the rubber content ranging from 0 to 30%.Based on intensive numerical simulation data,empirical DIFs is used as a function of strain rate and rubber content to predict the dynamic strength of rubberised concrete.展开更多
Cylindrical specimens are commonly used in Split Hopkinson pressure bar(SHPB)tests to study the uniaxial dynamic properties of concrete-like materials.In recent years,true tri-axial SHPB equipment has also been develo...Cylindrical specimens are commonly used in Split Hopkinson pressure bar(SHPB)tests to study the uniaxial dynamic properties of concrete-like materials.In recent years,true tri-axial SHPB equipment has also been developed or is under development to investigate the material dynamic properties under tri-axial impact loads.For such tests,cubic specimens are needed.It is well understood that static material strength obtained from cylinder and cube specimens are different.Conversion factors are obtained and adopted in some guidelines to convert the material streng th obtained from the two types of specimens.Previous uniaxial impact tests have also demonstrated that the failure mode and the strain rate effect of cubic specimens are very different from that of cylindrical ones.However,the mechanical background of these findings is unclear.As an extension of the previous laboratory study,this study performs numerical SHPB tests of cubic and cylindrical concrete specimens subjected to uniaxial impact load with the validated numerical model.The stress states of cubic specimens in relation to its failure mode under different strain rates is analyzed and compared with cylindrical specimens.The detailed analyses of the numerical simulation results show that the lateral inertial confinement of the cylindrical specimen is higher than that of the cubic specimen under the same strain rates.For cubic specimen,the corners aremore severely damaged because of the lower lateral confinement and the occurrence of the tensile radial stress which is not observed in cylindrical specimens.These results explain why the dynamic material strengths obtained from the two types of specimens are different and are strain rate dependent.Based on the simulation results,an empirical formula of conversion factor as a function of strain rate is proposed,which supplements the traditional conversion factor for quasi-static material strength.It can be used for transforming the dynamic compressive strength from cylinders to cubes obtained from impact tests at different strain rates.展开更多
文摘背景与目的m6A RNA甲基化修饰在肺癌的发生与进展中起着重要作用,可以调节肿瘤免疫进而影响疾病预后。目前很多集中在某些特定的m6A效应器的差异表达及对肿瘤免疫细胞浸润的影响,但单个效应器表达的变化远远不足以反映m6A修饰特征的全貌,且关于m6A修饰对肺腺癌免疫微环境影响的研究仍较少。本研究拟探讨不同m6A修饰模式对肺腺癌中免疫微环境的影响。方法从癌症基因组图谱数据库(e Cancer Genome Atlas,TCGA)、加州大学圣克鲁兹分校泛癌全基因数据分析工具数据库(University of California Santa Cruz Xena,UCSC Xena)、基因表达综合数据库(Gene Expression Omnibus,GEO)获取肺腺癌相关数据信息。使用Maftools R分析肺腺癌队列中24个m6A效应器的基因突变,比较肺腺癌组织和正常组织中m6A效应器的表达差异,并通过Cox回归分析进行生存分析。通过Consensus Cluster Plus R非监督聚类的方法构建m6A修饰模式,进行m6A聚类生存分析、GSVA通路富集分析、免疫评分及免疫细胞浸润分析。在68例肺腺癌组织中,通过免疫组化分析LRPPRC蛋白表达水平与CD8、CD68的表达水平,验证LRPPRC与CD8;细胞毒性T细胞及巨噬细胞浸润的关系。结果在567例肺腺癌样本中有150例发生了m6A效应器突变,频率为26.46%。与正常组织相比,肺腺癌组织中共有6个读取器和3个写入器的表达明显上调。IGF2BP1和HNRNPC是影响肺腺癌患者预后的独立危险因素,且各效应器之间也存在大量的相互作用。构建了3种具有不同免疫细胞浸润特征和临床预后的m6A修饰模式。发现LRPPRC的表达与包括杀伤性T细胞和巨噬细胞在内的多种免疫细胞的浸润呈负相关,并在68例肺腺癌组织中得到验证。结论m6A修饰对肺腺癌免疫微环境的调节起着重要作用,LRPPRC有可能作为预测抗PD1免疫治疗效果的潜在生物标记物。
基金supported by the National Natural Science Foundation of China[Grant Nos.51938011 and 51908405]Australian Research Council。
文摘Adopting the classical theory of hydrocodes,the constitutive relations of concretes are separated into an equation of state(EoS)which describes the volumetric behavior of concrete material and a strength model which depicts the shear properties of concrete.The experiments on the EoS of concrete is always challenging due to the technical difficulties and equipment limitations,especially for the specimen size effect on the EoS.Although some researchers investigate the shock properties of concretes by fly-plate impact tests,the specimens used in their tests are usually in one size.In this paper,the fly-plate impact tests on concrete specimens with different sizes are performed to investigate the size effect on the shock properties of concrete materials.The mechanical background of the size effect on the shock properties are revealed,which is related to the lateral rarefaction effect and the deviatoric stress produced in the specimen.According to the tests results,the modified EoS considering the size effect on the shock properties of concrete are proposed,which the bulk modulus of concrete is unpredicted by up to 20% if size effects are not accounted for.
文摘As a green environmentally-friendly material,rubberised concrete(Ru C),which has the characteristics of low elastic modulus,large deformation capacity,high damping,good energy dissipation and good crack resistance,has attracted extensive attention and research in the civil engineering discipline.However,most of existing studies are based on experimental tests on Ru C material properties,and there has been no numerical study based on meso-scale modelling of Ru C yet.To more comprehensively investigate the Ru C dynamic material properties without conducting intensive experimental tests,this study developed a high-fidelity meso-scale model considering coarse and fine aggregates and rubber crumbs to numerically investigate the mechanical properties of rubberised concrete under different strain rates.The meso-scale model was verified against both quasi-static compressive testing data and Split Hopkinson Pressure Bar(SHPB)dynamic testing data.Using the verified numerical model,the dynamic properties of rubberised concrete with various rubber content(0%-30%)under different strain rates were studied.The numerical results show that the developed meso-scale model can use to predict the static and dynamic properties of rubberised concrete with high accuracy.The dynamic compressive strength of the rubberised concrete increases with the increment of the strain rate,and the strain rate sensitivity increases with the rubber content ranging from 0 to 30%.Based on intensive numerical simulation data,empirical DIFs is used as a function of strain rate and rubber content to predict the dynamic strength of rubberised concrete.
基金Funding:This work was supported by the National Natural Science Foundation of China Igrant number 51908405 and 51938011l and Australian Research Council.
文摘Cylindrical specimens are commonly used in Split Hopkinson pressure bar(SHPB)tests to study the uniaxial dynamic properties of concrete-like materials.In recent years,true tri-axial SHPB equipment has also been developed or is under development to investigate the material dynamic properties under tri-axial impact loads.For such tests,cubic specimens are needed.It is well understood that static material strength obtained from cylinder and cube specimens are different.Conversion factors are obtained and adopted in some guidelines to convert the material streng th obtained from the two types of specimens.Previous uniaxial impact tests have also demonstrated that the failure mode and the strain rate effect of cubic specimens are very different from that of cylindrical ones.However,the mechanical background of these findings is unclear.As an extension of the previous laboratory study,this study performs numerical SHPB tests of cubic and cylindrical concrete specimens subjected to uniaxial impact load with the validated numerical model.The stress states of cubic specimens in relation to its failure mode under different strain rates is analyzed and compared with cylindrical specimens.The detailed analyses of the numerical simulation results show that the lateral inertial confinement of the cylindrical specimen is higher than that of the cubic specimen under the same strain rates.For cubic specimen,the corners aremore severely damaged because of the lower lateral confinement and the occurrence of the tensile radial stress which is not observed in cylindrical specimens.These results explain why the dynamic material strengths obtained from the two types of specimens are different and are strain rate dependent.Based on the simulation results,an empirical formula of conversion factor as a function of strain rate is proposed,which supplements the traditional conversion factor for quasi-static material strength.It can be used for transforming the dynamic compressive strength from cylinders to cubes obtained from impact tests at different strain rates.
