An in-depth understanding of the fracture behavior and mechanism of metallic shells under internal explosive loading can help develop material designs for warheads and regulate the quantity and mass distribution of th...An in-depth understanding of the fracture behavior and mechanism of metallic shells under internal explosive loading can help develop material designs for warheads and regulate the quantity and mass distribution of the fragments formed.This study investigated the fragmentation performance of a new high-carbon silicon-manganese(HCSiMn)steel cylindrical shell through fragment recovery experiments.Compared with the conventional 45Cr steel shell,the number of small mass fragments produced by the HCSi Mn steel shell was significantly increased with a scale parameter of 0.57 g fitted by the Weibull distribution model.The fragmentation process of the HCSi Mn shell exhibited more brittle tensile fracture characteristics,with the microcrack damage zone on the outer surface being the direct cause of its high fragmentation.On the one hand,the doping of alloy elements resulted in grain refinement by forming metallographic structure of tempered sorbite,so that microscopic intergranular fracture reduces the characteristic mass of the fragments;on the other hand,the distribution of alloy carbides can exert a"pinning"effect on the substrate grains,causing more initial cracks to form and propagate along the brittle carbides,further improving the shell fragmentation.Although the killing power radius for light armored vehicles was slightly reduced by about 6%,the dense killing radius of HCSiMn steel projectile against personnel can be significantly increased by about 26%based on theoretical assessment.These results provided an experimental basis for high fragmentation warhead design,and to some extent,revealed the correlation mechanism between metallographic structure and shell fragmentation.展开更多
Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing stud...Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.展开更多
基金funded by the National Natural Science Foundation of China (Grant Nos.12302444 and 12202349)。
文摘An in-depth understanding of the fracture behavior and mechanism of metallic shells under internal explosive loading can help develop material designs for warheads and regulate the quantity and mass distribution of the fragments formed.This study investigated the fragmentation performance of a new high-carbon silicon-manganese(HCSiMn)steel cylindrical shell through fragment recovery experiments.Compared with the conventional 45Cr steel shell,the number of small mass fragments produced by the HCSi Mn steel shell was significantly increased with a scale parameter of 0.57 g fitted by the Weibull distribution model.The fragmentation process of the HCSi Mn shell exhibited more brittle tensile fracture characteristics,with the microcrack damage zone on the outer surface being the direct cause of its high fragmentation.On the one hand,the doping of alloy elements resulted in grain refinement by forming metallographic structure of tempered sorbite,so that microscopic intergranular fracture reduces the characteristic mass of the fragments;on the other hand,the distribution of alloy carbides can exert a"pinning"effect on the substrate grains,causing more initial cracks to form and propagate along the brittle carbides,further improving the shell fragmentation.Although the killing power radius for light armored vehicles was slightly reduced by about 6%,the dense killing radius of HCSiMn steel projectile against personnel can be significantly increased by about 26%based on theoretical assessment.These results provided an experimental basis for high fragmentation warhead design,and to some extent,revealed the correlation mechanism between metallographic structure and shell fragmentation.
基金We thank the families for participation in this study,and we thank Novogene Technology Co.,Ltd.,for the WES sequencing and analysis.This work was supported by the National Natural Science Foundation Project of China(82070951,82271078)the National Natural Science Foundation Key Program(81930023)+3 种基金The Innovative Research Group Project of Chongqing Education Commission(CXQT19015)the Innovation Supporting Plan of Overseas Study of Chongqing(cx2018010)the National Key Clinical Specialties Construction Program of China,the Chongqing Branch of the National Clinical Research Center for Ocular Diseases,the Chongqing Key Laboratory of Ophthalmology(CSTC,2008CA5003)the Program for Youth Innovation in Future Medicine,Chongqing Medical University(w0047).
文摘Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.
