Aiming at the problem of tool wear and breakage, the low accuracy of machined surface duringthe milling process of automobile panel splicing dies, the cutting force modeling of micro element is carriedout. The cutting...Aiming at the problem of tool wear and breakage, the low accuracy of machined surface duringthe milling process of automobile panel splicing dies, the cutting force modeling of micro element is carriedout. The cutting chip thickness of each cutting cycle is built as a function of the cutting angle and the shearforce according to the different hardness of machining materials, and a plow force model are obtained underng angles. By introducing a single degree of freedom italic collision model, the Hopkinsontest is used to obtain the elastic deformation δ of the tool workpiece impact under different spindle speeds,sults showforce on the tool in the transition area is obtained. Combining above models together,of milling force in the transition area can be obtained. Experiment and simulation reconslstendirections is studied. Fromcythto prove the accuracy of the model. The surface quality under different feede analysis results of machined surface quality, surfacedifference between workpieces, it is concluded that better surface quality can be obtaineness and heightness and low hardness workpiece. The results provide theoretical support for the optimizationing process in the splicing die of the automobile panel highof the milling process in the splicing die of the automobile panel.展开更多
Spinal muscular atrophy(SMA)is a rare hereditary neuromuscular disease with a high lethality rate in infants.Variants in the homologous genes survival of motor neuron(SMN)1 and SMN2 have been reported to be SMA pathog...Spinal muscular atrophy(SMA)is a rare hereditary neuromuscular disease with a high lethality rate in infants.Variants in the homologous genes survival of motor neuron(SMN)1 and SMN2 have been reported to be SMA pathogenic factors.Previous studies showed that a highinclusion rate of SMN2 exon 7 increased SMN expression,which in turn reduced the severity of SMA.The inclusion rate of SMN2 exon 7 was higher in neural tissues than in non-neural tissues.Neuro-oncological ventral antigen(NOVA)is a splicing factor that is specifically and highly expressed in neurons.It plays a key role in nervous system development and in the induction of nervous system diseases.Howeve r,it remains unclear whether this splicing factor affects SMA.In this study,we analyzed the inclusion of SMN2 exon 7 in different tissues in a mouse model of SMA(genotype smn^(-/-)SMN2^(2 tg/0))and litter mate controls(genotype smn^(+/-)SMN2^(2 tg/0)).We found that inclusion level of SMN2 exon 7 was high in the brain and spinal co rd tissue,and that NOVA1 was also highly expressed in nervous system tissues.In addition,SMN2 exon 7 and NOVA1 were expressed synchronously in the central nervous system.We further investigated the effects of NOVA1 on disease and found that the number of neurons in the anterior horn of spinal cord decreased in the mouse model of SMA during postnatal days 1-7,and that NOVA1 expression levels in motor neurons decreased simultaneously as spinal muscular atrophy developed.We also found that in vitro expression of NOVA1 increased the inclusion of SMN2 exon 7 and expression ofthe SMN2 protein in the U87 MG cell line,whereas the opposite was observed when NOVA1 was knocked down.Finally,point mutation and RNA pull-down showed that the UCAC motif in SMN2 exon 7 plays a critical role in NOVA1 binding and promoting the inclusion of exon 7.Moreove r,CA was more essential for the inclusion of exon 7 than the order of Y residues in the motif.Collectively,these findings indicate that NOVA1 intera cts with the UCAC motif in exon 7 of SMN2,there by enhancing inclusion of exon 7 in SMN2,which in turn increases expression of the SMN protein.展开更多
Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA...Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA;the small nucleolar RNA RBII-52 is complementary to exon Vb and promotes its inclusion. The expression of HBII-52 (the human equivalent of RBII-52) is reduced in Prader-Willi syndrome, patients of which have a high pain threshold. Here, we measured the pain threshold in a rat model of orofacial neuropathic pain and related it to the expression levels of wild-type and variant 5HTR2C and RBII-52. We generated an infraorbital nerve loose ligation model of neuropathic pain in rats and measured the pain threshold of the animals using mechanical stimulation with von Frey filaments. We then sacrificed the animals and examined the RNA levels of 5HTR2C and RBII-52 in the cervical spinal cord by real-time PCR. On post-injury day 28, pain threshold values in injured rats were significantly lower than in sham-operated or na?ve animals. The levels of total and exon Vb-skipped 5HTR2C mRNA were significantly lower in injured rats than in that sham-operated or na?ve rats, and the ratio of exon Vb-skipped 5HTR2C to total 5HTR2C was significantly higher. There were no significant differences in RBII-52 expression among the groups. Our data suggest that neuropathic pain induces serotonergic dysfunction mediated by 5HTR2C alternative splicing. 5HTR2C might be subject to complicated and fine regulation both by RNA editing and by alternative splicing.展开更多
In order to develop a method to break the aircrafts canopy,a miniature detonating cords (MDC) of 1 mm in diameter were manufactured and its detonation properties were studied.MDC in a heavy lead confinement were also ...In order to develop a method to break the aircrafts canopy,a miniature detonating cords (MDC) of 1 mm in diameter were manufactured and its detonation properties were studied.MDC in a heavy lead confinement were also manufactured and were examined for breaking of organic glass plates.Results showthat MDC in lead confinement with 1g plastic explosive per metre,cuts organic glass plate 10 mm thick.展开更多
文摘Aiming at the problem of tool wear and breakage, the low accuracy of machined surface duringthe milling process of automobile panel splicing dies, the cutting force modeling of micro element is carriedout. The cutting chip thickness of each cutting cycle is built as a function of the cutting angle and the shearforce according to the different hardness of machining materials, and a plow force model are obtained underng angles. By introducing a single degree of freedom italic collision model, the Hopkinsontest is used to obtain the elastic deformation δ of the tool workpiece impact under different spindle speeds,sults showforce on the tool in the transition area is obtained. Combining above models together,of milling force in the transition area can be obtained. Experiment and simulation reconslstendirections is studied. Fromcythto prove the accuracy of the model. The surface quality under different feede analysis results of machined surface quality, surfacedifference between workpieces, it is concluded that better surface quality can be obtaineness and heightness and low hardness workpiece. The results provide theoretical support for the optimizationing process in the splicing die of the automobile panel highof the milling process in the splicing die of the automobile panel.
基金the National Natural Science Foundation of China,No.32000841(to JJS)a grant from Science and Technology Project of Nantong of Jiangsu Province,No.JC2018090(to LCW)a grant from Graduate Research and Innovation Project of Jiangsu Province,No.KYCX18-2415(to LLD)。
文摘Spinal muscular atrophy(SMA)is a rare hereditary neuromuscular disease with a high lethality rate in infants.Variants in the homologous genes survival of motor neuron(SMN)1 and SMN2 have been reported to be SMA pathogenic factors.Previous studies showed that a highinclusion rate of SMN2 exon 7 increased SMN expression,which in turn reduced the severity of SMA.The inclusion rate of SMN2 exon 7 was higher in neural tissues than in non-neural tissues.Neuro-oncological ventral antigen(NOVA)is a splicing factor that is specifically and highly expressed in neurons.It plays a key role in nervous system development and in the induction of nervous system diseases.Howeve r,it remains unclear whether this splicing factor affects SMA.In this study,we analyzed the inclusion of SMN2 exon 7 in different tissues in a mouse model of SMA(genotype smn^(-/-)SMN2^(2 tg/0))and litter mate controls(genotype smn^(+/-)SMN2^(2 tg/0)).We found that inclusion level of SMN2 exon 7 was high in the brain and spinal co rd tissue,and that NOVA1 was also highly expressed in nervous system tissues.In addition,SMN2 exon 7 and NOVA1 were expressed synchronously in the central nervous system.We further investigated the effects of NOVA1 on disease and found that the number of neurons in the anterior horn of spinal cord decreased in the mouse model of SMA during postnatal days 1-7,and that NOVA1 expression levels in motor neurons decreased simultaneously as spinal muscular atrophy developed.We also found that in vitro expression of NOVA1 increased the inclusion of SMN2 exon 7 and expression ofthe SMN2 protein in the U87 MG cell line,whereas the opposite was observed when NOVA1 was knocked down.Finally,point mutation and RNA pull-down showed that the UCAC motif in SMN2 exon 7 plays a critical role in NOVA1 binding and promoting the inclusion of exon 7.Moreove r,CA was more essential for the inclusion of exon 7 than the order of Y residues in the motif.Collectively,these findings indicate that NOVA1 intera cts with the UCAC motif in exon 7 of SMN2,there by enhancing inclusion of exon 7 in SMN2,which in turn increases expression of the SMN protein.
文摘Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA;the small nucleolar RNA RBII-52 is complementary to exon Vb and promotes its inclusion. The expression of HBII-52 (the human equivalent of RBII-52) is reduced in Prader-Willi syndrome, patients of which have a high pain threshold. Here, we measured the pain threshold in a rat model of orofacial neuropathic pain and related it to the expression levels of wild-type and variant 5HTR2C and RBII-52. We generated an infraorbital nerve loose ligation model of neuropathic pain in rats and measured the pain threshold of the animals using mechanical stimulation with von Frey filaments. We then sacrificed the animals and examined the RNA levels of 5HTR2C and RBII-52 in the cervical spinal cord by real-time PCR. On post-injury day 28, pain threshold values in injured rats were significantly lower than in sham-operated or na?ve animals. The levels of total and exon Vb-skipped 5HTR2C mRNA were significantly lower in injured rats than in that sham-operated or na?ve rats, and the ratio of exon Vb-skipped 5HTR2C to total 5HTR2C was significantly higher. There were no significant differences in RBII-52 expression among the groups. Our data suggest that neuropathic pain induces serotonergic dysfunction mediated by 5HTR2C alternative splicing. 5HTR2C might be subject to complicated and fine regulation both by RNA editing and by alternative splicing.
文摘In order to develop a method to break the aircrafts canopy,a miniature detonating cords (MDC) of 1 mm in diameter were manufactured and its detonation properties were studied.MDC in a heavy lead confinement were also manufactured and were examined for breaking of organic glass plates.Results showthat MDC in lead confinement with 1g plastic explosive per metre,cuts organic glass plate 10 mm thick.
