Heterotopic ossification(HO),true bone formation in soft tissue,is closely associated with abnormal injury/immune responses.We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation o...Heterotopic ossification(HO),true bone formation in soft tissue,is closely associated with abnormal injury/immune responses.We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation of immune checkpoint proteins(ICs).We found that the earliest stages of HO are characterized by enhanced infiltration of polarized macrophages into sites of minor injuries in an animal model of HO.The non-specific immune suppressants,Rapamycin and Ebselen,prevented HO providing evidence of the central role of the immune responses.We examined the expression pattern of ICs and found that they are dysregulated in HO lesions.More importantly,loss of function of inhibitory ICs(including PD1,PD-L1,and CD152)markedly inhibited HO,whereas loss of function of stimulatory ICs(including CD40L and OX-40L)facilitated HO.These findings suggest that IC inhibitors may provide a therapeutic approach to prevent or limit the extent of HO.展开更多
This paper focuses on the issue of reliability and global sensitivity analysis for an airplane slat mechanism considering the uncertainties in the wear process of mechanical components.First,the multi-body kinematic m...This paper focuses on the issue of reliability and global sensitivity analysis for an airplane slat mechanism considering the uncertainties in the wear process of mechanical components.First,the multi-body kinematic model of the slat mechanism is built in the ADAMS software.The geometrical sizes of the roller wheels after wear degradation are considered as input variables and the angle the slat should turn is considered as the output response.To accurately identify the influential roller wheels to the reliability and robustness of the slat mechanism,the failure probability based sensitivity and variance-based sensitivity indices are introduced.Comprehensive analysis of the results have shown that the reliability analysis and global sensitivity theory can help engineers find significant parts by their contributions,thus provide guidance for mechanical design and maintenance.展开更多
基金supported by NIH grant RO1 AR066539supported in part by National Natural Science Foundation of China (81472087)Natural Science Foundation of Anhui province (1508085MC45)
文摘Heterotopic ossification(HO),true bone formation in soft tissue,is closely associated with abnormal injury/immune responses.We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation of immune checkpoint proteins(ICs).We found that the earliest stages of HO are characterized by enhanced infiltration of polarized macrophages into sites of minor injuries in an animal model of HO.The non-specific immune suppressants,Rapamycin and Ebselen,prevented HO providing evidence of the central role of the immune responses.We examined the expression pattern of ICs and found that they are dysregulated in HO lesions.More importantly,loss of function of inhibitory ICs(including PD1,PD-L1,and CD152)markedly inhibited HO,whereas loss of function of stimulatory ICs(including CD40L and OX-40L)facilitated HO.These findings suggest that IC inhibitors may provide a therapeutic approach to prevent or limit the extent of HO.
基金supported by the National Natural Science Foundation of China(NSFC51975476)the Natural Science Basic Research Plan in Shaanxi Province(2020JM-135)Aerospace Science and Technology Foundation of China。
文摘This paper focuses on the issue of reliability and global sensitivity analysis for an airplane slat mechanism considering the uncertainties in the wear process of mechanical components.First,the multi-body kinematic model of the slat mechanism is built in the ADAMS software.The geometrical sizes of the roller wheels after wear degradation are considered as input variables and the angle the slat should turn is considered as the output response.To accurately identify the influential roller wheels to the reliability and robustness of the slat mechanism,the failure probability based sensitivity and variance-based sensitivity indices are introduced.Comprehensive analysis of the results have shown that the reliability analysis and global sensitivity theory can help engineers find significant parts by their contributions,thus provide guidance for mechanical design and maintenance.
