A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body＇s front lines in defense agai...A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body＇s front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 （Nrf2-/-） exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf2-/- mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells （BMSCs） from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine （NAC）, suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf2-/- animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis.展开更多
Owing to the lack of a direct link with the operations in short-range air combat,conventional aircraft flying qualities criteria are inappropriate to guide the design of a task-tailored flight control law.By applying ...Owing to the lack of a direct link with the operations in short-range air combat,conventional aircraft flying qualities criteria are inappropriate to guide the design of a task-tailored flight control law.By applying the mission-oriented flying qualities evaluation approach,various aircraft with different control law parameters are evaluated on a ground-based simulator.This paper compares the evaluation results with several conventional flying qualities criteria,and discusses the appropriate parameter combination to reflect the flying qualities requirements of short-range air combat.The comparison and analysis show that a short-range air combat mission requires a higher minimum short period mode natural frequency and a smaller maximum roll mode time constant,and allows a lower minimum pitch attitude bandwidth and a higher maximum short period mode damp ratio than those of conventional flying qualities criteria.Furthermore,a combination of the pitch attitude bandwidth,the pitch attitude magnitude at the bandwidth frequency,and the pitch attitude transfer function gain can define the flying qualities requirements of short-range air combat.The new metric can successfully predict the flying quality levels of aircraft in a short-range air combat mission.展开更多
基金supported by a Johns Hopkins Musculoskeletal Research Pilot and Feasibility Grant (RKT) and NIH R01 AR062074 (DJD)
文摘A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body＇s front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 （Nrf2-/-） exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf2-/- mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells （BMSCs） from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine （NAC）, suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf2-/- animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis.
文摘Owing to the lack of a direct link with the operations in short-range air combat,conventional aircraft flying qualities criteria are inappropriate to guide the design of a task-tailored flight control law.By applying the mission-oriented flying qualities evaluation approach,various aircraft with different control law parameters are evaluated on a ground-based simulator.This paper compares the evaluation results with several conventional flying qualities criteria,and discusses the appropriate parameter combination to reflect the flying qualities requirements of short-range air combat.The comparison and analysis show that a short-range air combat mission requires a higher minimum short period mode natural frequency and a smaller maximum roll mode time constant,and allows a lower minimum pitch attitude bandwidth and a higher maximum short period mode damp ratio than those of conventional flying qualities criteria.Furthermore,a combination of the pitch attitude bandwidth,the pitch attitude magnitude at the bandwidth frequency,and the pitch attitude transfer function gain can define the flying qualities requirements of short-range air combat.The new metric can successfully predict the flying quality levels of aircraft in a short-range air combat mission.
