Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RAN...Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.展开更多
Data transmission in multimedia WSNs are required high bandwidth and reliable transfer because of large amount of data size. However, some applications of WSNs are required high quality. In this context, main factor i...Data transmission in multimedia WSNs are required high bandwidth and reliable transfer because of large amount of data size. However, some applications of WSNs are required high quality. In this context, main factor in quality of services (QoS) metrics in WSNs becomes longevity of the network and high quality. In sensor nodes, choosing relevant transceiver and microcontroller components plays important role in assembling sensor devices, in which data controls should be designed so that packet loss is minimized. Available QoS metrics based on queuing/buffer management in wired and other wireless networks don’t applicable in WSNs because of its unique characteristics. In this paper the simplest model of QoS model-bufferless system were proposed. In the proposed model, measurement of the probability of blocking of the arrival packets was suggested by using queuing theory in order to increase QoS. Given probability of blocking (PB) illustrates clear picture how system specification should be chosen so that blocking state would be minimized.展开更多
In this paper model of integrated voice/data cellular wireless networks (CWN) are investigated. The unified approximate approach to calculate the desired Quality of Service (QoS) metrics in an isolated cell of such ne...In this paper model of integrated voice/data cellular wireless networks (CWN) are investigated. The unified approximate approach to calculate the desired Quality of Service (QoS) metrics in an isolated cell of such networks under two multi-parametric call admission control (CAC) strategies is developed. One of them is based on the guard channels scheme while the second is based on a threshold scheme. Results of the numerical experiments are given and a comparison of QoS metrics under different CAC strategies is carried out.展开更多
基金supported by the Intramural Research Program of the NIDCR, NICHD,and Clinical Center, National Institutes of Healthsupported by Amgen, Inc.+2 种基金supported in part by the NIDCR Genomics and Computational Biology Core:ZIC DC000086Veterinary Resources Core:ZIC DE000740-05supported by the Research on Women’s Health(ORWH)through the Bench to Bedside Program award#884515.
文摘Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.
文摘Data transmission in multimedia WSNs are required high bandwidth and reliable transfer because of large amount of data size. However, some applications of WSNs are required high quality. In this context, main factor in quality of services (QoS) metrics in WSNs becomes longevity of the network and high quality. In sensor nodes, choosing relevant transceiver and microcontroller components plays important role in assembling sensor devices, in which data controls should be designed so that packet loss is minimized. Available QoS metrics based on queuing/buffer management in wired and other wireless networks don’t applicable in WSNs because of its unique characteristics. In this paper the simplest model of QoS model-bufferless system were proposed. In the proposed model, measurement of the probability of blocking of the arrival packets was suggested by using queuing theory in order to increase QoS. Given probability of blocking (PB) illustrates clear picture how system specification should be chosen so that blocking state would be minimized.
文摘In this paper model of integrated voice/data cellular wireless networks (CWN) are investigated. The unified approximate approach to calculate the desired Quality of Service (QoS) metrics in an isolated cell of such networks under two multi-parametric call admission control (CAC) strategies is developed. One of them is based on the guard channels scheme while the second is based on a threshold scheme. Results of the numerical experiments are given and a comparison of QoS metrics under different CAC strategies is carried out.
