Primary cilia function as critical sensory organelles that mediate multiple signaling pathways,including the Hedgehog(Hh)pathway,which is essential for organ patterning and morphogenesis.Disruptions in Hh signaling ha...Primary cilia function as critical sensory organelles that mediate multiple signaling pathways,including the Hedgehog(Hh)pathway,which is essential for organ patterning and morphogenesis.Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice.Cilk1,a highly conserved serine/threonine-protein kinase localized within primary cilia,plays a critical role in ciliary transport.Loss of Cilk1 results in severe ciliopathy phenotypes,including polydactyly,edema,and cleft palate.However,the role of Cilk1 in tooth development remains unexplored.In this study,we investigated the role of Cilk1 in tooth development.Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars.Cilk1 deficiency resulted in altered ciliary dynamics,characterized by reduced frequency and increased length,accompanied by downregulation of Hh target genes,such as Ptch1 and Sostdc1,leading to the formation of diastemal supernumerary teeth.Furthermore,in Cilk1^(-/-);PCS1–MRCS1^(△/△)mice,which exhibit a compounded suppression of Hh signaling,we uncovered a novel phenomenon:diastemal supernumerary teeth can be larger than first molars.Based on these findings,we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning:initially inducing diastemal supernumerary teeth,then enlarging them,and ultimately leading to molar fusion.This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.展开更多
针对实际道路路网的一类路径寻优问题,提出了带回退机制的蚁群搜索算法,求解在实际道路路网中完成遍历所有规定节点的一条较优路径。为解决大规模实际道路路网数据量大、蚁群算法收敛速度慢的问题,分别采用Intel Threading Building Blo...针对实际道路路网的一类路径寻优问题,提出了带回退机制的蚁群搜索算法,求解在实际道路路网中完成遍历所有规定节点的一条较优路径。为解决大规模实际道路路网数据量大、蚁群算法收敛速度慢的问题,分别采用Intel Threading Building Blocks(TBB)和Cilk++并行编程模型实现了并行蚁群搜索。与基于WinAPI函数的多线程蚁群算法相比,这两种模型均避免了手动启动线程及识别临界区资源等复杂操作,开发难度降低;在运行效率方面,基于TBB的并行蚁群算法和基于WinAPI的并行蚁群算法效率接近,而基于Cilk++的并行蚁群算法在双核环境下,运行效率和加速比都超过了基于WinAPI的并行蚁群算法。展开更多
基金supported by the National Research Foundation of Korea(NRF)grants funded by the Korean government(MSIT)(NRF-2020R1A2C2005790,NRF2023R1A2C1007510,RS-2023-00269830,RS-2024-00438542)。
文摘Primary cilia function as critical sensory organelles that mediate multiple signaling pathways,including the Hedgehog(Hh)pathway,which is essential for organ patterning and morphogenesis.Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice.Cilk1,a highly conserved serine/threonine-protein kinase localized within primary cilia,plays a critical role in ciliary transport.Loss of Cilk1 results in severe ciliopathy phenotypes,including polydactyly,edema,and cleft palate.However,the role of Cilk1 in tooth development remains unexplored.In this study,we investigated the role of Cilk1 in tooth development.Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars.Cilk1 deficiency resulted in altered ciliary dynamics,characterized by reduced frequency and increased length,accompanied by downregulation of Hh target genes,such as Ptch1 and Sostdc1,leading to the formation of diastemal supernumerary teeth.Furthermore,in Cilk1^(-/-);PCS1–MRCS1^(△/△)mice,which exhibit a compounded suppression of Hh signaling,we uncovered a novel phenomenon:diastemal supernumerary teeth can be larger than first molars.Based on these findings,we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning:initially inducing diastemal supernumerary teeth,then enlarging them,and ultimately leading to molar fusion.This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
文摘针对实际道路路网的一类路径寻优问题,提出了带回退机制的蚁群搜索算法,求解在实际道路路网中完成遍历所有规定节点的一条较优路径。为解决大规模实际道路路网数据量大、蚁群算法收敛速度慢的问题,分别采用Intel Threading Building Blocks(TBB)和Cilk++并行编程模型实现了并行蚁群搜索。与基于WinAPI函数的多线程蚁群算法相比,这两种模型均避免了手动启动线程及识别临界区资源等复杂操作,开发难度降低;在运行效率方面,基于TBB的并行蚁群算法和基于WinAPI的并行蚁群算法效率接近,而基于Cilk++的并行蚁群算法在双核环境下,运行效率和加速比都超过了基于WinAPI的并行蚁群算法。
