Primary ciliary dyskinesia(PCD)is a rare disorder characterized by extensive genetic heterogeneity.However,in the genetic pathogenesis of PCD,copy number variation(CNV)has not received sufcient attention and has rarel...Primary ciliary dyskinesia(PCD)is a rare disorder characterized by extensive genetic heterogeneity.However,in the genetic pathogenesis of PCD,copy number variation(CNV)has not received sufcient attention and has rarely been reported,especially in China.Next-generation sequencing(NGS)followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing(WES)analysis.Quantitative real-time polymerase chain reaction(qPCR)and Sanger sequencing were used to confrm these CNVs.To further characterize the ciliary phenotypes,high-speed video microscopy analysis(HSVA),transmission electron microscopy(TEM),and immunofuorescence(IF)analysis were used.Patient 1(F1:II-1),a 0.6-year-old girl,came from a nonconsanguineous family-I.She presented with situs inversus totalis,neonatal respiratory distress,and sinusitis.The nasal nitric oxide level was markedly reduced.The respiratory cilia beat with reduced amplitude.TEM revealed shortened outer dynein arms(ODA)of cilia.chr5:13717907-13722661del spanning exons 71–72 was identifed by NGS-based CNV analysis.Patient 2(F2:IV-4),a 37-year-old man,and his eldest brother Patient 3(F2:IV-2)came from a consanguineous family-II.Both had sinusitis,bronchiectasis and situs inversus totalis.The respiratory cilia of Patient 2 and Patient 3 were found to be uniformly immotile,with ODA defects.Two novel homozygous deletions chr5:13720087_13733030delinsGTTTTC and chr5:13649539_13707643del,spanning exons 69–71 and exons 77–79 were identifed by NGS-based CNV analysis.Abnormalities in DNA copy number were confrmed by qPCR amplifcation.IF showed that the respiratory cilia of Patient 1 and Patient 2 were defcient in dynein axonemal heavy chain 5(DNAH5)protein expression.This report identifed three novel DNAH5 disease-associated variants by WES-based CNV analysis.Our study expands the genetic spectrum of PCD with DNAH5 in the Chinese population.展开更多
As the computer system has developed much in this highly information-oriented society, database security has become a very important problem and its backup strategies need to be made more efficiently and safety. The i...As the computer system has developed much in this highly information-oriented society, database security has become a very important problem and its backup strategies need to be made more efficiently and safety. The image copy method has been used as the most simple and dependable recovery mechanism for media failure. However, this method spends high overhead costs for massive data transmission and much processing time in the normal operation of the database. To cover such weak points, incremental and full backup methods are adopted before updated trucks reach a predetermined level. Moreover, when the number of full backup files exceeded a predetermined level, we stop incremental and full backups and switch it to the image copy. This paper applies cumulative damage model to backup of files in a database system, by putting damage shock by update, failure shock by database failure and damage by dumped files, and considers the tradeoff among overhead costs of image copy and incremental, full backup methods, and discusses analytically an optimal policy for the image copy backup interval. Finally, numerical examples are given in the case of Poisson process and exponential distributions.展开更多
主/副版本备份技术是分布式系统常用的实时容错调度方法,然而传统的主动方式副版本即使在无处理机故障时也需要在备份处理机上完全运行,增加了处理机消耗.提出一种基于固定优先级调度算法的延迟主动副版本(deferred active backup-copy...主/副版本备份技术是分布式系统常用的实时容错调度方法,然而传统的主动方式副版本即使在无处理机故障时也需要在备份处理机上完全运行,增加了处理机消耗.提出一种基于固定优先级调度算法的延迟主动副版本(deferred active backup-copy)备份技术,该技术通过尽量向后调度主动方式的副版本,并在主版本成功执行时终止副版本的执行来减少备份的冗余度.在此基础上,提出一种基于该技术的以最小化处理机数目为优化目标的启发式任务分配算法——基于延迟主动副版本的最佳适应算法DABCBF(deferred active backup-copy based best-fit algorithm).DABCBF在保证系统的实时性和容错能力的前提条件下,通过尽量减少主版本的最坏响应时间来最大程度地减少冗余,以节省处理机.最后通过仿真实验,证明了算法的可行性和有效性.展开更多
基金Shanghai Natural Science Foundation of Science and Technology Innovation Action Plan(Grant Number:21ZR1410200 and 21ZR1409900).
文摘Primary ciliary dyskinesia(PCD)is a rare disorder characterized by extensive genetic heterogeneity.However,in the genetic pathogenesis of PCD,copy number variation(CNV)has not received sufcient attention and has rarely been reported,especially in China.Next-generation sequencing(NGS)followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing(WES)analysis.Quantitative real-time polymerase chain reaction(qPCR)and Sanger sequencing were used to confrm these CNVs.To further characterize the ciliary phenotypes,high-speed video microscopy analysis(HSVA),transmission electron microscopy(TEM),and immunofuorescence(IF)analysis were used.Patient 1(F1:II-1),a 0.6-year-old girl,came from a nonconsanguineous family-I.She presented with situs inversus totalis,neonatal respiratory distress,and sinusitis.The nasal nitric oxide level was markedly reduced.The respiratory cilia beat with reduced amplitude.TEM revealed shortened outer dynein arms(ODA)of cilia.chr5:13717907-13722661del spanning exons 71–72 was identifed by NGS-based CNV analysis.Patient 2(F2:IV-4),a 37-year-old man,and his eldest brother Patient 3(F2:IV-2)came from a consanguineous family-II.Both had sinusitis,bronchiectasis and situs inversus totalis.The respiratory cilia of Patient 2 and Patient 3 were found to be uniformly immotile,with ODA defects.Two novel homozygous deletions chr5:13720087_13733030delinsGTTTTC and chr5:13649539_13707643del,spanning exons 69–71 and exons 77–79 were identifed by NGS-based CNV analysis.Abnormalities in DNA copy number were confrmed by qPCR amplifcation.IF showed that the respiratory cilia of Patient 1 and Patient 2 were defcient in dynein axonemal heavy chain 5(DNAH5)protein expression.This report identifed three novel DNAH5 disease-associated variants by WES-based CNV analysis.Our study expands the genetic spectrum of PCD with DNAH5 in the Chinese population.
文摘As the computer system has developed much in this highly information-oriented society, database security has become a very important problem and its backup strategies need to be made more efficiently and safety. The image copy method has been used as the most simple and dependable recovery mechanism for media failure. However, this method spends high overhead costs for massive data transmission and much processing time in the normal operation of the database. To cover such weak points, incremental and full backup methods are adopted before updated trucks reach a predetermined level. Moreover, when the number of full backup files exceeded a predetermined level, we stop incremental and full backups and switch it to the image copy. This paper applies cumulative damage model to backup of files in a database system, by putting damage shock by update, failure shock by database failure and damage by dumped files, and considers the tradeoff among overhead costs of image copy and incremental, full backup methods, and discusses analytically an optimal policy for the image copy backup interval. Finally, numerical examples are given in the case of Poisson process and exponential distributions.
文摘主/副版本备份技术是分布式系统常用的实时容错调度方法,然而传统的主动方式副版本即使在无处理机故障时也需要在备份处理机上完全运行,增加了处理机消耗.提出一种基于固定优先级调度算法的延迟主动副版本(deferred active backup-copy)备份技术,该技术通过尽量向后调度主动方式的副版本,并在主版本成功执行时终止副版本的执行来减少备份的冗余度.在此基础上,提出一种基于该技术的以最小化处理机数目为优化目标的启发式任务分配算法——基于延迟主动副版本的最佳适应算法DABCBF(deferred active backup-copy based best-fit algorithm).DABCBF在保证系统的实时性和容错能力的前提条件下,通过尽量减少主版本的最坏响应时间来最大程度地减少冗余,以节省处理机.最后通过仿真实验,证明了算法的可行性和有效性.
