针对目前EPCglobal ONS(Object Name Service)系统存在的信息容易被偷听、篡改、欺骗等威胁,提出一种基于DNSCurve协议和椭圆曲线加密机制的ONS系统来实现产品动态信息在查询过程中的安全性和隐私性,并通过实验验证此系统的安全性能,能...针对目前EPCglobal ONS(Object Name Service)系统存在的信息容易被偷听、篡改、欺骗等威胁,提出一种基于DNSCurve协议和椭圆曲线加密机制的ONS系统来实现产品动态信息在查询过程中的安全性和隐私性,并通过实验验证此系统的安全性能,能够抵御偷听、篡改、欺骗等攻击,有效地加强了ONS系统安全,对整个物联网的发展具有很重要的现实意义。展开更多
AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer(CRC) predisposing genes in early-onset or familial CRC cases.METHODS: We performed whole...AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer(CRC) predisposing genes in early-onset or familial CRC cases.METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with nonpolyposis CRC diagnosed at ≤ 40 years of age, or from multiple affected CRC families with at least 1 firstdegree relative diagnosed with CRC at ≤ 55 years of age.Genomic DNA from blood was enriched for exome sequences using the Sure Select Human All Exon Kit, version 2(Agilent Technologies) and sequencing was performed on an Illumina Hi Seq 2000 platform.Data were processed through an analytical pipeline to search for rare germline variants in known or novel CRC predisposing genes.RESULTS: In total, 32 germline variants in 23 genes were identified and confirmed by Sanger sequencing.In 6 of the 21 families(29%), we identified 7 mutations in 3 known CRC predisposing genes including MLH1(5 patients), MSH2(1 patient), and MUTYH(biallelic, 1 patient), five of which were reported as pathogenic.Inthe remaining 15 families, we identified 20 rare and novel potentially deleterious variants in 19 genes, six of which were truncating mutations.One previously unreported variant identified in a conserved region of EIF2AK4(p.Glu738_Asp739insA rgA rg) was found to represent a local Chinese variant, which was significantly enriched in our early-onset CRC patient cohort compared to a control cohort of 100 healthy Chinese individuals scored negative by colonoscopy(33.3% vs 7%, P < 0.001).CONCLUSION: Whole-exome sequencing of early-onset or familial CRC cases serves as an efficient method to identify known and potential pathogenic variants in established and novel candidate CRC predisposing genes.展开更多
Key epidemiological parameters,including the effective reproduction number,,and the instantaneous growth rate,,generated from an ensemble of models,have been informing public health policy throughout the COVID-19 pand...Key epidemiological parameters,including the effective reproduction number,,and the instantaneous growth rate,,generated from an ensemble of models,have been informing public health policy throughout the COVID-19 pandemic in the four nations of the United Kingdom of Great Britain and Northern Ireland(UK).However,estimation of these quantities became challenging with the scaling down of surveillance systems as part of the transition from the“emergency”to“endemic”phase of the pandemic.The Office for National Statistics(ONS)COVID-19 Infection Survey(CIS)provided an opportunity to continue estimating these parameters in the absence of other data streams.We used a penalised spline model fitted to the publicly-available ONS CIS test positivity estimates to produce a smoothed estimate of the prevalence of SARS-CoV-2 positivity over time.The resulting fitted curve was used to estimate the“ONS-based”and across the four nations of the UK.Estimates produced under this model are compared to government-published estimates with particular consideration given to the contribution that this single data stream can offer in the estimation of these parameters.Depending on the nation and parameter,we found that up to 77%of the variance in the government-published estimates can be explained by the ONS-based estimates,demonstrating the value of this singular data stream to track the epidemic in each of the four nations.We additionally find that the ONS-based estimates uncover epidemic trends earlier than the corresponding government-published estimates.Our work shows that the ONS CIS can be used to generate key COVID-19 epidemiological parameters across the four UK nations,further underlining the enormous value of such population-level studies of infection.This is not intended as an alternative to ensemble modelling,rather it is intended as a potential solution to the aforementioned challenge faced by public health officials in the UK in early 2022.展开更多
文摘针对目前EPCglobal ONS(Object Name Service)系统存在的信息容易被偷听、篡改、欺骗等威胁,提出一种基于DNSCurve协议和椭圆曲线加密机制的ONS系统来实现产品动态信息在查询过程中的安全性和隐私性,并通过实验验证此系统的安全性能,能够抵御偷听、篡改、欺骗等攻击,有效地加强了ONS系统安全,对整个物联网的发展具有很重要的现实意义。
基金Supported by research grants from the Dutch Cancer Society(KWF,KUN-4335)the Netherlands Organization for Scientific Research(NWO,91710358)+2 种基金the Royal Dutch Academy of Sciences(KNAW)National Natural Science Foundation of China(NSFC,81272194 and 81072041)a scholarship from the China Scholarship Council(CSC)to Zhang JX
文摘AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer(CRC) predisposing genes in early-onset or familial CRC cases.METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with nonpolyposis CRC diagnosed at ≤ 40 years of age, or from multiple affected CRC families with at least 1 firstdegree relative diagnosed with CRC at ≤ 55 years of age.Genomic DNA from blood was enriched for exome sequences using the Sure Select Human All Exon Kit, version 2(Agilent Technologies) and sequencing was performed on an Illumina Hi Seq 2000 platform.Data were processed through an analytical pipeline to search for rare germline variants in known or novel CRC predisposing genes.RESULTS: In total, 32 germline variants in 23 genes were identified and confirmed by Sanger sequencing.In 6 of the 21 families(29%), we identified 7 mutations in 3 known CRC predisposing genes including MLH1(5 patients), MSH2(1 patient), and MUTYH(biallelic, 1 patient), five of which were reported as pathogenic.Inthe remaining 15 families, we identified 20 rare and novel potentially deleterious variants in 19 genes, six of which were truncating mutations.One previously unreported variant identified in a conserved region of EIF2AK4(p.Glu738_Asp739insA rgA rg) was found to represent a local Chinese variant, which was significantly enriched in our early-onset CRC patient cohort compared to a control cohort of 100 healthy Chinese individuals scored negative by colonoscopy(33.3% vs 7%, P < 0.001).CONCLUSION: Whole-exome sequencing of early-onset or familial CRC cases serves as an efficient method to identify known and potential pathogenic variants in established and novel candidate CRC predisposing genes.
基金This work was supported by the NIHR HPRU in Emerging and Zoonotic Infections,a partnership between the United Kingdom Health Security Agency(UKHSA),University of Oxford,University of Liverpool and Liverpool School of Tropical Medicine[grant number NIHR200907 supporting RM and CAD]the MRC Centre for Global Infectious Disease Analysis[grant number MR/X020258/1],funded by the UK Medical Research Council(MRC)This UK funded award is carried out in the frame of the Global Health EDCTP3 Joint Undertaking.RM was also supported by the UKHSA and the Isaac Newton Institute(INI)Knowledge Transfer Network(KTN)in funding and coordinating a 3-month placement at the UK Health Security Agency,respectively.
文摘Key epidemiological parameters,including the effective reproduction number,,and the instantaneous growth rate,,generated from an ensemble of models,have been informing public health policy throughout the COVID-19 pandemic in the four nations of the United Kingdom of Great Britain and Northern Ireland(UK).However,estimation of these quantities became challenging with the scaling down of surveillance systems as part of the transition from the“emergency”to“endemic”phase of the pandemic.The Office for National Statistics(ONS)COVID-19 Infection Survey(CIS)provided an opportunity to continue estimating these parameters in the absence of other data streams.We used a penalised spline model fitted to the publicly-available ONS CIS test positivity estimates to produce a smoothed estimate of the prevalence of SARS-CoV-2 positivity over time.The resulting fitted curve was used to estimate the“ONS-based”and across the four nations of the UK.Estimates produced under this model are compared to government-published estimates with particular consideration given to the contribution that this single data stream can offer in the estimation of these parameters.Depending on the nation and parameter,we found that up to 77%of the variance in the government-published estimates can be explained by the ONS-based estimates,demonstrating the value of this singular data stream to track the epidemic in each of the four nations.We additionally find that the ONS-based estimates uncover epidemic trends earlier than the corresponding government-published estimates.Our work shows that the ONS CIS can be used to generate key COVID-19 epidemiological parameters across the four UK nations,further underlining the enormous value of such population-level studies of infection.This is not intended as an alternative to ensemble modelling,rather it is intended as a potential solution to the aforementioned challenge faced by public health officials in the UK in early 2022.
