近年来,随着监控摄像头的不断增多和互联网的迅速发展,监控视频与网络视频越来越多,对视频进行自动行为冲突检测对降低人为审核导致的隐私信息泄露风险及维护社会治安、净化网络环境等具有重要意义.为了充分提取视频中的行为冲突特征,...近年来,随着监控摄像头的不断增多和互联网的迅速发展,监控视频与网络视频越来越多,对视频进行自动行为冲突检测对降低人为审核导致的隐私信息泄露风险及维护社会治安、净化网络环境等具有重要意义.为了充分提取视频中的行为冲突特征,并获得有较好泛化能力与检测效果的模型,采用I3D(inflated 3D convolutional network)与VGGish,基于XD-Violence进行多模态特征的提取,并提出了基于Transformer和图卷积网络的行为冲突检测模型TG-BCDM(behavior conflict detection model based on Transformer and graph convolution networks).该模型包含Transformer编码器模块和图卷积模块,可以在有效捕捉视频中长距离依赖关系的同时,关注视频特征的全局信息和局部信息.经过实验证明,该模型优于现有的8种方法.展开更多
为及时跟踪全球及中国植物修复技术的研究现状及发展趋势,以便为该研究领域的科研工作者及决策者提供参考,运用文献计量学方法,利用Web of Science核心数据库对2003-2020年间发表的全球植物修复研究文献进行了统计分析。全球植物修复的...为及时跟踪全球及中国植物修复技术的研究现状及发展趋势,以便为该研究领域的科研工作者及决策者提供参考,运用文献计量学方法,利用Web of Science核心数据库对2003-2020年间发表的全球植物修复研究文献进行了统计分析。全球植物修复的研究文献呈快速增长趋势,其中中国、美国和印度三国的总发文量和总被引频次均位居世界前三位,中国的发文量已经超过全球总发文量的三分之一,但中国的篇均被引频次较低。中国与美国、巴基斯坦、澳大利亚等国家在植物修复方面展开了广泛的国际交流与合作。比利时学者Vangronsveld在发文量等各项指标均占据世界首位,中国有5名学者发文量进入世界前10名,其中杨肖娥、骆永明、周启星等是学术影响力较大的国内作者。高质量论文主要发表在欧美国家主办的环境类期刊。我国植物修复研究虽然发展较快,但缺乏有国际影响力的核心成果,在研究创新性和发文质量上还有待提升。利用VOSviewer可视化软件分析了世界和中国发文的高频关键词,并根据聚类分析结果将当前植物修复研究分为5个不同的研究方向。此外,利用CiteSpace软件分析了植物修复研究在不同时期的突现关键词,最后总结了目前植物修复的研究热点和未来的研究方向。展开更多
为及时了解国内外黄曲霉毒素的研究现状、热点及发展趋势,为相关研究领域的科研工作者与决策者提供参考,本文采用文献计量学方法对Web of Science核心数据库收录的2003—2020年间黄曲霉毒素研究文献进行了统计分析。结果表明,目前全球...为及时了解国内外黄曲霉毒素的研究现状、热点及发展趋势,为相关研究领域的科研工作者与决策者提供参考,本文采用文献计量学方法对Web of Science核心数据库收录的2003—2020年间黄曲霉毒素研究文献进行了统计分析。结果表明,目前全球黄曲霉毒素研究的文献数量呈快速增长趋势,其中美国和中国是发文量最高,也是开展国际合作最活跃的两个国家。发表黄曲霉毒素相关研究最多的期刊是Food Control,而食品科学技术是发文最多的学科方向。美国的Cotty P J在发文量和H指数方面均居世界首位。仅1篇中国学者的论文进入了该领域高被引论文的前100名,表明国内目前缺乏具有国际影响力的重要成果,在研究创新性和发文质量上还有上升空间。此外,利用VOSviewer和CiteSpace文献可视化分析软件分析了不同时期及不同国家黄曲霉毒素研究的高频关键词,并对关键词进行了聚类分析和突现分析。黄曲霉毒素的新型检测技术、高效解毒方法、生物防治以及生物合成的调控机制等将可能成为该领域未来的研究热点和前沿。展开更多
[Objective] The experiment aimed to explore physiological and biochemical changes of leaves after plants were mutated. [Method] A rice double mutant with stripes on stems, leaves and spikelets were taken as experiment...[Objective] The experiment aimed to explore physiological and biochemical changes of leaves after plants were mutated. [Method] A rice double mutant with stripes on stems, leaves and spikelets were taken as experimental materials to study the enzyme activity changes in different growth stages and amino acid variation in rice. [ Result] The SOD activity in mutant was higher than that in wild plant at tillering metaphase, but lower than that in wild type before heading stage and late flowering; the POD activity in three stages increased firstly then declined and the activity showed highest maximal activity at before heading stage. However, the POD activity in wild type showed the opposite change trend; the CAT activity presented degression at three stages, especially high at tillering metaphase, but reverse changes in wild type; the MDA activity decreased at three stages, but it was still higher than that in wild type, besides, the soluble sugar content of mutant was lower, but total amino acid content was increased. [ Conclusion] The expression of mutant characteristics was correlated with SOD, POD, CAT and MDA activity Changes and these changes made the mutant survive and rice quality change at last.展开更多
Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by ...Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay.Results The cell line bore a missense mutation in the 6th coding exon (c.676 C〉T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.展开更多
AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Gen...AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.展开更多
AIM:To clarify the strategy for early diagnosis of pancreaticobiliary maljunction(PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.METHODS:The anatomy of the union of th...AIM:To clarify the strategy for early diagnosis of pancreaticobiliary maljunction(PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.METHODS:The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography(ERCP).Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM.Of these,patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation.The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated.Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted.RESULTS:Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain(n = 16) or jaundice(n = 12).Radical surgery for gallbladder cancer was only possible in 11 patients(31%) and only 4 patients(11%) survived for 5 years.Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography(MRCP).The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer.All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred.Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls,and hyperplastic changes,hypertrophic muscular layer,subserosal fibrosis,and adenomyomatosis were detected in 7(88%),5(63%),7(88%) and 5(63%) patients,respectively.Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients.CONCLUSION:To detect PBM without biliary dilatation before onset of gallbladder cancer,we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.展开更多
Most transactional memory (TM) research focused on multi-core processors, and others investigated at the clusters, leaving the area of non-uniform memory access (NUMA) system unexplored. The existing TM implementation...Most transactional memory (TM) research focused on multi-core processors, and others investigated at the clusters, leaving the area of non-uniform memory access (NUMA) system unexplored. The existing TM implementations made significant performance degradation on NUMA system because they ignored the slower remote memory access. To solve this problem, a latency-based conflict detection and a forecasting-based conflict prevention method were proposed. Using these techniques, the NUMA aware TM system was presented. By reducing the remote memory access and the abort rate of transaction, the experiment results show that the NUMA aware strategies present good practical TM performance on NUMA system.展开更多
The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers, and KRAS mutational status testing has been highlighted in recent years. The most frequent mutations in this gene, point substitutions in co...The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers, and KRAS mutational status testing has been highlighted in recent years. The most frequent mutations in this gene, point substitutions in codons 12 and 13, were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies. Therefore, determining the KRAS mutational status of tumor samples has become an essential tool for managing patients with colorectal cancers. Currently, a variety of detection methods have been established to analyze the mutation status in the key regions of the KRAS gene; however, several challenges remain related to standardized and uniform testing, including the selection of tumor samples, tumor sample processing and optimal testing methods. Moreover, new testing strategies, in combination with the mutation analysis of BRAF , PIK3CA and loss of PTEN proposed by many researchers and pathologists, should be promoted. In addition, we recommend that microsatellite instability, a prognostic factor, be added to the abovementioned concomitant analysis. This review provides an overview of KRAS biology and the recent advances in KRAS mutation testing. This review also addresses other aspects of status testing for determining the appropriate treatment and offers insight into the potential drawbacks of mutational testing.展开更多
Whether recent Arctic sea ice loss is responsible for recent severe winters over mid-latitude continents has emerged as a major debate among climate scientists owing to short records of observations and large internal...Whether recent Arctic sea ice loss is responsible for recent severe winters over mid-latitude continents has emerged as a major debate among climate scientists owing to short records of observations and large internal variability in mid- and high-latitudes. In this study, the authors divide the evolution of autumn Arctic sea ice extent during 1979–2014 into three epochs, 1979–1986(high), 1987–2006(moderate), and 2007–2014(low), using a regime shift identification method. The authors then compare the associations between autumn Arctic sea ice and winter climate anomalies over central and eastern Eurasia for the three epochs with a focus on extreme events. The results show robust and detectable signals of Arctic sea ice loss in weather and climate over western Siberia and East Asia. Associated with sea ice loss, the latitude(speed) of the jet stream shifts southward(reduces),the wave extent amplifies, and blocking high events increase over the Ural Mountains, leading to increased frequency of cold air outbreaks extending from central Asia to northeast China. These associations bear a high degree of similarity to the observed atmospheric anomalies during the low sea ice epoch. By contrast, the patterns of atmospheric anomalies for the high sea ice epoch are different from those congruent with sea ice variability, which is related to the persistent negative phase of the Arctic Oscillation.展开更多
AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with c...AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.展开更多
AIM: To characterize the types of mutations present in the 23S rRNA genes of Malaysian isolates of clarithromycin-resistant Helicobacter pylori (H pylorl~. METHODS: Clarithromycin susceptibility of H pylori isolate...AIM: To characterize the types of mutations present in the 23S rRNA genes of Malaysian isolates of clarithromycin-resistant Helicobacter pylori (H pylorl~. METHODS: Clarithromycin susceptibility of H pylori isolates was determined by E test. Analyses for point mutations in the domain V of 23S rRNA genes in clarithromycin-resistant and -sensitive strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using Bsa I and MboI enzymes to detect restriction sites that correspond to the mutations in the clarithromycin- resistant strains. RESULTS: Of 187 isolates from 120 patients, four were resistant to clarithromycin, while 183 were sensitive. The MIC of the resistant strains ranged from 1.5 to 24 pg/mL. Two isolates had an A2142G mutation and another two had A2143G mutations. A T2182C mutation was detected in two out of four clarithromycin-resistant isolates and in 13 of 14 clarithromycin-sensitive isolates. Restriction enzyme analyses with Bsa I and Mbo I were able to detect the mutations. CONCLUSION: Clarithromycin resistance is an uncommon occurrence among Malaysian isolates of Hpylori strains and the mutations A2142G and A2143G detected were associated with low-level resistance.展开更多
Objective To identify the pathogenic variant responsible for restrictive cardiomyopathy (RCM) in aChinese family.Methods Next generation sequencing was used for detecting the mutation and results verified bysequenci...Objective To identify the pathogenic variant responsible for restrictive cardiomyopathy (RCM) in aChinese family.Methods Next generation sequencing was used for detecting the mutation and results verified bysequencing. We used restriction enzyme digestion to test the mutation in the family members and 200 unrelatednormal subjects without any cardiac inherited diseases when the mutation was identified.Results Five individuals died from cardiac diseases, two of whom suffered from sudden cardiacdeath. Two individuals have suffered from chronic cardiac disorders. Mutation analysis revealed a novelmissense mutation in exon 7 of troponin I type 3 (TNNI3), resulting in substitution of serine (S) withproline (P) at amino acid position 150, which cosegregated with the disease in the family, which is predictedto be probably damaging using PolyPhen-2. The mutation was not detected in the 200 unrelated subjectswe tested.Conclusion Using next generation sequencing, which has very recently been shown to be successfulin identifying novel causative mutations of rare Mendelian disorders, we found a novel mutation of TNNI3 in aChinese family with RCM.展开更多
The global view of firewall policy conflict is important for administrators to optimize the policy.It has been lack of appropriate firewall policy global conflict analysis,existing methods focus on local conflict dete...The global view of firewall policy conflict is important for administrators to optimize the policy.It has been lack of appropriate firewall policy global conflict analysis,existing methods focus on local conflict detection.We research the global conflict detection algorithm in this paper.We presented a semantic model that captures more complete classifications of the policy using knowledge concept in rough set.Based on this model,we presented the global conflict formal model,and represent it with OBDD(Ordered Binary Decision Diagram).Then we developed GFPCDA(Global Firewall Policy Conflict Detection Algorithm) algorithm to detect global conflict.In experiment,we evaluated the usability of our semantic model by eliminating the false positives and false negatives caused by incomplete policy semantic model,of a classical algorithm.We compared this algorithm with GFPCDA algorithm.The results show that GFPCDA detects conflicts more precisely and independently,and has better performance.展开更多
To minimize the inventory costs of detecting demand change, an acceptance/rejection method ( threshold) is proposed. The proposed threshold can be identified by the newsvendor based on the excess cost, the shortage ...To minimize the inventory costs of detecting demand change, an acceptance/rejection method ( threshold) is proposed. The proposed threshold can be identified by the newsvendor based on the excess cost, the shortage cost, the transitional probability of the demand change, and the magnitude of the demand change. Compared with the single exponential smoothing method, it is proved that the proposed method can save many more inventory costs when detecting a step change in demand. By analyzing the proposed method, it shows that as the magnitude of step change increases, the supply chain members turn to synchronously judge a step change, and as excess ( shortage) cost increases, a newsvendor tends to respond slowly (early) to an increase in demand and responds early (slowly) to a decrease in demand. Observations from this study suggest that supply chain members should pay careful attention to different profit-margin products and different magnitude demand changes in cooperating and sharing demand information with others.展开更多
文摘近年来,随着监控摄像头的不断增多和互联网的迅速发展,监控视频与网络视频越来越多,对视频进行自动行为冲突检测对降低人为审核导致的隐私信息泄露风险及维护社会治安、净化网络环境等具有重要意义.为了充分提取视频中的行为冲突特征,并获得有较好泛化能力与检测效果的模型,采用I3D(inflated 3D convolutional network)与VGGish,基于XD-Violence进行多模态特征的提取,并提出了基于Transformer和图卷积网络的行为冲突检测模型TG-BCDM(behavior conflict detection model based on Transformer and graph convolution networks).该模型包含Transformer编码器模块和图卷积模块,可以在有效捕捉视频中长距离依赖关系的同时,关注视频特征的全局信息和局部信息.经过实验证明,该模型优于现有的8种方法.
文摘为及时跟踪全球及中国植物修复技术的研究现状及发展趋势,以便为该研究领域的科研工作者及决策者提供参考,运用文献计量学方法,利用Web of Science核心数据库对2003-2020年间发表的全球植物修复研究文献进行了统计分析。全球植物修复的研究文献呈快速增长趋势,其中中国、美国和印度三国的总发文量和总被引频次均位居世界前三位,中国的发文量已经超过全球总发文量的三分之一,但中国的篇均被引频次较低。中国与美国、巴基斯坦、澳大利亚等国家在植物修复方面展开了广泛的国际交流与合作。比利时学者Vangronsveld在发文量等各项指标均占据世界首位,中国有5名学者发文量进入世界前10名,其中杨肖娥、骆永明、周启星等是学术影响力较大的国内作者。高质量论文主要发表在欧美国家主办的环境类期刊。我国植物修复研究虽然发展较快,但缺乏有国际影响力的核心成果,在研究创新性和发文质量上还有待提升。利用VOSviewer可视化软件分析了世界和中国发文的高频关键词,并根据聚类分析结果将当前植物修复研究分为5个不同的研究方向。此外,利用CiteSpace软件分析了植物修复研究在不同时期的突现关键词,最后总结了目前植物修复的研究热点和未来的研究方向。
文摘为及时了解国内外黄曲霉毒素的研究现状、热点及发展趋势,为相关研究领域的科研工作者与决策者提供参考,本文采用文献计量学方法对Web of Science核心数据库收录的2003—2020年间黄曲霉毒素研究文献进行了统计分析。结果表明,目前全球黄曲霉毒素研究的文献数量呈快速增长趋势,其中美国和中国是发文量最高,也是开展国际合作最活跃的两个国家。发表黄曲霉毒素相关研究最多的期刊是Food Control,而食品科学技术是发文最多的学科方向。美国的Cotty P J在发文量和H指数方面均居世界首位。仅1篇中国学者的论文进入了该领域高被引论文的前100名,表明国内目前缺乏具有国际影响力的重要成果,在研究创新性和发文质量上还有上升空间。此外,利用VOSviewer和CiteSpace文献可视化分析软件分析了不同时期及不同国家黄曲霉毒素研究的高频关键词,并对关键词进行了聚类分析和突现分析。黄曲霉毒素的新型检测技术、高效解毒方法、生物防治以及生物合成的调控机制等将可能成为该领域未来的研究热点和前沿。
基金Supported by Program for New Century Excellent Talents in University(NCET-04-0907)the Innovative Research Team in University (IRT0453)~~
文摘[Objective] The experiment aimed to explore physiological and biochemical changes of leaves after plants were mutated. [Method] A rice double mutant with stripes on stems, leaves and spikelets were taken as experimental materials to study the enzyme activity changes in different growth stages and amino acid variation in rice. [ Result] The SOD activity in mutant was higher than that in wild plant at tillering metaphase, but lower than that in wild type before heading stage and late flowering; the POD activity in three stages increased firstly then declined and the activity showed highest maximal activity at before heading stage. However, the POD activity in wild type showed the opposite change trend; the CAT activity presented degression at three stages, especially high at tillering metaphase, but reverse changes in wild type; the MDA activity decreased at three stages, but it was still higher than that in wild type, besides, the soluble sugar content of mutant was lower, but total amino acid content was increased. [ Conclusion] The expression of mutant characteristics was correlated with SOD, POD, CAT and MDA activity Changes and these changes made the mutant survive and rice quality change at last.
基金Supported by the National Science and Technology Major Project(2011ZX09102-010-04)
文摘Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay.Results The cell line bore a missense mutation in the 6th coding exon (c.676 C〉T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.
基金Supported by The Department of Education of Zhejiang Province of China,grant No.Y200804314the Zhejiang Provincial Natural Science Foundation,grant No.R2090353+1 种基金the Department of Science and Technology of Zhejiang Province,grant No.2008C33039the Chinese Ministry of Health,grant No.N20100148
文摘AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.
文摘AIM:To clarify the strategy for early diagnosis of pancreaticobiliary maljunction(PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.METHODS:The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography(ERCP).Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM.Of these,patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation.The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated.Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted.RESULTS:Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain(n = 16) or jaundice(n = 12).Radical surgery for gallbladder cancer was only possible in 11 patients(31%) and only 4 patients(11%) survived for 5 years.Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography(MRCP).The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer.All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred.Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls,and hyperplastic changes,hypertrophic muscular layer,subserosal fibrosis,and adenomyomatosis were detected in 7(88%),5(63%),7(88%) and 5(63%) patients,respectively.Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients.CONCLUSION:To detect PBM without biliary dilatation before onset of gallbladder cancer,we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.
基金Projects(61003075, 61170261) supported by the National Natural Science Foundation of China
文摘Most transactional memory (TM) research focused on multi-core processors, and others investigated at the clusters, leaving the area of non-uniform memory access (NUMA) system unexplored. The existing TM implementations made significant performance degradation on NUMA system because they ignored the slower remote memory access. To solve this problem, a latency-based conflict detection and a forecasting-based conflict prevention method were proposed. Using these techniques, the NUMA aware TM system was presented. By reducing the remote memory access and the abort rate of transaction, the experiment results show that the NUMA aware strategies present good practical TM performance on NUMA system.
基金Supported by Science and Technology Commission of Shanghai Municipality, No. 10DJ1400501
文摘The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers, and KRAS mutational status testing has been highlighted in recent years. The most frequent mutations in this gene, point substitutions in codons 12 and 13, were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies. Therefore, determining the KRAS mutational status of tumor samples has become an essential tool for managing patients with colorectal cancers. Currently, a variety of detection methods have been established to analyze the mutation status in the key regions of the KRAS gene; however, several challenges remain related to standardized and uniform testing, including the selection of tumor samples, tumor sample processing and optimal testing methods. Moreover, new testing strategies, in combination with the mutation analysis of BRAF , PIK3CA and loss of PTEN proposed by many researchers and pathologists, should be promoted. In addition, we recommend that microsatellite instability, a prognostic factor, be added to the abovementioned concomitant analysis. This review provides an overview of KRAS biology and the recent advances in KRAS mutation testing. This review also addresses other aspects of status testing for determining the appropriate treatment and offers insight into the potential drawbacks of mutational testing.
基金supported by the National Natural Science Foundation of China[grant number 41176169]the National Basic Research Program of China[grant number 2011CB309704]
文摘Whether recent Arctic sea ice loss is responsible for recent severe winters over mid-latitude continents has emerged as a major debate among climate scientists owing to short records of observations and large internal variability in mid- and high-latitudes. In this study, the authors divide the evolution of autumn Arctic sea ice extent during 1979–2014 into three epochs, 1979–1986(high), 1987–2006(moderate), and 2007–2014(low), using a regime shift identification method. The authors then compare the associations between autumn Arctic sea ice and winter climate anomalies over central and eastern Eurasia for the three epochs with a focus on extreme events. The results show robust and detectable signals of Arctic sea ice loss in weather and climate over western Siberia and East Asia. Associated with sea ice loss, the latitude(speed) of the jet stream shifts southward(reduces),the wave extent amplifies, and blocking high events increase over the Ural Mountains, leading to increased frequency of cold air outbreaks extending from central Asia to northeast China. These associations bear a high degree of similarity to the observed atmospheric anomalies during the low sea ice epoch. By contrast, the patterns of atmospheric anomalies for the high sea ice epoch are different from those congruent with sea ice variability, which is related to the persistent negative phase of the Arctic Oscillation.
基金Supported by MRIN Funding (Budget No.cc041/2009)
文摘AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.
基金Supported by A grant from the Ministry of Science,Technology and Innovation,Malaysia
文摘AIM: To characterize the types of mutations present in the 23S rRNA genes of Malaysian isolates of clarithromycin-resistant Helicobacter pylori (H pylorl~. METHODS: Clarithromycin susceptibility of H pylori isolates was determined by E test. Analyses for point mutations in the domain V of 23S rRNA genes in clarithromycin-resistant and -sensitive strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using Bsa I and MboI enzymes to detect restriction sites that correspond to the mutations in the clarithromycin- resistant strains. RESULTS: Of 187 isolates from 120 patients, four were resistant to clarithromycin, while 183 were sensitive. The MIC of the resistant strains ranged from 1.5 to 24 pg/mL. Two isolates had an A2142G mutation and another two had A2143G mutations. A T2182C mutation was detected in two out of four clarithromycin-resistant isolates and in 13 of 14 clarithromycin-sensitive isolates. Restriction enzyme analyses with Bsa I and Mbo I were able to detect the mutations. CONCLUSION: Clarithromycin resistance is an uncommon occurrence among Malaysian isolates of Hpylori strains and the mutations A2142G and A2143G detected were associated with low-level resistance.
文摘Objective To identify the pathogenic variant responsible for restrictive cardiomyopathy (RCM) in aChinese family.Methods Next generation sequencing was used for detecting the mutation and results verified bysequencing. We used restriction enzyme digestion to test the mutation in the family members and 200 unrelatednormal subjects without any cardiac inherited diseases when the mutation was identified.Results Five individuals died from cardiac diseases, two of whom suffered from sudden cardiacdeath. Two individuals have suffered from chronic cardiac disorders. Mutation analysis revealed a novelmissense mutation in exon 7 of troponin I type 3 (TNNI3), resulting in substitution of serine (S) withproline (P) at amino acid position 150, which cosegregated with the disease in the family, which is predictedto be probably damaging using PolyPhen-2. The mutation was not detected in the 200 unrelated subjectswe tested.Conclusion Using next generation sequencing, which has very recently been shown to be successfulin identifying novel causative mutations of rare Mendelian disorders, we found a novel mutation of TNNI3 in aChinese family with RCM.
基金supported by the National Nature Science Foundation of China under Grant No.61170295 the Project of National ministry under Grant No.A2120110006+2 种基金 the Co-Funding Project of Beijing Municipal Education Commission under Grant No.JD100060630 the Beijing Education Committee General Program under Grant No. KM201211232010 the National Nature Science Foundation of China under Grant NO. 61370065
文摘The global view of firewall policy conflict is important for administrators to optimize the policy.It has been lack of appropriate firewall policy global conflict analysis,existing methods focus on local conflict detection.We research the global conflict detection algorithm in this paper.We presented a semantic model that captures more complete classifications of the policy using knowledge concept in rough set.Based on this model,we presented the global conflict formal model,and represent it with OBDD(Ordered Binary Decision Diagram).Then we developed GFPCDA(Global Firewall Policy Conflict Detection Algorithm) algorithm to detect global conflict.In experiment,we evaluated the usability of our semantic model by eliminating the false positives and false negatives caused by incomplete policy semantic model,of a classical algorithm.We compared this algorithm with GFPCDA algorithm.The results show that GFPCDA detects conflicts more precisely and independently,and has better performance.
基金The National Natural Science Foundation of China(No.71171049,71390335)
文摘To minimize the inventory costs of detecting demand change, an acceptance/rejection method ( threshold) is proposed. The proposed threshold can be identified by the newsvendor based on the excess cost, the shortage cost, the transitional probability of the demand change, and the magnitude of the demand change. Compared with the single exponential smoothing method, it is proved that the proposed method can save many more inventory costs when detecting a step change in demand. By analyzing the proposed method, it shows that as the magnitude of step change increases, the supply chain members turn to synchronously judge a step change, and as excess ( shortage) cost increases, a newsvendor tends to respond slowly (early) to an increase in demand and responds early (slowly) to a decrease in demand. Observations from this study suggest that supply chain members should pay careful attention to different profit-margin products and different magnitude demand changes in cooperating and sharing demand information with others.