APOB CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants

Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the APOB gene, a condition associated with fatty liver and steatohepatitis. Nevertheless, many families with a FHBL phenotype carry APOB missense variants of uncertain significance (VUS). We here aimed to develop a proof-of-principle experiment to assess the pathogenicity of VUS using the genome editing of human liver cells. We identified a novel heterozygous APOB-VUS (p.Leu351Arg), in a FHBL family. We generated APOB knock-out (KO) and APOB-p.Leu351Arg knock-in Huh7 cells using CRISPR-Cas9 technology and studied the APOB expression, synthesis and secretion by digital droplet PCR and ELISA quantification. The APOB expression was decreased by 70% in the heterozygous APOB-KO cells and almost abolished in the homozygous-KO cells, with a consistent decrease in apoB production and secretion. The APOB-p.Leu351Arg homozygous cells presented with a 40% decreased APOB expression and undetectable apoB levels in cellular extracts and supernatant. Thus, the p.Leu351Arg affected the apoB secretion, which led us to classify this new variant as likely pathogenic and to set up a hepatic follow-up in this family. Therefore, the functional assessment of APOB-missense variants, using gene-editing technologies, will lead to improvements in the molecular diagnosis of FHBL and the personalized follow-up of these patients.     

招掖地区郭家岭花岗岩控矿的几点证据及找矿指示意义

尽管胶西北郭家岭花岗闪长岩与金矿化存在着密切的时空关系,但不同学者对二者间的物质联系尚存在歧义.文中汇集了招掖地区近年来部分找矿勘查成果,结合笔者工作认识,对郭家岭花岗闪长岩的控矿作用给予了客观评述.提出了焦家-玲珑式金矿床受郭家岭花岗闪长岩体接触带形态和断裂构造蚀变带联合控制的论断.在此基础上,对本区以往找矿工作思路进行了反思,给出了本区深部及外围找矿的新思路.     

iAES:面向网络安全博客的IOC自动抽取方法

网络威胁指标(IOC)作为网络威胁的行为特征,可以按照标准组织起来并部署在安全系统中防御攻击.博客是重要的网络威胁情报来源,及时从中收集网络威胁指标能够快速应对新的安全威胁,但人工阅读并抽取IOC的方式耗时耗力,所以我们迫切需要一种从网络安全博客中自动抽取IOC的方法.为此,本文提出了一种面向网络安全博客的IOC自动抽...     

宣恩县滕家湾铅锌矿基本特征、成矿规律与找矿意义

宣恩县滕家湾沉积型铅锌矿产于下奥陶统南津关组底部生物碎屑灰岩中,与生物化学作用有关,形成于开阔潮下带。含棕红色闪锌矿条带生物碎屑灰岩是最重要的找矿标志。与滕家湾铅锌矿相类似的矿点还有曾家垱、郑家、郭家坡、肖家湾、陆家坡5处,形成北东向铅锌矿化带,长20 km以上。铅锌矿化带中存在明显的Pb、Zn异常,具有较大的找矿潜力。     

一种新的属性重要性度量及其规则获取

在分析规则知识条件和结论所在等价类包含关系基础上,提出了一个新的属性相对重要性的定义,并给出一种以决策类为基础的逐渐增加条件属性直接获取最简分类规则方法,同时用实例进行了验证。     

基于时间戳的多文档自动文摘

网站的新闻专题往往包含大量的网页,多文档自动文摘可以帮助人们从中快速获取主要信息。该文提出了利用时间戳改善文摘句子抽取质量和排序的方法。介绍了句子抽取方法、句子重要度计算、句子冗余减小方法。实验表明,形成的文摘性能良好,可以应用于实际系统中。     

融合依存句法的深度学习藏语句子分割研究

藏语句子分割是藏语自然语言处理中的一项重要且基础性的研究工作。该文根据藏语句子结构特征,在分析藏语句子分割规则与难点的基础上,提出一种融合依存句法的藏语句子分割模型。该模型首先通过词嵌入和藏语依存句法信息嵌入将输入序列映射成实值向量;然后构建融合藏语依存句法的双向LSTM,拼接词语和句法信息特征,提高上下文时序特征的学习能力;最后利用CRF预测出最佳句子分割点。通过对比实验,验证了该模型对藏语句子分割的有效性。实验结果表明,该模型的F₁值为99.4%。     

The cascaded nature of lexical selection and integration in auditory sentence processing.

An event-related brain potential experiment was carried out to investigate the temporal relationship between lexical selection and the semantic integration in auditory sentence processing. Participants were presented with spoken sentences that ended with a word that was either semantically congruent or anomalous. Information about the moment in which a sentence-final word could uniquely be identified, its isolation point (IP), was compared with the onset of the elicited N400 congruity effect, reflecting semantic integration processing. The results revealed that the onset of the N400 effect occurred prior to the IP of the sentence-final words. Moreover, the factor early or late IP did not affect the onset of the N400. These findings indicate that lexical selection and semantic integration are cascading processes, in that semantic integration processing can start before the acoustic information allows the selection of a unique candidate and seems to be attempted in parallel for multiple candidates that are still compatible with the bottom-up acoustic input. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

关于师范生免费教育政策的思考

师范生免费教育政策对于解决贫困师范生的就学问题、保障基础教育师资质量、促进教育发展和教育公平具有重大的现实意义。该政策在具体实施过程中,可能出现新的问题：对非部属师范院校会产生新的不公平;真正热爱教育事业的师范生不一定能享受政策优惠;落实免费师范毕业生的职后保障成本太高;免费师范生的学习动力、培养质量难以保证等。对此．有必要采取相应的对策：提高我国教师的待遇;增强师范生的学习动机;注重免费师范生的培养质量;积极探索师范教育免费制度的多种模式。     

陕西金龙山金矿古楼山矿段元素地球化学特征

古楼山矿段位于金龙山金矿田的西北部,与丘岭矿段处于同一地球化学异常中,是另一异常浓集中心,目前在丘岭矿段已探明储量超过50 t,古楼山矿段由于工作程度较低,未取得大的突破.通过对古楼山矿段原生晕的分析,发现原生晕中As、Sb、Au元素相关性高且呈正相关关系,表明As、Sb、Au为该区金矿预测的主要元素组合,建立了地球化...