Whole Exome Sequencing Identifies a Heterozygous Variant in the Cav1.3 Gene CACNA1D Associated with Familial Sinus Node Dysfunction and Focal Idiopathic Epilepsy

Cav1.3 voltage-gated L-type calcium channels (LTCCs) are involved in cardiac pacemaking, hearing and hormone secretion, but are also expressed postsynaptically in neurons. So far, homozygous loss of function mutations in CACNA1D encoding the Cav1.3 α₁-subunit are described in congenital sinus node dysfunction and deafness. In addition, germline mutations in CACNA1D have been linked to neurodevelopmental syndromes including epileptic seizures, autism, intellectual disability and primary hyperaldosteronism. Here, a three-generation family with a syndromal phenotype of sinus node dysfunction, idiopathic epilepsy and attention deficit hyperactivity disorder (ADHD) is investigated. Whole genome sequencing and functional heterologous expression studies were used to identify the disease-causing mechanisms in this novel syndromal disorder. We identified a heterozygous non-synonymous variant (p.Arg930His) in the CACNA1D gene that cosegregated with the combined clinical phenotype in an autosomal dominant manner. Functional heterologous expression studies showed that the CACNA1D variant induces isoform-specific alterations of Cav1.3 channel gating: a gain of ion channel function was observed in the brain-specific short CACNA1D isoform (Cav1.3_S), whereas a loss of ion channel function was seen in the long (Cav1.3_L) isoform. The combined gain-of-function (GOF) and loss-of-function (LOF) induced by the R930H variant are likely to be associated with the rare combined clinical and syndromal phenotypes in the family. The GOF in the Cav1.3_S variant with high neuronal expression is likely to result in epilepsy, whereas the LOF in the long Cav1.3_L variant results in sinus node dysfunction.     

Cytogenetic and Molecular Marker Analyses of a Novel Wheat–Psathyrostachys huashanica 7Ns Disomic Addition Line with Powdery Mildew Resistance

Powdery mildew caused by Blumeria graminis f. sp. tritici is a devastating disease that reduces wheat yield and quality worldwide. The exploration and utilization of new resistance genes from wild wheat relatives is the most effective strategy against this disease. Psathyrostachys huashanica Keng f. ex P. C. Kuo (2n = 2x = 14, NsNs) is an important tertiary gene donor with multiple valuable traits for wheat genetic improvement, especially disease resistance. In this study, we developed and identified a new wheat—P. huashanica disomic addition line, 18-1-5—derived from a cross between P. huashanica and common wheat lines Chinese Spring and CSph2b. Sequential genomic and multicolor fluorescence in situ hybridization analyses revealed that 18-1-5 harbored 21 pairs of wheat chromosomes plus a pair of alien Ns chromosomes. Non-denaturing fluorescence in situ hybridization and molecular marker analyses further demonstrated that the alien chromosomes were derived from chromosome 7Ns of P. huashanica. The assessment of powdery mildew response revealed that line 18-1-5 was highly resistant at the adult stage to powdery mildew pathogens prevalent in China. The evaluation of agronomic traits indicated that 18-1-5 had a significantly reduced plant height and an increased kernel length compared with its wheat parents. Using genotyping-by-sequencing technology, we developed 118 PCR-based markers specifically for chromosome 7Ns of P. huashanica and found that 26 of these markers could be used to distinguish the genomes of P. huashanica and other wheat-related species. Line 18-1-5 can therefore serve as a promising bridging parent for wheat disease resistance breeding. These markers should be conducive for the rapid, precise detection of P. huashanica chromosomes and chromosomal segments carrying Pm resistance gene(s) during marker-assisted breeding and for the investigation of genetic differences and phylogenetic relationships among diverse Ns genomes and other closely related ones.     

ANSYS系统在户外广告设施安全检测中的应用

结合对户外广告牌的结构进行安全检测的工程实例,介绍了利用ANSYS时户外广告牌的实际结构进行受力校核以及对结构进行优化的过程,并提出了目前户外广告牌的典型结构存在的安全隐患以及结构调整的意见.     

NaOH溶液处理对鸡肉品质的影响

为研究NaOH溶液处理对鸡肉品质的影响,选取市售黄羽肉鸡60 只,随机分为对照组和NaOH溶液浸泡组（pH 9组、pH 11组和pH 13组,每组15 只）,并对其进行肉品质和微生物指标检测。结果表明：NaOH溶液浸泡可以显著增加鸡肉的质量和腐败指标（总挥发性盐基氮、组胺、酪胺和亚精胺）含量（P＜0.05）,显著降低剪切力、风味营养物质（蛋白质、肌内脂肪、肌苷酸和氨基酸）含量（P＜0.05）;低pH值NaOH溶液浸泡的鸡肉,其菌落总数和大肠菌群数明显升高,而高pH值NaOH溶液具有一定的杀菌效果。     

试谈安装Eclipse插件的方法

Eclipse的设计思想是通过插件构建Java开发环境,插件可以大大地提高开发效率,主要介绍安装Eclipse插件的常用方法。     

一种新的基于遗传算法的参差MTI滤波器设计

提出一种新的搜索最优参差码的方法,该方法是以遗传算法为基础,在每一代群体中,执行完编码、复制、交叉、变异操作后,计算每一个体的适应度.然后每一个体按照一定的条件确定一组新的个体,随机抽取其中的一个个体,计算由其确定的适应度较原个体适应度的增量,决定是否由新抽取的个体代替原个体,达到终止条件时结束.该方法能够使得滤波器的第一零点尽可能地浅,是一种全局随机搜索算法,不依赖于初始种子都可以搜索到全局最优点,而且实现的个体平均适应度更高.     

通过Boosting改进基于EP的分类器

显露模式(EP)是支持度从一个数据集到另一个数据集显著提高的项集. EP具有很强的区分能力,可以建立很好的分类器.提出了一种通过Boosting改进基于EP的分类器的算法BoostEP. BoostEP使用Boosting技术建立多个基于EP的基分类器形成组合分类器,并对每个基分类器预测加权投票得到未知样本的类标号.在UCI机器学习数据库的21个基准数据集上的实验表明,BoostEP的分类准确率足以与NB,C4.5,CBA和CAEP等优秀分类法相媲美.     

基于虚拟机的软件保护研究与设计

虚拟机技术一直是当今计算机安全领域研究的热点之一。从软件保护的角度出发,介绍了基于虚拟机的软件保护设计方案中的关键技术,并给出了一个范例,说明具体步骤和方法。该方法将保护对象细化为函数,给出了单函数识别的具体步骤和方法,利用基本的x86编码来构造虚拟机,对基本指令集采用基于字节码的加解密技术,此外还对各类指令进行了必要的模块化扩展以增加保护力度。目前国内对于虚拟机的保护技术处于起步阶段,因而对于虚拟机技术的理论基础研究和技术实践应用均具有较高的研究价值和发展空间。     

炔丙基二甲基海因的合成及表征

为了改善推进剂的力学性能,采用盖布瑞尔(Gabriel)合成法合成了3-炔丙基-5,5-二甲基海因(PDMH),反应条件为:n(5,5-二甲基海因):n(溴丙炔):n(KOH的醇溶液)=1∶1∶1,水为溶剂,温度为65 ℃,反应时间为3 h,产率为50%.通过红外、核磁共振、质谱、元素分析、X射线衍射和热分析对产物进行了全面的分析表征.结果表明,产物为目标物,熔点为170～171 ℃,初始分解温度为185.5 ℃,目标物有望在复合固体推进剂中得到较好的应用.     

对邮件过滤技术发展现状的比较与分析

对自学习的过滤技术进行比较和分析,包括已经商品化的方法和目前还处于理论研究阶段的方法,尤其介绍基于机器学习的过滤技术的发展现状,重点研究该领域内的一些新兴过滤技术.在综合比较了一系列的过滤技术的优缺点之后,分析结果表明基于规则的方法和贝叶斯方法是最有潜力的过滤技术.