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.     

钢框架结构二阶弹塑性稳定极限承载力试验研究

为研究钢框架结构的受力、变形性能及破坏特点,对４榀平面钢框架进行了极限承载力静力试验。介绍试验情况,分析试验现象,并将理论分析与试验结果进行了比较。     

Eigenvalue translation method for stabilizing an unsymmetric Lanczos reduction process

The Unsymmetric Lanczos Reduction method has been recently developed to reduce the size of a large-scale linear system which is the discretized form of a time-dependent partial differential equation problem with a large physical domain. This has been applied to solve the time-dependent advection–dispersion equation discretized by finite element or finite difference methods. However, the reduced system sometimes suffers time instability because of relocation of the approximate eigenvalues into the left half plane. This paper develops a method for stabilizing the reduced system while preserving the accuracy of the solution. The unstable eigenvalues are translated from the left half complex plane to the right half, leaving eigenvalues in right half plane unchanged. The results of numerical simulations of the synthetic and practical field contaminant transport problems show the efficiency and accuracy of this method. © 1998 John Wiley & Sons, Ltd.     

岩体结构面流变特性研究进展

在综述国内外关于岩体流变特性研究现状的基础上,着重探讨了有关岩体流变试验及流变理论中的若干问题,指出岩体结构面的蠕变特性研究对解决岩石力学实际问题具有很重要的意义,最后提出了岩体流变今后研究发展的方向以及可以引进的研究新手段。     

单层平面钢框架连续倒塌动力效应分析

为研究结构连续倒塌由于初始破坏引起的动力效应,该文采用瞬时加载法,对中柱失效的单层平面钢框架分别采用简化模型和杆单元模型进行动力反应分析。分析结果表明:当结构处于线弹性状态时,动力放大效应仅与构件失效时间和阻尼比有关,动力放大系数最大值为2,且随着构件失效时间和阻尼比的增大而减小;当结构屈服进入塑性状态后,动力放大效应还与需求能力比(DCR)有关,动力放大系数随着DCR的增大而增大,直至结构出现动力发散。     

A fast, FPGA-based MPEG-2 video encoder with a novel automatic quality control scheme

A novel video encoder that controls image quality on the fly is presented along with its FPGA implementation. As a result of this new feature, which uses a concept called pruning, the processing speed increases by a factor of two when compared to the conventional method of processing without pruning. The FPGA implementation conforms to MPEG-2 standards and is capable of processing color pictures of sizes up to 1024×768 pixels at the real time rate of 25 frames/s.     

Cutting plane methods for Lagrangian relaxation‐based unit commitment algorithm

In this paper, we study cutting plane methods for a Lagrangian relaxation‐based unit commitment algorithm. In the algorithm, nondifferentiable optimization methods can be applied to optimize the dual function, and a subgradient method which needs parameter tuning and has some drawbacks such as computational inefficiency and oscillating behavior is commonly used. The cutting plane method and the central cutting plane method are applied to the algorithm and implemented using reoptimization techniques. A numerical example shows that both methods are accelerated by the reoptimization techniques and have good convergence without parameter tuning. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(3): 17–29, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.10066     

Lower and upper bounds for the mixed capacitated arc routing problem

This paper presents a linear formulation, valid inequalities, and a lower bounding procedure for the mixed capacitated arc routing problem (MCARP). Moreover, three constructive heuristics and a memetic algorithm are described. Lower and upper bounds have been compared on two sets of randomly generated instances. Computational results show that the average gaps between lower and upper bounds are 0.51% and 0.33%, respectively.     

凝视红外焦平面CCD非均匀性校正

对CCD器件的非均匀性校正的理论方法进行了讨论、分析和比较,并对32×64元硅化铂肖特基势垒红外焦平面器件进行了响应率非均匀性的校正,针对该器件响应率非线性度大、传输率低、疵点数目多和噪声大等问题,选取先进的多点定标分段校正算法,实现了实时校正及显示。校正后,不均匀度为2%,图像质量明显得到改善。     

钢结构构件在高应力集中区脆性破坏倾向性

含高应力集中钢结构构件的厚度是影响其发生脆性破坏的一个重要因素，它的影响是和其应力集中区的复杂应力状态相联系的。本文介绍含缺口的受拉钢构件应力应变关系在不同厚度和缺口曲率半径情况下的变化及其对构件发生脆性破坏可能性的影响。