Translesion Synthesis or Repair by Specialized DNA Polymerases Limits Excessive Genomic Instability upon Replication Stress

DNA can experience “replication stress”, an important source of genome instability, induced by various external or endogenous impediments that slow down or stall DNA synthesis. While genome instability is largely documented to favor both tumor formation and heterogeneity, as well as drug resistance, conversely, excessive instability appears to suppress tumorigenesis and is associated with improved prognosis. These findings support the view that karyotypic diversity, necessary to adapt to selective pressures, may be limited in tumors so as to reduce the risk of excessive instability. This review aims to highlight the contribution of specialized DNA polymerases in limiting extreme genetic instability by allowing DNA replication to occur even in the presence of DNA damage, to either avoid broken forks or favor their repair after collapse. These mechanisms and their key regulators Rad18 and Polθ not only offer diversity and evolutionary advantage by increasing mutagenic events, but also provide cancer cells with a way to escape anti-cancer therapies that target replication forks.     

基于模极大值小波域和TLS-ESPRIT的振荡瞬态识别方法

对于电能质量扰动检测和定位中振荡瞬态的检测、识别,目前普遍采用的是时频特征矢量提取和智能模式识别方法,此类方法无法准确提取电能质量振荡瞬态信号不同频率分量的组成。结合模极大值小波域和总体最小二乘法旋转不变技术的信号参数估计(total least squares-estimation of signal parameters via rotational invariance techniques,TLS-ESPRIT)可以很好地实现振荡信号的检测与识别。对于输入信号,首先采用模极大值小波域检测振荡发生的起始时刻和终止时刻,然后利用振荡时间间隔内的信号建立观测空间矩阵,通过奇异值分解和总体最小二乘法实现特征值截尾,将采样信号观测空间分解为信号子空间和噪声子空间,得到振荡信号每个构成频率分量的相应参数。仿真结果证实了所提出方法的可行性。     

基于性能预测的推测多线程循环选择方法

线程级推测(Thread-Level Speculation, TLS)是多核上一种加速串行程序的线程级自动并行化技术。循环具有规则的结构并在运行时占有大量的执行时间,因此循环是挖掘并行性的理想对象。然而,选择哪些循环并行才能提高程序的加速比是一个很难决定的问题。为了解决该问题,该文提出一种基于性能预测的循环选择方法。基于输入训练集获取程序预执行的剖析信息,同时结合各种推测因素,构建了循环结构的性能预测模型。预测结果定量评估了循环推测并行的加速比并决定该循环在运行时是否适合并行。实验结果表明,该文提出的方法能有效地预测循环并行时所蕴含的并行性,并依据预测结果准确地选择具有并行收益的循环推测并行,最终Olden基准测试集加速比性能平均提升了12.34%。     

基于欠奈奎斯特采样的超宽带信号总体最小二乘重建算法

该文针对超宽带无线通信中需要设计高速模数转换器的问题,提出了一种欠奈奎斯特采样方法,该方法所要求的采样率仅与信号新息率相关,低于奈奎斯特率1个数量级。基于欠采样得到的离散时间超宽带信号,从理论上推导出信号的傅里叶频谱表达式,由此给出了一种总体最小二乘参数估计算法,能够准确地估计出冲激串信号的幅度和时移;通过将估计出的冲激串信号与高斯单脉冲波形卷积,完成超宽带信号的波形重建。仿真和实验结果表明,该文算法能够准确地重建原始超宽带信号,且算法性能优于现有的零化滤波重建算法。     

一种新的稳健的TDOA定位算法

该文提出了一种利用TDOA进行定位的新算法,它利用了有关相对量测误差上限和站址扰动上限的先验知识基础上,对伪线性TDOA方程组进行求解,其算法较为稳定,通过仿真发现可知该算法有较好的性能,在定位精度上比传统定位方法有所提高。     

TLS中加密算法的安全性分析

阐述了TLS协议的握手过程中服务器端与客户端之间的交互,对其中关键的RC4加密技术即密钥调度算法（ KSA）、伪随机书生成算法（ PRGA）等进行分析,着重就目前的加密过程中伪随机书生成算法（ PRGA）存在的安全性问题进行分析。在猜测赋值分析方法基础上分析了PRGA初始状态已知值数量及分布规律与 RC4破解的复杂度的相关性。特定情况下,该方法能有效的破译RC4。     

TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer

TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA polymerases bypass unrepaired DNA lesions. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase η and RAD18 E3 ligase, which guides the polymerase to replication stalling sites and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD and via the long non-coding antisense RNA PAXIP1-AS2, which had no known function. Knocking down the expression of TENT4A or CYLD, or overexpression of PAXIP1-AS2 led each to reduced amounts of the RAD18 protein and DNA polymerase η, leading to reduced TLS, highlighting PAXIP1-AS2 as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and their TENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer.     

存在阵列误差条件下的信号波达方向和多普勒频率估计

在均匀线阵存在阵列误差的情况下，提出了一种信号波达方向和多普勒频率估计方法。首先建立了阵列误差模型，采用总体最小二乘法和最大似然法，估计出多个信号的波达方向和多普勒频率，并分析了相位模糊性及给出了解模糊方法。仿真结果表明，此算法是有效的，并具有一定的稳健性。     

两种网络安全协议分析与比较

对SSL／TLS和IPSec两种网络安全协议进行了研究，分析了协议的目的、特点，比较了性能、实用性和应用，并给出可能的优化途径。     

一般阵列误差情况下信号二维方向角和多普勒频率的联合估计

针对平面阵列，推导出基于一般阵列误差模型的信号时空DOA矩阵，采用总体最小二乘法（TLS）估计出多个信号的方位角。俯仰角和多普勒频率，解决了大多数估计算法的性能因阵列误差而严重下降和“频率兼并”问题。此算法对噪声不敏感，不需进行谱峰搜索，仿真结果表明了此算法的有效性。