Rapid determination of RMSDs corresponding to macromolecular rigid body motions

Finding the root mean sum of squared deviations (RMSDs) between two coordinate vectors that correspond to the rigid body motion of a macromolecule is an important problem in structural bioinformatics, computational chemistry, and molecular modeling. Standard algorithms compute the RMSD with time proportional to the number of atoms in the molecule. Here, we present RigidRMSD, a new algorithm that determines a set of RMSDs corresponding to a set of rigid body motions of a macromolecule in constant time with respect to the number of atoms in the molecule. Our algorithm is particularly useful for rigid body modeling applications, such as rigid body docking, and also for high‐throughput analysis of rigid body modeling and simulation results. We also introduce a constant‐time rotation RMSD as a similarity measure for rigid molecules. A C++ implementation of our algorithm is available at http://nano‐d.inrialpes.fr/software/RigidRMSD . © 2014 Wiley Periodicals, Inc.     

On the induced‐fit mechanism of substrate‐enzyme binding structures of nylon‐oligomer hydrolase

We present a detailed computational investigation of the induced‐fit motion in a nylon‐oligomer hydrolase (NylB) upon substrate binding. To this aim, we resort on the recently introduced parallel cascade selection molecular dynamics approach, allowing for an accelerated access to the set of conformational changes from an open‐ to a closed‐state structure to form the enzyme‐substrate complex in a specific induce‐fit mechanism. The structural investigation is quantitatively complemented by free energy analyses within the umbrella sampling algorithm accompanied by weighted histogram analysis. We find that the stabilization free energy is about 1.4 kcal/mol, whereas the highest free energy barrier to be overcome is about 2.3 kcal/mol. Conversely, the energetic contribution for the substrate binding is about 20 kcal/mol, as estimated from Generalized Born/Surface Area. This means that the open‐close induced‐fit motion could occur frequently once the substrate binds to the open state of NylB. © 2014 Wiley Periodicals, Inc.     

Isometric artifacts from polymerase chain reaction-massively parallel sequencing analysis of short tandem repeat loci: An emerging issue from a new technology?

The recent introduction of polymerase chain reaction (PCR)-massively parallel sequencing (MPS) technologies in forensics has changed the approach to allelic short tandem repeat (STR) typing because sequencing cloned PCR fragments enables alleles with identical molecular weights to be distinguished based on their nucleotide sequences. Therefore, because PCR fidelity mainly depends on template integrity, new technical issues could arise in the interpretation of the results obtained from the degraded samples. In this work, a set of DNA samples degraded in vitro was used to investigate whether PCR-MPS could generate “isometric drop-ins” (IDIs; i.e., molecular products having the same length as the original allele but with a different nucleotide sequence within the repeated units). The Precision ID GlobalFiler NGS STR panel kit was used to analyze 0.5 and 1 ng of mock samples in duplicate tests (for a total of 16 PCR-MPS analyses). As expected, several well-known PCR artifacts (such as allelic dropout, stutters above the threshold) were scored; 95 IDIs with an average occurrence of 5.9 IDIs per test (min: 1, max: 11) were scored as well. In total, IDIs represented one of the most frequent artifacts. The coverage of these IDIs reached up to 981 reads (median: 239 reads), and the ratios with the coverage of the original allele ranged from 0.069 to 7.285 (median: 0.221). In addition, approximately 5.2% of the IDIs showed coverage higher than that of the original allele. Molecular analysis of these artifacts showed that they were generated in 96.8% of cases through a single nucleotide change event, with the C > T transition being the most frequent (85.7%). Thus, in a forensic evaluation of evidence, IDIs may represent an actual issue, particularly when DNA mixtures need to be interpreted because they could mislead the operator regarding the number of contributors. Overall, the molecular features of the IDIs described in this work, as well as the performance of duplicate tests, may be useful tools for managing this new class of artifacts otherwise not detected by capillary electrophoresis technology.     

受限于两平行板间的对称星形共聚物Am Bm熔体相行为的格子自洽场理论研究

采用格子自洽场理论计算研究了受限于2个平行板间的对称星形共聚物AmBm(m=1,2,3,4,5)熔体形成的层状相结构.在给定的相互作用下(χNAB不变,χ为Flory-Huggins相互作用参数,NAB=(N?1)/m为单个聚合物分子中一对AB臂的总链节数目),针对平行板间距为体相周期的情况,系统考察了共聚物链长N和单个聚合物分子中A(或B)臂数目m对受限层结构细节及层取向的影响.由计算结果,当N或NAB不变时,受限层的归一化界面宽度随m的增大而减小.受限板为中性时,垂直层结构的单链自由能比平行层结构的低.随着板对共聚物中一种嵌段的选择作用Λ的增大,体系发生垂直层到平行层的转变,该转变为一阶相变.当m不变时,N越小,上述转变出现在越大的Λ值处,体系越容易保持垂直层结构.并且N越小,层状结构周期越小.当N或NAB不变时,m越大体系越容易保持垂直层结构.总之,星形共聚物的链长越短、臂数越多时,垂直层稳定的Λ区间越大、层状结构的界面宽度越小.这些结论可以指导刻蚀应用中对体系参数的选择.     

基于改进DPSO算法的并行测试任务优化调度研究

并行测试以减少测试时间和降低测试成本的强大优势,已成为当前自动测试系统发展的方向。针对并行自动测试过程中,测试任务调度复杂,难以优化的问题,以PSO算法为基础,通过对问题空间编码的重新定义,并运用交叉、变异算子给出了新的粒子位置的更新公式,提出了一种改进后的DPSO算法。依据并行测试完成时间极限定理,给出了并行测试任务调度的目标函数与约束条件。以某雷达电子装备并行测试系统中三块电路板并行测试为例,对改进的DPSO算法进行了仿真验证,得到了最优调度测试序列。结果表明：与遗传算法相比,改进后的DPSO算法迭代次数更少,寻优性能更好,适用于工程应用。     

A local parallel superconvergence method for the incompressible flow by coarsening projection

In this article, we investigate a local parallel superconvergence method by coarsening projection for the incompressible Stokes flow. The method is a combination of the local superconvergence technique and the given framework of local parallel method. For the smooth subdomains, the local superconvergence method is applied in a higher order finite dimensional space corresponding to an appropriate coarse mesh on interior domain. Moreover, a useful and flexible local parallel method is designed to obtain the local parallel superconvergence results of presented method, which offset theoretical limitation of the model without the smoothness of the exact solution and a priori regularity of the underlying problem over the whole domain. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 1209–1223, 2015     

Noninvasive prenatal paternity testing by maternal plasma DNA sequencing in twin pregnancies

SNPs, combined with massively parallel sequencing technology, have proven applicability in noninvasive prenatal paternity testing (NIPPT) for singleton pregnancies in our previous research, using circulating cell-free DNA in maternal plasma. However, the feasibility of NIPPT in twin pregnancies has remained uncertain. As a pilot study, we developed a practical method to noninvasively determine the paternity of twin pregnancies by maternal plasma DNA sequencing based on a massively parallel sequencing platform. Blood samples were collected from 15 pregnant women (twin pregnancies at 9–18 weeks of gestation). Parental DNA and maternal plasma cell-free DNA were analyzed with custom-designed probes covering 5226 polymorphic SNP loci. A mathematical model for data interpretation was established, including the zygosity determination and paternity index calculations. Each plasma sample was independently tested against the alleged father and 90 unrelated males. As a result, the zygosity in each twin case was correctly determined, prior to paternity analysis. Further, the correct biological father was successfully identified, and the paternity of all 90 unrelated males was excluded in each case. Our study demonstrates that NIPPT can be performed for twin pregnancies. This finding may contribute to development in NIPPT and diagnosis of certain genetic diseases.     

Characterization of sequence variation at 30 autosomal STRs in Chinese Han and Tibetan populations

Massively parallel sequencing (MPS) technologies have the ability to reveal sequence variations within STR alleles as well as their nominal allele lengths, which have traditionally been detected by CE instruments. Recently, Thermo Fisher Scientific has updated the MPS-STR panel, named the Precision ID GlobalFiler next-generation sequencing (NGS) STR Panel version 2, with primers redesigned to add two pentanucleotide tandem repeat loci and profile interpretation supported by the Converge software. Using the Ion Chef System, the Ion S5XL System, and the Converge software, genetic variations were characterized within STR repeat and flanking regions of 30 autosomal STR markers in 115 unrelated individuals from two Chinese population groups (58 Tibetans and 57 Hans). Nineteen STRs demonstrated a relative increase in diversity with the variant sequence alleles compared with those of traditional nominal length alleles. In total, 390 alleles were identified by their sequences compared with 258 alleles that were identified by length. Of these 92 sequence variants found within the STR repeat regions, 40 variants were located in STR flanking regions. Additionally, the agreement of the results with CE data was evaluated, as was the ability of this new MPS panel to analyze case-type (11 samples) and artificially degraded samples (seven samples in triplicate). The results generated from this study illustrate that extensive sequence variation exists in commonly used STR markers in the selected population samples and indicate that this NGS STR panel has the potential to be used as an effective tool for human forensics.     

双螺旋叠栅条纹检测光束准直性的两种方法

介绍双螺旋叠栅条纹检测光束准直性的基本原理,进一步就双螺旋叠栅条纹的特征参量与被测光束发散角(即光束准直精度)的关系进行分析和推导。在分析双螺旋叠栅条纹进行时,首先采用频域低通滤波提取纯叠栅条纹,然后提取纯叠栅条纹的特征参量。提出两种特征参量的提取方法,一种依次进行傅里叶变换计算相位信息的傅里叶变换方法,另一种是受传统时间相移算法启发而提出的空间相移算法,讨论了在两种方法中极坐标的重采样问题和相应的计算公式,并进行了计算机模拟。结果表明,傅里叶变换方法和空间相移算法实质都是获取叠栅条纹全场趋势的平均值,使最终光束发散角的检测具有很高的精度,对自成像条纹周期的检测误差在±2.8‰以内。     

Right Spread序的若干封闭性质

§1Introductionandmotivation Itisalwaysofinteresttocomparethevariabilityoftworandomvariablesinreliability theoryandeconomics.Thecomparisonsbasedonmomentssuchasvarianceandstandard deviationarenotveryinformativealthoughsuchmeasuresaresimpletouse.Meanwhile,sincethesecomparisonsarestaticones,andhencetheirapplicationsinsomefields,e.g.,reliabilityandfinance,arerestricted.Inthesefields,however,somedynamicalcomparisons areneeded.Asaresult,severalstochasticordersthataremorerefinedhavebeen establishedi…