High penetrance of sequencing errors and interpretative shortcomings in mtDNA sequence analysis of LHON patients

For identifying mutation(s) that are potentially pathogenic it is essential to determine the entire mitochondrial DNA (mtDNA) sequences from patients suffering from a particular mitochondrial disease, such as Leber hereditary optic neuropathy (LHON). Howe

WAVELENGTH POSITIONING ERRORS AND TRUE DETECTION LIMIT IN RELATION TO MULTICOMPONENT ANALYSIS TECHNIQUES FOR THE CORRECTION OF LINE INTERFERENCES IN INDUCTIVELY COUPLED PLASMA ATOMIC EMISSION-SPECTROMETRY

The present paper deals with the evaluation of the relative error (DELTA(A)) in estimated analyte concentrations originating from the wavelength positioning error in a sample scan when multicomponent analysis (MCA) techniques are used for correcting line interferences in inductively coupled plasma atomic emission spectrometry. In the theoretical part, a quantitative relation of DELTA(A) with the extent of line overlap, bandwidth and the magnitude of the positioning error is developed under the assumption of Gaussian line profiles. The measurements of eleven samples covering various typical line interferences showed that the calculated DELTA(A) generally agrees well with the experimental one. An expression of the true detection limit associated with MCA techniques was thus formulated. With MCA techniques, the determination of the analyte and interferent concentrations depend on each other while with conventional correction techniques, such as the three-point method, the estimate of interfering signals is independent of the analyte signals. Therefore. a given positioning error results in a larger DELTA(A) and hence a higher true detection limit in the case of MCA techniques than that in the case of conventional correction methods. although the latter could be a reasonable approximation of the former when the peak distance expressed in the effective width of the interfering line is larger than 0.4. In the light of the effect of wavelength positioning errors, MCA techniques have no advantages over conventional correction methods unless the former can bring an essential reduction ot the positioning error.

Split-aperture laser pulse compressor design tolerant to alignment and line-density differences

We introduce a four-pass laser pulse compressor design based on two grating apertures with two gratings per aperture that is tolerant to some alignment errors and, importantly, to grating-to-grating period variations. Each half-beam samples each grating in a diamond-shaped compressor that is symmetric about a central bisecting plane. For any given grating, the two half-beams impinge on opposite sides of its surface normal. It is shown that the two split beams have no pointing difference from paired gratings with different periods. Furthermore, no phase shift between half-beams is incurred as long as the planes containing a grating line and the surface normal for each grating of the pair are parallel. For grating pairs satisfying this condition, gratings surfaces need not be on the same plane, as changes in the gap between the two can compensate to bring the beams back in phase. © 2008 Optical Society of America.

Dynamics of nonlinear error growth and season-dependent predictability of El Nino events in the Zebiak-Cane model

With the intermediate-complexity Zebiak-Cane model, we investigate the 'spring predictability barrier' (SPB) problem for El Nino events by tracing the evolution of conditional nonlinear optimal perturbation (CNOP), where CNOP is superimposed on the El Nino events and acts as the initial error with the biggest negative effect on the El Nino prediction. We show that the evolution of CNOP-type errors has obvious seasonal dependence and yields a significant SPB, with the most severe occurring in predictions made before the boreal spring in the growth phase of El Nino. The CNOP-type errors can be classified into two types: one possessing a sea-surface-temperature anomaly pattern with negative anomalies in the equatorial central-western Pacific, positive anomalies in the equatorial eastern Pacific, and a thermocline depth anomaly pattern with positive anomalies along the Equator, and another with patterns almost opposite to those of the former type. In predictions through the spring in the growth phase of El Nino, the initial error with the worst effect on the prediction tends to be the latter type of CNOP error, whereas in predictions through the spring in the decaying phase, the initial error with the biggest negative effect on the prediction is inclined to be the former type of CNOP error. Although the linear singular vector (LSV)-type errors also have patterns similar to the CNOP-type errors, they cover a more localized area than the CNOP-type errors and cause a much smaller prediction error, yielding a less significant SPB. Random errors in the initial conditions are also superimposed on El Nino events to investigate the SPB. We find that, whenever the predictions start, the random errors neither exhibit an obvious season-dependent evolution nor yield a large prediction error, and thus may not be responsible for the SPB phenomenon for El Nino events. These results suggest that the occurrence of the SPB is closely related to particular initial error patterns. The two kinds of CNOP-type error are most likely to cause a significant SPB. They have opposite signs and, consequently, opposite growth behaviours, a result which may demonstrate two dynamical mechanisms of error growth related to SPB: in one case, the errors grow in a manner similar to El Nino; in the other, the errors develop with a tendency opposite to El Nino. The two types of CNOP error may be most likely to provide the information regarding the 'sensitive area' of El Nino-Southern Oscillation (ENSO) predictions. If these types of initial error exist in realistic ENSO predictions and if a target method or a data assimilation approach can filter them, the ENSO forecast skill may be improved. Copyright (C) 2009 Royal Meteorological Society

The accuracy of Kirchhoff's approximation in describing the far field speckles produced by random self-affine fractal surfaces

Based on the rigorous formulation of integral equations for the propagations of light waves at the medium interface, we carry out the numerical solutions of the random light field scattered from self-affine fractal surface samples. The light intensities produced by the same surface samples are also calculated in Kirchhoff's approximation, and their comparisons with the corresponding rigorous results show directly the degree of the accuracy of the approximation. It is indicated that Kirchhoff's approximation is of good accuracy for random surfaces with small roughness value w and large roughness exponent alpha. For random surfaces with larger w and smaller alpha, the approximation results in considerable errors, and detailed calculations show that the inaccuracy comes from the simplification that the transmitted light field is proportional to the incident field and from the neglect of light field derivative at the interface.

NUMERICAL STUDY OF DAMMANN ARRAY ILLUMINATORS

The numerical solutions of binary-phase (0, tau) gratings for one-dimensional array illuminators up to 32 are presented. Some fabrication errors, which are due to position-quantization errors, phase errors, dilation (or erosion) errors, and the side-slope error, are calculated and show that even-number array illuminators are superior to odd-number array illuminators when these fabrication errors are considered. One (0, tau) binary-phase, 8 x 16 array illuminator made with the wet-chemical-etching method is given in this paper.

拼接光栅压缩器的时域特性

在拼接光栅和拼接光栅压缩器的设计中,子光栅调节偏差不可避免,各维偏差与拼接光栅的时间特性之间的关系很关键。通过脉冲压缩理论分析得到各维偏差和聚焦脉冲时间宽度展宽之间的解析关系,从数值计算结果分析,面平行左右偏差对脉冲的时间宽度影响较大,必须控制在21.08 μrad内；条纹密度差异对脉冲宽度的影响很显著,相对条纹密度的比值应控制在10-5以内；从消除角色散的角度分析,面平行俯仰偏差和条纹平行度偏差可以相互补偿,条纹密度差异和面平行左右偏差也可以相互补偿。

阵列光栅压缩器的空域特性

引入角度偏差、位移偏差作为拼接光栅系统的物理参数，定义了拼接光栅的孔径函数，利用傅里叶角谱理论研究了高斯脉冲入射拼接光栅压缩器后的远场分布特性。研究表明；出射脉冲仍然是高斯型脉冲，但包络中心发生偏移，偏移量由角度偏差量和光束口径决定；位移偏差引入的相位随着拼接光栅压缩器传递，其对远场焦斑的影响，取决于每片子光栅的非整数倍光栅常数的横向位移偏差和纵向位移偏差的综合作用。通过数值计算得到了各维偏差对阵列光栅压缩器空域特性的影响，计算表明：光栅面外角度偏差（俯仰左右）和条纹平行度偏差都必须控制在1μrad以内，

立方反射镜失调特性的研究

结合理想坐标系下立方镜镜面微小倾斜后其三个平面法线坐标，利用刚体微量转动的反射法线向量公式，获得非理想立方镜反射矩阵；为了研究在光斜入射时镜面倾斜对出射光方向的影响，利用立方镜绕顶点旋转等效于光斜入射的方法，计算出光束夹角δ与单一镜面偏差角ε和立方镜旋转角θ之间的关系式；对于理想情况下的立方镜，利用几何光学可以证明出射光与入射光不但平行，而且过顶点作任意截面交于两光线所得的两个交点关于顶点对称，从而计算出立方镜绕顶点以外任意轴旋转造成出射光束相对原出射光的偏移量与旋转角关系式，理论计算值与实验数据吻合得很

Techniques for fabrication of large-size graded reflectivity mirrors

According to the parameter requirements of a graded reflectivity mirror with a Gaussian profile, the layer structure and the mask pattern are designed using a graded-thickness middle layer. The mask and the automatic mask-switchover equipment are designed considering the actual requirement of the thin films and the specific deposit facility. The uniformity of the layer thickness is analyzed. The measurement results indicate that samples prepared with this technique are basically in accordance with the design parameter. The scattering effect between the material molecules and the mask, thickness errors, and the alignment error between the mask and the substrate are the main factors that influence the deposit result. (c) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3027595]

A call for mtDNA data quality control in forensic science

There is increasing evidence that many of the mitochondrial DNA (mtDNA) databases published in the fields of forensic science and molecular anthropology are flawed. An a posteriori phylogenetic analysis of the sequences could help to eliminate most of the errors and thus greatly improve data quality. However, previously published caveats and recommendations along these lines were not yet picked up by all researchers. Here we call for stringent quality control of mtDNA data by haplogroup-directed database comparisons. We take some problematic databases of East Asian mtDNAs, published in the Journal of Forensic Sciences and Forensic Science International, as examples to demonstrate the process of pinpointing obvious errors. Our results show that data sets are not only notoriously plagued by base shifts and artificial recombination but also by lab-specific phantom mutations, especially in the second hypervariable region (HVR-II). (C) 2003 Elsevier Ireland Ltd. All rights reserved.

A critical reassessment of the role of mitochondria in tumorigenesis

Background Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. Methods and Findings In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis. Conclusion The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research.

A reappraisal of complete mtDNA variation in East Asian families with hearing impairment

In a number of recent studies, we summarized the obvious errors and shortcomings that can be spotted in many (if not most) mitochondrial DNA (mtDNA) data sets published in medical genetics. We have reanalyzed here the complete mtDNA genome data published

Java程序中数组越界和空指针错误的静态分析

介绍了静态分析的相关背景知识,对Java程序中数组越界和空指针错误的常见表现形式进行了归类,并通过实验评估了现有的Java静态分析工具功能,指出了其在跨过程分析中的不足,并对如何改进进行了讨论.

Double neutron-proton differential transverse flow as a probe for the high density behavior of the nuclear symmetry energy

The double neutron-proton differential transverse flow taken from two reaction systems using different isotopes of the same element is studied at incident beam energies of 400 and 800 MeV/nucleon within the framework of an isospin- and momentum-dependent hadronic transport model IBUU04. The double differential flow is found to retain about the same sensitivity to the density dependence of the nuclear symmetry energy as the single differential flow in the more neutron-rich reaction. Because the double differential flow reduces significantly both the systematic errors and the influence of the Coulomb force, it is thus more effective probe for the high-density behavior of the nuclear symmetry energy.