Phantom mutation hotspots in human mitochondrial DNA

Phantom mutations are systematic artifacts generated in the course of the sequencing process. Contra common belief these artificial mutations are nearly ubiquitous in sequencing results, albeit at frequencies that may vary dramatically. The amount of artifacts depends not only on the sort of automated sequencer and sequencing chemistry employed, but also on other lab-specific factors. An experimental study executed on four samples under various combinations of sequencing conditions revealed a number of phantom mutations occurring at the same sites of mitochondrial DNA (mtDNA) repeatedly. To confirm these and identify further hotspots for artifacts, > 5000 mtDNA electropherograms were screened for artificial patterns. Further, > 30000 published hypervariable segment 1 sequences were compared at potential hotspots for phantom mutations, especially for variation at positions 16085 and 16197. Resequencing of several samples confirmed the artificial nature of these and other polymorphisms in the original publications. Single-strand sequencing, as typically executed in medical and anthropological studies, is thus highly vulnerable to this kind of artifacts. In particular, phantom mutation hotspots could easily lead to misidentification of somatic mutations and to misinterpretations in all kinds of clinical mtDNA studies.

Crossing the phantom divide in brane cosmology with curvature corrections and brane-bulk energy transfer

We consider the Randall-Sundrum brane-world model with bulk-brane energy transfer where the Einstein-Hilbert action is modified by curvature correction terms: a four-dimensional scalar curvature from induced gravity on the brane, and a five-dimensional Gauss-Bonnet curvature term. It is remarkable that these curvature terms will not change the dynamics of the brane universe at low energy. Parameterizing the energy transfer and taking the dark radiation term into account, we find that the phantom divide of the equation of state of effective dark energy could be crossed, without the need of any new dark energy components. Fitting the two most reliable and robust SNIa datasets, the 182 Gold dataset and the Supernova Legacy Survey (SNLS), our model indeed has a small tendency of phantom divide crossing for the Gold dataset, but not for the SNLS dataset. Furthermore, combining the recent detection of the SDSS baryon acoustic oscillations peak (BAO) with lower matter density parameter prior, we find that the SNLS dataset also mildly favors phantom divide crossing.

Can the occurrence of rare insertion/deletion polymorphisms in human mtDNA be verified from phylogeny?

Due to its specific characteristics, such as maternal inheritance and absence of recombination, each mtDNA belongs to certain monophyletic clade in the rooted mtDNA tree (haplogroup) according to the mutations it harbors. Rare mutation (excluding parallel mutation) occurring at multiple times in different haplogroups could thus be a potential reading error according to the mtDNA phylogeny. This experience has been widely used in double-checking the credibility of the rare mutations in human mtDNA sequences. However, no test has been performed so far for the feasibility of applying this strategy to the rare insertion/deletion (indel) events in mtDNA sequences. In this study, we attempted to relate the rare indels in mtDNAs to their haplogroup status in a total of 2352 individuals from 50 populations in China. Our results show that the insertion of A at position 16259 is restricted to a subclade of haplogroup C and can be verified. The other indel polymorphisms, which occur in the repeat of the deleted or inserted nucleotide(s), may not be distinguished from phantom mutations from a phylogenetic point of view. Independently and multiply sequencing the fragment with the indel is the best and the most reliable way for confirmation.

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.

Micro Insert: A Prototype Full-Ring PET Device for Improving the Image Resolution of a Small-Animal PET Scanner

A full-ring PET insert device should be able to enhance the image resolution of existing small-animal PET scanners. Methods: The device consists of 18 high-resolution PET detectors in a cylindric enclosure. Each detector contains a cerium-doped lutetium oxyorthosilicate array (12 x 12 crystals, 0.72 x 1.51 x 3.75 mm each) coupled to a position-sensitive photomultiplier tube via an optical fiber bundle made of 8 x 16 square multiclad fibers. Signals from the insert detectors are connected to the scanner through the electronics of the disabled first ring of detectors, which permits coincidence detection between the 2 systems. Energy resolution of a detector was measured using a Ge-68 point source, and a calibrated 68Ge point source stepped across the axial field of view (FOV) provided the sensitivity profile of the system. A Na-22 point source imaged at different offsets from the center characterized the in-plane resolution of the insert system. Imaging was then performed with a Derenzo phantom filled with 19.5 MBq of F-18-fluoride and imaged for 2 h; a 24.3-g mouse injected with 129.5 MBq of F-18-fluoride and imaged in 5 bed positions at 3.5 h after injection; and a 22.8-g mouse injected with 14.3 MBq of F-18-FDG and imaged for 2 h with electrocardiogram gating. Results: The energy resolution of a typical detector module at 511 keV is 19.0% +/- 3.1 %. The peak sensitivity of the system is approximately 2.67%. The image resolution of the system ranges from 1.0- to 1.8-mm full width at half maximum near the center of the FOV, depending on the type of coincidence events used for image reconstruction. Derenzo phantom and mouse bone images showed significant improvement in transaxial image resolution using the insert device. Mouse heart images demonstrated the gated imaging capability of the device. Conclusion: We have built a prototype full-ring insert device for a small-animal PET scanner to provide higher-resolution PET images within a reduced imaging FOV. Development of additional correction techniques are needed to achieve quantitative imaging with such an insert.

The generalized second law of thermodynamics in generalized gravity theories

We investigate the generalized second law of thermodynamics (GSL) in generalized theories of gravity. We examine the total entropy evolution with time including the horizon entropy, the non-equilibrium entropy production, and the entropy of all matter, field and energy components. We derive a universal condition to protect the generalized second law and study its validity in different gravity theories. In Einstein gravity (even in the phantom-dominated universe with a Schwarzschild black hole), Lovelock gravity and braneworld gravity, we show that the condition to keep the GSL can always be satisfied. In f ( R) gravity and scalar-tensor gravity, the condition to protect the GSL can also hold because the temperature should be positive, gravity is always attractive and the effective Newton constant should be an approximate constant satisfying the experimental bounds.

力觉触觉再现技术及其应用研究

力觉确虫觉再现技术是近年来发展起来的一项新兴技术，在遥操作机器人、虚拟现实、医疗仿真、原形设计、纳米操作等很多领域中获得了相当广泛的应用。力觉／触觉再现接口是一种力反射设备，它可以使用户触摸、感觉、操作、创建和变换虚拟环境中仿真的虚拟3维物体。根据能量来源的方式，力觉确虫觉再现接日分为有源和无源两类。本论文针对有源力觉／触觉再现接口的动力学进行了分析，并以虚拟手术和机器人遥操作为背景，做了一些力觉／触觉再现技术的应用性研究工作。具体说来，本文主要进行了如下四项有创造和有价值的工作：（1)分析了有源力觉／触觉再现接口设计时所要考虑的几个基本问题，推导了力觉确虫觉再现接口的动力学模型。(2)以PHANTOM和GHOST SDK为开发平台，构造了一个虚拟仿真系统，研究实现力觉确虫觉再现接口涉及的几个基本问题。(3)以力觉／触觉再现接口PHANTOM为主端，全方位移动机器人M.BOT为从端建立了遥操作实验系统。提出了两种系统结构：位置给定系统和速度给定系统，并根据速度给定系统给出了具体设计。（4）遥操作实验研究。对于速度给定系统，给出了虚拟平面、虚拟障碍和虚拟墙实验。对位置给定系统与速度给定系统进行了对比分析。实验主要体现力觉／触觉再现技术对遥操作精确定位与避免碰撞的作用。