19 resultados para copy number variant

em Chinese Academy of Sciences Institutional Repositories Grid Portal


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The mitochondrial DNA (mtDNA) control region is believed to play an important biological role in mtDNA replication. Large deletions in this region are rarely found, but when they do occur they might be expected to interfere with the replication of the molecule, thus leading to a reduction of mtDNA copy number. During a survey for mtDNA sequence variations in 5,559 individuals from the general Chinese population and 2,538 individuals with medical disorders, we identified a 50-bp deletion (m.298_347del50) in the mtDNA control region in a member of a healthy Han Chinese family belonging to haplogroup B4c1b2, as suggested by complete mtDNA genome sequencing. This deletion removes the conserved sequence block II (CSBII; region 299-315) and the replication primer location (region 317-321). However, quantification of the mtDNA copy number in this subject showed a value within a range that was observed in 20 healthy subjects without the deletion. The deletion was detected in the hair samples of the maternal relatives of the subject and exhibited variable heteroplasmy. Our current observation, together with a recent report for a benign 154-bp deletion in the mtDNA control region, suggests that the control of mtDNA replication may be more complex than we had thought. Hum Mutat 31:538-543, 2010. (C) 2010 Wiley-Liss, Inc.

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With current gene-transfer techniques in fish, insertion of DNA into the genome occurs randomly and in many instances at multiple sites. Associated position effects, copy number differences, and multiple gene interactions make gene expression experiments difficult to interpret and fish phenotype less predictable. To meet different fish engineering needs, we describe here a gene targeting model in zebrafish. At first, four target zebrafish lines, each harboring a single genomic lox71 target site, were generated by zebrafish transgenesis. The zygotes of transgenic zebrafish lines were coinjected with capped Cre mRNA and a knockin vector pZklox66RFP. Site-specific integration event happened from one target zebrafish line. In this line two integrant zebrafish were obtained from more than 80,000 targeted embryos (integrating efficiency about 10(-4) to 10(-5)) and confirmed to have a sole copy of the integrating DNA at the target genome site. Genomic polymerase chain reaction analysis and DNA sequencing verified the correct gene target events where lox71 and lox66 have accurately recombined into double mutant lox72 and wild-type loxP. Each integrant zebrafish chosen for analysis harbored the transgene rfp at the designated egfp concatenates. Although the Cre-mediated recombination is site specific, it is dependent on a randomly placed target site. That is, a genomic target cannot be preselected for integration based solely on its sequence. Conclusively, an rfp reporter gene was successfully inserted into the egfp target locus of zebrafish genome by Cre-lox-mediated recombination. This site-directed knockin system using the lox71/lox66 combination should be a promising gene-targeting platform serving various purposes in fish genetic engineering.

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The evolution of dispersed short-fatigue-cracks is analysed based on the equilibrium of crack-number-density (CND). By separating the mean value and the stochastic fluctuation of local CND, the equilibrium equation of overall CND is derived. Comparing with the mean-field equilibrium equation, the equilibrium equation of overall CND has different forms in the expression of crack-nucleation-rate or crack-growth-rate. The simulation results are compared with experimental measurements showing the stochastic analyses provide consistent tendency with experiments. The discrepancy in simulation results between overall CND and mean-field CND is discussed.

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A dimensionless number, termed as response number in Zhao [Archive of Applied Mechanics 68 (1998) 524], has been suggested for the dynamic plastic response of beams and plates made up of rigidly perfect plastic materials subjected to dynamic loading. Many theoretical and experimental results can be reformulated into new concise forms with the response number. The concept of a new dimensionless number, response number, termed as Rn(n), is generalized in Zhao [Forschung im Ingenieurwesen 65 (1999) 107] to study the elastic, plastic, dynamic elastic as well as dynamic plastic buckling problems of columns, plates as well as shells. The response number Rn(n) is generalized to the dynamic behaviour of shells of various shapes in the present paper.

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A dimensionless number, termed response number, is applied to the dynamic plastic response of plates subjected to dynamic loading. Many theoretical and experimental results presented by different researchers are reformulated into new concise forms with the response number. The advantage of the new forms is twofold: (1) they are more physically meaningful, and (2) they are independent of the choice of units, thus, they have wider range of applications.

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A perturbation method is used to examine the linear instability of thermocapillary convection in a liquid bridge of floating half-zone filled with a small Prandtl number fluid. The influence of liquid bridge volume on critical Marangoni number and flow features is analyzed. The neutral modes show that the instability is mainly caused by the bulk flow that is driven by the nonuniform thermocapillary forces acting on the free surface. The hydrodynamic instability is dominant in the case of small Prandtl number fluid and the first instability mode is a stationary bifurcation. The azimuthal wave number for the most dangerous mode depends on the liquid bridge volume, and is not always two as in the case of a cylindrical liquid bridge with aspect ratio near 0.6. Its value may be equal to unity when the liquid bridge is relatively slender.

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To overcome the difficulty in the DNS of compressible turbulence at high turbulent Mach number, a new difference scheme called GVC8 is developed. We have succeeded in the direct numerical simulation of decaying compressible turbulence up to turbulent Mach number 0.95. The statistical quantities thus obtained at lower turbulent Mach number agree well with those from previous authors with the same initial conditions, but they are limited to simulate at lower turbulent Mach numbers due to the so-called start-up problem. The energy spectrum and coherent structure of compressible turbulent flow are analysed. The scaling law of compressible turbulence is studied. The computed results indicate that the extended self-similarity holds in decaying compressible turbulence despite the occurrence of shocklets, and compressibility has little effects on relative scaling exponents when turbulent Mach number is not very high.

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A dimensionless number, termed response number in the present paper, is suggested for the dynamic plastic response of beams and plates made of rigid-perfectly plastic materials subjected to dynamic loading. It is obtained at dimensional reduction of the basic governing equations of beams and plates. The number is defined as the product of the Johnson's damage number and the square of the half of the slenderness ratio for a beam; the product of the damage number and the square of the half of the aspect ratio for a plate or membrane loaded dynamically. Response number can also be considered as the ratio of the inertia force at the impulsive loading to the plastic limit load of the structure. Three aspects are reflected in this dimensionless number: the inertia of the applied dynamic loading, the resistance ability of the material to the deformation caused by the loading and the geometrical influence of the structure on the dynamic response. For an impulsively loaded beam or plate, the final dimensionless deflection is solely dependent upon the response number. When the secondary effects of finite deflections, strain-rate sensitivity or transverse shear are taken into account, the response number is as useful as in the case of simple bending theory. Finally, the number is not only suitable to idealized dynamic loads but also applicable to dynamic loads of general shape.

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The Peclet number is a useful index to estimate the importance of sedimentation as compared to the Brownian motion. However, how to choose the characteristic length scale for the Peclet number evaluation is rather critical because the diffusion length increases as the square root of the time whereas the drifting length is linearly related to time. Our Brownian dynamics simulation shows that the degree of sedimentation influence on the coagulation decreases when the dispersion volume fraction increases. Therefore using a fixed length, such as the diameter of particle, as the characteristic length scale for Peclet number evaluation is not a good choice when dealing with the influence of sedimentation on coagulation. The simulations demonstrated that environmental factors in the coagulation process, such as dispersion volume fraction and size distribution, should be taken into account for more reasonable evaluation of the sedimentation influence.

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The linear instability analysis of the present paper shows that the thermocapillary convection in a half floating zone of larger Prandtl number has a steady instability mode w(i) = 0 and m = 1 for a fat liquid bridge V = 1.2 with small geometrical aspect ratio A = 0.6. This conclusion is different from the usual idea of hydrothermal instability, and implies that the instability of the system may excite a steady and axial asymmetric state before the onset of oscillation in the ease of large Prandtl number.

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It is proved that Johnson's damage number is the sole similarity parameter for dynamic plastic shear failure of structures loaded impulsively, therefore, dynamic plastic shear failure can be understood when damage number reaches a critical value. It is suggested that the damage number be generally used to predict the dynamic plastic shear failure of structures under various kinds of dynamic loads (impulsive loading, rectangular pressure pulse, exponential pressure pulse, etc.,). One of the advantages for using the damage number to predict such kind of failure is that it is conveniently used for dissimilar material modeling.

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Processes of the onset oscillation in the thermocapillaxy convection under the Earth's gravity are investigated by the numerical simulation and experiments in a floating half zone of large Prandtl number with different volume ratio. Both computational and experimental results show that the steady and axisymmetric convection turns to the oscillatory convection of m=1 for the slender liquid bridge, and to the oscillatory convection before a steady and 3D asymmetric state for the case of a fat liquid bridge. It implies that, there are two critical Marangoni numbers related, respectively, to these two bifurcation transitions for the fat liquid bridge. The computational results agree with the results of ground-based experiments.

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The hydrothermal wave was investigated numerically for large-Prandtl-number fluid (Pr = 105.6) in a shallow cavity with different heated sidewalls. The traveling wave appears and propagates in the direction opposite to the surface flow (upstream) in the case of zero gravity when the applied temperature difference grows and over the critical value. The phase relationships of the disturbed velocity, temperature and pressure demonstrate that the traveling wave is driven by the disturbed temperature, which is named hydrothermal wave. The hydrothermal wave is so weak that the oscillatory flow field and temperature distribution can hardly be observed in the liquid layer. The exciting mechanism of hydrothermal wave is analyzed and discussed in the present paper.