Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays.

Determination of copy number variants (CNVs) inferred in genome wide single nucleotide polymorphism arrays has shown increasing utility in genetic variant disease associations. Several CNV detection methods are available, but differences in CNV call thresholds and characteristics exist. We evaluated the relative performance of seven methods: circular binary segmentation, CNVFinder, cnvPartition, gain and loss of DNA, Nexus algorithms, PennCNV and QuantiSNP. Tested data included real and simulated Illumina HumHap 550 data from the Singapore cohort study of the risk factors for Myopia (SCORM) and simulated data from Affymetrix 6.0 and platform-independent distributions. The normalized singleton ratio (NSR) is proposed as a metric for parameter optimization before enacting full analysis. We used 10 SCORM samples for optimizing parameter settings for each method and then evaluated method performance at optimal parameters using 100 SCORM samples. The statistical power, false positive rates, and receiver operating characteristic (ROC) curve residuals were evaluated by simulation studies. Optimal parameters, as determined by NSR and ROC curve residuals, were consistent across datasets. QuantiSNP outperformed other methods based on ROC curve residuals over most datasets. Nexus Rank and SNPRank have low specificity and high power. Nexus Rank calls oversized CNVs. PennCNV detects one of the fewest numbers of CNVs.

Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators.

Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises from the binding of a regulatory protein to a promoter in the chromosomal DNA. In this study, we focus on two minimal oscillators based on activator titration and repressor titration to understand the key parameters that are important for oscillations and for overcoming binary noise. We show that the rate of unbinding from the DNA, despite traditionally being considered a fast parameter, needs to be slow to broaden the space of oscillatory solutions. The addition of multiple, independent DNA binding sites further expands the oscillatory parameter space for the repressor-titration oscillator and lengthens the period of both oscillators. This effect is a combination of increased effective delay of the unbinding kinetics due to multiple binding sites and increased promoter ultrasensitivity that is specific for repression. We then use stochastic simulation to show that multiple binding sites increase the coherence of oscillations by mitigating the binary noise. Slow values of DNA unbinding rate are also effective in alleviating molecular noise due to the increased distance from the bifurcation point. Our work demonstrates how the number of DNA binding sites and slow unbinding kinetics, which are often omitted in biophysical models of gene circuits, can have a significant impact on the temporal and stochastic dynamics of genetic oscillators.

Ill-Posedness, Regularization and Number of Degrees of Freedom

info:eu-repo/semantics/published

Superresolution and number of degrees of freedom in inverse diffraction with subwavelength sources

info:eu-repo/semantics/published

Number of degrees of freedom in inverse diffraction

The problem of inverse diffraction from plane to plane is considered in the case where a finite aperture exists in the boundary plane. Singular values and singular functions for the problem are introduced, and the number of degrees of freedom is defined in terms of the distribution of the singular values. Numerical computations are presented for the one-dimensional problem, and it is shown that the effect of evanescent waves disappears at a distance of approximately one wavelength from the boundary plane, even when the dimension of the slit is comparable with the wavelength of the diffracted field. © 1983 Taylor & Francis Group, LLC.

High number of antigen binding cells in unimmunized mice and possible occurrence of multispecific lymphocytes

A high frequency of Tobacco Mosaic virus (TMV) binding cells was found in spleen cells from unimmunized mice (about 3 to 4%). TMV binding is strongly inhibited by previous incubation with anti immunoglobulin antisera. After stripping of membrane receptors, a full recovery for antigen binding capacity can be observed after 24 hr culture. Experiments are presented to exclude artefactual fluorescent cells: interaction of TMV with some non immunoglobulin membrane components; interaction of fluorescent anti TMV antibody with the Fc receptor of B cells; the binding of TMV to cytophilic immunoglobulins. The occurrence of lymphocytes able to bind several non crossreactive antigens is suggested by three lines of evidence: the high number of antigen binding cells in unimmunized mice, presence of surface immunoglobulins on some TMV binding cells after complete capping of TMV receptors and the direct demonstration of lymphocytes binding TMV and hemocyanin at different membrane sites.

Difficulties and errors in number reasoning development

The detailed study of difficulties and errors in young learner comprehension is a relevant and productive research field in Mathematics Education. Studies in the field are numerous although somewhat too varied. The present paper is suggesting methodological perspectives and principles applying to the field of research; we also show an example with school work. The use of figurate numbers as a representation system gives richer conceptual values, boosts visual reasoning and facilitates learner understanding.

Monotone scheme and boundary conditions for finite volume simulation of magnetohydrodynamic internal flows at high Hartmann number

A monotone scheme for finite volume simulation of magnetohydrodynamic internal flows at high Hartmann number is presented. The numerical stability is analysed with respect to the electromagnetic force. Standard central finite differences applied to finite volumes can only be numerically stable if the vector products involved in this force are computed with a scheme using a fully staggered grid. The electromagnetic quantities (electric currents and electric potential) must be shifted by half the grid size from the mechanical ones (velocity and pressure). An integral treatment of the boundary layers is used in conjunction with boundary conditions for electrically conducting walls. The simulations are performed with inhomogeneous electrical conductivities of the walls and reach high Hartmann numbers in three-dimensional simulations, even though a non-adaptive grid is used.

Low Reynolds number turbulence models for accurate thermal simulations of electronic components

The electronics industry and the problems associated with the cooling of microelectronic equipment are developing rapidly. Thermal engineers now find it necessary to consider the complex area of equipment cooling at some level. This continually growing industry also faces heightened pressure from consumers to provide electronic product miniaturization, which in itself increases the demand for accurate thermal management predictions to assure product reliability. Computational fluid dynamics (CFD) is considered a powerful and almost essential tool for the design, development and optimization of engineering applications. CFD is now widely used within the electronics packaging design community to thermally characterize the performance of both the electronic component and system environment. This paper discusses CFD results for a large variety of investigated turbulence models. Comparison against experimental data illustrates the predictive accuracy of currently used models and highlights the growing demand for greater mathematical modelling accuracy with regards to thermal characterization. Also a newly formulated low Reynolds number (i.e. transitional) turbulence model is proposed with emphasis on hybrid techniques.

On Reynolds number and scaling effects in microchannel flows

This paper presents a numerical study of the Reynolds number and scaling effects in microchannel flows. The configuration includes a rectangular, high-aspect ratio microchannel with heat sinks, similar to an experimental setup. Water at ambient temperature is used as a coolant fluid and the source of heating is introduced via electronic cartridges in the solids. Two channel heights, measuring 0.3 mm and 1 mm are considered at first. The Reynolds number varies in a range of 500-2200, based on the hydraulic diameter. Simulations are focused on the Reynolds number and channel height effects on the Nusselt number. It is found that the Reynolds number has noticeable influences on the local Nusselt number distributions, which are in agreement with other studies. The numerical predictions of the dimensionless temperature of the fluid agree fairly well with experimental measurements; however the dimensionless temperature of the solid does exhibit a significant discrepancy near the channel exit, similar to those reported by other researchers. The present study demonstrates that there is a significant scaling effect at small channel height, typically 0.3 mm, in agreement with experimental observations. This scaling effect has been confirmed by three additional simulations being carried out at channel heights of 0.24 mm, 0.14 mm and 0.1 mm, respectively. A correlation between the channel height and the normalized Nusselt number is thus proposed, which agrees well with results presented.