CollapsABEL: An R library for detecting compound heterozygote alleles in genome-wide association studies

Background: Compound Heterozygosity (CH) in classical genetics is the presence of two different recessive mutations at a particular gene locus. A relaxed form of CH alleles may account for an essential proportion of the missing heritability, i.e. heritability of phenotypes so far not accounted for by single genetic variants. Methods to detect CH-like effects in genome-wide association studies (GWAS) may facilitate explaining the missing heritability, but to our knowledge no viable software tools for this purpose are currently available. Results: In this work we present the Generalized Compound Double Heterozygosity (GCDH) test and its implementation in the R package CollapsABEL. Time-consuming procedures are optimized for computational efficiency using Java or C++. Intermediate results are stored either in an SQL database or in a so-called big.matrix file to achieve reasonable memory footprint. Our large scale simulation studies show that GCDH is capable of discovering genetic associations due to CH-like interactions with much higher power than a conventional single-SNP approach under various settings, whether the causal genetic variations are available or not. CollapsABEL provides a user-friendly pipeline for genotype collapsing, statistical testing, power estimation, type I error control and graphics generation in the R language. Conclusions: CollapsABEL provides a computationally efficient solution for screening general forms of CH alleles in densely imputed microarray or whole genome sequencing datasets. The GCDH test provides an improved power over single-SNP based methods in detecting the prevalence of CH in human complex phenotypes, offering an opportunity for tackling the missing heritability problem. Binary and source packages of CollapsABEL are available on CRAN (https://cran.r-project.org/web/packages/CollapsABEL) and the website of the GenABEL project (http://www.genabel.org/packages)

A note on the geometric phase in adiabatic approximation

The adiabatic theorem shows that the instantaneous eigenstate is a good approximation of the exact solution for a quantum system in adiabatic evolution. One may therefore expect that the geometric phase calculated by using the eigenstate should be also a good approximation of exact geometric phase. However, we find that the former phase may differ appreciably from the latter if the evolution time is large enough.Comment: 11 pages, no figure, modified and Journal-ref adde

Рифма в рамках средневекового крымскотатарского силлабического стиха

В предложенной статье представлен теоретический материал, который раскрывает сущность и особенности рифмы, подкреплённый необходимым материалом из крымскотатарской литературы.У запропонованій статті представлений теоретичний матеріал, що розкриває сутність і особливості рими, підкріплений необхідним матеріалом із кримськотатарської літератури.In offered article the theoretical material which opens essence and features of the rhyme, supported by a necessary material from crimean tatars literatures is submitted

Quantum cloning machines for equatorial qubits

Quantum cloning machines for equatorial qubits are studied. For the case of 1 to 2 phase-covariant quantum cloning machine, we present the networks consisting of quantum gates to realize the quantum cloning transformations. The copied equatorial qubits are shown to be separable by using Peres-Horodecki criterion. The optimal 1 to M phase-covariant quantum cloning transformations are given.Comment: Revtex, 9 page

Modelling the Interfacial Flow of Two Immiscible Liquids in Mixing Processes

This paper presents an interface tracking method for modelling the flow of immiscible metallic liquids in mixing processes. The methodology can provide an insight into mixing processes for studying the fundamental morphology development mechanisms for immiscible interfaces. The volume-of-fluid (VOF) method is adopted in the present study, following a review of various modelling approaches for immiscible fluid systems. The VOF method employed here utilises the piecewise linear for interface construction scheme as well as the continuum surface force algorithm for surface force modelling. A model coupling numerical and experimental data is established. The main flow features in the mixing process are investigated. It is observed that the mixing of immiscible metallic liquids is strongly influenced by the viscosity of the system, shear forces and turbulence. The numerical results show good qualitative agreement with experimental results, and are useful for optimisating the design of mixing casting processes

Radiative corrections to the excitonic molecule state in GaAs microcavities

The optical properties of excitonic molecules (XXs) in GaAs-based quantum well microcavities (MCs) are studied, both theoretically and experimentally. We show that the radiative corrections to the XX state, the Lamb shift $\Delta^{\rm MC}_{\rm XX}$ and radiative width $\Gamma^{\rm MC}_{\rm XX}$, are large, about $10-30$ of the molecule binding energy $\epsilon_{\rm XX}$, and definitely cannot be neglected. The optics of excitonic molecules is dominated by the in-plane resonant dissociation of the molecules into outgoing 1$\lambda$-mode and 0$\lambda$-mode cavity polaritons. The later decay channel, ``excitonic molecule $\to$ 0$\lambda$-mode polariton + 0$\lambda$-mode polariton'', deals with the short-wavelength MC polaritons invisible in standard optical experiments, i.e., refers to ``hidden'' optics of microcavities. By using transient four-wave mixing and pump-probe spectroscopies, we infer that the radiative width, associated with excitonic molecules of the binding energy $\epsilon_{\rm XX} \simeq 0.9-1.1$ meV, is $\Gamma^{\rm MC}_{\rm XX} \simeq 0.2-0.3$ meV in the microcavities and $\Gamma^{\rm QW}_{\rm XX} \simeq 0.1$ meV in a reference GaAs single quantum well (QW). We show that for our high-quality quasi-two-dimensional nanostructures the $T_2 = 2 T_1$ limit, relevant to the XX states, holds at temperatures below 10 K, and that the bipolariton model of excitonic molecules explains quantitatively and self-consistently the measured XX radiative widths. We also find and characterize two critical points in the dependence of the radiative corrections against the microcavity detuning, and propose to use the critical points for high-precision measurements of the molecule bindingenergy and microcavity Rabi splitting.Comment: 16 pages, 11 figures, accepted for publication in Phys. Rev.

Global skin colour prediction from DNA

Human skin colour is highly heritable and externally visible with relevance in medical, forensic, and anthropological genetics. Although eye and hair colour can already be predicted with high accuracies from small sets of carefully selected DNA markers, knowledge about the genetic predictability of skin colour is limited. Here, we investigate the skin colour predictive value of 77 single-nucleotide polymorphisms (SNPs) from 37 genetic loci previously associated with human pigmentation using 2025 individuals from 31 global populations. We identified a minimal set of 36 highly informative skin colour predictive SNPs and developed a statistical prediction model capable of skin colour prediction on a global scale. Average cross-validated prediction accuracies expressed as area under the receiver-operating characteristic curve (AUC) ± standard deviation were 0.97 ± 0.02 for Light, 0.83 ± 0.11 for Dark, and 0.96 ± 0.03 for Dark-Black. When using a 5-category, this resulted in 0.74 ± 0.05 for Very Pale, 0.72 ± 0.03 for Pale, 0.73 ± 0.03 for Intermediate, 0.87±0.1 for Dark, and 0.97 ± 0.03 for Dark-Black. A comparative analysis in 194 independent samples from 17 populations demonstrated that our model outperformed a previously proposed 10-SNP-classifier approach with AUCs rising from 0.79 to 0.82 for White, comparable at the intermediate level of 0.63 and 0.62, respectively, and a large increase from 0.64 to 0.92 for Black. Overall, this study demonstrates that the chosen DNA markers and prediction model, particularly the 5-category level; allow skin colour predictions within and between continental regions for the first time, which will serve as a valuable resource for future applications in forensic and anthropologic genetics

Employment change in occupations in urban India : implications for wage inequality

This article analyses employment and wage change patterns in India for a period spanning almost three decades, from 1983–84 to 2011–12. Using data from the National Sample Survey Organization, the study finds evidence of job polarization (employment growth in low‐ and high‐skill jobs and decline in middle‐skill jobs) in urban India during the 1990s and 2000s, and employment upgrading in the 1980s. Consistent with the literature on job polarization, the article finds a reduction in employment share in routine task intensive occupations. The author argues that this reduction is a result of both mechanization and technological upgrading within Indian industry. On the other hand, an increase in employment share in both low‐skill and high‐skill occupations is argued to be a result of growing self‐employment and informal sector employment in urban India. The wage change patterns are largely consistent with the employment change patterns. The analysis suggests that structural change in occupation is an important factor for understanding earnings inequality in India

Characterization of a novel model for atherosclerosis imaging:the apolipoprotein E-deficient rat

Background: The apolipoprotein E-deficient (apoE −/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE −/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE −/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging.Results: ApoE −/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p &lt; 0.001) and abdominal aorta (+ 31.0%, p &lt; 0.001) at weeks 12, 26, and 51. ApoE −/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE −/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE −/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE −/− rats. Conclusion: These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE −/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.</p

Characterization of a novel model for atherosclerosis imaging:the apolipoprotein E-deficient rat

Background: The apolipoprotein E-deficient (apoE −/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE −/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE −/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging.Results: ApoE −/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p &lt; 0.001) and abdominal aorta (+ 31.0%, p &lt; 0.001) at weeks 12, 26, and 51. ApoE −/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE −/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE −/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE −/− rats. Conclusion: These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE −/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.</p