Intragenic recombination between pseudogenes as a source of new disease specificity at a simple resistance locus

BACKGROUND: Pooling of multi-site MRI data is often necessary when a large cohort is desired. However, different scanning platforms can introduce systematic differences which confound true effects of interest. One may reduce multi-site bias by calibrating pivotal scanning parameters, or include them as covariates to improve the data integrity. NEW METHOD: In the present study we use a source-based morphometry (SBM) model to explore scanning effects in multi-site sMRI studies and develop a data-driven correction. Specifically, independent components are extracted from the data and investigated for associations with scanning parameters to assess the influence. The identified scanning-related components can be eliminated from the original data for correction. RESULTS: A small set of SBM components captured most of the variance associated with the scanning differences. In a dataset of 1460 healthy subjects, pronounced and independent scanning effects were observed in brainstem and thalamus, associated with magnetic field strength-inversion time and RF-receiving coil. A second study with 110 schizophrenia patients and 124 healthy controls demonstrated that scanning effects can be effectively corrected with the SBM approach. COMPARISON WITH EXISTING METHOD(S): Both SBM and GLM correction appeared to effectively eliminate the scanning effects. Meanwhile, the SBM-corrected data yielded a more significant patient versus control group difference and less questionable findings. CONCLUSIONS: It is important to calibrate scanning settings and completely examine individual parameters for the control of confounding effects in multi-site sMRI studies. Both GLM and SBM correction can reduce scanning effects, though SBM's data-driven nature provides additional flexibility and is better able to handle collinear effects

Collider signals from slow decays in supersymmetric models with an intermediate-scale solution to the mu problem

The problem of the origin of the mu parameter in the Minimal Supersymmetric Standard Model can be solved by introducing singlet supermultiplets with non-renormalizable couplings to the ordinary Higgs supermultiplets. The Peccei-Quinn symmetry is broken at a scale which is the geometric mean between the weak scale and the Planck scale, yielding a mu term of the right order of magnitude and an invisible axion. These models also predict one or more singlet fermions which have electroweak-scale masses and suppressed couplings to MSSM states. I consider the case that such a singlet fermion, containing the axino as an admixture, is the lightest supersymmetric particle. I work out the relevant couplings in several of the simplest models of this type, and compute the partial decay widths of the next-to-lightest supersymmetric particle involving leptons or jets. Although these decays will have an average proper decay length which is most likely much larger than a typical collider detector, they can occasionally occur within the detector, providing a striking signal. With a large sample of supersymmetric events, there will be an opportunity to observe these decays, and so gain direct information about physics at very high energy scales.Comment: 24 pages, LaTeX, 4 figure

Development of a high-resolution NGS-based HLA-typing and analysis pipeline

The human leukocyte antigen (HLA) complex contains the most polymorphic genes in the human genome. The classical HLA class I and II genes define the specificity of adaptive immune responses. Genetic variation at the HLA genes is associated with susceptibility to autoimmune and infectious diseases and plays a major role in transplantation medicine and immunology. Currently, the HLA genes are characterized using Sanger- or next-generation sequencing (NGS) of a limited amplicon repertoire or labeled oligonucleotides for allele-specific sequences. High-quality NGS-based methods are in proprietary use and not publicly available. Here, we introduce the first highly automated open-kit/open-source HLA-typing method for NGS. The method employs in-solution targeted capturing of the classical class I (HLA-A, HLA-B, HLA-C) and class II HLA genes (HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1). The calling algorithm allows for highly confident allele-calling to three-field resolution (cDNA nucleotide variants). The method was validated on 357 commercially available DNA samples with known HLA alleles obtained by classical typing. Our results showed on average an accurate allele call rate of 0.99 in a fully automated manner, identifying also errors in the reference data. Finally, our method provides the flexibility to add further enrichment target regions

The Hamiltonian of Einstein affine-metric formulation of General Relativity

It is shown that the Hamiltonian of the Einstein affine-metric (first order) formulation of General Relativity (GR) leads to a constraint structure that allows the restoration of its unique gauge invariance, four-diffeomorphism, without the need of any field dependent redefinition of gauge parameters as is the case for the second order formulation. In the second order formulation of ADM gravity the need for such a redefinition is the result of the non-canonical change of variables [arXiv: 0809.0097]. For the first order formulation, the necessity of such a redefinition "to correspond to diffeomorphism invariance" (reported by Ghalati [arXiv: 0901.3344]) is just an artifact of using the Henneaux-Teitelboim-Zanelli ansatz [Nucl. Phys. B 332 (1990) 169], which is sensitive to the choice of linear combination of tertiary constraints. This ansatz cannot be used as an algorithm for finding a gauge invariance, which is a unique property of a physical system, and it should not be affected by different choices of linear combinations of non-primary first class constraints. The algorithm of Castellani [Ann. Phys. 143 (1982) 357] is free from such a deficiency and it leads directly to four-diffeomorphism invariance for first, as well as for second order Hamiltonian formulations of GR. The distinct role of primary first class constraints, the effect of considering different linear combinations of constraints, the canonical transformations of phase-space variables, and their interplay are discussed in some detail for Hamiltonians of the second and first order formulations of metric GR. The first order formulation of Einstein-Cartan theory, which is the classical background of Loop Quantum Gravity, is also discussed.Comment: 74 page

Contributions from SUSY-FCNC couplings to the interpretation of the HyperCP events for the decay \Sigma^+ \to p \mu^+ \mu^-

The observation of three events for the decay $\Sigma^+ \to p \mu^+ \mu^-$ with a dimuon invariant mass of $214.3\pm0.5$MeV by the HyperCP collaboration imply that a new particle X may be needed to explain the observed dimuon invariant mass distribution. We show that there are regions in the SUSY-FCNC parameter space where the $A^0_1$ in the NMSSM can be used to explain the HyperCP events without contradicting all the existing constraints from the measurements of the kaon decays, and the constraints from the $K^0-\bar{K}^0$ mixing are automatically satisfied once the constraints from kaon decays are satisfied.Comment: 18 pages, 7 figure

Magnetic phases of skyrmion-hosting GaV4S8−ySey (y = 0, 2, 4, 8) probed with muon spectroscopy

We present the results of a muon-spin spectroscopy investigation of GaV4S8−ySey with y = 0, 2, 4, and 8. Zero-field measurements suggest that GaV4Se8 and GaV4S8 have distinct magnetic ground states, with the latter material showing an anomalous temperature dependence of the local magnetic field. It is not possible to evolve the magnetic state continuously between these two systems, with the intermediate y = 2 and 4 materials showing glassy magnetic behavior at low temperature. The skyrmion lattice (SkL) phase is evident in the y = 0 and 8 materials through an enhanced response of the muon-spin relaxation to the emergent dynamics that accompany the SkL. For our polycrystalline samples of GaV4Se8, this enhanced dynamic response is confined to a smaller region of the magnetic field-temperature phase diagram than the previous reports of the SkL in single crystals

Towards Solving QCD - The Transverse Zero Modes in Light-Cone Quantization

We formulate QCD in (d+1) dimensions using Dirac's front form with periodic boundary conditions, that is, within Discretized Light-Cone Quantization. The formalism is worked out in detail for SU(2) pure glue theory in (2+1) dimensions which is approximated by restriction to the lowest {\it transverse} momentum gluons. The dimensionally-reduced theory turns out to be SU(2) gauge theory coupled to adjoint scalar matter in (1+1) dimensions. The scalar field is the remnant of the transverse gluon. This field has modes of both non-zero and zero {\it longitudinal} momentum. We categorize the types of zero modes that occur into three classes, dynamical, topological, and constrained, each well known in separate contexts. The equation for the constrained mode is explicitly worked out. The Gauss law is rather simply resolved to extract physical, namely color singlet states. The topological gauge mode is treated according to two alternative scenarios related to the In the one, a spectrum is found consistent with pure SU(2) gluons in (1+1) dimensions. In the other, the gauge mode excitations are estimated and their role in the spectrum with genuine Fock excitations is explored. A color singlet state is given which satisfies Gauss' law. Its invariant mass is estimated and discussed in the physical limit.Comment: LaTex document, 26 pages, one figure (obtainable by contacting authors). To appear in Physical. Review

Biochemical profile, eating habits, and telomere length among Brazilian children and adolescents

Objectives: Lifestyle, obesity, and eating habits are emerging as determinants for the instability of telomeres. The increase in childhood and adolescent obesity and the association of biochemical profiles and dietary components with telomere length (TL) makes it an important issue in nutritional research. The aim of the present study was to investigate TL and its association with ethnic background, adiposity, clinical and biochemical parameters, and dietary patterns among Brazilian children and adolescents. Methods: A cross-sectional study encompassing 981 children and adolescents between 7 and 17 y of age was performed. Dietary intake habits, anthropometry, and clinical data were collected. TL analysis was performed by quantitative polymerase chain reaction. Results: Children presented significantly longer TL than adolescents (P = 0.046). Participants who self-declared as black, mulatto, or brown (P < 0.001) also showed longer TL than those who were white. Regarding biochemical parameters, individuals with altered glucose levels had shorter TL than normoglycemic participants in the total sample (P = 0.014). Such difference remained statistically significant in adolescents (P = 0.019). Participants who reported eating fruits and vegetables regularly had longer TL than those who did not (P < 0.001). Conclusion: The results suggested that both biochemical parameters and the intake of antioxidant-rich food, such as fruits and vegetables, are associated with the stability of telomere biology among young Brazilians

The Hamiltonian formulation of General Relativity: myths and reality

A conventional wisdom often perpetuated in the literature states that: (i) a 3+1 decomposition of space-time into space and time is synonymous with the canonical treatment and this decomposition is essential for any Hamiltonian formulation of General Relativity (GR); (ii) the canonical treatment unavoidably breaks the symmetry between space and time in GR and the resulting algebra of constraints is not the algebra of four-dimensional diffeomorphism; (iii) according to some authors this algebra allows one to derive only spatial diffeomorphism or, according to others, a specific field-dependent and non-covariant four-dimensional diffeomorphism; (iv) the analyses of Dirac [Proc. Roy. Soc. A 246 (1958) 333] and of ADM [Arnowitt, Deser and Misner, in "Gravitation: An Introduction to Current Research" (1962) 227] of the canonical structure of GR are equivalent. We provide some general reasons why these statements should be questioned. Points (i-iii) have been shown to be incorrect in [Kiriushcheva et al., Phys. Lett. A 372 (2008) 5101] and now we thoroughly re-examine all steps of the Dirac Hamiltonian formulation of GR. We show that points (i-iii) above cannot be attributed to the Dirac Hamiltonian formulation of GR. We also demonstrate that ADM and Dirac formulations are related by a transformation of phase-space variables from the metric $g_{\mu\nu}$ to lapse and shift functions and the three-metric $g_{km}$, which is not canonical. This proves that point (iv) is incorrect. Points (i-iii) are mere consequences of using a non-canonical change of variables and are not an intrinsic property of either the Hamilton-Dirac approach to constrained systems or Einstein's theory itself.Comment: References are added and updated, Introduction is extended, Subsection 3.5 is added, 83 pages; corresponds to the published versio

Detecting a stochastic gravitational wave background with the Laser Interferometer Space Antenna

The random superposition of many weak sources will produce a stochastic background of gravitational waves that may dominate the response of the LISA (Laser Interferometer Space Antenna) gravitational wave observatory. Unless something can be done to distinguish between a stochastic background and detector noise, the two will combine to form an effective noise floor for the detector. Two methods have been proposed to solve this problem. The first is to cross-correlate the output of two independent interferometers. The second is an ingenious scheme for monitoring the instrument noise by operating LISA as a Sagnac interferometer. Here we derive the optimal orbital alignment for cross-correlating a pair of LISA detectors, and provide the first analytic derivation of the Sagnac sensitivity curve.Comment: 9 pages, 11 figures. Significant changes to the noise estimate