Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for cancer epigenomics

Background: The use of tumour xenografts is a well-established research tool in cancer genomics but has not yet been comprehensively evaluated for cancer epigenomics. Methods: In this study, we assessed the suitability of patient-derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K Beadchips and MeDIP-seq. Results: Controlled for confounding host (mouse) sequences, comparison of primary PDXs and matching patient tumours in a rare (osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the assayed CpG sites undergo major (Δβ ≥ 0.51) methylation changes in a cancer-specific manner as a result of the xenografting procedure. No significant subsequent methylation changes were observed after a second round of xenografting between primary and secondary PDXs. Based on computational simulation using publically available methylation data, we additionally show that future studies comparing two groups of PDXs should use 15 or more samples in each group to minimise the impact of xenografting-associated changes in methylation on comparison results. Conclusions: Our results from rare and common cancers indicate that PDXs are a suitable discovery tool for cancer epigenomics and we provide guidance on how to overcome the observed limitations

Low-Energy Universality in Atomic and Nuclear Physics

An effective field theory developed for systems interacting through short-range interactions can be applied to systems of cold atoms with a large scattering length and to nucleons at low energies. It is therefore the ideal tool to analyze the universal properties associated with the Efimov effect in three- and four-body systems. In this "progress report", we will discuss recent results obtained within this framework and report on progress regarding the inclusion of higher order corrections associated with the finite range of the underlying interaction.Comment: Commissioned article for Few-Body Systems, 47 pp, 16 fig

Spin Glass Behavior in RuSr2Gd1.5Ce0.5Cu2O10

The dynamics of the magnetic properties of polycrystalline RuSr2Gd1.5Ce0.5Cu2O10 (Ru-1222) have been studied by ac susceptibility and dc magnetization measurements, including relaxation and ageing studies. Ru-1222 is a reported magneto-superconductor with Ru spins magnetic ordering at temperatures near 100 K and superconductivity in Cu-O2 planes below Tc ~ 40 K. The exact nature of Ru spins magnetic ordering is still debated and no conclusion has been reached yet. In this work, a frequency-dependent cusp was observed in ac susceptibility vs. T measurements, which is interpreted as a spin glass transition. The change in the cusp position with frequency follows the Vogel-Fulcher law, which is commonly accepted to describe a spin glass with magnetically interacting clusters. Such interpretation is supported by themoremanaent magnetization (TRM) measurements at T = 60 K. TRM relaxations are well described by a stretched exponential relation, and present significant ageing effects.Comment: 4 pages, 6 figures, submitted to Phys. Rev.

Pervasive protein thermal stability variation during the cell cycle

Quantitative mass spectrometry has established proteome-wide regulation of protein abundance and post-translational modifications in various biological processes. Here, we used quantitative mass spectrometry to systematically analyze the thermal stability and solubility of proteins on a proteome-wide scale during the eukaryotic cell cycle. We demonstrate pervasive variation of these biophysical parameters with most changes occurring in mitosis and G1. Various cellular pathways and components vary in thermal stability, such as cell-cycle factors, polymerases, and chromatin remodelers. We demonstrate that protein thermal stability serves as a proxy for enzyme activity, DNA binding, and complex formation in situ. Strikingly, a large cohort of intrinsically disordered and mitotically phosphorylated proteins is stabilized and solubilized in mitosis, suggesting a fundamental remodeling of the biophysical environment of the mitotic cell. Our data represent a rich resource for cell, structural, and systems biologists interested in proteome regulation during biological transitions

Impact of Patching and Atropine Treatment on the Child and Family in the Amblyopia Treatment Study

Objective To assess the psychosocial impact on the child and family of patching and atropine as treatments for moderate amblyopia in children younger than 7 years. Methods In a randomized, controlled clinical trial, 419 children younger than 7 years with amblyopic eye visual acuity in the range of 20/40 to 20/100 were assigned to receive treatment with either patching or atropine at 47 clinical sites. After 5 weeks of treatment, a parental quality-of-life questionnaire was completed for 364 (87%) of the 419 patients. Main Outcome Measure Overall and subscale scores on the Amblyopia Treatment Index. Results High internal validity and reliability were demonstrated for the Amblyopia Treatment Index questionnaire. The overall Amblyopia Treatment Index scores and the 3 subscale scores were consistently higher (worse) in the patching group compared with the atropine-treated group (overall mean, 2.52 vs 2.02, P<.001; adverse effects of treatment: mean, 2.35 vs 2.11, P = .002; difficulty with compliance: mean, 2.46 vs 1.99, P<.001; and social stigma: mean, 3.09 vs 1.84, P<.001, respectively). Conclusion Although the Amblyopia Treatment Index questionnaire results indicated that both atropine and patching treatments were well tolerated by the child and family, atropine received more favorable scores overall and on all 3 questionnaire subscales

Pion photoproduction on the nucleon in the quark model

We present a detailed quark-model study of pion photoproduction within the effective Lagrangian approach. Cross sections and single-polarization observables are investigated for the four charge channels, $\gamma p\to \pi^+ n$, $\gamma n\to \pi^- p$, $\gamma p\to \pi^0 p$, and $\gamma n\to \pi^0 n$. Leaving the $\pi N\Delta$ coupling strength to be a free parameter, we obtain a reasonably consistent description of these four channels from threshold to the first resonance region. Within this effective Lagrangian approach, strongly constrainted by the quark model, we consider the issue of double-counting which may occur if additional {\it t}-channel contributions are included.Comment: Revtex, 35 pages, 16 eps figures; version to appear on PR

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Phenomenology of the Lense-Thirring effect in the Solar System

Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio