Multi-membership gene regulation in pathway based microarray analysis

This article is available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. Results: We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. Conclusions: We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes.The work was sponsored by the studentship scheme of the School of Information Systems, Computing and Mathematics, Brunel Universit

Evaluation of non-chemical seed treatment methods for the control of Alternaria dauci and A. radicina on carrot seeds

The current study was initiated to evaluate the efficacy of physical methods (hot water, aerated steam, electron treatment) and agents of natural origin (resistance inducers, plant derived products, micro-organisms) as seed treatments of carrots for control of Alternaria dauci and A. radicina. Control of both Alternaria species by seed treatment with the resistance inducers was generally poor. Results were also not satisfactory with most of the formulated commercial micro-organism preparations. Based on the average of five field trials, one of these, BA 2552 (Pseudomonas chlororaphis), provided a low but significant increase in plant stand. Among the experimental micro-organisms, the best results were obtained with Pseudomonas sp. strain MF 416 and Clonostachys rosea strain IK726. A similar level of efficacy was provided by seed treatment with an emulsion (1%) of thyme oil in water. Good and consistent control was generally achieved with the physical methods aerated steam, hot water and electron treatment. Aerated steam treatment was, apart from the thiram-containing chemical standard, the best single treatment, and its performance may at least partially be due to extensive pre-testing, resulting in dosages optimally adapted to the respective seed lot. In some of the experiments the effect of the hot water treatment, which was tested at a fixed, not specifically adapted dosage, was significantly improved when combined with a Pseudomonas sp. MF 416 or C. rosea IK726 treatment. The results are discussed in relation to the outcome of experiments in which the same seed treatment methods and agents were tested in other seed-borne vegetable pathosystems

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio

Sensitivity of the T2K accelerator-based neutrino experiment with an Extended run to 20×102120\times10^{21} POT

18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figuresRecent measurements at the T2K experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We explore the physics program of an extension to the currently approved T2K running of $7.8\times 10^{21}$ protons-on-target to $20\times 10^{21}$ protons-on-target,aiming at initial observation of CP violation with 3$\,\sigma$ or higher significance for the case of maximum CP violation. With accelerator and beam line upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026.We acknowledge the support of MEXT, Japan; NSERC (Grant No. SAPPJ-2014-00031), NRC and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SERI, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, and GridPP in the United Kingdom. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), H2020 Grant No. RISE-GA644294-JENNIFER, EU; JSPS, Japan; Royal Society, UK; and the DOE Early Career program, USA. CNRS/IN2P3: Centre National de la Recherche ScientifiqueInstitut National de Physique Nucleaire et de Physique des Particules RSF: Russian Science Foundation MES: Ministry of Education and Science, Russia ERDF: European Regional Development Fund SNSF: Swiss National Science Foundation SER (should be SERI): State Secretariat for Education, Research and Innovatio

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

When outcome is a balance: methods to measure combined utility for the choice between induction of labour and expectant management in mild risk pregnancy at term

Background: When the primary and secondary outcomes of clinical studies yield ambiguous or conflicting recommendations, preference or valuation studies may help to overcome the decision problem. The present preference study is attached to two clinical studies (DIGTAT, ISRCT10363217; HYPITAT, ISRCT08132825) that evaluate induction of labour versus expectant management in term pregnancies with a mild risk profile. The purpose of the present study is to compare four methods of valuation/preference measurement. Met

The Burden of Trachoma in South Sudan: Assessing the Health Losses from a Condition of Graded Severity

Trachoma is an infectious disease that is endemic to the Republic of South Sudan. In the absence of appropriate treatment recurrent re-infection in an individual will lead to progressively severe states of trachoma, eventually leading to the loss of visual acuity and finally blindness. Here we distinguish between three separate states of disease: trachoma with normal vision, trachoma with low vision and trachoma with blindness. The first of these states, trachoma with normal vision, is the least severe and the impact of this state on a population has not been well investigated. Trachoma, even before any loss of vision, comes with a great deal of pain and social consequences, and thus disability. In this study we employ data from South Sudan and estimate the burden caused by trachoma with normal vision for the first time. In doing so, we also reveal the extent of the gaps in our knowledge surrounding the natural history of trachoma and highlight areas of research that require urgent attention

Proposal for an Extended Run of T2K to 20×102120\times10^{21} POT

68 pages, 31 figures68 pages, 31 figures68 pages, 31 figuresRecent measurements by the T2K neutrino oscillation experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We propose an extension to the currently approved T2K running from 7.8\times 10^{21}~\mbox{POT} to 20\times 10^{21}~\mbox{POT}, aiming at initial observation of CP violation with 3$\,\sigma$ or higher significance for the case of maximum CP violation. The program also contains a measurement of mixing parameters, $\theta_{23}$ and $\Delta m^2_{32}$, with a precision of 1.7$^\circ$ or better and 1%, respectively. With accelerator and beamline upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026