Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57

BackgroundTransient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24. One of the mechanisms leading to overexpression of the locus is hypomethylation of the maternal allele of PLAGL1 and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor involved in establishment and maintenance of methylation of imprinted loci. Our objective was to investigate whether additional regions are aberrantly methylated in ZFP57 mutation carriers.MethodsGenome-wide DNA methylation analysis was performed on four individuals with homozygous or compound heterozygous ZFP57 mutations, three relatives with heterozygous ZFP57 mutations and five controls. Methylation status of selected regions showing aberrant methylation in the patients was verified using bisulfite-sequencing.ResultsWe found large variability among the patients concerning the number and identity of the differentially methylated regions, but more than 60 regions were aberrantly methylated in two or more patients and a novel region within PPP1R13L was found to be hypomethylated in all the patients. The hypomethylated regions in common between the patients are enriched for the ZFP57 DNA binding motif.ConclusionsWe have expanded the epimutational spectrum of TNDM1 associated with ZFP57 mutations and found one novel region within PPP1R13L which is hypomethylated in all TNDM1 patients included in this study. Functional studies of the locus might provide further insight into the etiology of the disease.<br/

FiberGLAST: a scintillating fiber approach to the GLAST mission

FiberGLAST is a scintillating fiber gamma-ray detector designed for the GLAST mission. The system described below provides superior effective area and field of view for modest cost and risk. An overview of the FiberGLAST instrument is presented, as well as a more detailed description of the principle elements of the primary detector volume. The triggering and readout electronics are described, and Monte Carlo Simulations of the instrument performance are presented

Collective Intelligence for Control of Distributed Dynamical Systems

We consider the El Farol bar problem, also known as the minority game (W. B. Arthur, ``The American Economic Review'', 84(2): 406--411 (1994), D. Challet and Y.C. Zhang, ``Physica A'', 256:514 (1998)). We view it as an instance of the general problem of how to configure the nodal elements of a distributed dynamical system so that they do not ``work at cross purposes'', in that their collective dynamics avoids frustration and thereby achieves a provided global goal. We summarize a mathematical theory for such configuration applicable when (as in the bar problem) the global goal can be expressed as minimizing a global energy function and the nodes can be expressed as minimizers of local free energy functions. We show that a system designed with that theory performs nearly optimally for the bar problem.Comment: 8 page

Development and testing of a fiber/multianode photomultiplier system for use on FiberGLAST

A scintillating fiber detector is currently being studied for the NASA Gamma-Ray Large Area Space Telescope (GLAST) mission. This detector utilizes modules composed of a thin converter sheet followed by an x, y plane of scintillating fibers to examine the shower of particles created by high energy gamma-rays interacting in the converter material. The detector is composed of a tracker with 90 such modular planes and a calorimeter with 36 planes. The two major component of this detector are the scintillating fibers and their associated photodetectors. Here we present current status of development and test result of both of these. The Hamamatsu R5900-00-M64 multianode photomultiplier tube (MAPMT) is the baseline readout device. A characterization of this device has been performed including noise, cross- talk, gain variation, vibration, and thermal/vacuum test. A prototype fiber/MAPMT system has been tested at the Center for Advanced Microstructures and Devices at Louisiana State University with a photon beam and preliminary results are presented

Estimation of GRB detection by FiberGLAST

FiberGLAST is one of several instrument concepts being developed for possible inclusion as the primary Gamma-ray Large Area Space Telescope (GLAST) instrument. The predicted FiberGLAST effective area is more than 12,000 cm2 for energies between 30 MeV and 300 GeV, with a field of view that is essentially flat from 0°–80°. The detector will achieve a sensitivity more than 10 times that of EGRET. We present results of simulations that illustrate the sensitivity of FiberGLAST for the detection of gamma-ray bursts

Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery

Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc

Tracking and imaging gamma ray experiment (TIGRE) for 1 to 100 MEV gamma ray astronomy

A large international collaboration from the high energy astrophysics community has proposed the Tracking and Imaging Gamma Ray Experiment (TIGRE) for future space observations. TIGRE will image and perform energy spectroscopy measurements on celestial sources of gamma rays in the energy range from 1 to 100 MeV. This has been a difficult energy range experimentally for gamma ray astronomy but is vital for the future considering the recent exciting measurements below 1 and above 100 MeV. TIGRE is both a double scatter Compton and gamma ray pair telescope with direct imaging of individual gamma ray events. Multi‐layers of Si strip detectors are used as Compton and pair converters CsI(Tl) scintillation detectors are used as a position sensitive calorimeter. Alternatively, thick GE strip detectors may be used for the calorimeter. The Si detectors are able to track electrons and positrons through successive Si layers and measure their directions and energy losses. Compton and pair events are completely reconstructed allowing each event to be imaged on the sky. TIGRE will provide an order‐of‐magnitude improvement in discrete source sensitivity in the 1 to 100 MeV energy range and determine spectra with excellent energy and excellent angular resolutions. It’s wide field‐of‐view of π sr permits observations of the entire sky for extended periods of time over the life of the mission

Milagrito Detection of TeV Emission from Mrk 501

The Milagro water Cherenkov detector near Los Alamos, New Mexico, has been operated as a sky monitor at energies of a few TeV between February 1997 and April 1998. Serving as a test run for the full Milagro detector, Milagrito has taken data during the strong and long-lasting 1997 flare of Mrk 501. We present results from the analysis of Mrk 501 and compare the excess and background rates with expectations from the detector simulations.Comment: 4 pages, submitted to XXVI International Cosmic Ray Conference, Salt Lake Cit

Calibration of the Milagro Cosmic Ray Telescope

The Milagro detector is an air shower array which uses the water Cherenkov technique and is capable of continuously monitoring the sky at energies near 1 TeV. The detector consists of 20000 metric tons of pure water instrumented with 723 photo-multiplier tubes (PMTs). The PMTs are arranged in a two-layer structure on a lattice of 3 m spacing covering 5000 $m^2$ area. The direction of the shower is determined from the relative timing of the PMT signals, necessitating a common time reference and amplitude slewing corrections to improve the time resolution. The calibration system to provide these consists of a pulsed laser driving 30 diffusing light sources deployed in the pond to allow cross-calibration of the PMTs. The system is capable of calibrating times and the pulse-heights from the PMTs using the time-over-threshold technique. The absolute energy scale is provided using single muons passing through the detector. The description of the calibration system of the Milagro detector and its prototype Milagrito will be presented.Comment: 4 pages, submitted to the XXVI International Cosmic Ray Conferenc

TeV Observations of Markarian 501 with the Milagrito Water Cherenkov Detector

The Milagrito water Cherenkov detector near Los Alamos, New Mexico, operated as a sky monitor at energies of a few TeV between February 1997 and May 1998 including the period of the strong, long-lasting 1997 flare of Markarian 501. Milagrito served as a test run for the full Milagro detector. An event excess with a significance of 3.7 sigma from Markarian 501 was observed, in agreement with expectations.Comment: 10 pages, 3 figures (figure 2 in color). accepted for publication in ApJ Letter