Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient

Mucolipidosis type II α/β is a severe, autosomal recessive lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for the α/β subunits of the GlcNAc-phosphotransferase. To date, over 100 different mutations have been identified in MLII α/β patients, but no large deletions have been reported. Here we present the first case of a large homozygous intragenic GNPTAB gene deletion (c.3435-386_3602 + 343del897) encompassing exon 19, identified in a ML II α/β patient. Long-range PCR and sequencing methodologies were used to refine the characterization of this rearrangement, leading to the identification of a 21 bp repetitive motif in introns 18 and 19. Further analysis revealed that both the 5' and 3' breakpoints were located within highly homologous Alu elements (Alu-Sz in intron 18 and Alu-Sq2, in intron 19), suggesting that this deletion has probably resulted from Alu-Alu unequal homologous recombination. RT-PCR methods were used to further evaluate the consequences of the alteration for the processing of the mutant pre mRNA GNPTAB, revealing the production of three abnormal transcripts: one without exon 19 (p.Lys1146_Trp1201del); another with an additional loss of exon 20 (p.Arg1145Serfs*2), and a third in which exon 19 was substituted by a pseudoexon inclusion consisting of a 62 bp fragment from intron 18 (p.Arg1145Serfs*16). Interestingly, this 62 bp fragment corresponds to the Alu-Sz element integrated in intron 18.This represents the first description of a large deletion identified in the GNPTAB gene and contributes to enrich the knowledge on the molecular mechanisms underlying causative mutations in ML II.This work was supported by FCT - project PIC/IC/83252/2007 (http://alfa.fct.mctes.pt/). Coutinho MF and Quental S received grants from the FCT (SFRH/BD/48103/2008; SFRH/BPD/64025/2009)

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

The high-energy Sun - probing the origins of particle acceleration on our nearest star

As a frequent and energetic particle accelerator, our Sun provides us with an excellent astrophysical laboratory for understanding the fundamental process of particle acceleration. The exploitation of radiative diagnostics from electrons has shown that acceleration operates on sub-second time scales in a complex magnetic environment, where direct electric fields, wave turbulence, and shock waves all must contribute, although precise details are severely lacking. Ions were assumed to be accelerated in a similar manner to electrons, but γ-ray imaging confirmed that emission sources are spatially separated from X-ray sources, suggesting distinctly different acceleration mechanisms. Current X-ray and γ-ray spectroscopy provides only a basic understanding of accelerated particle spectra and the total energy budgets are therefore poorly constrained. Additionally, the recent detection of relativistic ion signatures lasting many hours, without an electron counterpart, is an enigma. We propose a single platform to directly measure the physical conditions present in the energy release sites and the environment in which the particles propagate and deposit their energy. To address this fundamental issue, we set out a suite of dedicated instruments that will probe both electrons and ions simultaneously to observe; high (seconds) temporal resolution photon spectra (4 keV – 150 MeV) with simultaneous imaging (1 keV – 30 MeV), polarization measurements (5–1000 keV) and high spatial and temporal resolution imaging spectroscopy in the UV/EUV/SXR (soft X-ray) regimes. These instruments will observe the broad range of radiative signatures produced in the solar atmosphere by accelerated particles

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Study of B Meson Production in p plus Pb Collisions at root s(NN)=5.02 TeV Using Exclusive Hadronic Decays

Peer reviewe

Search for supersymmetry in pp collisions at 7 TeV in events with jets and missing transverse energy

This is the Pre-print version of the Article. The official published version of the paper can be accessed from the link below - Copyright @ 2011 ElsevierA search for supersymmetry with R-parity conservation in proton-proton collisions at a centre-of-mass energy of 7 TeV is presented. The data correspond to an integrated luminosity of 35 inverse picobarns collected by the CMS experiment at the LHC. The search is performed in events with jets and significant missing transverse energy, characteristic of the decays of heavy, pair-produced squarks and gluinos. The primary background, from standard model multijet production, is reduced by several orders of magnitude to a negligible level by the application of a set of robust kinematic requirements. With this selection, the data are consistent with the standard model backgrounds, namely t t-bar, W + jet and Z + jet production, which are estimated from data control samples. Limits are set on the parameters of the constrained minimal supersymmetric extension of the standard model. These limits extend those set previously by experiments at the Tevatron and LEP colliders.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Dijet azimuthal decorrelations in pp collisions at √s = 7TeV

This is the pre-print version of the Published Article which can be accessed from the link below.Measurements of dijet azimuthal decorrelations in pp collisions at √s=7  TeV using the CMS detector at the CERN LHC are presented. The analysis is based on an inclusive dijet event sample corresponding to an integrated luminosity of 2.9  pb-1. The results are compared to predictions from perturbative QCD calculations and various Monte Carlo event generators. The dijet azimuthal distributions are found to be sensitive to initial-state gluon radiation

Measurement of the differential and double-differential Drell-Yan cross sections in proton-proton collisions at root s=7 TeV

Copyright @ 2013 CERN, for the bene t of the CMS collaboration. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.Measurements of the differential and double-differential Drell-Yan cross sections are presented using an integrated luminosity of 4.5 (4.8) fb−1 in the dimuon (dielectron) channel of proton-proton collision data recorded with the CMS detector at the LHC at s√ = 7 TeV. The measured inclusive cross section in the Z-peak region (60–120 GeV) is σ(ℓℓ) = 986.4 ± 0.6 (stat.) ± 5.9 (exp. syst.) ± 21.7 (th. syst.) ± 21.7 (lum.) pb for the combination of the dimuon and dielectron channels. Differential cross sections dσ/dm for the dimuon, dielectron, and combined channels are measured in the mass range 15 to 1500 GeV and corrected to the full phase space. Results are also presented for the measurement of the double-differential cross section d2σ/dm d|y| in the dimuon channel over the mass range 20 to 1500 GeV and absolute dimuon rapidity from 0 to 2.4. These measurements are compared to the predictions of perturbative QCD calculations at next-to-leading and next-to-next-to-leading orders using various sets of parton distribution functions.The Austrian Federal Ministry of Science and Research and the Austrian Science Fund; the Belgian Fonds de la Recherche Scienti que, and Fonds voor Wetenschappelijk Onderzoek; the Brazilian Funding Agencies (CNPq, CAPES, FAPERJ, and FAPESP); the Bulgarian Ministry of Education and Science; CERN; the Chinese Academy of Sciences, Ministry of Science and Technology, and National Natural Science Foundation of China; the Colombian Funding Agency (COLCIENCIAS); the Croatian Ministry of Science, Education and Sport; the Research Promotion Foundation, Cyprus; the Ministry of Education and Research, Recurrent nancing contract SF0690030s09 and European Regional Development Fund, Estonia; the Academy of Finland, Finnish Ministry of Education and Culture, and Helsinki Institute of Physics; the Institut National de Physique Nucl eaire et de Physique des Particules / CNRS, and Commissariat a l' Energie Atomique et aux Energies Alternatives / CEA, France; the Bundesministerium f ur Bildung und Forschung, Deutsche Forschungsgemeinschaft, and Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany; the General Secretariat for Research and Technology, Greece; the National Scienti c Research Foundation, and National Innovation O ce, Hungary; the Department of Atomic Energy and the Department of Science and Technology, India; the Institute for Studies in Theoretical Physics and Mathematics, Iran; the Science Foundation, Ireland; the Istituto Nazionale di Fisica Nucleare, Italy; the Korean Ministry of Education, Science and Technology and the World Class University program of NRF, Republic of Korea; the Lithuanian Academy of Sciences; the Mexican Funding Agencies (CINVESTAV, CONACYT, SEP, and UASLP-FAI); the Ministry of Business, Innovation and Employment, New Zealand; the Pakistan Atomic Energy Commission; the Ministry of Science and Higher Education and the National Science Centre, Poland; the Funda c~ao para a Ci^encia e a Tecnologia, Portugal; JINR, Dubna; the Ministry of Education and Science of the Russian Federation, the Federal Agency of Atomic Energy of the Russian Federation, Russian Academy of Sciences, and the Russian Foundation for Basic Research; the Ministry of Education, Science and Technological Development of Serbia; the Secretar a de Estado de Investigaci on, Desarrollo e Innovaci on and Programa Consolider-Ingenio 2010, Spain; the Swiss Funding Agencies (ETH Board, ETH Zurich, PSI, SNF, UniZH, Canton Zurich, and SER); the National Science Council, Taipei; the Thailand Center of Excellence in Physics, the Institute for the Promotion of Teaching Science and Technology of Thailand, Special Task Force for Activating Research and the National Science and Technology Development Agency of Thailand; the Scienti c and Technical Research Council of Turkey, and Turkish Atomic Energy Authority; the Science and Technology Facilities Council, UK; the US Department of Energy, and the US National Science Foundation