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      • European 1: A globally important clonal complex of Mycobacterium bovis

        Smith, N.H.,Berg, S.,Dale, J.,Allen, A.,Rodriguez, S.,Romero, B.,Matos, F.,Ghebremichael, S.,Karoui, C.,Donati, C.,Machado, A.d.C.,Mucavele, C.,Kazwala, R.R.,Hilty, M.,Cadmus, S.,Ngandolo, B.N.R.,Habt Elsevier Science 2011 Infection, genetics and evolution Vol.11 No.6

        We have identified a globally important clonal complex of Mycobacterium bovis by deletion analysis of over one thousand strains from over 30 countries. We initially show that over 99% of the strains of M. bovis, the cause of bovine tuberculosis, isolated from cattle in the Republic of Ireland and the UK are closely related and are members of a single clonal complex marked by the deletion of chromosomal region RDEu1 and we named this clonal complex European 1 (Eu1). Eu1 strains were present at less than 14% of French, Portuguese and Spanish isolates of M. bovis but are rare in other mainland European countries and Iran. However, strains of the Eu1 clonal complex were found at high frequency in former trading partners of the UK (USA, South Africa, New Zealand, Australia and Canada). The Americas, with the exception of Brazil, are dominated by the Eu1 clonal complex which was at high frequency in Argentina, Chile, Ecuador and Mexico as well as North America. Eu1 was rare or absent in the African countries surveyed except South Africa. A small sample of strains from Taiwan were non-Eu1 but, surprisingly, isolates from Korea and Kazakhstan were members of the Eu1 clonal complex. The simplest explanation for much of the current distribution of the Eu1 clonal complex is that it was spread in infected cattle, such as Herefords, from the UK to former trading partners, although there is evidence of secondary dispersion since. This is the first identification of a globally dispersed clonal complex M. bovis and indicates that much of the current global distribution of this important veterinary pathogen has resulted from relatively recent International trade in cattle.

      • The human AQP4 gene : Definition of the locus encoding two water channel polypeptides in brain

        LU, MINGOI,LEE, M.DOUGLAS,SMITH, BARBARA L.,JUNG, JIN SUP,AGRE, PETER,VERDUK, MARIAN A.J.,MERKX, GERARD,RUSS, JOHAN P.L.,DEEN, PETER M.T. 부산대학교 유전공학연구소 1996 분자생물학 연구보 Vol.12 No.-

        The aquaporin family of membrane water transport proteins are expressed in diverse tissues, and in brain the predominant water channel protein is AQP4. Here we report the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Two cDNAs were isolated corresponding to the two initiating methionines (M1 in a 323-aa polypeptide and M23 in a 301-aa polypeptide) previously indentified in rat [Jung, J. S., Bhat, R. V., Preston, G. M., Guggino, W. B. & Agre, P. (1994) Proc. Natl. Acad. Sci. USA 91, 13052-13056]. Similar to other aquaporins, the AQP4 gene is composed of four exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. Transcription initiation sites have been mapped in the proximal promoters of exons 0 and 1. RNase protection revealed distinct transcripts corresponding to M1 and M23 mRNAs, and AQP4 immunoblots of cerebellum demonstrated reactive polypeptides of 31 and 34 kDa. Using a P1 and a λEMBL subclone, the chromosomal site of the human AQP4 gene was mapped to chromosome 18 at the junction of q11.2 and q12.1 by fluorescence in situ hybridization. These studies may now permit molecular characterization of AQP4 during human development and in clinical disorders.

      • Physical properties of giant molecular clouds in the Large Magellanic Cloud

        Hughes, A.,Wong, T.,Ott, J.,Muller, E.,Pineda, J. L.,Mizuno, Y.,Bernard, J.-P.,Paradis, D.,Maddison, S.,Reach, W. T.,Staveley-Smith, L.,Kawamura, A.,Meixner, M.,Kim, S.,Onishi, T.,Mizuno, N.,Fukui, Y. Blackwell Publishing Ltd 2010 Monthly notices of the Royal Astronomical Society Vol.406 No.3

        <P>ABSTRACT</P><P>The Magellanic Mopra Assessment (MAGMA) is a high angular resolution <SUP>12</SUP>CO (<I>J</I>= 1 → 0) mapping survey of giant molecular clouds (GMCs) in the Large Magellanic Cloud (LMC) and Small Magellanic Cloud using the Mopra Telescope. Here we report on the basic physical properties of 125 GMCs in the LMC that have been surveyed to date. The observed clouds exhibit scaling relations that are similar to those determined for Galactic GMCs, although LMC clouds have narrower linewidths and lower CO luminosities than Galactic clouds of a similar size. The average mass surface density of the LMC clouds is 50 M<SUB>⊙</SUB> pc<SUP>−2</SUP>, approximately half that of GMCs in the inner Milky Way. We compare the properties of GMCs with and without signs of massive star formation, finding that non-star-forming GMCs have lower peak CO brightness than star-forming GMCs. We compare the properties of GMCs with estimates for local interstellar conditions: specifically, we investigate the H <SMALL>I</SMALL> column density, radiation field, stellar mass surface density and the external pressure. Very few cloud properties demonstrate a clear dependence on the environment; the exceptions are significant positive correlations between (i) the H <SMALL>I</SMALL> column density and the GMC velocity dispersion, (ii) the stellar mass surface density and the average peak CO brightness and (iii) the stellar mass surface density and the CO surface brightness. The molecular mass surface density of GMCs without signs of massive star formation shows no dependence on the local radiation field, which is inconsistent with the photoionization-regulated star formation theory proposed by McKee. We find some evidence that the mass surface density of the MAGMA clouds increases with the interstellar pressure, as proposed by Elmegreen, but the detailed predictions of this model are not fulfilled once estimates for the local radiation field, metallicity and GMC envelope mass are taken into account.</P>

      • SCISCIESCOPUS

        MOLECULAR AND ATOMIC GAS IN THE LARGE MAGELLANIC CLOUD. II. THREE-DIMENSIONAL CORRELATION BETWEEN CO AND H I

        Fukui, Y.,Kawamura, A.,Wong, T.,Murai, M.,Iritani, H.,Mizuno, N.,Mizuno, Y.,Onishi, T.,Hughes, A.,Ott, J.,Muller, E.,Staveley-Smith, L.,Kim, S. IOP Publishing 2009 The Astrophysical journal Vol.705 No.1

        <P>We compare the CO (J = 1-0) and HI emission in the Large Magellanic Cloud in three dimensions, i.e., including a velocity axis in addition to the two spatial axes, with the aim of elucidating the physical connection between giant molecular clouds (GMCs) and their surrounding Hi gas. The CO J = 1-0 data set is from the second NANTEN CO survey and the HI data set is from the merged Australia Telescope Compact Array ( ATCA) and Parkes Telescope surveys. The major findings of our analysis are as follows: (1) GMCs are associated with an envelope of HI emission, (2) in GMCs [average CO intensity] proportional to [ average Hi intensity](1.1 +/- 0.1), and (3) the HI intensity tends to increase with the star formation activity within GMCs, from Type I to Type III. An analysis of the HI envelopes associated with GMCs shows that their average line width is 14 km s(-1) and the mean density in the envelope is 10 cm(-3). We argue that the HI envelopes are gravitationally bound by GMCs. These findings are consistent with a continual increase in the mass of GMCs via HI accretion at an accretion rate of 0.05 M-circle dot yr(-1) over a timescale of 10 Myr. The growth of GMCs is terminated via dissipative ionization and/or stellar-wind disruption in the final stage of GMC evolution.</P>

      • SCISCIESCOPUS

        A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors

        Mateo, Joaquin,Ganji, Gopinath,Lemech, Charlotte,Burris, Howard A.,Han, Sae-Won,Swales, Karen,Decordova, Shaun,DeYoung, M. Phillip,Smith, Deborah A.,Kalyana-Sundaram, Shanker,Wu, Jiuhua,Motwani, Monic American Association for Cancer Research 2017 Clinical Cancer Research Vol.23 No.19

        <P><B>Background:</B> The PI3K/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on- and off-target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.</P><P><B>Methods:</B> We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended phase II dose (RP2D). During the dose-selection and dose-escalation stages (parts 1 and 2), patients with <I>PTEN</I>-deficient advanced solid tumors received escalating doses of GSK2636771 (25–500 mg once daily) using a modified 3+3 design to determine the RP2D; tumor type-specific expansion cohorts (part 3) were implemented to further assess tumor responses at the RP2D.</P><P><B>Results:</B> A total of 65 patients were enrolled; dose-limiting toxicities were hypophosphatemia and hypocalcemia. Adverse events included diarrhea (48%), nausea (40%), and vomiting (31%). Single- and repeat-dose exposure increased generally dose proportionally. GSK2636771 400 mg once daily was the RP2D. Phospho/total AKT ratio decreased with GSK2636771 in tumor and surrogate tissue. A castrate-resistant prostate cancer (CRPC) patient harboring <I>PIK3CB</I> amplification had a partial response for over a year; an additional 10 patients derived durable (≥24 weeks) clinical benefit, including two other patients with CRPC with <I>PIK3CB</I> alterations (≥34 weeks). GSK2636771 400 mg once daily orally induced sufficient exposure and target inhibition with a manageable safety profile.</P><P><B>Conclusions:</B> Genomic aberrations of <I>PIK3CB</I> may be associated with clinical benefit from GSK2636771. <I>Clin Cancer Res; 23(19); 5981–92. ©2017 AACR</I>.</P>

      • Proceedings from the Ice Hockey Summit III: Action on Concussion

        Aynsley M Smith(Aynsley M Smith ),Patrick A Alford(Patrick A Alford ),Mark Aubry(Mark Aubry ),Brian Benson(Brian Benson ),Amanda Black(Amanda Black ),Alison Brooks(Alison Brooks ),Charles Burke(Charle 사피엔시아 2019 Exercise Medicine Vol.3 No.-

        Objectives: The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: (1) describe sport related concussion (SRC) epidemiology, (2) classify prevention strategies, (3) define objective, diagnostic tests, (4) identify treatment and (5) integrate science and clinical care into prioritized action plans and policy. Methods: Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches and officials) voted to prioritize these action items in the final Summit session. Results: (1) establish a national and international hockey data base for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care (POC); and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions: Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity and consequences of concussion in the sport of ice hockey.

      • KCI등재

        Coulomb Blockade Oscillations as a Noninvasive Probe of Screening

        R. Nemutudi,C. G. Smith,C.-T. Liang,D. A. Ritchie,G. A. C. Jones,I. Farrer,M. Pepper,M. J. Murphy 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.48 No.6

        Noninvasive measurement techniques utilize the fact that the local conditions in an electrical circuit can affect a nearby, but electrically isolated circuit. Such a technique can be used to measure the screening ability of an electron system. In this work, we study non-invasively the screening characteristics of a one-dimensional (1D) channel in close lateral proximity to a quantum dot that forms a separate and electrically isolated circuit. We use a one-dimensional (1D) channel to screen and in-plane electric field between the gate and the lateral quantum dot. The Coulomb blockade oscillations we observe through the quantum dot circuit and the corresponding variation in their periodicity at different gate voltage regions are a signature of the screening characteristics of a 1D channel both at zero magnetic field and in the quantum Hall region. The screening ability of the 1D channel is found to be approximately two orders of magnitude smaller than that of an ungated GaAs two-dimensional electron system.

      • SCISCIESCOPUS

        A model for characterizing the frequency-dependent variation in sensitivity with temperature of underwater acoustic transducers from historical calibration data

        Nam, G H,Cox, M G,Harris, P M,Robinson, S P,Hayman, G,Beamiss, G A,Esward, T J,Smith, I M IOP Pub 2007 Measurement science & technology Vol.18 No.5

        <P>The performance of underwater electroacoustic transducers often depends on water temperature and, for accurate calibrations, it is necessary to take account of this influence on measurement data. Doing so is particularly important for open-water calibration facilities where the environmental conditions cannot be controlled and seasonal variations in temperature can contribute significant measurement uncertainty. This paper describes the characterization of the sensitivity of underwater electroacoustic transducers in terms of their variation with water temperature. A model containing adjustable parameters is developed for providing frequency-dependent temperature coefficients whose use enables measurement data to be corrected for temperature. Estimates of these coefficients are determined by applying the model to the time history of measurement data obtained over a period of several years. The influence of seasonal temperature variation can then be separated from the slow temporal drift in the transducer sensitivity. The uncertainties associated with the corrected sensitivity values are evaluated.</P>

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