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        Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase.

        Hughes, Timothy,Saglio, Giuseppe,Branford, Susan,Soverini, Simona,Kim, Dong-Wook,,ller, Martin C,Martinelli, Giovanni,Cortes, Jorge,Beppu, Lan,Gottardi, Enrico,Kim, Dongho,Erben, Philipp,Shou, Y Grune Stratton ; American Society of Clinical Onco 2009 Journal of clinical oncology Vol.27 No.25

        <P>PURPOSE: Nilotinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase (CP; CML-CP) and accelerated phase (AP; CML-AP) who are resistant to or intolerant of prior imatinib therapy. In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed. PATIENTS AND METHODS: Baseline mutation data were assessed in 281 (88%) of 321 patients with CML-CP in the phase II nilotinib registration trial. RESULTS: Among imatinib-resistant patients, the frequency of mutations at baseline was 55%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 40%, and major molecular response (MMR) in 29% of patients without baseline mutations versus 49% (P = .145), 32% (P = .285), and 22% (P = .366), respectively, of patients with mutations. Responses in patients who harbored mutations with high in vitro sensitivity to nilotinib (50% inhibitory concentration [IC(50)] <or= 150 nM) or mutations with unknown nilotinib sensitivity were equivalent to those responses for patients without mutations (not significant). Patients with mutations that were less sensitive to nilotinib in vitro (IC(50) > 150 nM; Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR; none achieved CCyR. CONCLUSION: For most patients with imatinib resistance and with mutations, nilotinib offers a substantial probability of response. However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib.</P>

      • SCISCIESCOPUS

        STRINGENT LIMITS ON THE POLARIZED SUBMILLIMETER EMISSION FROM PROTOPLANETARY DISKS

        Hughes, A. Meredith,Wilner, David J.,Cho, Jungyeon,Marrone, Daniel P.,Lazarian, Alexandre,Andrews, Sean M.,Rao, Ramprasad IOP Publishing 2009 The Astrophysical journal Vol.704 No.2

        <P>We present arcsecond-resolution Submillimeter Array (SMA) polarimetric observations of the 880 mu m continuum emission from the protoplanetary disks around two nearby stars, HD 163296 and TW Hydrae. Although previous observations and theoretical work have suggested that a 2%-3% polarization fraction should be common for the millimeter continuum emission from such disks, we detect no polarized continuum emission above a 3 sigma upper limit of 7 mJy in each arcsecond-scale beam, or <1% in integrated continuum emission. We compare the SMA upper limits with the predictions from the exploratory Cho & Lazarian model of polarized emission from T Tauri disks threaded by toroidal magnetic fields, and rule out their fiducial model at the similar to 10 sigma level. We explore some potential causes for this discrepancy, focusing on model parameters that describe the shape, magnetic field alignment, and size distribution of grains in the disk. We also investigate related effects like the magnetic field strength and geometry, scattering off of large grains, and the efficiency of grain alignment, including recent advances in grain alignment theory, which are not considered in the fiducial model. We discuss the impact each parameter would have on the data and determine that the suppression of polarized emission plausibly arises from rounding of large grains, reduced efficiency of grain alignment with the magnetic field, and/or some degree of magnetic field tangling ( perhaps due to turbulence). A poloidal magnetic field geometry could also reduce the polarization signal, particularly for a face-on viewing geometry like the TW Hya disk. The data provided here offer the most stringent limits to-date on the polarized millimeter-wavelength emission from disks around young stars.</P>

      • 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>

      • 학습전략 교수의 두 가지 측면

        Charles A. Hughes 학습전략중재학회 2010 학습전략중재연구 Vol.1 No.2

        Hughes 교수는 이 학회지의 지난 호에 학습전략의 내용 자체만큼이나 학습전략 교수방법이 왜 중요한가를 논의하였었다. 이번 호의 논문에서는 학습전략을 학습장애 학생들에게 가르치는 데에 관련된 두 가지 측면을 제시하고 있다. 첫째로는 초등학교 고학년들과 같은 어린 학생들도 학습전략 교수로부터 이득을 볼 수가 있다는 것과 이를 위해서는 교사들이 나이 든 학생들을 가르치기 위해 개발된 교수절차를 수정해야 할 필요가 있음을 제시하고 있다. 이에 따라 어떻게 교수적 수정을 해야 하는가에 대해 구체적으로 설명하고 있다. 둘째로는 교사가 필요하다고 생각되는 학습전략을 직접 개발하는 방법으로서 학습전략 개발의 9단계를 제시하고 있다. 교사가 학습전략 개발방법을 안다는 것은 학생들의 요구를 충족시키기 위해 중요하며, 학습전략 개발방법을 모른다면 교사들은 학습전략 개발을 저술하는 기회를 가질 수가 없을 것이다. 따라서 학습전략 교수의 또 다른 주요 측면으로서 어떻게 학습전략을 개발하는가에 대한 지식은 교사와 학습장애 학생 모두에게 이득을 줄 수 있다.

      • SCISCIE

        An Australia Telescope Compact Array 20-cm radio continuum study of the Large Magellanic Cloud

        Hughes, A.,Staveley-Smith, L.,Kim, S.,Wolleben, M.,Filipović,, M. Blackwell Publishing Ltd 2007 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.382 No.2

        <P>ABSTRACT</P><P>We present a mosaic image of the 1.4-GHz radio continuum emission from the Large Magellanic Cloud (LMC) observed with the Australia Telescope Compact Array (ATCA) and the Parkes Telescope. The mosaic covers <IMG SRC='http://onlinelibrary.wiley.com/store/10.1111/j.1365-2966.2007.12466.x/asset/equation/MNR_12466_mu1.gif?v=1&s=3c55d39c3da8b7009e1ce58371b88f172bd55796'/> with an angular resolution of 40 arcsec, corresponding to a spatial scale of ∼10 pc in the LMC. The final image is suitable for studying emission on all scales between 40 arcsec and the surveyed area. In this paper, we discuss (i) the characteristics of the LMC's diffuse and compact radio continuum emission, (ii) the fraction of the emission produced by thermal processes and the implied star formation rate in the LMC and (iii) variations in the radio spectral index across the LMC. Two non-standard reduction techniques that we used to process the ATCA visibility data may be of interest for future wide-field radio continuum surveys. The data are open to the astronomical community and should be a rich resource for studies of individual objects such as supernova remnants, H <SMALL>II</SMALL> regions and planetary nebulae as well as extended features such as the diffuse emission from synchrotron radiation.</P>

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