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The clonal origins of leukemic progression of myelodysplasia
Kim, T,Tyndel, M S,Kim, H J,Ahn, J-S,Choi, S H,Park, H J,Kim, Y-k,Yang, D-H,Lee, J-J,Jung, S-H,Kim, S Y,Min, Y H,Cheong, J-W,Sohn, S K,Moon, J H,Choi, M,Lee, M,Zhang, Z,Kim, D(D H) Nature Publishing Group 2017 Leukemia Vol.31 No.9
<P>The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.</P>
c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-β Type II Receptor
Zuo, W.,Huang, F.,Chiang, Y.,Li, M.,Du, J.,Ding, Y.,Zhang, T.,Lee, H.,Jeong, L.,Chen, Y.,Deng, H.,Feng, X.H.,Luo, S.,Gao, C.,Chen, Y.G. Cell Press 2013 Molecular cell Vol.49 No.3
Transforming growth factor β (TGF-β) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-β signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-β signaling by neddylating and stabilizing the type II receptor (TβRII). Knockout of c-Cbl decreases the TβRII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-β stimulation, while c-Cbl overexpression stabilizes TβRII and sensitizes leukemia cells to TGF-β. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TβRII at Lys556 and Lys567. Neddylation of TβRII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting TβRII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant TβRII neddylation and leukemia development.
Zhang, P.,Phan, T.L.,Dan, N.H.,Thanh, T.D.,Yu, S.C. Elsevier Sequoia 2014 Journal of alloys and compounds Vol.615 No.suppl1
The magnetic phase transition behavior were investigated in detail in Ni<SUB>50-y</SUB>Gd<SUB>y</SUB>Mn<SUB>37</SUB>Sn<SUB>13</SUB> (y=1 and 3) alloys prepared by arc-melting method. The martensite phase was found to be strongly suppressed by a small amount of Gd doping. Based on isothermal magnetization curves around Curie temperature of the austenite (T<SUB>C</SUB><SUP>A</SUP>) phase, critical behavior in the austenite phases of both alloys were determined carefully by the Kouvel-Fisher method. The critical exponents were found to be β=0.473+/-0.020 and γ=1.141+/-0.017 with T<SUB>C</SUB><SUP>A</SUP>=299.0+/-0.2K for y=1, and β=0.469+/-0.068 and γ=1.214+/-0.042 with T<SUB>C</SUB><SUP>A</SUP>=302.9+/-0.7K for y=3, respectively. The values of the critical exponents for the ferromagnetic phase transition in the A phase of two alloys can be basically ascribed in the mean-field model (with β=0.5, γ=1) with slightly deviation, revealing a long-range order of ferromagnetic interactions. Such critical behavior can be attributed to the magnetic inhomogeneities originated from the atomic disorder introduced by Gd doping.
Watanabe, H.,Zhang, G.X.,Yoshida, K.,Walker, P.M.,Liu, J.J.,Wu, J.,Regan, P.H.,Soderstrom, P.A.,Kanaoka, H.,Korkulu, Z.,Lee, P.S.,Nishimura, S.,Yagi, A.,Ahn, D.S.,Alharbi, T.,Baba, H.,Browne, F.,Bruce North-Holland Pub. Co 2016 Physics letters. Section B Vol.760 No.-
The level structure of <SUP>172</SUP>Dy has been investigated for the first time by means of decay spectroscopy following in-flight fission of a <SUP>238</SUP>U beam. A long-lived isomeric state with T<SUB>½</SUB>=0.71(5) s and K<SUP>π</SUP>=8<SUP>-</SUP> has been identified at 1278 keV, which decays to the ground-state and γ-vibrational bands through hindered electromagnetic transitions, as well as to the daughter nucleus <SUP>172</SUP>Ho via allowed β decays. The robust nature of the K<SUP>π</SUP>=8<SUP>-</SUP> isomer and the ground-state rotational band reveals an axially-symmetric structure for this nucleus. Meanwhile, the γ-vibrational levels have been identified at unusually low excitation energy compared to the neighboring well-deformed nuclei, indicating the significance of the microscopic effect on the non-axial collectivity in this doubly mid-shell region. The underlying mechanism of enhanced γ vibration is discussed in comparison with the deformed Quasiparticle Random-Phase Approximation based on a Skyrme energy-density functional.
Phan, T.L.,Thanh, P.T.,Dan, N.H.,Zhang, P.,Thanh, T.D.,Phan, M.H.,Yu, S.C. Elsevier Sequoia 2014 JOURNAL OF ALLOYS AND COMPOUNDS Vol.615 No.suppl1
We have studied the magnetic and magnetocaloric (MC) properties of Ni<SUB>50-x</SUB>Pr<SUB>x</SUB>Mn<SUB>37</SUB>Sn<SUB>13</SUB> (x=0, 1, 3, and 5) alloy ingots fabricated by arc-melting. Experimental results revealed a coexistence of the conventional and inverse MC effects in the samples with x=0, 1, and 3. There is a gradual decrease of the magnetization and magnetic-entropy change (ΔS<SUB>m</SUB>) when Pr-doping content increases. However, the Curie temperature of the austenitic phase (T<SUB>C</SUB><SUP>A</SUP>) around room temperature was not changed very much. Particularly, doping a small amount of Pr with x=1 enhances remarkably the linewidth of the peaks in its ΔS<SUB>m</SUB>(T) curves. This increases the relative cooling power (RCP) of Ni<SUB>50-x</SUB>Pr<SUB>x</SUB>Mn<SUB>37</SUB>Sn<SUB>13</SUB> alloys when they are used as coolants in refrigeration devices. For example, under an applied field of H=50 kOe, the RCP increases from 150 for x=0 to ~200J/kg for x=1. Higher Pr contents reduce quickly the MC effect because of the formation of nonmagnetic secondary phases.
Ferromagnetic Order in Rapidly Cooled Nd-Fe-Co-Al Alloy Ribbons
Phan, T. L.,Zhang, Y. D.,Dan, N. H.,Thang, D. D.,Thanh, T. D.,Zhang, P.,Yu, S. C. IEEE 2013 IEEE transactions on magnetics Vol.49 No.7
<P>We have studied the magnetic properties of Nd<SUB>45</SUB>Fe<SUB>30</SUB>Co<SUB>15</SUB>Al<SUB>10</SUB> alloy ribbons with various thicknesses of about 120 (N<SUB>1</SUB>) and 50 μm (N<SUB>2</SUB>) prepared by melt-spinning. Structural analyses based on an X-ray diffractometer and a high-resolution transmission electron microscope revealed an existence of nanocrystals with sizes of 10 ~ 20 nm surrounded by an amorphous host matrix. With decreasing ribbon thickness and nanocrystalline size, magnetic studies upon a vibrating sample magnetometer indicated the decrease of the Curie temperature (T<SUB>C</SUB>), coercive force (H<SUB>c</SUB>), and magnetic entropy change (ΔS<SUB>m</SUB>). In the ferromagnetic region, however, magnetization values determined for N<SUB>2</SUB> are greater than those determined for N<SUB>1</SUB>. These results are related to the differences in the critical exponents of N<SUB>1</SUB> (β=0.418 and γ=1.173), and N<SUB>2</SUB> (β=0.512 and γ=1.077), which are characteristic for the ferromagnetic nature existing in the alloy ribbons with different thicknesses.</P>
Characteristic molecular vibrations of adenosine receptor ligands
Chee, H.K.,Yang, J.S.,Joung, J.G.,Zhang, B.T.,Oh, S.J. North-Holland Pub ; Elsevier Science Ltd 2015 FEBS letters Vol.589 No.4
Although the regulation of membrane receptor activation is known to be crucial for molecular signal transduction, the molecular mechanism underlying receptor activation is not fully elucidated. Here we study the physicochemical nature of membrane receptor behavior by investigating the characteristic molecular vibrations of receptor ligands using computational chemistry and informatics methods. By using information gain, t-tests, and support vector machines, we have identified highly informative features of adenosine receptor (AdoR) ligand and corresponding functional amino acid residues such as Asn (6.55) of AdoR that has informative significance and is indispensable for ligand recognition of AdoRs. These findings may provide new perspectives and insights into the fundamental mechanism of class A G protein-coupled receptor activation.
China Spallation Neutron Source: Accelerator Design Iterations and R&D Status
J. Wei,C.-D. Deng,C.-H. Wang,C.-T. Shi,H. Sun,H.-F. Ouyang,H.-M. Qu,H.-Y. Dong,J. Li,J. Zhang,J.-S. Cao,J.-Y. Tang,L. Dong,L.-L. Wang,Q. Qin,Q.-B. Wang,S. Wang,S.-N. Fu,S.-X Fang,T. -G. Xu,W. Kang,Y.- 한국물리학회 2007 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.50 No.I
The China Spallation Neutron Source (CSNS) is a high-power, accelerator-based project currently under preparation. The accelerator complex consists of an H$^-$ ion source, an H$^-$ linac, a rapid-cycling proton synchrotron, and the transport lines. During the past year, the design of most accelerator systems went through major iterations, and initial research and developments was started on the prototyping of several key components.