The Nature of the Stable Soft X-ray Emissions in Several Types of Active Galactic Nuclei Observed by Suzaku

To constrain the origin of the soft X-ray excess phenomenon seen in many active galactic nuclei, the intensity-correlated spectral analysis, developed by Noda et al. (2011b) for Markarian 509, was applied to wide-band (0.5-45 keV) Suzaku data of five representative objects with relatively weak reflection signature. They are the typical bare-nucleus type 1 Seyfert Fairall 9, the bright and typical type 1.5 Seyfert MCG-2-58-22, 3C382 which is one of the X-ray brightest broad line radio galaxies, the typical Seyfert-like radio loud quasar 4C+74.26, and the X-ray brightest radio quiet quasar MR2251-178. In all of them, soft X-ray intensities in energies below 3 keV were tightly correlated with that in 3-10 keV, but with significant positive offsets. These offsets, when calculated in finer energy bands, define a stable soft component in 0.5-3 keV. In each object, this component successfully explained the soft excess above a power-law fit. These components were interpreted in several alternative ways, including a thermal Comptonization component which is independent of the dominant power-law emission. This interpretation, considered physically most reasonable, is discussed from a viewpoint of Multi-Zone Comptonization, which was proposed for the black hole binary Cygnus X-1 (Makishima et al. 2008).Comment: 18 pages, 12 figures, 7 table

Fine-pitch and thick-foil gas electron multipliers for cosmic x-ray polarimeters

We have produced various gas electron multiplier foils (GEMs) by using laser etching technique for cosmic X-ray polarimeters. The finest structure GEM we have fabricated has 30 μm-diameter holes on a 50 μm-pitch. The effective gain of the GEM reaches around 5000 at the voltage of 570 V between electrodes. The gain is slightly higher than that of the CERN standard GEM with 70 μm-diameter holes on a 140 μm-pitch. We have fabricated GEMs with thickness of 100 μm which has two times thicker than the standard GEM. The effective gain of the thick-foil GEM is 104 at the applied voltage of 350 V per 50 μm of thickness. The gain is about two orders higher than that of the standard GEM. The remarkable characteristic of the thick-foil GEM is that the effective gain at the beginning of micro-discharge is quite improved. For fabricating the thick-foil GEMs, we have employed new material, liquid crystal polymer (LCP) which has little moisture absorption rate, as an insulator layer instead of polyimide. One of the thick-foil GEM we have fabricated has 8 μm copper layer in the middle of the 100 μm-thick insulator layer. The metal layer in the middle of the foil works as a field-shaper in the multiplication channels, though it slightly decreases the effective gain

Development of cosmic x-ray polarimeter

We present a performance study of a cosmic X-ray polarimeter which is based on the photoelectric effect in gas, and sensitive to a few to 30 keV range. In our polarimeter, the key device would be the 50 μm pitch Gas Electron Multiplier (GEM). We have evaluated the modulation factor using highly polarized X-ray, provided by a synchrotron accelerator. In the analysis, we selected events by the eccentricity of the charge cloud of the photoelectron track. As a result, we obtained the relationship between the selection criteria for the eccentricity and the modulation factors; for example, when we selected the events which have their eccentricity of > 0.95, the polarimeter exhibited with the modulation factor of 0.32. In addition, we estimated the Minimum Detectable Polarization degree (MDP) of Crab Nebula with our polarimeter and found 10 ksec observation is enough to detect the polarization, if we adopt suitable X-ray mirrors

STAT3 gene mutations and their association with pure red cell aplasia in large granular lymphocyte leukemia

Large granular lymphocyte leukemia (LGLL) has been morphologically characterized as a group of lymphoproliferative diseases that include T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of natural killer cells (CLPD-NK). We investigated mutations in the Src homology 2 (SH2) domain of the signal transducer and activator of transcription 3 (STAT3) gene in Asian cohorts of T-LGLL and CLPD-NK (n=42 and 11, respectively). Two mutations, Y640F and D661Y, were identified using direct sequencing or allele-specific (AS) PCR. Y640F and D661Y mutations were found in seven and 18 patients, respectively. Two patients were positive for both mutations. Frequencies of STAT3 mutations in T-LGLL and CLPD-NK were 47.6% and 27.2%, respectively. Pure red cell aplasia (PRCA) was associated with the mutations (P=0.005). The mutations were persistently found at stable levels in some patients after more than 5years using AS-quantitative PCR. The results of the present study indicate that the SH2 domain of the STAT3 gene is frequently mutated in Asian T-LGLL and CLPD-NK, and that PRCA is closely correlated with the mutations. SH2 domain of the STAT3 gene is frequently mutated in Asian T cell large granular lymphocyte leukemia and chronic lymphoproliferative disorders of NK cells. Pure red cell aplasia is closely associated with the mutations.ArticleCANCER SCIENCE. 105(3):342-346 (2014)journal articl

Fine-pitch and thick-foil gas electron multipliers for cosmic x-ray polarimeters

We have produced various gas electron multiplier foils (GEMs) by using laser etching technique for cosmic X-ray polarimeters. The finest structure GEM we have fabricated has 30 μm-diameter holes on a 50 μm-pitch. The effective gain of the GEM reaches around 5000 at the voltage of 570 V between electrodes. The gain is slightly higher than that of the CERN standard GEM with 70 μm-diameter holes on a 140 μm-pitch. We have fabricated GEMs with thickness of 100 μm which has two times thicker than the standard GEM. The effective gain of the thick-foil GEM is 104 at the applied voltage of 350 V per 50 μm of thickness. The gain is about two orders higher than that of the standard GEM. The remarkable characteristic of the thick-foil GEM is that the effective gain at the beginning of micro-discharge is quite improved. For fabricating the thick-foil GEMs, we have employed new material, liquid crystal polymer (LCP) which has little moisture absorption rate, as an insulator layer instead of polyimide. One of the thick-foil GEM we have fabricated has 8 μm copper layer in the middle of the 100 μm-thick insulator layer. The metal layer in the middle of the foil works as a field-shaper in the multiplication channels, though it slightly decreases the effective gain

The temperature dependence of gamma-ray responses of YAG:Ce ceramic scintillators

The temperature dependence (from -20 to +20 degrees C) of gamma-ray irradiated light outputs, energy resolutions, and decay time profiles of three YAG:Ce poly-ceramic scintillators are studied. The Ce concentrations are 0.5, 0.05, and 0.005 mol%.0 The relative light yield of the YAG:Ce with 0.5 mol% with a 2 μs shaping time was measured as 1 : 1.08 : 1.14 at +20, 0, and -20 degrees C, respectively, including the temperature dependence of the phototube (-0.2% /degree). The energy resolution stays almost constant at 7.2-1.984238or 662 keV gamma-rays. The ceramic with 0.05 mol??к_?ۿ?Sڟ?hows the almost same properties, while the light yield of that with 0.005 mol-1230736516s 2-4 times lower (hence the energy resolution becomes 14-19%). All the scintillators exhibit good linearities within ∼ 1 % between the light output and the irradiated gamma-ray energy from 59.5 keV to 662 keV. The decay time constants of the dominant decay components are about 80 ns and 300 ns at +20 degrees C. As the temperature increases from -20 to +20 degrees C, the effective decay of all the ceramics becomes faster, because the decay time constants and fractions of the slower components shorten and decrease, respectively. This result suggests that carriers which are captured in shallow traps before transferring excitation to Ce ions can escape the traps more easily at higher temperatures. Considering the decrease of the total light yield toward higher temperatures, it is thought that thermal quenching starts to dominate the temperature dependence of the ceramic YAG:Ce around the room temperature. The 0.5 mol?ڿ?R?@ʿ???S?cintillator shows a lower quenching energy than the 0.05 mol1001122502ne. This can be explained in terms of self absorption of Ce emission

Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

<p>Abstract</p> <p>Background</p> <p>While lenalidomide (LEN) shows high efficacy in myelodysplastic syndromes (MDS) with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN.</p> <p>Design and methods</p> <p>We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by metaphase cytogenetics (MC) who underwent therapy with LEN.</p> <p>Results</p> <p>Fluorescence in situ hybridization (FISH) or single nucleotide polymorphism array (SNP-A)-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8%) additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, <it>p </it>= .08) and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% <it>p </it>= .11). However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of <it>TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2</it>, and <it>DNMT-3A </it>was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN.</p> <p>Conclusions</p> <p>Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.</p

Myeloid Malignancies with Chromosome 5q Deletions Acquire a Dependency on an Intrachromosomal NF-κB Gene Network

SummaryChromosome 5q deletions (del[5q]) are common in high-risk (HR) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR MDS/AML and miR-146a−/− hematopoietic stem/progenitor cells (HSPCs) results in TRAF6/NF-κB activation. Increased survival and proliferation of HSPCs from miR-146alow HR MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-κB-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-κB signaling, as disrupting the p62-TRAF6 signaling complex results in cell-cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-κB to sustain TRAF6/NF-κB signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML

Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells

TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2?/? mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2?/? tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies. Single-cell-targeted sequencing of wild-type and premalignant Tet2?/? Lin?c-Kit+ cells shows higher mutation frequencies in Tet2?/? cells. We further show that the increased mutational burden is particularly high at genomic sites that gained 5-hydroxymethylcytosine, where TET2 normally binds. Furthermore, TET2-mutated myeloid malignancy patients have significantly more mutational events than patients with wild-type TET2. Thus, Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells, suggesting a novel TET2 loss-mediated mechanism of haematological malignancy pathogenesis