Suzaku Observation of the Anomalous X-ray Pulsar 1E 1841-045

We report the results of a Suzaku observation of the anomalous X-ray pulsar (AXP) 1E 1841-045 at a center of the supernova remnant Kes 73. We confirmed that the energy-dependent spectral models obtained by the previous separate observations were also satisfied over a wide energy range from 0.4 to ~70 keV, simultaneously. Here, the models below ~10 keV were a combination of blackbody (BB) and power-law (PL) functions or of two BBs wit h different temperatures at 0.6 - 7.0 keV (Morii et al. 2003), and that above ~20 keV was a PL function (Kuiper Hermsen Mendez 2004). The combination BB + PL + PL was found to best represent the phase-averaged spectrum. Phase-resolved spectroscopy indicated the existence of two emission regions, one with a thermal and the other with a non-thermal nature. The combination BB + BB + PL was also found to represent the phase-averaged spectrum well. However, we found that this model is physically unacceptable due to an excessively large area of the emission region of the blackbody. Nonetheless, we found that the temperatures and radii of the two blackbody components showed moderate correlations in the phase-resolved spectra. The fact that the same correlations have been observed between the phase-averaged spectra of various magnetars (Nakagawa et al. 2009) suggests that a self-similar function can approximate the intrinsic energy spectra of magnetars below ~10 keV.Comment: Accepted for publication in the PAS

Assessment of antitumor activity and acute peripheral neuropathy of 1,2-diaminocyclohexane platinum (II)-incorporating micelles (NC-4016)

13301甲第4166号博士（医学）金沢大学博士論文本文Full 以下に掲載：International Journal of Nanomedicine 9(1) pp.3005-3012 2014. Dove press. 共著者：Takayoshi Ueno, Kazuhira Endo, Kiyomi Hori, Noriyuki Ozaki, Akira Tsuji, Satoru Kondo, Naohiro Wakisaka, Shigeyuki Murono, Kazunori Kataoka, Yasuki Kato, Tomokazu Yoshizak

Recommendations related to the analytical equivalence assessment of gene panel testing

Advances in cancer genome care over the past few years have included the development of gene panel testing for various biomarkers. This article summarizes issues and provides recommendations related to analytical performance evaluations for new oncology gene panels. The scope of these recommendations includes comprehensive genomic profiling assays related to gene panel testing that uses histological or serum specimens to detect gene mutations. As a research project of the Japan Agency for Medical Research and Development Research on Regulatory Science of Pharmaceuticals and Medical Devices, we convened the working group committee that consisted of more than 30 experts from academia, industry, and government. We have discussed the points that should be considered to allow maximal simplification of assessments using clinical specimens in evaluating accuracy and limit of detection in equivalence and analytical performance for three years. We provide recommendations specific to each type of gene mutation as well as to reference standards or specimens used for evaluations. In addition, in order to facilitate the discussion on the analytical performance of gene panel tests by multidisciplinary tumor boards of hospitals, the present recommendations also describe the items that companies are expected to provide information on in their packaging inserts and reports, and the items that are expected to be discussed by multidisciplinary tumor boards. Our working group document will be important for participants in multidisciplinary tumor boards including medical oncologists and genome scientists, and developers of gene panels not only in Japan but also in other countries

Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart

ObjectiveThe development of right ventricular dysfunction has become a common problem after surgical repair of complex congenital heart disease. A recent study reported that tissue-engineered skeletal myoblast sheet transplantation improves left ventricular function in patients with dilated and ischemic cardiomyopathy. Therefore myoblast sheet transplantation might also improve ventricular performance in a rat model of a pressure-overloaded right ventricle.MethodsSeven-week-old male Lewis rats underwent pulmonary artery banding. Four weeks after pulmonary artery banding, myoblast sheet transplantation to the right ventricle was performed in the myoblast sheet transplantation group (n = 20), whereas a sham operation was performed in the sham group (n = 20).ResultsFour weeks after performing the procedure, a hemodynamic assessment with a pressure–volume loop showed a compensatory increase in systolic function in both groups. However, only the myoblast sheet transplantation group showed a significant improvement in the diastolic function: end-diastolic pressure (sham vs myoblast sheet transplantation, 10.3 ± 3.1 vs 5.0 ± 3.7 mm Hg; P < .001), time constant of isovolumic relaxation (11.1 ± 2.5 vs 7.6 ± 1.2 ms, P < .001), and end-diastolic pressure–volume relationship (16.1 ± 4.5 vs 7.6 ± 2.4/mL, P < .005). The right ventricular weight and cell size similarly increased in both groups. A histologic assessment demonstrated significantly suppressed ventricular fibrosis and increased capillary density in the myoblast sheet transplantation group in comparison with those in the sham group. Reverse transcription–polymerase chain reaction demonstrated an increased myocardial gene expression of hepatocyte growth factor and vascular endothelial growth factor in the myoblast sheet transplantation group but not in the sham group.ConclusionsSkeletal myoblast sheet transplantation improved the diastolic dysfunction and suppressed ventricular fibrosis with increased capillary density in a rat model of a pressure-overloaded right ventricle. This method might become a novel strategy for the myocardial regeneration of right ventricular failure in patients with congenital heart disease

Fermi level tuning of Ag-doped Bi2Se3 topological insulator

The temperature dependence of the resistivity (rho) of Ag-doped Bi2Se3 (AgxBi2-xSe3) shows insulating behavior above 35 K, but below 35 K, rho suddenly decreases with decreasing temperature, in contrast to the metallic behavior for non-doped Bi2Se3 at 1.5-300 K. This significant change in transport properties from metallic behavior clearly shows that the Ag doping of Bi2Se3 can effectively tune the Fermi level downward. The Hall effect measurement shows that carrier is still electron in AgxBi2-xSe3 and the electron density changes with temperature to reasonably explain the transport properties. Furthermore, the positive gating of AgxBi2-xSe3 provides metallic behavior that is similar to that of non-doped Bi2Se3, indicating a successful upward tuning of the Fermi level

Tumor-targeted chemotherapy with the nanopolymer-based drug NC-6004 for oral squamous cell carcinoma

医薬保健研究域医学系Cisplatin (CDDP) has been a key drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity is one of its adverse reactions that are dose limiting. To increase its antitumor effects and reduce such toxicity problems, polymeric micelles carrying CDDP (NC-6004) have been developed. The present study was designed to evaluate the efficacy and safety of NC-6004 for oral squamous cell carcinoma. In vitro antitumor activity was assayed in four oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of NC-6004, nude mice bearing OSC-19 were administered NC-6004 or CDDP. The in vitro growth-inhibitory effect of NC-6004 was significantly less than that of CDDP. However, both NC-6004 and CDDP showed equivalent antitumor effects in vivo. Mice with CDDP developed renal cell apoptosis; however, those injected with NC-6004 were almost free of renal cell injury. Moreover, in an orthotopic tongue cancer model using OSC-19, NC-6004 reduced the rate of sentinel lymph node metastasis to lower than that with CDDP. In conclusion, considering the potential advantages in terms of noticeable antitumor activity, lymphatic drug delivery and reduced nephrotoxicity, NC-6004 represents a significant structural improvement in the development of a platinum complex. © 2012 Japanese Cancer Association

Suzaku Observations of HESS J1616-508: Evidence for a Dark Particle Accelerator

We observed the bright unidentified TeV gamma-ray source HESS J1616-508 with the X-ray Imaging Spectrometers onboard the Suzaku satellite. No X-ray counterpart was found to a limiting flux of 3.1e-13 erg/s/cm^2 in the 2--10 keV band, which is some 60 times below the gamma-ray flux in the 1--10 TeV band. This object is bright in TeV gamma-rays but very dim in the X-ray band, and thus is one of the best examples in the Galaxy of a "dark particle accelerator." We also detected soft thermal emission with kT=0.3--0.6 keV near the location of HESSJ1616. This may be due to the dust grain scattering halo from the nearby bright supernova remnant RCW103.Comment: 10 pages, 9 figures. Accepted for publication in PASJ Suzaku Special Issue (vol. 59 sp. 1

Potential interest in circulating miR-BART17-5p as a post-treatment biomarker for prediction of recurrence in Epstein-Barr virus-related nasopharyngeal carcinoma

Objectives: Epstein-Barr virus (EBV)-related micoRNAs (miRNAs), BamHI-A rightward transcripts (BART)-miRNAs, are released in a stable form from viable cells, which are abundant in patients with EBV-positive nasopharyngeal carcinoma (NPC). We estimated copy numbers of circulating miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p as well as BamHI-W DNA as biomarkers. Materials and Methods: Serums from 31 EBV-positive (confirmed by in situ hybridization for EBV-encoded small RNAs) NPC patients and 40 non-NPC controls were analyzed. Among the 31 NPC patients, serums at the initial diagnosis and three months after treatment were obtained from 20 patients, and serums only at three months after treatment were obtained from 11 patients. Results: The sensitivity/specificity of circulating BamHI-W DNA, miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p for the diagnosis of NPC before treatment were 100/100, 85/85, 60/95, and 25/100%, respectively. For BamHI-W DNA, NPC patients with stage IV disease had significantly higher copy numbers than those with I-III. Copy numbers decreased significantly post-treatment. In contrast, copy numbers of the three BART-miRNAs showed no significant correlation with the clinical stage at diagnosis or any significant post-treatment change. After treatment, BamHI-W DNA and miR-BART17-5p were detected in 5 and 6 cases out of 11 patients with recurrent or residual tumors, respectively. However, BamHI-W DNA and miR-BART17-5p were absent in all 20 patients without relapse or residual tumors. Conclusion: The copy number of circulating BamHI-W DNA is a more useful biomarker for the initial diagnosis of NPC than the three BART-miRNAs examined. Post-treatment detection of miR-BART17-5p is a potential biomarker of a poor prognosis. © 2016 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited