X-rays from the Power Sources of the Cepheus A Star-Forming Region

We report an observation of X-ray emission from the exciting region of Cepheus A with the Chandra/ACIS instrument. What had been an unresolved X-ray source comprising the putative power sources is now resolved into at least 3 point-like sources, each with similar X-ray properties and differing radio and submillimeter properties. The sources are HW9, HW3c, and a new source that is undetected at other wavelengths "h10." They each have inferred X-ray luminosities >= 10^31 erg s^-1 with hard spectra, T >= 10^7 K, and high low-energy absorption equivalent to tens to as much as a hundred magnitudes of visual absorption. The star usually assumed to be the most massive and energetic, HW2, is not detected with an upper limit about 7 times lower than the detections. The X-rays may arise via thermal bremsstrahlung in diffuse emission regions associated with a gyrosynchrotron source for the radio emission, or they could arise from powerful stellar winds. We also analyzed the Spitzer/IRAC mid-IR observation from this star-formation region and present the X-ray results and mid-IR classifications of the nearby stars. HH 168 is not as underluminous in X-rays as previously reported.Comment: Accepted in the ApJ, 30 pages, 11 figures, in one .pdf fil

Carbon-Ion Beam Irradiation Alone or in Combination with Zoledronic acid Effectively Kills Osteosarcoma Cells

Osteosarcoma(OSA)isthemostcommonmalignantbonetumorinchildrenandadolescents. The overall five-year survival rate for all bone cancers is below 70%; however, when the cancer has spread beyond the bone, it is about 15–30%. Herein, we evaluated the effects of carbon-ion beam irradiation alone or in combination with zoledronic acid (ZOL) on OSA cells. Carbon-ion beam irradiation in combination with ZOL significantly inhibited OSA cell proliferation by arresting cell cycle progression and initiating KHOS and U2OS cell apoptosis, compared to treatments with carbon-ion beam irradiation, X-ray irradiation, and ZOL alone. Moreover, we observed that this combination greatly inhibited OSA cell motility and invasion, accompanied by the suppression of the Pi3K/Akt and MAPK signaling pathways, which are related to cell proliferation and survival, compared to individual treatments with carbon-ion beam or X-ray irradiation, or ZOL. Furthermore, ZOL treatment upregulated microRNA (miR)-29b expression; the combination with a miR-29b mimic further decreased OSA cell viability via activation of the caspase 3 pathway. Thus, ZOL-mediated enhancement of carbon-ion beam radiosensitivity may occur via miR-29b upregulation; co-treatment with the miR-29b mimic further decreased OSA cell survival. These findings suggest that the carbon-ion beam irradiation in combination with ZOL has high potential to increase OSA cell death

A Large X-ray Flare from a Single Weak-lined T Tauri Star TWA-7 Detected with MAXI GSC

We present a large X-ray flare from a nearby weak-lined T Tauri star TWA-7 detected with the Gas Slit Camera (GSC) on the Monitor of All-sky X-ray Image (MAXI). The GSC captured X-ray flaring from TWA-7 with a flux of $3\times10^{-9}$ ergs cm$^{-2}$ s$^{-1}$ in 2--20 keV band during the scan transit starting at UT 2010-09-07 18:24:30.The estimated X-ray luminosity at the scan in the energy band is 3$\times10^{32}$ ergs s$^{-1}$,indicating that the event is among the largest X-ray flares fromT Tauri stars.Since MAXI GSC monitors a target only during a scan transit of about a minute per 92 min orbital cycle, the luminosity at the flare peak might have been higher than that detected. At the scan transit, we observed a high X-ray-to-bolometric luminosity ratio, log $L_{\rm X}/L_{\rm bol}$ = $-0.1^{+0.2}_{-0.3}$; i.e., the X-ray luminosity is comparable to the bolometric luminosity. Since TWA-7 has neither an accreting disk nor a binary companion, the observed event implies that none of those are essential to generate such big flares in T Tauri stars.Comment: 4 pages, 2 figures, 1 table accepted for publication in PAS

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Biologocal Intercomparison using Gut Crypt Survivals for Proton and Carbon-Ion Beams

harged particle therapy depends on biological information for the dose prescription. Relative biological effectiveness or RBE for this requirement could basically be provided by experimental data. As RBE values of protons and carbon ions depend on several factors such as cell/tissue type, biological endpoint, dose and fractionation schedule, a single RBE value could not deal with all different radiosensitivities. However, any biological model with accurate reproducibility is useful for comparing biological effectiveness between different facilities. We used mouse gut crypt survivals as endpoint, and compared the cell killing efficiency of proton beams at three Japanese facilities. Three Linac X-ray machines with 4 and 6 MeV were used as reference beams, and there was only a small variation (coefficient of variance < 2%) in biological effectiveness among them. The RBE values of protons relative to Linac X-rays ranged from 1.0 to 1.11 at the middle of a 6-cm SOBP (spread-out Bragg peak) and from 0.96 to 1.01 at the entrance plateau. The coefficient of variance for protons ranged between 4.0 and 5.1%. The biological comparison of carbon ions showed fairly good agreement in that the difference in biological effectiveness between NIRS/HIMAC and GSI/SIS was 1% for three positions within the 6-cm SOBP. The coefficient of variance was < 1.7, < 0.6 and < 1.6% for proximal, middle and distal SOBP, respectively. We conclude that the inter-institutional variation of biological effectiveness is smaller for carbon ions than protons, and that beam-spreading methods of carbon ions do not critically influence gut crypt survival

OK-432 reduces mortality and bacterial translocation in irradiated and granulocyte-colony stimulating factor (G-CSF)-treated mice.

Bacterial translocation/Acute radiation syndrome/Endotoxin/G-CSF/OK-432 Acute radiation induces bacterial translocation from the gut,followed by systemic infection and sepsis. In order to reduce the mortality after acute whole body irradiation, it is essential to control bacterialtranslocation. In this study, we established a bacterial translocation assay as a sensitive method to detect minor mucosal injury by radiation. By utilizing this assay, we evaluated the adverse effects, if any, of hematopoietic reagents on the mucosal integrity in the respiratory and gastro-intestinal tracts. Bacterial translocation to the liver and spleen occurred after whole-body irradiation if the dose exceeded 6 Gy. The administration of G-CSF unexpectedly increased the bacterial translocation in 8 Gy-irradiated mice. The pharmaceutical preparation oflow-virulent Streptococcus pyogenes, OK-432, significantly reduced the endotoxin levels in peripheral blood without any reduction of bacterialtranslocation. A combined treatment with G-CSF and OK-432 decreased bacterial translocation and prevented death. This result indicates that the early administration of G-CSF has an adverse effect on bacterial translocation, and that a combined treatment of G-CSF and OK-432 attenuates the adverse effect of G-CSF and improves the survival rate after acute irradiation

In vivo radiobiological assessment of the CNAO clinical carbon beams

To assess CNAO carbon beam in order to ensure safe and accurate patient therapy. We performed radiobiological study in vivo concerning the uniformity of biological doses in PTV and to calculate the values of the RBE at different depths in the SOBP. Uniformity of the biological dose; (physical Dose) x (biological RBE) in SOBP / PTV of the CNAO carbon ion beams were determined using jejunal crypt regeneration in mice as biological system at three different depths along with a 6 cm SOBP at proximal, middle and distal positions. Groups of each three C3H/He female mice at 11-12 weeks old were kept in a Lucite jig under anesthesia and irradiated at each depth position. The jig was positioned perpendicularly to the beam axis in order to irradiate mice in abdomen-dorsum direction. This study was approved by the Ethical Committee of the University of Pavia. We irradiated 71 mice with the CNAO carbon ion therapeutic beams. The dose-effect curves for jejunal crypt after the irradiation at the three positions along the SOBP were found to be at the expected position and separated among each other, with the distal one more effective than the proximal and center. The RBE values calculated from the isoeffect doses to reduce crypt survival per circumference to 30 and 10, well corresponded to those obtained from other carbon ion facilities#. According to the criteria already used for the comparisons of the carbon ion beams by NIRS and GSI, we can conclude that the clinical carbon ion beam by CNAO has similar biological characteristics by NIRS and GSI.Heavy Ion in Therapy and Space Radiation Symposium 2013 (HITSRS2013

Glycine betaine, a beer component, protects radiation-induced injury

Human hole-blood was exposed t