Src activation by Chk1 promotes actin patch formation and prevents chromatin bridge breakage in cytokinesis

In cytokinesis with chromatin bridges, cells delay abscission and retain actin patches at the intercellular canal to prevent chromosome breakage. In this study, we show that inhibition of Src, a protein-tyrosine kinase that regulates actin dynamics, or Chk1 kinase correlates with chromatin breakage and impaired formation of actin patches but not with abscission in the presence of chromatin bridges. Chk1 is required for optimal localization and complete activation of Src. Furthermore, Chk1 phosphorylates human Src at serine 51, and phosphorylated Src localizes to actin patches, the cell membrane, or the nucleus. Nonphosphorylatable mutation of S51 to alanine reduces Src catalytic activity and impairs formation of actin patches, whereas expression of a phosphomimicking Src-S51D protein rescues actin patches and prevents chromatin breakage in Chk1-deficient cells. We propose that Chk1 phosphorylates Src-S51 to fully induce Src kinase activity and that phosphorylated Src promotes formation of actin patches and stabilizes chromatin bridges. These results identify proteins that regulate formation of actin patches in cytokinesis

Search for GeV Gamma-ray Counterparts of Gravitational Wave Events by CALET

We present results on searches for gamma-ray counterparts of the LIGO/Virgo gravitational-wave events using CALorimetric Electron Telescope ({\sl CALET}) observations. The main instrument of {\sl CALET}, CALorimeter (CAL), observes gamma-rays from $\sim1$ GeV up to 10 TeV with a field of view of nearly 2 sr. In addition, the {\sl CALET} gamma-ray burst monitor (CGBM) views $\sim$3 sr and $\sim2\pi$ sr of the sky in the 7 keV -- 1 MeV and the 40 keV -- 20 MeV bands, respectively, by using two different crystal scintillators. The {\sl CALET} observations on the International Space Station started in October 2015, and here we report analyses of events associated with the following gravitational wave events: GW151226, GW170104, GW170608, GW170814 and GW170817. Although only upper limits on gamma-ray emission are obtained, they correspond to a luminosity of $10^{49}\sim10^{53}$ erg s$^{-1}$ in the GeV energy band depending on the distance and the assumed time duration of each event, which is approximately the order of luminosity of typical short gamma-ray bursts. This implies there will be a favorable opportunity to detect high-energy gamma-ray emission in further observations if additional gravitational wave events with favorable geometry will occur within our field-of-view. We also show the sensitivity of {\sl CALET} for gamma-ray transient events which is the order of $10^{-7}$~erg\,cm$^{-2}$\,s$^{-1}$ for an observation of 100~s duration.Comment: 12 pages, 8 figures, 1 table. Accepted for publication in Astrophysical Journa

On-orbit Operations and Offline Data Processing of CALET onboard the ISS

The CALorimetric Electron Telescope (CALET), launched for installation on the International Space Station (ISS) in August, 2015, has been accumulating scientific data since October, 2015. CALET is intended to perform long-duration observations of high-energy cosmic rays onboard the ISS. CALET directly measures the cosmic-ray electron spectrum in the energy range of 1 GeV to 20 TeV with a 2% energy resolution above 30 GeV. In addition, the instrument can measure the spectrum of gamma rays well into the TeV range, and the spectra of protons and nuclei up to a PeV. In order to operate the CALET onboard ISS, JAXA Ground Support Equipment (JAXA-GSE) and the Waseda CALET Operations Center (WCOC) have been established. Scientific operations using CALET are planned at WCOC, taking into account orbital variations of geomagnetic rigidity cutoff. Scheduled command sequences are used to control the CALET observation modes on orbit. Calibration data acquisition by, for example, recording pedestal and penetrating particle events, a low-energy electron trigger mode operating at high geomagnetic latitude, a low-energy gamma-ray trigger mode operating at low geomagnetic latitude, and an ultra heavy trigger mode, are scheduled around the ISS orbit while maintaining maximum exposure to high-energy electrons and other high-energy shower events by always having the high-energy trigger mode active. The WCOC also prepares and distributes CALET flight data to collaborators in Italy and the United States. As of August 31, 2017, the total observation time is 689 days with a live time fraction of the total time of approximately 84%. Nearly 450 million events are collected with a high-energy (E>10 GeV) trigger. By combining all operation modes with the excellent-quality on-orbit data collected thus far, it is expected that a five-year observation period will provide a wealth of new and interesting results.Comment: 11 pages, 7 figures, published online 27 February 201

Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a global health problem, and current therapy for COPD is poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. Imbalance of oxidant/antioxidant balance caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g. NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervening COPD

CALET UPPER LIMITS on X-RAY and GAMMA-RAY COUNTERPARTS of GW151226

We present upper limits in the hard X-ray and gamma-ray bands at the time of the Laser Interferometer Gravitational-wave Observatory (LIGO) gravitational-wave event GW151226 derived from the CALorimetric Electron Telescope (CALET) observation. The main instrument of CALET, CALorimeter (CAL), observes gamma-rays from ∼1 GeV up to 10 TeV with a field of view of ∼2 sr. The CALET gamma-ray burst monitor (CGBM) views ∼3 sr and ∼2π sr of the sky in the 7 keV-1 MeV and the 40 keV-20 MeV bands, respectively, by using two different scintillator-based instruments. The CGBM covered 32.5% and 49.1% of the GW151226 sky localization probability in the 7 keV-1 MeV and 40 keV-20 MeV bands respectively. We place a 90% upper limit of 2 ×10-7 erg cm-2 s-1 in the 1-100 GeV band where CAL reaches 15% of the integrated LIGO probability (∼1.1 sr). The CGBM 7σ upper limits are 1.0 ×10-6 erg cm-2 s-1 (7-500 keV) and 1.8 ×10-6 erg cm-2 s-1 (50-1000 keV) for a 1 s exposure. Those upper limits correspond to the luminosity of 3-5 ×1049 erg s-1, which is significantly lower than typical short GRBs

The CALorimetric Electron Telescope (CALET) on the international space station: Results from the first two years on orbit

The CALorimetric Electron Telescope (CALET) is a high-energy astroparticle physics space experiment installed on the International Space Station (ISS), developed and operated by Japan in collaboration with Italy and the United States. The CALET mission goals include the investigation of possible nearby sources of high-energy electrons, of the details of galactic particle acceleration and propagation, and of potential signatures of dark matter. CALET measures the cosmic-ray electron+positron flux up to 20 TeV, gamma-rays up to 10 TeV, and nuclei with Z=1 to 40 up to 1, 000 TeV for the more abundant elements during a long-term observation aboard the ISS. Starting science operation in mid-October 2015, CALET performed continuous observation without major interruption with close to 20 million triggered events over 10 GeV per month. Based on the data taken during the first two-years, we present an overview of CALET observations: 1) Electron+positron energy spectrum, 2) Nuclei analysis, 3) Gamma-ray observation including a characterization of on-orbit performance. Results of the electromagnetic counterpart search for LIGO/Virgo gravitational wave events are discussed as well

Direct Measurement of the Cosmic-Ray Proton Spectrum from 50 GeV to 10 TeV with the Calorimetric Electron Telescope on the International Space Station

In this paper, we present the analysis and results of a direct measurement of the cosmic-ray proton spectrum with the CALET instrument onboard the International Space Station, including the detailed assessment of systematic uncertainties. The observation period used in this analysis is from October 13, 2015 to August 31, 2018 (1054 days). We have achieved the very wide energy range necessary to carry out measurements of the spectrum from 50 GeV to 10 TeV covering, for the first time in space, with a single instrument the whole energy interval previously investigated in most cases in separate subranges by magnetic spectrometers (BESS-TeV, PAMELA, and AMS-02) and calorimetric instruments (ATIC, CREAM, and NUCLEON). The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index from-2.81±0.03 (50-500 GeV) neglecting solar modulation effects (or-2.87±0.06 including solar modulation effects in the lower energy region) to-2.56±0.04 (1-10 TeV), thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ

Energy Spectrum of Cosmic-Ray Electron and Positron from 10 GeV to 3 TeV Observed with the Calorimetric Electron Telescope on the International Space Station

First results of a cosmic-ray electron and positron spectrum from 10 GeV to 3 TeV is presented based upon observations with the CALET instrument on the International Space Station starting in October, 2015. Nearly a half million electron and positron events are included in the analysis. CALET is an all-calorimetric instrument with total vertical thickness of 30 X0 and a fine imaging capability designed to achieve a large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum over 30 GeV can be fit with a single power law with a spectral index of -3.152±0.016 (stat+syst). Possible structure observed above 100 GeV requires further investigation with increased statistics and refined data analysis

On-orbit operations and offline data processing of CALET onboard the ISS

The CALorimetric Electron Telescope (CALET), launched for installation on the International Space Station (ISS) in August, 2015, has been accumulating scientific data since October, 2015. CALET is intended to perform long-duration observations of high-energy cosmic rays onboard the ISS. CALET directly measures the cosmic-ray electron spectrum in the energy range of 1 GeV to 20 TeV with a 2% energy resolution above 30 GeV. In addition, the instrument can measure the spectrum of gamma rays well into the TeV range, and the spectra of protons and nuclei up to a PeV. In order to operate the CALET onboard ISS, JAXA Ground Support Equipment (JAXA-GSE) and the Waseda CALET Operations Center (WCOC) have been established at JAXA and Waseda University, respectively. Scientific operations using CALET are planned at WCOC, taking into account orbital variations of geomagnetic rigidity cutoff. Scheduled command sequences are used to control the CALET observation modes on orbit. Calibration data acquisition by, for example, recording pedestal and penetrating particle events, a low-energy electron trigger mode operating at high geomagnetic latitude, a low-energy gamma-ray trigger mode operating at low geomagnetic latitude, and an ultra heavy trigger mode, are scheduled around the ISS orbit while maintaining maximum exposure to high-energy electrons and other high-energy shower events by always having the high-energy trigger mode active. The WCOC also prepares and distributes CALET flight data to collaborators in Italy and the United States. As of August 31, 2017, the total observation time is 689 days with a live time fraction of the total time of ∼ 84%. Nearly 450 million events are collected with a high-energy (E \u3e 10 GeV) trigger. In addition, calibration data acquisition and low-energy trigger modes, as well as an ultra-heavy trigger mode, are consistently scheduled around the ISS orbit. By combining all operation modes with the excellent-quality on-orbit data collected thus far, it is expected that a five-year observation period will provide a wealth of new and interesting results