Similar levels of complement activation in both patients with thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome: The report from the Korean TTP registry

Background: Uncontrolled complement activation has a major role in the pathogenesis of atypical HUS (aHUS) and the restraint of this process by eculizumab is life saving. However, the evidence of complement dysregulation in the pathogenesis of Thrombotic Thrombocytopenic Purpura (TTP) is still unclear. In this study we examined the presence of complement activation biomarkers in patients with aHUS and TTP and the levels were compared to normal healthy controls . Patients and Methods: Patients with thrombotic microangiopathic thrombocytopenia diagnosed either as TTP with low ADAMTS13 activity less than 10% or aHUS with impaired renal function, Cr> 2mg/dL and normal ADAMTS13 activity were chosen from the Korean TTP registry from February 2012 to June 2014. Prospective plasma and serum samples prior to intervention were collected from newly diagnosed patients with TTP (n=20), aHUS (n=20), and 20 healthy controls and frozen at -700C. Complement activation products (C3a, Bb as alternative pathway; C4d as classic pathway; C5a, C5b-9; terminal pathway) were measured by ELISA. Results: Significantly increased levels of Bb and C5b-9 were observed in TTP (median [range], ng/mL; Bb, 1220 [540.0 – 16560], p=0.048; C5b - 9, 390.1 [238.5 - 938.7], p<0.0001) when compared with controls (Bb, 870.0 [630.0 - 2070]; C5b - 9, 190.8 [77.96 - 458.9]). Increased levels of C3a, C5a, C5b - 9, and Factor Bb were observed in HUS (C3a, 231.3 [80.70 - 791.8], p<0.0001; C5a, 21.38 [5.590 - 34.96], p= 0.006; C5b - 9, 0.49 [0.21 - 1.41], p<0.0001; Bb, 1490 [540.0 – 11800], p= 0.0003) as compared with controls (C3a, 108.7 [30.98 - 425.1]; C5a, 8.620 [2.660 - 26.93]; C5b - 9, 0.49 [0.21 - 1.41]; Bb, 870.0 [630.0 - 2070]). These suggested alternative and terminal complement pathways were activated in initial episodes of TTP or HUS. However levels of C4d were not different in HUS and TTP as compared with controls which suggested classic complement pathways were not important in this process. There were no significant differences in complement levels between TTP and HUS although levels of C3a, C4d, C5b - 9 in HUS (C3a, 231.3 [80.70 - 791.8]; C4d, 2140 [10.00 - 960.0]; C5b - 9, 488.4 [212.7 – 1414]) tended to be increased as compared with TTP (C3a, 134.5 [61.97 - 378.4]; C4d, 1330 [2.000 - 699.0]; C5b - 9, 390.1 [238.5 - 938.7]). Conclusion: Complement biomarkers are activated to a similar level in both newly diagnosed cases of TTP and aHUS. Complement activation product levels did not differentiate aHUS from TTP

Cosmic-ray Heavy Nuclei Spectra Using the ISS-CREAM Instrument

International audienceCosmic Ray Energetics And Mass for the International Space Station (ISS-CREAM) was designed to study high-energy cosmic rays up to PeV and recorded data from August 22nd, 2017 to February 12th, 2019 on the ISS. In this analysis, the Silicon Charge Detector (SCD), CALorimeter (CAL), and Top and Bottom Counting Detectors (TCD/BCD) are used. The SCD is composed of four layers and provides the measurement of cosmic-ray charges with a resolution of $\sim$0.2e. The CAL comprises 20 interleaved tungsten plates and scintillators, measures the incident cosmic-ray particles' energies, and provides a high energy trigger. The TCD/BCDs consist of photodiode arrays and plastic scintillators and provide a low-energy trigger. In this analysis, the SCD top layer is used for charge determination. Here, we present the heavy nuclei analysis using the ISS-CREAM instrument

Measurement of High-energy Cosmic-Ray Proton Spectrum from the ISS-CREAM Experiment

International audienceThe Cosmic Ray Energetics And Mass for the International Space Station (ISS-CREAM) experiment successfully recorded data for 539 days from 2017 August to 2019 February. We report the energy spectrum of cosmic-ray protons from the ISS-CREAM experiment at energies from 1.60 × 10$^{3}$ to 6.55 × 10$^{5}$ GeV. The measured spectrum deviates from a single power law. A smoothly broken power-law fit to the data, including statistical and systematic uncertainties, shows the spectral index change at 9.0 × 10$^{3}$ GeV from 2.57 ± 0.03 to 2.82 ± 0.02 with a significance of greater than 3σ. This bump-like structure is consistent with a spectral softening recently reported by the balloon-borne CREAM, DAMPE, and NUCLEON, but ISS-CREAM extends measurements to higher energies

e/p Separation Study Using the ISS-CREAM Top and Bottom Counting Detectors

International audienceCosmic Ray Energetics And Mass for the International Space Station (ISS-CREAM) is an experiment for studying the origin, acceleration, and propagation mechanisms of high-energy cosmic rays. The ISS-CREAM instrument was launched on the 14th of August 2017 to the ISS aboard the SpaceX-12 Dragon spacecraft. The Top and Bottom Counting Detectors (TCD/BCD) are parts of the ISS-CREAM instrument and designed for studying electron and gamma-ray physics. The TCD/BCD each consist of an array of 20 × 20 photodiodes on a plastic scintillator. The TCD/BCD can separate electrons from protons by using the difference between the shapes of electromagnetic and hadronic showers in the high energy region. The Boosted Decision Tree (BDT) method, which is a deep learning method, is used in this separation study. We will present results of the electron/proton separation study and rejection power in various energy ranges

ISS-CREAM Flight Operation

International audienceThe Cosmic Ray Energetics And Mass experiment for the International Space Station (ISS-CREAM) is designed and built to measure the elemental energy spectra of cosmic-ray particles (1 ≤ Z ≤ 26) and electrons. It measures the energy of incident cosmic rays from 10^12 to 10^15 eV. ISS-CREAM was launched and deployed to the ISS in August 2017. The Science Operations Center (SOC) at the University of Maryland has been operating the payload on the Interna-tional Space Station (ISS) in coordination with the Payload Operations Integration Center (POIC) at NASA’s Marshall Space Flight Center. The SOC has been responsible for sending commands to and receiving data from the Science Flight Computer (SFC) on board ISS-CREAM. The ISS-CREAM data taking program interfaces with the POIC using the Telescience Resources Kit through the Software Toolkit for Ethernet Lab-Like Architecture developed by the Boeing Company. The command uplink and data downlink have been through the Track-ing and Data Relay Satellite System. We present the ISS-CREAM flight operations including ISS communications, SFC performance, etc

On-orbit Performance of the ISS-CREAM Calorimeter

International audienceCosmic Ray Energetics And Mass for the International Space Station (ISS-CREAM) experi-ment is designed to study the composition and energy spectra of cosmic-ray particles from 10^12 to 10^15 eV. ISS-CREAM was launched and deployed to the ISS in August 2017. The ISS-CREAM payload employs a Silicon Charge Detector for charge measurements, Top and Bot-tom Counting Detector for electron-hadron separation and a low-energy trigger, a Boronated Scintillator Detector for additional electron-hadron separation, and a Calorimeter (CAL) for en-ergy measurements and a high-energy trigger. The CAL is constructed of 20 layers of tungsten plates interleaved with scintillating fiber ribbons read out by hybrid-photodiodes (HPDs) and densified carbon targets. Each CAL layer is made of 3.5 mm (1 X_0) thick tungsten plates alter-nating with fifty 0.5 mm thick and 1 cm wide scintillating fiber ribbons. Consecutive layers of fiber ribbons are installed orthogonal to each other. Energy deposition in the CAL determines the particle energy and provides tracking information to determine which segment(s) of the charge detectors to use for the charge measurement. Tracking for showers is accomplished by extrapolating each shower axis back to the charge detectors. The performance of the ISS-CREAM CAL during flight is presented