Sepsis is a life-threatening disease characterized by excessive inflammation leading to organ dysfunction. During sepsis, pulmonary microvascular endothelial cells (PMVEC) lose barrier function ...associated with inter-PMVEC junction disruption. Matrix metalloproteinases (MMP) and a disintegrin and metalloproteinases (ADAM), which are regulated by tissue inhibitors of metalloproteinases (TIMPs), can cleave cell-cell junctional proteins, suggesting a role in PMVEC barrier dysfunction. We hypothesize that septic PMVEC barrier dysfunction is due to a disruption in the balance between PMVEC-specific metalloproteinases and TIMPs leading to increased metalloproteinase activity. The effects of sepsis on TIMPs and metalloproteinases were assessed ex vivo in PMVEC from healthy (sham) and septic (cecal ligation and perforation) mice, as well as in vitro in isolated PMVEC stimulated with cytomix, lipopolysaccharide (LPS), and cytomix + LPS vs. PBS. PMVEC had high basal
expression and lower metalloproteinase expression, and septic stimulation shifted expression in favour of metalloproteinases. Septic stimulation increased MMP13 and ADAM17 activity associated with a loss of inter-PMVEC junctional proteins and barrier dysfunction, which was rescued by treatment with metalloproteinase inhibitors. Collectively, our studies support a role for metalloproteinase-TIMP imbalance in septic PMVEC barrier dysfunction, and suggest that inhibition of specific metalloproteinases may be a therapeutic avenue for septic patients.
The High-energy Particle Detector (HEPD) on board the China Seismo-Electromagnetic Satellite (CSES-01)-launched on 2018 February 2-is a light and compact payload suitable for measuring electrons ...(3-100 MeV), protons (30-250 MeV), and light nuclei (up to a few hundreds of MeV). The Sun-synchronous orbit and large acceptance allow HEPD to measure cosmic-ray particles near the 65° latitude limit for a fair amount of time per day. In this work, three semiannual galactic hydrogen energy spectra between ∼40 and 250 MeV are presented, including a comparison with theoretical spectra from HelMod, a 2D Monte Carlo model developed to simulate the solar modulation of cosmic rays throughout the heliosphere. To our knowledge, these are the first hydrogen energy spectra below 250 MeV measured at 1 au between 2018 and 2020.
Abstract The Electric Field Detector (EFD-02) on board the second China Seismo-Electromagnetic Satellite (CSES-02) will measure the electric field components at a Low Earth Orbit (LEO) over a wide ...frequency band (DC – 3.5 MHz) and with 1 μV/m sensitivity in the Low Frequency band. EFD-02 will measure the voltage differences between pairs of probes installed at the tips of four booms deployed from the satellite. In this article, we describe the Zynq System on Chip (SoC)-based digital hardware subsystem dedicated to signal processing, and the selected implementation strategy, which successfully complied to the specific requirements of the space mission. Furthermore, we present a comprehensive overview of the assessed instrument performance.
Manned space missions towards Moon and Mars planned in the next decades require a reliable radiation risk assessment considering the long time exposure of astronauts (up to years) to different ...radiation fields. The radiation environment inside a human space habitat, generated by the interaction of the Galactic Cosmic Rays and occasionally of Solar Particle Events with the spacecraft hull, is peculiar due to its composition (ions from Hydrogen to Iron, knock out neutrons) and the large kinetic energy range of the particles. For this reason the risk assessment approach used for astronauts in space is quite different from the one used on Earth. In this approach the risk for astronauts is evaluated calculating factors which score the risk in function of physical characteristics of the single particle, like the quality factor Q (related to the radiation ionizing power) or the squared ratio between the charge (Z) and velocity (β) of the particle (Z2/β2). LIDAL-ALTEA (Light Ion Detector for ALTEA - Anomalous Long Term Effects on Astronauts) is an experimental apparatus which will allow to evaluate for the first time in the field the Z2/β2 risk factor of the single detected particle on-board the International Space Station. The LIDAL system is a Time-Of-Flight detector designed to work paired to three Silicon Detector Units of the ALTEA, which will measure the deposited energy of the passing particle. The velocity of the particle (β), calculated from the Time-Of-Flight measurement performed by LIDAL, allows to evaluate the particle electric charge once related to the deposited energy measured by ALTEA. A first LIDAL prototype has been developed by the University of Rome "Tor Vergata" and tested at TIFPA (Trento Insistute for Fundamental Physics Applications) proton beam line, in order to evaluate the timing performances of the detector. Results are briefly presented and the current status of the apparatus production is discussed in view of the launch scheduled for 2019.
The LIDAL (Light Ion Detector for ALTEA) is a device designed to work paired with three silicon detector units of ALTEA (Anomalous Long Term Effects on Astronauts) in order to improve the particle ...identification capabilities of ALTEA on the International Space Station also providing Time-of-Flight measurements. The LIDAL-ALTEA goal is to measure ions from protons up to iron in real time. The improved measurements of the radiation environment inside ISS will be very valuable for radiation risk assessment and mitigation. It is necessary to have a detailed simulation of the apparatus response to cosmic ray nuclei in order to assess the detector response, its observational capabilities and to set the relevant parameters of the device. Here a new Monte Carlo simulation of the LIDAL-ALTEA setup and physics processes, in the framework of FLUKA, is presented. A comparison between Monte Carlo simulations and calibration data is also shown.
The HEPD apparatus for the CSES mission Panico, Beatrice; Osteria, G.; Perfetto, F. ...
Journal of physics. Conference series,
01/2020, Letnik:
1342, Številka:
1
Journal Article
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The High-Energy Particle Detector (HEPD) is one of the payloads of the CSES space mission. The HEPD is built by the Italian Limadou collaboration and has different goals. It will study the temporal ...stability of the inner Van Allen radiation belts, the precipitation of trapped particles in the atmosphere and the low energy component of the cosmic rays (5-100 MeV for electrons and 15 - 300 MeV for protons). It has been tested at the Beam Test Facility of the INFN National Laboratory of Frascati, for electrons, and at the Proton Cyclotron of Trento, for protons. Here is presented a study of the performance of the apparatus to separate electrons and protons and identify nuclei up to iron.
Endothelial cells (EC), especially the microvascular EC (MVEC), have critical functions in health and disease. For example, healthy MVEC provide a barrier between the fluid and protein found within ...the blood, and the surrounding tissue. Following tissue injury or infection, the microvascular barrier is often disrupted due to activation and dysfunction of the MVEC. Multiple mechanisms promote MVEC activation and dysfunction, including stimulation by cytokines, mechanical interaction with activated leukocytes, and exposure to harmful leukocyte-derived molecules, which collectively result in a loss of MVEC barrier function. However, MVEC activation is also critical to facilitate recruitment of inflammatory cells, such as neutrophils (PMNs) and monocytes, into the injured or infected tissue. Metalloproteinases, including the matrix metalloproteinases (MMPs) and the closely related, a disintegrin and metalloproteinases (ADAMs), have been implicated in regulating both MVEC barrier function, through cleavage of adherens and tight junctions proteins between adjacent MVEC and through degradation of the extracellular matrix, as well as PMN-MVEC interaction, through shedding of cell surface PMN receptors. Moreover, the tissue inhibitors of metalloproteinases (TIMPs), which collectively inhibit most MMPs and ADAMs, are critical regulators of MVEC activation and dysfunction through their ability to inhibit metalloproteinases and thereby promote MVEC stability. However, TIMPs have been also found to modulate MVEC function through metalloproteinase-independent mechanisms, such as regulation of vascular endothelial growth factor signaling. This chapter is focused on examining the role of the metalloproteinases and TIMPs in regulation of MVEC function in both health and disease.
Patients with chronic obstructive pulmonary disease (COPD) have a reduced quality of life (QoL) and exacerbations that drive health service utilization (HSU). A majority of patients with COPD are ...managed in primary care. Our objective was to evaluate an integrated disease management, self-management, and structured follow-up intervention (IDM) for high-risk patients with COPD in primary care. This was a one-year multi-center randomized controlled trial. High-risk, exacerbation-prone COPD patients were randomized to IDM provided by a certified respiratory educator and physician, or usual physician care. IDM received case management, self-management education, and skills training. The primary outcome, COPD-related QoL, was measured using the COPD Assessment Test (CAT). Of 180 patients randomized from 8 sites, 81.1% completed the study. Patients were 53.6% women, mean age 68.2 years, post-bronchodilator FEV
52.8% predicted, and 77.4% were Global Initiative for Obstructive Lung Disease Stage D. QoL-CAT scores improved in IDM patients, 22.6 to 14.8, and worsened in usual care, 19.3 to 22.0, adjusted difference 9.3 (p < 0.001). Secondary outcomes including the Clinical COPD Questionnaire, Bristol Knowledge Questionnaire, and FEV1 demonstrated differential improvements in favor of IDM of 1.29 (p < 0.001), 29.6% (p < 0.001), and 100 mL, respectively (p = 0.016). Compared to usual care, significantly fewer IDM patients had a severe exacerbation, -48.9% (p < 0.001), required an urgent primary care visit for COPD, -30.2% (p < 0.001), or had an emergency department visit, -23.6% (p = 0.001). We conclude that IDM self-management and structured follow-up substantially improved QoL, knowledge, FEV1, reduced severe exacerbations, and HSU, in a high-risk primary care COPD population. Clinicaltrials.gov NCT02343055.
The China Seismo-Electromagnetic Satellite (CSES) aims to monitor electromagnetic, particle, and plasma perturbations in the iono-magnetosphere and inner Van Allen radiation belts originated by ...electromagnetic sources external and internal to the geomagnetic cavity, cosmic rays, and solar events. In particular, the objective of the space mission is to investigate lithosphere-atmosphere-ionosphere coupling mechanisms (including the effects of lightning, earthquakes, volcanoes, and artificial electromagnetic emissions) that induce perturbations of the top side of the ionosphere and lower boundary of the radiation belts. To this purpose, the mission has been conceived to take advantage of a multi-instrument payload comprising nine detectors for the measurement of electromagnetic field components, plasma parameters, and energetic particles, as well as X-ray flux. The Italian team participating in the CSES mission has built one of these devices, the High-Energy Particle Detector (HEPD), for high-precision observations of electrons, protons, and light nuclei. During its trip along the orbit, and thanks to the large set of detectors operated on board, CSES completely monitors the Earth, acting as an excellent instrument for space weather. The satellite was launched on 2018 February 2, with an expected life span of 5 yr. This article describes the CSES mission with a particular focus on the HEPD apparatus and its in-flight performance.
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