Patients with chronic lung disease, obesity, and other co-morbid conditions are at increased risk of severe illness and death when infected with severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2). Hypercapnia, the elevation of CO
in blood and tissue, commonly occurs in patients with severe acute and chronic lung disease, including those with pulmonary infections, and is also associated with high mortality risk. We previously reported that hypercapnia increases viral replication and mortality of influenza A virus infection in mice. We have also shown that culture in elevated CO
upregulates expression of cholesterol synthesis genes in primary human bronchial epithelial cells. Interestingly, factors that increase the cholesterol content of lipid rafts and lipid droplets, platforms for viral entry and assembly, enhance SARS-CoV-2 infection. In the current study, we investigated the effects of hypercapnia on ACE2 expression and entry of SARS-CoV-2 pseudovirus (p-SARS-CoV-2) into airway epithelial cells. We found that hypercapnia increased ACE2 expression and p-SARS-CoV-2 uptake by airway epithelium in mice, and in cultured VERO and human bronchial epithelial cells. Hypercapnia also increased total cellular and lipid raft-associated cholesterol in epithelial cells. Moreover, reducing cholesterol synthesis with inhibitors of sterol regulatory element binding protein 2 (SREBP2) or statins, and depletion of cellular cholesterol, each blocked the hypercapnia-induced increases in ACE2 expression and p-SARS-CoV-2 entry into epithelial cells. Cigarette smoke extract (CSE) also increased ACE2 expression, p-SARS-CoV-2 entry and cholesterol accumulation in epithelial cells, an effect not additive to that of hypercapnia, but also inhibited by statins. These findings reveal a mechanism that may account, in part, for poor clinical outcomes of SARS-CoV-2 infection in patients with advanced lung disease and hypercapnia, and in those who smoke cigarettes. Further, our results suggest the possibility that cholesterol-lowering therapies may be of particular benefit in patients with hypercapnia when exposed to or infected with SARS-CoV-2.
Hypercapnia, the elevation of CO2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and it is associated with high mortality. We ...previously reported that hypercapnia alters expression of host defense genes, inhibits phagocytosis, and increases the mortality of Pseudomonas pneumonia in mice. However, the effect of hypercapnia on autophagy, a conserved process by which cells sequester and degrade proteins and damaged organelles that also plays a key role in antimicrobial host defense and pathogen clearance, has not previously been examined. In the present study we show that hypercapnia inhibits autophagy induced by starvation, rapamycin, LPS, heat-killed bacteria, and live bacteria in the human macrophage. Inhibition of autophagy by elevated CO2 was not attributable to acidosis. Hypercapnia also reduced macrophage killing of Pseudomonas aeruginosa. Moreover, elevated CO2 induced the expression of Bcl-2 and Bcl-xL, antiapoptotic factors that negatively regulate autophagy by blocking Beclin 1, an essential component of the autophagy initiation complex. Furthermore, small interfering RNA targeting Bcl-2 and Bcl-xL and the small molecule Z36, which blocks Bcl-2 and Bcl-xL binding to Beclin 1, prevented hypercapnic inhibition of autophagy and bacterial killing. These results suggest that targeting the Bcl-2/Bcl-xL-Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression and improving resistance to infection in patients with advanced lung disease and hypercapnia.
Measurements of electromagnetic waves in space plasmas are an important tool for our understanding of physical processes in this environment. Inter‐calibration of data from different spacecraft ...missions is necessary for combining their measurements in empirical models or case studies. We show results collected during a close conjunction of the Van Allen Probes and Arase spacecraft. The inter‐calibration is based on a fortuitous case of common observations of strong whistlers at frequencies between a few hundred hertz and 10 kHz, which are generated by the same lightning strokes and which propagate along very similar paths to the two spacecraft. Measured amplitudes of the magnetic field fluctuations are the same within ∼14% precision of our analysis, corresponding to 1.2 dB. Currently, archived electric field measurements show twice larger amplitudes on Arase compared to Van Allen Probes but they start to match within ∼33% precision (2.5 dB) once the newest results on the interface of the antennas to the surrounding plasma are included in the calibration procedures. Ray tracing simulations help us to build a consistent scenario of wave propagation to both spacecraft reflected by a successful inter‐calibration of the polarization and propagation parameters obtained from multicomponent measurements. We succeed in linking the spacecraft observations to localizations of lightning return strokes by two different ground‐based networks which independently verify the correctness of the Universal Time tags of waveform measurements by both spacecraft missions, with an uncertainty better than 10 ms.
Key Points
Measurements of electromagnetic waves on Van Allen Probes and Arase are inter‐calibrated with intense whistlers during a close conjunction
Magnetic search coil measurements are the same within 14%, polarization and propagation parameters are consistent, timing is within 10 ms
Electric field amplitudes match within 33% when we include the newest results on antenna‐plasma interface with measured plasma densities
We have developed the automatic detection scheme for upper hybrid resonance (UHR) frequency using a convolutional neural network (CNN) from the electric field spectra obtained by the plasma wave ...experiment (PWE) aboard Arase. In this paper, we investigate the practical capability of this scheme in terms of actual scientific use case. We find that the average error rate is below 7.8% when the wave frequency is above 30 kHz and the wave spectral intensity is less than 10−5 mV 2/m2/Hz. About 91% of the data obtained by the high‐frequency analyzer (HFA) aboard the Arase satellite satisfies these conditions. To improve the accuracy of the determined UHR frequencies in a wide frequency range, we used another receiver, the onboard frequency analyzer (OFA), which enables us to detect low‐frequency UHR emissions. We confirmed that the averaged error rate derived by the OFA spectra becomes better than that derived from the HFA spectra in a frequency range below 20 kHz. We report the performance of the UHR frequency determination under the different geomagnetic conditions. We find that the UHR frequency can be determined with good accuracy using the CNN from the frequency‐time diagram both during geomagnetically quiet and disturbed conditions. We conclude that the CNN‐based UHR frequency determination is a reliable method to derive the electron density along the satellite orbit through observations of UHR frequencies, and this method contributes to studies on dynamics of the plasmasphere.
Plain Language Summary
Determining the upper hybrid resonance (UHR) frequency is the most popular way to determine the quantitative electron density in space. The high‐frequency analyzer (HFA) and onboard frequency analyzer (OFA) aboard the Arase satellite measure electric field spectra at high‐ and low‐frequency ranges. The nominal time resolutions of the HFA and OFA spectra are 8 and 1 s, respectively. Determining the UHR frequency by conventional visual inspection requires huge resources for researchers; therefore, some automatic determination methods have been proposed in recent years. In this study, we evaluate the accuracy of UHR frequency determination by convolutional neural networks (CNN). We find that the averaged error rate of the automatically determined UHR frequency is less than 7.8% for the most events (91% of the data set), and we conclude that the CNN‐based UHR frequency determination is the reliable method to estimate the electron density along the satellite orbit.
Key Points
We investigated the practical capability of the CNN‐based UHR frequency detection and found that the error is below 7.8% for most events
We successfully improved the accuracy of UHR frequency determination in a low‐frequency range by combining the OFA spectra
We confirmed that the UHR emissions in plasmasphere can be determined with good accuracy both during quiet and disturbance periods
Acrylic polymers have high potential as matrix polymers for carbon fiber reinforced thermoplastic polymers (CFRTP) due to their superior mechanical properties and the fact that they can be fabricated ...at relatively low temperatures. We focused on improving the interfacial adhesion between carbon fibers (CFs) and acrylic polymers using several functional monomers for co-polymerization with methyl methacrylate (MMA). The copolymerized acrylic matrices showed good adhesion to the CF surfaces. In particular, an acrylic copolymer with acrylamide (AAm) showed high interfacial adhesive strength with CFs compared to pure PMMA, and a hydroxyethyl acrylamide (HEAA) copolymer containing both amide and hydroxyl groups showed high flexural strength of the CFRTP. A 3 mol% HEAA-copolymerized CFRTP achieved a flexural strength almost twice that of pure PMMA matrix CFRTP, and equivalent to that of an epoxy matrix CFRP.
Pulsating auroras (PsAs) are thought to be generated by precipitating electrons scattered by lower‐band chorus (LBC) waves near the magnetic equator. One‐to‐one correlation between the LBC intensity ...and the PsA intensity has been reported. Electrostatic electron cyclotron harmonic (ECH) waves can also scatter electrons. However, direct correlation between ECH and PsA has not been reported yet. In this study, using a coordinated Exploration of energization and Radiation in Geospace (Arase) satellite and ground‐based imager observation, we report that not only LBC but also ECH have correlation with PsA. We estimated the precipitating electron energy by assuming that the time lag when the cross‐correlation coefficient became the highest was travel time of electrons from the modulation region. We found that the estimated energies show reasonable values as the cyclotron resonance energy of each wave.
Plain Language Summary
Pulsating auroras (PsAs), which have quasiperiodic on‐off switching emission, are caused by the intermittent electron precipitation from the magnetosphere. Such electrons are precipitated by wave‐particle interactions. The candidate waves to interact with electrons are lower‐band chorus (LBC) and electrostatic electron cyclotron harmonic (ECH) waves. One‐to‐one correspondence between the LBC wave intensity and the PsA intensity has been reported by previous studies. However, the correlation between ECH and PsA has not been reported yet. In this study, using a coordinated Exploration of energization and Radiation in Geospace (Arase) satellite and ground‐based all‐sky imager observation, we report that not only LBC but also ECH waves have correlation with PsAs.
Key Points
The lower‐band chorus and electrostatic electron cyclotron harmonic wave intensities had correlation with the pulsating auroral intensity
Taking advantage of high sampling rate of the imager, we estimated the energy of precipitating electrons
The energy of precipitating electrons was reasonable compared with the cyclotron resonance energy of each wave
Rheumatoid arthritis (RA) is known to cause secondary osteoporosis and fragility fractures. This study aimed to identify biomarkers predictive of bone mineral density (BMD) change at three anatomical ...sites in patients with RA.
We conducted a prospective longitudinal study in patients with RA. In 2012, we recruited 379 patients from an RA cohort, 329 of whom underwent evaluation of blood and urine biomarkers together with measurement of BMD in the lumbar spine, proximal femur, and distal forearm. The BMD in these three regions was reassessed in 2014. We performed multivariate linear regression analysis to identify those factors associated with BMD change.
The averages of age, body mass index, and disease activity score in 28 joints (DAS28) at baseline were 63.2 (minimum to maximum, 32-85), 21.3 (12.3-30.0), and 3.2 (0.1-5.9), respectively. Univariate analysis showed that the annual BMD change was significantly associated with the use of steroid, bisphosphonate (BP) or vitamin D (VitD), and serum homocysteine in the lumber spine; DAS28, the use of BP or VitD, CRP, and anti-cyclic citrullinated peptide antibody (ACPA) in the proximal femur; and the dosage of MTX, the use of BP or VitD, and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) in the distal forearm, respectively.
Predictive biomarkers for BMD change in RA patients differ at each anatomical site. Practitioners should treat each anatomical site with different markers and prescribe osteoporosis drugs to prevent fractures for RA patients.
We report on deformation of electron pitch angle distributions associated with upper band chorus observed by the Arase satellite. The deformation is characterized by flux increase of 17–30 keV ...electrons in a narrow and oblique pitch angle range (65–80°) and by flux decrease in 7–17 keV electron flux in the smaller pitch angle range than the flux increase. Comparison of change in electron pitch angle distributions with resonant ellipses of the upper band chorus shows that the deformation appears where effective wave‐particle interaction is expected in the velocity space, and the flux increase takes place along the resonant ellipse of the upper frequency of the wave. This strongly suggests that the deformation is a consequence of wave‐particle interactions between electrons and upper band chorus. The Arase observation demonstrates that the deformation occurs within 30 s, which is faster than expected from the quasi‐linear diffusion theory.
Plain Language Summary
Wave‐particle interaction is a fundamental and universal process in space plasmas. It has been suggested that whistler mode chorus waves play crucial roles in the acceleration and loss of energetic electrons in geospace. Numerical simulations have shown that electron distribution function is rapidly deformed by chorus waves in association with the wave generation, while clear observational support has not been presented. On 20 December 2016, the Exploration of energization and Radiation in Geospace (ERG; also called “Arase”) satellite was launched. Medium Energy Particle experiment‐electron analyzer (MEP‐e) onboard the Arase satellite is the newly developed particle detector, which measures electrons in the energy range of 7–87 keV with good energy and angular resolutions as well as high detection efficiency compared to previous instruments. Based on observations by MEP‐e, this paper shows that electron distribution function is rapidly deformed in association with the appearance of chorus emissions. In cooperation with the simultaneous plasma wave measurement, MEP‐e reveals that the deformation is likely to result from acceleration and loss of electrons by chorus waves. The observed distribution is similar to that seen in the simulation result, suggesting that MEP‐e captures rapid deformation of electron distribution functions by wave‐particle interactions.
Key Points
The Arase satellite observed deformation of electron pitch angle distributions in conjunction with upper band chorus
The deformation is characterized by increase in 17–30 keV electron fluxes and decrease in fluxes in lower energy range within 30 s
The deformation appears where wave‐particle interactions with electrons and upper band chorus is expected in the velocity space
Background
The aim of this study was to assess the long-term annual functional results and quality of life (QOL) after laparoscopic ventral rectopexy (LVR) for rectoanal intussusception (RAI) and/or ...rectocele.
Methods
This study was a retrospective analysis of prospectively collected data. The study was conducted on patients who underwent LVR for RAI and/or rectocele at our institution between February 2012 and July 2015. The Fecal Incontinence Severity Index (FISI), Constipation Scoring System (CSS), and QOL instruments (i.e., 36-item Short-form Health Survey SF-36, Patient Assessment of Constipation-QOL PAC-QOL scale, and Fecal Incontinence-QOL FIQL) were administered before and annually after surgery. The sustainability of substantial symptom improvement (reduction of at least 50% in CSS or FISI scores) postoperatively was evaluated.
Results
Fifty-one patients (median age 76 range 60–93 years, 48 women 94%) were analyzed. No mortality or major morbidity occurred. After a median follow-up of 60 months (range 12–84 months), no mesh-related complications occurred. The median CSS and FISI scores were significantly reduced at 1 year and remained significantly reduced for 7 years. In patients who reported symptom scores ≥ 3 times postoperatively, sustained improvement of constipation and fecal incontinence was found in about 50% (18/38) and 75% (26/35) of relevant patients, respectively. All PAC-QOL and FIQL scales significantly improved over time for 5 years. Of the SF-36 scales, four showed significant improvement at 1 year but none was significantly improved after 3 years, except for the social functioning scale.
Conclusions
LVR for RAI and/or rectocele was associated with low morbidity and long-term improvement in symptom-specific QOL. The sustainability of postoperative improvement in fecal incontinence was satisfactory, and that in constipation was fair.
PDF
