Analysis of Sun photometer measured and satellite retrieved aerosol optical depth (AOD) datahas shown that major aerosol pollution events with very highfine mode AOD (>1.0 in midvisible) in ...theChina/Korea/Japan region are often observed to be associated with significant cloud cover. This makesremote sensing of these events difficult even for high temporal resolution Sun photometer measurements.Possible physical mechanisms for these events that have high AOD include a combination of aerosolhumidification, cloud processing, and meteorological covariation with atmospheric stability andconvergence. The new development of Aerosol Robotic Network Version 3 Level 2 AOD with improved cloudscreening algorithms now allow for unprecedented ability to monitor these extremefine mode pollutionevents. Further, the spectral deconvolution algorithm (SDA) applied to Level 1 data (L1; no cloud screening)provides an even more comprehensive assessment offine mode AOD than L2 in current and previous dataversions. Studying the 2012 winter-summer period, comparisons of Aerosol Robotic Network L1 SDA dailyaveragefine mode AOD data showed that Moderate Resolution Imaging Spectroradiometer satellite remotesensing of AOD often did not retrieve and/or identify some of the highestfine mode AOD events in thisregion. Also, compared to models that include data assimilation of satellite retrieved AOD, the L1 SDAfinemode AOD was significantly higher in magnitude, particularly for the highest AOD events that were oftenassociated with significant cloudiness.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle ...cumulants, v_{2}{2} and v_{2}{4}, for charged hadrons from U+U collisions at sqrts_{NN}=193 GeV and Au+Au collisions at sqrts_{NN}=200 GeV. Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs). Within this sample, the observed dependence of v_{2}{2} on multiplicity demonstrates that ZDC information combined with multiplicity can preferentially select different overlap configurations in U+U collisions. We also show that v_{2} vs multiplicity can be better described by models, such as gluon saturation or quark participant models, that eliminate the dependence of the multiplicity on the number of binary nucleon-nucleon collisions.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and vitreous. Here, ...an inhibitor responsible for the avascularity of these ocular compartments is identified as pigment epithelium-derived factor (PEDF), a protein previously shown to have neurotrophic activity. The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization. These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
BackgroundA double-blind, placebo-controlled trial that involved 38,546 subjects ⩾60 years old demonstrated efficacy of a high-potency live-attenuated Oka/Merck varicella-zoster virus (VZV) vaccine. ...The trial included an immunology substudy to determine the relationship of VZV-specific immune responses to vaccination and clinical outcome MethodsThe immunology substudy enrolled 1395 subjects at 2 sites where blood samples obtained prior to vaccination, at 6 weeks after vaccination, and at 1, 2, and 3 years thereafter were tested for VZV-specific cell-mediated immunity (VZV-CMI) by γ-interferon ELISPOT and responder cell frequency assays and for VZV antibody by glycoprotein ELISA ResultsVZV-CMI and VZV antibodies were significantly increased in vaccine recipients at 6 weeks after vaccination. The vaccine-induced increases in VZV-CMI persisted during the 3 years of follow-up, although their magnitude decreased over time. The magnitude of these VZV-specific immune responses was greater in subjects 60–69 years old than in subjects ⩾70 years old ConclusionsThe zoster vaccine induced a significant increase in VZV-CMI and VZV antibody. The magnitude and duration of the boost in VZV-CMI in vaccine recipients and the relationship of this boost to age paralleled the clinical effects of the vaccine observed during the efficacy trial. These findings support the hypothesis that boosting VZV-CMI protects older adults against herpes zoster and postherpetic neuralgia
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Bone destruction is the most frequent disease-defining clinical feature of multiple myeloma (MM), resulting in skeletal-related events such as back pain, pathological fractures, or neurologic ...compromise including epidural spinal cord compression (ESCC). Up to 24% of patients with MM will be affected by ESCC. Radiation therapy has been proven to be highly effective in pain relief in patients with MM. However, a critical knowledge gap remains with regard to neurologic outcomes in patients with high-grade ESCC treated with radiation.
We retrospectively included 162 patients with MM and high-grade ESCC (grade 2 or 3) who underwent radiation therapy of the spine between January 2010 and July 2021. The primary outcome was the American Spinal Injury Association (ASIA) score after 12 to 24 months, or the last known ASIA score if the patient had had a repeat treatment or died. Multivariable logistic regression was used to assess factors associated with poor neurologic outcomes after radiation, defined as neurologic deterioration or lack of improvement.
After radiation therapy, 34 patients (21%) had no improvement in their impaired neurologic function and 27 (17%) deteriorated neurologically. Thirty-six patients (22%) underwent either surgery or repeat irradiation after the initial radiation therapy. There were 100 patients who were neurologically intact at baseline (ASIA score of E), of whom 16 (16%) had neurologic deterioration. Four variables were independently associated with poor neurologic outcomes: baseline ASIA (odds ratio OR = 6.50; 95% confidence interval CI = 2.70 to 17.38; p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 6.19; 95% CI = 1.49 to 29.49; p = 0.015), number of levels affected by ESCC (OR = 4.02; 95% CI = 1.19 to 14.18; p = 0.026), and receiving steroids prior to radiation (OR = 4.42; 95% CI = 1.41 to 16.10; p = 0.015).
Our study showed that 38% of patients deteriorated or did not improve neurologically after radiation therapy for high-grade ESCC. The results highlight the need for multidisciplinary input and efforts in the treatment of high-grade ESCC in patients with MM. Future studies will help to improve patient selection for specific and standardized treatments and to clearly delineate which patients are likely to benefit from radiation therapy.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
New-particle formation in the plumes of coal-fired power plants and other anthropogenic sulfur sources may be an important source of particles in the atmosphere. It remains unclear, however, how best ...to reproduce this formation in global and regional aerosol models with grid-box lengths that are 10s of kilometers and larger. The predictive power of these models is thus limited by the resultant uncertainties in aerosol size distributions. In this paper, we focus on sub-grid sulfate aerosol processes within coal-fired power plant plumes: the sub-grid oxidation of SO2 with condensation of H2SO4 onto newly-formed and pre-existing particles. We have developed a modeling framework with aerosol microphysics in the System for Atmospheric Modelling (SAM), a Large-Eddy Simulation/Cloud-Resolving Model (LES/CRM). The model is evaluated against aircraft observations of new-particle formation in two different power-plant plumes and reproduces the major features of the observations. We show how the downwind plume aerosols can be greatly modified by both meteorological and background aerosol conditions. In general, new-particle formation and growth is greatly reduced during polluted conditions due to the large pre-existing aerosol surface area for H2SO4 condensation and particle coagulation. The new-particle formation and growth rates are also a strong function of the amount of sunlight and NOx since both control OH concentrations. The results of this study highlight the importance for improved sub-grid particle formation schemes in regional and global aerosol models.
Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the ...function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC. Multiplex immunohistochemistry shows low MHC class I (MHCI) expression and lack of CD8
T cell infiltration in PGRN-high tumors. Inhibition of PGRN abrogates autophagy-dependent MHCI degradation and restores MHCI expression on PDAC cells. Antibody-based blockade of PGRN in a PDAC mouse model remarkably decelerates tumor initiation and progression. Notably, tumors expressing LCMV-gp33 as a model antigen are sensitized to gp33-TCR transgenic T cell-mediated cytotoxicity upon PGRN blockade. Overall, our study shows a crucial function of tumor-derived PGRN in regulating immunogenicity of primary PDAC.
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