Background
Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our ...objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.
Methods
The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro.
Results
The patients were well‐controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL‐5, IL‐13 and IL‐9 in response to IL‐25, IL‐33 plus IL‐2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL‐5, IL‐13 and IL‐9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.
Conclusion
The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK‐STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.
High circulating ILC2s were found in asthma and asthma with allergic rhinitis patients, and significantly decreased after treatment of glucocorticoid. High levels of IL‐5, IL‐13 and IL‐9 in response to epithelium‐derived cytokines were mostly produced by the increased ILC2s from asthma patients. Glucocorticoid treatment is able to reverse the high levels of IL‐5 and IL‐13 produced by ILC2s via STAT3, STAT5 and STAT6 signalling pathways.
Background/Objectives
Endotoxin tolerance is characterized by a state of hyporesponsiveness after confrontation with endotoxins such as lipopolysaccharides (LPS) at low concentrations. The aim of ...this study was to investigate, whether pretreatment with Porphyromonas gingivalis leads to endotoxin tolerance induction and possible alterations in toll‐like receptor (TLR) 2‐ and 4‐induced response in human periodontal ligament cells (hPDLCs).
Material and Methods
Primary hPDLCs were pretreated with P. gingivalis (0.1 or 0.3 μg/mL) LPS for 24 hours and afterwards treated with one of the following stimuli: P. gingivalis LPS (1 μg/mL); TLR4 agonist Escherichia coli LPS (0.1 μg/mL; 1 μg/mL); TLR2 agonist Pam3CSK4 (0.1 μg/mL; 1 μg/mL). The protein expression of interleukin (IL)‐6, IL‐8 and monocyte chemotactic protein‐1 was analyzed with quantitative polymerase chain reaction and enzyme‐linked immunosorbent assay. Gene expression levels of TLR2 and TLR4 were determined by quantitative polymerase chain reaction.
Results
Pretreatment of cells with low concentrations of P. gingivalis LPS did not result in lower production of IL‐6, IL‐8 and monocyte chemotactic protein‐1 compared to control group. In some cases, pretreated cells exhibited lower gene expression levels of TLR2 and TLR4 compared to non‐pretreated cells.
Conclusion
The results of this study implicate that hPDLCs do not develop endotoxin tolerance. Furthermore, the amplitude of the inflammatory response shows no significant dependency on TLR2 and TLR4 expression levels.
Observations of a regular pulse burst (RPB) at the end of a K‐event are analyzed utilizing a simple geometric model and particle swarm optimization (PSO) to estimate the currents and propagation ...speeds of successive pulses of the RPB. The results show that the current of successive pulses is strongly overlapped and, for typical speeds of continuously propagating K‐events, are unphysically large (88 kA), exceeding the currents of most strokes to ground. By default, the unphysical nature of the result, coupled with very high frequency interferometer observations of an RPB in Florida, shows that the propagation speed of the pulses is significantly faster than expected, namely ∼0.6–1.8 × 108 m/s. This reduces the inferred current from 88 kA down to 6–18 kA, typical of intracloud events. The fast propagation speed of the stepping is explained by successive pulses retracing much of the path of the preceding pulses due to the successive pulses being strongly overlapped.
Plain Language Summary
Regular pulse bursts (RBP) are a spectacular phenomenon in lightning studies, in which rapidly propagating, conductive channels called K‐events transition from a smoothly and continually lengthening channel to an intermittent but regularly‐spaced stepping process, with each step producing a highly‐impulsive current and electric field change, or “sferic.” Here we introduce a new approach for analyzing sferic observations that models the K‐event as a series of successive segments, with the parameters of the current and extent of each pulse being determined by searching the multi‐dimensional parameter space that best fits the corresponding pulse waveforms. This was done using a process called PSO, and indicated that the RBP pulses were caused by a succession of overlapping fast breakdown events, but having unphysically strong currents. For the distant measurements of the study, the sferic amplitudes can determine only the product of current and propagation speed of the pulses, causing their current and speed values to be ambiguous. However, for the currents to have reasonable values, we are able to conclude that the speeds needed to be faster than assumed maximum value of 1.5 × 107 m/s value in the analysis. This contention is supported by observations of similar RPBs being studied by the authors.
Key Points
A new, innovative method is developed for estimating the currents and extents of fast electric field change pulses
The method is applied to the study of a regular pulse burst, showing that it consisted of a succession of fast overlapping events
The speed of the pulses is inferred to be significantly higher than that of continuously‐developing K‐leader
We utilize data from the 2010–2019 Consumer Expenditure Surveys to examine middle‐class achievement of English‐speaking and non‐English‐speaking Hispanic households compared to non‐Hispanic white ...households in the United States. Using an innovative expenditure‐based middle‐class measure, our findings show that non‐English‐speaking Hispanics lag English‐speaking Hispanics, and English‐speaking Hispanics lag whites, in middle‐class attainment. We also identify significant structural differences among the three groups, particularly in how education, marriage, and employment affect middle‐class achievement. Non‐English‐speaking Hispanics have a lower rate of return on education compared to both whites and English‐speaking Hispanics. Non‐English‐speaking Hispanics experience lower marriage and employment premiums compared to their English‐speaking Hispanic counterparts, and English‐speaking Hispanics experience lower marriage and employment premiums compared to whites. This study contributes to the literature by introducing the innovative expenditure‐based middle‐class measure and emphasizing the importance of considering within‐group differences among Hispanics to reduce the Hispanic‐white economic disparity.
In this study, we evaluated the effectiveness of thermotherapy in eliminating apple rubbery wood virus 2 (ARWV-2) in six infected apple varieties collected from regions in China. These plants were ...subjected to high-temperature treatment, followed by excision of shoot tips, which were subsequently grafted onto the rootstock. All varieties exhibited high thermostability, but the survival rates (average: 30.5%) of the shoot tips varied markedly. The regenerated plants were tested using semi-nested PCR; the results showed that the ARWV-2 elimination efficiencies differed greatly among the varieties. The elimination rates were > 80% for Baxianzaofu and Ruixue and < 50% for HL, Longkou no. 3, and Yishuihong. Notably, all surviving Longkou no. 3 plants remained infected with ARWV-2. The average ARWV-2 elimination efficiency was 44.3%, closely aligning with that of the apple stem pitting virus and apple stem grooving virus. This suggests that the presence of ARWV-2 may influence the ability of certain varieties to yield virus-free germplasm. Moreover, analysis of the ARWV-2 sequences from Baxianzaofu, Ruixue, Longkou no. 3, and Yishuihong revealed that the elimination rate exhibited minimal correlation with the virus diversity. The consistency and identity of the different variants within the same isolates or among the four isolates were high. Our findings can serve as a valuable foundation for developing treatment strategies to address ARWV-2 infections.
Quasars (QSOs) at the highest known redshift (z ~ 6) are unique probes of the early growth of supermassive black holes (BHs). Until now, only the most luminous QSOs have been studied, often one ...object at a time. Here we present the most extensive consistent analysis to date of 4 < z < 6.5 QSOs with observed near-infrared spectra, combining three new z ~ 6 objects from our ongoing Very Large Telescope-Infrared Spectrometer And Array Camera program with nineteen sources from the literature. The new sources extend the existing Sloan Digital Sky Survey (SDSS) sample toward the faint end of the QSO luminosity function. Using a maximum likelihood fitting routine optimized for our spectral decomposition, we estimate the BH mass (M BH), the Eddington ratio (defined as L bol/L Edd), and the Fe II/Mg II line ratio, a proxy for the chemical abundance, to characterize both the central object and the broad-line region gas. The QSOs in our sample host BHs with masses of ~109 M that are accreting close to the Eddington luminosity, consistent with earlier results. We find that the distribution of observed Eddington ratios is significantly different than that of a luminosity-matched comparison sample of SDSS QSOs at lower redshift (0.35 < z < 2.25): the average log (L bol/L Edd) = --0.37 (L bol/L Edd ~ 0.43) with a scatter of 0.20 dex for the z > 4 sample and the log (L bol/L Edd) = --0.80 (L bol/L Edd ~ 0.16) with a scatter of 0.24 dex for the 0.35 < z < 2.25 sample. This implies that, at a given luminosity, the M BH at high-z is typically lower than the average M BH of the lower-redshift population, i.e., the z > 4 sources are accreting significantly faster than the lower-redshift ones. We show that the derived Fe II/Mg II ratios depend sensitively on the analysis performed: our self-consistent, homogeneous analysis significantly reduces the Fe II/Mg II scatter found in previous studies. The measured Fe II/Mg II line ratios show no sign of evolution with cosmic time in the redshift range 4 < z < 6.5. If the Fe II/Mg II line ratio is used as a secondary proxy of the Fe/Mg abundance ratio, this implies that the QSOs in our sample have undergone a major episode of Fe enrichment in the few 100 Myr preceding the cosmic age at which they are observed.
Smoothed particle hydrodynamics (SPH) has been widely applied in simulating fluid flow because of its attractive properties, for example, it is fully Lagrangian and mesh free. However, this method ...usually uses the explicit method to solve the conservation equations and in this form it is only suitable to momentum dominated flows with low viscosity. In polymer processing, the fluid is non-Newtonian with high viscosity, O(10
3) to O(10
4)
Pa-s say, and the pressure is high as O(10
6) to O(10
10)
Pa. The algorithm of the standard SPH is infeasible in this case, because only very small time steps can be used for a stable simulation. We have developed an implicit SPH for non-Newtonian flow, which is completely matrix free, to solve the equation system iteratively and robustly. The artificial pressure is introduced between particles to stabilize the SPH system avoiding the tensile instability. The fluid is compressible under high pressure. Realistic state equations for polymers, such as the Tait and SSY
16 equations are adopted to describe the density/pressure relations. The method is finally applied to the simulation of moulding flow of a modified power law fluid with the zero shear rate viscosity of 1.22
×
10
4
Pa-s, Reynolds number of 3
×
10
−4 to 6
×
10
−5 and the highest pressure of O(10
8) to O(10
10)
Pa.
We present Searches After Gravitational-waves Using ARizona Observatories (SAGUARO), a comprehensive effort dedicated to the discovery and characterization of optical counterparts to ...gravitational-wave (GW) events. SAGUARO utilizes ground-based facilities ranging from 1.5 to 10 m in diameter, located primarily in the Northern Hemisphere. We provide an overview of SAGUARO's telescopic resources, its pipeline for transient detection, and its database for candidate visualization. We describe SAGUARO's discovery component, which utilizes the 5 deg2 field of view optical imager on the Mt. Lemmon 1.5 m telescope, reaching limits of 21.3 AB mag while rapidly tiling large areas. We also describe the follow-up component of SAGUARO, used for rapid vetting and monitoring of optical candidates. With the onset of Advanced LIGO/Virgo's third observing run, we present results from the first three SAGUARO searches following the GW events S190408an, S190425z and S190426c, which serve as a valuable proof-of-concept of SAGUARO. We triggered and searched 15, 60, and 60 deg2 respectively, 17.6, 1.4, and 41.8 hr after the initial GW alerts. We covered 7.8%, 3.0%, and 5.1% of the total probability within the GW event localizations, reaching 3 limits of 19.8, 21.3, and 20.8 AB mag, respectively. Although no viable counterparts associated with these events were found, we recovered six known transients and ruled out five potential candidates. We also present Large Binocular Telescope spectroscopy of PS19eq/SN2019ebq, a promising kilonova candidate that was later determined to be a supernova. With the ability to tile large areas and conduct detailed follow-up, SAGUARO represents a significant addition to GW counterpart searches.
PDF
