Potential Inhibitory Influence of miRNA 210 on Regulatory T Cells during Epicutaneous Chemical Sensitization

Toluene diisocyanate (TDI) is a potent low molecular weight chemical sensitizer and a leading cause of chemical-induced occupational asthma. The regulatory potential of microRNAs (miRNAs) has been recognized in a variety of disease states, including allergic disease; however, the roles of miRNAs in chemical sensitization are largely unknown. In a previous work, increased expression of multiple miRNAs during TDI sensitization was observed and several putative mRNA targets identified for these miRNAs were directly related to regulatory T-cell (Treg) differentiation and function including Foxp3 and Runx3. In this work, we show that miR-210 expression is increased in the mouse draining lymph node (dLN) and Treg subsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of Treg related genes/putative miR-210 targets (foxp3, runx3, ctla4, and cd25) were observed at multiple time points following TDI exposure and in ex vivo systems. A Treg suppression assay, including a miR-210 mimic, was utilized to investigate the suppressive ability of Tregs. Cells derived from TDI sensitized mice treated with miR-210 mimic had less expression of miR-210 compared to the acetone control suggesting other factors, such as additional miRNAs, might be involved in the regulation of the functional capabilities of these cells. These novel findings indicate that miR-210 may have an inhibitory role in Treg function during TDI sensitization. Because the functional roles of miRNAs have not been previously elucidated in a model of chemical sensitization, these data contribute to the understanding of the potential immunologic mechanisms of chemical induced allergic disease

LEGUS Discovery of a Light Echo Around Supernova 2012aw

We have discovered a luminous light echo around the normal Type II-Plateau Supernova (SN) 2012aw in Messier 95 (M95; NGC 3351), detected in images obtained approximately two years after explosion with the Wide Field Channel 3 on-board the Hubble Space Telescope (HST) by the Legacy ExtraGalactic Ultraviolet Survey (LEGUS). The multi-band observations span from the near-ultraviolet through the optical (F275W, F336W, F438W, F555W, and F814W). The apparent brightness of the echo at the time was ~21--22 mag in all of these bands. The echo appears circular, although less obviously as a ring, with an inhomogeneous surface brightness, in particular, a prominent enhanced brightness to the southeast. The SN itself was still detectable, particularly in the redder bands. We are able to model the light echo as the time-integrated SN light scattered off of diffuse interstellar dust in the SN environment. We have assumed that this dust is analogous to that in the Milky Way with R_V=3.1. The SN light curves that we consider also include models of the unobserved early burst of light from the SN shock breakout. Our analysis of the echo suggests that the distance from the SN to the scattering dust elements along the echo is ~45 pc. The implied visual extinction for the echo-producing dust is consistent with estimates made previously from the SN itself. Finally, our estimate of the SN brightness in F814W is fainter than that measured for the red supergiant star at the precise SN location in pre-SN images, possibly indicating that the star has vanished and confirming it as the likely SN progenitor.Comment: 10 pages, 9 figures, to appear in the Astrophysical Journa

Topical application of the anti-microbial chemical triclosan induces immunomodulatory responses through the S100A8/A9-TLR4 pathway

The anti-microbial compound triclosan is incorporated into numerous consumer products and is detectable in the urine of 75% of the general United States population. Recent epidemiological studies report positive associations with urinary triclosan levels and allergic disease. Although not sensitizing, earlier studies previously found that repeated topical application of triclosan augments the allergic response to ovalbumin (OVA) though a thymic stromal lymphopoietin (TSLP) pathway in mice. In the present study, early immunological effects following triclosan exposure were further evaluated following topical application in a murine model. These investigations revealed abundant expression of S100A8/A9, which reportedly acts as an endogenous ligand for Toll-like Receptor 4 (TLR4), in skin tissues and in infiltrating leukocytes during topical application of 0.75–3.0% triclosan. Expression of Tlr4 along with Tlr1, Tlr2 and Tlr6 increased in skin tissues over time with triclosan exposure; high levels of TLR4 were expressed on skin-infiltrating leukocytes. In vivo antibody blockade of the TLR4/MD-2 receptor complex impaired local inflammatory responses after four days, as evidenced by decreased Il6, Tnfα, S100a8, S100a9, Tlr1, Tlr2, Tlr4 and Tlr6 expression in the skin and decreased lymph node cellularity and production of IL-4 and IL-13 by lymph node T-cells. After nine days of triclosan exposure with TLR4/MD-2 blockade, impaired T-helper cell type 2 (TH2) cytokine responses were sustained, but other early effects on skin and lymph node cellularity were lost; this suggested alternative ligands/receptors compensated for the loss of TLR4 signaling. Taken together, these data suggest the S100A8/A9-TLR4 pathway plays an early role in augmenting immunomodulatory responses with triclosan exposure and support a role for the innate immune system in chemical adjuvancy

A k-shell decomposition method for weighted networks

We present a generalized method for calculating the k-shell structure of weighted networks. The method takes into account both the weight and the degree of a network, in such a way that in the absence of weights we resume the shell structure obtained by the classic k-shell decomposition. In the presence of weights, we show that the method is able to partition the network in a more refined way, without the need of any arbitrary threshold on the weight values. Furthermore, by simulating spreading processes using the susceptible-infectious-recovered model in four different weighted real-world networks, we show that the weighted k-shell decomposition method ranks the nodes more accurately, by placing nodes with higher spreading potential into shells closer to the core. In addition, we demonstrate our new method on a real economic network and show that the core calculated using the weighted k-shell method is more meaningful from an economic perspective when compared with the unweighted one.Comment: 17 pages, 6 figure

Just enough structure at the edge of chaos: Agile information system development in practice

Agile information systems development is not well understood and suffers from a lack of sustainable theories, which are based on empirical research of practice. We use a framework that focuses on the ‘edge of chaos’ as the area, where agile information systems development takes place to fill in this gap. Our study identifies for a concrete project under investigation, where the beneficial balance between stability and instability lies. It discusses the circumstances, which influence this balance and the relationships of the elements, which constitute it

Impacts of ambient air quality on acute asthma hospital admissions during the COVID-19 pandemic in Oxford City, UK:a time-series study

OBJECTIVES: The study aims to investigate the short-term associations between exposure to ambient air pollution (nitrogen dioxide (NO2), particulate matter pollution-particles with diameter&lt;2.5 µm (PM2.5) and PM10) and incidence of asthma hospital admissions among adults, in Oxford, UK.DESIGN: Retrospective time-series study.SETTING: Oxford City (postcode areas OX1-OX4), UK.PARTICIPANTS: Adult population living within the postcode areas OX1-OX4 in Oxford, UK from 1 January 2015 to 31 December 2021.PRIMARY AND SECONDARY OUTCOME MEASURES: Hourly NO2, PM2.5 and PM10 concentrations and meteorological data for the period 1 January 2015 to 31 December 2020 were analysed and used as exposures. We used Poisson linear regression analysis to identify independent associations between air pollutant concentrations and asthma admissions rate among the adult study population, using both single (NO2, PM2.5, PM10) and multipollutant (NO2 and PM2.5, NO2 and PM10) models, where they adjustment for temperature and relative humidity.RESULTS: The overall 5-year average asthma admissions rate was 78 per 100 000 population during the study period. The annual average rate decreased to 46 per 100 000 population during 2020 (incidence rate ratio 0.58, 95% CI 0.42 to 0.81, p&lt;0.001) compared to the prepandemic years (2015-2019). In single-pollutant analysis, we observed a significantly increased risk of asthma admission associated with each 1 μg/m3 increase in monthly concentrations of NO2 4% (95% CI 1.009% to 1.072%), PM2.5 3% (95% CI 1.006% to 1.052%) and PM10 1.8% (95% CI 0.999% to 1.038%). However, in the multipollutant regression model, the effect of each individual pollutant was attenuated.CONCLUSIONS: Ambient NO2 and PM2.5 air pollution exposure increased the risk of asthma admissions in this urban setting. Improvements in air quality during COVID-19 lockdown periods may have contributed to a substantially reduced acute asthma disease burden. Large-scale measures to improve air quality have potential to protect vulnerable people living with chronic asthma in urban areas.</p

Willing suspension of disbelief: a study in online learning through simulation, and its potential for deeper learning in Higher Education

This article describes the replacement of a 'traditionally taught' law of probate course (lectures and workshops/tutorials) with an on-line collaborative learning exercise using simulation and role-play which is referred to hereafter as the Transactional Learning Project ('TLP'). The article considers the theory that the emotional engagement that comes about through role play in simulation leads to deeper learning, a process Maharg (2010) has dubbed as the 'integration of the cognitive and the affective'. The article includes statistical analysis of student feedback on the TLP in an attempt to measure how easy it is to carry students predisposed to expect information to be 'given' rather than 'acquired' along the journey leading away from traditional didactic teaching. The project was motivated partly by the dearth of such learning practices on the Legal Practice Course. It is suggested that the findings of the project add to the body of research which tends to illustrate the success in terms of student learning from working in leaderless (i.e. where the tutor is absent from the collaborative group) groups engaged in practical tasks involving simulation

Geophysical constraints on mirror matter within the Earth

We have performed a detailed investigation of geophysical constraints on the possible admixture of mirror matter inside the Earth. On the basis of the Preliminary Reference Earth Model (PREM) -- the `Standard Model' of the Earth's interior -- we have developed a method which allows one to compute changes in various quantities characterising the Earth (mass, moment of inertia, normal mode frequencies etc.)due to the presence of mirror matter. As a result we have been able to obtain for the first time the direct upper bounds on the possible concentration of the mirror matter in the Earth. In terms of the ratio of the mirror mass to the Earth mass a conservative upper bound is $3.8\times 10^{-3}$. We then analysed possible mechanisms (such as lunar and solar tidal forces, meteorite impacts and earthquakes) of exciting mirror matter oscillations around the Earth centre. Such oscillations could manifest themselves through global variations of the gravitational acceleration at the Earth's surface. We conclude that such variations are too small to be observed. Our results are valid for other types of hypothetical matter coupled to ordinary matter by gravitation only (e.g. the shadow matter of superstring theories).Comment: 25 pages, in RevTeX, to appear in Phys.Rev.

Optimizing patient care and outcomes through the congenital heart center of the 21st century

Pediatric cardiovascular services are responding to the dynamic changes in the medical environment, including the business of medicine. The opportunity to advance our pediatric cardiology field through collaboration is now realized, permitting us to define meaningful quality metrics and establish national benchmarks through multicenter efforts. In March 2016, the American College of Cardiology hosted the first Adult Congenital/Pediatric Cardiology Section Congenital Heart Community Day. This was an open participation meeting for clinicians, administrators, patients/parents to propose metrics that optimize patient care and outcomes for a stateâ ofâ theâ art congenital heart center of the 21st century. Care center collaboration helps overcome the barrier of relative small volumes at any given program. Patients and families have become active collaborative partners with care centers in the definition of acute and longitudinal outcomes and our quality metrics. Understanding programmatic metrics that create an environment to provide outstanding congenital heart care will allow centers to improve their structure, processes and ultimately outcomes, leading to an increasing number of centers that provide excellent care. This manuscript provides background, as well listing of proposed specialty domain quality metrics for centers, and thus serves as an updated baseline for the ongoing dynamic process of optimizing care and realizing patient value.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143653/1/chd12575_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143653/2/chd12575.pd