Activating transcription factor 3 is a negative regulator of allergic pulmonary inflammation

We recently demonstrated the pivotal role of the transcription factor (TF) activating TF 3 (ATF3) in dampening inflammation. We demonstrate that ATF3 also ameliorates allergen-induced airway inflammation and hyperresponsiveness in a mouse model of human asthma. ATF3 expression was increased in the lungs of mice challenged with ovalbumin allergen, and this was associated with its recruitment to the promoters of genes encoding Th2-associated cytokines. ATF3-deficient mice developed significantly increased airway hyperresponsiveness, pulmonary eosinophilia, and enhanced chemokine and Th2 cytokine responses in lung tissue and in lung-derived CD4+ lymphocytes. Although several TFs have been associated with enhanced inflammatory responses in the lung, ATF3 attenuates the inflammatory responses associated with allergic airway disease

Toward Composite Pain Biomarkers of Neuropathic Pain—Focus on Peripheral Neuropathic Pain

Chronic pain affects ~10–20% of the U.S. population with an estimated annual cost of $600 billion, the most significant economic cost of any disease to-date. Neuropathic pain is a type of chronic pain that is particularly difficult to manage and leads to significant disability and poor quality of life. Pain biomarkers offer the possibility to develop objective pain-related indicators that may help diagnose, treat, and improve the understanding of neuropathic pain pathophysiology. We review neuropathic pain mechanisms related to opiates, inflammation, and endocannabinoids with the objective of identifying composite biomarkers of neuropathic pain. In the literature, pain biomarkers typically are divided into physiological non-imaging pain biomarkers and brain imaging pain biomarkers. We review both types of biomarker types with the goal of identifying composite pain biomarkers that may improve recognition and treatment of neuropathic pain

The role of biophysical cohesion on subaqueous bed form size

Biologically active, fine-grained sediment forms abundant sedimentary deposits on Earth's surface, and mixed mud-sand dominates many coasts, deltas, and estuaries. Our predictions of sediment transport and bed roughness in these environments presently rely on empirically based bed form predictors that are based exclusively on biologically inactive cohesionless silt, sand, and gravel. This approach underpins many paleoenvironmental reconstructions of sedimentary successions, which rely on analysis of cross-stratification and bounding surfaces produced by migrating bed forms. Here we present controlled laboratory experiments that identify and quantify the influence of physical and biological cohesion on equilibrium bed form morphology. The results show the profound influence of biological cohesion on bed form size and identify how cohesive bonding mechanisms in different sediment mixtures govern the relationships. The findings highlight that existing bed form predictors require reformulation for combined biophysical cohesive effects in order to improve morphodynamic model predictions and to enhance the interpretations of these environments in the geological record

The Multi-Object, Fiber-Fed Spectrographs for SDSS and the Baryon Oscillation Spectroscopic Survey

We present the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999 on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II surveys, enabling a wide variety of Galactic and extra-galactic science including the first observation of baryon acoustic oscillations in 2005. The spectrographs were upgraded in 2009 and are currently in use for BOSS, the flagship survey of the third-generation SDSS-III project. BOSS will measure redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha absorption of 160,000 high redshift quasars over 10,000 square degrees of sky, making percent level measurements of the absolute cosmic distance scale of the Universe and placing tight constraints on the equation of state of dark energy. The twin multi-object fiber spectrographs utilize a simple optical layout with reflective collimators, gratings, all-refractive cameras, and state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in two channels over a bandpass covering the near ultraviolet to the near infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven heritage, the spectrographs were upgraded for BOSS with volume-phase holographic gratings and modern CCD detectors, improving the peak throughput by nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000 nm, and increasing the number of fibers from 640 to 1000 per exposure. In this paper we describe the original SDSS spectrograph design and the upgrades implemented for BOSS, and document the predicted and measured performances.Comment: 43 pages, 42 figures, revised according to referee report and accepted by AJ. Provides background for the instrument responsible for SDSS and BOSS spectra. 4th in a series of survey technical papers released in Summer 2012, including arXiv:1207.7137 (DR9), arXiv:1207.7326 (Spectral Classification), and arXiv:1208.0022 (BOSS Overview

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Acid gases and aerosol measurements in the UK (1999–2015): regional distributions and trends

The UK Acid Gases and Aerosol Monitoring Network (AGANet) was established in 1999 (12 sites, increased to 30 sites from 2006), to provide long-term national monitoring of acid gases (HNO3, SO2, HCl) and aerosol components (NO3-, SO42-, Cl-, Na+, Ca2+, Mg2+). An extension of a low-cost denuder-filter pack system (DELTA) that is used to measure NH3 and NH4+ in the UK National Ammonia Monitoring Network (NAMN) provides additional monthly speciated measurements for the AGANet. A comparison of the monthly DELTA measurement with averaged daily results from an annular denuder system showed close agreement, while the sum of HNO3 and NO3- and the sum of NH3 and NH4+ from the DELTA are also consistent with previous filter pack determination of total inorganic nitrogen and total inorganic ammonium, respectively. With the exception of SO2 and SO42-, the AGANet provides for the first time the UK concentration fields and seasonal cycles for each of the other measured species. The largest concentrations of HNO3, SO2, and aerosol NO3- and SO42- are found in south and east England and smallest in western Scotland and Northern Ireland, whereas HCl are highest in the southeast, southwest and central England, that may be attributed to dual contribution from anthropogenic (coal combustion) and marine sources (reaction of sea salt with acid gases to form HCl). Na+ and Cl- are spatially correlated, with largest concentrations at coastal sites, reflecting a contribution from sea salt. Temporally, peak concentrations in HNO3 occurred in late winter and early spring attributed to photochemical processes. NO3- and SO42- have a spring maxima that coincides with the peak in concentrations of NH3 and NH4+, and are therefore likely attributable to formation of NH4NO3 and (NH4)2SO4 from reaction with higher concentrations of NH3 in spring. By contrast, peak concentrations of SO2, Na+ and Cl- during winter are consistent with combustion sources for SO2 and marine sources in winter for sea salt aerosol. Key pollutant events were captured by the AGANet. In 2003, a spring episode with elevated concentrations of HNO3 and NO3¬- was driven by meteorology and transboundary transport of NH4NO3 from Europe. A second, but smaller episode occurred in September 2014, with elevated concentrations of SO2, HNO3, SO42-, NO3- and NH4+ that was shown to be from the Icelandic Holuhraun volcanic eruptions. Since 1999, AGANet has shown substantial decrease in SO2 concentrations relative to HNO3 and NH3, consistent with estimated decline in UK emissions. At the same time, large reductions and changes in the aerosol components provides evidence of a shift in the particulate phase from (NH4)2SO4 to NH4NO3. The potential for NH4NO3 to release NH3 and HNO3 in warm weather, together with the surfeit of NH3 also means that a larger fraction of the reduced and oxidised N is remaining in the gas phase as NH3 and HNO3 as indicated by the increasing trend in ratios of NH3:NH4+ and HNO3:NO3- over the 16 year period. Due to different removal rates of the component species by wet and dry deposition, this change is expected to affect spatial patterns of pollutant deposition with consequences for sensitive habitats with exceedance of critical loads of acidity and eutrophication. The changes are also relevant for human health effects assessment, particularly in urban areas as NH4NO3 constitutes a significant fraction of fine particulate matter (< 2.5 µm) that are linked to increased mortality from respiratory and cardiopulmonary diseases

Identification of Tuberculosis Susceptibility Genes with Human Macrophage Gene Expression Profiles

Although host genetics influences susceptibility to tuberculosis (TB), few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of Mycobacterium tuberculosis (Mtb) infection would have distinct gene expression profiles and that polymorphisms in these genes may also be associated with susceptibility to TB. We measured gene expression levels of >38,500 genes from ex vivo Mtb-stimulated macrophages in 12 subjects with 3 clinical phenotypes: latent, pulmonary, and meningeal TB (n = 4 per group). After identifying differentially expressed genes, we confirmed these results in 34 additional subjects by real-time PCR. We also used a case-control study design to examine whether polymorphisms in differentially regulated genes were associated with susceptibility to these different clinical forms of TB. We compared gene expression profiles in Mtb-stimulated and unstimulated macrophages and identified 1,608 and 199 genes that were differentially expressed by >2- and >5-fold, respectively. In an independent sample set of 34 individuals and a subset of highly regulated genes, 90% of the microarray results were confirmed by RT-PCR, including expression levels of CCL1, which distinguished the 3 clinical groups. Furthermore, 6 single nucleotide polymorphisms (SNPs) in CCL1 were found to be associated with TB in a case-control genetic association study with 273 TB cases and 188 controls. To our knowledge, this is the first identification of CCL1 as a gene involved in host susceptibility to TB and the first study to combine microarray and DNA polymorphism studies to identify genes associated with TB susceptibility. These results suggest that genome-wide studies can provide an unbiased method to identify critical macrophage response genes that are associated with different clinical outcomes and that variation in innate immune response genes regulate susceptibility to TB

The diffusion of financial supervisory governance ideas

Who is watching the financial services industry? Since 1980, there have been multiple waves of thought about whether the ministry of finance, the central bank, a specialized regulator or some combination of these should have supervisory authority. These waves have been associated with the convergence of actual practices. How much and through what channels did internationally promoted ideas about supervisory 'best practice' influence institutional design choices? I use a new dataset of 83 countries and jurisdictions between the 1980s and 2007 to examine the diffusion of supervisory ideas. With this data, I employ Cox Proportional Hazard and Competing Risks Event History Analyses to evaluate the possible causal roles best practice policy ideas might have played. I find that banking crises and certain peer groups can encourage policy convergence on heavily promoted ideas