Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis.

In several species caloric restriction (CR) extends life span. In this paper we integrate data from studies on CR and other sources to articulate the hypothalamic deregulation hypothesis by which estrogen receptor-alpha (ER-α) signaling in the hypothalamus and limbic system affects life span under the stress of CR in mammals. ER-α is one of two principal estrogen-binding receptors differentially expressed in the amygdala, hippocampus, and several key hypothalamic nuclei: the arcuate nucleus (ARN), preoptic area (POA), ventromedial nucleus (VMN), antero ventral periventricular nucleus (AVPV), paraventricular nucleus (PVN), supraoptic nucleus (SON), and suprachiasmatic nucleus (SCN). Estradiol signaling via ER-α is essential in basal level functioning of reproductive cycle, sexually receptive behaviors, physiological stress responses, as well as sleep cycle, and other nonsexual behaviors. When an organism is placed under long-term CR, which introduces an external stress to this ER-α signaling, the reduction of ER-α expression is attenuated over time in the hypothalamus. This review paper seeks to characterize the downstream effects of ER-α in the hypothalamus and limbic system that affect normal endocrine functioning

Determination of urban volatile organic compound emission ratios and comparison with an emissions database

During the NEAQS-ITCT2k4 campaign in New England, anthropogenic VOCs and CO were measured downwind from New York City and Boston. The emission ratios of VOCs relative to CO and acetylene were calculated using a method in which the ratio of a VOC with acetylene is plotted versus the photochemical age. The intercept at the photochemical age of zero gives the emission ratio. The so determined emission ratios were compared to other measurement sets, including data from the same location in 2002, canister samples collected inside New York City and Boston, aircraft measurements from Los Angeles in 2002, and the average urban composition of 39 U.S. cities. All the measurements generally agree within a factor of two. The measured emission ratios also agree for most compounds within a factor of two with vehicle exhaust data indicating that a major source of VOCs in urban areas is automobiles. A comparison with an anthropogenic emission database shows less agreement. Especially large discrepancies were found for the C2-C4 alkanes and most oxygenated species. As an example, the database overestimated toluene by almost a factor of three, which caused an air quality forecast model (WRF-CHEM) using this database to overpredict the toluene mixing ratio by a factor of 2.5 as well. On the other hand, the overall reactivity of the measured species and the reactivity of the same compounds in the emission database were found to agree within 30%. Copyright 2007 by the American Geophysical Union

Quicksort Revisited: Verifying Alternative Versions of Quicksort

© Springer International Publishing Switzerland 2016.We verify the correctness of a recursive version of Tony Hoare’s quicksort algorithm using the Hoare-logic based verification tool Dafny. We then develop a non-standard, iterative version which is based on a stack of pivot-locations rather than the standard stack of ranges. We outline an incomplete Dafny proof for the latter

On the Integration of Automatic Deployment into the ABS Modeling Language

In modern software systems, deployment is an integral and critical part of application development (see, e.g., the DevOps approach to software development). Nevertheless, deployment is usually overlooked at the modeling level, thus losing the possibility to perform deployment conscious decisions during the early stages of development. In this paper, we address the problem of promoting deployment as an integral part of modeling, by focusing on the Abstract Behavioral Specification (ABS) language used for the specification of models of systems composed of concurrent objects consuming resources provided by deployment components. We extend ABS with class annotations expressing the resource requirements of the objects of that class. Then we define a tool that, starting from a high-level declaration of the desired system, computes a model instance of such system that optimally distributes objects over available deployment components

Origins and composition of fine atmospheric carbonaceous aerosol in the Sierra Nevada Mountains, California

In this paper we report chemically resolved measurements of organic aerosol (OA) and related tracers during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX) at the Blodgett Forest Research Station, California from 15 August–10 October 2007. OA contributed the majority of the mass to the fine atmospheric particles and was predominately oxygenated (OOA). The highest concentrations of OA were during sporadic wildfire influence when aged plumes were impacting the site. In situ measurements of particle phase molecular markers were dominated by secondary compounds and along with gas phase compounds could be categorized into six factors or sources: (1) aged biomass burning emissions and oxidized urban emissions, (2) oxidized urban emissions (3) oxidation products of monoterpene emissions, (4) monoterpene emissions, (5) anthropogenic emissions and (6) local methyl chavicol emissions and oxidation products. There were multiple biogenic components that contributed to OA at this site whose contributions varied diurnally, seasonally and in response to changing meteorological conditions, e.g. temperature and precipitation events. Concentrations of isoprene oxidation products were larger when temperatures were higher during the first half of the campaign (15 August–12 September) due to more substantial emissions of isoprene and enhanced photochemistry. The oxidation of methyl chavicol, an oxygenated terpene emitted by ponderosa pine trees, contributed similarly to OA throughout the campaign. In contrast, the abundances of monoterpene oxidation products in the particle phase were greater during the cooler conditions in the latter half of the campaign (13 September–10 October), even though emissions of the precursors were lower, although the mechanism is not known. OA was correlated with the anthropogenic tracers 2-propyl nitrate and carbon monoxide (CO), consistent with previous observations, while being comprised of mostly non-fossil carbon (>75%). The correlation between OA and an anthropogenic tracer does not necessarily identify the source of the carbon as being anthropogenic but instead suggests a coupling between the anthropogenic and biogenic components in the air mass that might be related to the source of the oxidant and/or the aerosol sulfate. Observations of organosulfates of isoprene and α-pinene provided evidence for the likely importance of aerosol sulfate in spite of neutralized aerosol although acidic plumes might have played a role upwind of the site. This is in contrast to laboratory studies where strongly acidic seed aerosols were needed in order to form these compounds. These compounds together represented only a minor fraction (<1%) of the total OA mass, which may be the result of the neutralized aerosol at the site or because only a small number of organosulfates were quantified. The low contribution of organosulfates to total OA suggests that other mechanisms, e.g. NO_x enhancement of oxidant levels, are likely responsible for the majority of the anthropogenic enhancement of biogenic secondary organic aerosol observed at this site

Measurements of Gas‐Phase Inorganic and Organic Acids from Biomass Fires by Negative‐Ion Proton‐Transfer Chemical‐Ionization Mass Spectrometry

[1] Emissions from 34 laboratory biomass fires were investigated at the combustion facility of the U.S. Department of Agriculture Fire Sciences Laboratory in Missoula, Montana. Gas-phase organic and inorganic acids were quantified using negative-ion proton-transfer chemical-ionization mass spectrometry (NI-PT-CIMS), open-path Fourier transform infrared spectroscopy (OP-FTIR), and proton-transfer-reaction mass spectrometry (PTR-MS). NI-PT-CIMS is a novel technique that measures the mass-to-charge ratio (m/z) of ions generated from reactions of acetate (CH3C(O)O−) ions with inorganic and organic acids. The emission ratios for various important reactive acids with respect to CO were determined. Emission ratios for isocyanic acid (HNCO), 1,2 and 1,3-benzenediols (catechol, resorcinol), nitrous acid (HONO), acrylic acid, methacrylic acid, propionic acid, formic acid, pyruvic acid, and glycolic acid were measured from biomass burning. Our measurements show that there is a significant amount of HONO in fresh smoke. The NI-PT-CIMS measurements were validated by comparison with OP-FTIR measurements of HONO and formic acid (HCOOH) and with PTR-MS measurements of HCOOH

Global atmospheric budget of acetaldehyde: 3-D model analysis and constraints from in-situ and satellite observations

We construct a global atmospheric budget for acetaldehyde using a 3-D model of atmospheric chemistry (GEOS-Chem), and use an ensemble of observations to evaluate present understanding of its sources and sinks. Hydrocarbon oxidation provides the largest acetaldehyde source in the model (128 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;, a factor of 4 greater than the previous estimate), with alkanes, alkenes, and ethanol the main precursors. There is also a minor source from isoprene oxidation. We use an updated chemical mechanism for GEOS-Chem, and photochemical acetaldehyde yields are consistent with the Master Chemical Mechanism. We present a new approach to quantifying the acetaldehyde air-sea flux based on the global distribution of light absorption due to colored dissolved organic matter (CDOM) derived from satellite ocean color observations. The resulting net ocean emission is 57 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;, the second largest global source of acetaldehyde. A key uncertainty is the acetaldehyde turnover time in the ocean mixed layer, with quantitative model evaluation over the ocean complicated by known measurement artifacts in clean air. Simulated concentrations in surface air over the ocean generally agree well with aircraft measurements, though the model tends to overestimate the vertical gradient. PAN:NO&lt;sub&gt;x&lt;/sub&gt; ratios are well-simulated in the marine boundary layer, providing some support for the modeled ocean source. We introduce the Model of Emissions of Gases and Aerosols from Nature (MEGANv2.1) for acetaldehyde and ethanol and use it to quantify their net flux from living terrestrial plants. Including emissions from decaying plants the total direct acetaldehyde source from the land biosphere is 23 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;. Other terrestrial acetaldehyde sources include biomass burning (3 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;) and anthropogenic emissions (2 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;). Simulated concentrations in the continental boundary layer are generally unbiased and capture the spatial gradients seen in observations over North America, Europe, and tropical South America. However, the model underestimates acetaldehyde levels in urban outflow, suggesting a missing source in polluted air. Ubiquitous high measured concentrations in the free troposphere are not captured by the model, and based on present understanding are not consistent with concurrent measurements of PAN and NO&lt;sub&gt;x&lt;/sub&gt;: we find no compelling evidence for a widespread missing acetaldehyde source in the free troposphere. We estimate the current US source of ethanol and acetaldehyde (primary + secondary) at 1.3 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt; and 7.8 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;, approximately 60{%} and 480% of the corresponding increases expected for a national transition from gasoline to ethanol fuel

Peribiliary glands are key in regeneration of the human biliary epithelium after severe bile duct injury

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We, therefore, developed a novel ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Post-ischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation and maturation. Proliferation of PBG cells increased after 24 h of oxygenated incubation, reaching a peak after 72 h. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (Nanog+/Sox9+) to a mature (CFTR+/secretin receptor+) and activated phenotype (increased expression of HIF-1α, Glut-1, and VEGF-A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. CONCLUSION: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behaviour of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury. This article is protected by copyright. All rights reserved

Aerosol optical properties and trace gas emissions by PAX and OP-FTIR for laboratory-simulated western US wildfires during FIREX

Western wildfires have a major impact on air quality in the US. In the fall of 2016, 107 test fires were burned in the large-scale combustion facility at the US Forest Service Missoula Fire Sciences Laboratory as part of the Fire Influence on Regional and Global Environments Experiment (FIREX). Canopy, litter, duff, dead wood, and other fuel components were burned in combinations that represented realistic fuel complexes for several important western US coniferous and chaparral ecosystems including ponderosa pine, Douglas fir, Engelmann spruce, lodgepole pine, subalpine fir, chamise, and manzanita. In addition, dung, Indonesian peat, and individual coniferous ecosystem fuel components were burned alone to investigate the effects of individual components (e.g., duff ) and fuel chemistry on emissions. The smoke emissions were characterized by a large suite of state-of-the-art instruments. In this study we report emission factor (EF, grams of compound emitted per kilogram of fuel burned) measurements in fresh smoke of a diverse suite of critically important trace gases measured using open-path Fourier transform infrared spectroscopy (OPFTIR). We also report aerosol optical properties (absorption EF; single-scattering albedo, SSA; and Ångström absorption exponent, AAE) as well as black carbon (BC) EF measured by photoacoustic extinctiometers (PAXs) at 870 and 401 nm. The average trace gas emissions were similar across the coniferous ecosystems tested and most of the variability observed in emissions could be attributed to differences in the consumption of components such as duff and litter, rather than the dominant tree species. Chaparral fuels produced lower EFs than mixed coniferous fuels for most trace gases except for NOx and acetylene. A careful comparison with available field measurements of wildfires confirms that several methods can be used to extract data representative of real wildfires from the FIREX laboratory fire data. This is especially valuable for species rarely or not yet measured in the field. For instance, the OP-FTIR data alone show that ammonia (1.62 g kg-1/, acetic acid (2.41 g kg-1/, nitrous acid (HONO, 0.61 g kg-1/, and other trace gases such as glycolaldehyde (0.90 g kg-1/ and formic acid (0.36 g kg-1/ are signific-1ant emissions that were poorly characterized or not characterized for US wildfires in previous work. The PAX measurements show that the ratio of brown carbon (BrC) absorption to BC absorption is strongly dependent on modified combustion efficiency (MCE) and that BrC absorption is most dominant for combustion of duff (AAE 7.13) and rotten wood (AAE 4.60): fuels that are consumed in greater amounts during wildfires than prescribed fires. Coupling our laboratory data with field data suggests that fresh wildfire smoke typically has an EF for BC near 0.2 g kg-1, an SSA of ~0.91, and an AAE of ~3.50, with the latter implying that about 86% of the aerosol absorption at 401 nm is due to BrC