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We investigated interfacial processes affecting metal mobility by wood ash under laboratory-controlled conditions using aqueous chemistry, microscopy, and spectroscopy. The Valles Caldera National Preserve in New Mexico experiences catastrophic wildfires of devastating effects. Wood samples of Ponderosa Pine, Colorado Blue Spruce, and Quaking Aspen collected from this site were exposed to temperatures of 60, 350, and 550 °C. The 350 °C Pine ash had the highest content of Cu (4997 ± 262 mg kg-1), Cr (543 ± 124 mg kg-1), and labile dissolved organic carbon (DOC, 11.3 ± 0.28 mg L-1). Sorption experiments were conducted by reacting 350 °C Pine, Spruce, and Aspen ashes separately with 10 µM Cu(II) and Cr(VI) solutions. Up to a 94% decrease in Cu(II) concentration was observed in solution while Cr(VI) concentration showed a limited decrease (up to 13%) after 180 min of reaction. X-ray photoelectron spectroscopy (XPS) analyses detected increased association of Cu(II) on the near surface region of the reacted 350 °C Pine ash from the sorption experiments compared to the unreacted ash. The results suggest that dissolution and sorption processes should be considered to better understand the potential effects of metals transported by wood ash on water quality that have important implications for postfire recovery and response strategies.

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There is urgent need for rapid, point-of-care diagnostic tools for tuberculosis (TB) and drug sensitivity. Current methods based on in vitro growth take weeks, while DNA amplification can neither differentiate live from dead organisms nor determine phenotypic drug resistance. Here we show the development and evaluation of a rapid breath test for isoniazid (INH)-sensitive TB based on detection of labelled N2 gas formed specifically from labelled INH by mycobacterial KatG enzyme. In vitro data show that the assay is specific, dependent on mycobacterial abundance and discriminates between INH-sensitive and INH-resistant (S315T mutant KatG) TB. In vivo, the assay is rapid with maximal detection of (15)N2 in exhaled breath of infected rabbits within 5-10 min. No increase in (15)N2 is detected in uninfected animals, and the increases in (15)N2 are dependent on infection dose. This test may allow rapid detection of INH-sensitive TB.

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One of the major hurdles in treating tuberculosis (TB) is the time-consuming and difficult methodology for diagnosis. Stable-isotope breath tests hold great potential for rapidly diagnosing an infectious disease, monitoring therapy, and determining a bacterial phenotype in a rapid, point-of-care manner that does not require invasive sampling. Here we describe the preclinical development of a potentially highly selective TB diagnostic breath test based upon the organism's CO dehydrogenase activity. After development of the test in vitro, we were able to use the breath test to discriminate between infected and control rabbits, demonstrating that a diagnosis can potentially be made and also that a complex bacterial phenotype can be noninvasively and rapidly studied in the host. IMPORTANCE Tuberculosis (TB) remains a major infectious cause of disease and death worldwide, and effective diagnosis and then treatment are the tools with which we fight TB. The more quickly and more specific the diagnosis can be made, the better, and this is also true of diagnosis being as close to the patient (point of care) as possible. Here we report our preclinical development of breath tests based upon specific mycobacterial metabolism that could, with development, allow rapid point-of-care diagnosis through measuring the mycobacterial conversion of labeled CO to labeled CO2.

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The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeotemperature proxies to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C(4) plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles ∼2 °C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6 °C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase.

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PURPOSE: Counterfeit drug products have become a major problem worldwide and a number of techniques to detect counterfeit products or reduce the potential for counterfeiting have been investigated. This study examined the use of stable isotope-labeled excipients in solid dosage forms as a method to identify drug products and to detect counterfeits. METHODS: (2)H- and (13)C-glucose were used as model excipients and incorporated in wet granulated formulations at a variety of different isotopic ratios. The ratios of (2)H/(1)H and (13)C/(12)C in each product were then determined by isotope ratio mass spectrometry. RESULTS: Results demonstrated the ability to detect the isotope-labeled glucose in both granules and tablets. CONCLUSIONS: It was possible to use the isotope ratios to differentiate between specific batches of granules, demonstrating the potential of this technique for in-product, batch-specific identification.

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Dypingite, a hydrated Mg-carbonate mineral, was precipitated from high-pH, high salinity solutions to investigate controls on carbon fixation and to identify the isotopic characteristics of mineral sequestration in mine tailings. δ(13)C values of dissolved inorganic carbon content and synthetic dypingite are significantly more negative than those predicted for equilibrium exchange of CO(2) gas between the atmosphere and solution. The measured δ(13)C of aqueous carbonate species is consistent with a kinetic fractionation that results from a slow diffusion of atmospheric CO(2) into solution. During dypingite precipitation, dissolved inorganic carbon concentrations decrease and δ(13)C values become more negative, indicating that the rate of CO(2) uptake into solution was outpaced by the rate of carbon fixation within the precipitate. This implies that CO(2) gas uptake is rate-limiting to CO(2) fixation. δ(13)C of carbonate mineral precipitates in mine tailings and of DIC in mine process waters display similar (13)C-depletions that are inconsistent with equilibrium fractionation. Thus, the rate of carbon fixation in mine tailings may also be limited by supply of CO(2). Carbon sequestration could be accelerated by increasing the partial pressure of CO(2) in tailings ponds or by using chemicals that enhance the uptake of gaseous CO(2) into aqueous solution.

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BACKGROUND: Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeled substrates and detection of labeled products in exhaled breath using portable infrared spectrometers. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether mycobacterial urease activity could be utilized in such a breath test format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent bronchoscopic infection with either Mycobacterium bovis or Mycobacterium tuberculosis. Rabbits were treated with 25 mg/kg of isoniazid (INH) approximately 2 months after infection when significant cavitary lung pathology was present. [(13)C] urea was instilled directly into the lungs of intubated rabbits at selected time points, exhaled air samples analyzed, and the kinetics of delta(13)CO(2) formation were determined. Samples obtained prior to inoculation served as control samples for background (13)CO(2) conversion in the rabbit model. (13)CO(2), from metabolic conversion of [(13)C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15 minutes of administration. Analyses showed a rapid increase in the rate of (13)CO(2) formation both early in disease and prior to treatment with INH. Following INH treatment, all evaluable rabbits showed a decrease in the rate of (13)CO(2) formation. CONCLUSIONS/SIGNIFICANCE: Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of unlabeled urea, which would prevent the delta(13)CO(2) signal from urease-positive gastrointestinal organisms.

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Studies with intravenously injected ultrafine particles have shown that the liver is the major organ of their uptake from the blood circulation. Measuring translocation of inhaled ultrafine particles to extrapulmonary organs via the blood compartment is hampered by methodological difficulties (i.e., label may come off, partial solubilization) and analytical limitations (measurement of very small amounts). The objective of our pilot study was to determine whether ultrafine elemental carbon particles translocate to the liver and other extrapulmonary organs following inhalation as singlet particles by rats. We generated ultrafine (13)C particles as an aerosol with count median diameters (CMDs) of 20-29 nm (GSD 1.7) using electric spark discharge of (13)C graphite electrodes in argon. Nine Fischer 344 rats were exposed to these particles for 6 h. in whole-body inhalation chambers at concentrations of 180 and 80 microg/m(3); 3 animals each were killed at 0.5, 18, and 24 h postexposure. Six unexposed rats served as controls. Lung lobes, liver, heart, brain, olfactory bulb, and kidney were excised, homogenized, and freeze-dried for analysis of the added (13)C by isotope ratio mass spectrometry. Organic (13)C was not detected in the (13)C particles. The (13)C retained in the lung at 0.5 h postexposure was about 70% less than predicted by rat deposition models for ultrafine particles, and did not change significantly during the 24-h postexposure period. Normalized to exposure concentration, the added (13)C per gram of lung on average in the postexposure period was approximately 9 ng/g organ/microg/m(3). Significant amounts of (13)C had accumulated in the liver by 0.5 h postinhalation only at the high exposure concentration, whereas by 18 and 24 h postexposure the (13)C amount of the livers of all exposed rats was about fivefold greater than the (13)C burden retained in the lung. No significant increase in (13)C was detected in the other organs which were examined. These results demonstrate effective translocation of ultrafine elemental carbon particles to the liver by 1 d after inhalation exposure. Translocation pathways include direct input into the blood compartment from ultrafine carbon particles deposited throughout the respiratory tract. However, since predictive particle deposition models indicate that respiratory tract deposits alone may not fully account for the hepatic (13)C burden, input from ultrafine particles present in the GI tract needs to be considered as well. Such translocation to blood and extrapulmonary tissues may well be different between ultrafine carbon and other insoluble (metal) ultrafine particles.

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Our ability to link the breeding locations of individual passerines to migration stopover sites and wintering locations is limited. Stable isotopes of hydrogen contained in bird feathers have recently shown potential in this regard. We measured hydrogen stable-isotope ratios (δD) of feathers from breeding, migrating, and wintering Wilson's Warblers. Analyses of feathers from museum specimens collected throughout the western portion of the breeding range indicate that δD values are significantly negatively related to latitude of collection (R 2=0.52), which is an indication that δD values are a good descriptor of breeding latitude. Analyses of feathers collected from birds migrating through the Bosque del Apache National Wildlife Refuge, New Mexico (USA), revealed a significantly positive relationship between δD values and the timing of autumn migration (R 2=0.34), but not the timing of spring migration. This pattern indicates that Wilson's Warblers that bred furthest north migrated earliest in the autumn. Finally, analysis of feathers collected on the wintering grounds indicate that the hydrogen isotope ratio is significantly positively related to wintering latitude (R 2=0.80), which indicates that birds that bred furthest north wintered furthest south. In combination, these patterns suggest that in the western portion of their range, Wilson's Warblers have a leapfrog migration system in which the northern-most breeding birds pass through New Mexico early in the autumn to arrive on the wintering grounds in southern Central America, the southern edge of the Wilson's Warblers winter range. We know of no other literature documenting or suggesting that Wilson's Warbler engage in leapfrog migration. We think the novelty of these results is a reflection of the potential for stable-isotope techniques to revise our understanding of bird migration.