233 research outputs found

    Assessing fossil fuel CO_2 emissions in California using atmospheric observations and models

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    Analysis systems incorporating atmospheric observations could provide a powerful tool for validating fossil fuel CO_2 (ffCO_2) emissions reported for individual regions, provided that fossil fuel sources can be separated from other CO_2 sources or sinks and atmospheric transport can be accurately accounted for. We quantified ffCO_2 by measuring radiocarbon (^(14)C) in CO_2, an accurate fossil-carbon tracer, at nine observation sites in California for three months in 2014–15. There is strong agreement between the measurements and ffCO_2 simulated using a high-resolution atmospheric model and a spatiotemporally-resolved fossil fuel flux estimate. Inverse estimates of total in-state ffCO_2 emissions are consistent with the California Air Resources Board's reported ffCO_2 emissions, providing tentative validation of California's reported ffCO_2 emissions in 2014–15. Continuing this prototype analysis system could provide critical independent evaluation of reported ffCO_2 emissions and emissions reductions in California, and the system could be expanded to other, more data-poor regions

    Starting of rocket engine at conditions of simulated altitude using crude monoethylaniline and other fuels with mixed acid

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    Experiments were conducted at sea level and pressure altitude of about 55,000 feet at various temperatures to determine starting characteristics of a commercial rocket engine using crude monoethylaniline and other fuels with mixed acid. With crude monoethylaniline, ignition difficulties were encountered at temperatures below about 20 degrees F. With mixed butyl mercaptans, water-white turpentine, and x-pinene, no starting difficulties were experienced at temperatures as low as minus 74 degrees F. Turpentine and x-pinene, however, sometimes left deposits on the injector face. With blends containing furfuryl alcohol and with other blends, difficulties were experienced either from appreciable deposits or from starting

    Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary: Effects on the gonadotrope axis and sex-specific reproductive disease

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    The LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2-LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit ( ΑGSU ) promoter was used to produce LHX3a, LHX3b, and M2-LHX3 in the pituitary glands of transgenic mice. Alpha GSU-beta galactosidase animals were generated as controls. Male ΑGSU-LHX3a and ΑGSU-LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female ΑGSU-LHX3a and ΑGSU-LHX3b transgenic mice are viable but have reduced fertility. By contrast, ΑGSU-M2-LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology. J. Cell. Physiol. 212: 105–117, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56051/1/21010_ftp.pd

    Recent Progress in the Use of Glucagon and Glucagon Receptor Antagonists in the Treatment of Diabetes Mellitus

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    Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques

    Recommended Guanidine Suppressor for the Next-Generation Caustic-Side Solvent Extraction Process

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    The guanidine recommended for the Next-Generation Caustic-Side is N,N ,N -tris(3,7-dimethyloctyl)guanidine (TiDG). Systematic testing has shown that it is significantly more lipophilic than the previously recommended guanidine DCiTG, the active extractant in the commercial guanidine product LIX -79, while not otherwise changing the solvent performance. Previous testing indicated that the extent of partitioning of the DCiTG suppressor to the aqueous strip solution is significantly greater than expected, potentially leading to rapid depletion of the suppressor from the solvent and unwanted organic concentrations in process effluents. Five candidate guanidines were tested as potential replacements for DCiTG. The tests included batch extraction with simulated waste and flowsheet solutions, third-phase formation, emulsion formation, and partition ratios of the guanidine between the solvent and aqueous strip solution. Preliminary results of a thermal stability test of the TiDG solvent at one month duration indicated performance approximately equivalent to DCiTG. Two of the guanidines proved adequate in all respects, and the choice of TiDG was deemed slightly preferable vs the next best guanidine BiTABG

    Evaluation of ENTLN Performance Characteristics Based on the Ground Truth Natural and Rocket-Triggered Lightning Data Acquired in Florida

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    The performance characteristics of the Earth Networks Total Lightning Network (ENTLN) were evaluated by using as ground truth natural cloud-to-ground (CG) lightning data acquired at the Lightning Observatory in Gainesville (LOG) and rocket-triggered lightning data obtained at Camp Blanding (CB), Florida, in 2014 and 2015. Two ENTLN processors (data processing algorithms) were evaluated. The old processor (P2014) was put into use in June 2014 and the new one (P2015) has been operational since August 2015. Based on the natural-CG-lightning data set (219 flashes containing 608 strokes), the flash detection efficiency (DE), flash classification accuracy (CA), stroke DE, and stroke CA for the new processor were found to be 99%, 97%, 96%, and 91%, respectively, and the corresponding values for the old processor were 99%, 91%, 97%, and 68%. The stroke DE and stroke CA for first strokes are higher than those for subsequent strokes. Based on the rocket-triggered lightning data set (36 CG flashes containing 175 strokes), the flash DE, flash CA, stroke DE, and stroke CA for the new processor were found to be 100%, 97%, 97%, and 86%, respectively, while the corresponding values for the old processor were 100%, 92%, 97%, and 42%. The median values of location error and absolute peak current estimation error were 215 m and 15% for the new processor, and 205 m and 15% for the old processor. For both natural and triggered CG lightning, strokes with higher peak currents were more likely to be both detected and correctly classified by the ENTLN

    Inactivation of Staphylococcal Phenol Soluble Modulins by Serum Lipoprotein Particles

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    Staphylococcus aureus virulence has been associated with the production of phenol soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils. However, the functional characterizations were generally performed in the absence of human serum. Here, we demonstrate that human serum can inhibit all the previously-described activities of PSM. We observed that serum can fully block both the cell lysis and FPR2 activation of neutrophils. We show a direct interaction between PSM and serum lipoproteins in human serum and whole blood. Subsequent analysis using purified high, low, and very low density lipoproteins (HDL, LDL, and VLDL) revealed that they indeed neutralize PSM. The lipoprotein HDL showed highest binding and antagonizing capacity for PSM. Furthermore, we show potential intracellular production of PSM by S. aureus upon phagocytosis by neutrophils, which opens a new area for exploration of the intracellular lytic capacity of PSM. Collectively, our data show that in a serum environment the function of PSM as important extracellular toxins should be reconsidered

    Assessing fossil fuel CO_2 emissions in California using atmospheric observations and models

    Get PDF
    Analysis systems incorporating atmospheric observations could provide a powerful tool for validating fossil fuel CO_2 (ffCO_2) emissions reported for individual regions, provided that fossil fuel sources can be separated from other CO_2 sources or sinks and atmospheric transport can be accurately accounted for. We quantified ffCO_2 by measuring radiocarbon (^(14)C) in CO_2, an accurate fossil-carbon tracer, at nine observation sites in California for three months in 2014–15. There is strong agreement between the measurements and ffCO_2 simulated using a high-resolution atmospheric model and a spatiotemporally-resolved fossil fuel flux estimate. Inverse estimates of total in-state ffCO_2 emissions are consistent with the California Air Resources Board's reported ffCO_2 emissions, providing tentative validation of California's reported ffCO_2 emissions in 2014–15. Continuing this prototype analysis system could provide critical independent evaluation of reported ffCO_2 emissions and emissions reductions in California, and the system could be expanded to other, more data-poor regions

    Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes

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    <p>Abstract</p> <p>Background</p> <p>Glucagon is an important hormone in the regulation of glucose homeostasis, particularly in the maintenance of euglycemia and prevention of hypoglycemia. In type 2 Diabetes Mellitus (T2DM), glucagon levels are elevated in both the fasted and postprandial states, which contributes to inappropriate hyperglycemia through excessive hepatic glucose production. Efforts to discover and evaluate glucagon receptor antagonists for the treatment of T2DM have been ongoing for approximately two decades, with the challenge being to identify an agent with appropriate pharmaceutical properties and efficacy relative to potential side effects. We sought to determine the hepatic & systemic consequence of full glucagon receptor antagonism through the study of the glucagon receptor knock-out mouse (Gcgr<sup>-/-</sup>) compared to wild-type littermates.</p> <p>Results</p> <p>Liver transcriptomics was performed using Affymetric expression array profiling, and liver proteomics was performed by iTRAQ global protein analysis. To complement the transcriptomic and proteomic analyses, we also conducted metabolite profiling (~200 analytes) using mass spectrometry in plasma. Overall, there was excellent concordance (R = 0.88) for changes associated with receptor knock-out between the transcript and protein analysis. Pathway analysis tools were used to map the metabolic processes in liver altered by glucagon receptor ablation, the most notable being significant down-regulation of gluconeogenesis, amino acid catabolism, and fatty acid oxidation processes, with significant up-regulation of glycolysis, fatty acid synthesis, and cholesterol biosynthetic processes. These changes at the level of the liver were manifested through an altered plasma metabolite profile in the receptor knock-out mice, e.g. decreased glucose and glucose-derived metabolites, and increased amino acids, cholesterol, and bile acid levels.</p> <p>Conclusions</p> <p>In sum, the results of this study suggest that the complete ablation of hepatic glucagon receptor function results in major metabolic alterations in the liver, which, while promoting improved glycemic control, may be associated with adverse lipid changes.</p
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