Institution
Research Triangle Park
Nonprofit•Durham, North Carolina, United States•
About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Environmental exposure. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.
Topics: Population, Environmental exposure, Receptor, Poison control, Agonist
Papers published on a yearly basis
Papers
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TL;DR: Benzo(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester induces SAR based on all of the physiological and biochemical criteria that define SAR in tobacco.
Abstract: Summary
Systemic acquired resistance (SAR) is a pathogen-induced disease resistance response in plants that is characterized by broad spectrum disease control and an associated coordinate expression of a set of SAR genes. Benzo(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) is a novel synthetic chemical capable of inducing disease resistance in a number of dicotyledenous and monocotyledenous plant species. In this report, the response of tobacco plants to BTH treatment is characterized and the fact that it controls disease by activating SAR is demonstrated. BTH does not cause an accumulation of salicylic acid (SA), an intermediate in the SAR signal transduction pathway. As BTH also induces disease resistance and gene expression in transgenic plants expressing the nahG gene, it appears to activate the SAR signal transduction pathway at the site of or downstream of SA accumulation. BTH, SA and TMV induce the PR-1a promoter using similar cis-acting elements and gene expression is blocked by cycloheximide treatment. Thus, BTH induces SAR based on all of the physiological and biochemical criteria that define SAR in tobacco.
704 citations
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TL;DR: Five algorithms proposed in the literature for library search identification of unknown compounds from their low resolution mass spectra were optimized and tested by matching test spectra against reference spectra in the NIST-EPA-NIH Mass Spectral Database.
702 citations
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TL;DR: The mechanism of action of buPropion appears to have an unusual, not fully understood, noradrenergic link, and the mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms.
Abstract: Background The mechanism of action of the novel antidepressant bupropion remains unclear after many years of study. A review of the relevant biochemical, in vivo brain microdialysis, electrophysiologic, behavioral, and clinical data clarifies what is known about this unique compound and suggests possible modes of action. Method A panel of 11 experts was convened for a conference to discuss bupropion's mechanism of antidepressant activity. Four of the panelists presented current research findings, followed by a discussion. Results (1) Biochemical studies suggest down-regulation of postsynaptic beta-adrenoceptors and desensitization of the norepinephrine-stimulated adenylate cyclase in the rat cortex occur only after chronic administration of very high doses of bupropion. (2) In vivo brain microdialysis studies demonstrate that, after chronic administration, there is an enhancement of bupropion-induced increases in extracellular dopamine in the nucleus accumbens. (3) Electrophysiologic data show that with acute dosing, bupropion reduces the firing rates of noradrenergic neurons in the locus ceruleus. The firing rates of dopaminergic neurons are reduced by bupropion in the A9 and A10 areas of the brain, but only at very high doses, and bupropion does not alter the firing rates of serotonergic neurons in the dorsal raphe. (4) Behavioral studies show that the most active metabolite of bupropion, hydroxybupropion (306U73), appears to be responsible for a large part of the compound's effects in animal models of antidepressant activity. (5) Clinical studies indicate that bupropion enhances noradrenergic functional activity as reflected by an increased excretion of the hydroxy metabolite of melatonin, while at the same time producing a presumably compensatory decrease in norepinephrine turnover. In one study, bupropion elevated plasma levels of the dopamine metabolite homovanillic acid in nonresponders, but not in responders. Conclusion The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated.
701 citations
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University of Barcelona1, Research Triangle Park2, University of Nebraska Medical Center3, University of Edinburgh4, GlaxoSmithKline5, University of Manchester6, University of Copenhagen7, University of Cambridge8, University of Liverpool9, Maastricht University10, Brigham and Women's Hospital11, University of British Columbia12, University of Bergen13
TL;DR: Overall, the results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment and show associations but do not prove causality.
Abstract: Background: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552). Methods and Findings: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-a levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 nonsmoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p,0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p,0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice. Conclusions: Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.
700 citations
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TL;DR: Emissions of metals and other particle-phase species from on-road motor vehicles were measured in two tunnels in Milwaukee, WI during the summer of 2000 and winter of 2001 and correlations between these elements in PM2.5 indicate that direct brake wear emissions are also important.
Abstract: Emissions of metals and other particle-phase species from on-road motor vehicles were measured in two tunnels in Milwaukee, WI during the summer of 2000 and winter of 2001. Emission factors were calculated from measurements of fine (PM2.5) and coarse (PM10) particulate matter at tunnel entrances and exits, and effects of fleet composition and season were investigated. Cascade impactors (MOUDI) were used to obtain size-resolved metal emission rates. Metals were quantified with inductively-coupled plasma mass spectrometry (ICP-MS) and X-ray fluorescence (XRF). PM10 emission rates ranged from 38.7 to 201 mg km(-1) and were composed mainly of organic carbon (OC, 30%), inorganic ions (sulfate, chloride, nitrate, ammonium, 20%), metals (19%), and elemental carbon (EC, 9.3%). PM10 metal emissions were dominated by crustal elements Si, Fe, Ca, Na, Mg, Al, and K, and elements associated with tailpipe emissions and brake and tire wear, including Cu, Zn, Sb, Ba, Pb, and S. Metals emitted in PM2.5 were lower (11.6% of mass). Resuspension of roadway dust was dependent on weather and road surface conditions, and increased emissions were related to higher traffic volumes and fractions of heavy trucks. Emission of noble metals from catalytic converters appeared to be impacted by the presence of older vehicles. Elements related to brake wear were impacted by enriched road dust resuspension, but correlations between these elements in PM2.5 indicate that direct brake wear emissions are also important. A submicrometer particle mode was observed in the emissions of Pb, Ca, Fe, and Cu.
700 citations
Authors
Showing all 25006 results
Name | H-index | Papers | Citations |
---|---|---|---|
Douglas G. Altman | 253 | 1001 | 680344 |
Lewis C. Cantley | 196 | 748 | 169037 |
Ronald Klein | 194 | 1305 | 149140 |
Daniel J. Jacob | 162 | 656 | 76530 |
Christopher P. Cannon | 151 | 1118 | 108906 |
James B. Meigs | 147 | 574 | 115899 |
Lawrence Corey | 146 | 773 | 78105 |
Jeremy K. Nicholson | 141 | 773 | 80275 |
Paul M. Matthews | 140 | 617 | 88802 |
Herbert Y. Meltzer | 137 | 1148 | 81371 |
Charles J. Yeo | 136 | 672 | 76424 |
Benjamin F. Cravatt | 131 | 666 | 61932 |
Timothy R. Billiar | 131 | 838 | 66133 |
Peter Brown | 129 | 908 | 68853 |
King K. Holmes | 124 | 606 | 56192 |