54 research outputs found

    Inclusion of Evaporation Physics in the Modeling of Water Availability in the Savannah River Basin

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    2012 S.C. Water Resources Conference - Exploring Opportunities for Collaborative Water Research, Policy and Managemen

    The Intriguing Effects of Substituents in the N-Phenethyl Moiety of Norhydromorphone: A Bifunctional Opioid from a Set of ā€œTail Wags Dogā€ Experiments

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    This work is licensed under a Creative Commons Attribution 4.0 International License.(āˆ’)-N-Phenethyl analogs of optically pure N-norhydromorphone were synthesized and pharmacologically evaluated in several in vitro assays (opioid receptor binding, stimulation of [35S]GTPĪ³S binding, forskolin-induced cAMP accumulation assay, and MOR-mediated Ī²-arrestin recruitment assays). ā€œBodyā€ and ā€œtailā€ interactions with opioid receptors (a subset of Portogheseā€™s message-address theory) were used for molecular modeling and simulations, where the ā€œaddressā€ can be considered the ā€œbodyā€ of the hydromorphone molecule and the ā€œmessageā€ delivered by the substituent (tail) on the aromatic ring of the N-phenethyl moiety. One compound, N-p-chloro-phenethynorhydromorphone ((7aR,12bS)-3-(4-chlorophenethyl)-9-hydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one, 2i), was found to have nanomolar binding affinity at MOR and DOR. It was a potent partial agonist at MOR and a full potent agonist at DOR with a Ī“/Ī¼ potency ratio of 1.2 in the ([35S]GTPĪ³S) assay. Bifunctional opioids that interact with MOR and DOR, the latter as agonists or antagonists, have been reported to have fewer side-effects than MOR agonists. The p-chlorophenethyl compound 2i was evaluated for its effect on respiration in both mice and squirrel monkeys. Compound 2i did not depress respiration (using normal air) in mice or squirrel monkeys. However, under conditions of hypercapnia (using air mixed with 5% CO2), respiration was depressed in squirrel monkeys.NIDA grant P30 DA13429NIDA grant DA039997NIDA grant DA018151NIDA grant DA035857NIDA grant DA047574NIH Intramural Research Programs of the National Institute on Drug AbuseNational Institute of Alcohol Abuse and AlcoholismNIH Intramural Research Programs of the National Institute on Drug AbuseNIH Intramural Research Program through the Center for Information TechnologyNIH Intramural Research Programs of the National Institute on Drug Abus

    The Neutron star Interior Composition Explorer (NICER): design and development

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    Tumour genomic and microenvironmental heterogeneity as integrated predictors for prostate cancer recurrence: a retrospective study

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    Clinical prognostic groupings for localised prostate cancers are imprecise, with 30ā€“50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors

    The Effect of Uncertainty in Evaporation Rate on Predictions of Water Availability in the Savannah River Basin

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    2014 S.C. Water Resources Conference - Informing Strategic Water Planning to Address Natural Resource, Community and Economic Challenge
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