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The potent general anesthetic etomidate produces its effects by enhancing GABA(A) receptor activation. Its photolabel analog [(3)H]azi-etomidate labels residues within transmembrane domains on alpha and beta subunits: alphaMet236 and betaMet286. We hypothesized that these methionines contribute to etomidate sites formed at alpha-beta subunit interfaces and(More)
A molecule as simple in structure as tetramethylammonium gates the nicotinic acetylcholine receptor (nAChR) with high efficacy. To compare the structure of the nAChR transmitter binding site in the open channel state with that of the ACh binding protein, we determined the efficacy of nAChR gating by -S(CH(2))(n)N(CH(3))(3)(+) (n = 1-4) tethered to(More)
Etomidate is a potent general anesthetic that acts as an allosteric co-agonist at GABAA receptors. Photoreactive etomidate derivatives labeled αMet-236 in transmembrane domain M1, which structural models locate in the β+/α- subunit interface. Other nearby residues may also contribute to etomidate binding and/or transduction through rearrangement of the(More)
The two-phase mixture model developed by Baer and Nunziato ͑BN͒ to study the deflagration-to-detonation transition ͑DDT͒ in granular explosives is critically reviewed. The continuum-mixture theory foundation of the model is examined, with particular attention paid to the manner in which its constitutive functions are formulated. Connections between the(More)
Etomidate and propofol are potent general anesthetics that act via GABAA receptor allosteric co-agonist sites located at transmembrane β+/α- inter-subunit interfaces. Early experiments in heteromeric receptors identified βN265 (M2-15') on β2 and β3 subunits as an important determinant of sensitivity to these drugs. Mechanistic analyses suggest that(More)
We present an accurate and fast wave tracking method that uses parametric representations of tracked fronts, combined with modifications of level-set methods that use narrow bands. Our strategy generates accurate computation of the front curvature and other geometric properties of the front. We introduce data structures that can store discrete(More)
We synthesized 2,6-diisopropyl-4-[3-(3-methyl-3H-diazirin-3-yl)propyl]phenol (p-(4-azipentyl)propofol), or p-4-AziC5-Pro, a novel photoactivable derivative of the general anesthetic propofol. p-4-AziC5-Pro has an anesthetic potency similar to that of propofol. Like propofol, the compound potentiates inhibitory GABA(A) receptor current responses and(More)
BACKGROUND Etomidate is a potent hypnotic agent that acts via γ-aminobutyric acid receptor type A (GABA(A)) receptors. Evidence supports the presence of two etomidate sites per GABA(A) receptor, and current models assume that each site contributes equally and noncooperatively to drug effects. These assumptions remain untested. METHODS We used concatenated(More)
A new, one-dimensional, two-phase model appropriate for describing the detonation of granulated solid propellants or explosives is presented. The model satisfies the principle that the mixture mass, momentum, and energy are conserved, is strictly hyperbolic, and is frame indifferent. Conditions are presented for satisfying the second law of thennodynamics.(More)