Potential Modes of Interaction of 9-Aminomethyl-9,10-dihydroanthracene (AMDA) Derivatives with the 5-HT 2A Receptor: A Ligand Structure-Affinity Relationship, Receptor Mutagenesis and Receptor Modeling Investigation

The effects of 3-position substitution of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on 5-HT2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2-aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT2A receptor models that suggest that members of the DOB-like series can bind to the receptor in two distinct modes that correlate with the compounds’ functional activity. Automated ligand docking and molecular dynamics suggest that all of the AMDA derivatives, the parent of which is a 5-HT2A antagonist, bind in a fashion analogous to that for the sterically demanding antagonist DOB-like compounds. The failure of the F3406.52L mutation to adversely affect the affinity of AMDA and the 3-bromo derivative is consistent with the proposed modes of orientation. Evaluation of ligand-receptor complex models suggest that a valine/threonine exchange between the 5-HT2A and D2 receptors may be the origin of selectivity for AMDA and two substituted derivatives

Ammonia, methane and hydrogen for gas turbines

Ammonia has been identified as a sustainable fuel for transport and power applications. Similar to hydrogen, ammonia is a synthetic product that can be obtained either from fossil fuels, biomass or other renewable sources. Since the 1960’s, considerable research has taken place to develop systems capable of burning the material in gas turbines. However, it is not until recently, that interest in ammonia has regained some momentum in the energy agenda as it is a carbon free carrier and offers an energy density higher than compressed hydrogen. . Therefore, this work examines combustion stability and emissions from gaseous ammonia blended with methane or hydrogen in gas turbines. Experiments were carried out in a High Pressure Combustion Rig under atmospheric conditions employing a bespoke generic swirl burner. OH* Chemiluminescense was used for all trials to determine reactivity of the radical. Emissions were measured and correlated to equilibrium calculations using GASEQ. Results show that efficient combustion can be achieved with high power but at very narrow equivalence ratios using both hydrogen and methane blends. Moreover, low concentrations of OH radicals are observed at high hydrogen content, probably as a consequence of the high NH2 production

New Frontiers-class Uranus Orbiter: Exploring the feasibility of achieving multidisciplinary science with a mid-scale mission

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Structure of the human κ-opioid receptor in complex with JDTic

Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and—in the case of κ-opioid receptor (κ-OR)—dysphoria and psychotomimesis. Here we report the crystal structure of the human κ-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 Å resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human κ-OR. Modelling of other important κ-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5′-guanidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure–activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for κ-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human κ-OR

Study guide and solutions manual to accompany: fundamentals of behavioral statistics

Statistics is a language. As with any language, statistics is a form of communication that uses abstract symbols to refer to concepts, events, and places in an efficient manner. As you will learn in this text, behavioral scientists use statistics to communicate to others the results of their research