Ab initio study of aspartic and glutamic acid: supplementary evidence for structural requirements at position 9 for glucagon activity

Abstract Our previous work established that position 9 aspartic acid in glucagon was a critical residue for transduction of the hormone response. An uncoupling of the binding interaction from adenylate cyclase activation was demonstrated by the observation that amino acid replacements at position 9 resulted in peptides that had no measurable adenylate cyclase activity yet were still recognized by the glucagon receptor. It was also later shown that His' played a major role in activation, and it was suggested that an electrostatic interaction between the aspartic acid carboxylate and the histidine imidazole occurred as part of the activation mechanism. This did not preclude intermolecular interactions of this aspartic acid with other residues within the receptor binding site. The observation that a conservative substitution of glutamic acid for aspartic acid at position 9 was sufficient to result in the potent antagonist, des-His'd[Glu']glucagon amide, implied that even glutamic acid possessed the minimum properties necessary for inhibition, and that the precise position of the carboxyl group at position 9 in glucagon was an absolute requirement for full agonist activity. The present investigation was conducted with ab initio calculations and molecular modeling to shed some light on the source of this phenomenon

The Two-Column Aerosol Project: Phase I-Overview and impact of elevated aerosol layers on aerosol optical depth

The Two-Column Aerosol Project (TCAP), conducted from June 2012 through June 2013, was a unique study designed to provide a comprehensive data set that can be used to investigate a number of important climate science questions, including those related to aerosol mixing state and aerosol radiative forcing. The study was designed to sample the atmosphere between and within two atmospheric columnsone fixed near the coast of North America (over Cape Cod, MA) and a second moveable column over the Atlantic Ocean several hundred kilometers from the coast. The U.S. Department of Energy's (DOE) Atmospheric Radiation Measurement (ARM) Mobile Facility (AMF) was deployed at the base of the Cape Cod column, and the ARM Aerial Facility was utilized for the summer and winter intensive observation periods. One important finding from TCAP is that four of six nearly cloud-free flight days had aerosol layers aloft in both the Cape Cod and maritime columns that were detected using the nadir pointing second-generation NASA high-spectral resolution lidar (HSRL-2). These layers contributed up to 60% of the total observed aerosol optical depth (AOD). Many of these layers were also intercepted by the aircraft configured for in situ sampling, and the aerosol in the layers was found to have increased amounts of biomass burning material and nitrate compared to aerosol found near the surface. In addition, while there was a great deal of spatial and day-to-day variability in the aerosol chemical composition and optical properties, no systematic differences between the two columns were observed

The Two-Column Aerosol Project: Phase I - Overview and Impact of Elevated Aerosol Layers on Aerosol Optical Depth

The Two-Column Aerosol Project (TCAP), conducted from June 2012 through June 2013, was a unique study designed to provide a comprehensive data set that can be used to investigate a number of important climate science questions, including those related to aerosol mixing state and aerosol radiative forcing. The study was designed to sample the atmosphere be tween and within two atmospheric columns; one fixed near the coast of North America (over Cape Cod, MA) and a second moveable column over the Atlantic Ocean several hundred kilometers from the coast. The U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Mobile Facility (AMF) was deployed at the base of the Cape Cod column, and the ARM Aerial Facility was utilized for the summer and winter intensive observation periods. One important finding from TCAP is that four of six nearly cloud-free flight days had aerosol layers aloft in both the Cape Cod and maritime columns that were detected using the nadir pointing second-generation NASA high-spectral resolution lidar (HSRL-2).These layer s contributed up to 60 of the total observed aerosol optical depth (AOD). Many of these layers were also intercepted by the aircraft configured for in situ sampling, and the aerosol in the layers was found to have increased amounts of biomass burning material and nitrate compared to aerosol found near the surface. In addition, while there was a great deal of spatial and day-to-day variability in the aerosol chemical composition and optical properties, no systematic differences between the two columns were observed