Methylglyoxal is a potent glycating agent under physiological conditions. Human serum albumin is modified by methylglyoxal in vivo. The glycation adducts formed and structural and functional changes induced by methylglyoxal modification have not been fully disclosed. Methylglyoxal reacted with human serum albumin under physiological conditions to form mainly the hydroimidazolone N ␦ -(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (92% of total modification) with a minor formation of argpyrimidine, N ⑀ -(1-carboxyethyl)lysine, and methylglyoxal lysine dimer. When human serum albumin was modified minimally with methylglyoxal, tryptic peptide mapping indicated a hotspot of modification at Arg-410 located in drug-binding site II and the active site of albumin-associated esterase activity. Modification of Arg-410 by methylglyoxal was found in albumin glycated in vivo. Other sites of minor modification were: Arg-114, Arg-186, Arg-218, and Arg-428. Hydroimidazolone formation at Arg-410 inhibited ketoprofen binding and esterase activity; correspondingly, glycation in the presence of ketoprofen inhibited Arg-410 modification and loss of esterase activity. The pH dependence of esterase activity indicated a catalytic group with pK a ‫؍‬ 7.9 ؎ 0.1, assigned to the catalytic base Tyr-411 with the conjugate base stabilized by interaction with the guanidinium group of Arg-410. Modification by methylglyoxal destabilized Tyr-411 and increased the pK a to 8.8 ؎ 0.1. Molecular dynamics and modeling studies indicated that hydroimidazolone formation caused structural distortion leading to disruption of argininedirected hydrogen bonding and loss of electrostatic interactions. Methylglyoxal modification of critical arginine residues, therefore, whether experimental or physiological, is expected to disrupt protein-ligand interactions and inactivate enzyme activity by hydroimidazolone formation.

Apparently mistaken decisions are ubiquitous. To what extent does this reflect irrationality, as opposed to a rational trade-off between the costs of information acquisition and the expected benefits of learning? We develop a revealed preference test that characterizes all patterns of choice "mistakes" consistent with a general model of optimal costly information acquisition and identify the extent to which information costs can be recovered from choice data.Limits on attention impact choice. Shoppers may buy unnecessarily expensive products due to their failure to notice whether or not sales tax is included in stated prices (Chetty, Looney, and Kroft 2009). Buyers of secondhand cars focus their attention on the leftmost digit of the odometer (Lacetera, Pope, and Sydnor 2012). Purchasers limit their attention to a relatively small number of websites when buying over the Internet (De Los Santos, Hortaçsu, and Wildenbeest 2012).While apparently mistaken decisions are ubiquitous, this does not imply that decision makers are irrational. The standard theory of choice asserts only that individuals act optimally, given what they know. At least since the work of Hayek (1945) and Stigler (1961), there has been a focus on the optimization of knowledge itself, with decision makers trading off the cost of learning against improved decision quality. As the universality of knowledge constraints has been increasingly recognized, so the range of information cost functions used to model them has expanded. Verrecchia (1982) models choice of variance of a normal signal; Sims (2003) an unrestricted choice of information structure with costs based on Shannon entropy; and Reis (2006) the binary choice of whether or not to become fully informed. 1 1 See, for example, van Nieuwerburgh and Veldkamp (2009) and Woodford (2012) for other informational cost functions.

Neuroimaging studies typically identify neural activity correlated with the predictions of highly parameterized models, like the many reward prediction error (RPE) models used to study reinforcement learning. Identified brain areas might encode RPEs or, alternatively, only have activity correlated with RPE model predictions. Here, we use an alternate axiomatic approach rooted in economic theory to formally test the entire class of RPE models on neural data. We show that measurements of human neural activity from the striatum, medial prefrontal cortex, amygdala, and posterior cingulate cortex satisfy necessary and sufficient conditions for the entire class of RPE models. However, activity measured from the anterior insula falsifies the axiomatic model, and therefore no RPE model can account for measured activity. Further analysis suggests the anterior insula might instead encode something related to the salience of an outcome. As cognitive neuroscience matures and models proliferate, formal approaches of this kind that assess entire model classes rather than specific model exemplars may take on increased significance.

Many everyday decisions are made without full examination of all available options, and, as a result, the best available option may be missed. We develop a search-theoretic choice experiment to study the impact of incomplete consideration on the quality of choices. We find that many decisions can be understood using the satisficing model of Herbert Simon (1955): most subjects search sequentially, stopping when a "satisficing" level of reservation utility is realized. We find that reservation utilities and search order respond systematically to changes in the decision making environment. (JEL D03, D12, D83)