The test scores of some examinees on a multiple choice test may not provide satisfactory measures of their abilities. The goal of appropriateness measurement is to identify such individuals. Earlier theoretical and expcrimcntal work considered examinees answering all, or almost all, test items. This article reports research that extends appropriateness measurement methods to examinees with moderately high non-response ratcs. These methods treat non-response as if it were a deliberate option choice and then attempt to measure the 'appropriateness' of the pattern of option choices. Earlier studies used only the dichotomous pattern of 'right' and 'not right' answers. A general polychotomous model is introduced along with a technique called 'standardization' designed to reduce the observed confounding between measured appropriateness and ability. A standardized appropriateness index based on a polychotomous model yielded higher rates of detection of simulated spuriously low examinees than the analogous index based on a dichotomous model. However, the converse was true for simulated spuriously high examinees. Standardization was found to reduce greatly the interaction between ability and measured appropriateness.

This study examined how well current software implementations of four polytomous item response theory models fit several multiple-choice tests. The models were Bock's (1972) nominal model, Samejima's (1979) multiple-choice Model C, Thissen & Steinberg's (1984) multiple-choice model, and Levine's (1993) maximum-likelihood formula scoring model. The parameters of the first three of these models were estimated with Thissen's (1986) MULTILOG computer program; Williams & Levine's (1993) FORSCORE program was used for Levine's model. Tests from the Armed Services Vocational Aptitude Battery, the Scholastic Aptitude Test, and the American College Test Assessment were analyzed. The models were fit in estimation samples of approximately 3,000; cross-validation samples of approximately 3,000 were used to evaluate goodness of fit. Both fit plots and X2 statistics were used to determine the adequacy of fit. Bock's model provided surprisingly good fit; adding parameters to the nominal model did not yield improvements in fit. FORSCORE provided generally good fit for Levine's nonparametric model across all tests. Index terms: Bock's nominal model, FORSCORE, maximum likelihood formula scoring, MULTILOG, polytomous IRT.

We present the dynamic mechanism of concerted motions in a full-length molecular model of the human dopamine transporter (hDAT), a member of the neurotransmitter/sodium symporter (NSS) family, involved in state-to-state transitions underlying function. The findings result from an analysis of unbiased atomistic molecular dynamics simulation trajectories (totaling >14 μs) of the hDAT molecule immersed in lipid membrane environments with or without phosphatidylinositol 4,5-biphosphate (PIP2) lipids. The N-terminal region of hDAT (N-term) is shown to have an essential mechanistic role in correlated rearrangements of specific structural motifs relevant to state-to-state transitions in the hDAT. The mechanism involves PIP2-mediated electrostatic interactions between the N-term and the intracellular loops of the transporter molecule. Quantitative analyses of collective motions in the trajectories reveal that these interactions correlate with the inward-opening dynamics of hDAT and are allosterically coupled to the known functional sites of the transporter. The observed large-scale motions are enabled by specific reconfiguration of the network of ionic interactions at the intracellular end of the protein. The isomerization to the inward-facing state in hDAT is accompanied by concomitant movements in the extracellular vestibule and results in the release of an Na+ ion from the Na2 site and destabilization of the substrate dopamine in the primary substrate binding S1 site. The dynamic mechanism emerging from the findings highlights the involvement of the PIP2-regulated interactions between the N-term and the intracellular loop 4 in the functionally relevant conformational transitions that are also similar to those found to underlie state-to-state transitions in the leucine transporter (LeuT), a prototypical bacterial homologue of the NSS.

Complex networks of interacting residues and microdomains in the structures of biomolecular systems underlie the reliable propagation of information from an input signal, such as the concentration of a ligand, to sites that generate the appropriate output signal, such as enzymatic activity. This information transduction often carries the signal across relatively large distances at the molecular scale in a form of allostery that is essential for the physiological functions performed by biomolecules. While allosteric behaviors have been documented from experiments and computation, the mechanism of this form of allostery proved difficult to identify at the molecular level. Here, we introduce a novel analysis framework, called N-body Information Theory (NbIT) analysis, which is based on information theory and uses measures of configurational entropy in a biomolecular system to identify microdomains and individual residues that act as (i)-channels for long-distance information sharing between functional sites, and (ii)-coordinators that organize dynamics within functional sites. Application of the new method to molecular dynamics (MD) trajectories of the occluded state of the bacterial leucine transporter LeuT identifies a channel of allosteric coupling between the functionally important intracellular gate and the substrate binding sites known to modulate it. NbIT analysis is shown also to differentiate residues involved primarily in stabilizing the functional sites, from those that contribute to allosteric couplings between sites. NbIT analysis of MD data thus reveals rigorous mechanistic elements of allostery underlying the dynamics of biomolecular systems.

A student may be so atypical and unlike other students that his aptitude test score fails to be a completely appropriate measure of his relative ability. We consider the problem of using the student's pattern of multiple-choice aptitude test answers to decide whether his score is an appropriate ability measure. Several indicators of appropriateness are formulated and evaluated with a simulation of the Scholastic Aptitude Test.