Comparison Group Identification for Difficult-to-Evaluate Populations: Lessons from Evaluating 1n10 LGBTQ Youth Support Services

programs is largely absent of quantitative studies, likely in part due to the challenge of using experimental or quasi-experimental evaluation designs. This paper proposes the creative use of a national data set to overcome the problem of estimating a counterfactual for this population. In addition to discussing lessons from this approach, we describe the program and its impacts. Evidence suggests that the program under study—1n10, a local support group for LGBTQ youth in the Phoenix, AZ, metropolitan area—draws a relatively more disadvantaged group than the national average but that their levels of suicide ideation are lower. By addressing key threats to the internal validity of evaluation designs, we rule out plausible rival explanations for program impacts. hile many stressors are evident in yout

Sequential Analysis: A Methodology for Monitoring Approval Plans

published or submitted for publicatio

A general theory of the spectroscopic properties of partially ordered ensembles. II. Two‐vector problems

We have expanded on the results of an earlier paper [J. Chem. Phys. 72, 221 (1980)] which deals with a method for determining the response of a static, partially ordered ensemble of molecules to various types of electromagnetic probes. In this paper we consider types of spectroscopy whose response depends on the location of two vectors in an axis system fixed with respect to the molecule. Examples of such spectroscopies discussed in detail include fluorescence polarization, photoselection linear dichroism, Raman spectroscopy, and two‐photon absorption. We outline the kinds of structural information available from polarization experiments on partially ordered ensembles.Keywords: ENSEMBLE, POLARIZATION, SPECTROSCOPY, ORIENTATION, RAMAN SPECTRA, MOLECULES, DICHROISM, FLUORESCENC

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al