Comparative analysis of homology models of the Ah receptor ligand binding domain: Verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness. © 2013 American Chemical Society

The pseudo‐brookite spin‐glass system studied by means of muon spin relaxation

Zero-field muon spin relaxation (µSR) experiments have been performed on the spin glass Fe1.75Ti1.25O5. Above the spin-glass temperature of 44 K a distinct exponential µSR rate (¿) is observed, while below Tg a square-root exponential decay occurs, indicating fast spin fluctuations. Near 8 K, a maximum in ¿ is indicative of transverse spin ordering. The low ¿ values and the sharp ¿ peak at Tg are very promising for the study of spin freezing models like the Vogel–Fulcher law or the power law

Optimising decision trees using multi-objective particle swarm optimisation

Copyright © 2009 Springer-Verlag Berlin Heidelberg. The final publication is available at link.springer.comBook title: Swarm Intelligence for Multi-objective Problems in Data MiningSummary. Although conceptually quite simple, decision trees are still among the most popular classifiers applied to real-world problems. Their popularity is due to a number of factors – core among these is their ease of comprehension, robust performance and fast data processing capabilities. Additionally feature selection is implicit within the decision tree structure. This chapter introduces the basic ideas behind decision trees, focusing on decision trees which only consider a rule relating to a single feature at a node (therefore making recursive axis-parallel slices in feature space to form their classification boundaries). The use of particle swarm optimization (PSO) to train near optimal decision trees is discussed, and PSO is applied both in a single objective formulation (minimizing misclassification cost), and multi-objective formulation (trading off misclassification rates across classes). Empirical results are presented on popular classification data sets from the well-known UCI machine learning repository, and PSO is demonstrated as being fully capable of acting as an optimizer for trees on these problems. Results additionally support the argument that multi-objectification of a problem can improve uni-objective search in classification problems

A linear RFQ ion trap for the Enriched Xenon Observatory

The design, construction, and performance of a linear radio-frequency ion trap (RFQ) intended for use in the Enriched Xenon Observatory (EXO) are described. EXO aims to detect the neutrinoless double-beta decay of $^{136}$Xe to $^{136}$Ba. To suppress possible backgrounds EXO will complement the measurement of decay energy and, to some extent, topology of candidate events in a Xe filled detector with the identification of the daughter nucleus ($^{136}$Ba). The ion trap described here is capable of accepting, cooling, and confining individual Ba ions extracted from the site of the candidate double-beta decay event. A single trapped ion can then be identified, with a large signal-to-noise ratio, via laser spectroscopy.Comment: 18 pages, pdflatex, submitted to NIM

Transmission of Methicillin‐Resistant Staphylococcus aureus Infection Through Solid Organ Transplantation: Confirmation Via Whole Genome Sequencing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109324/1/ajt12898.pd

Design and Bolometer Characterization of the SPT-3G First-year Focal Plane

During the austral summer of 2016-17, the third-generation camera, SPT-3G, was installed on the South Pole Telescope, increasing the detector count in the focal plane by an order of magnitude relative to the previous generation. Designed to map the polarization of the cosmic microwave background, SPT-3G contains ten 6-in-hexagonal modules of detectors, each with 269 trichroic and dual-polarization pixels, read out using 68x frequency-domain multiplexing. Here we discuss design, assembly, and layout of the modules, as well as early performance characterization of the first-year array, including yield and detector properties.Comment: Conference proceeding for Low Temperature Detectors 2017. Accepted for publication: 27 August 201

Cosmological constraints combining H(z), CMB shift and SNIa observational data

Recently H(z) data obtained from differential ages of galaxies have been proposed as a new geometrical probe of dark energy. In this paper we use those data, combined with other background tests (CMB shift and SNIa data), to constrain a set of general relativistic dark energy models together with some other models motivated by extra dimensions. Our analysis rests mostly on Bayesian statistics, and we conclude that LCDM is at least substantially favoured, and that braneworld models are less favoured than general relativistic ones.Comment: 17 pages, 11 figures; improved discussion, new figures, updated to match published versio