Structural Insights into Differences in Drug-binding Selectivity between Two Forms of Human α1-Acid Glycoprotein Genetic Variants, the A and F1*S Forms

Human α1-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type. In this study, we determined the crystal structures of this mutant hAGP alone and complexed with disopyramide (DSP), amitriptyline (AMT), and the nonspecific drug chlorpromazine (CPZ). The crystal structures revealed that the drug-binding pocket on the A variant is located within an eight-stranded β-barrel, similar to that found in the F1*S variant and other lipocalin family proteins. However, the binding region of the A variant is narrower than that of the F1*S variant. In the crystal structures of complexes with DSP and AMT, the two aromatic rings of each drug interact with Phe-49 and Phe-112 at the bottom of the binding pocket. Although the structure of CPZ is similar to those of DSP and AMT, its fused aromatic ring system, which is extended in length by the addition of a chlorine atom, appears to dictate an alternative mode of binding, which explains its nonselective binding to the F1*S and A variant hAGPs. Modeling experiments based on the co-crystal structures suggest that, in complexes of DSP, AMT, or CPZ with the F1*S variant, Phe-114 sterically hinders interactions with DSP and AMT, but not CPZ. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

1 um Excess Sources in the UKIDSS - I. Three T Dwarfs in the SDSS Southern Equatorial Stripe

We report the discovery of two field brown dwarfs, ULAS J0128-0041 and ULAS J0321+0051, and the rediscovery of ULAS J0226+0051 (IfA 0230-Z1), in the Sloan Digital Sky Survey (SDSS) southern equatorial stripe. They are found in the course of our follow-up observation program of 1 um excess sources in the United Kingdom Infrared Telescope Infrared Deep Sky Survey. The Gemini Multi-Object Spectrographs spectra at red optical wavelengths (6500-10500 A) are presented, which reveal that they are early-T dwarfs. The classification is also supported by their optical to near-infrared colors. It is noted that ULAS J0321+0051 is one of the faintest currently known T dwarfs. The estimated distances to the three objects are 50-110 pc, thus they are among the most distant field T dwarfs known. Dense temporal coverage of the target fields achieved by the SDSS-II Supernova Survey allows us to perform a simple time-series analysis, which leads to the finding of significant proper motions of 150-290 mas/yr or the transverse velocities of 40-100 km/s for ULAS J0128-0041 and ULAS J0226+0051. We also find that there are no detectable, long-term (a-few-year) brightness variations above a few times 0.1 mag for the two brown dwarfs.Comment: Accepted for publication in the Astronomical Journal; Typos correcte

Effects of alloying on the strain response of critical currents in Nb/sub 3/Sn conductors

The critical current, I/sub c/, of bronze-processed Nb/sub 3/Sn conductors vary when the conductors are mechanically strained in tension or compression. The variations in I/sub c/ are reversible until the strains are large enough to cause cracking of the Nb/sub 3/Sn compound. After cracking occurs the changes in I/sub c/ with strain are irreversible. The reversible and irreversible characteristics of I/sub c/ are influenced by alloy additions to the conductors. Alloy additions to both the bronze matrix and the filament core are examined from the standpoint of their effects on the reversible and irreversible changes. Interpretation is based on our present understanding of the micromechanical aspects of these composite materials

Towards atomically precise manipulation of 2D nanostructures in the electron microscope

Despite decades of research, the ultimate goal of nanotechnology—top-down manipulation of individual atoms—has been directly achieved with only one technique: scanning probe microscopy. In this review, we demonstrate that scanning transmission electron microscopy (STEM) is emerging as an alternative method for the direct assembly of nanostructures, with possible applications in plasmonics, quantum technologies, and materials science. Atomically precise manipulation with STEM relies on recent advances in instrumentation that have enabled non-destructive atomicresolution imaging at lower electron energies. While momentum transfer from highly energetic electrons often leads to atom ejection, interesting dynamics can be induced when the transferable kinetic energies are comparable to bond strengths in the material. Operating in this regime, very recent experiments have revealed the potential for single-atom manipulation using the Ångströmsized electron beam. To truly enable control, however, it is vital to understand the relevant atomicscale phenomena through accurate dynamical simulations. Although excellent agreement between experiment and theory for the specific case of atomic displacements from graphene has been recently achieved using density functional theory molecular dynamics, in many other cases quantitative accuracy remains a challenge. We provide a comprehensive reanalysis of available experimental data on beam-driven dynamics in light of the state-of-the-art in simulations, and identify important targets for improvement. Overall, the modern electron microscope has great potential to become an atom-scale fabrication platform, especially for covalently bonded 2D nanostructures. We review the developments that have made this possible, argue that graphene is an ideal starting material, and assess the main challenges moving forward

Toward Confined Carbyne with Tailored Properties

Confining carbyne to a space that allows for stability and controlled reactivity is a very appealing approach to have access to materials with tunable optical and electronic properties without rival. Here, we show how controlling the diameter of single-walled carbon nanotubes opens the possibility to grow a confined carbyne with a defined and tunable band gap. The metallicity of the tubes has a minimal influence on the formation of the carbyne, whereas the diameter plays a major role in the growth. It has been found that the properties of confined carbyne can be tailored independently from its length and how these are mostly determined by its interaction with the carbon nanotube. Molecular dynamics simulations have been performed to interpret these findings. Furthermore, the choice of a single-walled carbon nanotube host has been proven crucial even to synthesize an enriched carbyne with the smallest energy gap currently reported and with remarkable homogeneity

Atomic Configuration of Nitrogen Doped Single-Walled Carbon Nanotubes

Having access to the chemical environment at the atomic level of a dopant in a nanostructure is crucial for the understanding of its properties. We have performed atomically-resolved electron energy-loss spectroscopy to detect individual nitrogen dopants in single-walled carbon nanotubes and compared with first principles calculations. We demonstrate that nitrogen doping occurs as single atoms in different bonding configurations: graphitic-like and pyrrolic-like substitutional nitrogen neighbouring local lattice distortion such as Stone-Thrower-Wales defects. The stability under the electron beam of these nanotubes has been studied in two extreme cases of nitrogen incorporation content and configuration. These findings provide key information for the applications of these nanostructures.Comment: 25 pages, 13 figure