2,731 research outputs found
Dynamic routing model and solution methods for fleet management with mobile technologies
Author name used in this publication: K. L. ChoyAuthor name used in this publication: Wenzhong Shi2007-2008 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe
Uncovering the Global Life Cycles of the Rare Earth Elements
The rare earth elements (REE) are a group of fifteen elements with unique properties that make them indispensable for a wide variety of emerging, critical technologies. Knowledge of the life cycles of REE remains sparse, despite the current heightened interest in their future availability. Mining is heavily concentrated in China, whose monopoly position and potential restriction of exports render primary supplies vulnerable to short and long-term disruption. To provide an improved perspective we derived the first quantitative life cycles (for the year 2007) for ten REE: lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), and yttrium (Y). Of these REE, Ce and Nd in-use stocks are highest; the in-use stocks of most REE show significant accumulation in modern society. Industrial scrap recycling occurs only from magnet manufacture. We believe there is no post-customer recycling of any of these elements
Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces
TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al
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
Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts
The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al
Higher-order multipole amplitudes in charmonium radiative transitions
Using 24 million decays in CLEO-c, we have searched
for higher multipole admixtures in electric-dipole-dominated radiative
transitions in charmonia. We find good agreement between our data and
theoretical predictions for magnetic quadrupole (M2) amplitudes in the
transitions and ,
in striking contrast to some previous measurements. Let and
denote the normalized M2 amplitudes in the respective aforementioned decays,
where the superscript refers to the angular momentum of the . By
performing unbinned maximum likelihood fits to full five-parameter angular
distributions, we determine the ratios and , where
the theoretical predictions are independent of the charmed quark magnetic
moment and are and .Comment: 32 pages, 7 figures, acceptance updat
Counter-current chromatography for the separation of terpenoids: A comprehensive review with respect to the solvent systems employed
Copyright @ 2014 The Authors.This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Natural products extracts are commonly highly complex mixtures of active compounds and consequently their purification becomes a particularly challenging task. The development of a purification protocol to extract a single active component from the many hundreds that are often present in the mixture is something that can take months or even years to achieve, thus it is important for the natural product chemist to have, at their disposal, a broad range of diverse purification techniques. Counter-current chromatography (CCC) is one such separation technique utilising two immiscible phases, one as the stationary phase (retained in a spinning coil by centrifugal forces) and the second as the mobile phase. The method benefits from a number of advantages when compared with the more traditional liquid-solid separation methods, such as no irreversible adsorption, total recovery of the injected sample, minimal tailing of peaks, low risk of sample denaturation, the ability to accept particulates, and a low solvent consumption. The selection of an appropriate two-phase solvent system is critical to the running of CCC since this is both the mobile and the stationary phase of the system. However, this is also by far the most time consuming aspect of the technique and the one that most inhibits its general take-up. In recent years, numerous natural product purifications have been published using CCC from almost every country across the globe. Many of these papers are devoted to terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide opportunities to discover new drugs but many of them are available at very low levels in nature and a huge number of them still remain unexplored. The collective knowledge on performing successful CCC separations of terpenoids has been gathered and reviewed by the authors, in order to create a comprehensive document that will be of great assistance in performing future purifications. © 2014 The Author(s)
Search for D0 to p e- and D0 to pbar e+
Using data recorded by CLEO-c detector at CESR, we search for simultaneous
baryon and lepton number violating decays of the D^0 meson, specifically, D^0
--> p-bar e^+, D^0-bar --> p-bar e^+, D^0 --> p e^- and D^0-bar --> p e^-. We
set the following branching fraction upper limits: D^0 --> p-bar e^+ (D^0-bar
--> p-bar e^+) p e^- (D^0-bar --> p e^-) < 1.2 *
10^{-5}, both at 90% confidence level.Comment: 10 pages, available through http://www.lns.cornell.edu/public/CLNS/,
submitted to PRD. Comments: changed abstract, added reference for section 1,
vertical axis in Fig.5 changed (starts from 1.5 rather than 2.0), fixed typo
Dalitz Plot Analysis of Ds to K+K-pi+
We perform a Dalitz plot analysis of the decay Ds to K+K-pi+ with the CLEO-c
data set of 586/pb of e+e- collisions accumulated at sqrt(s) = 4.17 GeV. This
corresponds to about 0.57 million D_s+D_s(*)- pairs from which we select 14400
candidates with a background of roughly 15%. In contrast to previous
measurements we find good agreement with our data only by including an
additional f_0(1370)pi+ contribution. We measure the magnitude, phase, and fit
fraction of K*(892) K+, phi(1020)pi+, K0*(1430)K+, f_0(980)pi+, f_0(1710)pi+,
and f_0(1370)pi+ contributions and limit the possible contributions of other KK
and Kpi resonances that could appear in this decay.Comment: 21 Pages,available through http://www.lns.cornell.edu/public/CLNS/,
submitted to PR
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