Structure of the ThDP-dependent enzyme benzaldehyde lyase refined to 1.65 Å resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maraite, Andy; Schmidt, Thomas; Ansörge-Schumacher, Marion B.

2007-07-01

The X-ray crystal structure of the ThDP-dependent enzyme benzaldehyde lyase has been refined to 1.65 Å. Benzaldehyde lyase (BAL; EC 4.1.2.38) is a thiamine diphosphate (ThDP) dependent enzyme that catalyses the enantioselective carboligation of two molecules of benzaldehyde to form (R)-benzoin. BAL has hence aroused interest for its potential in the industrial synthesis of optically active benzoins and derivatives. The structure of BAL was previously solved to a resolution of 2.6 Å using MAD experiments on a selenomethionine derivative [Mosbacher et al. (2005 ▶), FEBS J.272, 6067–6076]. In this communication of parallel studies, BAL was crystallized in an alternative spacemore » group (P2{sub 1}2{sub 1}2{sub 1}) and its structure refined to a resolution of 1.65 Å, allowing detailed observation of the water structure, active-site interactions with ThDP and also the electron density for the co-solvent 2-methyl-2,4-pentanediol (MPD) at hydrophobic patches of the enzyme surface.« less

Structural refinement of vitreous silica bilayers

NASA Astrophysics Data System (ADS)

Sadjadi, Mahdi; Wilson, Mark; Thorpe, M. F.

The importance of glasses resides not only in their applications but in fundamental questions that they put forth. The continuous random network model can successfully describe the glass structure, but determining details, like ring statistics, has always been difficult using only diffraction data. But recent atomic images of 2D vitreous silica bilayers can offer valuable new insights which are hard to be observed directly in 3D silica models/experiments (for references see). However, the experimental results are prone to uncertainty in atomic positions, systematic errors, and being finite. We employ special boundary conditions developed for such networks to refine the experimental structures. We show the best structure can be found by using various potentials to maximize information gained from the experimental samples. We find a range of densities, the so-called flexibility window, in which tetrahedra are perfect. We compare results from simulations using harmonic potentials, MD with atomic polarizabilities included and DFT. We should thank David Drabold and Bishal Bhattarai for useful discussions. Support through NSF Grant # DMS 1564468 is gratefully acknowledged.

Improved ligand geometries in crystallographic refinement using AFITT in PHENIX

DOE PAGES

Janowski, Pawel A.; Moriarty, Nigel W.; Kelley, Brian P.; ...

2016-08-31

Modern crystal structure refinement programs rely on geometry restraints to overcome the challenge of a low data-to-parameter ratio. While the classical Engh and Huber restraints work well for standard amino-acid residues, the chemical complexity of small-molecule ligands presents a particular challenge. Most current approaches either limit ligand restraints to those that can be readily described in the Crystallographic Information File (CIF) format, thus sacrificing chemical flexibility and energetic accuracy, or they employ protocols that substantially lengthen the refinement time, potentially hindering rapid automated refinement workflows.PHENIX–AFITTrefinement uses a full molecular-mechanics force field for user-selected small-molecule ligands during refinement, eliminating the potentiallymore » difficult problem of finding or generating high-quality geometry restraints. It is fully integrated with a standard refinement protocol and requires practically no additional steps from the user, making it ideal for high-throughput workflows.PHENIX–AFITTrefinements also handle multiple ligands in a single model, alternate conformations and covalently bound ligands. Here, the results of combiningAFITTand thePHENIXsoftware suite on a data set of 189 protein–ligand PDB structures are presented. Refinements usingPHENIX–AFITTsignificantly reduce ligand conformational energy and lead to improved geometries without detriment to the fit to the experimental data. Finally, for the data presented,PHENIX–AFITTrefinements result in more chemically accurate models for small-molecule ligands.« less

Protein Structure Validation and Refinement Using Amide Proton Chemical Shifts Derived from Quantum Mechanics

PubMed Central

Christensen, Anders S.; Linnet, Troels E.; Borg, Mikael; Boomsma, Wouter; Lindorff-Larsen, Kresten; Hamelryck, Thomas; Jensen, Jan H.

2013-01-01

We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond (h3 JNC') spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to obtain this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding. PMID:24391900

FUN3D Grid Refinement and Adaptation Studies for the Ares Launch Vehicle

NASA Technical Reports Server (NTRS)

Bartels, Robert E.; Vasta, Veer; Carlson, Jan-Renee; Park, Mike; Mineck, Raymond E.

2010-01-01

This paper presents grid refinement and adaptation studies performed in conjunction with computational aeroelastic analyses of the Ares crew launch vehicle (CLV). The unstructured grids used in this analysis were created with GridTool and VGRID while the adaptation was performed using the Computational Fluid Dynamic (CFD) code FUN3D with a feature based adaptation software tool. GridTool was developed by ViGYAN, Inc. while the last three software suites were developed by NASA Langley Research Center. The feature based adaptation software used here operates by aligning control volumes with shock and Mach line structures and by refining/de-refining where necessary. It does not redistribute node points on the surface. This paper assesses the sensitivity of the complex flow field about a launch vehicle to grid refinement. It also assesses the potential of feature based grid adaptation to improve the accuracy of CFD analysis for a complex launch vehicle configuration. The feature based adaptation shows the potential to improve the resolution of shocks and shear layers. Further development of the capability to adapt the boundary layer and surface grids of a tetrahedral grid is required for significant improvements in modeling the flow field.

In situ data collection and structure refinement from microcapillary protein crystallization

PubMed Central

Yadav, Maneesh K.; Gerdts, Cory J.; Sanishvili, Ruslan; Smith, Ward W.; Roach, L. Spencer; Ismagilov, Rustem F.; Kuhn, Peter; Stevens, Raymond C.

2007-01-01

In situ X-ray data collection has the potential to eliminate the challenging task of mounting and cryocooling often fragile protein crystals, reducing a major bottleneck in the structure determination process. An apparatus used to grow protein crystals in capillaries and to compare the background X-ray scattering of the components, including thin-walled glass capillaries against Teflon, and various fluorocarbon oils against each other, is described. Using thaumatin as a test case at 1.8 Å resolution, this study demonstrates that high-resolution electron density maps and refined models can be obtained from in situ diffraction of crystals grown in microcapillaries. PMID:17468785

i3Drefine software for protein 3D structure refinement and its assessment in CASP10.

PubMed

Bhattacharya, Debswapna; Cheng, Jianlin

2013-01-01

Protein structure refinement refers to the process of improving the qualities of protein structures during structure modeling processes to bring them closer to their native states. Structure refinement has been drawing increasing attention in the community-wide Critical Assessment of techniques for Protein Structure prediction (CASP) experiments since its addition in 8(th) CASP experiment. During the 9(th) and recently concluded 10(th) CASP experiments, a consistent growth in number of refinement targets and participating groups has been witnessed. Yet, protein structure refinement still remains a largely unsolved problem with majority of participating groups in CASP refinement category failed to consistently improve the quality of structures issued for refinement. In order to alleviate this need, we developed a completely automated and computationally efficient protein 3D structure refinement method, i3Drefine, based on an iterative and highly convergent energy minimization algorithm with a powerful all-atom composite physics and knowledge-based force fields and hydrogen bonding (HB) network optimization technique. In the recent community-wide blind experiment, CASP10, i3Drefine (as 'MULTICOM-CONSTRUCT') was ranked as the best method in the server section as per the official assessment of CASP10 experiment. Here we provide the community with free access to i3Drefine software and systematically analyse the performance of i3Drefine in strict blind mode on the refinement targets issued in CASP10 refinement category and compare with other state-of-the-art refinement methods participating in CASP10. Our analysis demonstrates that i3Drefine is only fully-automated server participating in CASP10 exhibiting consistent improvement over the initial structures in both global and local structural quality metrics. Executable version of i3Drefine is freely available at http://protein.rnet.missouri.edu/i3drefine/.

Deformable complex network for refining low-resolution X-ray structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Chong; Wang, Qinghua; Ma, Jianpeng, E-mail: jpma@bcm.edu

2015-10-27

A new refinement algorithm called the deformable complex network that combines a novel angular network-based restraint with a deformable elastic network model in the target function has been developed to aid in structural refinement in macromolecular X-ray crystallography. In macromolecular X-ray crystallography, building more accurate atomic models based on lower resolution experimental diffraction data remains a great challenge. Previous studies have used a deformable elastic network (DEN) model to aid in low-resolution structural refinement. In this study, the development of a new refinement algorithm called the deformable complex network (DCN) is reported that combines a novel angular network-based restraint withmore » the DEN model in the target function. Testing of DCN on a wide range of low-resolution structures demonstrated that it constantly leads to significantly improved structural models as judged by multiple refinement criteria, thus representing a new effective refinement tool for low-resolution structural determination.« less

Improved cryoEM-Guided Iterative Molecular Dynamics–Rosetta Protein Structure Refinement Protocol for High Precision Protein Structure Prediction

PubMed Central

2016-01-01

Many excellent methods exist that incorporate cryo-electron microscopy (cryoEM) data to constrain computational protein structure prediction and refinement. Previously, it was shown that iteration of two such orthogonal sampling and scoring methods – Rosetta and molecular dynamics (MD) simulations – facilitated exploration of conformational space in principle. Here, we go beyond a proof-of-concept study and address significant remaining limitations of the iterative MD–Rosetta protein structure refinement protocol. Specifically, all parts of the iterative refinement protocol are now guided by medium-resolution cryoEM density maps, and previous knowledge about the native structure of the protein is no longer necessary. Models are identified solely based on score or simulation time. All four benchmark proteins showed substantial improvement through three rounds of the iterative refinement protocol. The best-scoring final models of two proteins had sub-Ångstrom RMSD to the native structure over residues in secondary structure elements. Molecular dynamics was most efficient in refining secondary structure elements and was thus highly complementary to the Rosetta refinement which is most powerful in refining side chains and loop regions. PMID:25883538

TOWARDS REFINED USE OF TOXICITY DATA IN STATISTICALLY BASED SAR MODELS FOR DEVELOPMENTAL TOXICITY.

EPA Science Inventory

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

i3Drefine Software for Protein 3D Structure Refinement and Its Assessment in CASP10

PubMed Central

Bhattacharya, Debswapna; Cheng, Jianlin

2013-01-01

Protein structure refinement refers to the process of improving the qualities of protein structures during structure modeling processes to bring them closer to their native states. Structure refinement has been drawing increasing attention in the community-wide Critical Assessment of techniques for Protein Structure prediction (CASP) experiments since its addition in 8th CASP experiment. During the 9th and recently concluded 10th CASP experiments, a consistent growth in number of refinement targets and participating groups has been witnessed. Yet, protein structure refinement still remains a largely unsolved problem with majority of participating groups in CASP refinement category failed to consistently improve the quality of structures issued for refinement. In order to alleviate this need, we developed a completely automated and computationally efficient protein 3D structure refinement method, i3Drefine, based on an iterative and highly convergent energy minimization algorithm with a powerful all-atom composite physics and knowledge-based force fields and hydrogen bonding (HB) network optimization technique. In the recent community-wide blind experiment, CASP10, i3Drefine (as ‘MULTICOM-CONSTRUCT’) was ranked as the best method in the server section as per the official assessment of CASP10 experiment. Here we provide the community with free access to i3Drefine software and systematically analyse the performance of i3Drefine in strict blind mode on the refinement targets issued in CASP10 refinement category and compare with other state-of-the-art refinement methods participating in CASP10. Our analysis demonstrates that i3Drefine is only fully-automated server participating in CASP10 exhibiting consistent improvement over the initial structures in both global and local structural quality metrics. Executable version of i3Drefine is freely available at http://protein.rnet.missouri.edu/i3drefine/. PMID:23894517

Structural exploration for the refinement of anticancer matrix metalloproteinase-2 inhibitor designing approaches through robust validated multi-QSARs

NASA Astrophysics Data System (ADS)

Adhikari, Nilanjan; Amin, Sk. Abdul; Saha, Achintya; Jha, Tarun

2018-03-01

Matrix metalloproteinase-2 (MMP-2) is a promising pharmacological target for designing potential anticancer drugs. MMP-2 plays critical functions in apoptosis by cleaving the DNA repair enzyme namely poly (ADP-ribose) polymerase (PARP). Moreover, MMP-2 expression triggers the vascular endothelial growth factor (VEGF) having a positive influence on tumor size, invasion, and angiogenesis. Therefore, it is an urgent need to develop potential MMP-2 inhibitors without any toxicity but better pharmacokinetic property. In this article, robust validated multi-quantitative structure-activity relationship (QSAR) modeling approaches were attempted on a dataset of 222 MMP-2 inhibitors to explore the important structural and pharmacophoric requirements for higher MMP-2 inhibition. Different validated regression and classification-based QSARs, pharmacophore mapping and 3D-QSAR techniques were performed. These results were challenged and subjected to further validation to explain 24 in house MMP-2 inhibitors to judge the reliability of these models further. All these models were individually validated internally as well as externally and were supported and validated by each other. These results were further justified by molecular docking analysis. Modeling techniques adopted here not only helps to explore the necessary structural and pharmacophoric requirements but also for the overall validation and refinement techniques for designing potential MMP-2 inhibitors.

Solution NMR Refinement of a Metal Ion Bound Protein Using Metal Ion Inclusive Restrained Molecular Dynamics Methods

PubMed Central

Chakravorty, Dhruva K.; Wang, Bing; Lee, Chul Won; Guerra, Alfredo J.; Giedroc, David P.; Merz, Kenneth M.

2013-01-01

Correctly calculating the structure of metal coordination sites in a protein during the process of nuclear magnetic resonance (NMR) structure determination and refinement continues to be a challenging task. In this study, we present an accurate and convenient means by which to include metal ions in the NMR structure determination process using molecular dynamics (MD) constrained by NMR-derived data to obtain a realistic and physically viable description of the metal binding site(s). This method provides the framework to accurately portray the metal ions and its binding residues in a pseudo-bond or dummy-cation like approach, and is validated by quantum mechanical/molecular mechanical (QM/MM) MD calculations constrained by NMR-derived data. To illustrate this approach, we refine the zinc coordination complex structure of the zinc sensing transcriptional repressor protein Staphylococcus aureus CzrA, generating over 130 ns of MD and QM/MM MD NMR-data compliant sampling. In addition to refining the first coordination shell structure of the Zn(II) ion, this protocol benefits from being performed in a periodically replicated solvation environment including long-range electrostatics. We determine that unrestrained (not based on NMR data) MD simulations correlated to the NMR data in a time-averaged ensemble. The accurate solution structure ensemble of the metal-bound protein accurately describes the role of conformational dynamics in allosteric regulation of DNA binding by zinc and serves to validate our previous unrestrained MD simulations of CzrA. This methodology has potentially broad applicability in the structure determination of metal ion bound proteins, protein folding and metal template protein-design studies. PMID:23609042

Solidification Based Grain Refinement in Steels

DTIC Science & Technology

2009-07-24

pearlite (See Figure 1). No evidence of the as-cast austenite dendrite structure was observed. The gating system for this sample resides at the thermal...possible nucleating compounds. 3) Extend grain refinement theory and solidification knowledge through experimental data. 4) Determine structure ...refine the structure of a casting through heat treatment. The energy required for grain refining via thermomechanical processes or heat treatment

Structure Refinement of Protein Low Resolution Models Using the GNEIMO Constrained Dynamics Method

PubMed Central

Park, In-Hee; Gangupomu, Vamshi; Wagner, Jeffrey; Jain, Abhinandan; Vaidehi, Nagara-jan

2012-01-01

The challenge in protein structure prediction using homology modeling is the lack of reliable methods to refine the low resolution homology models. Unconstrained all-atom molecular dynamics (MD) does not serve well for structure refinement due to its limited conformational search. We have developed and tested the constrained MD method, based on the Generalized Newton-Euler Inverse Mass Operator (GNEIMO) algorithm for protein structure refinement. In this method, the high-frequency degrees of freedom are replaced with hard holonomic constraints and a protein is modeled as a collection of rigid body clusters connected by flexible torsional hinges. This allows larger integration time steps and enhances the conformational search space. In this work, we have demonstrated the use of a constraint free GNEIMO method for protein structure refinement that starts from low-resolution decoy sets derived from homology methods. In the eight proteins with three decoys for each, we observed an improvement of ~2 Å in the RMSD to the known experimental structures of these proteins. The GNEIMO method also showed enrichment in the population density of native-like conformations. In addition, we demonstrated structural refinement using a “Freeze and Thaw” clustering scheme with the GNEIMO framework as a viable tool for enhancing localized conformational search. We have derived a robust protocol based on the GNEIMO replica exchange method for protein structure refinement that can be readily extended to other proteins and possibly applicable for high throughput protein structure refinement. PMID:22260550

REFMAC5 for the refinement of macromolecular crystal structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murshudov, Garib N., E-mail: garib@ysbl.york.ac.uk; Skubák, Pavol; Lebedev, Andrey A.

The general principles behind the macromolecular crystal structure refinement program REFMAC5 are described. This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part of the CCP4 suite. REFMAC5 utilizes different likelihood functions depending on the diffraction data employed (amplitudes or intensities), the presence of twinning and the availability of SAD/SIRAS experimental diffraction data. To ensure chemical and structural integrity of the refined model, REFMAC5 offers several classes of restraints and choices of model parameterization. Reliable models at resolutions at least as low as 4 Å can be achieved thanks to low-resolution refinement toolsmore » such as secondary-structure restraints, restraints to known homologous structures, automatic global and local NCS restraints, ‘jelly-body’ restraints and the use of novel long-range restraints on atomic displacement parameters (ADPs) based on the Kullback–Leibler divergence. REFMAC5 additionally offers TLS parameterization and, when high-resolution data are available, fast refinement of anisotropic ADPs. Refinement in the presence of twinning is performed in a fully automated fashion. REFMAC5 is a flexible and highly optimized refinement package that is ideally suited for refinement across the entire resolution spectrum encountered in macromolecular crystallography.« less

Implementation of a parallel protein structure alignment service on cloud.

PubMed

Hung, Che-Lun; Lin, Yaw-Ling

2013-01-01

Protein structure alignment has become an important strategy by which to identify evolutionary relationships between protein sequences. Several alignment tools are currently available for online comparison of protein structures. In this paper, we propose a parallel protein structure alignment service based on the Hadoop distribution framework. This service includes a protein structure alignment algorithm, a refinement algorithm, and a MapReduce programming model. The refinement algorithm refines the result of alignment. To process vast numbers of protein structures in parallel, the alignment and refinement algorithms are implemented using MapReduce. We analyzed and compared the structure alignments produced by different methods using a dataset randomly selected from the PDB database. The experimental results verify that the proposed algorithm refines the resulting alignments more accurately than existing algorithms. Meanwhile, the computational performance of the proposed service is proportional to the number of processors used in our cloud platform.

Implementation of a Parallel Protein Structure Alignment Service on Cloud

PubMed Central

Hung, Che-Lun; Lin, Yaw-Ling

2013-01-01

Protein structure alignment has become an important strategy by which to identify evolutionary relationships between protein sequences. Several alignment tools are currently available for online comparison of protein structures. In this paper, we propose a parallel protein structure alignment service based on the Hadoop distribution framework. This service includes a protein structure alignment algorithm, a refinement algorithm, and a MapReduce programming model. The refinement algorithm refines the result of alignment. To process vast numbers of protein structures in parallel, the alignment and refinement algorithms are implemented using MapReduce. We analyzed and compared the structure alignments produced by different methods using a dataset randomly selected from the PDB database. The experimental results verify that the proposed algorithm refines the resulting alignments more accurately than existing algorithms. Meanwhile, the computational performance of the proposed service is proportional to the number of processors used in our cloud platform. PMID:23671842

X-ray structure determination at low resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brunger, Axel T., E-mail: brunger@stanford.edu; Department of Molecular and Cellular Physiology, Stanford University; Department of Neurology and Neurological Sciences, Stanford University

2009-02-01

Refinement is meaningful even at 4 Å or lower, but with present methodologies it should start from high-resolution crystal structures whenever possible. As an example of structure determination in the 3.5–4.5 Å resolution range, crystal structures of the ATPase p97/VCP, consisting of an N-terminal domain followed by a tandem pair of ATPase domains (D1 and D2), are discussed. The structures were originally solved by molecular replacement with the high-resolution structure of the N-D1 fragment of p97/VCP, whereas the D2 domain was manually built using its homology to the D1 domain as a guide. The structure of the D2 domain alonemore » was subsequently solved at 3 Å resolution. The refined model of D2 and the high-resolution structure of the N-D1 fragment were then used as starting models for re-refinement against the low-resolution diffraction data for full-length p97. The re-refined full-length models showed significant improvement in both secondary structure and R values. The free R values dropped by as much as 5% compared with the original structure refinements, indicating that refinement is meaningful at low resolution and that there is information in the diffraction data even at ∼4 Å resolution that objectively assesses the quality of the model. It is concluded that de novo model building is problematic at low resolution and refinement should start from high-resolution crystal structures whenever possible.« less

Enzymatic Synthesis of Refined Olive Oil-Based Structured Lipid Containing Omega -3 and -6 Fatty Acids for Potential Application in Infant Formula.

PubMed

Li, Ruoyu; Sabir, Jamal S M; Baeshen, Nabih A; Akoh, Casimir C

2015-11-01

Structured lipids (SLs) containing palmitic, docosahexaenoic (DHA), and gamma-linolenic (GLA) acids were produced using refined olive oil, tripalmitin, and ethyl esters of DHA single cell oil and GLA ethyl esters. Immobilized Lipozyme TL IM lipase was used as the biocatalyst. The SLs were characterized for fatty acid profile, triacylglycerol (TAG) molecular species, solid fat content, oxidative stability index, and melting and crystallization profiles and compared to physical blend of substrates, extracted fat from commercial infant formula (IFF), and milk fat. 49.28 mol% of palmitic acid was found at the sn-2 position of SL TAG and total DHA and GLA composition were 0.73 and 5.00 mol%, respectively. The total oleic acid content was 36.13 mol% which was very close to the 30.49% present in commercial IFF. Comparable solid fat content profiles were also found between SLs and IFF. The SLs produced have potential for use in infant formulas. © 2015 Institute of Food Technologists®

Improving the accuracy of macromolecular structure refinement at 7 Å resolution.

PubMed

Brunger, Axel T; Adams, Paul D; Fromme, Petra; Fromme, Raimund; Levitt, Michael; Schröder, Gunnar F

2012-06-06

In X-ray crystallography, molecular replacement and subsequent refinement is challenging at low resolution. We compared refinement methods using synchrotron diffraction data of photosystem I at 7.4 Å resolution, starting from different initial models with increasing deviations from the known high-resolution structure. Standard refinement spoiled the initial models, moving them further away from the true structure and leading to high R(free)-values. In contrast, DEN refinement improved even the most distant starting model as judged by R(free), atomic root-mean-square differences to the true structure, significance of features not included in the initial model, and connectivity of electron density. The best protocol was DEN refinement with initial segmented rigid-body refinement. For the most distant initial model, the fraction of atoms within 2 Å of the true structure improved from 24% to 60%. We also found a significant correlation between R(free) values and the accuracy of the model, suggesting that R(free) is useful even at low resolution. Copyright © 2012 Elsevier Ltd. All rights reserved.

GalaxyRefineComplex: Refinement of protein-protein complex model structures driven by interface repacking.

PubMed

Heo, Lim; Lee, Hasup; Seok, Chaok

2016-08-18

Protein-protein docking methods have been widely used to gain an atomic-level understanding of protein interactions. However, docking methods that employ low-resolution energy functions are popular because of computational efficiency. Low-resolution docking tends to generate protein complex structures that are not fully optimized. GalaxyRefineComplex takes such low-resolution docking structures and refines them to improve model accuracy in terms of both interface contact and inter-protein orientation. This refinement method allows flexibility at the protein interface and in the overall docking structure to capture conformational changes that occur upon binding. Symmetric refinement is also provided for symmetric homo-complexes. This method was validated by refining models produced by available docking programs, including ZDOCK and M-ZDOCK, and was successfully applied to CAPRI targets in a blind fashion. An example of using the refinement method with an existing docking method for ligand binding mode prediction of a drug target is also presented. A web server that implements the method is freely available at http://galaxy.seoklab.org/refinecomplex.

Predicting X-ray diffuse scattering from translation–libration–screw structural ensembles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Benschoten, Andrew H.; Afonine, Pavel V.; Terwilliger, Thomas C.

2015-07-28

A method of simulating X-ray diffuse scattering from multi-model PDB files is presented. Despite similar agreement with Bragg data, different translation–libration–screw refinement strategies produce unique diffuse intensity patterns. Identifying the intramolecular motions of proteins and nucleic acids is a major challenge in macromolecular X-ray crystallography. Because Bragg diffraction describes the average positional distribution of crystalline atoms with imperfect precision, the resulting electron density can be compatible with multiple models of motion. Diffuse X-ray scattering can reduce this degeneracy by reporting on correlated atomic displacements. Although recent technological advances are increasing the potential to accurately measure diffuse scattering, computational modeling andmore » validation tools are still needed to quantify the agreement between experimental data and different parameterizations of crystalline disorder. A new tool, phenix.diffuse, addresses this need by employing Guinier’s equation to calculate diffuse scattering from Protein Data Bank (PDB)-formatted structural ensembles. As an example case, phenix.diffuse is applied to translation–libration–screw (TLS) refinement, which models rigid-body displacement for segments of the macromolecule. To enable the calculation of diffuse scattering from TLS-refined structures, phenix.tls-as-xyz builds multi-model PDB files that sample the underlying T, L and S tensors. In the glycerophosphodiesterase GpdQ, alternative TLS-group partitioning and different motional correlations between groups yield markedly dissimilar diffuse scattering maps with distinct implications for molecular mechanism and allostery. These methods demonstrate how, in principle, X-ray diffuse scattering could extend macromolecular structural refinement, validation and analysis.« less

Structure refinement of membrane proteins via molecular dynamics simulations.

PubMed

Dutagaci, Bercem; Heo, Lim; Feig, Michael

2018-07-01

A refinement protocol based on physics-based techniques established for water soluble proteins is tested for membrane protein structures. Initial structures were generated by homology modeling and sampled via molecular dynamics simulations in explicit lipid bilayer and aqueous solvent systems. Snapshots from the simulations were selected based on scoring with either knowledge-based or implicit membrane-based scoring functions and averaged to obtain refined models. The protocol resulted in consistent and significant refinement of the membrane protein structures similar to the performance of refinement methods for soluble proteins. Refinement success was similar between sampling in the presence of lipid bilayers and aqueous solvent but the presence of lipid bilayers may benefit the improvement of lipid-facing residues. Scoring with knowledge-based functions (DFIRE and RWplus) was found to be as good as scoring using implicit membrane-based scoring functions suggesting that differences in internal packing is more important than orientations relative to the membrane during the refinement of membrane protein homology models. © 2018 Wiley Periodicals, Inc.

Applying an Empirical Hydropathic Forcefield in Refinement May Improve Low-Resolution Protein X-Ray Crystal Structures

PubMed Central

Koparde, Vishal N.; Scarsdale, J. Neel; Kellogg, Glen E.

2011-01-01

Background The quality of X-ray crystallographic models for biomacromolecules refined from data obtained at high-resolution is assured by the data itself. However, at low-resolution, >3.0 Å, additional information is supplied by a forcefield coupled with an associated refinement protocol. These resulting structures are often of lower quality and thus unsuitable for downstream activities like structure-based drug discovery. Methodology An X-ray crystallography refinement protocol that enhances standard methodology by incorporating energy terms from the HINT (Hydropathic INTeractions) empirical forcefield is described. This protocol was tested by refining synthetic low-resolution structural data derived from 25 diverse high-resolution structures, and referencing the resulting models to these structures. The models were also evaluated with global structural quality metrics, e.g., Ramachandran score and MolProbity clashscore. Three additional structures, for which only low-resolution data are available, were also re-refined with this methodology. Results The enhanced refinement protocol is most beneficial for reflection data at resolutions of 3.0 Å or worse. At the low-resolution limit, ≥4.0 Å, the new protocol generated models with Cα positions that have RMSDs that are 0.18 Å more similar to the reference high-resolution structure, Ramachandran scores improved by 13%, and clashscores improved by 51%, all in comparison to models generated with the standard refinement protocol. The hydropathic forcefield terms are at least as effective as Coulombic electrostatic terms in maintaining polar interaction networks, and significantly more effective in maintaining hydrophobic networks, as synthetic resolution is decremented. Even at resolutions ≥4.0 Å, these latter networks are generally native-like, as measured with a hydropathic interactions scoring tool. PMID:21246043

Cultivating Peace through Design Thinking: Problem Solving with PAST Foundation

ERIC Educational Resources Information Center

Deaner, Kat; McCreery-Kellert, Heather

2018-01-01

Design thinking is a methodology that emphasizes reasoning and decision-making as part of the problem-solving process. It is a structured framework for identifying challenges, gathering information, generating potential solutions, refining ideas, and testing solutions. Design thinking offers valuable skills that will serve students well as they…

Automated main-chain model building by template matching and iterative fragment extension.

PubMed

Terwilliger, Thomas C

2003-01-01

An algorithm for the automated macromolecular model building of polypeptide backbones is described. The procedure is hierarchical. In the initial stages, many overlapping polypeptide fragments are built. In subsequent stages, the fragments are extended and then connected. Identification of the locations of helical and beta-strand regions is carried out by FFT-based template matching. Fragment libraries of helices and beta-strands from refined protein structures are then positioned at the potential locations of helices and strands and the longest segments that fit the electron-density map are chosen. The helices and strands are then extended using fragment libraries consisting of sequences three amino acids long derived from refined protein structures. The resulting segments of polypeptide chain are then connected by choosing those which overlap at two or more C(alpha) positions. The fully automated procedure has been implemented in RESOLVE and is capable of model building at resolutions as low as 3.5 A. The algorithm is useful for building a preliminary main-chain model that can serve as a basis for refinement and side-chain addition.

Electrostatic properties of the pyrimethamine-2,4-dihydroxybenzoic acid cocrystal in methanol studied using transferred electron-density parameters.

PubMed

Faroque, Muhammad Umer; Noureen, Sajida; Ahmed, Maqsood; Tahir, Muhammad Nawaz

2018-01-01

The crystal structure of the cocrystal salt form of the antimalarial drug pyrimethamine with 2,4-dihydroxybenzoic acid in methanol [systematic name: 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2,4-dihydroxybenzoate methanol monosolvate, C 12 H 14 ClN 4 + ·C 7 H 5 O 4 - ·CH 3 OH] has been studied using X-ray diffraction data collected at room temperature. The crystal structure was refined using the classical Independent Atom Model (IAM) and the Multipolar Atom Model by transferring electron-density parameters from the ELMAM2 database. The Cl atom was refined anharmonically. The results of both refinement methods have been compared. The intermolecular interactions have been characterized on the basis of Hirshfeld surface analysis and topological analysis using Bader's theory of Atoms in Molecules. The results show that the molecular assembly is built primarily on the basis of charge transfer between 2,4-dihydroxybenzoic acid and pyrimethamine, which results in strong intermolecular hydrogen bonds. This fact is further validated by the calculation of the electrostatic potential based on transferred electron-density parameters.

Hydrothermal synthesis of a photovoltaic material based on CuIn0.5Ga0.5Se2

NASA Astrophysics Data System (ADS)

Castellanos Báez, Y. T.; Fuquen Peña, D. A.; Gómez-Cuaspud, J. A.; Vera-López, E.; Pineda-Triana, Y.

2017-12-01

The present work report, the synthesis and characterization of the CuIn0.5Ga0.5Se2 system (abbreviated CIGS), by the implementation of a hydrothermal route, in order to obtain a solid with appropriate properties in terms of surface, morphological and texture properties for potential applications in the design of photovoltaic cells. The synthesis was carried out using the corresponding stoichiometric quantities (Cu:In:Ga:Se 1:0.5:0.5:2), which were mixed in a Teflon vessel under stirring conditions. The homogeneous solution was treated in a steel autoclave at 300°C for 72 hours at the end of which the resulting material was characterized by X-Ray Diffraction (XRD) and Rietveld refinement. The results of the structural characterization allowed to confirm the obtaining of a chalcopyrite type structure, with a I-42 d (122) structure and cell parameters a=0.570, b=0.570, c=1.140nm, α=90, β=90, γ=90° oriented along (1 0 4) facet, detecting the presence of a secondary phases, related with CuInSe and CuIn metallic selenides, derived from synthesis process. The structural refinement allowing to validate the obtaining of a nanometric crystalline material (10-20nm) for potential applications in field of photovoltaic technology.

Variability of Protein Structure Models from Electron Microscopy.

PubMed

Monroe, Lyman; Terashi, Genki; Kihara, Daisuke

2017-04-04

An increasing number of biomolecular structures are solved by electron microscopy (EM). However, the quality of structure models determined from EM maps vary substantially. To understand to what extent structure models are supported by information embedded in EM maps, we used two computational structure refinement methods to examine how much structures can be refined using a dataset of 49 maps with accompanying structure models. The extent of structure modification as well as the disagreement between refinement models produced by the two computational methods scaled inversely with the global and the local map resolutions. A general quantitative estimation of deviations of structures for particular map resolutions are provided. Our results indicate that the observed discrepancy between the deposited map and the refined models is due to the lack of structural information present in EM maps and thus these annotations must be used with caution for further applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard.

PubMed

Terwilliger, Thomas C; Grosse-Kunstleve, Ralf W; Afonine, Pavel V; Moriarty, Nigel W; Zwart, Peter H; Hung, Li Wei; Read, Randy J; Adams, Paul D

2008-01-01

The PHENIX AutoBuild wizard is a highly automated tool for iterative model building, structure refinement and density modification using RESOLVE model building, RESOLVE statistical density modification and phenix.refine structure refinement. Recent advances in the AutoBuild wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model-completion algorithms and automated solvent-molecule picking. Model-completion algorithms in the AutoBuild wizard include loop building, crossovers between chains in different models of a structure and side-chain optimization. The AutoBuild wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 to 3.2 A, resulting in a mean R factor of 0.24 and a mean free R factor of 0.29. The R factor of the final model is dependent on the quality of the starting electron density and is relatively independent of resolution.

PREFMD: a web server for protein structure refinement via molecular dynamics simulations.

PubMed

Heo, Lim; Feig, Michael

2018-03-15

Refinement of protein structure models is a long-standing problem in structural bioinformatics. Molecular dynamics-based methods have emerged as an avenue to achieve consistent refinement. The PREFMD web server implements an optimized protocol based on the method successfully tested in CASP11. Validation with recent CASP refinement targets shows consistent and more significant improvement in global structure accuracy over other state-of-the-art servers. PREFMD is freely available as a web server at http://feiglab.org/prefmd. Scripts for running PREFMD as a stand-alone package are available at https://github.com/feiglab/prefmd.git. feig@msu.edu. Supplementary data are available at Bioinformatics online.

Predicting X-ray diffuse scattering from translation–libration–screw structural ensembles

PubMed Central

Van Benschoten, Andrew H.; Afonine, Pavel V.; Terwilliger, Thomas C.; Wall, Michael E.; Jackson, Colin J.; Sauter, Nicholas K.; Adams, Paul D.; Urzhumtsev, Alexandre; Fraser, James S.

2015-01-01

Identifying the intramolecular motions of proteins and nucleic acids is a major challenge in macromolecular X-ray crystallography. Because Bragg diffraction describes the average positional distribution of crystalline atoms with imperfect precision, the resulting electron density can be compatible with multiple models of motion. Diffuse X-ray scattering can reduce this degeneracy by reporting on correlated atomic displacements. Although recent technological advances are increasing the potential to accurately measure diffuse scattering, computational modeling and validation tools are still needed to quantify the agreement between experimental data and different parameterizations of crystalline disorder. A new tool, phenix.diffuse, addresses this need by employing Guinier’s equation to calculate diffuse scattering from Protein Data Bank (PDB)-formatted structural ensembles. As an example case, phenix.diffuse is applied to translation–libration–screw (TLS) refinement, which models rigid-body displacement for segments of the macromolecule. To enable the calculation of diffuse scattering from TLS-refined structures, phenix.tls_as_xyz builds multi-model PDB files that sample the underlying T, L and S tensors. In the glycerophos­phodiesterase GpdQ, alternative TLS-group partitioning and different motional correlations between groups yield markedly dissimilar diffuse scattering maps with distinct implications for molecular mechanism and allostery. These methods demonstrate how, in principle, X-ray diffuse scattering could extend macromolecular structural refinement, validation and analysis. PMID:26249347

Predicting X-ray diffuse scattering from translation–libration–screw structural ensembles

DOE PAGES

Van Benschoten, Andrew H.; Afonine, Pavel V.; Terwilliger, Thomas C.; ...

2015-07-28

Identifying the intramolecular motions of proteins and nucleic acids is a major challenge in macromolecular X-ray crystallography. Because Bragg diffraction describes the average positional distribution of crystalline atoms with imperfect precision, the resulting electron density can be compatible with multiple models of motion. Diffuse X-ray scattering can reduce this degeneracy by reporting on correlated atomic displacements. Although recent technological advances are increasing the potential to accurately measure diffuse scattering, computational modeling and validation tools are still needed to quantify the agreement between experimental data and different parameterizations of crystalline disorder. A new tool, phenix.diffuse, addresses this need by employing Guinier'smore » equation to calculate diffuse scattering from Protein Data Bank (PDB)-formatted structural ensembles. As an example case, phenix.diffuse is applied to translation–libration–screw (TLS) refinement, which models rigid-body displacement for segments of the macromolecule. To enable the calculation of diffuse scattering from TLS-refined structures, phenix.tls_as_xyz builds multi-model PDB files that sample the underlying T, L and S tensors. In the glycerophosphodiesterase GpdQ, alternative TLS-group partitioning and different motional correlations between groups yield markedly dissimilar diffuse scattering maps with distinct implications for molecular mechanism and allostery. In addition, these methods demonstrate how, in principle, X-ray diffuse scattering could extend macromolecular structural refinement, validation and analysis.« less

On the Use of Dynamical Diffraction Theory To Refine Crystal Structure from Electron Diffraction Data: Application to KLa5O5(VO4)2, a Material with Promising Luminescent Properties.

PubMed

Colmont, Marie; Palatinus, Lukas; Huvé, Marielle; Kabbour, Houria; Saitzek, Sébastien; Djelal, Nora; Roussel, Pascal

2016-03-07

A new lanthanum oxide, KLa5O5(VO4)2, was synthesized using a flux growth technique that involved solid-state reaction under an air atmosphere at 900 °C. The crystal structure was solved and refined using an innovative approach recently established and based on three-dimensional (3D) electron diffraction data, using precession of the electron beam and then validated against Rietveld refinement and denisty functional theory (DFT) calculations. It crystallizes in a monoclinic unit cell with space group C2/m and has unit cell parameters of a = 20.2282(14) Å, b = 5.8639(4) Å, c = 12.6060(9) Å, and β = 117.64(1)°. Its structure is built on Cresnel-like two-dimensional (2D) units (La5O5) of 4*3 (OLa4) tetrahedra, which run parallel to (001) plane, being surrounded by isolated VO4 tetrahedra. Four isolated vanadate groups create channels that host K(+) ions. Substitution of K(+) cations by another alkali metal is possible, going from lithium to rubidium. Li substitution led to a similar phase with a primitive monoclinic unit cell. A complementary selected area electron diffraction (SAED) study highlighted diffuse streaks associated with stacking faults observed on high-resolution electron microscopy (HREM) images of the lithium compound. Finally, preliminary catalytic tests for ethanol oxidation are reported, as well as luminescence evidence. This paper also describes how solid-state chemists can take advantages of recent progresses in electron crystallography, assisted by DFT calculations and powder X-ray diffraction (PXRD) refinements, to propose new structural types with potential applications to the physicist community.

Refinement of NMR structures using implicit solvent and advanced sampling techniques.

PubMed

Chen, Jianhan; Im, Wonpil; Brooks, Charles L

2004-12-15

NMR biomolecular structure calculations exploit simulated annealing methods for conformational sampling and require a relatively high level of redundancy in the experimental restraints to determine quality three-dimensional structures. Recent advances in generalized Born (GB) implicit solvent models should make it possible to combine information from both experimental measurements and accurate empirical force fields to improve the quality of NMR-derived structures. In this paper, we study the influence of implicit solvent on the refinement of protein NMR structures and identify an optimal protocol of utilizing these improved force fields. To do so, we carry out structure refinement experiments for model proteins with published NMR structures using full NMR restraints and subsets of them. We also investigate the application of advanced sampling techniques to NMR structure refinement. Similar to the observations of Xia et al. (J.Biomol. NMR 2002, 22, 317-331), we find that the impact of implicit solvent is rather small when there is a sufficient number of experimental restraints (such as in the final stage of NMR structure determination), whether implicit solvent is used throughout the calculation or only in the final refinement step. The application of advanced sampling techniques also seems to have minimal impact in this case. However, when the experimental data are limited, we demonstrate that refinement with implicit solvent can substantially improve the quality of the structures. In particular, when combined with an advanced sampling technique, the replica exchange (REX) method, near-native structures can be rapidly moved toward the native basin. The REX method provides both enhanced sampling and automatic selection of the most native-like (lowest energy) structures. An optimal protocol based on our studies first generates an ensemble of initial structures that maximally satisfy the available experimental data with conventional NMR software using a simplified force field and then refines these structures with implicit solvent using the REX method. We systematically examine the reliability and efficacy of this protocol using four proteins of various sizes ranging from the 56-residue B1 domain of Streptococcal protein G to the 370-residue Maltose-binding protein. Significant improvement in the structures was observed in all cases when refinement was based on low-redundancy restraint data. The proposed protocol is anticipated to be particularly useful in early stages of NMR structure determination where a reliable estimate of the native fold from limited data can significantly expedite the overall process. This refinement procedure is also expected to be useful when redundant experimental data are not readily available, such as for large multidomain biomolecules and in solid-state NMR structure determination.

Advanced Structural Analyses by Third Generation Synchrotron Radiation Powder Diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakata, M.; Aoyagi, S.; Ogura, T.

2007-01-19

Since the advent of the 3rd generation Synchrotron Radiation (SR) sources, such as SPring-8, the capabilities of SR powder diffraction increased greatly not only in an accurate structure refinement but also ab initio structure determination. In this study, advanced structural analyses by 3rd generation SR powder diffraction based on the Large Debye-Scherrer camera installed at BL02B2, SPring-8 is described. Because of high angular resolution and high counting statistics powder data collected at BL02B2, SPring-8, ab initio structure determination can cope with a molecular crystals with 65 atoms including H atoms. For the structure refinements, it is found that a kindmore » of Maximum Entropy Method in which several atoms are omitted in phase calculation become very important to refine structural details of fairy large molecule in a crystal. It should be emphasized that until the unknown structure is refined very precisely, the obtained structure by Genetic Algorithm (GA) or some other ab initio structure determination method using real space structural knowledge, it is not possible to tell whether the structure obtained by the method is correct or not. In order to determine and/or refine crystal structure of rather complicated molecules, we cannot overemphasize the importance of the 3rd generation SR sources.« less

SFESA: a web server for pairwise alignment refinement by secondary structure shifts.

PubMed

Tong, Jing; Pei, Jimin; Grishin, Nick V

2015-09-03

Protein sequence alignment is essential for a variety of tasks such as homology modeling and active site prediction. Alignment errors remain the main cause of low-quality structure models. A bioinformatics tool to refine alignments is needed to make protein alignments more accurate. We developed the SFESA web server to refine pairwise protein sequence alignments. Compared to the previous version of SFESA, which required a set of 3D coordinates for a protein, the new server will search a sequence database for the closest homolog with an available 3D structure to be used as a template. For each alignment block defined by secondary structure elements in the template, SFESA evaluates alignment variants generated by local shifts and selects the best-scoring alignment variant. A scoring function that combines the sequence score of profile-profile comparison and the structure score of template-derived contact energy is used for evaluation of alignments. PROMALS pairwise alignments refined by SFESA are more accurate than those produced by current advanced alignment methods such as HHpred and CNFpred. In addition, SFESA also improves alignments generated by other software. SFESA is a web-based tool for alignment refinement, designed for researchers to compute, refine, and evaluate pairwise alignments with a combined sequence and structure scoring of alignment blocks. To our knowledge, the SFESA web server is the only tool that refines alignments by evaluating local shifts of secondary structure elements. The SFESA web server is available at http://prodata.swmed.edu/sfesa.

COMPUTATIONAL METHODOLOGIES for REAL-SPACE STRUCTURAL REFINEMENT of LARGE MACROMOLECULAR COMPLEXES

PubMed Central

Goh, Boon Chong; Hadden, Jodi A.; Bernardi, Rafael C.; Singharoy, Abhishek; McGreevy, Ryan; Rudack, Till; Cassidy, C. Keith; Schulten, Klaus

2017-01-01

The rise of the computer as a powerful tool for model building and refinement has revolutionized the field of structure determination for large biomolecular systems. Despite the wide availability of robust experimental methods capable of resolving structural details across a range of spatiotemporal resolutions, computational hybrid methods have the unique ability to integrate the diverse data from multimodal techniques such as X-ray crystallography and electron microscopy into consistent, fully atomistic structures. Here, commonly employed strategies for computational real-space structural refinement are reviewed, and their specific applications are illustrated for several large macromolecular complexes: ribosome, virus capsids, chemosensory array, and photosynthetic chromatophore. The increasingly important role of computational methods in large-scale structural refinement, along with current and future challenges, is discussed. PMID:27145875

Methane hydrate formation and decomposition: structural studies via neutron diffraction and empirical potential structure refinement.

PubMed

Thompson, Helen; Soper, Alan K; Buchanan, Piers; Aldiwan, Nawaf; Creek, Jefferson L; Koh, Carolyn A

2006-04-28

Neutron diffraction studies with hydrogen/deuterium isotope substitution measurements are performed to investigate the water structure at the early, medium, and late periods of methane clathrate hydrate formation and decomposition. These measurements are coupled with simultaneous gas consumption measurements to track the formation of methane hydrate from a gas/water mixture, and then the complete decomposition of hydrate. Empirical potential structure refinement computer simulations are used to analyze the neutron diffraction data and extract from the data the water structure in the bulk methane hydrate solution. The results highlight the significant changes in the water structure of the remaining liquid at various stages of hydrate formation and decomposition, and give further insight into the way in which hydrates form. The results also have important implications on the memory effect, suggesting that the water structure in the presence of hydrate crystallites is significantly different at equivalent stages of forming compared to decomposing. These results are in sharp contrast to the previously reported cases when all remaining hydrate crystallites are absent from the solution. For these systems there is no detectable change in the water structure or the methane hydration shell before hydrate formation and after decomposition. Based on the new results presented in this paper, it is clear that the local water structure is affected by the presence of hydrate crystallites, which may in turn be responsible for the "history" or "memory" effect where the production of hydrate from a solution of formed and then subsequently melted hydrate is reportedly much quicker than producing hydrate from a fresh water/gas mixture.

Refining and defining riverscape genetics: How rivers influence population genetic structure

Treesearch

Chanté D. Davis; Clinton W. Epps; Rebecca L. Flitcroft; Michael A. Banks

2018-01-01

Traditional analysis in population genetics evaluates differences among groups of individuals and, in some cases, considers the effects of distance or potential barriers to gene flow. Genetic variation of organisms in complex landscapes, seascapes, or riverine systems, however, may be shaped by many forces. Recent research has linked habitat heterogeneity and landscape...

Refinement of learned skilled movement representation in motor cortex deep output layer

PubMed Central

Li, Qian; Ko, Ho; Qian, Zhong-Ming; Yan, Leo Y. C.; Chan, Danny C. W.; Arbuthnott, Gordon; Ke, Ya; Yung, Wing-Ho

2017-01-01

The mechanisms underlying the emergence of learned motor skill representation in primary motor cortex (M1) are not well understood. Specifically, how motor representation in the deep output layer 5b (L5b) is shaped by motor learning remains virtually unknown. In rats undergoing motor skill training, we detect a subpopulation of task-recruited L5b neurons that not only become more movement-encoding, but their activities are also more structured and temporally aligned to motor execution with a timescale of refinement in tens-of-milliseconds. Field potentials evoked at L5b in vivo exhibit persistent long-term potentiation (LTP) that parallels motor performance. Intracortical dopamine denervation impairs motor learning, and disrupts the LTP profile as well as the emergent neurodynamical properties of task-recruited L5b neurons. Thus, dopamine-dependent recruitment of L5b neuronal ensembles via synaptic reorganization may allow the motor cortex to generate more temporally structured, movement-encoding output signal from M1 to downstream circuitry that drives increased uniformity and precision of movement during motor learning. PMID:28598433

Investigation on the structure of liquid N-methylformamide-dimethylsulfoxide mixtures

NASA Astrophysics Data System (ADS)

Cordeiro, João M. M.; Soper, Alan K.

2011-03-01

The structures of liquid mixtures of N-methylformamide (NMF) and dimethyl sulfoxide (DMSO) at two concentrations (80% and 50% NMF) are investigated using a combination of neutron diffraction augmented with isotopic substitution and empirical potential structure refinement simulations. The results indicate that the NMF and DMSO molecules are hydrogen-bonded to one another with a preference for NMF-DMSO hydrogen bonding, compared to the NMF-NMF ones. The liquid is orientationally structured as a consequence of these hydrogen bonds between molecules. NMF-DMSO dimers are very stable species in the bulk of the mixture. The structure of the dimers is such that the angle between the molecular dipole moments is around 60°. The NMF molecules are well solvated in DMSO with potential implications for peptides solvation in this solvent.

A grid-enabled web service for low-resolution crystal structure refinement.

PubMed

O'Donovan, Daniel J; Stokes-Rees, Ian; Nam, Yunsun; Blacklow, Stephen C; Schröder, Gunnar F; Brunger, Axel T; Sliz, Piotr

2012-03-01

Deformable elastic network (DEN) restraints have proved to be a powerful tool for refining structures from low-resolution X-ray crystallographic data sets. Unfortunately, optimal refinement using DEN restraints requires extensive calculations and is often hindered by a lack of access to sufficient computational resources. The DEN web service presented here intends to provide structural biologists with access to resources for running computationally intensive DEN refinements in parallel on the Open Science Grid, the US cyberinfrastructure. Access to the grid is provided through a simple and intuitive web interface integrated into the SBGrid Science Portal. Using this portal, refinements combined with full parameter optimization that would take many thousands of hours on standard computational resources can now be completed in several hours. An example of the successful application of DEN restraints to the human Notch1 transcriptional complex using the grid resource, and summaries of all submitted refinements, are presented as justification.

Towards solution and refinement of organic crystal structures by fitting to the atomic pair distribution function.

PubMed

Prill, Dragica; Juhás, Pavol; Billinge, Simon J L; Schmidt, Martin U

2016-01-01

A method towards the solution and refinement of organic crystal structures by fitting to the atomic pair distribution function (PDF) is developed. Approximate lattice parameters and molecular geometry must be given as input. The molecule is generally treated as a rigid body. The positions and orientations of the molecules inside the unit cell are optimized starting from random values. The PDF is obtained from carefully measured X-ray powder diffraction data. The method resembles `real-space' methods for structure solution from powder data, but works with PDF data instead of the diffraction pattern itself. As such it may be used in situations where the organic compounds are not long-range-ordered, are poorly crystalline, or nanocrystalline. The procedure was applied to solve and refine the crystal structures of quinacridone (β phase), naphthalene and allopurinol. In the case of allopurinol it was even possible to successfully solve and refine the structure in P1 with four independent molecules. As an example of a flexible molecule, the crystal structure of paracetamol was refined using restraints for bond lengths, bond angles and selected torsion angles. In all cases, the resulting structures are in excellent agreement with structures from single-crystal data.

Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard

PubMed Central

Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.; Moriarty, Nigel W.; Zwart, Peter H.; Hung, Li-Wei; Read, Randy J.; Adams, Paul D.

2008-01-01

The PHENIX AutoBuild wizard is a highly automated tool for iterative model building, structure refinement and density modification using RESOLVE model building, RESOLVE statistical density modification and phenix.refine structure refinement. Recent advances in the AutoBuild wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model-completion algorithms and automated solvent-molecule picking. Model-completion algorithms in the AutoBuild wizard include loop building, crossovers between chains in different models of a structure and side-chain optimization. The AutoBuild wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 to 3.2 Å, resulting in a mean R factor of 0.24 and a mean free R factor of 0.29. The R factor of the final model is dependent on the quality of the starting electron density and is relatively independent of resolution. PMID:18094468

DiffPy-CMI-Python libraries for Complex Modeling Initiative

DOE Office of Scientific and Technical Information (OSTI.GOV)

Billinge, Simon; Juhas, Pavol; Farrow, Christopher

2014-02-01

Software to manipulate and describe crystal and molecular structures and set up structural refinements from multiple experimental inputs. Calculation and simulation of structure derived physical quantities. Library for creating customized refinements of atomic structures from available experimental and theoretical inputs.

Sensitivity and Limitations of Structures from X-ray and Neutron-Based Diffraction Analyses of Transition Metal Oxide Lithium-Battery Electrodes

DOE PAGES

Liu, Hao; Liu, Haodong; Lapidus, Saul H.; ...

2017-06-21

Lithium transition metal oxides are an important class of electrode materials for lithium-ion batteries. Binary or ternary (transition) metal doping brings about new opportunities to improve the electrode’s performance and often leads to more complex stoichiometries and atomic structures than the archetypal LiCoO 2. Rietveld structural analyses of X-ray and neutron diffraction data is a widely-used approach for structural characterization of crystalline materials. But, different structural models and refinement approaches can lead to differing results, and some parameters can be difficult to quantify due to the inherent limitations of the data. Here, through the example of LiNi 0.8Co 0.15Al 0.05Omore » 2 (NCA), we demonstrated the sensitivity of various structural parameters in Rietveld structural analysis to different refinement approaches and structural models, and proposed an approach to reduce refinement uncertainties due to the inexact X-ray scattering factors of the constituent atoms within the lattice. Furthermore, this refinement approach was implemented for electrochemically-cycled NCA samples and yielded accurate structural parameters using only X-ray diffraction data. The present work provides the best practices for performing structural refinement of lithium transition metal oxides.« less

Sensitivity and Limitations of Structures from X-ray and Neutron-Based Diffraction Analyses of Transition Metal Oxide Lithium-Battery Electrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Hao; Liu, Haodong; Lapidus, Saul H.

Lithium transition metal oxides are an important class of electrode materials for lithium-ion batteries. Binary or ternary (transition) metal doping brings about new opportunities to improve the electrode’s performance and often leads to more complex stoichiometries and atomic structures than the archetypal LiCoO 2. Rietveld structural analyses of X-ray and neutron diffraction data is a widely-used approach for structural characterization of crystalline materials. But, different structural models and refinement approaches can lead to differing results, and some parameters can be difficult to quantify due to the inherent limitations of the data. Here, through the example of LiNi 0.8Co 0.15Al 0.05Omore » 2 (NCA), we demonstrated the sensitivity of various structural parameters in Rietveld structural analysis to different refinement approaches and structural models, and proposed an approach to reduce refinement uncertainties due to the inexact X-ray scattering factors of the constituent atoms within the lattice. Furthermore, this refinement approach was implemented for electrochemically-cycled NCA samples and yielded accurate structural parameters using only X-ray diffraction data. The present work provides the best practices for performing structural refinement of lithium transition metal oxides.« less

Estimates of immediate effects on world markets of a hypothetical disruption to Russia’s supply of six mineral commodities

USGS Publications Warehouse

Safirova, Elena; Barry, James J.; Hastorun, Sinan; Matos, Grecia R.; Perez, Alberto Alexander; Bedinger, George M.; Bray, E. Lee; Jasinski, Stephen M.; Kuck, Peter H.; Loferski, Patricia J.

2017-05-18

The potential immediate effects of a hypothetical shock to Russia’s supply of selected mineral commodities on the world market and on individual countries were determined and monetized (in 2014 U.S. dollars). The mineral commodities considered were aluminum (refined primary), nickel (refined primary), palladium (refined) and platinum (refined), potash, and titanium (mill products), and the regions and countries of primary interest were the United States, the European Union (EU–28), and China. The shock is assumed to have infinite duration, but only the immediate effects, those limited by a 1-year period, are considered.A methodology for computing and monetizing the potential impacts was developed. Then the data pertaining to all six mineral commodities were collected and the most likely effects were computed. Because of the uncertainties associated with some of the data, sensitivity analyses were conducted to confirm the validity of the results.Results indicate that the impact on the United States arising from a shock to Russia’s supply, in terms of the value of net exports, would range from a gain of \\$336 million for titanium mill products to a loss of \\$237 million for potash; thus, the overall effect of a supply shock is likely to be quite modest. The study also demonstrates that, taken alone, Russia’s share in the world production of a particular commodity is not necessarily indicative of the size of potential impacts resulting from a supply shock; other factors, such as prices, domestic production, and the structure of international commodity flows were found to be important as well.

3Drefine: an interactive web server for efficient protein structure refinement

PubMed Central

Bhattacharya, Debswapna; Nowotny, Jackson; Cao, Renzhi; Cheng, Jianlin

2016-01-01

3Drefine is an interactive web server for consistent and computationally efficient protein structure refinement with the capability to perform web-based statistical and visual analysis. The 3Drefine refinement protocol utilizes iterative optimization of hydrogen bonding network combined with atomic-level energy minimization on the optimized model using a composite physics and knowledge-based force fields for efficient protein structure refinement. The method has been extensively evaluated on blind CASP experiments as well as on large-scale and diverse benchmark datasets and exhibits consistent improvement over the initial structure in both global and local structural quality measures. The 3Drefine web server allows for convenient protein structure refinement through a text or file input submission, email notification, provided example submission and is freely available without any registration requirement. The server also provides comprehensive analysis of submissions through various energy and statistical feedback and interactive visualization of multiple refined models through the JSmol applet that is equipped with numerous protein model analysis tools. The web server has been extensively tested and used by many users. As a result, the 3Drefine web server conveniently provides a useful tool easily accessible to the community. The 3Drefine web server has been made publicly available at the URL: http://sysbio.rnet.missouri.edu/3Drefine/. PMID:27131371

Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smart, Oliver S., E-mail: osmart@globalphasing.com; Womack, Thomas O.; Flensburg, Claus

2012-04-01

Local structural similarity restraints (LSSR) provide a novel method for exploiting NCS or structural similarity to an external target structure. Two examples are given where BUSTER re-refinement of PDB entries with LSSR produces marked improvements, enabling further structural features to be modelled. Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct ‘target’ structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less thanmore » 5.5 Å between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and @@target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -target enables the correct ligand-binding structure to be found, and http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand.« less

Properties of nanocellulose isolated from corncob residue using sulfuric acid, formic acid, oxidative and mechanical methods.

PubMed

Liu, Chao; Li, Bin; Du, Haishun; Lv, Dong; Zhang, Yuedong; Yu, Guang; Mu, Xindong; Peng, Hui

2016-10-20

In this work, nanocellulose was extracted from bleached corncob residue (CCR), an underutilized lignocellulose waste from furfural industry, using four different methods (i.e. sulfuric acid hydrolysis, formic acid (FA) hydrolysis, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation, and pulp refining, respectively). The self-assembled structure, morphology, dimension, crystallinity, chemical structure and thermal stability of prepared nanocellulose were investigated. FA hydrolysis produced longer cellulose nanocrystals (CNCs) than the one obtained by sulfuric acid hydrolysis, and resulted in high crystallinity and thermal stability due to its preferential degradation of amorphous cellulose and lignin. The cellulose nanofibrils (CNFs) with fine and individualized structure could be isolated by TEMPO-mediated oxidation. In comparison with other nanocellulose products, the intensive pulp refining led to the CNFs with the longest length and the thickest diameter. This comparative study can help to provide an insight into the utilization of CCR as a potential source for nanocellulose production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficient Unstructured Cartesian/Immersed-Boundary Method with Local Mesh Refinement to Simulate Flows in Complex 3D Geometries

NASA Astrophysics Data System (ADS)

de Zelicourt, Diane; Ge, Liang; Sotiropoulos, Fotis; Yoganathan, Ajit

2008-11-01

Image-guided computational fluid dynamics has recently gained attention as a tool for predicting the outcome of different surgical scenarios. Cartesian Immersed-Boundary methods constitute an attractive option to tackle the complexity of real-life anatomies. However, when such methods are applied to the branching, multi-vessel configurations typically encountered in cardiovascular anatomies the majority of the grid nodes of the background Cartesian mesh end up lying outside the computational domain, increasing the memory and computational overhead without enhancing the numerical resolution in the region of interest. To remedy this situation, the method presented here superimposes local mesh refinement onto an unstructured Cartesian grid formulation. A baseline unstructured Cartesian mesh is generated by eliminating all nodes that reside in the exterior of the flow domain from the grid structure, and is locally refined in the vicinity of the immersed-boundary. The potential of the method is demonstrated by carrying out systematic mesh refinement studies for internal flow problems ranging in complexity from a 90 deg pipe bend to an actual, patient-specific anatomy reconstructed from magnetic resonance.

High-resolution structure of the M14-type cytosolic carboxypeptidase from Burkholderia cenocepacia refined exploiting PDB-REDO strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rimsa, Vadim; Eadsforth, Thomas C.; Joosten, Robbie P.

2014-02-01

The structure of a bacterial M14-family carboxypeptidase determined exploiting microfocus synchrotron radiation and highly automated refinement protocols reveals its potential to act as a polyglutamylase. A potential cytosolic metallocarboxypeptidase from Burkholderia cenocepacia has been crystallized and a synchrotron-radiation microfocus beamline allowed the acquisition of diffraction data to 1.9 Å resolution. The asymmetric unit comprises a tetramer containing over 1500 amino acids, and the high-throughput automated protocols embedded in PDB-REDO were coupled with model–map inspections in refinement. This approach has highlighted the value of such protocols for efficient analyses. The subunit is constructed from two domains. The N-terminal domain has previouslymore » only been observed in cytosolic carboxypeptidase (CCP) proteins. The C-terminal domain, which carries the Zn{sup 2+}-containing active site, serves to classify this protein as a member of the M14D subfamily of carboxypeptidases. Although eukaryotic CCPs possess deglutamylase activity and are implicated in processing modified tubulin, the function and substrates of the bacterial family members remain unknown. The B. cenocepacia protein did not display deglutamylase activity towards a furylacryloyl glutamate derivative, a potential substrate. Residues previously shown to coordinate the divalent cation and that contribute to peptide-bond cleavage in related enzymes such as bovine carboxypeptidase are conserved. The location of a conserved basic patch in the active site adjacent to the catalytic Zn{sup 2+}, where an acetate ion is identified, suggests recognition of the carboxy-terminus in a similar fashion to other carboxypeptidases. However, there are significant differences that indicate the recognition of substrates with different properties. Of note is the presence of a lysine in the S1′ recognition subsite that suggests specificity towards an acidic substrate.« less

Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER.

PubMed

Smart, Oliver S; Womack, Thomas O; Flensburg, Claus; Keller, Peter; Paciorek, Włodek; Sharff, Andrew; Vonrhein, Clemens; Bricogne, Gérard

2012-04-01

Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct 'target' structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less than 5.5 Å between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and -target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries 5rnt, where -target enables the correct ligand-binding structure to be found, and 1osg, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand.

Enrichment of refined olive oil with phenolic compounds: evaluation of their antioxidant activity and their effect on the bitter index.

PubMed

Artajo, Luz S; Romero, María P; Morelló, José R; Motilva, María J

2006-08-09

The study of the antioxidant effects of biophenolic compounds is supported by the current interest in natural products and the ongoing replacement of synthetic antioxidants by natural antioxidants from plant sources. Olives and olive oil, especially extra virgin olive oil, contain a variety of bioactive compounds (phytochemicals) widely considered to be potentially beneficial for health. This research was focused on evaluating the antioxidant activity of the enriched refined olive oil to discover a possible functional food application. Different concentrations of individual and combined phenolic compounds were added to the refined olive oil as lipid matrix, and the antioxidant activity expressed as oxidative stability in hours was determined by using the Rancimat method. Additionally, the bitter index was evaluated to assess the effect of the enrichment in relation to the organoleptic quality. The results showed that the antioxidant activity depends on the concentration of the phenol used for the assay and the chemical structure. In general, the most positive effects were observed in 3,4-dihydroxy and 3,4,5-trihydroxy structures linked to an aromatic ring that conferred to the moiety a higher proton dislocation, thus facilitating the scavenging activity.

Water-refined solution structure of the human Grb7-SH2 domain in complex with the erbB2 receptor peptide pY1139.

PubMed

Pias, Sally C; Johnson, Dennis L; Smith, David E; Lyons, Barbara A

2012-08-01

We report a refinement in implicit water of the previously published solution structure of the Grb7-SH2 domain bound to the erbB2 receptor peptide pY1139. Structure quality measures indicate substantial improvement, with residues in the most favored regions of the Ramachandran plot increasing by 14 % and with WHAT IF statistics (Vriend, G. J. Mol. Graph., 1990, 8(1), 52-56) falling closer to expected values for well-refined structures.

Towards solution and refinement of organic crystal structures by fitting to the atomic pair distribution function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prill, Dragica; Juhas, Pavol; Billinge, Simon J. L.

2016-01-01

In this study, a method towards the solution and refinement of organic crystal structures by fitting to the atomic pair distribution function (PDF) is developed. Approximate lattice parameters and molecular geometry must be given as input. The molecule is generally treated as a rigid body. The positions and orientations of the molecules inside the unit cell are optimized starting from random values. The PDF is obtained from carefully measured X-ray powder diffraction data. The method resembles `real-space' methods for structure solution from powder data, but works with PDF data instead of the diffraction pattern itself. As such it may bemore » used in situations where the organic compounds are not long-range-ordered, are poorly crystalline, or nanocrystalline. The procedure was applied to solve and refine the crystal structures of quinacridone (β phase), naphthalene and allopurinol. In the case of allopurinol it was even possible to successfully solve and refine the structure in P1 with four independent molecules. As an example of a flexible molecule, the crystal structure of paracetamol was refined using restraints for bond lengths, bond angles and selected torsion angles. In all cases, the resulting structures are in excellent agreement with structures from single-crystal data.« less

3Drefine: an interactive web server for efficient protein structure refinement.

PubMed

Bhattacharya, Debswapna; Nowotny, Jackson; Cao, Renzhi; Cheng, Jianlin

2016-07-08

3Drefine is an interactive web server for consistent and computationally efficient protein structure refinement with the capability to perform web-based statistical and visual analysis. The 3Drefine refinement protocol utilizes iterative optimization of hydrogen bonding network combined with atomic-level energy minimization on the optimized model using a composite physics and knowledge-based force fields for efficient protein structure refinement. The method has been extensively evaluated on blind CASP experiments as well as on large-scale and diverse benchmark datasets and exhibits consistent improvement over the initial structure in both global and local structural quality measures. The 3Drefine web server allows for convenient protein structure refinement through a text or file input submission, email notification, provided example submission and is freely available without any registration requirement. The server also provides comprehensive analysis of submissions through various energy and statistical feedback and interactive visualization of multiple refined models through the JSmol applet that is equipped with numerous protein model analysis tools. The web server has been extensively tested and used by many users. As a result, the 3Drefine web server conveniently provides a useful tool easily accessible to the community. The 3Drefine web server has been made publicly available at the URL: http://sysbio.rnet.missouri.edu/3Drefine/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Optimization of Melt Treatment for Austenitic Steel Grain Refinement

NASA Astrophysics Data System (ADS)

Lekakh, Simon N.; Ge, Jun; Richards, Von; O'Malley, Ron; TerBush, Jessica R.

2017-02-01

Refinement of the as-cast grain structure of austenitic steels requires the presence of active solid nuclei during solidification. These nuclei can be formed in situ in the liquid alloy by promoting reactions between transition metals (Ti, Zr, Nb, and Hf) and metalloid elements (C, S, O, and N) dissolved in the melt. Using thermodynamic simulations, experiments were designed to evaluate the effectiveness of a predicted sequence of reactions targeted to form precipitates that could act as active nuclei for grain refinement in austenitic steel castings. Melt additions performed to promote the sequential precipitation of titanium nitride (TiN) onto previously formed spinel (Al2MgO4) inclusions in the melt resulted in a significant refinement of the as-cast grain structure in heavy section Cr-Ni-Mo stainless steel castings. A refined as-cast structure consisting of an inner fine-equiaxed grain structure and outer columnar dendrite zone structure of limited length was achieved in experimental castings. The sequential of precipitation of TiN onto Al2MgO4 was confirmed using automated SEM/EDX and TEM analyses.

Overview of refinement procedures within REFMAC5: utilizing data from different sources.

PubMed

Kovalevskiy, Oleg; Nicholls, Robert A; Long, Fei; Carlon, Azzurra; Murshudov, Garib N

2018-03-01

Refinement is a process that involves bringing into agreement the structural model, available prior knowledge and experimental data. To achieve this, the refinement procedure optimizes a posterior conditional probability distribution of model parameters, including atomic coordinates, atomic displacement parameters (B factors), scale factors, parameters of the solvent model and twin fractions in the case of twinned crystals, given observed data such as observed amplitudes or intensities of structure factors. A library of chemical restraints is typically used to ensure consistency between the model and the prior knowledge of stereochemistry. If the observation-to-parameter ratio is small, for example when diffraction data only extend to low resolution, the Bayesian framework implemented in REFMAC5 uses external restraints to inject additional information extracted from structures of homologous proteins, prior knowledge about secondary-structure formation and even data obtained using different experimental methods, for example NMR. The refinement procedure also generates the `best' weighted electron-density maps, which are useful for further model (re)building. Here, the refinement of macromolecular structures using REFMAC5 and related tools distributed as part of the CCP4 suite is discussed.

Improving virtual screening of G protein-coupled receptors via ligand-directed modeling

PubMed Central

Simms, John; Christopoulos, Arthur; Wootten, Denise

2017-01-01

G protein-coupled receptors (GPCRs) play crucial roles in cell physiology and pathophysiology. There is increasing interest in using structural information for virtual screening (VS) of libraries and for structure-based drug design to identify novel agonist or antagonist leads. However, the sparse availability of experimentally determined GPCR/ligand complex structures with diverse ligands impedes the application of structure-based drug design (SBDD) programs directed to identifying new molecules with a select pharmacology. In this study, we apply ligand-directed modeling (LDM) to available GPCR X-ray structures to improve VS performance and selectivity towards molecules of specific pharmacological profile. The described method refines a GPCR binding pocket conformation using a single known ligand for that GPCR. The LDM method is a computationally efficient, iterative workflow consisting of protein sampling and ligand docking. We developed an extensive benchmark comparing LDM-refined binding pockets to GPCR X-ray crystal structures across seven different GPCRs bound to a range of ligands of different chemotypes and pharmacological profiles. LDM-refined models showed improvement in VS performance over origin X-ray crystal structures in 21 out of 24 cases. In all cases, the LDM-refined models had superior performance in enriching for the chemotype of the refinement ligand. This likely contributes to the LDM success in all cases of inhibitor-bound to agonist-bound binding pocket refinement, a key task for GPCR SBDD programs. Indeed, agonist ligands are required for a plethora of GPCRs for therapeutic intervention, however GPCR X-ray structures are mostly restricted to their inactive inhibitor-bound state. PMID:29131821

The Collaborative Seismic Earth Model Project

NASA Astrophysics Data System (ADS)

Fichtner, A.; van Herwaarden, D. P.; Afanasiev, M.

2017-12-01

We present the first generation of the Collaborative Seismic Earth Model (CSEM). This effort is intended to address grand challenges in tomography that currently inhibit imaging the Earth's interior across the seismically accessible scales: [1] For decades to come, computational resources will remain insufficient for the exploitation of the full observable seismic bandwidth. [2] With the man power of individual research groups, only small fractions of available waveform data can be incorporated into seismic tomographies. [3] The limited incorporation of prior knowledge on 3D structure leads to slow progress and inefficient use of resources. The CSEM is a multi-scale model of global 3D Earth structure that evolves continuously through successive regional refinements. Taking the current state of the CSEM as initial model, these refinements are contributed by external collaborators, and used to advance the CSEM to the next state. This mode of operation allows the CSEM to [1] harness the distributed man and computing power of the community, [2] to make consistent use of prior knowledge, and [3] to combine different tomographic techniques, needed to cover the seismic data bandwidth. Furthermore, the CSEM has the potential to serve as a unified and accessible representation of tomographic Earth models. Generation 1 comprises around 15 regional tomographic refinements, computed with full-waveform inversion. These include continental-scale mantle models of North America, Australasia, Europe and the South Atlantic, as well as detailed regional models of the crust beneath the Iberian Peninsula and western Turkey. A global-scale full-waveform inversion ensures that regional refinements are consistent with whole-Earth structure. This first generation will serve as the basis for further automation and methodological improvements concerning validation and uncertainty quantification.

Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER

PubMed Central

Smart, Oliver S.; Womack, Thomas O.; Flensburg, Claus; Keller, Peter; Paciorek, Włodek; Sharff, Andrew; Vonrhein, Clemens; Bricogne, Gérard

2012-01-01

Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct ‘target’ structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less than 5.5 Å between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and -­target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries 5rnt, where -target enables the correct ligand-binding structure to be found, and 1osg, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand. PMID:22505257

Adaptive mesh refinement and load balancing based on multi-level block-structured Cartesian mesh

NASA Astrophysics Data System (ADS)

Misaka, Takashi; Sasaki, Daisuke; Obayashi, Shigeru

2017-11-01

We developed a framework for a distributed-memory parallel computer that enables dynamic data management for adaptive mesh refinement and load balancing. We employed simple data structure of the building cube method (BCM) where a computational domain is divided into multi-level cubic domains and each cube has the same number of grid points inside, realising a multi-level block-structured Cartesian mesh. Solution adaptive mesh refinement, which works efficiently with the help of the dynamic load balancing, was implemented by dividing cubes based on mesh refinement criteria. The framework was investigated with the Laplace equation in terms of adaptive mesh refinement, load balancing and the parallel efficiency. It was then applied to the incompressible Navier-Stokes equations to simulate a turbulent flow around a sphere. We considered wall-adaptive cube refinement where a non-dimensional wall distance y+ near the sphere is used for a criterion of mesh refinement. The result showed the load imbalance due to y+ adaptive mesh refinement was corrected by the present approach. To utilise the BCM framework more effectively, we also tested a cube-wise algorithm switching where an explicit and implicit time integration schemes are switched depending on the local Courant-Friedrichs-Lewy (CFL) condition in each cube.

Prediction of protein tertiary structure to low resolution: performance for a large and structurally diverse test set.

PubMed

Eyrich, V A; Standley, D M; Friesner, R A

1999-05-14

We report the tertiary structure predictions for 95 proteins ranging in size from 17 to 160 residues starting from known secondary structure. Predictions are obtained from global minimization of an empirical potential function followed by the application of a refined atomic overlap potential. The minimization strategy employed represents a variant of the Monte Carlo plus minimization scheme of Li and Scheraga applied to a reduced model of the protein chain. For all of the cases except beta-proteins larger than 75 residues, a native-like structure, usually 4-6 A root-mean-square deviation from the native, is located. For beta-proteins larger than 75 residues, the energy gap between native-like structures and the lowest energy structures produced in the simulation is large, so that low RMSD structures are not generated starting from an unfolded state. This is attributed to the lack of an explicit hydrogen bond term in the potential function, which we hypothesize is necessary to stabilize large assemblies of beta-strands. Copyright 1999 Academic Press.

[Can the local energy minimization refine the PDB structures of different resolution universally?].

PubMed

Godzi, M G; Gromova, A P; Oferkin, I V; Mironov, P V

2009-01-01

The local energy minimization was statistically validated as the refinement strategy for PDB structure pairs of different resolution. Thirteen pairs of structures with the only difference in resolution were extracted from PDB, and the structures of 11 identical proteins obtained by different X-ray diffraction techniques were represented. The distribution of RMSD value was calculated for these pairs before and after the local energy minimization of each structure. The MMFF94 field was used for energy calculations, and the quasi-Newton method was used for local energy minimization. By comparison of these two RMSD distributions, the local energy minimization was proved to statistically increase the structural differences in pairs so that it cannot be used for refinement purposes. To explore the prospects of complex refinement strategies based on energy minimization, randomized structures were obtained by moving the initial PDB structures as far as the minimized structures had been moved in a multidimensional space of atomic coordinates. For these randomized structures, the RMSD distribution was calculated and compared with that for minimized structures. The significant differences in their mean values proved the energy surface of the protein to have only few minima near the conformations of different resolution obtained by X-ray diffraction for PDB. Some other results obtained by exploring the energy surface near these conformations are also presented. These results are expected to be very useful for the development of new protein refinement strategies based on energy minimization.

Microstructural characteristics of adiabatic shear localization in a metastable beta titanium alloy deformed at high strain rate and elevated temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhan, Hongyi, E-mail: h.zhan@uq.edu.au; Zeng, Weidong; Wang, Gui

2015-04-15

The microstructural evolution and grain refinement within adiabatic shear bands in the Ti6554 alloy deformed at high strain rates and elevated temperatures have been characterized using transmission electron microscopy. No stress drops were observed in the corresponding stress–strain curve, indicating that the initiation of adiabatic shear bands does not lead to the loss of load capacity for the Ti6554 alloy. The outer region of the shear bands mainly consists of cell structures bounded by dislocation clusters. Equiaxed subgrains in the core area of the shear band can be evolved from the subdivision of cell structures or reconstruction and transverse segmentationmore » of dislocation clusters. It is proposed that dislocation activity dominates the grain refinement process. The rotational recrystallization mechanism may operate as the kinetic requirements for it are fulfilled. The coexistence of different substructures across the shear bands implies that the microstructural evolution inside the shear bands is not homogeneous and different grain refinement mechanisms may operate simultaneously to refine the structure. - Graphical abstract: Display Omitted - Highlights: • The microstructure within the adiabatic shear band was characterized by TEM. • No stress drops were observed in the corresponding stress–strain curve. • Dislocation activity dominated the grain refinement process. • The kinetic requirements for rotational recrystallization mechanism were fulfilled. • Different grain refinement mechanisms operated simultaneously to refine the structure.« less

Distance matrix-based approach to protein structure prediction.

PubMed

Kloczkowski, Andrzej; Jernigan, Robert L; Wu, Zhijun; Song, Guang; Yang, Lei; Kolinski, Andrzej; Pokarowski, Piotr

2009-03-01

Much structural information is encoded in the internal distances; a distance matrix-based approach can be used to predict protein structure and dynamics, and for structural refinement. Our approach is based on the square distance matrix D = [r(ij)(2)] containing all square distances between residues in proteins. This distance matrix contains more information than the contact matrix C, that has elements of either 0 or 1 depending on whether the distance r (ij) is greater or less than a cutoff value r (cutoff). We have performed spectral decomposition of the distance matrices D = sigma lambda(k)V(k)V(kT), in terms of eigenvalues lambda kappa and the corresponding eigenvectors v kappa and found that it contains at most five nonzero terms. A dominant eigenvector is proportional to r (2)--the square distance of points from the center of mass, with the next three being the principal components of the system of points. By predicting r (2) from the sequence we can approximate a distance matrix of a protein with an expected RMSD value of about 7.3 A, and by combining it with the prediction of the first principal component we can improve this approximation to 4.0 A. We can also explain the role of hydrophobic interactions for the protein structure, because r is highly correlated with the hydrophobic profile of the sequence. Moreover, r is highly correlated with several sequence profiles which are useful in protein structure prediction, such as contact number, the residue-wise contact order (RWCO) or mean square fluctuations (i.e. crystallographic temperature factors). We have also shown that the next three components are related to spatial directionality of the secondary structure elements, and they may be also predicted from the sequence, improving overall structure prediction. We have also shown that the large number of available HIV-1 protease structures provides a remarkable sampling of conformations, which can be viewed as direct structural information about the dynamics. After structure matching, we apply principal component analysis (PCA) to obtain the important apparent motions for both bound and unbound structures. There are significant similarities between the first few key motions and the first few low-frequency normal modes calculated from a static representative structure with an elastic network model (ENM) that is based on the contact matrix C (related to D), strongly suggesting that the variations among the observed structures and the corresponding conformational changes are facilitated by the low-frequency, global motions intrinsic to the structure. Similarities are also found when the approach is applied to an NMR ensemble, as well as to atomic molecular dynamics (MD) trajectories. Thus, a sufficiently large number of experimental structures can directly provide important information about protein dynamics, but ENM can also provide a similar sampling of conformations. Finally, we use distance constraints from databases of known protein structures for structure refinement. We use the distributions of distances of various types in known protein structures to obtain the most probable ranges or the mean-force potentials for the distances. We then impose these constraints on structures to be refined or include the mean-force potentials directly in the energy minimization so that more plausible structural models can be built. This approach has been successfully used by us in 2006 in the CASPR structure refinement (http://predictioncenter.org/caspR).

ADAPTIVE TETRAHEDRAL GRID REFINEMENT AND COARSENING IN MESSAGE-PASSING ENVIRONMENTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hallberg, J.; Stagg, A.

2000-10-01

A grid refinement and coarsening scheme has been developed for tetrahedral and triangular grid-based calculations in message-passing environments. The element adaption scheme is based on an edge bisection of elements marked for refinement by an appropriate error indicator. Hash-table/linked-list data structures are used to store nodal and element formation. The grid along inter-processor boundaries is refined and coarsened consistently with the update of these data structures via MPI calls. The parallel adaption scheme has been applied to the solution of a transient, three-dimensional, nonlinear, groundwater flow problem. Timings indicate efficiency of the grid refinement process relative to the flow solvermore » calculations.« less

Princeton_TIGRESS 2.0: High refinement consistency and net gains through support vector machines and molecular dynamics in double-blind predictions during the CASP11 experiment.

PubMed

Khoury, George A; Smadbeck, James; Kieslich, Chris A; Koskosidis, Alexandra J; Guzman, Yannis A; Tamamis, Phanourios; Floudas, Christodoulos A

2017-06-01

Protein structure refinement is the challenging problem of operating on any protein structure prediction to improve its accuracy with respect to the native structure in a blind fashion. Although many approaches have been developed and tested during the last four CASP experiments, a majority of the methods continue to degrade models rather than improve them. Princeton_TIGRESS (Khoury et al., Proteins 2014;82:794-814) was developed previously and utilizes separate sampling and selection stages involving Monte Carlo and molecular dynamics simulations and classification using an SVM predictor. The initial implementation was shown to consistently refine protein structures 76% of the time in our own internal benchmarking on CASP 7-10 targets. In this work, we improved the sampling and selection stages and tested the method in blind predictions during CASP11. We added a decomposition of physics-based and hybrid energy functions, as well as a coordinate-free representation of the protein structure through distance-binning Cα-Cα distances to capture fine-grained movements. We performed parameter estimation to optimize the adjustable SVM parameters to maximize precision while balancing sensitivity and specificity across all cross-validated data sets, finding enrichment in our ability to select models from the populations of similar decoys generated for targets in CASPs 7-10. The MD stage was enhanced such that larger structures could be further refined. Among refinement methods that are currently implemented as web-servers, Princeton_TIGRESS 2.0 demonstrated the most consistent and most substantial net refinement in blind predictions during CASP11. The enhanced refinement protocol Princeton_TIGRESS 2.0 is freely available as a web server at http://atlas.engr.tamu.edu/refinement/. Proteins 2017; 85:1078-1098. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

MAIN software for density averaging, model building, structure refinement and validation

PubMed Central

Turk, Dušan

2013-01-01

MAIN is software that has been designed to interactively perform the complex tasks of macromolecular crystal structure determination and validation. Using MAIN, it is possible to perform density modification, manual and semi-automated or automated model building and rebuilding, real- and reciprocal-space structure optimization and refinement, map calculations and various types of molecular structure validation. The prompt availability of various analytical tools and the immediate visualization of molecular and map objects allow a user to efficiently progress towards the completed refined structure. The extraordinary depth perception of molecular objects in three dimensions that is provided by MAIN is achieved by the clarity and contrast of colours and the smooth rotation of the displayed objects. MAIN allows simultaneous work on several molecular models and various crystal forms. The strength of MAIN lies in its manipulation of averaged density maps and molecular models when noncrystallographic symmetry (NCS) is present. Using MAIN, it is possible to optimize NCS parameters and envelopes and to refine the structure in single or multiple crystal forms. PMID:23897458

Avian abundance thresholds, human-altered landscapes, and the challenge of assemblage-level conservation

Treesearch

Kevin J. Gutzwiller; Samuel K. Riffell; Curtis H. Flather

2015-01-01

Context: Land-use change is a global phenomenon with potential to generate abrupt spatial changes in species’ distributions. Objectives: We assessed whether theory about the internal structure of bird species’ geographic ranges can be refined to reflect abrupt changes in distribution and abundance associated with human influences on landscapes, and whether the...

Focus Groups in Elderly Ophthalmologic Patients: Setting the Stage for Quantitative Preference Elicitation.

PubMed

Danner, Marion; Vennedey, Vera; Hiligsmann, Mickaël; Fauser, Sascha; Stock, Stephanie

2016-02-01

Patients suffering from age-related macular degeneration (AMD) are rarely actively involved in decision-making, despite facing preference-sensitive treatment decisions. This paper presents a qualitative study to prepare quantitative preference elicitation in AMD patients. The aims of this study were (1) to gain familiarity with and learn about the special requirements of the AMD patient population for quantitative data collection; and (2) to select/refine patient-relevant treatment attributes and levels, and gain insights into preference structures. Semi-structured focus group interviews were performed. An interview guide including preselected categories in the form of seven potentially patient-relevant treatment attributes was followed. To identify the most patient-relevant treatment attributes, a ranking exercise was performed. Deductive content analyses were done by two independent reviewers for each attribute to derive subcategories (potential levels of attributes) and depict preference trends. The focus group interviews included 21 patients. The interviews revealed that quantitative preference surveys in this population will have to be interviewer assisted to make the survey feasible for patients. The five most patient-relevant attributes were the effect on visual function [ranking score (RS): 139], injection frequency (RS: 101), approval status (RS: 83), side effects (RS: 79), and monitoring frequency (RS: 76). Attribute and level refinement was based on patients' statements. Preference trends and dependencies between attributes informed the quantitative instrument design. This study suggests that qualitative research is a very helpful step to prepare the design and administration of quantitative preference elicitation instruments. It especially facilitated familiarization with the target population and its preferences, and it supported attribute/level refinement.

Iterative refinement of structure-based sequence alignments by Seed Extension

PubMed Central

Kim, Changhoon; Tai, Chin-Hsien; Lee, Byungkook

2009-01-01

Background Accurate sequence alignment is required in many bioinformatics applications but, when sequence similarity is low, it is difficult to obtain accurate alignments based on sequence similarity alone. The accuracy improves when the structures are available, but current structure-based sequence alignment procedures still mis-align substantial numbers of residues. In order to correct such errors, we previously explored the possibility of replacing the residue-based dynamic programming algorithm in structure alignment procedures with the Seed Extension algorithm, which does not use a gap penalty. Here, we describe a new procedure called RSE (Refinement with Seed Extension) that iteratively refines a structure-based sequence alignment. Results RSE uses SE (Seed Extension) in its core, which is an algorithm that we reported recently for obtaining a sequence alignment from two superimposed structures. The RSE procedure was evaluated by comparing the correctly aligned fractions of residues before and after the refinement of the structure-based sequence alignments produced by popular programs. CE, DaliLite, FAST, LOCK2, MATRAS, MATT, TM-align, SHEBA and VAST were included in this analysis and the NCBI's CDD root node set was used as the reference alignments. RSE improved the average accuracy of sequence alignments for all programs tested when no shift error was allowed. The amount of improvement varied depending on the program. The average improvements were small for DaliLite and MATRAS but about 5% for CE and VAST. More substantial improvements have been seen in many individual cases. The additional computation times required for the refinements were negligible compared to the times taken by the structure alignment programs. Conclusion RSE is a computationally inexpensive way of improving the accuracy of a structure-based sequence alignment. It can be used as a standalone procedure following a regular structure-based sequence alignment or to replace the traditional iterative refinement procedures based on residue-level dynamic programming algorithm in many structure alignment programs. PMID:19589133

An object-oriented approach for parallel self adaptive mesh refinement on block structured grids

NASA Technical Reports Server (NTRS)

Lemke, Max; Witsch, Kristian; Quinlan, Daniel

1993-01-01

Self-adaptive mesh refinement dynamically matches the computational demands of a solver for partial differential equations to the activity in the application's domain. In this paper we present two C++ class libraries, P++ and AMR++, which significantly simplify the development of sophisticated adaptive mesh refinement codes on (massively) parallel distributed memory architectures. The development is based on our previous research in this area. The C++ class libraries provide abstractions to separate the issues of developing parallel adaptive mesh refinement applications into those of parallelism, abstracted by P++, and adaptive mesh refinement, abstracted by AMR++. P++ is a parallel array class library to permit efficient development of architecture independent codes for structured grid applications, and AMR++ provides support for self-adaptive mesh refinement on block-structured grids of rectangular non-overlapping blocks. Using these libraries, the application programmers' work is greatly simplified to primarily specifying the serial single grid application and obtaining the parallel and self-adaptive mesh refinement code with minimal effort. Initial results for simple singular perturbation problems solved by self-adaptive multilevel techniques (FAC, AFAC), being implemented on the basis of prototypes of the P++/AMR++ environment, are presented. Singular perturbation problems frequently arise in large applications, e.g. in the area of computational fluid dynamics. They usually have solutions with layers which require adaptive mesh refinement and fast basic solvers in order to be resolved efficiently.

Partial unfolding and refolding for structure refinement: A unified approach of geometric simulations and molecular dynamics.

PubMed

Kumar, Avishek; Campitelli, Paul; Thorpe, M F; Ozkan, S Banu

2015-12-01

The most successful protein structure prediction methods to date have been template-based modeling (TBM) or homology modeling, which predicts protein structure based on experimental structures. These high accuracy predictions sometimes retain structural errors due to incorrect templates or a lack of accurate templates in the case of low sequence similarity, making these structures inadequate in drug-design studies or molecular dynamics simulations. We have developed a new physics based approach to the protein refinement problem by mimicking the mechanism of chaperons that rehabilitate misfolded proteins. The template structure is unfolded by selectively (targeted) pulling on different portions of the protein using the geometric based technique FRODA, and then refolded using hierarchically restrained replica exchange molecular dynamics simulations (hr-REMD). FRODA unfolding is used to create a diverse set of topologies for surveying near native-like structures from a template and to provide a set of persistent contacts to be employed during re-folding. We have tested our approach on 13 previous CASP targets and observed that this method of folding an ensemble of partially unfolded structures, through the hierarchical addition of contact restraints (that is, first local and then nonlocal interactions), leads to a refolding of the structure along with refinement in most cases (12/13). Although this approach yields refined models through advancement in sampling, the task of blind selection of the best refined models still needs to be solved. Overall, the method can be useful for improved sampling for low resolution models where certain of the portions of the structure are incorrectly modeled. © 2015 Wiley Periodicals, Inc.

Multidataset Refinement Resonant Diffraction, and Magnetic Structures

PubMed Central

Attfield, J. Paul

2004-01-01

The scope of Rietveld and other powder diffraction refinements continues to expand, driven by improvements in instrumentation, methodology and software. This will be illustrated by examples from our research in recent years. Multidataset refinement is now commonplace; the datasets may be from different detectors, e.g., in a time-of-flight experiment, or from separate experiments, such as at several x-ray energies giving resonant information. The complementary use of x rays and neutrons is exemplified by a recent combined refinement of the monoclinic superstructure of magnetite, Fe3O4, below the 122 K Verwey transition, which reveals evidence for Fe2+/Fe3+ charge ordering. Powder neutron diffraction data continue to be used for the solution and Rietveld refinement of magnetic structures. Time-of-flight instruments on cold neutron sources can produce data that have a high intensity and good resolution at high d-spacings. Such profiles have been used to study incommensurate magnetic structures such as FeAsO4 and β–CrPO4. A multiphase, multidataset refinement of the phase-separated perovskite (Pr0.35Y0.07Th0.04Ca0.04Sr0.5)MnO3 has been used to fit three components with different crystal and magnetic structures at low temperatures. PMID:27366599

Total Scattering Analysis of Disordered Nanosheet Materials

NASA Astrophysics Data System (ADS)

Metz, Peter C.

Two dimensional materials are of increasing interest as building blocks for functional coatings, catalysts, and electrochemical devices. While increasingly sophisticated processing routes have been designed to obtain high-quality exfoliated nanosheets and controlled, self-assembled mesostructures, structural characterization of these materials remains challenging. This work presents a novel method of analyzing pair distribution function (PDF) data for disordered nanosheet ensembles, where supercell stacking models are used to infer atom correlations over as much as 50 A. Hierarchical models are used to reduce the parameter space of the refined model and help eliminate strongly correlated parameters. Three data sets for restacked nanosheet assemblies with stacking disorder are analyzed using these methods: simulated data for graphene-like layers, experimental data for 1 nm thick perovskite layers, and experimental data for highly defective delta-MnO2 layers. In each case, the sensitivity of the PDF to the real-space distribution of layer positions is demonstrated by exploring the fit residual as a function of stacking vectors. The refined models demonstrate that nanosheets tend towards local interlayer ordering, which is hypothesized to be driven by the electrostatic potential of the layer surfaces. Correctly accounting for interlayer atom correlations permits more accurate refinement of local structural details including local structure perturbations and defect site occupancies. In the delta-MnO2 nanosheet material, the new modeling approach identified 14% Mn vacancies while application of 3D periodic crystalline models to the < 7 A PDF region suggests a 25% vacancy concentration. In contrast, the perovskite nanosheet material is demonstrated to exhibit almost negligible structural relaxation in contrast with the bulk crystalline material from which it is derived.

Nitroxoline Molecule: Planar or Not? A Story of Battle between π-π Conjugation and Interatomic Repulsion.

PubMed

Tikhonov, Denis S; Sharapa, Dmitry I; Otlyotov, Arseniy A; Solyankin, Peter M; Rykov, Anatolii N; Shkurinov, Alexander P; Grikina, Olga E; Khaikin, Leonid S

2018-02-15

The conformational properties of the nitro group in nitroxoline (8-hydroxy-5-nitroquinoline, NXN) were investigated in the gas phase by means of gas electron diffraction (GED) and quantum chemical calculations, and also with solid-state analysis performed using terahertz time-domain spectroscopy (THz-TDS). The results of the GED refinement show that in the equilibrium structure the NO 2 group is twisted by angle ϕ = 8 ± 3° with respect to the 8-hydroxyoquinoline plane. This is the result of interatomic repulsion of oxygen in the NO 2 group from the closest hydrogen, which overcomes the energy gain from the π-π conjugation of the nitro group and aromatic system of 8-hydroxyoquinoline. The computation of equilibrium geometry using MP2/cc-pVXZ (X = T, Q) shows a large overestimation of the ϕ value, while DFT with the cc-pVTZ basis set performs reasonably well. On the other hand, DFT computations with double-ζ basis sets yield a planar structure of NXN. The refined potential energy surface of the torsion vibration the of nitro group in the condensed phase derived from the THz-TDS data indicates the NXN molecule to be planar. This result stays in good agreement with the previous X-ray structure determination. The strength of the π-system conjugation for the NO 2 group and 8-hydroxyoquinoline is discussed using NBO analysis, being further supported by comparison of the refined semiexperimental gas-phase structure of NXN from GED with other nitrocompounds.

Template-based modeling and ab initio refinement of protein oligomer structures using GALAXY in CAPRI round 30.

PubMed

Lee, Hasup; Baek, Minkyung; Lee, Gyu Rie; Park, Sangwoo; Seok, Chaok

2017-03-01

Many proteins function as homo- or hetero-oligomers; therefore, attempts to understand and regulate protein functions require knowledge of protein oligomer structures. The number of available experimental protein structures is increasing, and oligomer structures can be predicted using the experimental structures of related proteins as templates. However, template-based models may have errors due to sequence differences between the target and template proteins, which can lead to functional differences. Such structural differences may be predicted by loop modeling of local regions or refinement of the overall structure. In CAPRI (Critical Assessment of PRotein Interactions) round 30, we used recently developed features of the GALAXY protein modeling package, including template-based structure prediction, loop modeling, model refinement, and protein-protein docking to predict protein complex structures from amino acid sequences. Out of the 25 CAPRI targets, medium and acceptable quality models were obtained for 14 and 1 target(s), respectively, for which proper oligomer or monomer templates could be detected. Symmetric interface loop modeling on oligomer model structures successfully improved model quality, while loop modeling on monomer model structures failed. Overall refinement of the predicted oligomer structures consistently improved the model quality, in particular in interface contacts. Proteins 2017; 85:399-407. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reductions in Northeast Refining Activity: Potential Implications for Petroleum Product Markets

EIA Publications

2011-01-01

This report is the Energy Information Administration's (EIA) initial effort to provide information and analysis on the potential impacts on petroleum product markets from reductions in Northeast petroleum refining activity.

Solidification of Magnesium (AM50A) / vol%. SiCp composite

NASA Astrophysics Data System (ADS)

Zhang, X.; Hu, H.

2012-01-01

Magnesium matrix composite is one of the advanced lightweight materials with high potential to be used in automotive and aircraft industries due to its low density and high specific mechanical properties. The magnesium composites can be fabricated by adding the reinforcements of fibers or/and particles. In the previous literature, extensive studies have been performed on the development of matrix grain structure of aluminum-based metal matrix composites. However, there is limited information available on the development of grain structure during the solidification of particulate-reinforced magnesium. In this work, a 5 vol.% SiCp particulate-reinforced magnesium (AM50A) matrix composite (AM50A/SiCp) was prepared by stir casting. The solidification behavior of the cast AM50A/SiCp composite was investigated by computer-based thermal analysis. Optical and scanning electron microscopies (SEM) were employed to examine the occurrence of nucleation and grain refinement involved. The results indicate that the addition of SiCp particulates leads to a finer grain structure in the composite compared with the matrix alloy. The refinement of grain structure should be attributed to both the heterogeneous nucleation and the restricted primary crystal growth.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Los Alamos National Laboratory, Mailstop M888, Los Alamos, NM 87545, USA; Lawrence Berkeley National Laboratory, One Cyclotron Road, Building 64R0121, Berkeley, CA 94720, USA; Department of Haematology, University of Cambridge, Cambridge CB2 0XY, England

The PHENIX AutoBuild Wizard is a highly automated tool for iterative model-building, structure refinement and density modification using RESOLVE or TEXTAL model-building, RESOLVE statistical density modification, and phenix.refine structure refinement. Recent advances in the AutoBuild Wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model completion algorithms, and automated solvent molecule picking. Model completion algorithms in the AutoBuild Wizard include loop-building, crossovers between chains in different models of a structure, and side-chain optimization. The AutoBuild Wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 {angstrom} tomore » 3.2 {angstrom}, resulting in a mean R-factor of 0.24 and a mean free R factor of 0.29. The R-factor of the final model is dependent on the quality of the starting electron density, and relatively independent of resolution.« less

In search of a consensus model of the resting state of a voltage-sensing domain.

PubMed

Vargas, Ernesto; Bezanilla, Francisco; Roux, Benoît

2011-12-08

Voltage-sensing domains (VSDs) undergo conformational changes in response to the membrane potential and are the critical structural modules responsible for the activation of voltage-gated channels. Structural information about the key conformational states underlying voltage activation is currently incomplete. Through the use of experimentally determined residue-residue interactions as structural constraints, we determine and refine a model of the Kv channel VSD in the resting conformation. The resulting structural model is in broad agreement with results that originate from various labs using different techniques, indicating the emergence of a consensus for the structural basis of voltage sensing. Copyright © 2011 Elsevier Inc. All rights reserved.

Composite materials for rail transit systems

NASA Technical Reports Server (NTRS)

Griffin, O. Hayden, Jr.; Guerdal, Zafer; Herakovich, Carl T.

1987-01-01

The potential is explored for using composite materials in urban mass transit systems. The emphasis was to identify specific advantages of composite materials in order to determine their actual and potential usage for carbody and guideway structure applications. The literature was reviewed, contacts were made with major domestic system operators, designers, and builders, and an analysis was made of potential composite application to railcar construction. Composites were found to be in use throughout the transit industry, usually in secondary or auxiliary applications such as car interior and nonstructural exterior panels. More recently, considerable activity has been initiated in the area of using composites in the load bearing elements of civil engineering structures such as highway bridges. It is believed that new and improved manufacturing refinements in pultrusion and filament winding will permit the production of beam sections which can be used in guideway structures. The inherent corrosion resistance and low maintenance characteristics of composites should result in lowered maintenance costs over a prolonged life of the structure.

Value-added potential of expeller-pressed canola oil refining: characterization of sinapic acid derivatives and tocopherols from byproducts.

PubMed

Chen, Yougui; Thiyam-Hollander, Usha; Barthet, Veronique J; Aachary, Ayyappan A

2014-10-08

Valuable phenolic antioxidants are lost during oil refining, but evaluation of their occurrence in refining byproducts is lacking. Rapeseed and canola oil are both rich sources of sinapic acid derivatives and tocopherols. The retention and loss of sinapic acid derivatives and tocopherols in commercially produced expeller-pressed canola oils subjected to various refining steps and the respective byproducts were investigated. Loss of canolol (3) and tocopherols were observed during bleaching (84.9%) and deodorization (37.6%), respectively. Sinapic acid (2) (42.9 μg/g), sinapine (1) (199 μg/g), and canolol (344 μg/g) were found in the refining byproducts, namely, soap stock, spent bleaching clay, and wash water, for the first time. Tocopherols (3.75 mg/g) and other nonidentified phenolic compounds (2.7 mg sinapic acid equivalent/g) were found in deodistillates, a byproduct of deodorization. DPPH radical scavenging confirmed the antioxidant potential of the byproducts. This study confirms the value-added potential of byproducts of refining as sources of endogenous phenolics.

A template-based approach for parallel hexahedral two-refinement

DOE PAGES

Owen, Steven J.; Shih, Ryan M.; Ernst, Corey D.

2016-10-17

Here, we provide a template-based approach for generating locally refined all-hex meshes. We focus specifically on refinement of initially structured grids utilizing a 2-refinement approach where uniformly refined hexes are subdivided into eight child elements. The refinement algorithm consists of identifying marked nodes that are used as the basis for a set of four simple refinement templates. The target application for 2-refinement is a parallel grid-based all-hex meshing tool for high performance computing in a distributed environment. The result is a parallel consistent locally refined mesh requiring minimal communication and where minimum mesh quality is greater than scaled Jacobian 0.3more » prior to smoothing.« less

A template-based approach for parallel hexahedral two-refinement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Owen, Steven J.; Shih, Ryan M.; Ernst, Corey D.

Here, we provide a template-based approach for generating locally refined all-hex meshes. We focus specifically on refinement of initially structured grids utilizing a 2-refinement approach where uniformly refined hexes are subdivided into eight child elements. The refinement algorithm consists of identifying marked nodes that are used as the basis for a set of four simple refinement templates. The target application for 2-refinement is a parallel grid-based all-hex meshing tool for high performance computing in a distributed environment. The result is a parallel consistent locally refined mesh requiring minimal communication and where minimum mesh quality is greater than scaled Jacobian 0.3more » prior to smoothing.« less

Charge-density analysis of a protein structure at subatomic resolution: the human aldose reductase case.

PubMed

Guillot, Benoît; Jelsch, Christian; Podjarny, Alberto; Lecomte, Claude

2008-05-01

The valence electron density of the protein human aldose reductase was analyzed at 0.66 angstroms resolution. The methodological developments in the software MoPro to adapt standard charge-density techniques from small molecules to macromolecular structures are described. The deformation electron density visible in initial residual Fourier difference maps was significantly enhanced after high-order refinement. The protein structure was refined after transfer of the experimental library multipolar atom model (ELMAM). The effects on the crystallographic statistics, on the atomic thermal displacement parameters and on the structure stereochemistry are analyzed. Constrained refinements of the transferred valence populations Pval and multipoles Plm were performed against the X-ray diffraction data on a selected substructure of the protein with low thermal motion. The resulting charge densities are of good quality, especially for chemical groups with many copies present in the polypeptide chain. To check the effect of the starting point on the result of the constrained multipolar refinement, the same charge-density refinement strategy was applied but using an initial neutral spherical atom model, i.e. without transfer from the ELMAM library. The best starting point for a protein multipolar refinement is the structure with the electron density transferred from the database. This can be assessed by the crystallographic statistical indices, including Rfree, and the quality of the static deformation electron-density maps, notably on the oxygen electron lone pairs. The analysis of the main-chain bond lengths suggests that stereochemical dictionaries would benefit from a revision based on recently determined unrestrained atomic resolution protein structures.

Bulk Nanolaminated Nickel: Preparation, Microstructure, Mechanical Property, and Thermal Stability

NASA Astrophysics Data System (ADS)

Liu, Fan; Yuan, Hao; Goel, Sunkulp; Liu, Ying; Wang, Jing Tao

2018-02-01

A bulk nanolaminated (NL) structure with distinctive fractions of low- and high-angle grain boundaries ( f LAGBs and f HAGBs) is produced in pure nickel, through a two-step process of primary grain refinement by equal-channel angular pressing (ECAP), followed by a secondary geometrical refinement via liquid nitrogen rolling (LNR). The lamellar boundary spacings of 2N and 4N nickel are refined to 40 and 70 nm, respectively, and the yield strength of the NL structure in 2N nickel reaches 1.5 GPa. The impacts of the deformation path, material purity, grain boundary (GB) misorientation, and energy on the microstructure, refinement ability, mechanical strength, and thermal stability are investigated to understand the inherent governing mechanisms. GB migration is the main restoration mechanism limiting the refinement of an NL structure in 4N nickel, while in 2N nickel, shear banding occurs and mediates one-fifth of the total true normal rolling strain at the mesoscale, restricting further refinement. Three typical structures [ultrafine grained (UFG), NL with low f LAGBs, and NL with high f LAGBs] obtained through three different combinations of ECAP and LNR were studied by isochronal annealing for 1 hour at temperatures ranging from 433 K to 973 K (160 °C to 700 °C). Higher thermal stability in the NL structure with high f LAGBs is shown by a 50 K (50 °C) delay in the initiation temperature of recrystallization. Based on calculations and analyses of the stored energies of deformed structures from strain distribution, as characterized by kernel average misorientation (KAM), and from GB misorientations, higher thermal stability is attributed to high f LAGBs in this type of NL structure. This is confirmed by a slower change in the microstructure, as revealed by characterizing its annealing kinetics using KAM maps.

Structural Health Monitoring of Large Structures

NASA Technical Reports Server (NTRS)

Kim, Hyoung M.; Bartkowicz, Theodore J.; Smith, Suzanne Weaver; Zimmerman, David C.

1994-01-01

This paper describes a damage detection and health monitoring method that was developed for large space structures using on-orbit modal identification. After evaluating several existing model refinement and model reduction/expansion techniques, a new approach was developed to identify the location and extent of structural damage with a limited number of measurements. A general area of structural damage is first identified and, subsequently, a specific damaged structural component is located. This approach takes advantage of two different model refinement methods (optimal-update and design sensitivity) and two different model size matching methods (model reduction and eigenvector expansion). Performance of the proposed damage detection approach was demonstrated with test data from two different laboratory truss structures. This space technology can also be applied to structural inspection of aircraft, offshore platforms, oil tankers, ridges, and buildings. In addition, its applications to model refinement will improve the design of structural systems such as automobiles and electronic packaging.

Knowledge-Building Activity Structures in Japanese Elementary Science Pedagogy

ERIC Educational Resources Information Center

Oshima, Jun; Oshima, Ritsuko; Murayama, Isao; Inagaki, Shigenori; Takenaka, Makiko; Yamamoto, Tomokazu; Yamaguchi, Etsuji; Nakayama, Hayashi

2006-01-01

The purpose of this study is to refine Japanese elementary science activity structures by using a CSCL approach to transform the classroom into a knowledge-building community. We report design studies on two science lessons in two consecutive years and describe the progressive refinement of the activity structures. Through comparisons of student…

A refined Frequency Domain Decomposition tool for structural modal monitoring in earthquake engineering

NASA Astrophysics Data System (ADS)

Pioldi, Fabio; Rizzi, Egidio

2017-07-01

Output-only structural identification is developed by a refined Frequency Domain Decomposition ( rFDD) approach, towards assessing current modal properties of heavy-damped buildings (in terms of identification challenge), under strong ground motions. Structural responses from earthquake excitations are taken as input signals for the identification algorithm. A new dedicated computational procedure, based on coupled Chebyshev Type II bandpass filters, is outlined for the effective estimation of natural frequencies, mode shapes and modal damping ratios. The identification technique is also coupled with a Gabor Wavelet Transform, resulting in an effective and self-contained time-frequency analysis framework. Simulated response signals generated by shear-type frames (with variable structural features) are used as a necessary validation condition. In this context use is made of a complete set of seismic records taken from the FEMA P695 database, i.e. all 44 "Far-Field" (22 NS, 22 WE) earthquake signals. The modal estimates are statistically compared to their target values, proving the accuracy of the developed algorithm in providing prompt and accurate estimates of all current strong ground motion modal parameters. At this stage, such analysis tool may be employed for convenient application in the realm of Earthquake Engineering, towards potential Structural Health Monitoring and damage detection purposes.

Characterization and Evaluation of Re-Refined Engine Lubricating Oil.

DTIC Science & Technology

1981-12-01

performance of re-refineod and virgin oils and to Investigate the potential esubstantlal esquivalknced of re-refined and virgin lubricating oils. The...d 20. Abstract (continued) engine deposits derived from virgin and re-refined engine oils. (2) The effects of virgin and re-refined oils on engine...blowby composition and engine deposit generation were determined using a spark ignition engine and, 3) Virgin and re-refined basestock production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Xiujuan; Whalen, Scott A.; Darsell, Jens T.

Soft magnetic materials are often limited in scalability due to conventional processes that do not retain beneficial microstructures, and their associated physical properties, during densification. In this work, friction consolidation (FC) has been studied to fabricate Fe-Si soft magnetic materials from gas-atomized powder precursors. Fe-Si powder is consolidated using variable pressure and tool rotation speed in an effort to evaluate this unique densification approach for potential improvements in magnetic properties. FC, due to the high shear deformation involved, is shown to result in uniform gradual grain structure refinement across the consolidated workpiece from the center nearest the tool to themore » edge. Magnetic properties along different orientations indicate little, if any, textural orientation in the refined grain structure. The effect of annealing on the magnetic properties is evaluated and shown to decrease coercivity. FC processing was able to retain the magnetization of the original gas-atomized powders but further process optimization is needed to reach the optimal coercivity for the soft magnetic materials applications.« less

Structure refinement of Zn and Pr-doped Y-Ba-Cu-oxides

NASA Astrophysics Data System (ADS)

Naik, M. S.; Sarode, P. R.; Priolkar, K. R.; Prabhu, R. B.

2018-05-01

Superconducting compounds of composition Y0.9 Pr0.1Ba2 [Cu1-yZny]3O7-δ (0 ≤ y ≤ 0.10) have been synthesized. The structure of these materials has been studied using powder X-ray diffraction technique and refinement has been carried out by using Rietveld refinement procedure. It has been shown that all these compounds crystallize in orthorhombic structure with slight change in c parameter. Increase of parameter O(2) and decrease of parameter O(3)suggest the changes in the Cu-O2 plane of these orthorhombic materials on Zn substitution.

Electronic structure of lead pyrophosphate

NASA Astrophysics Data System (ADS)

Suewattana, Malliga; Singh, David

2007-03-01

Lead Pyrophosphate Pb2P2O7 is of interest for potential radiation detection applications and use in long term waste storage. It forms in triclinic P1 crystals and can also be grown as glasses. We performed electronic structure calculations using the crystal structure which determined by Mullica et. al (J. Solid State Chem (1986)) using x-ray diffraction and found large forces on atoms suggesting that the refined atomic positions were not fully correct. Here we report first principles structure relaxation and a revised crystal structure for this compound. We analyze the resulting structure using pair distribution functions and discuss the implications for the electronic properties. This work was supported by DOE NA22 and the Office of Naval Research.

Magnesium Recycling of Partially Oxidized, Mixed Magnesium-Aluminum Scrap through Combined Refining and Solid Oxide Membrane Electrolysis Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiaofei Guan; Peter A. Zink; Uday B. Pal

2012-01-01

Pure magnesium (Mg) is recycled from 19g of partially oxidized 50.5wt.% Mg-Aluminum (Al) alloy. During the refining process, potentiodynamic scans (PDS) were performed to determine the electrorefining potential for magnesium. The PDS show that the electrorefining potential increases over time as the magnesium content inside the Mg-Al scrap decreases. Up to 100% percent of magnesium is refined from the Mg-Al scrap by a novel refining process of dissolving magnesium and its oxide into a flux followed by vapor phase removal of dissolved magnesium and subsequently condensing the magnesium vapor. The solid oxide membrane (SOM) electrolysis process is employed in themore » refining system to enable additional recycling of magnesium from magnesium oxide (MgO) in the partially oxidized Mg-Al scrap. The combination of the refining and SOM processes yields 7.4g of pure magnesium.« less

Triclinic lysozyme at 0.65 angstrom resolution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J.; Dauter, M.; Alkire, R.

The crystal structure of triclinic hen egg-white lysozyme (HEWL) has been refined against diffraction data extending to 0.65 {angstrom} resolution measured at 100 K using synchrotron radiation. Refinement with anisotropic displacement parameters and with the removal of stereochemical restraints for the well ordered parts of the structure converged with a conventional R factor of 8.39% and an R{sub free} of 9.52%. The use of full-matrix refinement provided an estimate of the variances in the derived parameters. In addition to the 129-residue protein, a total of 170 water molecules, nine nitrate ions, one acetate ion and three ethylene glycol molecules weremore » located in the electron-density map. Eight sections of the main chain and many side chains were modeled with alternate conformations. The occupancies of the water sites were refined and this step is meaningful when assessed by use of the free R factor. A detailed description and comparison of the structure are made with reference to the previously reported triclinic HEWL structures refined at 0.925 {angstrom} (at the low temperature of 120 K) and at 0.95 {angstrom} resolution (at room temperature).« less

Center for Macromolecular Crystallography, University of Alabama in Birmingham

NASA Technical Reports Server (NTRS)

Navia, Manuel A.

1991-01-01

Porcine pancreatic elastase (PPE) crystals grown under microgravity conditions on mission STS-26 of the Space Shuttle Discovery were shown to diffract to considerably higher resolution than the best PPE crystals grown by us on the ground. We have now independently refined both the microgravity and ground-based data. Preliminary results of these refinements are summarized. These results show nearly a doubling of experimental diffraction data for this structure, exceeding 1.3 A resolution. Improved phase information derived from the refined structure of PPE based on this microgravity data has allowed us to interpret previously-uninterpretable electron density obtained from ground-based crystals of a complex of PPE with a chemically-reactive inhibitor. Intermediate stages in the enzyme-inhibitor reaction mechanism in the crystal can now be directly observed. Further refinement of PPE structures is in progress.

Atomic modeling of cryo-electron microscopy reconstructions--joint refinement of model and imaging parameters.

PubMed

Chapman, Michael S; Trzynka, Andrew; Chapman, Brynmor K

2013-04-01

When refining the fit of component atomic structures into electron microscopic reconstructions, use of a resolution-dependent atomic density function makes it possible to jointly optimize the atomic model and imaging parameters of the microscope. Atomic density is calculated by one-dimensional Fourier transform of atomic form factors convoluted with a microscope envelope correction and a low-pass filter, allowing refinement of imaging parameters such as resolution, by optimizing the agreement of calculated and experimental maps. A similar approach allows refinement of atomic displacement parameters, providing indications of molecular flexibility even at low resolution. A modest improvement in atomic coordinates is possible following optimization of these additional parameters. Methods have been implemented in a Python program that can be used in stand-alone mode for rigid-group refinement, or embedded in other optimizers for flexible refinement with stereochemical restraints. The approach is demonstrated with refinements of virus and chaperonin structures at resolutions of 9 through 4.5 Å, representing regimes where rigid-group and fully flexible parameterizations are appropriate. Through comparisons to known crystal structures, flexible fitting by RSRef is shown to be an improvement relative to other methods and to generate models with all-atom rms accuracies of 1.5-2.5 Å at resolutions of 4.5-6 Å. Copyright © 2013 Elsevier Inc. All rights reserved.

Homology‐based hydrogen bond information improves crystallographic structures in the PDB

PubMed Central

van Beusekom, Bart; Touw, Wouter G.; Tatineni, Mahidhar; Somani, Sandeep; Rajagopal, Gunaretnam; Luo, Jinquan; Gilliland, Gary L.; Perrakis, Anastassis

2017-01-01

Abstract The Protein Data Bank (PDB) is the global archive for structural information on macromolecules, and a popular resource for researchers, teachers, and students, amassing more than one million unique users each year. Crystallographic structure models in the PDB (more than 100,000 entries) are optimized against the crystal diffraction data and geometrical restraints. This process of crystallographic refinement typically ignored hydrogen bond (H‐bond) distances as a source of information. However, H‐bond restraints can improve structures at low resolution where diffraction data are limited. To improve low‐resolution structure refinement, we present methods for deriving H‐bond information either globally from well‐refined high‐resolution structures from the PDB‐REDO databank, or specifically from on‐the‐fly constructed sets of homologous high‐resolution structures. Refinement incorporating HOmology DErived Restraints (HODER), improves geometrical quality and the fit to the diffraction data for many low‐resolution structures. To make these improvements readily available to the general public, we applied our new algorithms to all crystallographic structures in the PDB: using massively parallel computing, we constructed a new instance of the PDB‐REDO databank (https://pdb-redo.eu). This resource is useful for researchers to gain insight on individual structures, on specific protein families (as we demonstrate with examples), and on general features of protein structure using data mining approaches on a uniformly treated dataset. PMID:29168245

Homology-based hydrogen bond information improves crystallographic structures in the PDB.

PubMed

van Beusekom, Bart; Touw, Wouter G; Tatineni, Mahidhar; Somani, Sandeep; Rajagopal, Gunaretnam; Luo, Jinquan; Gilliland, Gary L; Perrakis, Anastassis; Joosten, Robbie P

2018-03-01

The Protein Data Bank (PDB) is the global archive for structural information on macromolecules, and a popular resource for researchers, teachers, and students, amassing more than one million unique users each year. Crystallographic structure models in the PDB (more than 100,000 entries) are optimized against the crystal diffraction data and geometrical restraints. This process of crystallographic refinement typically ignored hydrogen bond (H-bond) distances as a source of information. However, H-bond restraints can improve structures at low resolution where diffraction data are limited. To improve low-resolution structure refinement, we present methods for deriving H-bond information either globally from well-refined high-resolution structures from the PDB-REDO databank, or specifically from on-the-fly constructed sets of homologous high-resolution structures. Refinement incorporating HOmology DErived Restraints (HODER), improves geometrical quality and the fit to the diffraction data for many low-resolution structures. To make these improvements readily available to the general public, we applied our new algorithms to all crystallographic structures in the PDB: using massively parallel computing, we constructed a new instance of the PDB-REDO databank (https://pdb-redo.eu). This resource is useful for researchers to gain insight on individual structures, on specific protein families (as we demonstrate with examples), and on general features of protein structure using data mining approaches on a uniformly treated dataset. © 2017 The Protein Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zask, Arie; Verheijen, Jeroen C.; Curran, Kevin

The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.

Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

PubMed

John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

2012-01-01

Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

Structure and atomic correlations in molecular systems probed by XAS reverse Monte Carlo refinement

NASA Astrophysics Data System (ADS)

Di Cicco, Andrea; Iesari, Fabio; Trapananti, Angela; D'Angelo, Paola; Filipponi, Adriano

2018-03-01

The Reverse Monte Carlo (RMC) algorithm for structure refinement has been applied to x-ray absorption spectroscopy (XAS) multiple-edge data sets for six gas phase molecular systems (SnI2, CdI2, BBr3, GaI3, GeBr4, GeI4). Sets of thousands of molecular replicas were involved in the refinement process, driven by the XAS data and constrained by available electron diffraction results. The equilibrated configurations were analysed to determine the average tridimensional structure and obtain reliable bond and bond-angle distributions. Detectable deviations from Gaussian models were found in some cases. This work shows that a RMC refinement of XAS data is able to provide geometrical models for molecular structures compatible with present experimental evidence. The validation of this approach on simple molecular systems is particularly important in view of its possible simple extension to more complex and extended systems including metal-organic complexes, biomolecules, or nanocrystalline systems.

xMDFF: molecular dynamics flexible fitting of low-resolution X-ray structures.

PubMed

McGreevy, Ryan; Singharoy, Abhishek; Li, Qufei; Zhang, Jingfen; Xu, Dong; Perozo, Eduardo; Schulten, Klaus

2014-09-01

X-ray crystallography remains the most dominant method for solving atomic structures. However, for relatively large systems, the availability of only medium-to-low-resolution diffraction data often limits the determination of all-atom details. A new molecular dynamics flexible fitting (MDFF)-based approach, xMDFF, for determining structures from such low-resolution crystallographic data is reported. xMDFF employs a real-space refinement scheme that flexibly fits atomic models into an iteratively updating electron-density map. It addresses significant large-scale deformations of the initial model to fit the low-resolution density, as tested with synthetic low-resolution maps of D-ribose-binding protein. xMDFF has been successfully applied to re-refine six low-resolution protein structures of varying sizes that had already been submitted to the Protein Data Bank. Finally, via systematic refinement of a series of data from 3.6 to 7 Å resolution, xMDFF refinements together with electrophysiology experiments were used to validate the first all-atom structure of the voltage-sensing protein Ci-VSP.

Model systems: how chemical biologists study RNA

PubMed Central

Rios, Andro C.; Tor, Yitzhak

2009-01-01

Ribonucleic acids are structurally and functionally sophisticated biomolecules and the use of models, frequently truncated or modified sequences representing functional domains of the natural systems, is essential to their exploration. Functional non-coding RNAs such as miRNAs, riboswitches, and, in particular, ribozymes, have changed the view of RNA’s role in biology and its catalytic potential. The well-known truncated hammerhead model has recently been refined and new data provide a clearer molecular picture of the elements responsible for its catalytic power. A model for the spliceosome, a massive and highly intricate ribonucleoprotein, is also emerging, although its true utility is yet to be cemented. Such catalytic model systems could also serve as “chemo-paleontological” tools, further refining the RNA world hypothesis and its relevance to the origin and evolution of life. PMID:19879179

Far-infrared laser magnetic resonance of vibrationally excited CD2

NASA Technical Reports Server (NTRS)

Evenson, K. M.; Sears, T. J.; Mckellar, A. R. W.

1984-01-01

The detection of 13 rotational transitions in the first excited bending state (010) of CD2 using the technique of far-infrared laser magnetic resonance spectroscopy is reported. Molecular parameters for this state are determined from these new data together with existing infrared observations of the v(2) band. Additional information on the ground vibrational state (000) is also provided by the observation of a new rotational transition, and this is combined with existing data to provide a refined set of molecular parameters for the CD2 ground state. One spectrum has been observed that is assigned as a rotational transition within the first excited symmetric stretching state (100) of CD2. These data will be of use in refining the structure and the potential function of the methylene radical.

An adaptive interpolation scheme for molecular potential energy surfaces

NASA Astrophysics Data System (ADS)

Kowalewski, Markus; Larsson, Elisabeth; Heryudono, Alfa

2016-08-01

The calculation of potential energy surfaces for quantum dynamics can be a time consuming task—especially when a high level of theory for the electronic structure calculation is required. We propose an adaptive interpolation algorithm based on polyharmonic splines combined with a partition of unity approach. The adaptive node refinement allows to greatly reduce the number of sample points by employing a local error estimate. The algorithm and its scaling behavior are evaluated for a model function in 2, 3, and 4 dimensions. The developed algorithm allows for a more rapid and reliable interpolation of a potential energy surface within a given accuracy compared to the non-adaptive version.

Measuring and modeling diffuse scattering in protein X-ray crystallography

PubMed Central

Van Benschoten, Andrew H.; Liu, Lin; Gonzalez, Ana; Brewster, Aaron S.; Sauter, Nicholas K.; Wall, Michael E.

2016-01-01

X-ray diffraction has the potential to provide rich information about the structural dynamics of macromolecules. To realize this potential, both Bragg scattering, which is currently used to derive macromolecular structures, and diffuse scattering, which reports on correlations in charge density variations, must be measured. Until now, measurement of diffuse scattering from protein crystals has been scarce because of the extra effort of collecting diffuse data. Here, we present 3D measurements of diffuse intensity collected from crystals of the enzymes cyclophilin A and trypsin. The measurements were obtained from the same X-ray diffraction images as the Bragg data, using best practices for standard data collection. To model the underlying dynamics in a practical way that could be used during structure refinement, we tested translation–libration–screw (TLS), liquid-like motions (LLM), and coarse-grained normal-modes (NM) models of protein motions. The LLM model provides a global picture of motions and was refined against the diffuse data, whereas the TLS and NM models provide more detailed and distinct descriptions of atom displacements, and only used information from the Bragg data. Whereas different TLS groupings yielded similar Bragg intensities, they yielded different diffuse intensities, none of which agreed well with the data. In contrast, both the LLM and NM models agreed substantially with the diffuse data. These results demonstrate a realistic path to increase the number of diffuse datasets available to the wider biosciences community and indicate that dynamics-inspired NM structural models can simultaneously agree with both Bragg and diffuse scattering. PMID:27035972

Measuring and modeling diffuse scattering in protein X-ray crystallography

DOE PAGES

Van Benschoten, Andrew H.; Liu, Lin; Gonzalez, Ana; ...

2016-03-28

X-ray diffraction has the potential to provide rich information about the structural dynamics of macromolecules. To realize this potential, both Bragg scattering, which is currently used to derive macromolecular structures, and diffuse scattering, which reports on correlations in charge density variations, must be measured. Until now, measurement of diffuse scattering from protein crystals has been scarce because of the extra effort of collecting diffuse data. Here, we present 3D measurements of diffuse intensity collected from crystals of the enzymes cyclophilin A and trypsin. The measurements were obtained from the same X-ray diffraction images as the Bragg data, using best practicesmore » for standard data collection. To model the underlying dynamics in a practical way that could be used during structure refinement, we tested translation–libration–screw (TLS), liquid-like motions (LLM), and coarse-grained normal-modes (NM) models of protein motions. The LLM model provides a global picture of motions and was refined against the diffuse data, whereas the TLS and NM models provide more detailed and distinct descriptions of atom displacements, and only used information from the Bragg data. Whereas different TLS groupings yielded similar Bragg intensities, they yielded different diffuse intensities, none of which agreed well with the data. In contrast, both the LLM and NM models agreed substantially with the diffuse data. In conclusion, these results demonstrate a realistic path to increase the number of diffuse datasets available to the wider biosciences community and indicate that dynamics-inspired NM structural models can simultaneously agree with both Bragg and diffuse scattering.« less

Multislice frozen phonon high angle annular dark-field image simulation study of Mo-V-Nb-Te-O complex oxidation catalyst "M1".

PubMed

Blom, Douglas A

2012-01-01

Multislice frozen phonon calculations were performed on a model structure of a complex oxide which has potential use as an ammoxidation catalyst. The structure has 11 cation sites in the framework, several of which exhibit mixed Mo/V substitution. In this paper the sensitivity of high-angle annular dark-field (HAADF) imaging to partial substitution of V for Mo in this structure is reported. While the relationship between the average V content in an atom column and the HAADF image intensity is not independent of thickness, it is a fairly weak function of thickness suggesting that HAADF STEM imaging in certain cases can provide a useful starting point for Rietveld refinements of mixed occupancy in complex materials. The thermal parameters of the various cations and oxygen anions in the model affect the amount of thermal diffuse scattering and therefore the intensity in the HAADF images. For complex materials where the structure has been derived via powder Rietveld refinement, the uncertainty in the thermal parameters may limit the accuracy of HAADF image simulations. With the current interest in quantitative microscopy, simulations need to accurately describe the electron scattering to the very high angles often subtended by a HAADF detector. For this system approximately 15% of the scattering occurs above 200 mrad at 200 kV. To simulate scattering to such high angles, very fine sampling of the projected potential is necessary which increases the computational cost of the simulation. Copyright © 2011 Elsevier B.V. All rights reserved.

Reintroducing electrostatics into macromolecular crystallographic refinement: application to neutron crystallography and DNA hydration.

PubMed

Fenn, Timothy D; Schnieders, Michael J; Mustyakimov, Marat; Wu, Chuanjie; Langan, Paul; Pande, Vijay S; Brunger, Axel T

2011-04-13

Most current crystallographic structure refinements augment the diffraction data with a priori information consisting of bond, angle, dihedral, planarity restraints, and atomic repulsion based on the Pauli exclusion principle. Yet, electrostatics and van der Waals attraction are physical forces that provide additional a priori information. Here, we assess the inclusion of electrostatics for the force field used for all-atom (including hydrogen) joint neutron/X-ray refinement. Two DNA and a protein crystal structure were refined against joint neutron/X-ray diffraction data sets using force fields without electrostatics or with electrostatics. Hydrogen-bond orientation/geometry favors the inclusion of electrostatics. Refinement of Z-DNA with electrostatics leads to a hypothesis for the entropic stabilization of Z-DNA that may partly explain the thermodynamics of converting the B form of DNA to its Z form. Thus, inclusion of electrostatics assists joint neutron/X-ray refinements, especially for placing and orienting hydrogen atoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reintroducing Electrostatics into Macromolecular Crystallographic Refinement: Application to Neutron Crystallography and DNA Hydration

PubMed Central

Fenn, Timothy D.; Schnieders, Michael J.; Mustyakimov, Marat; Wu, Chuanjie; Langan, Paul; Pande, Vijay S.; Brunger, Axel T.

2011-01-01

Summary Most current crystallographic structure refinements augment the diffraction data with a priori information consisting of bond, angle, dihedral, planarity restraints and atomic repulsion based on the Pauli exclusion principle. Yet, electrostatics and van der Waals attraction are physical forces that provide additional a priori information. Here we assess the inclusion of electrostatics for the force field used for all-atom (including hydrogen) joint neutron/X-ray refinement. Two DNA and a protein crystal structure were refined against joint neutron/X-ray diffraction data sets using force fields without electrostatics or with electrostatics. Hydrogen bond orientation/geometry favors the inclusion of electrostatics. Refinement of Z-DNA with electrostatics leads to a hypothesis for the entropic stabilization of Z-DNA that may partly explain the thermodynamics of converting the B form of DNA to its Z form. Thus, inclusion of electrostatics assists joint neutron/X-ray refinements, especially for placing and orienting hydrogen atoms. PMID:21481775

Role of bismuth on solidification, microstructure and mechanical properties of a near eutectic Al-Si alloys

NASA Astrophysics Data System (ADS)

Farahany, Saeed; Ourdjini, Ali; Bakar, Tuty Asma Abu; Idris, Mohd Hasbullah

2014-09-01

Computer aided thermal analysis and microstructural observation showed that addition of bismuth (Bi) within the range of 0.25 and 2 wt% produced a greater effect on the Al-Si eutectic phase than on primary aluminium and Al2Cu phases. Results showed that with addition of 1 wt% Bi the eutectic silicon structure was refined from flake-like morphology into lamellar. Bi refines rather than modifies the Si structure and increases the Al-Si eutectic fraction solid and more significantly there was no fading even up to 180 min of melt holding. Transmission electron microscopy study showed that the Si twin spacing decreased from 160 to 75 nm which is likely attributed to the refining effect of Bi. It was also found that addition of 1 wt% Bi increased the tensile strength, elongation and the absorbed energy for fracture due to the refined eutectic silicon structure.

Grain Refinement of AZ31 Magnesium Alloy Weldments by AC Pulsing Technique

NASA Astrophysics Data System (ADS)

Kishore Babu, N.; Cross, C. E.

2012-11-01

The current study has investigated the influence of alternating current pulsing on the structure and mechanical properties of AZ31 magnesium alloy gas tungsten arc (GTA) weldments. Autogenous full penetration bead-on-plate GTA welds were made under a variety of conditions including variable polarity (VP), variable polarity mixed (VPM), alternating current (AC), and alternating current pulsing (ACPC). AC pulsing resulted in significant refinement of weld metal when compared with the unpulsed conditions. AC pulsing leads to relatively finer and more equiaxed grain structure in GTA welds. In contrast, VP, VPM, and AC welding resulted in predominantly columnar grain structures. The reason for this grain refinement may be attributed to the periodic variations in temperature gradient and solidification rate associated with pulsing as well as weld pool oscillation observed in the ACPC welds. The observed grain refinement was shown to result in an appreciable increase in fusion zone hardness, tensile strength, and ductility.

A new adaptive mesh refinement strategy for numerically solving evolutionary PDE's

NASA Astrophysics Data System (ADS)

Burgarelli, Denise; Kischinhevsky, Mauricio; Biezuner, Rodney Josue

2006-11-01

A graph-based implementation of quadtree meshes for dealing with adaptive mesh refinement (AMR) in the numerical solution of evolutionary partial differential equations is discussed using finite volume methods. The technique displays a plug-in feature that allows replacement of a group of cells in any region of interest for another one with arbitrary refinement, and with only local changes occurring in the data structure. The data structure is also specially designed to minimize the number of operations needed in the AMR. Implementation of the new scheme allows flexibility in the levels of refinement of adjacent regions. Moreover, storage requirements and computational cost compare competitively with mesh refinement schemes based on hierarchical trees. Low storage is achieved for only the children nodes are stored when a refinement takes place. These nodes become part of a graph structure, thus motivating the denomination autonomous leaves graph (ALG) for the new scheme. Neighbors can then be reached without accessing their parent nodes. Additionally, linear-system solvers based on the minimization of functionals can be easily employed. ALG was not conceived with any particular problem or geometry in mind and can thus be applied to the study of several phenomena. Some test problems are used to illustrate the effectiveness of the technique.

An adaptively refined phase-space element method for cosmological simulations and collisionless dynamics

NASA Astrophysics Data System (ADS)

Hahn, Oliver; Angulo, Raul E.

2016-01-01

N-body simulations are essential for understanding the formation and evolution of structure in the Universe. However, the discrete nature of these simulations affects their accuracy when modelling collisionless systems. We introduce a new approach to simulate the gravitational evolution of cold collisionless fluids by solving the Vlasov-Poisson equations in terms of adaptively refineable `Lagrangian phase-space elements'. These geometrical elements are piecewise smooth maps between Lagrangian space and Eulerian phase-space and approximate the continuum structure of the distribution function. They allow for dynamical adaptive splitting to accurately follow the evolution even in regions of very strong mixing. We discuss in detail various one-, two- and three-dimensional test problems to demonstrate the performance of our method. Its advantages compared to N-body algorithms are: (I) explicit tracking of the fine-grained distribution function, (II) natural representation of caustics, (III) intrinsically smooth gravitational potential fields, thus (IV) eliminating the need for any type of ad hoc force softening. We show the potential of our method by simulating structure formation in a warm dark matter scenario. We discuss how spurious collisionality and large-scale discreteness noise of N-body methods are both strongly suppressed, which eliminates the artificial fragmentation of filaments. Therefore, we argue that our new approach improves on the N-body method when simulating self-gravitating cold and collisionless fluids, and is the first method that allows us to explicitly follow the fine-grained evolution in six-dimensional phase-space.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, X., E-mail: Xiujuan.jiang@pnnl.gov

Soft magnetic materials are often limited in scalability due to conventional processes that do not retain beneficial microstructures, and their associated physical properties, during densification. In this work, friction consolidation (FC) has been studied to fabricate Fe−Si soft magnetic materials from gas-atomized powder precursors. Fe−Si powder is consolidated using variable pressure and tool rotation speed in an effort to evaluate this unique densification approach for potential improvements in magnetic properties. FC, due to the high shear deformation involved, is shown to result in uniform gradual grain structure refinement across the consolidated workpiece from the center nearest the tool to themore » edge. Magnetic properties along different orientations indicate little, if any, textural orientation in the refined grain structure. The effect of annealing on the magnetic properties is evaluated and shown to decrease coercivity. FC processing was able to retain the magnetization of the original gas-atomized powders but further process optimization is needed to reach the optimal coercivity for the soft magnetic materials applications. - Highlights: •Friction stir processing was utilized to consolidate Fe−Si soft magnetic powders. •The resultant microstructure and magnetic properties were correlated to the processing conditions. •Friction consolidation refined the grain size of the materials by ~ 40%. •Annealing successfully reduced the coercivity induced by the stress during processing. •The results shine light on the possible scaling up of nanostructured materials.« less

Hierarchical prediction of industrial water demand based on refined Laspeyres decomposition analysis.

PubMed

Shang, Yizi; Lu, Shibao; Gong, Jiaguo; Shang, Ling; Li, Xiaofei; Wei, Yongping; Shi, Hongwang

2017-12-01

A recent study decomposed the changes in industrial water use into three hierarchies (output, technology, and structure) using a refined Laspeyres decomposition model, and found monotonous and exclusive trends in the output and technology hierarchies. Based on that research, this study proposes a hierarchical prediction approach to forecast future industrial water demand. Three water demand scenarios (high, medium, and low) were then established based on potential future industrial structural adjustments, and used to predict water demand for the structural hierarchy. The predictive results of this approach were compared with results from a grey prediction model (GPM (1, 1)). The comparison shows that the results of the two approaches were basically identical, differing by less than 10%. Taking Tianjin, China, as a case, and using data from 2003-2012, this study predicts that industrial water demand will continuously increase, reaching 580 million m 3 , 776.4 million m 3 , and approximately 1.09 billion m 3 by the years 2015, 2020 and 2025 respectively. It is concluded that Tianjin will soon face another water crisis if no immediate measures are taken. This study recommends that Tianjin adjust its industrial structure with water savings as the main objective, and actively seek new sources of water to increase its supply.

Application of Al-2La-1B Grain Refiner to Al-10Si-0.3Mg Casting Alloy

NASA Astrophysics Data System (ADS)

Jing, Lijun; Pan, Ye; Lu, Tao; Li, Chenlin; Pi, Jinhong; Sheng, Ningyue

2018-05-01

This paper reports the application and microstructure refining effect of an Al-2La-1B grain refiner in Al-10Si-0.3Mg casting alloy. Compared with the traditional Al-5Ti-1B refiner, Al-2La-1B refiner shows better performances on the grain refinement of Al-10Si-0.3Mg alloy. Transmission electron microscopy analysis suggests that the crystallite structure features of LaB6 are beneficial to the heterogeneous nucleation of α-Al grains. Regarding the mechanical performances, tensile properties of Al-10Si-0.3Mg casting alloy are prominently improved, due to the refined microstructures.

Synchrotron Powder X-ray Diffraction Study of the Structure and Dehydration Behavior of Sepiolite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Post,J.; Bish, D.; Heaney, P.

2007-01-01

Rietveld refinements using synchrotron powder X-ray diffraction data were used to study the crystal structure and dehydration behavior of sepiolite from Durango, Mexico. The room-temperature (RT) sepiolite structure in air compares well with previous models but reveals an additional zeolitic H{sub 2}O site. The RT structure under vacuum retained only {approx}1/8 of the zeolitic H{sub 2}O and the volume decreased by 1.3%. Real-time, temperature-resolved synchrotron powder X-ray diffraction data and Rietveld refinements were used to investigate the behavior of the sepiolite structure from 300 to 925 K. Rietveld refinements revealed that most of the zeolitic H{sub 2}O is lost bymore » {approx}390 K, accompanied by a decrease in the a and c unit-cell parameters. Above {approx}600 K the sepiolite structure folds as one-half of the crystallographically bound H{sub 2}O is lost. Rietveld refinements of the 'anhydrous' sepiolite structure reveal that, in general, unit-cell parameters a and b and volume steadily decrease with increasing temperature; there is an obvious change in slope at {approx}820 K suggesting a phase transformation coinciding with the loss of the remaining bound H{sub 2}O molecule.« less

Conformational Analysis of Free and Bound Retinoic Acid

PubMed Central

Fu, Zheng; Li, Xue; Merz, Kenneth M.

2012-01-01

The conformational profiles of unbound all-trans and 9-cis retinoic acid (RA) have been determined using classical and quantum mechanical calculations. Sixty-six all-trans-RA (ATRA) and forty-eight 9-cis-RA energy minimum conformers were identified via HF/6-31G* geometry optimizations in vacuo. Their relative conformational energies were estimated utilizing the M06, M06-2x and MP2 methods combined with the 6-311+G(d,p), aug-cc-pVDZ and aug-cc-pVTZ basis sets, as well as complete basis set MP2 extrapolations using the latter two basis sets. Single-point energy calculations performed with the M06-2x density functional were found to yield similar results to MP2/CBS for the low-energy retinoic acid conformations. Not unexpectedly, the conformational propensities of retinoic acid were governed by the orientation and arrangement of the torsion angles associated with the polyene tail. We also used previously reported QM/MM X-ray refinement results on four ATRA-protein crystal structures plus one newly refined 9-cis-RA complex (PDB ID 1XDK) in order to investigate the conformational preferences of bound retinoic acid. In the re-refined RA conformers the conjugated double bonds are nearly coplanar, which is consistent with the global minimum identified by the Omega/QM method rather than the corresponding crystallographically determined conformations given in the PDB. Consequently, a 91.3% average reduction of the local strain energy in the gas phase, as well as 92.1% in PCM solvent, was observed using the QM/MM refined structures versus the PDB deposited RA conformations. These results thus demonstrate that our QM/MM X-ray refinement approach can significantly enhance the quality of X-ray crystal structures refined by conventional refinement protocols, thereby providing reliable drug-target structural information for use in structure-based drug discovery applications. PMID:22844234

Advanced Computational Methods for High-accuracy Refinement of Protein Low-quality Models

NASA Astrophysics Data System (ADS)

Zang, Tianwu

Predicting the 3-dimentional structure of protein has been a major interest in the modern computational biology. While lots of successful methods can generate models with 3˜5A root-mean-square deviation (RMSD) from the solution, the progress of refining these models is quite slow. It is therefore urgently needed to develop effective methods to bring low-quality models to higher-accuracy ranges (e.g., less than 2 A RMSD). In this thesis, I present several novel computational methods to address the high-accuracy refinement problem. First, an enhanced sampling method, named parallel continuous simulated tempering (PCST), is developed to accelerate the molecular dynamics (MD) simulation. Second, two energy biasing methods, Structure-Based Model (SBM) and Ensemble-Based Model (EBM), are introduced to perform targeted sampling around important conformations. Third, a three-step method is developed to blindly select high-quality models along the MD simulation. These methods work together to make significant refinement of low-quality models without any knowledge of the solution. The effectiveness of these methods is examined in different applications. Using the PCST-SBM method, models with higher global distance test scores (GDT_TS) are generated and selected in the MD simulation of 18 targets from the refinement category of the 10th Critical Assessment of Structure Prediction (CASP10). In addition, in the refinement test of two CASP10 targets using the PCST-EBM method, it is indicated that EBM may bring the initial model to even higher-quality levels. Furthermore, a multi-round refinement protocol of PCST-SBM improves the model quality of a protein to the level that is sufficient high for the molecular replacement in X-ray crystallography. Our results justify the crucial position of enhanced sampling in the protein structure prediction and demonstrate that a considerable improvement of low-accuracy structures is still achievable with current force fields.

Magnesium Recycling of Partially Oxidized, Mixed Magnesium-Aluminum Scrap Through Combined Refining and Solid Oxide Membrane (SOM) Electrolysis Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guan, Xiaofei; Zink, Peter; Pal, Uday

2012-03-11

Pure magnesium (Mg) is recycled from 19g of partially oxidized 50.5wt.%Mg-Aluminum (Al) alloy. During the refining process, potentiodynamic scans (PDS) were performed to determine the electrorefining potential for magnesium. The PDS show that the electrorefining potential increases over time as the Mg content inside the Mg-Al scrap decreases. Up to 100% percent of magnesium is refined from the Mg-Al scrap by a novel refining process of dissolving magnesium and its oxide into a flux followed by vapor phase removal of dissolved magnesium and subsequently condensing the magnesium vapors in a separate condenser. The solid oxide membrane (SOM) electrolysis process ismore » employed in the refining system to enable additional recycling of magnesium from magnesium oxide (MgO) in the partially oxidized Mg-Al scrap. The combination of the refining and SOM processes yields 7.4g of pure magnesium; could not collect and weigh all of the magnesium recovered.« less

Profex: a graphical user interface for the Rietveld refinement program BGMN.

PubMed

Doebelin, Nicola; Kleeberg, Reinhard

2015-10-01

Profex is a graphical user interface for the Rietveld refinement program BGMN . Its interface focuses on preserving BGMN 's powerful and flexible scripting features by giving direct access to BGMN input files. Very efficient workflows for single or batch refinements are achieved by managing refinement control files and structure files, by providing dialogues and shortcuts for many operations, by performing operations in the background, and by providing import filters for CIF and XML crystal structure files. Refinement results can be easily exported for further processing. State-of-the-art graphical export of diffraction patterns to pixel and vector graphics formats allows the creation of publication-quality graphs with minimum effort. Profex reads and converts a variety of proprietary raw data formats and is thus largely instrument independent. Profex and BGMN are available under an open-source license for Windows, Linux and OS X operating systems.

Profex: a graphical user interface for the Rietveld refinement program BGMN

PubMed Central

Doebelin, Nicola; Kleeberg, Reinhard

2015-01-01

Profex is a graphical user interface for the Rietveld refinement program BGMN. Its interface focuses on preserving BGMN’s powerful and flexible scripting features by giving direct access to BGMN input files. Very efficient workflows for single or batch refinements are achieved by managing refinement control files and structure files, by providing dialogues and shortcuts for many operations, by performing operations in the background, and by providing import filters for CIF and XML crystal structure files. Refinement results can be easily exported for further processing. State-of-the-art graphical export of diffraction patterns to pixel and vector graphics formats allows the creation of publication-quality graphs with minimum effort. Profex reads and converts a variety of proprietary raw data formats and is thus largely instrument independent. Profex and BGMN are available under an open-source license for Windows, Linux and OS X operating systems. PMID:26500466

Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum.

PubMed

Brunger, Axel T; Das, Debanu; Deacon, Ashley M; Grant, Joanna; Terwilliger, Thomas C; Read, Randy J; Adams, Paul D; Levitt, Michael; Schröder, Gunnar F

2012-04-01

Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence.

Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum

PubMed Central

Brunger, Axel T.; Das, Debanu; Deacon, Ashley M.; Grant, Joanna; Terwilliger, Thomas C.; Read, Randy J.; Adams, Paul D.; Levitt, Michael; Schröder, Gunnar F.

2012-01-01

Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence. PMID:22505259

An accurate global potential energy surface, dipole moment surface, and rovibrational frequencies for NH3

NASA Astrophysics Data System (ADS)

Huang, Xinchuan; Schwenke, David W.; Lee, Timothy J.

2008-12-01

A global potential energy surface (PES) that includes short and long range terms has been determined for the NH3 molecule. The singles and doubles coupled-cluster method that includes a perturbational estimate of connected triple excitations and the internally contracted averaged coupled-pair functional electronic structure methods have been used in conjunction with very large correlation-consistent basis sets, including diffuse functions. Extrapolation to the one-particle basis set limit was performed and core correlation and scalar relativistic contributions were included directly, while the diagonal Born-Oppenheimer correction was added. Our best purely ab initio PES, denoted "mixed," is constructed from two PESs which differ in whether the ic-ACPF higher-order correlation correction was added or not. Rovibrational transition energies computed from the mixed PES agree well with experiment and the best previous theoretical studies, but most importantly the quality does not deteriorate even up to 10300cm-1 above the zero-point energy (ZPE). The mixed PES was improved further by empirical refinement using the most reliable J =0-2 rovibrational transitions in the HITRAN 2004 database. Agreement between high-resolution experiment and rovibrational transition energies computed from our refined PES for J =0-6 is excellent. Indeed, the root mean square (rms) error for 13 HITRAN 2004 bands for J =0-2 is 0.023cm-1 and that for each band is always ⩽0.06cm-1. For J =3-5 the rms error is always ⩽0.15cm-1. This agreement means that transition energies computed with our refined PES should be useful in the assignment of new high-resolution NH3 spectra and in correcting mistakes in previous assignments. Ideas for further improvements to our refined PES and for extension to other isotopolog are discussed.

Evaluation of the dermal carcinogenicity of lubricant base oils by the mouse skin painting bioassay and other proposed methods.

PubMed

Chasey, K L; McKee, R H

1993-01-01

Lubricant base oils are petroleum products that are predominantly derived from the vacuum distillation of crude oil. Various types of refinement can be employed during the manufacturing process, and evidence suggests that certain of the associated process streams produce skin cancer. Polycyclic aromatic compounds (PACs), some of which are considered as the causative agents, are removed, concentrated or chemically converted during the refinement process. In order to understand the effects of various types of refinement processes on carcinogenic potential, 94 oils were evaluated in the mouse epidermal cancer bioassay. This Exxon database is unique, because of the wide range of crude oils and processing histories represented. Seven processing history classifications are described, and conclusions concerning the impacts of each refinement process on dermal carcinogenicity are discussed. This research also included an evaluation of selected biological and chemical test methods for predicting carcinogenic potential. These included a modified version of the Ames test for mutagenicity, as well as analytical characterizations of the polycyclic aromatic structures in the oils. For classification purposes, a sample was considered to be carcinogenic if it resulted in the production of two or more tumor-bearing animals (in test groups of either 40 or 50 animals). The modified Ames test was considered to be positive if the mutagenicity index was > or = 2.0, and PAC analyses were similarly designated as positive or negative according to proposed guidelines. All of the alternative test methods showed similar agreement with dermal carcinogenicity bioassay data; concordance values were > or = 80%. However, each test was incorrect in ca. 10%-20% of the cases evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Correction of erroneously packed protein's side chains in the NMR structure based on ab initio chemical shift calculations.

PubMed

Zhu, Tong; Zhang, John Z H; He, Xiao

2014-09-14

In this work, protein side chain (1)H chemical shifts are used as probes to detect and correct side-chain packing errors in protein's NMR structures through structural refinement. By applying the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method for ab initio calculation of chemical shifts, incorrect side chain packing was detected in the NMR structures of the Pin1 WW domain. The NMR structure is then refined by using molecular dynamics simulation and the polarized protein-specific charge (PPC) model. The computationally refined structure of the Pin1 WW domain is in excellent agreement with the corresponding X-ray structure. In particular, the use of the PPC model yields a more accurate structure than that using the standard (nonpolarizable) force field. For comparison, some of the widely used empirical models for chemical shift calculations are unable to correctly describe the relationship between the particular proton chemical shift and protein structures. The AF-QM/MM method can be used as a powerful tool for protein NMR structure validation and structural flaw detection.

Correcting pervasive errors in RNA crystallography through enumerative structure prediction.

PubMed

Chou, Fang-Chieh; Sripakdeevong, Parin; Dibrov, Sergey M; Hermann, Thomas; Das, Rhiju

2013-01-01

Three-dimensional RNA models fitted into crystallographic density maps exhibit pervasive conformational ambiguities, geometric errors and steric clashes. To address these problems, we present enumerative real-space refinement assisted by electron density under Rosetta (ERRASER), coupled to Python-based hierarchical environment for integrated 'xtallography' (PHENIX) diffraction-based refinement. On 24 data sets, ERRASER automatically corrects the majority of MolProbity-assessed errors, improves the average R(free) factor, resolves functionally important discrepancies in noncanonical structure and refines low-resolution models to better match higher-resolution models.

The structural and Raman spectral studies on Ni0.5Cu0.5Fe2O4 ferrite

NASA Astrophysics Data System (ADS)

Somani, M.; Saleem, M.

2018-05-01

Spinel ferrite Ni0.5Cu0.5Fe2O4 has been successfully prepared via solid state reaction. The crystal structure studies using XRD technique revealed cubic structure of the sample. The XRD spectra was further refined via Retvield Refinement and all the parameters regarding structure were obtained which confirmed cubic structure. The assigned space group was found to be Fd-3m. Particle size was calculated to be 56 nm. The Raman Spectra revealed five active Raman modes which confirmed spinel structure.

Using more than 801 296 small-molecule crystal structures to aid in protein structure refinement and analysis

PubMed Central

Cole, Jason C.

2017-01-01

The Cambridge Structural Database (CSD) is the worldwide resource for the dissemination of all published three-dimensional structures of small-molecule organic and metal–organic compounds. This paper briefly describes how this collection of crystal structures can be used en masse in the context of macromolecular crystallography. Examples highlight how the CSD and associated software aid protein–ligand complex validation, and show how the CSD could be further used in the generation of geometrical restraints for protein structure refinement. PMID:28291758

Use of Bayesian Inference in Crystallographic Structure Refinement via Full Diffraction Profile Analysis

PubMed Central

Fancher, Chris M.; Han, Zhen; Levin, Igor; Page, Katharine; Reich, Brian J.; Smith, Ralph C.; Wilson, Alyson G.; Jones, Jacob L.

2016-01-01

A Bayesian inference method for refining crystallographic structures is presented. The distribution of model parameters is stochastically sampled using Markov chain Monte Carlo. Posterior probability distributions are constructed for all model parameters to properly quantify uncertainty by appropriately modeling the heteroskedasticity and correlation of the error structure. The proposed method is demonstrated by analyzing a National Institute of Standards and Technology silicon standard reference material. The results obtained by Bayesian inference are compared with those determined by Rietveld refinement. Posterior probability distributions of model parameters provide both estimates and uncertainties. The new method better estimates the true uncertainties in the model as compared to the Rietveld method. PMID:27550221

COMET-AR User's Manual: COmputational MEchanics Testbed with Adaptive Refinement

NASA Technical Reports Server (NTRS)

Moas, E. (Editor)

1997-01-01

The COMET-AR User's Manual provides a reference manual for the Computational Structural Mechanics Testbed with Adaptive Refinement (COMET-AR), a software system developed jointly by Lockheed Palo Alto Research Laboratory and NASA Langley Research Center under contract NAS1-18444. The COMET-AR system is an extended version of an earlier finite element based structural analysis system called COMET, also developed by Lockheed and NASA. The primary extensions are the adaptive mesh refinement capabilities and a new "object-like" database interface that makes COMET-AR easier to extend further. This User's Manual provides a detailed description of the user interface to COMET-AR from the viewpoint of a structural analyst.

Homoisoflavonoids as potential antiangiogenic agents for retinal neovascularization.

PubMed

Amin, Sk Abdul; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

2017-11-01

A number of people worldwide have been suffering from ocular neovascularization that may be treated by a variety of drugs but these may possess adverse effects. Therefore, small antiangiogenic molecules with higher potency and lower toxic effects are intended. However, homoisoflavonoids of natural origin show the potential antiangiogenic effect in ocular neovascularization. These homoisoflavonoids are judged quantitatively in terms of statistical validation through multi-chemometric modeling approaches for the betterment and refinement of their structures required for higher antiangiogenic activity targeted to ocular neovascularization. These approaches may be utilized to design better antiangiogenic homoisoflavonoids. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Importance of the ion-pair interactions in the OPEP coarse-grained force field: parametrization and validation.

PubMed

Sterpone, Fabio; Nguyen, Phuong H; Kalimeri, Maria; Derreumaux, Philippe

2013-10-08

We have derived new effective interactions that improve the description of ion-pairs in the OPEP coarse-grained force field without introducing explicit electrostatic terms. The iterative Boltzmann inversion method was used to extract these potentials from all atom simulations by targeting the radial distribution function of the distance between the center of mass of the side-chains. The new potentials have been tested on several systems that differ in structural properties, thermodynamic stabilities and number of ion-pairs. Our modeling, by refining the packing of the charged amino-acids, impacts the stability of secondary structure motifs and the population of intermediate states during temperature folding/unfolding; it also improves the aggregation propensity of peptides. The new version of the OPEP force field has the potentiality to describe more realistically a large spectrum of situations where salt-bridges are key interactions.

Evaluation of unrestrained replica-exchange simulations using dynamic walkers in temperature space for protein structure refinement.

PubMed

Olson, Mark A; Lee, Michael S

2014-01-01

A central problem of computational structural biology is the refinement of modeled protein structures taken from either comparative modeling or knowledge-based methods. Simulations are commonly used to achieve higher resolution of the structures at the all-atom level, yet methodologies that consistently yield accurate results remain elusive. In this work, we provide an assessment of an adaptive temperature-based replica exchange simulation method where the temperature clients dynamically walk in temperature space to enrich their population and exchanges near steep energetic barriers. This approach is compared to earlier work of applying the conventional method of static temperature clients to refine a dataset of conformational decoys. Our results show that, while an adaptive method has many theoretical advantages over a static distribution of client temperatures, only limited improvement was gained from this strategy in excursions of the downhill refinement regime leading to an increase in the fraction of native contacts. To illustrate the sampling differences between the two simulation methods, energy landscapes are presented along with their temperature client profiles.

Solution NMR structure of a designed metalloprotein and complementary molecular dynamics refinement.

PubMed

Calhoun, Jennifer R; Liu, Weixia; Spiegel, Katrin; Dal Peraro, Matteo; Klein, Michael L; Valentine, Kathleen G; Wand, A Joshua; DeGrado, William F

2008-02-01

We report the solution NMR structure of a designed dimetal-binding protein, di-Zn(II) DFsc, along with a secondary refinement step employing molecular dynamics techniques. Calculation of the initial NMR structural ensemble by standard methods led to distortions in the metal-ligand geometries at the active site. Unrestrained molecular dynamics using a nonbonded force field for the metal shell, followed by quantum mechanical/molecular mechanical dynamics of DFsc, were used to relax local frustrations at the dimetal site that were apparent in the initial NMR structure and provide a more realistic description of the structure. The MD model is consistent with NMR restraints, and in good agreement with the structural and functional properties expected for DF proteins. This work demonstrates that NMR structures of metalloproteins can be further refined using classical and first-principles molecular dynamics methods in the presence of explicit solvent to provide otherwise unavailable insight into the geometry of the metal center.

Carpet: Adaptive Mesh Refinement for the Cactus Framework

NASA Astrophysics Data System (ADS)

Schnetter, Erik; Hawley, Scott; Hawke, Ian

2016-11-01

Carpet is an adaptive mesh refinement and multi-patch driver for the Cactus Framework (ascl:1102.013). Cactus is a software framework for solving time-dependent partial differential equations on block-structured grids, and Carpet acts as driver layer providing adaptive mesh refinement, multi-patch capability, as well as parallelization and efficient I/O.

Three-Dimensional Molecular Modeling of a Diverse Range of SC Clan Serine Proteases

PubMed Central

Laskar, Aparna; Chatterjee, Aniruddha; Chatterjee, Somnath; Rodger, Euan J.

2012-01-01

Serine proteases are involved in a variety of biological processes and are classified into clans sharing structural homology. Although various three-dimensional structures of SC clan proteases have been experimentally determined, they are mostly bacterial and animal proteases, with some from archaea, plants, and fungi, and as yet no structures have been determined for protozoa. To bridge this gap, we have used molecular modeling techniques to investigate the structural properties of different SC clan serine proteases from a diverse range of taxa. Either SWISS-MODEL was used for homology-based structure prediction or the LOOPP server was used for threading-based structure prediction. The predicted models were refined using Insight II and SCRWL and validated against experimental structures. Investigation of secondary structures and electrostatic surface potential was performed using MOLMOL. The structural geometry of the catalytic core shows clear deviations between taxa, but the relative positions of the catalytic triad residues were conserved. Evolutionary divergence was also exhibited by large variation in secondary structure features outside the core, differences in overall amino acid distribution, and unique surface electrostatic potential patterns between species. Encompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on SC clan serine proteases. PMID:23213528

Development of Multidisciplinary, Multifidelity Analysis, Integration, and Optimization of Aerospace Vehicles

DTIC Science & Technology

2010-02-27

investigated in more detail. The intermediate level of fidelity, though more expensive, is then used to refine the analysis , add geometric detail, and...design stage is used to further refine the analysis , narrowing the design to a handful of options. Figure 1. Integrated Hierarchical Framework. In...computational structural and computational fluid modeling. For the structural analysis tool we used McIntosh Structural Dynamics’ finite element code CNEVAL

Fine refinement of solid state structure of racemic form of phospho-tyrosine employing NMR Crystallography approach.

PubMed

Paluch, Piotr; Pawlak, Tomasz; Oszajca, Marcin; Lasocha, Wieslaw; Potrzebowski, Marek J

2015-02-01

We present step by step facets important in NMR Crystallography strategy employing O-phospho-dl-tyrosine as model sample. The significance of three major techniques being components of this approach: solid state NMR (SS NMR), X-ray diffraction of powdered sample (PXRD) and theoretical calculations (Gauge Invariant Projector Augmented Wave; GIPAW) is discussed. Each experimental technique provides different set of structural constraints. From the PXRD measurement the size of the unit cell, space group and roughly refined molecular structure are established. SS NMR provides information about content of crystallographic asymmetric unit, local geometry, molecular motion in the crystal lattice and hydrogen bonding pattern. GIPAW calculations are employed for validation of quality of elucidation and fine refinement of structure. Crystal and molecular structure of O-phospho-dl-tyrosine solved by NMR Crystallography is deposited at Cambridge Crystallographic Data Center under number CCDC 1005924. Copyright © 2014 Elsevier Inc. All rights reserved.

The PDB_REDO server for macromolecular structure model optimization.

PubMed

Joosten, Robbie P; Long, Fei; Murshudov, Garib N; Perrakis, Anastassis

2014-07-01

The refinement and validation of a crystallographic structure model is the last step before the coordinates and the associated data are submitted to the Protein Data Bank (PDB). The success of the refinement procedure is typically assessed by validating the models against geometrical criteria and the diffraction data, and is an important step in ensuring the quality of the PDB public archive [Read et al. (2011 ▶), Structure, 19, 1395-1412]. The PDB_REDO procedure aims for 'constructive validation', aspiring to consistent and optimal refinement parameterization and pro-active model rebuilding, not only correcting errors but striving for optimal interpretation of the electron density. A web server for PDB_REDO has been implemented, allowing thorough, consistent and fully automated optimization of the refinement procedure in REFMAC and partial model rebuilding. The goal of the web server is to help practicing crystallo-graphers to improve their model prior to submission to the PDB. For this, additional steps were implemented in the PDB_REDO pipeline, both in the refinement procedure, e.g. testing of resolution limits and k-fold cross-validation for small test sets, and as new validation criteria, e.g. the density-fit metrics implemented in EDSTATS and ligand validation as implemented in YASARA. Innovative ways to present the refinement and validation results to the user are also described, which together with auto-generated Coot scripts can guide users to subsequent model inspection and improvement. It is demonstrated that using the server can lead to substantial improvement of structure models before they are submitted to the PDB.

The PDB_REDO server for macromolecular structure model optimization

PubMed Central

Joosten, Robbie P.; Long, Fei; Murshudov, Garib N.; Perrakis, Anastassis

2014-01-01

The refinement and validation of a crystallographic structure model is the last step before the coordinates and the associated data are submitted to the Protein Data Bank (PDB). The success of the refinement procedure is typically assessed by validating the models against geometrical criteria and the diffraction data, and is an important step in ensuring the quality of the PDB public archive [Read et al. (2011 ▶), Structure, 19, 1395–1412]. The PDB_REDO procedure aims for ‘constructive validation’, aspiring to consistent and optimal refinement parameterization and pro-active model rebuilding, not only correcting errors but striving for optimal interpretation of the electron density. A web server for PDB_REDO has been implemented, allowing thorough, consistent and fully automated optimization of the refinement procedure in REFMAC and partial model rebuilding. The goal of the web server is to help practicing crystallo­graphers to improve their model prior to submission to the PDB. For this, additional steps were implemented in the PDB_REDO pipeline, both in the refinement procedure, e.g. testing of resolution limits and k-fold cross-validation for small test sets, and as new validation criteria, e.g. the density-fit metrics implemented in EDSTATS and ligand validation as implemented in YASARA. Innovative ways to present the refinement and validation results to the user are also described, which together with auto-generated Coot scripts can guide users to subsequent model inspection and improvement. It is demonstrated that using the server can lead to substantial improvement of structure models before they are submitted to the PDB. PMID:25075342

A conservation and biophysics guided stochastic approach to refining docked multimeric proteins.

PubMed

Akbal-Delibas, Bahar; Haspel, Nurit

2013-01-01

We introduce a protein docking refinement method that accepts complexes consisting of any number of monomeric units. The method uses a scoring function based on a tight coupling between evolutionary conservation, geometry and physico-chemical interactions. Understanding the role of protein complexes in the basic biology of organisms heavily relies on the detection of protein complexes and their structures. Different computational docking methods are developed for this purpose, however, these methods are often not accurate and their results need to be further refined to improve the geometry and the energy of the resulting complexes. Also, despite the fact that complexes in nature often have more than two monomers, most docking methods focus on dimers since the computational complexity increases exponentially due to the addition of monomeric units. Our results show that the refinement scheme can efficiently handle complexes with more than two monomers by biasing the results towards complexes with native interactions, filtering out false positive results. Our refined complexes have better IRMSDs with respect to the known complexes and lower energies than those initial docked structures. Evolutionary conservation information allows us to bias our results towards possible functional interfaces, and the probabilistic selection scheme helps us to escape local energy minima. We aim to incorporate our refinement method in a larger framework which also enables docking of multimeric complexes given only monomeric structures.

An adaptive interpolation scheme for molecular potential energy surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kowalewski, Markus, E-mail: mkowalew@uci.edu; Larsson, Elisabeth; Heryudono, Alfa

The calculation of potential energy surfaces for quantum dynamics can be a time consuming task—especially when a high level of theory for the electronic structure calculation is required. We propose an adaptive interpolation algorithm based on polyharmonic splines combined with a partition of unity approach. The adaptive node refinement allows to greatly reduce the number of sample points by employing a local error estimate. The algorithm and its scaling behavior are evaluated for a model function in 2, 3, and 4 dimensions. The developed algorithm allows for a more rapid and reliable interpolation of a potential energy surface within amore » given accuracy compared to the non-adaptive version.« less

GRID: a high-resolution protein structure refinement algorithm.

PubMed

Chitsaz, Mohsen; Mayo, Stephen L

2013-03-05

The energy-based refinement of protein structures generated by fold prediction algorithms to atomic-level accuracy remains a major challenge in structural biology. Energy-based refinement is mainly dependent on two components: (1) sufficiently accurate force fields, and (2) efficient conformational space search algorithms. Focusing on the latter, we developed a high-resolution refinement algorithm called GRID. It takes a three-dimensional protein structure as input and, using an all-atom force field, attempts to improve the energy of the structure by systematically perturbing backbone dihedrals and side-chain rotamer conformations. We compare GRID to Backrub, a stochastic algorithm that has been shown to predict a significant fraction of the conformational changes that occur with point mutations. We applied GRID and Backrub to 10 high-resolution (≤ 2.8 Å) crystal structures from the Protein Data Bank and measured the energy improvements obtained and the computation times required to achieve them. GRID resulted in energy improvements that were significantly better than those attained by Backrub while expending about the same amount of computational resources. GRID resulted in relaxed structures that had slightly higher backbone RMSDs compared to Backrub relative to the starting crystal structures. The average RMSD was 0.25 ± 0.02 Å for GRID versus 0.14 ± 0.04 Å for Backrub. These relatively minor deviations indicate that both algorithms generate structures that retain their original topologies, as expected given the nature of the algorithms. Copyright © 2012 Wiley Periodicals, Inc.

Solution adaptive grids applied to low Reynolds number flow

NASA Astrophysics Data System (ADS)

de With, G.; Holdø, A. E.; Huld, T. A.

2003-08-01

A numerical study has been undertaken to investigate the use of a solution adaptive grid for flow around a cylinder in the laminar flow regime. The main purpose of this work is twofold. The first aim is to investigate the suitability of a grid adaptation algorithm and the reduction in mesh size that can be obtained. Secondly, the uniform asymmetric flow structures are ideal to validate the mesh structures due to mesh refinement and consequently the selected refinement criteria. The refinement variable used in this work is a product of the rate of strain and the mesh cell size, and contains two variables Cm and Cstr which determine the order of each term. By altering the order of either one of these terms the refinement behaviour can be modified.

PDB_REDO: automated re-refinement of X-ray structure models in the PDB.

PubMed

Joosten, Robbie P; Salzemann, Jean; Bloch, Vincent; Stockinger, Heinz; Berglund, Ann-Charlott; Blanchet, Christophe; Bongcam-Rudloff, Erik; Combet, Christophe; Da Costa, Ana L; Deleage, Gilbert; Diarena, Matteo; Fabbretti, Roberto; Fettahi, Géraldine; Flegel, Volker; Gisel, Andreas; Kasam, Vinod; Kervinen, Timo; Korpelainen, Eija; Mattila, Kimmo; Pagni, Marco; Reichstadt, Matthieu; Breton, Vincent; Tickle, Ian J; Vriend, Gert

2009-06-01

Structural biology, homology modelling and rational drug design require accurate three-dimensional macromolecular coordinates. However, the coordinates in the Protein Data Bank (PDB) have not all been obtained using the latest experimental and computational methods. In this study a method is presented for automated re-refinement of existing structure models in the PDB. A large-scale benchmark with 16 807 PDB entries showed that they can be improved in terms of fit to the deposited experimental X-ray data as well as in terms of geometric quality. The re-refinement protocol uses TLS models to describe concerted atom movement. The resulting structure models are made available through the PDB_REDO databank (http://www.cmbi.ru.nl/pdb_redo/). Grid computing techniques were used to overcome the computational requirements of this endeavour.

Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps.

PubMed

Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan; Stone, John E; Zhao, Jianhua; Schulten, Klaus

2016-07-07

Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a radius of convergence of ~25 Å demonstrated with the accurate modeling of β-galactosidase and TRPV1 proteins at 3.2 Å and 3.4 Å resolution, respectively. The MDFF refinements uniquely offer map-model validation and B-factor determination criteria based on the inherent dynamics of the macromolecules studied, captured by means of local root mean square fluctuations. The MDFF tools described are available to researchers through an easy-to-use and cost-effective cloud computing resource on Amazon Web Services.

Rietveld refined structural and room temperature vibrational properties of BaTiO3 doped La0.67Ba0.33MnO3 composites

NASA Astrophysics Data System (ADS)

Dar, M. A.; Sheikh, M. W.; Malla, M. S.; Varshney, Dinesh

2016-05-01

The composites of (1-x) La0.67Ba0.33MnO3 (LBMO) + xBaTiO3 (BTO) (x = 0, 0.25 and 1.0) were synthesized by conventional solid-state reaction method. Rietveld refinement was employed to characterize the structural information of the prepared ceramics. The result of the Rietveld refinement of X-ray powder diffraction of La0.67Ba0.33MnO3 and BaTiO3 shows that these compounds crystallize in rhombohedral (R3c) and tetragonal (P4mm), respectively. The structural parameters and the reliability factors for the LBMO-BTO composite ceramics were successfully determined by the Rietveld refinement. At room temperature, Raman active phonon modes predicted by the group theory were observed only in BaTiO3 and composite sample. Pure LBMO does not show any Raman active Phonon mode at room temperature.

Structure of catalase determined by MicroED

PubMed Central

Nannenga, Brent L; Shi, Dan; Hattne, Johan; Reyes, Francis E; Gonen, Tamir

2014-01-01

MicroED is a recently developed method that uses electron diffraction for structure determination from very small three-dimensional crystals of biological material. Previously we used a series of still diffraction patterns to determine the structure of lysozyme at 2.9 Å resolution with MicroED (Shi et al., 2013). Here we present the structure of bovine liver catalase determined from a single crystal at 3.2 Å resolution by MicroED. The data were collected by continuous rotation of the sample under constant exposure and were processed and refined using standard programs for X-ray crystallography. The ability of MicroED to determine the structure of bovine liver catalase, a protein that has long resisted atomic analysis by traditional electron crystallography, demonstrates the potential of this method for structure determination. DOI: http://dx.doi.org/10.7554/eLife.03600.001 PMID:25303172

Disordered Atom Molecular Potential for Water Parameterized against Neutron Diffraction Data. Application to the Structure of Ice Ih.

PubMed

Soper, Alan K

2015-07-23

A disordered atom molecular potential (DAMP) for water is described that accurately accounts for the observed neutron interference differential scattering cross sections for light water, heavy water, and two different mixtures of these liquids (x = 0.5 and x = 0.64, where x is the mole fraction of light water in the mixtures) at T = 283 K. This potential, when used in a NVT Monte Carlo computer simulation, produces an intermolecular pressure of ∼0 kbar and a configurational energy of approximately -50 kJ/mol, close to the values found in the ambient liquid at this temperature. The same potential is used as the reference potential in an empirical potential structure refinement of ice diffraction data at T = 258 K measured at the same time as the water data and under the same conditions. Particularly intriguing is the finding that the O···O-H angle in ice, which would be 0° for a linear hydrogen bond, is actually more disordered in ice than in the liquid. A rationalization of these findings is presented. It remains to be seen whether this potential has any value other than simply as a description of the ambient liquid structure.

Fiberboards from loblolly pine refiner groundwood: effects of gross wood characteristics and board density

Treesearch

Charles W. McMillin

1968-01-01

Boards for insulation and and structural uses are being manufactured in increasing quantities. The coarse fiber required for these products can be disk-refined from untreated wood chips. Since such fiber is produced in essentially one mechanical operation, continuous control is required of the raw material as well as the refining process.

PDB_REDO: constructive validation, more than just looking for errors.

PubMed

Joosten, Robbie P; Joosten, Krista; Murshudov, Garib N; Perrakis, Anastassis

2012-04-01

Developments of the PDB_REDO procedure that combine re-refinement and rebuilding within a unique decision-making framework to improve structures in the PDB are presented. PDB_REDO uses a variety of existing and custom-built software modules to choose an optimal refinement protocol (e.g. anisotropic, isotropic or overall B-factor refinement, TLS model) and to optimize the geometry versus data-refinement weights. Next, it proceeds to rebuild side chains and peptide planes before a final optimization round. PDB_REDO works fully automatically without the need for intervention by a crystallographic expert. The pipeline was tested on 12 000 PDB entries and the great majority of the test cases improved both in terms of crystallographic criteria such as R(free) and in terms of widely accepted geometric validation criteria. It is concluded that PDB_REDO is useful to update the otherwise `static' structures in the PDB to modern crystallographic standards. The publically available PDB_REDO database provides better model statistics and contributes to better refinement and validation targets.

PDB_REDO: constructive validation, more than just looking for errors

PubMed Central

Joosten, Robbie P.; Joosten, Krista; Murshudov, Garib N.; Perrakis, Anastassis

2012-01-01

Developments of the PDB_REDO procedure that combine re-refinement and rebuilding within a unique decision-making framework to improve structures in the PDB are presented. PDB_REDO uses a variety of existing and custom-built software modules to choose an optimal refinement protocol (e.g. anisotropic, isotropic or overall B-factor refinement, TLS model) and to optimize the geometry versus data-refinement weights. Next, it proceeds to rebuild side chains and peptide planes before a final optimization round. PDB_REDO works fully automatically without the need for intervention by a crystallographic expert. The pipeline was tested on 12 000 PDB entries and the great majority of the test cases improved both in terms of crystallographic criteria such as R free and in terms of widely accepted geometric validation criteria. It is concluded that PDB_REDO is useful to update the otherwise ‘static’ structures in the PDB to modern crystallographic standards. The publically available PDB_REDO database provides better model statistics and contributes to better refinement and validation targets. PMID:22505269

Knowledge-based versus experimentally acquired distance and angle constraints for NMR structure refinement.

PubMed

Cui, Feng; Jernigan, Robert; Wu, Zhijun

2008-04-01

Nuclear Overhauser effects (NOE) distance constraints and torsion angle constraints are major conformational constraints for nuclear magnetic resonance (NMR) structure refinement. In particular, the number of NOE constraints has been considered as an important determinant for the quality of NMR structures. Of course, the availability of torsion angle constraints is also critical for the formation of correct local conformations. In our recent work, we have shown how a set of knowledge-based short-range distance constraints can also be utilized for NMR structure refinement, as a complementary set of conformational constraints to the NOE and torsion angle constraints. In this paper, we show the results from a series of structure refinement experiments by using different types of conformational constraints--NOE, torsion angle, or knowledge-based constraints--or their combinations, and make a quantitative assessment on how the experimentally acquired constraints contribute to the quality of structural models and whether or not they can be combined with or substituted by the knowledge-based constraints. We have carried out the experiments on a small set of NMR structures. Our preliminary calculations have revealed that the torsion angle constraints contribute substantially to the quality of the structures, but require to be combined with the NOE constraints to be fully effective. The knowledge-based constraints can be functionally as crucial as the torsion angle constraints, although they are statistical constraints after all and are not meant to be able to replace the latter.

Monitoring the refinement of crystal structures with {sup 15}N solid-state NMR shift tensor data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalakewich, Keyton; Eloranta, Harriet; Harper, James K.

The {sup 15}N chemical shift tensor is shown to be extremely sensitive to lattice structure and a powerful metric for monitoring density functional theory refinements of crystal structures. These refinements include lattice effects and are applied here to five crystal structures. All structures improve based on a better agreement between experimental and calculated {sup 15}N tensors, with an average improvement of 47.0 ppm. Structural improvement is further indicated by a decrease in forces on the atoms by 2–3 orders of magnitude and a greater similarity in atom positions to neutron diffraction structures. These refinements change bond lengths by more thanmore » the diffraction errors including adjustments to X–Y and X–H bonds (X, Y = C, N, and O) of 0.028 ± 0.002 Å and 0.144 ± 0.036 Å, respectively. The acquisition of {sup 15}N tensors at natural abundance is challenging and this limitation is overcome by improved {sup 1}H decoupling in the FIREMAT method. This decoupling dramatically narrows linewidths, improves signal-to-noise by up to 317%, and significantly improves the accuracy of measured tensors. A total of 39 tensors are measured with shifts distributed over a range of more than 400 ppm. Overall, experimental {sup 15}N tensors are at least 5 times more sensitive to crystal structure than {sup 13}C tensors due to nitrogen’s greater polarizability and larger range of chemical shifts.« less

Real-space refinement in PHENIX for cryo-EM and crystallography

DOE PAGES

Afonine, Pavel V.; Poon, Billy K.; Read, Randy J.; ...

2018-06-01

This work describes the implementation of real-space refinement in the phenix.real_space_refine program from the PHENIX suite. The use of a simplified refinement target function enables very fast calculation, which in turn makes it possible to identify optimal data-restraint weights as part of routine refinements with little runtime cost. Refinement of atomic models against low-resolution data benefits from the inclusion of as much additional information as is available. In addition to standard restraints on covalent geometry, phenix.real_space_refine makes use of extra information such as secondary-structure and rotamer-specific restraints, as well as restraints or constraints on internal molecular symmetry. The re-refinement ofmore » 385 cryo-EM-derived models available in the Protein Data Bank at resolutions of 6 Å or better shows significant improvement of the models and of the fit of these models to the target maps.« less

Real-space refinement in PHENIX for cryo-EM and crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Afonine, Pavel V.; Poon, Billy K.; Read, Randy J.

This work describes the implementation of real-space refinement in the phenix.real_space_refine program from the PHENIX suite. The use of a simplified refinement target function enables very fast calculation, which in turn makes it possible to identify optimal data-restraint weights as part of routine refinements with little runtime cost. Refinement of atomic models against low-resolution data benefits from the inclusion of as much additional information as is available. In addition to standard restraints on covalent geometry, phenix.real_space_refine makes use of extra information such as secondary-structure and rotamer-specific restraints, as well as restraints or constraints on internal molecular symmetry. The re-refinement ofmore » 385 cryo-EM-derived models available in the Protein Data Bank at resolutions of 6 Å or better shows significant improvement of the models and of the fit of these models to the target maps.« less

Peptide crystal simulations reveal hidden dynamics

PubMed Central

Janowski, Pawel A.; Cerutti, David S.; Holton, James; Case, David A.

2013-01-01

Molecular dynamics simulations of biomolecular crystals at atomic resolution have the potential to recover information on dynamics and heterogeneity hidden in the X-ray diffraction data. We present here 9.6 microseconds of dynamics in a small helical peptide crystal with 36 independent copies of the unit cell. The average simulation structure agrees with experiment to within 0.28 Å backbone and 0.42 Å all-atom rmsd; a model refined against the average simulation density agrees with the experimental structure to within 0.20 Å backbone and 0.33 Å all-atom rmsd. The R-factor between the experimental structure factors and those derived from this unrestrained simulation is 23% to 1.0 Å resolution. The B-factors for most heavy atoms agree well with experiment (Pearson correlation of 0.90), but B-factors obtained by refinement against the average simulation density underestimate the coordinate fluctuations in the underlying simulation where the simulation samples alternate conformations. A dynamic flow of water molecules through channels within the crystal lattice is observed, yet the average water density is in remarkable agreement with experiment. A minor population of unit cells is characterized by reduced water content, 310 helical propensity and a gauche(−) side-chain rotamer for one of the valine residues. Careful examination of the experimental data suggests that transitions of the helices are a simulation artifact, although there is indeed evidence for alternate valine conformers and variable water content. This study highlights the potential for crystal simulations to detect dynamics and heterogeneity in experimental diffraction data, as well as to validate computational chemistry methods. PMID:23631449

Improving consensus structure by eliminating averaging artifacts

PubMed Central

KC, Dukka B

2009-01-01

Background Common structural biology methods (i.e., NMR and molecular dynamics) often produce ensembles of molecular structures. Consequently, averaging of 3D coordinates of molecular structures (proteins and RNA) is a frequent approach to obtain a consensus structure that is representative of the ensemble. However, when the structures are averaged, artifacts can result in unrealistic local geometries, including unphysical bond lengths and angles. Results Herein, we describe a method to derive representative structures while limiting the number of artifacts. Our approach is based on a Monte Carlo simulation technique that drives a starting structure (an extended or a 'close-by' structure) towards the 'averaged structure' using a harmonic pseudo energy function. To assess the performance of the algorithm, we applied our approach to Cα models of 1364 proteins generated by the TASSER structure prediction algorithm. The average RMSD of the refined model from the native structure for the set becomes worse by a mere 0.08 Å compared to the average RMSD of the averaged structures from the native structure (3.28 Å for refined structures and 3.36 A for the averaged structures). However, the percentage of atoms involved in clashes is greatly reduced (from 63% to 1%); in fact, the majority of the refined proteins had zero clashes. Moreover, a small number (38) of refined structures resulted in lower RMSD to the native protein versus the averaged structure. Finally, compared to PULCHRA [1], our approach produces representative structure of similar RMSD quality, but with much fewer clashes. Conclusion The benchmarking results demonstrate that our approach for removing averaging artifacts can be very beneficial for the structural biology community. Furthermore, the same approach can be applied to almost any problem where averaging of 3D coordinates is performed. Namely, structure averaging is also commonly performed in RNA secondary prediction [2], which could also benefit from our approach. PMID:19267905

High-resolution Measurement of Contact Ion-pair Structures in Aqueous RbCl Solutions from the Simultaneous Corefinement of their Rb and Cl K-edge XAFS and XRD Spectra

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pham, Van-Thai; Fulton, John L.

2016-06-21

In concentrated solutions of aqueous RbCl, all of the Rb+ and Cl- ions exist as contact ion pairs. This full structural assessment is derived from the refinement of three independent experimental measurements: the Rb and Cl K-edge x-ray absorption fine structure (XAFS) and the x-ray diffraction spectra (XRD). This simultaneous refinement of the XAFS and XRD data provides high accuracy since each method probes the structure of different local regions about the ions with high sensitivity. At high RbCl concentration (6 m (mol/kg )) the solution is dominated by Rb+ - Cl- contact ion pairs yielding an average of 1.5more » pairs at an Rb-Cl distance of 3.24 Å. Upon formation of these ion pairs, approximately 1.1 waters molecules are displaced from the Rb+ and 1.4 water molecules from Cl-. The hydration shells about both the cation and anion are also determined. These results greatly improve the understanding of monovalent ions and provide a basis for testing the Rb+-Cl- interaction potentials used in molecular dynamics (MD) simulation. This research was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences.« less

Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment.

PubMed Central

McKim, J M; Bradbury, S P; Niemi, G J

1987-01-01

Implementation of the Toxic Substances Control Act of 1977 creates the need to reliably establish testing priorities because laboratory resources are limited and the number of industrial chemicals requiring evaluation is overwhelming. The use of quantitative structure activity relationship (QSAR) models as rapid and predictive screening tools to select more potentially hazardous chemicals for in-depth laboratory evaluation has been proposed. Further implementation and refinement of quantitative structure-toxicity relationships in aquatic toxicology and hazard assessment requires the development of a "mode-of-action" database. With such a database, a qualitative structure-activity relationship can be formulated to assign the proper mode of action, and respective QSAR, to a given chemical structure. In this review, the development of fish acute toxicity syndromes (FATS), which are toxic-response sets based on various behavioral and physiological-biochemical measurements, and their projected use in the mode-of-action database are outlined. Using behavioral parameters monitored in the fathead minnow during acute toxicity testing, FATS associated with acetylcholinesterase (AChE) inhibitors and narcotics could be reliably predicted. However, compounds classified as oxidative phosphorylation uncouplers or stimulants could not be resolved. Refinement of this approach by using respiratory-cardiovascular responses in the rainbow trout, enabled FATS associated with AChE inhibitors, convulsants, narcotics, respiratory blockers, respiratory membrane irritants, and uncouplers to be correctly predicted. PMID:3297660

Accelerating Convolutional Sparse Coding for Curvilinear Structures Segmentation by Refining SCIRD-TS Filter Banks.

PubMed

Annunziata, Roberto; Trucco, Emanuele

2016-11-01

Deep learning has shown great potential for curvilinear structure (e.g., retinal blood vessels and neurites) segmentation as demonstrated by a recent auto-context regression architecture based on filter banks learned by convolutional sparse coding. However, learning such filter banks is very time-consuming, thus limiting the amount of filters employed and the adaptation to other data sets (i.e., slow re-training). We address this limitation by proposing a novel acceleration strategy to speed-up convolutional sparse coding filter learning for curvilinear structure segmentation. Our approach is based on a novel initialisation strategy (warm start), and therefore it is different from recent methods improving the optimisation itself. Our warm-start strategy is based on carefully designed hand-crafted filters (SCIRD-TS), modelling appearance properties of curvilinear structures which are then refined by convolutional sparse coding. Experiments on four diverse data sets, including retinal blood vessels and neurites, suggest that the proposed method reduces significantly the time taken to learn convolutional filter banks (i.e., up to -82%) compared to conventional initialisation strategies. Remarkably, this speed-up does not worsen performance; in fact, filters learned with the proposed strategy often achieve a much lower reconstruction error and match or exceed the segmentation performance of random and DCT-based initialisation, when used as input to a random forest classifier.

Glycidyl fatty acid esters in refined edible oils: A review on formation, occurrence, analysis, and elimination methods

USDA-ARS?s Scientific Manuscript database

Glycidyl fatty acid esters (GEs), one of the main contaminants in processed oil, are mainly formed during the deodorization step in the oil refining process of edible oils and therefore occur in almost all refined edible oils. GEs are potential carcinogens, due to the fact that they hydrolyze into t...

Crystal Structure of Cocosin, A Potential Food Allergen from Coconut (Cocos nucifera).

PubMed

Jin, Tengchuan; Wang, Cheng; Zhang, Caiying; Wang, Yang; Chen, Yu-Wei; Guo, Feng; Howard, Andrew; Cao, Min-Jie; Fu, Tong-Jen; McHugh, Tara H; Zhang, Yuzhu

2017-08-30

Coconut (Cocos nucifera) is an important palm tree. Coconut fruit is widely consumed. The most abundant storage protein in coconut fruit is cocosin (a likely food allergen), which belongs to the 11S globulin family. Cocosin was crystallized near a century ago, but its structure remains unknown. By optimizing crystallization conditions and cryoprotectant solutions, we were able to obtain cocosin crystals that diffracted to 1.85 Å. The cocosin gene was cloned from genomic DNA isolated from dry coconut tissue. The protein sequence deduced from the predicted cocosin coding sequence was used to guide model building and structure refinement. The structure of cocosin was determined for the first time, and it revealed a typical 11S globulin feature of a double layer doughnut-shaped hexamer.

Effect of Solutes on Grain Refinement of As-Cast Fe-4Si Alloy

NASA Astrophysics Data System (ADS)

Li, Ming; Li, Jian-Min; Zheng, Qing; Wang, Geoff; Zhang, Ming-Xing

2018-06-01

Grain size is one of the key microstructural factors that control the mechanical properties of steels. The present work aims to extend the theories of grain refinement which were established for cast light alloys to steel systems. Using a designed Fe-4 wt pct Si alloy (all-ferrite structure during whole solidification process), the solute effect on grain refinement/grain coarsening in ferritic systems was comprehensively investigated. Experimental results showed that boron (B), which is associated with the highest Q value (growth restriction factor) in ferrite, significantly refined the as-cast structure of the Fe-4 wt pct Si alloy. Cu and Mo with low Q values had no effect on grain refinement. However, although Y and Zr have relatively high Q values, addition of these two solutes led to grain coarsening in the Fe-4Si alloy. Understanding the results in regards to the growth restriction factor and the driving force for the solidification led to the conclusion that in addition to the grain growth restriction effect, the changes of thermodynamic driving force for solidification due to the solute addition also played a key role in grain refinement in ferritic alloys.

Effect of Solutes on Grain Refinement of As-Cast Fe-4Si Alloy

NASA Astrophysics Data System (ADS)

Li, Ming; Li, Jian-Min; Zheng, Qing; Wang, Geoff; Zhang, Ming-Xing

2018-03-01

Grain size is one of the key microstructural factors that control the mechanical properties of steels. The present work aims to extend the theories of grain refinement which were established for cast light alloys to steel systems. Using a designed Fe-4 wt pct Si alloy (all-ferrite structure during whole solidification process), the solute effect on grain refinement/grain coarsening in ferritic systems was comprehensively investigated. Experimental results showed that boron (B), which is associated with the highest Q value (growth restriction factor) in ferrite, significantly refined the as-cast structure of the Fe-4 wt pct Si alloy. Cu and Mo with low Q values had no effect on grain refinement. However, although Y and Zr have relatively high Q values, addition of these two solutes led to grain coarsening in the Fe-4Si alloy. Understanding the results in regards to the growth restriction factor and the driving force for the solidification led to the conclusion that in addition to the grain growth restriction effect, the changes of thermodynamic driving force for solidification due to the solute addition also played a key role in grain refinement in ferritic alloys.

Structural Refinement of Membrane Proteins by Restrained Molecular Dynamics and Solvent Accessibility Data

PubMed Central

Sompornpisut, Pornthep; Roux, Benoît; Perozo, Eduardo

2008-01-01

We present an approach for incorporating solvent accessibility data from electron paramagnetic resonance experiments in the structural refinement of membrane proteins through restrained molecular dynamics simulations. The restraints have been parameterized from oxygen (ΠO2) and nickel-ethylenediaminediacetic acid (ΠNiEdda) collision frequencies, as indicators of lipid or aqueous exposed spin-label sites. These are enforced through interactions between a pseudoatom representation of the covalently attached Nitroxide spin-label and virtual “solvent” particles corresponding to O2 and NiEdda in the surrounding environment. Interactions were computed using an empirical potential function, where the parameters have been optimized to account for the different accessibilities of the spin-label pseudoatoms to the surrounding environment. This approach, “pseudoatom-driven solvent accessibility refinement”, was validated by refolding distorted conformations of the Streptomyces lividans potassium channel (KcsA), corresponding to a range of 2–30 Å root mean-square deviations away from the native structure. Molecular dynamics simulations based on up to 58 electron paramagnetic resonance restraints derived from spin-label mutants were able to converge toward the native structure within 1–3 Å root mean-square deviations with minimal computational cost. The use of energy-based ranking and structure similarity clustering as selection criteria helped in the convergence and identification of correctly folded structures from a large number of simulations. This approach can be applied to a variety of integral membrane protein systems, regardless of oligomeric state, and should be particularly useful in calculating conformational changes from a known reference crystal structure. PMID:18676641

Structure resolution by electron diffraction tomography of the complex layered iron-rich Fe-2234-type Sr{sub 5}Fe{sub 6}O{sub 15.4}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lepoittevin, Christophe, E-mail: christophe.lepoittevin@neel.cnrs.fr

2016-10-15

The crystal structure of the strontium ferrite Sr{sub 5}Fe{sub 6}O{sub 15.4}, was solved by direct methods on electron diffraction tomography data acquired on a transmission electron microscope. The refined cell parameters are a=27.4047(3) Å, b=5.48590(7) Å and c=42.7442(4) Å in Fm2m symmetry. Its structure is built up from the intergrowth sequence between a quadruple perovskite-type layer with a complex rock-salt (RS)-type block. In the latter iron atoms are found in two different environments : tetragonal pyramid and tetrahedron. The structural model was refined by Rietveld method based on the powder X-ray diffraction pattern. - Highlights: • Complex structure of Sr{submore » 5}Fe{sub 6}O{sub 15.4} solved by electron diffraction tomography. • Observed Fourier maps allow determining missing oxygen atoms in the structure. • Structural model refined from powder X-ray diffraction data. • Intergrowth between quadruple perovskite layer with double rock-salt-type layer.« less

Computations of Unsteady Viscous Compressible Flows Using Adaptive Mesh Refinement in Curvilinear Body-fitted Grid Systems

NASA Technical Reports Server (NTRS)

Steinthorsson, E.; Modiano, David; Colella, Phillip

1994-01-01

A methodology for accurate and efficient simulation of unsteady, compressible flows is presented. The cornerstones of the methodology are a special discretization of the Navier-Stokes equations on structured body-fitted grid systems and an efficient solution-adaptive mesh refinement technique for structured grids. The discretization employs an explicit multidimensional upwind scheme for the inviscid fluxes and an implicit treatment of the viscous terms. The mesh refinement technique is based on the AMR algorithm of Berger and Colella. In this approach, cells on each level of refinement are organized into a small number of topologically rectangular blocks, each containing several thousand cells. The small number of blocks leads to small overhead in managing data, while their size and regular topology means that a high degree of optimization can be achieved on computers with vector processors.

Free kick instead of cross-validation in maximum-likelihood refinement of macromolecular crystal structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pražnikar, Jure; University of Primorska,; Turk, Dušan, E-mail: dusan.turk@ijs.si

2014-12-01

The maximum-likelihood free-kick target, which calculates model error estimates from the work set and a randomly displaced model, proved superior in the accuracy and consistency of refinement of crystal structures compared with the maximum-likelihood cross-validation target, which calculates error estimates from the test set and the unperturbed model. The refinement of a molecular model is a computational procedure by which the atomic model is fitted to the diffraction data. The commonly used target in the refinement of macromolecular structures is the maximum-likelihood (ML) function, which relies on the assessment of model errors. The current ML functions rely on cross-validation. Theymore » utilize phase-error estimates that are calculated from a small fraction of diffraction data, called the test set, that are not used to fit the model. An approach has been developed that uses the work set to calculate the phase-error estimates in the ML refinement from simulating the model errors via the random displacement of atomic coordinates. It is called ML free-kick refinement as it uses the ML formulation of the target function and is based on the idea of freeing the model from the model bias imposed by the chemical energy restraints used in refinement. This approach for the calculation of error estimates is superior to the cross-validation approach: it reduces the phase error and increases the accuracy of molecular models, is more robust, provides clearer maps and may use a smaller portion of data for the test set for the calculation of R{sub free} or may leave it out completely.« less

Grain Refinement Efficiency in Commercial-Purity Aluminum Influenced by the Addition of Al-4Ti Master Alloys with Varying TiAl3 Particles

PubMed Central

Zhao, Jianhua; He, Jiansheng; Tang, Qi; Wang, Tao; Chen, Jing

2016-01-01

A series of Al-4Ti master alloys with various TiAl3 particles were prepared via pouring the pure aluminum added with K2TiF6 or sponge titanium into three different molds made of graphite, copper, and sand. The microstructure and morphology of TiAl3 particles were characterized and analyzed by scanning electron microscope (SEM) with energy dispersive spectroscopy (EDS). The microstructure of TiAl3 particles in Al-4Ti master alloys and their grain refinement efficiency in commercial-purity aluminum were investigated in this study. Results show that there were three different morphologies of TiAl3 particles in Al-4Ti master alloys: petal-like structures, blocky structures, and flaky structures. The Al-4Ti master alloy with blocky TiAl3 particles had better and more stable grain refinement efficiency than the master alloys with petal-like and flaky TiAl3 particles. The average grain size of the refined commercial-purity aluminum always hereditarily followed the size of the original TiAl3 particles. In addition, the grain refinement efficiency of Al-4Ti master alloys with the same morphology, size, and distribution of TiAl3 particles prepared through different processes was almost identical. PMID:28773987

Grain Refinement Efficiency in Commercial-Purity Aluminum Influenced by the Addition of Al-4Ti Master Alloys with Varying TiAl₃ Particles.

PubMed

Zhao, Jianhua; He, Jiansheng; Tang, Qi; Wang, Tao; Chen, Jing

2016-10-26

A series of Al-4Ti master alloys with various TiAl₃ particles were prepared via pouring the pure aluminum added with K₂TiF₆ or sponge titanium into three different molds made of graphite, copper, and sand. The microstructure and morphology of TiAl₃ particles were characterized and analyzed by scanning electron microscope (SEM) with energy dispersive spectroscopy (EDS). The microstructure of TiAl₃ particles in Al-4Ti master alloys and their grain refinement efficiency in commercial-purity aluminum were investigated in this study. Results show that there were three different morphologies of TiAl₃ particles in Al-4Ti master alloys: petal-like structures, blocky structures, and flaky structures. The Al-4Ti master alloy with blocky TiAl₃ particles had better and more stable grain refinement efficiency than the master alloys with petal-like and flaky TiAl₃ particles. The average grain size of the refined commercial-purity aluminum always hereditarily followed the size of the original TiAl₃ particles. In addition, the grain refinement efficiency of Al-4Ti master alloys with the same morphology, size, and distribution of TiAl₃ particles prepared through different processes was almost identical.

Synthesis and crystal structure determination of yttrium ultraphosphate YP 5O 14

NASA Astrophysics Data System (ADS)

Mbarek, A.; Graia, M.; Chadeyron, G.; Zambon, D.; Bouaziz, J.; Fourati, M.

2009-03-01

The crystal structure of monoclinic YP 5O 14 (space group C2/ c, a=12.919(2) Å, b=12.796(4) Å, c=12.457(2) Å, β=91.30(1)°, Z=8) has been refined from single-crystal X-ray diffraction data. Full-matrix least-squares refinement on F2 using 2249 independent reflections for 183 refinable parameters results in a final R value of 0.027 ( ωR=0.069). The structure is isotypic with HoP 5O 14. This structure is built up from infinite layers of PO 4 tetrahedra linked through isolated YO 8 polyhedra. The three-dimensional cohesion of the framework results from Y-O-P bridges. This crystal structure refinement leads to the calculated X-ray diffraction powder pattern of this monoclinic polymorph, which has been the starting point of a thorough study of the solid-state synthesis of this ultraphosphate. This investigation further leads to a better outstanding of features observed during the synthesis of powdered samples. The thermal behavior of this ultraphosphate has been studied by DTA and TGA analyses. The infrared and Raman spectroscopic characterizations have been carried out on polycrystalline samples. The luminescence properties of the Eu 3+ ion incorporated in the monoclinic C2/ c polymorph of YP 5O 14 as local structural probe show that in YP 5O 14: 5% Eu 3+ sample, the Eu 3+ ions are distributed over the two Y 3+ crystallographic sites of C 2 symmetry of this structure.

Ion-pairing in aqueous CaCl 2 and RbBr solutions. Simultaneous structural refinement of XAFS and XRD data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pham, Thai V.; Fulton, John L.

2013-01-22

We present a new methodology involving the simultaneous refinement of both x-ray absorption and x-ray diffraction spectra (X-ray Absorption/Diffraction Structural Refinement,XADSR), to study hydration and ion pair structure of CaCl 2 and RbBr salts in concentrated aqueous solutions. The XADSR analysis includes the XAFS spectra analysis of both the cation and anion as a probe of their short-range structure with an XRD spectral analysis as a probe of the global structural. Together they deliver a comprehensive picture of the cation and anion hydration, the contact ion pair (CIP) structure and the solvent-separated ion pair (SSIP) structure. XADSR analysis of 6.0more » m aqueous CaCl 2 reveals that there are an insignificant number of Ca 2+-Cl- CIP’s, but there are approximately 3.4 SSIP’s separated by about 4.99 Å. In contrast XADSR analysis of aqueous RbBr yields about 0.7 pair CIP at a bond length 3.51 Å. The present work demonstrates a new approach for a direct co-refinement of XRD and XAFS spectra in a simple and reliable fashion, opening new opportunities for analysis in various disordered and crystalline systems. This work was supported by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. Pacific Northwest National Laboratory (PNNL) is operated for the U.S. Department of Energy by Battelle.« less

Active-learning strategies in computer-assisted drug discovery.

PubMed

Reker, Daniel; Schneider, Gisbert

2015-04-01

High-throughput compound screening is time and resource consuming, and considerable effort is invested into screening compound libraries, profiling, and selecting the most promising candidates for further testing. Active-learning methods assist the selection process by focusing on areas of chemical space that have the greatest chance of success while considering structural novelty. The core feature of these algorithms is their ability to adapt the structure-activity landscapes through feedback. Instead of full-deck screening, only focused subsets of compounds are tested, and the experimental readout is used to refine molecule selection for subsequent screening cycles. Once implemented, these techniques have the potential to reduce costs and save precious materials. Here, we provide a comprehensive overview of the various computational active-learning approaches and outline their potential for drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Crosslinking Constraints and Computational Models as Complementary Tools in Modeling the Extracellular Domain of the Glycine Receptor

PubMed Central

Liu, Zhenyu; Szarecka, Agnieszka; Yonkunas, Michael; Speranskiy, Kirill; Kurnikova, Maria; Cascio, Michael

2014-01-01

The glycine receptor (GlyR), a member of the pentameric ligand-gated ion channel superfamily, is the major inhibitory neurotransmitter-gated receptor in the spinal cord and brainstem. In these receptors, the extracellular domain binds agonists, antagonists and various other modulatory ligands that act allosterically to modulate receptor function. The structures of homologous receptors and binding proteins provide templates for modeling of the ligand-binding domain of GlyR, but limitations in sequence homology and structure resolution impact on modeling studies. The determination of distance constraints via chemical crosslinking studies coupled with mass spectrometry can provide additional structural information to aid in model refinement, however it is critical to be able to distinguish between intra- and inter-subunit constraints. In this report we model the structure of GlyBP, a structural and functional homolog of the extracellular domain of human homomeric α1 GlyR. We then show that intra- and intersubunit Lys-Lys crosslinks in trypsinized samples of purified monomeric and oligomeric protein bands from SDS-polyacrylamide gels may be identified and differentiated by MALDI-TOF MS studies of limited resolution. Thus, broadly available MS platforms are capable of providing distance constraints that may be utilized in characterizing large complexes that may be less amenable to NMR and crystallographic studies. Systematic studies of state-dependent chemical crosslinking and mass spectrometric identification of crosslinked sites has the potential to complement computational modeling efforts by providing constraints that can validate and refine allosteric models. PMID:25025226

Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta.

PubMed

Wang, Ray Yu-Ruei; Song, Yifan; Barad, Benjamin A; Cheng, Yifan; Fraser, James S; DiMaio, Frank

2016-09-26

Cryo-EM has revealed the structures of many challenging yet exciting macromolecular assemblies at near-atomic resolution (3-4.5Å), providing biological phenomena with molecular descriptions. However, at these resolutions, accurately positioning individual atoms remains challenging and error-prone. Manually refining thousands of amino acids - typical in a macromolecular assembly - is tedious and time-consuming. We present an automated method that can improve the atomic details in models that are manually built in near-atomic-resolution cryo-EM maps. Applying the method to three systems recently solved by cryo-EM, we are able to improve model geometry while maintaining the fit-to-density. Backbone placement errors are automatically detected and corrected, and the refinement shows a large radius of convergence. The results demonstrate that the method is amenable to structures with symmetry, of very large size, and containing RNA as well as covalently bound ligands. The method should streamline the cryo-EM structure determination process, providing accurate and unbiased atomic structure interpretation of such maps.

Structure-activity relationships for skin sensitization: recent improvements to Derek for Windows.

PubMed

Langton, Kate; Patlewicz, Grace Y; Long, Anthony; Marchant, Carol A; Basketter, David A

2006-12-01

Derek for Windows (DfW) is a knowledge-based expert system that predicts the toxicity of a chemical from its structure. Its predictions are based in part on alerts that describe structural features or toxicophores associated with toxicity. Recently, improvements have been made to skin sensitization alerts within the DfW knowledge base in collaboration with Unilever. These include modifications to the alerts describing the skin sensitization potential of aldehydes, 1,2-diketones, and isothiazolinones and consist of enhancements to the toxicophore definition, the mechanistic classification, and the extent of supporting evidence provided. The outcomes from this collaboration demonstrate the importance of updating and refining computer models for the prediction of skin sensitization as new information from experimental and theoretical studies becomes available.

Immunopharmacology of lipid A mimetics.

PubMed

Bowen, William S; Gandhapudi, Siva K; Kolb, Joseph P; Mitchell, Thomas C

2013-01-01

The structural core of bacterial lipopolysaccharide, lipid A, has played a role in medicine since the 1890s when William Coley sought to harness its immunostimulatory properties in the form of a crude bacterial extract. Recent decades have brought remarkable clarity to the structure of lipid A and the multicomponent endotoxin receptor system that evolved to detect it. A range of therapeutically useful versions of lipid A now exists, including preparations of detoxified lipid A, synthetic copies of naturally occurring biological intermediates such as lipid IVa, and synthetic mimetics. These agents are finding use as vaccine adjuvants, antagonists and immunostimulants whose structural features have been refined to potentiate efficacy while decreasing the risk of inflammatory side effects. Copyright © 2013 Elsevier Inc. All rights reserved.

Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms

PubMed Central

2015-01-01

JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile. PMID:26288683

Yoga Therapy: Building a Holding Environment for Somatic and Psyche Change.

PubMed

McClure, Bud

2015-01-01

Drawing on ideas from D.W. Winnicott and the work of Quaker theologian Parker Palmer, this article discusses the concept of a holding environment, its refined understanding in the literature over the years, and how it can be optimally used in yoga therapy. The evidence shows that effectively establishing a holding environment can facilitate both somatic and deep structural change in a client, facilitating healing from primal wounding as well as the potential reconnection to the true self.

Assessment of Detection and Refinement Strategies for de novo Protein Structures using Force Field and Statistical Potentials

DTIC Science & Technology

2007-01-01

energy landscape of real proteins . As such, real proteins may have a subtle free energy gradient toward the native that requires long folding times...some leaning, however slight, toward the lowest free - energy basin .9 One caveat in the connection between the scoring funnel and the folding funnel is... protein sets. The average DFIRE-AA scores from each cluster were ranked, and the lowest- energy conformers from each of the top 16 clusters

Comparison Between Self-Guided Langevin Dynamics and Molecular Dynamics Simulations for Structure Refinement of Protein Loop Conformations

DTIC Science & Technology

2011-01-01

SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT Same as Report (SAR) 18 . NUMBER OF PAGES 9 19a. NAME OF RESPONSIBLE PERSON a. REPORT...unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39- 18 sampling is based on...atom distance-scaled ideal-gas reference state (DFIRE-AA) statistical potential func- tion.[ 18 ] The third approach is the Rosetta all-atom energy func

Obtaining valid geologic models from 3-D resistivity inversion of magnetotelluric data at Pahute Mesa, Nevada

USGS Publications Warehouse

Rodriguez, Brian D.; Sweetkind, Donald S.

2015-01-01

The 3-D inversion was generally able to reproduce the gross resistivity structure of the “known” model, but the simulated conductive volcanic composite unit horizons were often too shallow when compared to the “known” model. Additionally, the chosen computation parameters such as station spacing appear to have resulted in computational artifacts that are difficult to interpret but could potentially be removed with further refinements of the 3-D resistivity inversion modeling technique.

Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

PubMed

Dalbey, Walden E; McKee, Richard H; Goyak, Katy Olsavsky; Biles, Robert W; Murray, Jay; White, Russell

2014-01-01

Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

NASA's Advanced Exploration Systems Mars Transit Habitat Refinement Point of Departure Design

NASA Technical Reports Server (NTRS)

Simon, Matthew; Latorella, Kara; Martin, John; Cerro, Jeff; Lepsch, Roger; Jefferies, Sharon; Goodliff, Kandyce; McCleskey, Carey; Smitherman, David; Stromgren, Chel

2017-01-01

This paper describes the recently developed point of departure design for a long duration, reusable Mars Transit Habitat, which was established during a 2016 NASA habitat design refinement activity supporting the definition of NASA's Evolvable Mars Campaign. As part of its development of sustainable human Mars mission concepts achievable in the 2030s, the Evolvable Mars Campaign has identified desired durations and mass/dimensional limits for long duration Mars habitat designs to enable the currently assumed solar electric and chemical transportation architectures. The Advanced Exploration Systems Mars Transit Habitat Refinement Activity brought together habitat subsystem design expertise from across NASA to develop an increased fidelity, consensus design for a transit habitat within these constraints. The resulting design and data (including a mass equipment list) contained in this paper are intended to help teams across the agency and potential commercial, academic, or international partners understand: 1) the current architecture/habitat guidelines and assumptions, 2) performance targets of such a habitat (particularly in mass, volume, and power), 3) the driving technology/capability developments and architectural solutions which are necessary for achieving these targets, and 4) mass reduction opportunities and research/design needs to inform the development of future research and proposals. Data presented includes: an overview of the habitat refinement activity including motivation and process when informative; full documentation of the baseline design guidelines and assumptions; detailed mass and volume breakdowns; a moderately detailed concept of operations; a preliminary interior layout design with rationale; a list of the required capabilities necessary to enable the desired mass; and identification of any worthwhile trades/analyses which could inform future habitat design efforts. As a whole, the data in the paper show that a transit habitat meeting the 43 metric tons launch mass/trans-Mars injection burn limits specified by the Evolvable Mars Campaign is achievable near the desired timeframe with moderate strategic investments including maintainable life support systems, repurposable structures and packaging, and lightweight exercise modalities. It also identifies operational and technological options to reduce this mass to less than 41 metric tons including staging of launch structure/packaging and alternate structural materials.

Rietveld Refinement on X-Ray Diffraction Patterns of Bioapatite in Human Fetal Bones

PubMed Central

Meneghini, Carlo; Dalconi, Maria Chiara; Nuzzo, Stefania; Mobilio, Settimio; Wenk, Rudy H.

2003-01-01

Bioapatite, the main constituent of mineralized tissue in mammalian bones, is a calcium-phosphate-based mineral that is similar in structure and composition to hydroxyapatite. In this work, the crystallographic structure of bioapatite in human fetuses was investigated by synchrotron radiation x-ray diffraction (XRD) and microdiffraction (μ-XRD) techniques. Rietveld refinement analyses of XRD and μ-XRD data allow for quantitative probing of the structural modifications of bioapatite as functions of the mineralization process and gestational age. PMID:12609904

Probing the structure of Leishmania major DHFR TS and structure based virtual screening of peptide library for the identification of anti-leishmanial leads.

PubMed

Rajasekaran, Rajalakshmi; Chen, Yi-Ping Phoebe

2012-09-01

Leishmaniasis, a multi-faceted ethereal disease is considered to be one of the World's major communicable diseases that demands exhaustive research and control measures. The substantial data on these protozoan parasites has not been utilized completely to develop potential therapeutic strategies against Leishmaniasis. Dihydrofolate reductase thymidylate synthase (DHFR-TS) plays a major role in the infective state of the parasite and hence the DHFR-TS based drugs remains of much interest to researchers working on Leishmaniasis. Although, crystal structures of DHFR-TS from different species including Plasmodium falciparum and Trypanosoma cruzi are available, the experimentally determined structure of the Leishmania major DHFR-TS has not yet been reported in the Protein Data Bank. A high quality three dimensional structure of L.major DHFR-TS has been modeled through the homology modeling approach. Carefully refined and the energy minimized structure of the modeled protein was validated using a number of structure validation programs to confirm its structure quality. The modeled protein structure was used in the process of structure based virtual screening to figure out a potential lead structure against DHFR TS. The lead molecule identified has a binding affinity of 0.51 nM and clearly follows drug like properties.

Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps

PubMed Central

Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan; Stone, John E; Zhao, Jianhua; Schulten, Klaus

2016-01-01

Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a radius of convergence of ~25 Å demonstrated with the accurate modeling of β-galactosidase and TRPV1 proteins at 3.2 Å and 3.4 Å resolution, respectively. The MDFF refinements uniquely offer map-model validation and B-factor determination criteria based on the inherent dynamics of the macromolecules studied, captured by means of local root mean square fluctuations. The MDFF tools described are available to researchers through an easy-to-use and cost-effective cloud computing resource on Amazon Web Services. DOI: http://dx.doi.org/10.7554/eLife.16105.001 PMID:27383269

Exploiting distant homologues for phasing through the generation of compact fragments, local fold refinement and partial solution combination.

PubMed

Millán, Claudia; Sammito, Massimo Domenico; McCoy, Airlie J; Nascimento, Andrey F Ziem; Petrillo, Giovanna; Oeffner, Robert D; Domínguez-Gil, Teresa; Hermoso, Juan A; Read, Randy J; Usón, Isabel

2018-04-01

Macromolecular structures can be solved by molecular replacement provided that suitable search models are available. Models from distant homologues may deviate too much from the target structure to succeed, notwithstanding an overall similar fold or even their featuring areas of very close geometry. Successful methods to make the most of such templates usually rely on the degree of conservation to select and improve search models. ARCIMBOLDO_SHREDDER uses fragments derived from distant homologues in a brute-force approach driven by the experimental data, instead of by sequence similarity. The new algorithms implemented in ARCIMBOLDO_SHREDDER are described in detail, illustrating its characteristic aspects in the solution of new and test structures. In an advance from the previously published algorithm, which was based on omitting or extracting contiguous polypeptide spans, model generation now uses three-dimensional volumes respecting structural units. The optimal fragment size is estimated from the expected log-likelihood gain (LLG) values computed assuming that a substructure can be found with a level of accuracy near that required for successful extension of the structure, typically below 0.6 Å root-mean-square deviation (r.m.s.d.) from the target. Better sampling is attempted through model trimming or decomposition into rigid groups and optimization through Phaser's gyre refinement. Also, after model translation, packing filtering and refinement, models are either disassembled into predetermined rigid groups and refined (gimble refinement) or Phaser's LLG-guided pruning is used to trim the model of residues that are not contributing signal to the LLG at the target r.m.s.d. value. Phase combination among consistent partial solutions is performed in reciprocal space with ALIXE. Finally, density modification and main-chain autotracing in SHELXE serve to expand to the full structure and identify successful solutions. The performance on test data and the solution of new structures are described.

Modeling and simulation studies of human β3 adrenergic receptor and its interactions with agonists.

PubMed

Sahi, Shakti; Tewatia, Parul; Malik, Balwant K

2012-12-01

β3 adrenergic receptor (β3AR) is known to mediate various pharmacological and physiological effects such as thermogenesis in brown adipocytes, lipolysis in white adipocytes, glucose homeostasis and intestinal smooth muscle relaxation. Several efforts have been made in this field to understand their function and regulation in different human tissues and they have emerged as potential attractive targets in drug discovery for the treatment of diabetes, depression, obesity etc. Although the crystal structures of Bovine Rhodopsin and β2 adrenergic receptor have been resolved, to date there is no three dimensional structural information on β3AR. Our aim in this study was to model 3D structure of β3AR by various molecular modeling and simulation techniques. In this paper, we describe a refined predicted model of β3AR using different algorithms for structure prediction. The structural refinement and minimization of the generated 3D model of β3AR were done by Schrodinger suite 9.1. Docking studies of β3AR model with the known agonists enabled us to identify specific residues, viz, Asp 117, Ser 208, Ser 209, Ser 212, Arg 315, Asn 332, within the β3AR binding pocket, which might play an important role in ligand binding. Receptor ligand interaction studies clearly indicated that these five residues showed strong hydrogen bonding interactions with the ligands. The results have been correlated with the experimental data available. The predicted ligand binding interactions and the simulation studies validate the methods used to predict the 3D-structure.

Finite element mesh refinement criteria for stress analysis

NASA Technical Reports Server (NTRS)

Kittur, Madan G.; Huston, Ronald L.

1990-01-01

This paper discusses procedures for finite-element mesh selection and refinement. The objective is to improve accuracy. The procedures are based on (1) the minimization of the stiffness matrix race (optimizing node location); (2) the use of h-version refinement (rezoning, element size reduction, and increasing the number of elements); and (3) the use of p-version refinement (increasing the order of polynomial approximation of the elements). A step-by-step procedure of mesh selection, improvement, and refinement is presented. The criteria for 'goodness' of a mesh are based on strain energy, displacement, and stress values at selected critical points of a structure. An analysis of an aircraft lug problem is presented as an example.

The Quality and Validation of Structures from Structural Genomics

PubMed Central

Domagalski, Marcin J.; Zheng, Heping; Zimmerman, Matthew D.; Dauter, Zbigniew; Wlodawer, Alexander; Minor, Wladek

2014-01-01

Quality control of three-dimensional structures of macromolecules is a critical step to ensure the integrity of structural biology data, especially those produced by structural genomics centers. Whereas the Protein Data Bank (PDB) has proven to be a remarkable success overall, the inconsistent quality of structures reveals a lack of universal standards for structure/deposit validation. Here, we review the state-of-the-art methods used in macromolecular structure validation, focusing on validation of structures determined by X-ray crystallography. We describe some general protocols used in the rebuilding and re-refinement of problematic structural models. We also briefly discuss some frontier areas of structure validation, including refinement of protein–ligand complexes, automation of structure redetermination, and the use of NMR structures and computational models to solve X-ray crystal structures by molecular replacement. PMID:24203341

Precipitation process in a Mg–Gd–Y alloy grain-refined by Al addition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Jichun; CAST Cooperative Research Centre, Department of Materials Engineering, Monash University, Victoria 3800; Zhu, Suming, E-mail: suming.zhu@monash.edu

2014-02-15

The precipitation process in Mg–10Gd–3Y (wt.%) alloy grain-refined by 0.8 wt.% Al addition has been investigated by transmission electron microscopy. The alloy was given a solution treatment at 520 °C for 6 h plus 550 °C for 7 h before ageing at 250 °C. Plate-shaped intermetallic particles with the 18R-type long-period stacking ordered structure were observed in the solution-treated state. Upon isothermal ageing at 250 °C, the following precipitation sequence was identified for the α-Mg supersaturated solution: β″ (D0{sub 19}) → β′ (bco) → β{sub 1} (fcc) → β (fcc). The observed precipitation process and age hardening response in themore » Al grain-refined Mg–10Gd–3Y alloy are compared with those reported in the Zr grain-refined counterpart. - Highlights: • The precipitation process in Mg–10Gd–3Y–0.8Al (wt.%) alloy has been investigated. • Particles with the 18R-type LPSO structure were observed in the solution state. • Upon ageing at 250 °C, the precipitation sequence is: β″ → β′ → β1 (fcc) → β. • The Al grain-refined alloy has a lower hardness than the Zr refined counterpart.« less

Transferability of electronic structure of four energetic materials by using single crystal and high resolution X-ray diffraction experiments

NASA Astrophysics Data System (ADS)

Chen, Yu-Sheng

The electronic structures of four energetic materials, trinitrodiazapentalene (C6H3N5O6, TNDAP), beta-1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (C4H8N8O8, beta-HMX), 1,3,3-trinitroazetidine (C3H4N4O6, TNAZ), and hexahydro-1,3,5-trinitro-1,3,5-s-triazine (C3H6N6O6, RDX), have been analyzed using Hansen-Coppens multipole refinements, using high resolution X-ray diffraction data collected at low temperature, as well as from theoretical calculated structure factors from the solid state phase using density functional theory (DFT), plus B3LYP level theory, and the 6-31G* basis set. However, when comparing both the deformation density and the electrostatic potentials from the theoretical results in TNDAP and TNAZ, they disagree with the experimental results. Therefore, those results have been deposited in appendices A4 and A6, for future reference. In HMX and RDX the theoretical results are in good agreement with experimental results. The physical properties derived from the electronic structure in these four energetic materials, such as multipole populations, the values of the electron density and its Laplacian of the electron density at the bond critical points, have also been calculated using "Atoms in Molecules" (AIM) theory both from the solid state phase calculation, and the experiment, as well as directly calculated from the free molecule in the gas phase. The electron density and the magnitude of its Laplacian from the gas phase are always larger than for the solid state phase calculation and the experiment. This may be due to the packing effect. The transferability of the experimental electronic structure of the NO 2 groups from HMX to TNDAP, TNAZ and RDX are also presented here. Even though the major populated multipoles are robust (small e.s.d.'s), these are few in number, compared with other lower populated multipoles for which the populations span a larger range. Since the deformation electron density distributions are reconstructed using linear combinations of the multipoles, it is necessary to give more degrees of freedom in the refinements. Therefore, those electron density distributions which have a wider range of the multipole populations should not be fixed in the refinements. Utilizing the same coordinate system setup in the multipole refinements of the functional groups, this system can be used as a starting point for solving the charge distribution of a larger system.

From deep TLS validation to ensembles of atomic models built from elemental motions

DOE PAGES

Urzhumtsev, Alexandre; Afonine, Pavel V.; Van Benschoten, Andrew H.; ...

2015-07-28

The translation–libration–screw model first introduced by Cruickshank, Schomaker and Trueblood describes the concerted motions of atomic groups. Using TLS models can improve the agreement between calculated and experimental diffraction data. Because the T, L and S matrices describe a combination of atomic vibrations and librations, TLS models can also potentially shed light on molecular mechanisms involving correlated motions. However, this use of TLS models in mechanistic studies is hampered by the difficulties in translating the results of refinement into molecular movement or a structural ensemble. To convert the matrices into a constituent molecular movement, the matrix elements must satisfy severalmore » conditions. Refining the T, L and S matrix elements as independent parameters without taking these conditions into account may result in matrices that do not represent concerted molecular movements. Here, a mathematical framework and the computational tools to analyze TLS matrices, resulting in either explicit decomposition into descriptions of the underlying motions or a report of broken conditions, are described. The description of valid underlying motions can then be output as a structural ensemble. All methods are implemented as part of the PHENIX project.« less

Comparison of oil refining and biodiesel production process between screw press and n-hexane techniques from beauty leaf feedstock

NASA Astrophysics Data System (ADS)

Bhuiya, M. M. K.; Rasul, M. G.; Khan, M. M. K.; Ashwath, N.

2016-07-01

The Beauty Leaf Tree (Callophylum inophyllum) is regarded as an alternative source of energy to produce 2nd generation biodiesel due to its potentiality as well as high oil yield content in the seed kernels. The treating process is indispensable during the biodiesel production process because it can augment the yield as well as quality of the product. Oil extracted from both mechanical screw press and solvent extraction using n-hexane was refined. Five replications each of 25 gm of crude oil for screw press and five replications each of 25 gm of crude oil for n-hexane were selected for refining as well as biodiesel conversion processes. The oil refining processes consists of degumming, neutralization as well as dewaxing. The degumming, neutralization and dewaxing processes were performed to remove all the gums (phosphorous-based compounds), free fatty acids, and waxes from the fresh crude oil before the biodiesel conversion process carried out, respectively. The results indicated that up to 73% and 81% of mass conversion efficiency of the refined oil in the screw press and n-hexane refining processes were obtained, respectively. It was also found that up to 88% and 90% of biodiesel were yielded in terms of mass conversion efficiency in the transesterification process for the screw press and n-hexane techniques, respectively. While the entire processes (refining and transesterification) were considered, the conversion of beauty leaf tree (BLT) refined oil into biodiesel was yielded up to 65% and 73% of mass conversion efficiency for the screw press and n-hexane techniques, respectively. Physico-chemical properties of crude and refined oil, and biodiesel were characterized according to the ASTM standards. Overall, BLT has the potential to contribute as an alternative energy source because of high mass conversion efficiency.

PURY: a database of geometric restraints of hetero compounds for refinement in complexes with macromolecular structures.

PubMed

Andrejasic, Miha; Praaenikar, Jure; Turk, Dusan

2008-11-01

The number and variety of macromolecular structures in complex with ;hetero' ligands is growing. The need for rapid delivery of correct geometric parameters for their refinement, which is often crucial for understanding the biological relevance of the structure, is growing correspondingly. The current standard for describing protein structures is the Engh-Huber parameter set. It is an expert data set resulting from selection and analysis of the crystal structures gathered in the Cambridge Structural Database (CSD). Clearly, such a manual approach cannot be applied to the vast and ever-growing number of chemical compounds. Therefore, a database, named PURY, of geometric parameters of chemical compounds has been developed, together with a server that accesses it. PURY is a compilation of the whole CSD. It contains lists of atom classes and bonds connecting them, as well as angle, chirality, planarity and conformation parameters. The current compilation is based on CSD 5.28 and contains 1978 atom classes and 32,702 bonding, 237,068 angle, 201,860 dihedral and 64,193 improper geometric restraints. Analysis has confirmed that the restraints from the PURY database are suitable for use in macromolecular crystal structure refinement and should be of value to the crystallographic community. The database can be accessed through the web server http://pury.ijs.si/, which creates topology and parameter files from deposited coordinates in suitable forms for the refinement programs MAIN, CNS and REFMAC. In the near future, the server will move to the CSD website http://pury.ccdc.cam.ac.uk/.

Using neutrons, X-rays and nuclear magnetism to determine the role of transition metal oxide inclusions on both glass structure and stability in automotive glass enamels.

PubMed

Bowron, Daniel T; Booth, Jonathan; Barrow, Nathan S; Sutton, Patricia; Johnson, Simon R

2018-05-23

Low levels of transition metal oxides in alkali borosilicate glass systems can drastically influence crystallisation and phase separation properties. We investigated the non-monotonic effect of manganese doping on suppressing crystallisation, and the influence on optical properties by iron oxide doping, in terms of local atomic structure. Structural models based on empirical potential structure refinement were generated from neutron and X-ray scattering data, and compared against multinuclear solid-state NMR. This revealed that a 2.5% manganese doping had a disruptive effect on the entire glass network, supressing crystallisation of an undesired bismuth silicate phase, and that iron species preferentially locate near borate tetrahedra. Preventing phase separation and controlling crystallisation behaviour of glass are critical to the ultimate properties of automotive glass enamels.

Preliminary Evaluation of the DUSTRAN Modeling Suite for Modeling Atmospheric Chloride Transport

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Philip; Tran, Tracy; Fritz, Bradley

2016-05-03

This study investigates the potential of DUSTRAN, a dust dispersion modeling system developed by Pacific Northwest National Laboratory, to model the transport of sea salt aerosols (SSA). Results from DUSTRAN simulations run with historical meteorological data were compared against privately-measured chloride data at the near coastal Maine Yankee Nuclear Power Plant (NPP) and the Environmental Protection Agency-measured CASTNET data from Acadia National Park (NP). The comparisons have provided both encouragement as to the practical value of DUSTRAN’s CALPUFF model and suggestions for further software development opportunities. All modeled concentrations were within one order of magnitude of those measured and amore » few test cases showed excellent agreement between modeled and measured concentrations. However, there is a lack of consistency in discrepancy which may be due to inaccurate extrapolation of meteorological data, underlying model physics, and the source term. Future research will refine the software to better capture physical phenomena. Overall, results indicate that with parameter refinement, DUSTRAN has the potential to simulate atmospheric chloride transport from known sources to inland sites for the purpose of determining the corrosion susceptibility of various structures, systems, and components at the site.« less

Refined structure of dimeric diphtheria toxin at 2.0 A resolution.

PubMed Central

Bennett, M. J.; Choe, S.; Eisenberg, D.

1994-01-01

The refined structure of dimeric diphtheria toxin (DT) at 2.0 A resolution, based on 37,727 unique reflections (F > 1 sigma (F)), yields a final R factor of 19.5% with a model obeying standard geometry. The refined model consists of 523 amino acid residues, 1 molecule of the bound dinucleotide inhibitor adenylyl 3'-5' uridine 3' monophosphate (ApUp), and 405 well-ordered water molecules. The 2.0-A refined model reveals that the binding motif for ApUp includes residues in the catalytic and receptor-binding domains and is different from the Rossmann dinucleotide-binding fold. ApUp is bound in part by a long loop (residues 34-52) that crosses the active site. Several residues in the active site were previously identified as NAD-binding residues. Glu 148, previously identified as playing a catalytic role in ADP-ribosylation of elongation factor 2 by DT, is about 5 A from uracil in ApUp. The trigger for insertion of the transmembrane domain of DT into the endosomal membrane at low pH may involve 3 intradomain and 4 interdomain salt bridges that will be weakened at low pH by protonation of their acidic residues. The refined model also reveals that each molecule in dimeric DT has an "open" structure unlike most globular proteins, which we call an open monomer. Two open monomers interact by "domain swapping" to form a compact, globular dimeric DT structure. The possibility that the open monomer resembles a membrane insertion intermediate is discussed. PMID:7833807

Structure of the Trypanosoma cruzi protein tyrosine phosphatase TcPTP1, a potential therapeutic target for Chagas' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lountos, George T.; Tropea, Joseph E.; Waugh, David S.

2013-06-05

Chagas’ disease, a neglected tropical affliction transmitted by the flagellated protozoan Trypanosoma cruzi, is prevalent in Latin America and affects nearly 18 million people worldwide, yet few approved drugs are available to treat the disease. Moreover, the currently available drugs exhibit severe toxicity or are poorly effective in the chronic phase of the disease. This limitation, along with the large population at risk, underscores the urgent need to discover new molecular targets and novel therapeutic agents. Recently, the T. cruzi protein tyrosine phosphatase TcPTP1 has been implicated in the cellular differentiation and infectivity of the parasite and is therefore amore » promising target for the design of novel anti-parasitic drugs. Here, we report the X-ray crystal structure of TcPTP1 refined to a resolution of 2.18 Å, which provides structural insights into the active site environment that can be used to initiate structure-based drug design efforts to develop specific TcPTP1 inhibitors. Potential strategies to develop such inhibitors are also discussed.« less

Adaptive Mesh Refinement in Curvilinear Body-Fitted Grid Systems

NASA Technical Reports Server (NTRS)

Steinthorsson, Erlendur; Modiano, David; Colella, Phillip

1995-01-01

To be truly compatible with structured grids, an AMR algorithm should employ a block structure for the refined grids to allow flow solvers to take advantage of the strengths of unstructured grid systems, such as efficient solution algorithms for implicit discretizations and multigrid schemes. One such algorithm, the AMR algorithm of Berger and Colella, has been applied to and adapted for use with body-fitted structured grid systems. Results are presented for a transonic flow over a NACA0012 airfoil (AGARD-03 test case) and a reflection of a shock over a double wedge.

Crystal chemistry and structure refinement of five hydrated calcium borates

USGS Publications Warehouse

Clark, J.R.; Appleman, D.E.; Christ, C.L.

1964-01-01

The crystal structures of the five known members of the series Ca2B6O11??xH2O (x = 1, 5, 5, 7, 9, and 13) have been refined by full-matrix least-squares techniques, yielding bond distances and angles with standard errors of less than 0??01 A?? and 0??5??, respectively. The results illustrate the crystal chemical principles that govern the structures of hydrated borate compounds. The importance of hydrogen bonding in the ferroelectric transition of colemanite is confirmed by more accurate proton assignments. ?? 1964.

Nanostructured Na2Ti9O19 for Hybrid Sodium-Ion Capacitors with Excellent Rate Capability.

PubMed

Bhat, Swetha S M; Babu, Binson; Feygenson, Mikhail; Neuefeind, Joerg C; Shaijumon, M M

2018-01-10

Herein, we report a new Na-insertion electrode material, Na 2 Ti 9 O 19 , as a potential candidate for Na-ion hybrid capacitors. We study the structural properties of nanostructured Na 2 Ti 9 O 19 , synthesized by a hydrothermal technique, upon electrochemical cycling vs Na. Average and local structures of Na 2 Ti 9 O 19 are elucidated from neutron Rietveld refinement and pair distribution function (PDF), respectively, to investigate the initial discharge and charge events. Rietveld refinement reveals electrochemical cycling of Na 2 Ti 9 O 19 is driven by single-phase solid solution reaction during (de)sodiation without any major structural deterioration, keeping the average structure intact. Unit cell volume and lattice evolution on discharge process is inherently related to TiO 6 distortion and Na ion perturbations, while the PDF reveals the deviation in the local structure after sodiation. Raman spectroscopy and X-ray photoelectron spectroscopy studies further corroborate the average and local structural behavior derived from neutron diffraction measurements. Also, Na 2 Ti 9 O 19 shows excellent Na-ion kinetics with a capacitve nature of 86% at 1.0 mV s -1 , indicating that the material is a good anode candidate for a sodium-ion hybrid capacitor. A full cell hybrid Na-ion capacitor is fabricated by using Na 2 Ti 9 O 19 as anode and activated porous carbon as cathode, which exhibits excellent electrochemical properties, with a maximum energy density of 54 Wh kg -1 and a maximum power density of 5 kW kg -1 . Both structural insights and electrochemical investigation suggest that Na 2 Ti 9 O 19 is a promising negative electrode for sodium-ion batteries and hybrid capacitors.

Zeta potential study of Sb2S3 nanoparticles synthesized by a facile polyol method in various surfactants

NASA Astrophysics Data System (ADS)

Saxena, Monika; Okram, Gunadhor Singh

2018-05-01

In the present work, we report the successful synthesis of stibnite Sb2S3 nanoparticles (NPs) by a facile polyol method using various surfactant. The structural and optical properties were investigated by X-ray diffraction (XRD), Raman spectroscopy and Zeta potential. Rietveld refinement of XRD data confirms the single phase orthorhombic crystal structure of stibnite Sb2S3. Presence of six obvious Raman modes further confirmed their stoichiometric formation. Effect of different surfactants on the surface charge of Sb2S3 NPs was studied using Zeta potential measurement in deionized water at different pH values. They reveal that these NPs are more stable when it was synthesized in presence of EDTA than that of CTAB or without surfactant samples with high zeta potential. The isoelectronic point was found at pH = 6.4 for pure sample, 3.5 and 7.2 for CTAB and not found for EDTA Sb2S3 samples. This information can be useful for many industrial applications like pharmaceuticals, ceramics, waste water treatment and medicines.

On the structure of an aqueous propylene glycol solution.

PubMed

Rhys, Natasha H; Gillams, Richard J; Collins, Louise E; Callear, Samantha K; Lawrence, M Jayne; McLain, Sylvia E

2016-12-14

Using a combination of neutron diffraction and empirical potential structure refinement computational modelling, the interactions in a 30 mol. % aqueous solution of propylene glycol (PG), which govern both the hydration and association of this molecule in solution, have been assessed. From this work it appears that PG is readily hydrated, where the most prevalent hydration interactions were found to be through both the PG hydroxyl groups but also alkyl groups typically considered hydrophobic. Hydration interactions of PG dominate the solution over PG self-self interactions and there is no evidence of more extensive association. This hydration behavior for PG in solutions suggests that the preference of PG to be hydrated rather than to be self-associated may translate into a preference for PG to bind to lipids rather than itself, providing a potential explanation for how PG is able to enhance the apparent solubility of drug molecules in vivo.

On the structure of an aqueous propylene glycol solution

NASA Astrophysics Data System (ADS)

Rhys, Natasha H.; Gillams, Richard J.; Collins, Louise E.; Callear, Samantha K.; Lawrence, M. Jayne; McLain, Sylvia E.

2016-12-01

Using a combination of neutron diffraction and empirical potential structure refinement computational modelling, the interactions in a 30 mol. % aqueous solution of propylene glycol (PG), which govern both the hydration and association of this molecule in solution, have been assessed. From this work it appears that PG is readily hydrated, where the most prevalent hydration interactions were found to be through both the PG hydroxyl groups but also alkyl groups typically considered hydrophobic. Hydration interactions of PG dominate the solution over PG self-self interactions and there is no evidence of more extensive association. This hydration behavior for PG in solutions suggests that the preference of PG to be hydrated rather than to be self-associated may translate into a preference for PG to bind to lipids rather than itself, providing a potential explanation for how PG is able to enhance the apparent solubility of drug molecules in vivo.

Pharmacophore modeling, docking, and principal component analysis based clustering: combined computer-assisted approaches to identify new inhibitors of the human rhinovirus coat protein.

PubMed

Steindl, Theodora M; Crump, Carolyn E; Hayden, Frederick G; Langer, Thierry

2005-10-06

The development and application of a sophisticated virtual screening and selection protocol to identify potential, novel inhibitors of the human rhinovirus coat protein employing various computer-assisted strategies are described. A large commercially available database of compounds was screened using a highly selective, structure-based pharmacophore model generated with the program Catalyst. A docking study and a principal component analysis were carried out within the software package Cerius and served to validate and further refine the obtained results. These combined efforts led to the selection of six candidate structures, for which in vitro anti-rhinoviral activity could be shown in a biological assay.

Isogeometric analysis: a powerful numerical tool for the elastic analysis of historical masonry arches

NASA Astrophysics Data System (ADS)

Cazzani, Antonio; Malagù, Marcello; Turco, Emilio

2016-03-01

We illustrate a numerical tool for analyzing plane arches such as those frequently used in historical masonry heritage. It is based on a refined elastic mechanical model derived from the isogeometric approach. In particular, geometry and displacements are modeled by means of non-uniform rational B-splines. After a brief introduction, outlining the basic assumptions of this approach and the corresponding modeling choices, several numerical applications to arches, which are typical of masonry structures, show the performance of this novel technique. These are discussed in detail to emphasize the advantage and potential developments of isogeometric analysis in the field of structural analysis of historical masonry buildings with complex geometries.

Electronic structure probed with positronium: Theoretical viewpoint

NASA Astrophysics Data System (ADS)

Kuriplach, Jan; Barbiellini, Bernardo

2018-05-01

We inspect carefully how the positronium can be used to study the electronic structure of materials. Recent combined experimental and computational study [A.C.L. Jones et al., Phys. Rev. Lett. 117, 216402 (2016)] has shown that the positronium affinity can be used to benchmark the exchange-correlation approximations in copper. Here we investigate whether an improvement can be achieved by increasing the numerical precision of calculations and by employing the strongly constrained and appropriately normed (SCAN) scheme, and extend the study to other selected systems like aluminum and high entropy alloys. From the methodological viewpoint, the computations of the positronium affinity are further refined and an alternative way of determining the electron chemical potential using charged supercells is examined.

Structural studies of TiC{sub 1−x}O{sub x} solid solution by Rietveld refinement and first-principles calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Bo, E-mail: youqin5912@yahoo.com.cn; Hou, Na; Huang, Shanyan

2013-08-15

The lattice parameters, structural stability and electronic structure of titanium oxycarbides (TiC{sub 1−x}O{sub x}, 0≤x≤1) solid solution were investigated by Rietveld refinement and first-principles calculations. Series of TiC{sub 1−x}O{sub x} were precisely synthesized by sintering process under the vacuum. Rietveld refinement results of XRD patterns show the properties of continuous solid solution in TiC{sub 1−x}O{sub x} over the whole composition range. The lattice parameters vary from 0.4324 nm to 0.4194 nm decreasing with increasing oxygen concentration. Results of first-principles calculations reveal that the disorder C/O structure is stable than the order C/O structure. Further investigations of the vacancy in Ti{submore » 1−Va}(C{sub 1−x}O{sub x}){sub 1−Va} solid solution present that the structure of vacancy segregated in TiO-part is more stable than the disorder C/O structure, which can be ascribed to the Ti–Ti bond across O-vacancy and the charge redistributed around Ti-vacancy via the analysis of the electron density difference plots and PDOS. - Graphical abstract: XRD of series of titanium oxycarbides (TiC{sub 1−x}O{sub x}, 0≤x≤1) solid solution prepared by adjusting the proportion of TiO in the starting material. Highlights: • Titanium oxycarbides were obtained by sintering TiO and TiC under carefully controlled conditions. • Rietveld refinement results show continuous solid solution with FCC structure in TiC{sub 1−x}O{sub x}. • The disorder C/O structure is stable than the order C/O structure. • Introduction of vacancy segregated in TiO-part is more stable than disorder C/O structure. • Ti–Ti bond across O-vacancy and the charge redistributed around Ti-vacancy enhance structural stability.« less

Evolutionary Optimization of a Geometrically Refined Truss

NASA Technical Reports Server (NTRS)

Hull, P. V.; Tinker, M. L.; Dozier, G. V.

2007-01-01

Structural optimization is a field of research that has experienced noteworthy growth for many years. Researchers in this area have developed optimization tools to successfully design and model structures, typically minimizing mass while maintaining certain deflection and stress constraints. Numerous optimization studies have been performed to minimize mass, deflection, and stress on a benchmark cantilever truss problem. Predominantly traditional optimization theory is applied to this problem. The cross-sectional area of each member is optimized to minimize the aforementioned objectives. This Technical Publication (TP) presents a structural optimization technique that has been previously applied to compliant mechanism design. This technique demonstrates a method that combines topology optimization, geometric refinement, finite element analysis, and two forms of evolutionary computation: genetic algorithms and differential evolution to successfully optimize a benchmark structural optimization problem. A nontraditional solution to the benchmark problem is presented in this TP, specifically a geometrically refined topological solution. The design process begins with an alternate control mesh formulation, multilevel geometric smoothing operation, and an elastostatic structural analysis. The design process is wrapped in an evolutionary computing optimization toolset.

Development of Phenol-Enriched Olive Oil with Phenolic Compounds Extracted from Wastewater Produced by Physical Refining.

PubMed

Venturi, Francesca; Sanmartin, Chiara; Taglieri, Isabella; Nari, Anita; Andrich, Gianpaolo; Terzuoli, Erika; Donnini, Sandra; Nicolella, Cristiano; Zinnai, Angela

2017-08-22

While in the last few years the use of olive cake and mill wastewater as natural sources of phenolic compounds has been widely considered and several studies have focused on the development of new extraction methods and on the production of functional foods enriched with natural antioxidants, no data has been available on the production of a phenol-enriched refined olive oil with its own phenolic compounds extracted from wastewater produced during physical refining. In this study; we aimed to: (i) verify the effectiveness of a multi-step extraction process to recover the high-added-value phenolic compounds contained in wastewater derived from the preliminary washing degumming step of the physical refining of vegetal oils; (ii) evaluate their potential application for the stabilization of olive oil obtained with refined olive oils; and (iii) evaluate their antioxidant activity in an in vitro model of endothelial cells. The results obtained demonstrate the potential of using the refining wastewater as a source of bioactive compounds to improve the nutraceutical value as well as the antioxidant capacity of commercial olive oils. In the conditions adopted, the phenolic content significantly increased in the prototypes of phenol-enriched olive oils when compared with the control oil.

Development of Phenol-Enriched Olive Oil with Phenolic Compounds Extracted from Wastewater Produced by Physical Refining

PubMed Central

Taglieri, Isabella; Nari, Anita; Andrich, Gianpaolo; Terzuoli, Erika; Donnini, Sandra; Nicolella, Cristiano; Zinnai, Angela

2017-01-01

While in the last few years the use of olive cake and mill wastewater as natural sources of phenolic compounds has been widely considered and several studies have focused on the development of new extraction methods and on the production of functional foods enriched with natural antioxidants, no data has been available on the production of a phenol-enriched refined olive oil with its own phenolic compounds extracted from wastewater produced during physical refining. In this study; we aimed to: (i) verify the effectiveness of a multi-step extraction process to recover the high-added-value phenolic compounds contained in wastewater derived from the preliminary washing degumming step of the physical refining of vegetal oils; (ii) evaluate their potential application for the stabilization of olive oil obtained with refined olive oils; and (iii) evaluate their antioxidant activity in an in vitro model of endothelial cells. The results obtained demonstrate the potential of using the refining wastewater as a source of bioactive compounds to improve the nutraceutical value as well as the antioxidant capacity of commercial olive oils. In the conditions adopted, the phenolic content significantly increased in the prototypes of phenol-enriched olive oils when compared with the control oil. PMID:28829365

Simple theoretical models for composite rotor blades

NASA Technical Reports Server (NTRS)

Valisetty, R. R.; Rehfield, L. W.

1984-01-01

The development of theoretical rotor blade structural models for designs based upon composite construction is discussed. Care was exercised to include a member of nonclassical effects that previous experience indicated would be potentially important to account for. A model, representative of the size of a main rotor blade, is analyzed in order to assess the importance of various influences. The findings of this model study suggest that for the slenderness and closed cell construction considered, the refinements are of little importance and a classical type theory is adequate. The potential of elastic tailoring is dramatically demonstrated, so the generality of arbitrary ply layup in the cell wall is needed to exploit this opportunity.

Nominal profile refinements report: Targets in 150 and 190 nautical mile circular orbits

NASA Technical Reports Server (NTRS)

Kreiter, T. J.

1975-01-01

Refinements for 150 and 190 n.mi. circular target orbits were examined along with the potential advantages of ground-hold as a means of reducing the phasing times associated with low orbit rendezvous.

Bandwidth Study on Energy Use and Potential Energy Savings Opportunities in U.S. Petroleum Refining

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabine Brueske, Caroline Kramer, Aaron Fisher

2015-06-01

Energy bandwidth studies of U.S. manufacturing sectors can serve as foundational references in framing the range (or bandwidth) of potential energy savings opportunities. This bandwidth study examines energy consumption and potential energy savings opportunities in U.S. petroleum refining. The study relies on multiple sources to estimate the energy used in nine individual process areas, representing 68% of sector-wide energy consumption. Energy savings opportunities for individual processes are based on technologies currently in use or under development; these potential savings are then extrapolated to estimate sector-wide energy savings opportunity.

Use of Molecular Dynamics for the Refinement of an Electrostatic Model for the In Silico Design of a Polymer Antidote for the Anticoagulant Fondaparinux

PubMed Central

Kwok, Ezra; Gopaluni, Bhushan; Kizhakkedathu, Jayachandran N.

2013-01-01

Molecular dynamics (MD) simulations results are herein incorporated into an electrostatic model used to determine the structure of an effective polymer-based antidote to the anticoagulant fondaparinux. In silico data for the polymer or its cationic binding groups has not, up to now, been available, and experimental data on the structure of the polymer-fondaparinux complex is extremely limited. Consequently, the task of optimizing the polymer structure is a daunting challenge. MD simulations provided a means to gain microscopic information on the interactions of the binding groups and fondaparinux that would have otherwise been inaccessible. This was used to refine the electrostatic model and improve the quantitative model predictions of binding affinity. Once refined, the model provided guidelines to improve electrostatic forces between candidate polymers and fondaparinux in order to increase association rate constants. PMID:27006916

Rapid Design of Knowledge-Based Scoring Potentials for Enrichment of Near-Native Geometries in Protein-Protein Docking.

PubMed

Sasse, Alexander; de Vries, Sjoerd J; Schindler, Christina E M; de Beauchêne, Isaure Chauvot; Zacharias, Martin

2017-01-01

Protein-protein docking protocols aim to predict the structures of protein-protein complexes based on the structure of individual partners. Docking protocols usually include several steps of sampling, clustering, refinement and re-scoring. The scoring step is one of the bottlenecks in the performance of many state-of-the-art protocols. The performance of scoring functions depends on the quality of the generated structures and its coupling to the sampling algorithm. A tool kit, GRADSCOPT (GRid Accelerated Directly SCoring OPTimizing), was designed to allow rapid development and optimization of different knowledge-based scoring potentials for specific objectives in protein-protein docking. Different atomistic and coarse-grained potentials can be created by a grid-accelerated directly scoring dependent Monte-Carlo annealing or by a linear regression optimization. We demonstrate that the scoring functions generated by our approach are similar to or even outperform state-of-the-art scoring functions for predicting near-native solutions. Of additional importance, we find that potentials specifically trained to identify the native bound complex perform rather poorly on identifying acceptable or medium quality (near-native) solutions. In contrast, atomistic long-range contact potentials can increase the average fraction of near-native poses by up to a factor 2.5 in the best scored 1% decoys (compared to existing scoring), emphasizing the need of specific docking potentials for different steps in the docking protocol.

Rosetta Structure Prediction as a Tool for Solving Difficult Molecular Replacement Problems.

PubMed

DiMaio, Frank

2017-01-01

Molecular replacement (MR), a method for solving the crystallographic phase problem using phases derived from a model of the target structure, has proven extremely valuable, accounting for the vast majority of structures solved by X-ray crystallography. However, when the resolution of data is low, or the starting model is very dissimilar to the target protein, solving structures via molecular replacement may be very challenging. In recent years, protein structure prediction methodology has emerged as a powerful tool in model building and model refinement for difficult molecular replacement problems. This chapter describes some of the tools available in Rosetta for model building and model refinement specifically geared toward difficult molecular replacement cases.

Molecular and Structural Characterization of the Tegumental 20.6-kDa Protein in Clonorchis sinensis as a Potential Druggable Target.

PubMed

Kim, Yu-Jung; Yoo, Won Gi; Lee, Myoung-Ro; Kang, Jung-Mi; Na, Byoung-Kuk; Cho, Shin-Hyeong; Park, Mi-Yeoun; Ju, Jung-Won

2017-03-04

The tegument, representing the membrane-bound outer surface of platyhelminth parasites, plays an important role for the regulation of the host immune response and parasite survival. A comprehensive understanding of tegumental proteins can provide drug candidates for use against helminth-associated diseases, such as clonorchiasis caused by the liver fluke Clonorchis sinensis . However, little is known regarding the physicochemical properties of C. sinensis teguments. In this study, a novel 20.6-kDa tegumental protein of the C. sinensis adult worm (CsTegu20.6) was identified and characterized by molecular and in silico methods. The complete coding sequence of 525 bp was derived from cDNA clones and encodes a protein of 175 amino acids. Homology search using BLASTX showed CsTegu20.6 identity ranging from 29% to 39% with previously-known tegumental proteins in C. sinensis . Domain analysis indicated the presence of a calcium-binding EF-hand domain containing a basic helix-loop-helix structure and a dynein light chain domain exhibiting a ferredoxin fold. We used a modified method to obtain the accurate tertiary structure of the CsTegu20.6 protein because of the unavailability of appropriate templates. The CsTegu20.6 protein sequence was split into two domains based on the disordered region, and then, the structure of each domain was modeled using I-TASSER. A final full-length structure was obtained by combining two structures and refining the whole structure. A refined CsTegu20.6 structure was used to identify a potential CsTegu20.6 inhibitor based on protein structure-compound interaction analysis. The recombinant proteins were expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid affinity chromatography. In C. sinensis , CsTegu20.6 mRNAs were abundant in adult and metacercariae, but not in the egg. Immunohistochemistry revealed that CsTegu20.6 localized to the surface of the tegument in the adult fluke. Collectively, our results contribute to a better understanding of the structural and functional characteristics of CsTegu20.6 and homologs of flukes. One compound is proposed as a putative inhibitor of CsTegu20.6 to facilitate further studies for anthelmintics.

Computational Amide I Spectroscopy for Refinement of Disordered Peptide Ensembles: Maximum Entropy and Related Approaches

NASA Astrophysics Data System (ADS)

Reppert, Michael; Tokmakoff, Andrei

The structural characterization of intrinsically disordered peptides (IDPs) presents a challenging biophysical problem. Extreme heterogeneity and rapid conformational interconversion make traditional methods difficult to interpret. Due to its ultrafast (ps) shutter speed, Amide I vibrational spectroscopy has received considerable interest as a novel technique to probe IDP structure and dynamics. Historically, Amide I spectroscopy has been limited to delivering global secondary structural information. More recently, however, the method has been adapted to study structure at the local level through incorporation of isotope labels into the protein backbone at specific amide bonds. Thanks to the acute sensitivity of Amide I frequencies to local electrostatic interactions-particularly hydrogen bonds-spectroscopic data on isotope labeled residues directly reports on local peptide conformation. Quantitative information can be extracted using electrostatic frequency maps which translate molecular dynamics trajectories into Amide I spectra for comparison with experiment. Here we present our recent efforts in the development of a rigorous approach to incorporating Amide I spectroscopic restraints into refined molecular dynamics structural ensembles using maximum entropy and related approaches. By combining force field predictions with experimental spectroscopic data, we construct refined structural ensembles for a family of short, strongly disordered, elastin-like peptides in aqueous solution.

Hirshfeld atom refinement for modelling strong hydrogen bonds.

PubMed

Woińska, Magdalena; Jayatilaka, Dylan; Spackman, Mark A; Edwards, Alison J; Dominiak, Paulina M; Woźniak, Krzysztof; Nishibori, Eiji; Sugimoto, Kunihisa; Grabowsky, Simon

2014-09-01

High-resolution low-temperature synchrotron X-ray diffraction data of the salt L-phenylalaninium hydrogen maleate are used to test the new automated iterative Hirshfeld atom refinement (HAR) procedure for the modelling of strong hydrogen bonds. The HAR models used present the first examples of Z' > 1 treatments in the framework of wavefunction-based refinement methods. L-Phenylalaninium hydrogen maleate exhibits several hydrogen bonds in its crystal structure, of which the shortest and the most challenging to model is the O-H...O intramolecular hydrogen bond present in the hydrogen maleate anion (O...O distance is about 2.41 Å). In particular, the reconstruction of the electron density in the hydrogen maleate moiety and the determination of hydrogen-atom properties [positions, bond distances and anisotropic displacement parameters (ADPs)] are the focus of the study. For comparison to the HAR results, different spherical (independent atom model, IAM) and aspherical (free multipole model, MM; transferable aspherical atom model, TAAM) X-ray refinement techniques as well as results from a low-temperature neutron-diffraction experiment are employed. Hydrogen-atom ADPs are furthermore compared to those derived from a TLS/rigid-body (SHADE) treatment of the X-ray structures. The reference neutron-diffraction experiment reveals a truly symmetric hydrogen bond in the hydrogen maleate anion. Only with HAR is it possible to freely refine hydrogen-atom positions and ADPs from the X-ray data, which leads to the best electron-density model and the closest agreement with the structural parameters derived from the neutron-diffraction experiment, e.g. the symmetric hydrogen position can be reproduced. The multipole-based refinement techniques (MM and TAAM) yield slightly asymmetric positions, whereas the IAM yields a significantly asymmetric position.

Coarse Grained Model for Biological Simulations: Recent Refinements and Validation

PubMed Central

Vicatos, Spyridon; Rychkova, Anna; Mukherjee, Shayantani; Warshel, Arieh

2014-01-01

Exploring the free energy landscape of proteins and modeling the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of various simplified coarse grained (CG) models offers an effective way of sampling the landscape, but most current models are not expected to give a reliable description of protein stability and functional aspects. The main problem is associated with insufficient focus on the electrostatic features of the model. In this respect our recent CG model offers significant advantage as it has been refined while focusing on its electrostatic free energy. Here we review the current state of our model, describing recent refinement, extensions and validation studies while focusing on demonstrating key applications. These include studies of protein stability, extending the model to include membranes and electrolytes and electrodes as well as studies of voltage activated proteins, protein insertion trough the translocon, the action of molecular motors and even the coupling of the stalled ribosome and the translocon. Our example illustrates the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins and large macromolecular complexes. PMID:25050439

TLS from fundamentals to practice

PubMed Central

Urzhumtsev, Alexandre; Afonine, Pavel V.; Adams, Paul D.

2014-01-01

The Translation-Libration-Screw-rotation (TLS) model of rigid-body harmonic displacements introduced in crystallography by Schomaker & Trueblood (1968) is now a routine tool in macromolecular studies and is a feature of most modern crystallographic structure refinement packages. In this review we consider a number of simple examples that illustrate important features of the TLS model. Based on these examples simplified formulae are given for several special cases that may occur in structure modeling and refinement. The derivation of general TLS formulae from basic principles is also provided. This manuscript describes the principles of TLS modeling, as well as some select algorithmic details for practical application. An extensive list of applications references as examples of TLS in macromolecular crystallography refinement is provided. PMID:25249713

Indigenous lunar construction materials

NASA Technical Reports Server (NTRS)

Rogers, Wayne P.; Sture, Stein

1991-01-01

The utilization of local resources for the construction and operation of a lunar base can significantly reduce the cost of transporting materials and supplies from Earth. The feasibility of processing lunar regolith to form construction materials and structural components is investigated. A preliminary review of potential processing methods such as sintering, hot-pressing, liquification, and cast basalt techniques, was completed. The processing method proposed is a variation on the cast basalt technique. It involves liquification of the regolith at 1200-1300 C, casting the liquid into a form, and controlled cooling. While the process temperature is higher than that for sintering or hot-pressing (1000-1100 C), this method is expected to yield a true engineering material with low variability in properties, high strength, and the potential to form large structural components. A scenario for this processing method was integrated with a design for a representative lunar base structure and potential construction techniques. The lunar shelter design is for a modular, segmented, pressurized, hemispherical dome which could serve as habitation and laboratory space. Based on this design, estimates of requirements for power, processing equipment, and construction equipment were made. This proposed combination of material processing method, structural design, and support requirements will help to establish the feasibility of lunar base construction using indigenous materials. Future work will refine the steps of the processing method. Specific areas where more information is needed are: furnace characteristics in vacuum; heat transfer during liquification; viscosity, pouring and forming behavior of molten regolith; design of high temperature forms; heat transfer during cooling; recrystallization of basalt; and refinement of estimates of elastic moduli, compressive and tensile strength, thermal expansion coefficient, thermal conductivity, and heat capacity. The preliminary design of the lunar shelter showed us that joining is a critical technology needed for building a structure from large segments. The problem of joining is important to the design of any structure that is not completely prefabricated. It is especially important when the structure is subjected to tensile loading by an internal pressure. For a lunar shelter constructed from large segments the joints between these large segments must be strong, and they must permit automated construction. With a cast basalt building material which is brittle, there is the additional problem of connecting the joint with the material and avoiding stress concentration that would cause failure. Thus, a well-defined project which we intend to pursue during this coming year is the design of joints for cast basalt structural elements.

PELEC

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-05-17

PeleC is an adaptive-mesh compressible hydrodynamics code for reacting flows. It solves the compressible Navier-Stokes with multispecies transport in a block structured framework. The resulting algorithm is well suited for flows with localized resolution requirements and robust to discontinuities. User controllable refinement crieteria has the potential to result in extremely small numerical dissipation and dispersion, making this code appropriate for both research and applied usage. The code is built on the AMReX library which facilitates hierarchical parallelism and manages distributed memory parallism. PeleC algorithms are implemented to express shared memory parallelism.

A comparison of choline:urea and choline:oxalic acid deep eutectic solvents at 338 K

NASA Astrophysics Data System (ADS)

Gilmore, Mark; Moura, Leila M.; Turner, Adam H.; Swadźba-Kwaśny, Małgorzata; Callear, Samantha K.; McCune, Jade A.; Scherman, Oren A.; Holbrey, John D.

2018-05-01

1:2 choline chloride:urea and 1:1 choline chloride:oxalic acid deep eutectic solvents are compared at 338 K using liquid-phase neutron diffraction with H/D isotopic substitution to obtain differential neutron scattering cross sections and fitting of models to the experimental data using Empirical Potential Structure Refinement. In comparison to the previously reported study of choline chloride:urea at 303 K, we observed significant weakening and lengthening of choline-OH⋯Cl- and choline-OH⋯hydrogen-bond acceptor correlations.

The Development of a Communication Tool to Facilitate the Cancer Trial Recruitment Process and Increase Research Literacy among Underrepresented Populations.

PubMed

Torres, Samantha; de la Riva, Erika E; Tom, Laura S; Clayman, Marla L; Taylor, Chirisse; Dong, Xinqi; Simon, Melissa A

2015-12-01

Despite increasing need to boost the recruitment of underrepresented populations into cancer trials and biobanking research, few tools exist for facilitating dialogue between researchers and potential research participants during the recruitment process. In this paper, we describe the initial processes of a user-centered design cycle to develop a standardized research communication tool prototype for enhancing research literacy among individuals from underrepresented populations considering enrollment in cancer research and biobanking studies. We present qualitative feedback and recommendations on the prototype's design and content from potential end users: five clinical trial recruiters and ten potential research participants recruited from an academic medical center. Participants were given the prototype (a set of laminated cards) and were asked to provide feedback about the tool's content, design elements, and word choices during semi-structured, in-person interviews. Results suggest that the prototype was well received by recruiters and patients alike. They favored the simplicity, lay language, and layout of the cards. They also noted areas for improvement, leading to card refinements that included the following: addressing additional topic areas, clarifying research processes, increasing the number of diverse images, and using alternative word choices. Our process for refining user interfaces and iterating content in early phases of design may inform future efforts to develop tools for use in clinical research or biobanking studies to increase research literacy.

Mesh quality control for multiply-refined tetrahedral grids

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Strawn, Roger

1994-01-01

A new algorithm for controlling the quality of multiply-refined tetrahedral meshes is presented in this paper. The basic dynamic mesh adaption procedure allows localized grid refinement and coarsening to efficiently capture aerodynamic flow features in computational fluid dynamics problems; however, repeated application of the procedure may significantly deteriorate the quality of the mesh. Results presented show the effectiveness of this mesh quality algorithm and its potential in the area of helicopter aerodynamics and acoustics.

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

PubMed

Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

2015-10-01

The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

Quantitative Analysis of the Morphology of {101} and {001} Faceted Anatase TiO 2 Nanocrystals and Its Implication on Photocatalytic Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jue; Olds, Daniel; Peng, Rui

The atomistic structure and morphology (shape and size) of nanomaterials have strong influences on their physical and chemical properties. However, many characterization techniques focus exclusively on one length-scale regime or another when developing quantitative morphology/structural models. In this article, we demonstrate that powder X-ray diffraction and neutron pair distribution function (PDF) can be used to obtain accurate average morphology and atomistic structure of {001} and {101} faceted anatase TiO 2 nanocrystals based on differential evolution refinements using Debye scattering equation calculations. It is also demonstrated that the morphology polydispersity of TiO 2 nanocrystals can be effectively obtained from the diffractionmore » data via a numerical refinement routine. The morphology refinement results are in good agreement with those from transmission electron microscopy and the modeling of small angle neutron scattering data. This method is successfully used to quantify the facet-specified photocatalytic hydrogen evolution activity of anatase TiO 2 nanocrystals with different {001} to {101} ratios. It is found that the sample with an intermediate amount of both {001} and {101} facets shows the best photocatalytic hydrogen evolution reaction (HER) activity. It is expected that the simultaneous structure and morphology refinement technique can be generally used to study the relationship between morphology and functionality of nanomaterials.« less

Quantitative Analysis of the Morphology of {101} and {001} Faceted Anatase TiO 2 Nanocrystals and Its Implication on Photocatalytic Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jue; Olds, Daniel; Peng, Rui

The atomistic structure and morphology (shape and size) of nanomaterials have strong influences on their physical and chemical properties. However, many characterization techniques focus exclusively on one length-scale regime or another when developing quantitative morphology/structural models. In this article, we demonstrate that powder X-ray diffraction and neutron pair distribution function (PDF) can be used to obtain accurate average morphology and atomistic structure of {001} and {101} faceted anatase TiO 2 nanocrystals based on differential evolution refinements using Debye scattering equation calculations. It is also demonstrated that the morphology polydispersity of TiO 2 nanocrystals can be effectively obtained from the diffractionmore » data via a numerical refinement routine. The morphology refinement results are in good agreement with those from transmission electron microscopy and the modeling of small angle neutron scattering data. This method is successfully used to quantify the facet-specified photocatalytic hydrogen evolution activity of anatase TiO 2 nanocrystals with different {001} to {101} ratios. It is found that the sample with an intermediate amount of both {001} and {101} facets shows the best photocatalytic hydrogen evolution reaction (HER) activity. As a result, it is expected that the simultaneous structure and morphology refinement technique can be generally used to study the relationship between morphology and functionality of nanomaterials.« less

On the complexity of Engh and Huber refinement restraints: the angle τ as example

DOE Office of Scientific and Technical Information (OSTI.GOV)

Touw, Wouter G.; Vriend, Gert, E-mail: vriend@cmbi.ru.nl

2010-12-01

The angle τ (backbone N—C{sup α}—C) is the most contested Engh and Huber refinement target parameter. It is shown that this parameter is ‘correct’ as a PDB-wide average, but can be improved by taking into account residue types, secondary structures and many other aspects of our knowledge of the biophysical relations between residue type and protein structure. The Engh and Huber parameters for bond lengths and bond angles have been used uncontested in macromolecular structure refinement from 1991 until very recently, despite critical discussion of their ubiquitous validity by many authors. An extensive analysis of the backbone angle τ (N—C{supmore » α}—C) illustrates that the Engh and Huber parameters can indeed be improved and a recent study [Tronrud et al. (2010 ▶), Acta Cryst. D66, 834–842] confirms these ideas. However, the present study of τ shows that improving the Engh and Huber parameters will be considerably more complex than simply making the parameters a function of the backbone ϕ, ψ angles. Many other aspects, such as the cooperativity of hydrogen bonds, the bending of secondary-structure elements and a series of biophysical aspects of the 20 amino-acid types, will also need to be taken into account. Different sets of Engh and Huber parameters will be needed for conceptually different refinement programs.« less

Quantitative Analysis of the Morphology of {101} and {001} Faceted Anatase TiO 2 Nanocrystals and Its Implication on Photocatalytic Activity

DOE PAGES

Liu, Jue; Olds, Daniel; Peng, Rui; ...

2017-06-14

The atomistic structure and morphology (shape and size) of nanomaterials have strong influences on their physical and chemical properties. However, many characterization techniques focus exclusively on one length-scale regime or another when developing quantitative morphology/structural models. In this article, we demonstrate that powder X-ray diffraction and neutron pair distribution function (PDF) can be used to obtain accurate average morphology and atomistic structure of {001} and {101} faceted anatase TiO 2 nanocrystals based on differential evolution refinements using Debye scattering equation calculations. It is also demonstrated that the morphology polydispersity of TiO 2 nanocrystals can be effectively obtained from the diffractionmore » data via a numerical refinement routine. The morphology refinement results are in good agreement with those from transmission electron microscopy and the modeling of small angle neutron scattering data. This method is successfully used to quantify the facet-specified photocatalytic hydrogen evolution activity of anatase TiO 2 nanocrystals with different {001} to {101} ratios. It is found that the sample with an intermediate amount of both {001} and {101} facets shows the best photocatalytic hydrogen evolution reaction (HER) activity. As a result, it is expected that the simultaneous structure and morphology refinement technique can be generally used to study the relationship between morphology and functionality of nanomaterials.« less

Post-treatment mechanical refining as a method to improve overall sugar recovery of steam pretreated hybrid poplar.

PubMed

Dou, Chang; Ewanick, Shannon; Bura, Renata; Gustafson, Rick

2016-05-01

This study investigates the effect of mechanical refining to improve the sugar yield from biomass processed under a wide range of steam pretreatment conditions. Hybrid poplar chips were steam pretreated using six different conditions with or without SO2. The resulting water insoluble fractions were subjected to mechanical refining. After refining, poplar pretreated at 205°C for 10min without SO2 obtained a 32% improvement in enzymatic hydrolysis and achieved similar overall monomeric sugar recovery (539kg/tonne) to samples pretreated with SO2. Refining did not improve hydrolyzability of samples pretreated at more severe conditions, nor did it improve the overall sugar recovery. By maximizing overall sugar recovery, refining could partially decouple the pretreatment from other unit operations, and enable the use of low temperature, non-sulfur pretreatment conditions. The study demonstrates the possibility of using post-treatment refining to accommodate potential pretreatment process upsets without sacrificing sugar yields. Copyright © 2016 Elsevier Ltd. All rights reserved.

Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design.

PubMed

Krajewski, Wojciech W; Collins, Ruairi; Holmberg-Schiavone, Lovisa; Jones, T Alwyn; Karlberg, Tobias; Mowbray, Sherry L

2008-01-04

Glutamine synthetase (GS) catalyzes the ligation of glutamate and ammonia to form glutamine, with concomitant hydrolysis of ATP. In mammals, the activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine; there are a number of links between changes in GS activity and neurodegenerative disorders, such as Alzheimer's disease. In plants, because of its importance in the assimilation and re-assimilation of ammonia, the enzyme is a target of some herbicides. GS is also a central component of bacterial nitrogen metabolism and a potential drug target. Previous studies had investigated the structures of bacterial and plant GSs. In the present publication, we report the first structures of mammalian GSs. The apo form of the canine enzyme was solved by molecular replacement and refined at a resolution of 3 A. Two structures of human glutamine synthetase represent complexes with: a) phosphate, ADP, and manganese, and b) a phosphorylated form of the inhibitor methionine sulfoximine, ADP and manganese; these structures were refined to resolutions of 2.05 A and 2.6 A, respectively. Loop movements near the active site generate more closed forms of the eukaryotic enzymes when substrates are bound; the largest changes are associated with the binding of the nucleotide. Comparisons with earlier structures provide a basis for the design of drugs that are specifically directed at either human or bacterial enzymes. The site of binding the amino acid substrate is highly conserved in bacterial and eukaryotic GSs, whereas the nucleotide binding site varies to a much larger degree. Thus, the latter site offers the best target for specific drug design. Differences between mammalian and plant enzymes are much more subtle, suggesting that herbicides targeting GS must be designed with caution.

Total antioxidant content of alternatives to refined sugar.

PubMed

Phillips, Katherine M; Carlsen, Monica H; Blomhoff, Rune

2009-01-01

Oxidative damage is implicated in the etiology of cancer, cardiovascular disease, and other degenerative disorders. Recent nutritional research has focused on the antioxidant potential of foods, while current dietary recommendations are to increase the intake of antioxidant-rich foods rather than supplement specific nutrients. Many alternatives to refined sugar are available, including raw cane sugar, plant saps/syrups (eg, maple syrup, agave nectar), molasses, honey, and fruit sugars (eg, date sugar). Unrefined sweeteners were hypothesized to contain higher levels of antioxidants, similar to the contrast between whole and refined grain products. To compare the total antioxidant content of natural sweeteners as alternatives to refined sugar. The ferric-reducing ability of plasma (FRAP) assay was used to estimate total antioxidant capacity. Major brands of 12 types of sweeteners as well as refined white sugar and corn syrup were sampled from retail outlets in the United States. Substantial differences in total antioxidant content of different sweeteners were found. Refined sugar, corn syrup, and agave nectar contained minimal antioxidant activity (<0.01 mmol FRAP/100 g); raw cane sugar had a higher FRAP (0.1 mmol/100 g). Dark and blackstrap molasses had the highest FRAP (4.6 to 4.9 mmol/100 g), while maple syrup, brown sugar, and honey showed intermediate antioxidant capacity (0.2 to 0.7 mmol FRAP/100 g). Based on an average intake of 130 g/day refined sugars and the antioxidant activity measured in typical diets, substituting alternative sweeteners could increase antioxidant intake an average of 2.6 mmol/day, similar to the amount found in a serving of berries or nuts. Many readily available alternatives to refined sugar offer the potential benefit of antioxidant activity.

Refined carbohydrate intake in relation to non-verbal intelligence among Tehrani schoolchildren.

PubMed

Abargouei, Amin Salehi; Kalantari, Naser; Omidvar, Nasrin; Rashidkhani, Bahram; Rad, Anahita Houshiar; Ebrahimi, Azizeh Afkham; Khosravi-Boroujeni, Hossein; Esmaillzadeh, Ahmad

2012-10-01

Nutrition has long been considered one of the most important environmental factors affecting human intelligence. Although carbohydrates are the most widely studied nutrient for their possible effects on cognition, limited data are available linking usual refined carbohydrate intake and intelligence. The present study was conducted to examine the relationship between long-term refined carbohydrate intake and non-verbal intelligence among schoolchildren. Cross-sectional study. Tehran, Iran. In this cross-sectional study, 245 students aged 6-7 years were selected from 129 elementary schools in two western regions of Tehran. Anthropometric measurements were carried out. Non-verbal intelligence and refined carbohydrate consumption were determined using Raven's Standard Progressive Matrices test and a modified sixty-seven-item FFQ, respectively. Data about potential confounding variables were collected. Linear regression analysis was applied to examine the relationship between non-verbal intelligence scores and refined carbohydrate consumption. Individuals in top tertile of refined carbohydrate intake had lower mean non-verbal intelligence scores in the crude model (P < 0.038). This association remained significant after controlling for age, gender, birth date, birth order and breast-feeding pattern (P = 0.045). However, further adjustments for mother's age, mother's education, father's education, parental occupation and BMI made the association statistically non-significant. We found a significant inverse association between refined carbohydrate consumption and non-verbal intelligence scores in regression models (β = -11.359, P < 0.001). This relationship remained significant in multivariate analysis after controlling for potential confounders (β = -8.495, P = 0.038). The study provides evidence indicating an inverse relationship between refined carbohydrate consumption and non-verbal intelligence among Tehrani children aged 6-7 years. Prospective studies are needed to confirm our findings.

Incremental triangulation by way of edge swapping and local optimization

NASA Technical Reports Server (NTRS)

Wiltberger, N. Lyn

1994-01-01

This document is intended to serve as an installation, usage, and basic theory guide for the two dimensional triangulation software 'HARLEY' written for the Silicon Graphics IRIS workstation. This code consists of an incremental triangulation algorithm based on point insertion and local edge swapping. Using this basic strategy, several types of triangulations can be produced depending on user selected options. For example, local edge swapping criteria can be chosen which minimizes the maximum interior angle (a MinMax triangulation) or which maximizes the minimum interior angle (a MaxMin or Delaunay triangulation). It should be noted that the MinMax triangulation is generally only locally optical (not globally optimal) in this measure. The MaxMin triangulation, however, is both locally and globally optical. In addition, Steiner triangulations can be constructed by inserting new sites at triangle circumcenters followed by edge swapping based on the MaxMin criteria. Incremental insertion of sites also provides flexibility in choosing cell refinement criteria. A dynamic heap structure has been implemented in the code so that once a refinement measure is specified (i.e., maximum aspect ratio or some measure of a solution gradient for the solution adaptive grid generation) the cell with the largest value of this measure is continually removed from the top of the heap and refined. The heap refinement strategy allows the user to specify either the number of cells desired or refine the mesh until all cell refinement measures satisfy a user specified tolerance level. Since the dynamic heap structure is constantly updated, the algorithm always refines the particular cell in the mesh with the largest refinement criteria value. The code allows the user to: triangulate a cloud of prespecified points (sites), triangulate a set of prespecified interior points constrained by prespecified boundary curve(s), Steiner triangulate the interior/exterior of prespecified boundary curve(s), refine existing triangulations based on solution error measures, and partition meshes based on the Cuthill-McKee, spectral, and coordinate bisection strategies.

Role of DNA secondary structures in fragile site breakage along human chromosome 10

PubMed Central

Dillon, Laura W.; Pierce, Levi C. T.; Ng, Maggie C. Y.; Wang, Yuh-Hwa

2013-01-01

The formation of alternative DNA secondary structures can result in DNA breakage leading to cancer and other diseases. Chromosomal fragile sites, which are regions of the genome that exhibit chromosomal breakage under conditions of mild replication stress, are predicted to form stable DNA secondary structures. DNA breakage at fragile sites is associated with regions that are deleted, amplified or rearranged in cancer. Despite the correlation, unbiased examination of the ability to form secondary structures has not been evaluated in fragile sites. Here, using the Mfold program, we predict potential DNA secondary structure formation on the human chromosome 10 sequence, and utilize this analysis to compare fragile and non-fragile DNA. We found that aphidicolin (APH)-induced common fragile sites contain more sequence segments with potential high secondary structure-forming ability, and these segments clustered more densely than those in non-fragile DNA. Additionally, using a threshold of secondary structure-forming ability, we refined legitimate fragile sites within the cytogenetically defined boundaries, and identified potential fragile regions within non-fragile DNA. In vitro detection of alternative DNA structure formation and a DNA breakage cell assay were used to validate the computational predictions. Many of the regions identified by our analysis coincide with genes mutated in various diseases and regions of copy number alteration in cancer. This study supports the role of DNA secondary structures in common fragile site instability, provides a systematic method for their identification and suggests a mechanism by which DNA secondary structures can lead to human disease. PMID:23297364

Kinetic Behavior and Microstructure of Pearlite Isothermal Transformation Under High Undercooling

NASA Astrophysics Data System (ADS)

Liang, Yu; Xu, Pingwei; Xiang, Song; Liang, Yilong; Xiong, Hu; Li, Jing

2018-06-01

The kinetic behavior of highly undercooled austenite and its effects on the microstructural evolution and mechanical properties of high-carbon steel are studied. The undercooling degree is increased through a temporary undercooling treatment at the bainite transformation temperature of 380 °C to 450 °C before the pearlite isothermal transformation at 500 °C to 620 °C. The transformation kinetics reveals an increased nose temperature and a rightward shift of the transformation curve under high undercooling conditions. In addition, the undercooling treatment leads to an increased driving force during pearlite transformation, which is responsible for the refined hierarchical structures of pearlite. As a result, a 20 to 40 pct size reduction is achieved for pearlite colonies and lamellae. Such refinement is in turn attributed to an 26 pct increase in reduction in area. This work provides both a new understanding of high-performance fully pearlitic steels for practical applications and new perspectives for potential technological applications in drawing processes for hypoeutectoid steels.

Chain conformations and phase behavior of conjugated polymers.

PubMed

Kuei, Brooke; Gomez, Enrique D

2016-12-21

Conjugated polymers may play an important role in various emerging optoelectronic applications because they combine the chemical versatility of organic molecules and the flexibility, stretchability and toughness of polymers with semiconducting properties. Nevertheless, in order to achieve the full potential of conjugated polymers, a clear description of how their structure, morphology, and macroscopic properties are interrelated is needed. We propose that the starting point for understanding conjugated polymers includes understanding chain conformations and phase behavior. Efforts to predict and measure the persistence length have significantly refined our intuition of the chain stiffness, and have led to predictions of nematic-to-isotropic transitions. Exploring mixing between conjugated polymers and small molecules or other polymers has demonstrated tremendous advancements in attaining the needed properties for various optoelectronic devices. Current efforts continue to refine our knowledge of chain conformations and phase behavior and the factors that influence these properties, thereby providing opportunities for the development of novel optoelectronic materials based on conjugated polymers.

Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals

DOE PAGES

Uervirojnangkoorn, Monarin; Zeldin, Oliver B.; Lyubimov, Artem Y.; ...

2015-03-17

There is considerable potential for X-ray free electron lasers (XFELs) to enable determination of macromolecular crystal structures that are difficult to solve using current synchrotron sources. Prior XFEL studies often involved the collection of thousands to millions of diffraction images, in part due to limitations of data processing methods. We implemented a data processing system based on classical post-refinement techniques, adapted to specific properties of XFEL diffraction data. When applied to XFEL data from three different proteins collected using various sample delivery systems and XFEL beam parameters, our method improved the quality of the diffraction data as well as themore » resulting refined atomic models and electron density maps. Moreover, the number of observations for a reflection necessary to assemble an accurate data set could be reduced to a few observations. In conclusion, these developments will help expand the applicability of XFEL crystallography to challenging biological systems, including cases where sample is limited.« less

Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals

DOE PAGES

Uervirojnangkoorn, Monarin; Zeldin, Oliver B.; Lyubimov, Artem Y.; ...

2015-03-17

There is considerable potential for X-ray free electron lasers (XFELs) to enable determination of macromolecular crystal structures that are difficult to solve using current synchrotron sources. Prior XFEL studies often involved the collection of thousands to millions of diffraction images, in part due to limitations of data processing methods. We implemented a data processing system based on classical post-refinement techniques, adapted to specific properties of XFEL diffraction data. When applied to XFEL data from three different proteins collected using various sample delivery systems and XFEL beam parameters, our method improved the quality of the diffraction data as well as themore » resulting refined atomic models and electron density maps. Moreover, the number of observations for a reflection necessary to assemble an accurate data set could be reduced to a few observations. These developments will help expand the applicability of XFEL crystallography to challenging biological systems, including cases where sample is limited.« less

Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals

PubMed Central

Uervirojnangkoorn, Monarin; Zeldin, Oliver B; Lyubimov, Artem Y; Hattne, Johan; Brewster, Aaron S; Sauter, Nicholas K; Brunger, Axel T; Weis, William I

2015-01-01

There is considerable potential for X-ray free electron lasers (XFELs) to enable determination of macromolecular crystal structures that are difficult to solve using current synchrotron sources. Prior XFEL studies often involved the collection of thousands to millions of diffraction images, in part due to limitations of data processing methods. We implemented a data processing system based on classical post-refinement techniques, adapted to specific properties of XFEL diffraction data. When applied to XFEL data from three different proteins collected using various sample delivery systems and XFEL beam parameters, our method improved the quality of the diffraction data as well as the resulting refined atomic models and electron density maps. Moreover, the number of observations for a reflection necessary to assemble an accurate data set could be reduced to a few observations. These developments will help expand the applicability of XFEL crystallography to challenging biological systems, including cases where sample is limited. DOI: http://dx.doi.org/10.7554/eLife.05421.001 PMID:25781634

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity

PubMed Central

Bennett, James E. M.; Bair, Wyeth

2015-01-01

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli. PMID:26308406

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity.

PubMed

Bennett, James E M; Bair, Wyeth

2015-08-01

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli.

Calcio-olivine γ-Ca2SiO4: I. Rietveld refinement of the crystal structure

NASA Astrophysics Data System (ADS)

Gobechiya, E. R.; Yamnova, N. A.; Zadov, A. E.; Gazeev, V. M.

2008-05-01

The structure of the natural mineral calcio-olivine (γ-Ca2SiO4) found in skarn xenoliths in the region of the Lakargi Mountain (North Caucasus, Kabardino-Balkaria, Russia) is refined by the Rietveld method [ a = 5.07389(7) Å, b = 11.21128(14) Å, c = 6.75340(9) Å, V = 384.170(5) Å3, Z = 4, ρcalcd = 2.98 g/cm3, space group Pbnm]. The X-ray diffraction pattern of a powdered sample is recorded on a STOE STADI MP diffractometer [λCu K α1; Ge(111) primary monochromator; 6.00° < 2θ < 100.88°; step width, 2.5° in 2θ; number of reflections, 224]. All calculations are performed with the WYRIET (version 3.3) software package. The structural model is refined in the anisotropic approximation to R p = 6.44, R wp = 8.52, R exp = 5.85, R B = 4.98, R F = 6.90, and s = 1.46. It is shown that the sample under investigation is a mixture of several mineral phases, among which calcio-olivine (the natural analogue of the γ-Ca2SiO4 compound) (83%), hillebrandite (13%), and wadalite (4%) are dominant. Only the scale factors and the unit cell parameters are refined for hillebrandite Ca2SiO3(OH)2 [ a = 3.63472(16) Å, b = 16.4140(10) Å, c = 11.7914(8) Å, space group Cmc21, Z = 6] and wadalite Ca6Al5Si2O16Cl3 ( a = 12.0088 Å, space group, I bar 4 3 d Z = 4). The results of the structure refinement of the main component of the sample confirm that the mineral calcio-olivine is isostructural to the synthetic compound γ-Ca2SiO4. The structure of this compound is formed by the heteropolyhedral framework composed of Ca octahedra joined together into olivine-like ribbons and isolated Si tetrahedra.

Weak data do not make a free lunch, only a cheap meal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Zhipu; Rajashankar, Kanagalaghatta; Dauter, Zbigniew, E-mail: dauter@anl.gov

2014-02-01

Refinement and analysis of four structures with various data resolution cutoffs suggests that at present there are no reliable criteria for judging the diffraction data resolution limit and the condition I/σ(I) = 2.0 is reasonable. However, extending the limit by about 0.2 Å beyond the resolution defined by this threshold does not deteriorate the quality of refined structures and in some cases may be beneficial. Four data sets were processed at resolutions significantly exceeding the criteria traditionally used for estimating the diffraction data resolution limit. The analysis of these data and the corresponding model-quality indicators suggests that the criteria ofmore » resolution limits widely adopted in the past may be somewhat conservative. Various parameters, such as R{sub merge} and I/σ(I), optical resolution and the correlation coefficients CC{sub 1/2} and CC*, can be used for judging the internal data quality, whereas the reliability factors R and R{sub free} as well as the maximum-likelihood target values and real-space map correlation coefficients can be used to estimate the agreement between the data and the refined model. However, none of these criteria provide a reliable estimate of the data resolution cutoff limit. The analysis suggests that extension of the maximum resolution by about 0.2 Å beyond the currently adopted limit where the I/σ(I) value drops to 2.0 does not degrade the quality of the refined structural models, but may sometimes be advantageous. Such an extension may be particularly beneficial for significantly anisotropic diffraction. Extension of the maximum resolution at the stage of data collection and structure refinement is cheap in terms of the required effort and is definitely more advisable than accepting a too conservative resolution cutoff, which is unfortunately quite frequent among the crystal structures deposited in the Protein Data Bank.« less

A Variable Resolution Atmospheric General Circulation Model for a Megasite at the North Slope of Alaska

NASA Astrophysics Data System (ADS)

Dennis, L.; Roesler, E. L.; Guba, O.; Hillman, B. R.; McChesney, M.

2016-12-01

The Atmospheric Radiation Measurement (ARM) climate research facility has three siteslocated on the North Slope of Alaska (NSA): Barrrow, Oliktok, and Atqasuk. These sites, incombination with one other at Toolik Lake, have the potential to become a "megasite" whichwould combine observational data and high resolution modeling to produce high resolutiondata products for the climate community. Such a data product requires high resolutionmodeling over the area of the megasite. We present three variable resolution atmosphericgeneral circulation model (AGCM) configurations as potential alternatives to stand-alonehigh-resolution regional models. Each configuration is based on a global cubed-sphere gridwith effective resolution of 1 degree, with a refinement in resolution down to 1/8 degree overan area surrounding the ARM megasite. The three grids vary in the size of the refined areawith 13k, 9k, and 7k elements. SquadGen, NCL, and GIMP are used to create the grids.Grids vary based upon the selection of areas of refinement which capture climate andweather processes that may affect a proposed NSA megasite. A smaller area of highresolution may not fully resolve climate and weather processes before they reach the NSA,however grids with smaller areas of refinement have a significantly reduced computationalcost compared with grids with larger areas of refinement. Optimal size and shape of thearea of refinement for a variable resolution model at the NSA is investigated.

Modelling dynamics in protein crystal structures by ensemble refinement

PubMed Central

Burnley, B Tom; Afonine, Pavel V; Adams, Paul D; Gros, Piet

2012-01-01

Single-structure models derived from X-ray data do not adequately account for the inherent, functionally important dynamics of protein molecules. We generated ensembles of structures by time-averaged refinement, where local molecular vibrations were sampled by molecular-dynamics (MD) simulation whilst global disorder was partitioned into an underlying overall translation–libration–screw (TLS) model. Modeling of 20 protein datasets at 1.1–3.1 Å resolution reduced cross-validated Rfree values by 0.3–4.9%, indicating that ensemble models fit the X-ray data better than single structures. The ensembles revealed that, while most proteins display a well-ordered core, some proteins exhibit a ‘molten core’ likely supporting functionally important dynamics in ligand binding, enzyme activity and protomer assembly. Order–disorder changes in HIV protease indicate a mechanism of entropy compensation for ordering the catalytic residues upon ligand binding by disordering specific core residues. Thus, ensemble refinement extracts dynamical details from the X-ray data that allow a more comprehensive understanding of structure–dynamics–function relationships. DOI: http://dx.doi.org/10.7554/eLife.00311.001 PMID:23251785

Protein homology model refinement by large-scale energy optimization.

PubMed

Park, Hahnbeom; Ovchinnikov, Sergey; Kim, David E; DiMaio, Frank; Baker, David

2018-03-20

Proteins fold to their lowest free-energy structures, and hence the most straightforward way to increase the accuracy of a partially incorrect protein structure model is to search for the lowest-energy nearby structure. This direct approach has met with little success for two reasons: first, energy function inaccuracies can lead to false energy minima, resulting in model degradation rather than improvement; and second, even with an accurate energy function, the search problem is formidable because the energy only drops considerably in the immediate vicinity of the global minimum, and there are a very large number of degrees of freedom. Here we describe a large-scale energy optimization-based refinement method that incorporates advances in both search and energy function accuracy that can substantially improve the accuracy of low-resolution homology models. The method refined low-resolution homology models into correct folds for 50 of 84 diverse protein families and generated improved models in recent blind structure prediction experiments. Analyses of the basis for these improvements reveal contributions from both the improvements in conformational sampling techniques and the energy function.

Rietveld refinement of the crystal structures of Rb2 XSi5O12 (X = Ni, Mn).

PubMed

Bell, Anthony M T; Henderson, C Michael B

2016-02-01

The synthetic leucite silicate framework mineral analogues Rb2 XSi5O12 {X = Ni [dirubidium nickel(II) penta-silicate] and Mn [dirubidium manganese(II) penta-silicate]} have been prepared by high-temperature solid-state synthesis. The results of Rietveld refinements, using X-ray powder diffraction data collected using Cu Kα X-rays, show that the title compounds crystallize in the space group Pbca and adopt the cation-ordered structure of Cs2CdSi5O12 and other leucites. The structures consist of tetra-hedral SiO4 and XO4 units sharing corners to form a partially substituted silicate framework. Extraframework Rb(+) cations sit in channels in the framework. All atoms occupy the 8c general position for this space group. In these refined structures, silicon and X atoms are ordered onto separate tetra-hedrally coordinated sites (T-sites). However, the Ni displacement parameter and the Ni-O bond lengths suggest that for the X = Ni sample, there may actually be some T-site cation disorder.

Rietveld refinement of the crystal structures of Rb2 XSi5O12 (X = Ni, Mn)

PubMed Central

Bell, Anthony M. T.; Henderson, C. Michael B.

2016-01-01

The synthetic leucite silicate framework mineral analogues Rb2 XSi5O12 {X = Ni [dirubidium nickel(II) penta­silicate] and Mn [dirubidium manganese(II) penta­silicate]} have been prepared by high-temperature solid-state synthesis. The results of Rietveld refinements, using X-ray powder diffraction data collected using Cu Kα X-rays, show that the title compounds crystallize in the space group Pbca and adopt the cation-ordered structure of Cs2CdSi5O12 and other leucites. The structures consist of tetra­hedral SiO4 and XO4 units sharing corners to form a partially substituted silicate framework. Extraframework Rb+ cations sit in channels in the framework. All atoms occupy the 8c general position for this space group. In these refined structures, silicon and X atoms are ordered onto separate tetra­hedrally coordinated sites (T-sites). However, the Ni displacement parameter and the Ni—O bond lengths suggest that for the X = Ni sample, there may actually be some T-site cation disorder. PMID:26958399

Fine refinement of solid-state molecular structures of Leu- and Met-enkephalins by NMR crystallography.

PubMed

Pawlak, Tomasz; Potrzebowski, Marek J

2014-03-27

This paper presents a methodology that allows the fine refinement of the crystal and molecular structure for compounds for which the data deposited in the crystallographic bases are of poor quality. Such species belong to the group of samples with molecular disorder. In the Cambridge Crystallographic Data Center (CCDC), there are approximately 22,000 deposited structures with an R-factor over 10. The powerful methodology we present employs crystal data for Leu-enkephalin (two crystallographic forms) with R-factor values of 14.0 and 8.9 and for Met-enkephalin (one form) with an R-factor of 10.5. NMR crystallography was employed in testing the X-ray data and the quality of the structure refinement. The GIPAW (gauge invariant projector augmented wave) method was used to optimize the coordinates of the enkephalins and to compute NMR parameters. As we reveal, this complementary approach makes it possible to generate a reasonable set of new coordinates that better correlate to real samples. This methodology is general and can be employed in the study of each compound possessing magnetically active nuclei.

Crystal structure of the heptamolybdate(VI) (paramolybdate) ion, [Mo7O24]6-, in the ammonium and potassium tetrahydrate salts

USGS Publications Warehouse

Evans, H.T.; Gatehouse, B.M.; Leverett, P.

1975-01-01

The crystal structures of the isomorphous salts MI6 [Mo7O24],4H2O (M = NH4 or K) have been refined by three-dimensional X-ray diffraction methods. Unit cell dimensions of these monoclinic compounds, space group P21/C with Z = 4, are, ammonium salt: a = 8.3934 ?? 0.0008, b = 36.1703 ?? 0.0045, c = 10.4715 ?? 0.0011 A??, ?? = 115.958?? ?? 0.008??; and potassium salt: a = 8.15 ?? 0.02, b = 35.68 ?? 0.1, c = 10.30 ?? 0.02 A??, ?? = 115.2?? ?? 02??. By use of multiple Weissenberg patterns, 8197 intensity data (Mo-K?? radiation) for the ammonium compound and 2178 (Cu-K?? radiation) for the potassium compound were estimated visually and used to test and refine Lindqvist's proposed structure in the space group P21/c. Lindqvist's structure was confirmed and the full matrix least-squares isotropic refinement led to R 0.076 (ammonium) 0.120 (potassium), with direct unambiguous location of the cations and water molecules in the potassium compound.

AssignFit: a program for simultaneous assignment and structure refinement from solid-state NMR spectra

PubMed Central

Tian, Ye; Schwieters, Charles D.; Opella, Stanley J.; Marassi, Francesca M.

2011-01-01

AssignFit is a computer program developed within the XPLOR-NIH package for the assignment of dipolar coupling (DC) and chemical shift anisotropy (CSA) restraints derived from the solid-state NMR spectra of protein samples with uniaxial order. The method is based on minimizing the difference between experimentally observed solid-state NMR spectra and the frequencies back calculated from a structural model. Starting with a structural model and a set of DC and CSA restraints grouped only by amino acid type, as would be obtained by selective isotopic labeling, AssignFit generates all of the possible assignment permutations and calculates the corresponding atomic coordinates oriented in the alignment frame, together with the associated set of NMR frequencies, which are then compared with the experimental data for best fit. Incorporation of AssignFit in a simulated annealing refinement cycle provides an approach for simultaneous assignment and structure refinement (SASR) of proteins from solid-state NMR orientation restraints. The methods are demonstrated with data from two integral membrane proteins, one α-helical and one β-barrel, embedded in phospholipid bilayer membranes. PMID:22036904

Construction of a 3D model of nattokinase, a novel fibrinolytic enzyme from Bacillus natto. A novel nucleophilic catalytic mechanism for nattokinase.

PubMed

Zheng, Zhong-liang; Zuo, Zhen-yu; Liu, Zhi-gang; Tsai, Keng-chang; Liu, Ai-fu; Zou, Guo-lin

2005-01-01

A three-dimensional structural model of nattokinase (NK) from Bacillus natto was constructed by homology modeling. High-resolution X-ray structures of Subtilisin BPN' (SB), Subtilisin Carlsberg (SC), Subtilisin E (SE) and Subtilisin Savinase (SS), four proteins with sequential, structural and functional homology were used as templates. Initial models of NK were built by MODELLER and analyzed by the PROCHECK programs. The best quality model was chosen for further refinement by constrained molecular dynamics simulations. The overall quality of the refined model was evaluated. The refined model NKC1 was analyzed by different protein analysis programs including PROCHECK for the evaluation of Ramachandran plot quality, PROSA for testing interaction energies and WHATIF for the calculation of packing quality. This structure was found to be satisfactory and also stable at room temperature as demonstrated by a 300ps long unconstrained molecular dynamics (MD) simulation. Further docking analysis promoted the coming of a new nucleophilic catalytic mechanism for NK, which is induced by attacking of hydroxyl rich in catalytic environment and locating of S221.

Collection of X-ray diffraction data from macromolecular crystals

PubMed Central

Dauter, Zbigniew

2017-01-01

Diffraction data acquisition is the final experimental stage of the crystal structure analysis. All subsequent steps involve mainly computer calculations. Optimally measured and accurate data make the structure solution and refinement easier and lead to more faithful interpretation of the final models. Here, the important factors in data collection from macromolecular crystals are discussed and strategies appropriate for various applications, such as molecular replacement, anomalous phasing, atomic-resolution refinement etc., are presented. Criteria useful for judging the diffraction data quality are also discussed. PMID:28573573

The Grain Structure of Castings: Some Aspects of Modelling

NASA Technical Reports Server (NTRS)

Hellawell, A.

1995-01-01

The efficacy of the modelling of the solidification of castings is typically tested against observed cooling curves and the final grain structures and sizes. Without thermo solutal convection, equiaxed grain formation is promoted by introduction of heterogeneous substrates into the melt, as grain refiners. With efficient thermo solutal convection, dendrite fragments from the mushy zone can act as an intrinsic source of equiaxed grains and resort to grain refining additions is unnecessary. The mechanisms of dendrite fragmentation and transport of these fragments are briefly considered.

Refinement of the crystal structures of biomimetic weddellites produced by microscopic fungus Aspergillus niger

NASA Astrophysics Data System (ADS)

Rusakov, A. V.; Frank-Kamenetskaya, O. V.; Gurzhiy, V. V.; Zelenskaya, M. S.; Izatulina, A. R.; Sazanova, K. V.

2014-05-01

The single-crystal structures of four biomimetic weddellites CaC2O4 · (2 + x)H2O with different contents of zeolitic water ( x = 0.10-0.24 formula units) produced by the microscopic fungus Aspergillus niger were refined from X-ray diffraction data ( R = 0.029-0.038). The effect of zeolitic water content on the structural stability of weddellite was analyzed. The parameter a was shown to increase with increasing x due to the increase in the distance between water molecules along this direction. The water content and structural parameters of the synthesized weddellites are similar to those of weddellites from biofilms and kidney stones.

Using Powder Cored Tubular Wire Technology to Enhance Electron Beam Freeform Fabricated Structures

NASA Technical Reports Server (NTRS)

Gonzales, Devon; Liu, Stephen; Domack, Marcia; Hafley, Robert

2016-01-01

Electron Beam Freeform Fabrication (EBF3) is an additive manufacturing technique, developed at NASA Langley Research Center, capable of fabricating large scale aerospace parts. Advantages of using EBF3 as opposed to conventional manufacturing methods include, decreased design-to-product time, decreased wasted material, and the ability to adapt controls to produce geometrically complex parts with properties comparable to wrought products. However, to fully exploit the potential of the EBF3 process development of materials tailored for the process is required. Powder cored tubular wire (PCTW) technology was used to modify Ti-6Al-4V and Al 6061 feedstock to enhance alloy content, refine grain size, and create a metal matrix composite in the as-solidified structures, respectively.

Hydration of Caffeine at High Temperature by Neutron Scattering and Simulation Studies.

PubMed

Tavagnacco, L; Brady, J W; Bruni, F; Callear, S; Ricci, M A; Saboungi, M L; Cesàro, A

2015-10-22

The solvation of caffeine in water is examined with neutron diffraction experiments at 353 K. The experimental data, obtained by taking advantage of isotopic H/D substitution in water, were analyzed by empirical potential structure refinement (EPSR) in order to extract partial structure factors and site-site radial distribution functions. In parallel, molecular dynamics (MD) simulations were carried out to interpret the data and gain insight into the intermolecular interactions in the solutions and the solvation process. The results obtained with the two approaches evidence differences in the individual radial distribution functions, although both confirm the presence of caffeine stacks at this temperature. The two approaches point to different accessibility of water to the caffeine sites due to different stacking configurations.

Self-disturbance and schizophrenia: structure, specificity, pathogenesis (Current issues, New directions).

PubMed

Sass, Louis A

2014-01-01

This paper offers an overview and clarification of the ipseity-disturbance or self-disorder hypothesis regarding schizophrenia, with focus on some recent and recommended research and theoretical refinements. There is need to expand research and theorizing in several directions-in order to: 1, specify more precisely what is truly distinctive in the schizophrenia spectrum, 2, explore internal structure and explanatory potential of this purported disturbance of minimal- or core-self experience, 3, generate testable hypotheses concerning pathogenetic pathways and psychotherapeutic interventions. Comparative studies can make a crucial scientific contribution. Some recent, exploratory studies are described: published reports were examined for alterations of self-experience in conditions outside the schizophrenia spectrum-mania, psychotic depression, and depersonalization disorder-and in one unusual attitudinal stance: intense introspection (as refined in early 20th century psychological research). Remarkable similarities (e.g., alienation/reification of thoughts and bodily experiences, fading of self and world) as well as some important differences (e.g., absence, outside schizophrenia, of severe erosion of minimal self-experience or real confusion of self and other) in types of self-anomalies were found. These support but also refine the ipseity-disturbance model. Future research should treat self-experience as an independent variable, manipulating and measuring this dimension (in both schizophrenic and non-schizophrenic populations) to study its associations with anomalies of cognition, affect, expression, and neural functioning already identified in schizophrenia. The self-disorder model offers an integrative and dynamic view of schizophrenia congruent with recent trends in cognitive neuroscience and consistent with the heterogeneous, varying, and holistic nature of this enigmatic illness. Copyright © 2013. Published by Elsevier B.V.

Summary of Data from the Fifth AIAA CFD Drag Prediction Workshop

NASA Technical Reports Server (NTRS)

Levy, David W.; Laflin, Kelly R.; Tinoco, Edward N.; Vassberg, John C.; Mani, Mori; Rider, Ben; Rumsey, Chris; Wahls, Richard A.; Morrison, Joseph H.; Brodersen, Olaf P.;

Ab initio structure determination and refinement of a scorpion protein toxin.

PubMed

Smith, G D; Blessing, R H; Ealick, S E; Fontecilla-Camps, J C; Hauptman, H A; Housset, D; Langs, D A; Miller, R

1997-09-01

The structure of toxin II from the scorpion Androctonus australis Hector has been determined ab initio by direct methods using SnB at 0.96 A resolution. For the purpose of this structure redetermination, undertaken as a test of the minimal function and the SnB program, the identity and sequence of the protein was withheld from part of the research team. A single solution obtained from 1 619 random atom trials was clearly revealed by the bimodal distribution of the final value of the minimal function associated with each individual trial. Five peptide fragments were identified from a conservative analysis of the initial E-map, and following several refinement cycles with X-PLOR, a model was built of the complete structure. At the end of the X-PLOR refinement, the sequence was compared with the published sequence and 57 of the 64 residues had been correctly identified. Two errors in sequence resulted from side chains with similar size while the rest of the errors were a result of severe disorder or high thermal motion in the side chains. Given the amino-acid sequence, it is estimated that the initial E-map could have produced a model containing 99% of all main-chain and 81% of side-chain atoms. The structure refinement was completed with PROFFT, including the contributions of protein H atoms, and converged at a residual of 0.158 for 30 609 data with F >or= 2sigma(F) in the resolution range 8.0-0.964 A. The final model consisted of 518 non-H protein atoms (36 disordered), 407 H atoms, and 129 water molecules (43 with occupancies less than unity). This total of 647 non-H atoms represents the largest light-atom structure solved to date.

Structural convergence properties of amorphous InGaZnO4 from simulated liquid-quench methods.

PubMed

Buchanan, Jacob C; Fast, Dylan B; Hanken, Benjamin E; Mustard, Thomas J L; Laurita, Geneva; Chiang, Tsung-Han; Keszler, Douglas A; Subramanian, Mas A; Wager, John F; Dolgos, Michelle R; Rustad, James R; Cheong, Paul Ha-Yeon

2017-11-14

The study of structural properties of amorphous structures is complicated by the lack of long-range order and necessitates the use of both cutting-edge computer modeling and experimental techniques. With regards to the computer modeling, many questions on convergence arise when trying to assess the accuracy of a simulated system. What cell size maximizes the accuracy while remaining computationally efficient? More importantly, does averaging multiple smaller cells adequately describe features found in bulk amorphous materials? How small is too small? The aims of this work are: (1) to report a newly developed set of pair potentials for InGaZnO 4 and (2) to explore the effects of structural parameters such as simulation cell size and numbers on the structural convergence of amorphous InGaZnO 4 . The total number of formula units considered over all runs is found to be the critical factor in convergence as long as the cell considered contains a minimum of circa fifteen formula units. There is qualitative agreement between these simulations and X-ray total scattering data - peak trends and locations are consistently reproduced while intensities are weaker. These new IGZO pair potentials are a valuable starting point for future structural refinement efforts.

Satisfaction of the Automotive Fleet Fuel Demand and Its Impact on the Oil Refining Industry

DOT National Transportation Integrated Search

1980-12-01

Because virtually all transportation fuels are based on petroleum, it is essential to include petroleum refining in any assessment of potential changes in the transportation system. A number of changes in the automotive fleet have been proposed to im...

High Performance, Robust Control of Flexible Space Structures: MSFC Center Director's Discretionary Fund

NASA Technical Reports Server (NTRS)

Whorton, M. S.

1998-01-01

Many spacecraft systems have ambitious objectives that place stringent requirements on control systems. Achievable performance is often limited because of difficulty of obtaining accurate models for flexible space structures. To achieve sufficiently high performance to accomplish mission objectives may require the ability to refine the control design model based on closed-loop test data and tune the controller based on the refined model. A control system design procedure is developed based on mixed H2/H(infinity) optimization to synthesize a set of controllers explicitly trading between nominal performance and robust stability. A homotopy algorithm is presented which generates a trajectory of gains that may be implemented to determine maximum achievable performance for a given model error bound. Examples show that a better balance between robustness and performance is obtained using the mixed H2/H(infinity) design method than either H2 or mu-synthesis control design. A second contribution is a new procedure for closed-loop system identification which refines parameters of a control design model in a canonical realization. Examples demonstrate convergence of the parameter estimation and improved performance realized by using the refined model for controller redesign. These developments result in an effective mechanism for achieving high-performance control of flexible space structures.

TIMES-SS--recent refinements resulting from an industrial skin sensitisation consortium.

PubMed

Patlewicz, G; Kuseva, C; Mehmed, A; Popova, Y; Dimitrova, G; Ellis, G; Hunziker, R; Kern, P; Low, L; Ringeissen, S; Roberts, D W; Mekenyan, O

2014-01-01

The TImes MEtabolism Simulator platform for predicting Skin Sensitisation (TIMES-SS) is a hybrid expert system, first developed at Bourgas University using funding and data from a consortium of industry and regulators. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic 3D QSARs. The model estimates semi-quantitative skin sensitisation potency classes and has been developed with the aim of minimising animal testing, and also to be scientifically valid in accordance with the OECD principles for (Q)SAR validation. In 2007 an external validation exercise was undertaken to fully address these principles. In 2010, a new industry consortium was established to coordinate research efforts in three specific areas: refinement of abiotic reactions in the skin (namely autoxidation) in the skin, refinement of the manner in which chemical reactivity was captured in terms of structure-toxicity rules (inclusion of alert reliability parameters) and defining the domain based on the underlying experimental data (study of discrepancies between local lymph node assay Local Lymph Node Assay (LLNA) and Guinea Pig Maximisation Test (GPMT)). The present paper summarises the progress of these activities and explains how the insights derived have been translated into refinements, resulting in increased confidence and transparency in the robustness of the TIMES-SS predictions.

The Bi{sub 2}O{sub 3}–Fe{sub 2}O{sub 3}–Sb{sub 2}O{sub 5} system phase diagram refinement, Bi{sub 3}FeSb{sub 2}O{sub 11} structure peculiarities and magnetic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Egorysheva, A.V., E-mail: anna_egorysheva@rambler.ru; Ellert, O.G.; Gajtko, O.M.

2015-05-15

The refinement of the Bi{sub 2}O{sub 3}–Fe{sub 2}O{sub 3}–Sb{sub 2}O{sub 5} system phase diagram has been performed and the existence of the two ternary compounds has been confirmed. The first one with a pyrochlore-type structure (sp. gr. Fd 3-barm) exists in the wide solid solution region, (Bi{sub 2−x}Fe{sub x})Fe{sub 1+y}Sb{sub 1−y}O{sub 7±δ}, where x=0.1–0.4 and y=−0.13–0.11. The second one, Bi{sub 3}FeSb{sub 2}O{sub 11}, corresponds to the cubic KSbO{sub 3}-type structure (sp. gr. Pn 3-bar) with unit cell parameter a=9.51521(2) Å. The Rietveld structure refinement showed that this compound is characterized by disordered structure. The Bi{sub 3}FeSb{sub 2}O{sub 11} factor groupmore » analysis has been carried out and a Raman spectrum has been investigated. According to magnetization measurements performed at the temperature range 2–300 K it may be concluded that the Bi{sub 3}FeSb{sub 2}O{sub 11} magnetic properties can be substantially described as a superposition of strong short-range antiferromagnetic exchange interactions realizing inside the [(FeSb{sub 2})O{sub 9}] 3D-framework via different pathways. - Graphical abstract: The refinement of the Bi{sub 2}O{sub 3}–Fe{sub 2}O{sub 3}–Sb{sub 2}O{sub 5} system phase diagram has been performed and the existence of the solid solution with a pyrochlore-type structure (sp. gr. Fd 3-barm) and Bi{sub 3}FeSb{sub 2}O{sub 11}, correspond of the cubic KSbO{sub 3}-type structure (sp. gr. Pn 3-bar has been confirmed. The structure refinement, Raman spectroscopy as well as magnetic measurements data of Bi{sub 3}FeSb{sub 2}O{sub 11} are presented. - Highlights: • The Bi{sub 2}O{sub 3}–Fe{sub 2}O{sub 3}–Sb{sub 2}O{sub 5} system phase diagram refinement has been performed. • The Bi{sub 3}FeSb{sub 2}O{sub 11} existence along with pyrochlore structure compound is shown. • It was determined that the Bi{sub 3}FeSb{sub 2}O{sub 11} is of disordered cubic KSbO{sub 3}-type structure. • Factor group analysis of Bi{sub 3}FeSb{sub 2}O{sub 11} vibrational spectrum has been performed. • Short-range antiferromagnetic interactions govern Bi{sub 3}FeSb{sub 2}O{sub 11} magnetic behavior.« less

An Efficient Means of Adaptive Refinement Within Systems of Overset Grids

NASA Technical Reports Server (NTRS)

Meakin, Robert L.

1996-01-01

An efficient means of adaptive refinement within systems of overset grids is presented. Problem domains are segregated into near-body and off-body fields. Near-body fields are discretized via overlapping body-fitted grids that extend only a short distance from body surfaces. Off-body fields are discretized via systems of overlapping uniform Cartesian grids of varying levels of refinement. a novel off-body grid generation and management scheme provides the mechanism for carrying out adaptive refinement of off-body flow dynamics and solid body motion. The scheme allows for very efficient use of memory resources, and flow solvers and domain connectivity routines that can exploit the structure inherent to uniform Cartesian grids.

Prospects for the U.S. energy and refining industries: Markets, profitability and key drivers for change

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burke, B.F.

The US refining industry has experienced an extended period of change covering the past 20 years. Growing regulatory requirements, combined with shifting market characteristics, have resulted in massive investments and significant and ongoing structural change. Despite excellent capacity utilization, recent profitability has been poor. Industry psychology can be described as depressed, with honest concern about the long-term attractiveness of domestic refining as an area for continued participation and investment. This paper provides an overview of how the industry arrived at these levels of poor profitability, examines the current situation and future drivers, and presents Chem Systems` views on the outlookmore » for domestic refining.« less

Simplified and refined structural modeling for economical flutter analysis and design

NASA Technical Reports Server (NTRS)

Ricketts, R. H.; Sobieszczanski, J.

1977-01-01

A coordinated use of two finite-element models of different levels of refinement is presented to reduce the computer cost of the repetitive flutter analysis commonly encountered in structural resizing to meet flutter requirements. One model, termed a refined model (RM), represents a high degree of detail needed for strength-sizing and flutter analysis of an airframe. The other model, called a simplified model (SM), has a relatively much smaller number of elements and degrees-of-freedom. A systematic method of deriving an SM from a given RM is described. The method consists of judgmental and numerical operations to make the stiffness and mass of the SM elements equivalent to the corresponding substructures of RM. The structural data are automatically transferred between the two models. The bulk of analysis is performed on the SM with periodical verifications carried out by analysis of the RM. In a numerical example of a supersonic cruise aircraft with an arrow wing, this approach permitted substantial savings in computer costs and acceleration of the job turn-around.

Joint refinement model for the spin resolved one-electron reduced density matrix of YTiO3 using magnetic structure factors and magnetic Compton profiles data.

PubMed

Gueddida, Saber; Yan, Zeyin; Kibalin, Iurii; Voufack, Ariste Bolivard; Claiser, Nicolas; Souhassou, Mohamed; Lecomte, Claude; Gillon, Béatrice; Gillet, Jean-Michel

2018-04-28

In this paper, we propose a simple cluster model with limited basis sets to reproduce the unpaired electron distributions in a YTiO 3 ferromagnetic crystal. The spin-resolved one-electron-reduced density matrix is reconstructed simultaneously from theoretical magnetic structure factors and directional magnetic Compton profiles using our joint refinement algorithm. This algorithm is guided by the rescaling of basis functions and the adjustment of the spin population matrix. The resulting spin electron density in both position and momentum spaces from the joint refinement model is in agreement with theoretical and experimental results. Benefits brought from magnetic Compton profiles to the entire spin density matrix are illustrated. We studied the magnetic properties of the YTiO 3 crystal along the Ti-O 1 -Ti bonding. We found that the basis functions are mostly rescaled by means of magnetic Compton profiles, while the molecular occupation numbers are mainly modified by the magnetic structure factors.

The solvent component of macromolecular crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weichenberger, Christian X.; Afonine, Pavel V.; Kantardjieff, Katherine

2015-04-30

On average, the mother liquor or solvent and its constituents occupy about 50% of a macromolecular crystal. Ordered as well as disordered solvent components need to be accurately accounted for in modelling and refinement, often with considerable complexity. The mother liquor from which a biomolecular crystal is grown will contain water, buffer molecules, native ligands and cofactors, crystallization precipitants and additives, various metal ions, and often small-molecule ligands or inhibitors. On average, about half the volume of a biomolecular crystal consists of this mother liquor, whose components form the disordered bulk solvent. Its scattering contributions can be exploited in initialmore » phasing and must be included in crystal structure refinement as a bulk-solvent model. Concomitantly, distinct electron density originating from ordered solvent components must be correctly identified and represented as part of the atomic crystal structure model. Herein, are reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk-solvent density modification in phase improvement, (iii) bulk-solvent models and refinement of bulk-solvent contributions and (iv) modelling and validation of ordered solvent constituents. A brief summary is provided of current tools for bulk-solvent analysis and refinement, as well as of modelling, refinement and analysis of ordered solvent components, including small-molecule ligands.« less

Unstructured Cartesian refinement with sharp interface immersed boundary method for 3D unsteady incompressible flows

NASA Astrophysics Data System (ADS)

Angelidis, Dionysios; Chawdhary, Saurabh; Sotiropoulos, Fotis

2016-11-01

A novel numerical method is developed for solving the 3D, unsteady, incompressible Navier-Stokes equations on locally refined fully unstructured Cartesian grids in domains with arbitrarily complex immersed boundaries. Owing to the utilization of the fractional step method on an unstructured Cartesian hybrid staggered/non-staggered grid layout, flux mismatch and pressure discontinuity issues are avoided and the divergence free constraint is inherently satisfied to machine zero. Auxiliary/hanging nodes are used to facilitate the discretization of the governing equations. The second-order accuracy of the solver is ensured by using multi-dimension Lagrange interpolation operators and appropriate differencing schemes at the interface of regions with different levels of refinement. The sharp interface immersed boundary method is augmented with local near-boundary refinement to handle arbitrarily complex boundaries. The discrete momentum equation is solved with the matrix free Newton-Krylov method and the Krylov-subspace method is employed to solve the Poisson equation. The second-order accuracy of the proposed method on unstructured Cartesian grids is demonstrated by solving the Poisson equation with a known analytical solution. A number of three-dimensional laminar flow simulations of increasing complexity illustrate the ability of the method to handle flows across a range of Reynolds numbers and flow regimes. Laminar steady and unsteady flows past a sphere and the oblique vortex shedding from a circular cylinder mounted between two end walls demonstrate the accuracy, the efficiency and the smooth transition of scales and coherent structures across refinement levels. Large-eddy simulation (LES) past a miniature wind turbine rotor, parameterized using the actuator line approach, indicates the ability of the fully unstructured solver to simulate complex turbulent flows. Finally, a geometry resolving LES of turbulent flow past a complete hydrokinetic turbine illustrates the potential of the method to simulate turbulent flows past geometrically complex bodies on locally refined meshes. In all the cases, the results are found to be in very good agreement with published data and savings in computational resources are achieved.

Effect of severe plastic deformation on microstructure of squeeze-cast magnesium alloy AZ31 plate

NASA Astrophysics Data System (ADS)

Fong, Kai Soon; Tan, Ming Jen; Atsushi, Danno; Chua, Beng Wah; Ho, Meng Kwong

2016-10-01

High cost and poor room temperature formability of magnesium alloy sheet are the key factors that limit its application as a feedstock material for press forming. Production of Mg plates by squeeze casting with further processing by severe plastic deformation (SPD) is a potential method to reduce cost and improve formability. In this study, AZ31 Mg plate of dimension 96×96×4 mm was successfully produced by squeeze casting, using a novel melt transfer technique, at a forging force and speed of 180 Ton and 200 mm/sec respectively. The effect of severe plastic deformation (SPD) using groove pressing on the mechanical properties of squeeze-casted Mg plate after partial homogenization was subsequently investigated. Observation of the microstructure after two cycles of groove pressing, under decreasing temperature from 543K to 493K, shows a significant grain refinement from 39 to 4.7 µm. The Vickers hardness increased by approximately 25% from 56 to 74.1 which suggests an improvement in mechanical strength as a result of both the grain refinement and work hardening. The result shows that squeeze casting combined with groove pressing is potentially an effective method for preparation of thin magnesium alloy plate with fine-grained structure and improved mechanical properties.

Separation of Lead from Crude Antimony by Pyro-Refining Process with NaPO3 Addition

NASA Astrophysics Data System (ADS)

Ye, Longgang; Hu, Yuejie; Xia, Zhimei; Chen, Yongming

2016-06-01

The main purpose of this study was to separate lead from crude antimony through an oxidation pyro-refining process and by using sodium metaphosphate as a lead elimination reagent. The process parameters that will affect the refining results were optimized experimentally under controlled conditions, such as the sodium metaphosphate charging dosage, the refining temperature and duration, and the air flow rate, to determine their effect on the lead content in refined antimony and the lead removal rate. A minimum lead content of 0.0522 wt.% and a 98.6% lead removal rate were obtained under the following optimal conditions: W_{{{NaPO}_{{3}} }} = 15% W Sb (where W represents weight), a refining temperature of 800°C, a refining time of 30 min, and an air flow rate of 3 L/min. X-ray diffractometry and scanning electron microscopy showed that high-purity antimony was obtained. The smelting operation is free from smoke or ammonia pollution when using monobasic sodium phosphate or ammonium dihydrogen phosphate as the lead elimination reagent. However, this refining process can also remove a certain amount of sulfur, cobalt, and silicon simultaneously, and smelting results also suggest that sodium metaphosphate can be used as a potential lead elimination reagent for bismuth and copper refining.

A refined methodology for modeling volume quantification performance in CT

NASA Astrophysics Data System (ADS)

Chen, Baiyu; Wilson, Joshua; Samei, Ehsan

2014-03-01

The utility of CT lung nodule volume quantification technique depends on the precision of the quantification. To enable the evaluation of quantification precision, we previously developed a mathematical model that related precision to image resolution and noise properties in uniform backgrounds in terms of an estimability index (e'). The e' was shown to predict empirical precision across 54 imaging and reconstruction protocols, but with different correlation qualities for FBP and iterative reconstruction (IR) due to the non-linearity of IR impacted by anatomical structure. To better account for the non-linearity of IR, this study aimed to refine the noise characterization of the model in the presence of textured backgrounds. Repeated scans of an anthropomorphic lung phantom were acquired. Subtracted images were used to measure the image quantum noise, which was then used to adjust the noise component of the e' calculation measured from a uniform region. In addition to the model refinement, the validation of the model was further extended to 2 nodule sizes (5 and 10 mm) and 2 segmentation algorithms. Results showed that the magnitude of IR's quantum noise was significantly higher in structured backgrounds than in uniform backgrounds (ASiR, 30-50%; MBIR, 100-200%). With the refined model, the correlation between e' values and empirical precision no longer depended on reconstruction algorithm. In conclusion, the model with refined noise characterization relfected the nonlinearity of iterative reconstruction in structured background, and further showed successful prediction of quantification precision across a variety of nodule sizes, dose levels, slice thickness, reconstruction algorithms, and segmentation software.

A refined model of claudin-15 tight junction paracellular architecture by molecular dynamics simulations

PubMed Central

Alberini, Giulio; Benfenati, Fabio

2017-01-01

Tight-junctions between epithelial cells of biological barriers are specialized molecular structures that regulate the flux of solutes across the barrier, parallel to cell walls. The tight-junction backbone is made of strands of transmembrane proteins from the claudin family, but the molecular mechanism of its function is still not completely understood. Recently, the crystal structure of a mammalian claudin-15 was reported, displaying for the first time the detailed features of transmembrane and extracellular domains. Successively, a structural model of claudin-15-based paracellular channels has been proposed, suggesting a putative assembly that illustrates how claudins associate in the same cell (via cis interactions) and across adjacent cells (via trans interactions). Although very promising, the model offers only a static conformation, with residues missing in the most important extracellular regions and potential steric clashes. Here we present detailed atomic models of paracellular single and double pore architectures, obtained from the putative assembly and refined via structural modeling and all-atom molecular dynamics simulations in double membrane bilayer and water environment. Our results show an overall stable configuration of the complex with a fluctuating pore size. Extracellular residue loops in trans interaction are able to form stable contacts and regulate the size of the pore, which displays a stationary radius of 2.5–3.0 Å at the narrowest region. The side-by-side interactions of the cis configuration are preserved via stable hydrogen bonds, already predicted by cysteine crosslinking experiments. Overall, this work introduces an improved version of the claudin-15-based paracellular channel model that strengthens its validity and that can be used in further computational studies to understand the structural features of tight-junctions regulation. PMID:28863193

Electron-density descriptors as predictors in quantitative structure--activity/property relationships and drug design.

PubMed

Matta, Chérif F; Arabi, Alya A

2011-06-01

The use of electron density-based molecular descriptors in drug research, particularly in quantitative structure--activity relationships/quantitative structure--property relationships studies, is reviewed. The exposition starts by a discussion of molecular similarity and transferability in terms of the underlying electron density, which leads to a qualitative introduction to the quantum theory of atoms in molecules (QTAIM). The starting point of QTAIM is the topological analysis of the molecular electron-density distributions to extract atomic and bond properties that characterize every atom and bond in the molecule. These atomic and bond properties have considerable potential as bases for the construction of robust quantitative structure--activity/property relationships models as shown by selected examples in this review. QTAIM is applicable to the electron density calculated from quantum-chemical calculations and/or that obtained from ultra-high resolution x-ray diffraction experiments followed by nonspherical refinement. Atomic and bond properties are introduced followed by examples of application of each of these two families of descriptors. The review ends with a study whereby the molecular electrostatic potential, uniquely determined by the density, is used in conjunction with atomic properties to elucidate the reasons for the biological similarity of bioisosteres.

An Adaptive Mesh Algorithm: Mesh Structure and Generation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scannapieco, Anthony J.

2016-06-21

The purpose of Adaptive Mesh Refinement is to minimize spatial errors over the computational space not to minimize the number of computational elements. The additional result of the technique is that it may reduce the number of computational elements needed to retain a given level of spatial accuracy. Adaptive mesh refinement is a computational technique used to dynamically select, over a region of space, a set of computational elements designed to minimize spatial error in the computational model of a physical process. The fundamental idea is to increase the mesh resolution in regions where the physical variables are represented bymore » a broad spectrum of modes in k-space, hence increasing the effective global spectral coverage of those physical variables. In addition, the selection of the spatially distributed elements is done dynamically by cyclically adjusting the mesh to follow the spectral evolution of the system. Over the years three types of AMR schemes have evolved; block, patch and locally refined AMR. In block and patch AMR logical blocks of various grid sizes are overlaid to span the physical space of interest, whereas in locally refined AMR no logical blocks are employed but locally nested mesh levels are used to span the physical space. The distinction between block and patch AMR is that in block AMR the original blocks refine and coarsen entirely in time, whereas in patch AMR the patches change location and zone size with time. The type of AMR described herein is a locally refi ned AMR. In the algorithm described, at any point in physical space only one zone exists at whatever level of mesh that is appropriate for that physical location. The dynamic creation of a locally refi ned computational mesh is made practical by a judicious selection of mesh rules. With these rules the mesh is evolved via a mesh potential designed to concentrate the nest mesh in regions where the physics is modally dense, and coarsen zones in regions where the physics is modally sparse.« less

Effect of cobalt doping on structural and optical properties of nanocrystalline La0.8Pb0.2CrO3 orthochromite

NASA Astrophysics Data System (ADS)

Zarrin, Naima; Shahidhusain

2018-04-01

We have synthesized nanocrystalline La0.8Pb0.2Cr1-xCoxO3 (0≤x≤0.3) through sol-gel process and studied their structural and optical properties. X-ray diffraction patterns reveal that the samples conform in the orthorhombic crystal symmetry with Pnma space group. Structural parameters are refined by Rietveld Refinement using Fullprof software. Lattice parameters and unit cell volume of doped samples are found to decrease with increase in Co doping. The optical energy band gapdecreases whereas Urbach energy increases with the increase in Co content.

STRCMACS: An extensive set of Macros for structured programming in OS/360 assembly language

NASA Technical Reports Server (NTRS)

Barth, C. W.

1974-01-01

Two techniques are discussed that have been most often referred to as structured programming. One is that of programming with high level control structures (such as the if and while) replacing the branch instruction (goto-less programming); the other is the process of developing a program by progressively refining descriptions of components in terms of more primitive components (called stepwise refinement or top-down programming). In addition to discussing what these techniques are, it is shown why their use is advised and how both can be implemented in OS assembly language by the use of a special macro instruction package.

6-Aminopenicillanic acid revisited: A combined solid state NMR and in silico refinement

NASA Astrophysics Data System (ADS)

Aguiar, Daniel Lima Marques de; San Gil, Rosane Aguiar da Silva; Alencastro, Ricardo Bicca de; Souza, Eugenio Furtado de; Borré, Leandro Bandeira; Vaiss, Viviane da Silva; Leitão, Alexandre Amaral

2016-09-01

13C/15N (experimental and ab initio) solid-state NMR was used to achieve an affordable way to improve hydrogen refinement of 6-aminopenicillanic acid (6-APA) structure. The lattice effect on the isotropic chemical shifts was probed by using two different magnetic shielding calculations: isolated molecules and periodic crystal structure. The electron density difference maps of optimized and non-optimized structures were calculated in order to investigate the interactions inside the 6-APA unit cell. The 13C and 15N chemical shifts assignments were unambiguously stablished. In addition, some of the literature 13C resonances ambiguities could be properly solved.

Michael Levitt and Computational Biology

Science.gov Websites

molecular structures, compute structural changes, refine experimental structure, model enzyme catalysis and (May 2004) Top Some links on this page may take you to non-federal websites. Their policies may differ

Hydrogen ADPs with Cu Kα data? Invariom and Hirshfeld atom modelling of fluconazole.

PubMed

Orben, Claudia M; Dittrich, Birger

2014-06-01

For the structure of fluconazole [systematic name: 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol] monohydrate, C13H12F2N6O·H2O, a case study on different model refinements is reported, based on single-crystal X-ray diffraction data measured at 100 K with Cu Kα radiation to a resolution of sin θ/λ of 0.6 Å(-1). The structure, anisotropic displacement parameters (ADPs) and figures of merit from the independent atom model are compared to `invariom' and `Hirshfeld atom' refinements. Changing from a spherical to an aspherical atom model lowers the figures of merit and improves both the accuracy and the precision of the geometrical parameters. Differences between results from the two aspherical-atom refinements are small. However, a refinement of ADPs for H atoms is only possible with the Hirshfeld atom density model. It gives meaningful results even at a resolution of 0.6 Å(-1), but requires good low-order data.

Comparative analysis of three-dimensional structures of homodimers of uridine phosphorylase from Salmonella typhimurium in the unligated state and in a complex with potassium ion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lashkov, A. A.; Zhukhlistova, N. E.; Gabdulkhakov, A. G.

2009-03-15

The spatial organization of the homodimer of unligated uridine phosphorylase from Salmonella typhimurium (St UPh) was determined with high accuracy. The structure was refined at 1.80 A resolution to R{sub work} = 16.1% and R{sub free} = 20.0%. The rms deviations for the bond lengths, bond angles, and chiral angles are 0.006 A, 1.042{sup o}, and 0.071{sup o}, respectively. The coordinate error estimated by the Luzzati plot is 0.166 A. The coordinate error based on the maximum likelihood is 0.199 A. A comparative analysis of the spatial organization of the homodimer in two independently refined structures and the structure ofmore » the homodimer St UPh in the complex with a K{sup +} ion was performed. The substrate-binding sites in the homodimers StUPhs in the unligated state were found to act asynchronously. In the presence of a potassium ion, the three-dimensional structures of the subunits in the homodimer are virtually identical, which is apparently of importance for the synchronous action of both substrate-binding sites. The atomic coordinates of the refined structure of the homodimer and structure factors have been deposited in the Protein Data Bank (PDB ID code 3DPS).« less

iATTRACT: simultaneous global and local interface optimization for protein-protein docking refinement.

PubMed

Schindler, Christina E M; de Vries, Sjoerd J; Zacharias, Martin

2015-02-01

Protein-protein interactions are abundant in the cell but to date structural data for a large number of complexes is lacking. Computational docking methods can complement experiments by providing structural models of complexes based on structures of the individual partners. A major caveat for docking success is accounting for protein flexibility. Especially, interface residues undergo significant conformational changes upon binding. This limits the performance of docking methods that keep partner structures rigid or allow limited flexibility. A new docking refinement approach, iATTRACT, has been developed which combines simultaneous full interface flexibility and rigid body optimizations during docking energy minimization. It employs an atomistic molecular mechanics force field for intermolecular interface interactions and a structure-based force field for intramolecular contributions. The approach was systematically evaluated on a large protein-protein docking benchmark, starting from an enriched decoy set of rigidly docked protein-protein complexes deviating by up to 15 Å from the native structure at the interface. Large improvements in sampling and slight but significant improvements in scoring/discrimination of near native docking solutions were observed. Complexes with initial deviations at the interface of up to 5.5 Å were refined to significantly better agreement with the native structure. Improvements in the fraction of native contacts were especially favorable, yielding increases of up to 70%. © 2014 Wiley Periodicals, Inc.

Effects of model structural uncertainty on carbon cycle projections: biological nitrogen fixation as a case study

NASA Astrophysics Data System (ADS)

Wieder, William R.; Cleveland, Cory C.; Lawrence, David M.; Bonan, Gordon B.

2015-04-01

Uncertainties in terrestrial carbon (C) cycle projections increase uncertainty of potential climate feedbacks. Efforts to improve model performance often include increased representation of biogeochemical processes, such as coupled carbon-nitrogen (N) cycles. In doing so, models are becoming more complex, generating structural uncertainties in model form that reflect incomplete knowledge of how to represent underlying processes. Here, we explore structural uncertainties associated with biological nitrogen fixation (BNF) and quantify their effects on C cycle projections. We find that alternative plausible structures to represent BNF result in nearly equivalent terrestrial C fluxes and pools through the twentieth century, but the strength of the terrestrial C sink varies by nearly a third (50 Pg C) by the end of the twenty-first century under a business-as-usual climate change scenario representative concentration pathway 8.5. These results indicate that actual uncertainty in future C cycle projections may be larger than previously estimated, and this uncertainty will limit C cycle projections until model structures can be evaluated and refined.

Toward Improved Description of DNA Backbone: Revisiting Epsilon and Zeta Torsion Force Field Parameters

PubMed Central

Zgarbová, Marie; Luque, F. Javier; Šponer, Jiří; Cheatham, Thomas E.; Otyepka, Michal; Jurečka, Petr

2013-01-01

We present a refinement of the backbone torsion parameters ε and ζ of the Cornell et al. AMBER force field for DNA simulations. The new parameters, denoted as εζOL1, were derived from quantum-mechanical calculations with inclusion of conformation-dependent solvation effects according to the recently reported methodology (J. Chem. Theory Comput. 2012, 7(9), 2886-2902). The performance of the refined parameters was analyzed by means of extended molecular dynamics (MD) simulations for several representative systems. The results showed that the εζOL1 refinement improves the backbone description of B-DNA double helices and G-DNA stem. In B-DNA simulations, we observed an average increase of the helical twist and narrowing of the major groove, thus achieving better agreement with X-ray and solution NMR data. The balance between populations of BI and BII backbone substates was shifted towards the BII state, in better agreement with ensemble-refined solution experimental results. Furthermore, the refined parameters decreased the backbone RMS deviations in B-DNA MD simulations. In the antiparallel guanine quadruplex (G-DNA) the εζOL1 modification improved the description of non-canonical α/γ backbone substates, which were shown to be coupled to the ε/ζ torsion potential. Thus, the refinement is suggested as a possible alternative to the current ε/ζ torsion potential, which may enable more accurate modeling of nucleic acids. However, long-term testing is recommended before its routine application in DNA simulations. PMID:24058302

Recycling of Magnesium Alloy Employing Refining and Solid Oxide Membrane (SOM) Electrolysis

NASA Astrophysics Data System (ADS)

Guan, Xiaofei; Zink, Peter A.; Pal, Uday B.; Powell, Adam C.

2013-04-01

Pure magnesium was recycled from partially oxidized 50.5 wt pct Mg-Al scrap alloy and AZ91 Mg alloy (9 wt pct Al, 1 wt pct Zn). Refining experiments were performed using a eutectic mixture of MgF2-CaF2 molten salt (flux). During the experiments, potentiodynamic scans were performed to determine the electrorefining potentials for magnesium dissolution and magnesium bubble nucleation in the flux. The measured electrorefining potential for magnesium bubble nucleation increased over time as the magnesium content inside the magnesium alloy decreased. Potentiostatic holds and electrochemical impedance spectroscopy were employed to measure the electronic and ionic resistances of the flux. The electronic resistivity of the flux varied inversely with the magnesium solubility. Up to 100 pct of the magnesium was refined from the Mg-Al scrap alloy by dissolving magnesium and its oxide into the flux followed by argon-assisted evaporation of dissolved magnesium and subsequently condensing the magnesium vapor. Solid oxide membrane electrolysis was also employed in the system to enable additional magnesium recovery from magnesium oxide in the partially oxidized Mg-Al scrap. In an experiment employing AZ91 Mg alloy, only the refining step was carried out. The calculated refining yield of magnesium from the AZ91 alloy was near 100 pct.

PARAMESH: A Parallel Adaptive Mesh Refinement Community Toolkit

NASA Technical Reports Server (NTRS)

MacNeice, Peter; Olson, Kevin M.; Mobarry, Clark; deFainchtein, Rosalinda; Packer, Charles

1999-01-01

In this paper, we describe a community toolkit which is designed to provide parallel support with adaptive mesh capability for a large and important class of computational models, those using structured, logically cartesian meshes. The package of Fortran 90 subroutines, called PARAMESH, is designed to provide an application developer with an easy route to extend an existing serial code which uses a logically cartesian structured mesh into a parallel code with adaptive mesh refinement. Alternatively, in its simplest use, and with minimal effort, it can operate as a domain decomposition tool for users who want to parallelize their serial codes, but who do not wish to use adaptivity. The package can provide them with an incremental evolutionary path for their code, converting it first to uniformly refined parallel code, and then later if they so desire, adding adaptivity.

On Correspondence of BRST-BFV, Dirac, and Refined Algebraic Quantizations of Constrained Systems

NASA Astrophysics Data System (ADS)

Shvedov, O. Yu.

2002-11-01

The correspondence between BRST-BFV, Dirac, and refined algebraic (group averaging, projection operator) approaches to quantizing constrained systems is analyzed. For the closed-algebra case, it is shown that the component of the BFV wave function corresponding to maximal (minimal) value of number of ghosts and antighosts in the Schrodinger representation may be viewed as a wave function in the refined algebraic (Dirac) quantization approach. The Giulini-Marolf group averaging formula for the inner product in the refined algebraic quantization approach is obtained from the Batalin-Marnelius prescription for the BRST-BFV inner product, which should be generally modified due to topological problems. The considered prescription for the correspondence of states is observed to be applicable to the open-algebra case. The refined algebraic quantization approach is generalized then to the case of nontrivial structure functions. A simple example is discussed. The correspondence of observables for different quantization methods is also investigated.

Cortical Feedback Regulates Feedforward Retinogeniculate Refinement

PubMed Central

Thompson, Andrew D; Picard, Nathalie; Min, Lia; Fagiolini, Michela; Chen, Chinfei

2016-01-01

SUMMARY According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiring of its downstream target. In the visual system, retinal circuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. In contrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window in development, beginning at postnatal day 20 in mice. Disrupting cortical activity during this window, pharmacologically or chemogenetically, increases the number of retinal ganglion cells innervating each thalamic relay neuron. These results suggest that primary sensory structures develop through the concurrent and interdependent remodeling of subcortical and cortical circuits in response to sensory experience, rather than through a simple feedforward process. Our findings also highlight an unexpected function for the corticothalamic projection. PMID:27545712

Empirical relations between large wood transport and catchment characteristics

NASA Astrophysics Data System (ADS)

Steeb, Nicolas; Rickenmann, Dieter; Rickli, Christian; Badoux, Alexandre

2017-04-01

The transport of vast amounts of large wood (LW) in water courses can considerably aggravate hazardous situations during flood events, and often strongly affects resulting flood damage. Large wood recruitment and transport are controlled by various factors which are difficult to assess and the prediction of transported LW volumes is difficult. Such information are, however, important for engineers and river managers to adequately dimension retention structures or to identify critical stream cross-sections. In this context, empirical formulas have been developed to estimate the volume of transported LW during a flood event (Rickenmann, 1997; Steeb et al., 2017). The data base of existing empirical wood load equations is, however, limited. The objective of the present study is to test and refine existing empirical equations, and to derive new relationships to reveal trends in wood loading. Data have been collected for flood events with LW occurrence in Swiss catchments of various sizes. This extended data set allows us to derive statistically more significant results. LW volumes were found to be related to catchment and transport characteristics, such as catchment size, forested area, forested stream length, water discharge, sediment load, or Melton ratio. Both the potential wood load and the fraction that is effectively mobilized during a flood event (effective wood load) are estimated. The difference of potential and effective wood load allows us to derive typical reduction coefficients that can be used to refine spatially explicit GIS models for potential LW recruitment.

Quantitative Pointwise Estimate of the Solution of the Linearized Boltzmann Equation

NASA Astrophysics Data System (ADS)

Lin, Yu-Chu; Wang, Haitao; Wu, Kung-Chien

2018-04-01

We study the quantitative pointwise behavior of the solutions of the linearized Boltzmann equation for hard potentials, Maxwellian molecules and soft potentials, with Grad's angular cutoff assumption. More precisely, for solutions inside the finite Mach number region (time like region), we obtain the pointwise fluid structure for hard potentials and Maxwellian molecules, and optimal time decay in the fluid part and sub-exponential time decay in the non-fluid part for soft potentials. For solutions outside the finite Mach number region (space like region), we obtain sub-exponential decay in the space variable. The singular wave estimate, regularization estimate and refined weighted energy estimate play important roles in this paper. Our results extend the classical results of Liu and Yu (Commun Pure Appl Math 57:1543-1608, 2004), (Bull Inst Math Acad Sin 1:1-78, 2006), (Bull Inst Math Acad Sin 6:151-243, 2011) and Lee et al. (Commun Math Phys 269:17-37, 2007) to hard and soft potentials by imposing suitable exponential velocity weight on the initial condition.

Quantitative Pointwise Estimate of the Solution of the Linearized Boltzmann Equation

NASA Astrophysics Data System (ADS)

Lin, Yu-Chu; Wang, Haitao; Wu, Kung-Chien

2018-06-01

We study the quantitative pointwise behavior of the solutions of the linearized Boltzmann equation for hard potentials, Maxwellian molecules and soft potentials, with Grad's angular cutoff assumption. More precisely, for solutions inside the finite Mach number region (time like region), we obtain the pointwise fluid structure for hard potentials and Maxwellian molecules, and optimal time decay in the fluid part and sub-exponential time decay in the non-fluid part for soft potentials. For solutions outside the finite Mach number region (space like region), we obtain sub-exponential decay in the space variable. The singular wave estimate, regularization estimate and refined weighted energy estimate play important roles in this paper. Our results extend the classical results of Liu and Yu (Commun Pure Appl Math 57:1543-1608, 2004), (Bull Inst Math Acad Sin 1:1-78, 2006), (Bull Inst Math Acad Sin 6:151-243, 2011) and Lee et al. (Commun Math Phys 269:17-37, 2007) to hard and soft potentials by imposing suitable exponential velocity weight on the initial condition.

Structure-based screening and molecular dynamics simulations offer novel natural compounds as potential inhibitors of Mycobacterium tuberculosis isocitrate lyase.

PubMed

Shukla, Rohit; Shukla, Harish; Sonkar, Amit; Pandey, Tripti; Tripathi, Timir

2018-06-01

Mycobacterium tuberculosis is the etiological agent of tuberculosis in humans and is responsible for more than two million deaths annually. M. tuberculosis isocitrate lyase (MtbICL) catalyzes the first step in the glyoxylate cycle, plays a pivotal role in the persistence of M. tuberculosis, which acts as a potential target for an anti-tubercular drug. To identify the potential anti-tuberculosis compound, we conducted a structure-based virtual screening of natural compounds from the ZINC database (n = 1,67,748) against the MtbICL structure. The ligands were docked against MtbICL in three sequential docking modes that resulted in 340 ligands having better docking score. These compounds were evaluated for Lipinski and ADMET prediction, and 27 compounds were found to fit well with re-docking studies. After refinement by molecular docking and drug-likeness analyses, three potential inhibitors (ZINC1306071, ZINC2111081, and ZINC2134917) were identified. These three ligands and the reference compounds were further subjected to molecular dynamics simulation and binding energy analyses to compare the dynamic structure of protein after ligand binding and the stability of the MtbICL and bound complexes. The binding free energy analyses were calculated to validate and capture the intermolecular interactions. The results suggested that the three compounds had a negative binding energy with -96.462, -143.549, and -122.526 kJ mol -1 for compounds with IDs ZINC1306071, ZINC2111081, and ZINC2134917, respectively. These lead compounds displayed substantial pharmacological and structural properties to be drug candidates. We concluded that ZINC2111081 has a great potential to inhibit MtbICL and would add to the drug discovery process against tuberculosis.

Crystal structure of human tooth enamel studied by neutron diffraction

NASA Astrophysics Data System (ADS)

Ouladdiaf, Bachir; Rodriguez-Carvajal, Juan; Goutaudier, Christelle; Ouladdiaf, Selma; Grosgogeat, Brigitte; Pradelle, Nelly; Colon, Pierre

2015-02-01

Crystal structure of human tooth enamel was investigated using high-resolution neutron powder diffraction. Excellent agreement between observed and refined patterns is obtained, using the hexagonal hydroxyapatite model for the tooth enamel, where a large hydroxyl deficiency ˜70% is found in the 4e site. Rietveld refinements method combined with the difference Fourier maps have revealed, however, that the hydroxyl ions are not only disordered along the c-axis but also within the basal plane. Additional H ions located at the 6h site and forming HPO42- anions were found.

Foundations for a multiscale collaborative Earth model

NASA Astrophysics Data System (ADS)

Afanasiev, Michael; Peter, Daniel; Sager, Korbinian; Simutė, Saulė; Ermert, Laura; Krischer, Lion; Fichtner, Andreas

2016-01-01

We present a computational framework for the assimilation of local to global seismic data into a consistent model describing Earth structure on all seismically accessible scales. This Collaborative Seismic Earth Model (CSEM) is designed to meet the following requirements: (i) Flexible geometric parametrization, capable of capturing topography and bathymetry, as well as all aspects of potentially resolvable structure, including small-scale heterogeneities and deformations of internal discontinuities. (ii) Independence of any particular wave equation solver, in order to enable the combination of inversion techniques suitable for different types of seismic data. (iii) Physical parametrization that allows for full anisotropy and for variations in attenuation and density. While not all of these parameters are always resolvable, the assimilation of data that constrain any parameter subset should be possible. (iv) Ability to accommodate successive refinements through the incorporation of updates on any scale as new data or inversion techniques become available. (v) Enable collaborative Earth model construction. The structure of the initial CSEM is represented on a variable-resolution tetrahedral mesh. It is assembled from a long-wavelength 3-D global model into which several regional-scale tomographies are embedded. We illustrate the CSEM workflow of successive updating with two examples from Japan and the Western Mediterranean, where we constrain smaller scale structure using full-waveform inversion. Furthermore, we demonstrate the ability of the CSEM to act as a vehicle for the combination of different tomographic techniques with a joint full-waveform and traveltime ray tomography of Europe. This combination broadens the exploitable frequency range of the individual techniques, thereby improving resolution. We perform two iterations of a whole-Earth full-waveform inversion using a long-period reference data set from 225 globally recorded earthquakes. At this early stage of the CSEM development, the broad global updates mostly act to remove artefacts from the assembly of the initial CSEM. During the future evolution of the CSEM, the reference data set will be used to account for the influence of small-scale refinements on large-scale global structure. The CSEM as a computational framework is intended to help bridging the gap between local, regional and global tomography, and to contribute to the development of a global multiscale Earth model. While the current construction serves as a first proof of concept, future refinements and additions will require community involvement, which is welcome at this stage already.

Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models.

PubMed

Li, Wenlin; Schaeffer, R Dustin; Otwinowski, Zbyszek; Grishin, Nick V

2016-01-01

The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a community-wide blind test experiment to reveal the best accomplishments of structure modeling. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differences between close models is difficult because of the lack of uncertainty estimations for this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to estimate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic resonance are deposited as ensembles of alternative conformers that reflect the structural flexibility, whereas standard X-ray refinement produces the static structure averaged over time and space for the dynamic ensembles. To recapitulate the structural heterogeneous ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets to generate structural ensembles for our GDT_TS uncertainty analysis. Using those generated ensembles, our study demonstrates that the time-averaged refinements produced structure ensembles with better agreement with the experimental datasets than the averaged X-ray structures with B-factors. The uncertainty of the GDT_TS scores, quantified by their standard deviations (SDs), increases for scores lower than 50 and 70, with maximum SDs of 0.3 and 1.23 for X-ray and NMR structures, respectively. We also applied our procedure to the high accuracy version of GDT-based score and produced similar results with slightly higher SDs. To facilitate score comparisons by the community, we developed a user-friendly web server that produces structure ensembles for NMR and X-ray structures and is accessible at http://prodata.swmed.edu/SEnCS. Our work helps to identify the significance of GDT_TS score differences, as well as to provide structure ensembles for estimating SDs of any scores.

An adaptive mesh-moving and refinement procedure for one-dimensional conservation laws

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Flaherty, Joseph E.; Arney, David C.

1993-01-01

We examine the performance of an adaptive mesh-moving and /or local mesh refinement procedure for the finite difference solution of one-dimensional hyperbolic systems of conservation laws. Adaptive motion of a base mesh is designed to isolate spatially distinct phenomena, and recursive local refinement of the time step and cells of the stationary or moving base mesh is performed in regions where a refinement indicator exceeds a prescribed tolerance. These adaptive procedures are incorporated into a computer code that includes a MacCormack finite difference scheme wih Davis' artificial viscosity model and a discretization error estimate based on Richardson's extrapolation. Experiments are conducted on three problems in order to qualify the advantages of adaptive techniques relative to uniform mesh computations and the relative benefits of mesh moving and refinement. Key results indicate that local mesh refinement, with and without mesh moving, can provide reliable solutions at much lower computational cost than possible on uniform meshes; that mesh motion can be used to improve the results of uniform mesh solutions for a modest computational effort; that the cost of managing the tree data structure associated with refinement is small; and that a combination of mesh motion and refinement reliably produces solutions for the least cost per unit accuracy.

Toward Mycobacterium tuberculosis DXR inhibitor design: homology modeling and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Singh, Nidhi; Avery, Mitchell A.; McCurdy, Christopher R.

2007-09-01

Mycobacterium tuberculosis 1-deoxy- d-xylulose-5-phosphate reductoisomerase ( MtDXR) is a potential target for antitubercular chemotherapy. In the absence of its crystallographic structure, our aim was to develop a structural model of MtDXR. This will allow us to gain early insight into the structure and function of the enzyme and its likely binding to ligands and cofactors and thus, facilitate structure-based inhibitor design. To achieve this goal, initial models of MtDXR were generated using MODELER. The best quality model was refined using a series of minimizations and molecular dynamics simulations. A protein-ligand complex was also developed from the initial homology model of the target protein by including information about the known ligand as spatial restraints and optimizing the mutual interactions between the ligand and the binding site. The final model was evaluated on the basis of its ability to explain several site-directed mutagenesis data. Furthermore, a comparison of the homology model with the X-ray structure published in the final stages of the project shows excellent agreement and validates the approach. The knowledge gained from the current study should prove useful in the design and development of inhibitors as potential novel therapeutic agents against tuberculosis by either de novo drug design or virtual screening of large chemical databases.

Small molecule inhibitors of mesotrypsin from a structure-based docking screen

DOE PAGES

Kayode, Olumide; Huang, Zunnan; Soares, Alexei S.; ...

2017-05-02

PRSS3/mesotrypsin is an atypical isoform of trypsin, the upregulation of which has been implicated in promoting tumor progression. To date there are no mesotrypsin-selective pharmacological inhibitors which could serve as tools for deciphering the pathological role of this enzyme, and could potentially form the basis for novel therapeutic strategies targeting mesotrypsin. A virtual screen of the Natural Product Database (NPD) and Food and Drug Administration (FDA) approved Drug Database was conducted by high-throughput molecular docking utilizing crystal structures of mesotrypsin. Twelve high-scoring compounds were selected for testing based on lowest free energy docking scores, interaction with key mesotrypsin active sitemore » residues, and commercial availability. Diminazene (C1D22956468), along with two similar compounds presenting the bis-benzamidine substructure, was validated as a competitive inhibitor of mesotrypsin and other human trypsin isoforms. Diminazene is the most potent small molecule inhibitor of mesotrypsin reported to date with an inhibitory constant (K i) of 3.6±0.3 pM. Diminazene was subsequently co-crystalized with mesotrypsin and the crystal structure was solved and refined to 1.25 Å resolution. This high resolution crystal structure can now offer a foundation for structure-guided efforts to develop novel and potentially more selective mesotrypsin inhibitors based on similar molecular substructures.« less

Small molecule inhibitors of mesotrypsin from a structure-based docking screen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kayode, Olumide; Huang, Zunnan; Soares, Alexei S.

PRSS3/mesotrypsin is an atypical isoform of trypsin, the upregulation of which has been implicated in promoting tumor progression. To date there are no mesotrypsin-selective pharmacological inhibitors which could serve as tools for deciphering the pathological role of this enzyme, and could potentially form the basis for novel therapeutic strategies targeting mesotrypsin. A virtual screen of the Natural Product Database (NPD) and Food and Drug Administration (FDA) approved Drug Database was conducted by high-throughput molecular docking utilizing crystal structures of mesotrypsin. Twelve high-scoring compounds were selected for testing based on lowest free energy docking scores, interaction with key mesotrypsin active sitemore » residues, and commercial availability. Diminazene (C1D22956468), along with two similar compounds presenting the bis-benzamidine substructure, was validated as a competitive inhibitor of mesotrypsin and other human trypsin isoforms. Diminazene is the most potent small molecule inhibitor of mesotrypsin reported to date with an inhibitory constant (K i) of 3.6±0.3 pM. Diminazene was subsequently co-crystalized with mesotrypsin and the crystal structure was solved and refined to 1.25 Å resolution. This high resolution crystal structure can now offer a foundation for structure-guided efforts to develop novel and potentially more selective mesotrypsin inhibitors based on similar molecular substructures.« less

Structure determination in 55-atom Li-Na and Na-K nanoalloys.

PubMed

Aguado, Andrés; López, José M

2010-09-07

The structure of 55-atom Li-Na and Na-K nanoalloys is determined through combined empirical potential (EP) and density functional theory (DFT) calculations. The potential energy surface generated by the EP model is extensively sampled by using the basin hopping technique, and a wide diversity of structural motifs is reoptimized at the DFT level. A composition comparison technique is applied at the DFT level in order to make a final refinement of the global minimum structures. For dilute concentrations of one of the alkali atoms, the structure of the pure metal cluster, namely, a perfect Mackay icosahedron, remains stable, with the minority component atoms entering the host cluster as substitutional impurities. At intermediate concentrations, the nanoalloys adopt instead a core-shell polyicosahedral (p-Ih) packing, where the element with smaller atomic size and larger cohesive energy segregates to the cluster core. The p-Ih structures show a marked prolate deformation, in agreement with the predictions of jelliumlike models. The electronic preference for a prolate cluster shape, which is frustrated in the 55-atom pure clusters due to the icosahedral geometrical shell closing, is therefore realized only in the 55-atom nanoalloys. An analysis of the electronic densities of states suggests that photoelectron spectroscopy would be a sufficiently sensitive technique to assess the structures of nanoalloys with fixed size and varying compositions.

Construction and Application of a Refined Hospital Management Chain.

PubMed

Lihua, Yi

2016-01-01

Large scale development was quite common in the later period of hospital industrialization in China. Today, Chinese hospital management faces such problems as service inefficiency, high human resources cost, and low rate of capital use. This study analyzes the refined management chain of Wuxi No.2 People's Hospital. This consists of six gears namely, "organizational structure, clinical practice, outpatient service, medical technology, and nursing care and logistics." The gears are based on "flat management system targets, chief of medical staff, centralized outpatient service, intensified medical examinations, vertical nursing management and socialized logistics." The core concepts of refined hospital management are optimizing flow process, reducing waste, improving efficiency, saving costs, and taking good care of patients as most important. Keywords: Hospital, Refined, Management chain

Combining 27Al Solid-State NMR and First-Principles Simulations To Explore Crystal Structure in Disordered Aluminum Oxynitride.

PubMed

Tu, Bingtian; Liu, Xin; Wang, Hao; Wang, Weimin; Zhai, Pengcheng; Fu, Zhengyi

2016-12-19

The nuclear magnetic resonance (NMR) technique gives insight into the local information in a crystal structure, while Rietveld refinement of powder X-ray diffraction (PXRD) sketches out the framework of a crystal lattice. In this work, first-principles calculations were combined with the solid-state NMR technique and Rietveld refinement to explore the crystal structure of a disordered aluminum oxynitride (γ-alon). The theoretical NMR parameters (chemical shift, δ iso , quadrupolar coupling constants, C Q , and asymmetry parameter, η) of Al 22.5 O 28.5 N 3.5 , predicted by the gauge-including projector augmented wave (GIPAW) algorithm, were used to facilitate the analytical investigation of the 27 Al magic-angle spinning (MAS) NMR spectra of the as-prepared sample, whose formula was confirmed to be Al 2.811 O 3.565 N 0.435 by quantitative analysis. The experimental δ iso , C Q , and η of 27 Al showed a small discrepancy compared with theoretical models. The ratio of aluminum located at the 8a to 16d sites was calculated to be 0.531 from the relative integration of peaks in the 27 Al NMR spectra. The occupancies of aluminum at the 8a and 16d positions were determined through NMR investigations to be 0.9755 and 0.9178, respectively, and were used in the Rietveld refinement to obtain the lattice parameter and anion parameter of Al 2.811 O 3.565 N 0.435 . The results from 27 Al NMR investigations and PXRD structural refinement complemented each other. This work provides a powerful and accessible strategy to precisely understand the crystal structure of novel oxynitride materials with multiple disorder.

Mesh Convergence Requirements for Composite Damage Models

NASA Technical Reports Server (NTRS)

Davila, Carlos G.

2016-01-01

The ability of the finite element method to accurately represent the response of objects with intricate geometry and loading renders the finite element method as an extremely versatile analysis technique for structural analysis. Finite element analysis is routinely used in industry to calculate deflections, stress concentrations, natural frequencies, buckling loads, and much more. The method works by discretizing complex problems into smaller, simpler approximations that are valid over small uniform domains. For common analyses, the maximum size of the elements that can be used is often be determined by experience. However, to verify the quality of a solution, analyses with several levels of mesh refinement should be performed to ensure that the solution has converged. In recent years, the finite element method has been used to calculate the resistance of structures, and in particular that of composite structures. A number of techniques such as cohesive zone modeling, the virtual crack closure technique, and continuum damage modeling have emerged that can be used to predict cracking, delaminations, fiber failure, and other composite damage modes that lead to structural collapse. However, damage models present mesh refinement requirements that are not well understood. In this presentation, we examine different mesh refinement issues related to the representation of damage in composite materials. Damage process zone sizes and their corresponding mesh requirements will be discussed. The difficulties of modeling discontinuities and the associated need for regularization techniques will be illustrated, and some unexpected element size constraints will be presented. Finally, some of the difficulties in constructing models of composite structures capable of predicting transverse matrix cracking will be discussed. It will be shown that to predict the initiation and propagation of transverse matrix cracks, their density, and their saturation may require models that are significantly more refined than those that have been contemplated in the past.

GRAIN REFINEMENT OF URANIUM BILLETS

DOEpatents

Lewis, L.

1964-02-25

A method of refining the grain structure of massive uranium billets without resort to forging is described. The method consists in the steps of beta- quenching the billets, annealing the quenched billets in the upper alpha temperature range, and extrusion upset of the billets to an extent sufficient to increase the cross sectional area by at least 5 per cent. (AEC)

Bio-Nanocombinatoric Synthesis and Quorum Sensing

DTIC Science & Technology

2015-10-09

inputs and biotemplating of nanomaterials; and 3) informatic /analytical feedback, which provides output measurement refinement 15. SUBJECT TERMS 16...nanomaterials; and 3) informatic /analytical feedback, which provides output measurement and refinement. To this end, we have successfully generated...microfibers. 5   Basic features of the experimental system and observations of the multicompartment structures: We can encapsulate oil droplets in

Controlling Reflections from Mesh Refinement Interfaces in Numerical Relativity

NASA Technical Reports Server (NTRS)

Baker, John G.; Van Meter, James R.

2005-01-01

A leading approach to improving the accuracy on numerical relativity simulations of black hole systems is through fixed or adaptive mesh refinement techniques. We describe a generic numerical error which manifests as slowly converging, artificial reflections from refinement boundaries in a broad class of mesh-refinement implementations, potentially limiting the effectiveness of mesh- refinement techniques for some numerical relativity applications. We elucidate this numerical effect by presenting a model problem which exhibits the phenomenon, but which is simple enough that its numerical error can be understood analytically. Our analysis shows that the effect is caused by variations in finite differencing error generated across low and high resolution regions, and that its slow convergence is caused by the presence of dramatic speed differences among propagation modes typical of 3+1 relativity. Lastly, we resolve the problem, presenting a class of finite-differencing stencil modifications which eliminate this pathology in both our model problem and in numerical relativity examples.

Automated protein structure modeling in CASP9 by I-TASSER pipeline combined with QUARK-based ab initio folding and FG-MD-based structure refinement

PubMed Central

Xu, Dong; Zhang, Jian; Roy, Ambrish; Zhang, Yang

2011-01-01

I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and FG-MD, were added to the I-TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I-TASSER structure assembly simulations. FG-MD is an atomic-level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen-bonding networks, torsion angles and steric clashes. Despite considerable progress in both the template-based and template-free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of beta-proteins are still needed to further improve the I-TASSER pipeline. PMID:22069036

DOE Office of Scientific and Technical Information (OSTI.GOV)

Von Dreele, Robert

One of the goals in developing GSAS-II was to expand from the capabilities of the original General Structure Analysis System (GSAS) which largely encompassed just structure refinement and post refinement analysis. GSAS-II has been written almost entirely in Python loaded with graphics, GUI and mathematical packages (matplotlib, pyOpenGL, wxpython, numpy and scipy). Thus, GSAS-II has a fully developed modern GUI as well as extensive graphical display of data and results. However, the structure and operation of Python has required new approaches to many of the algorithms used in crystal structure analysis. The extensions beyond GSAS include image calibration/integration as wellmore » as peak fitting and unit cell indexing for powder data which are precursors for structure solution. Structure solution within GSAS-II begins with either Pawley or LeBail extracted structure factors from powder data or those measured in a single crystal experiment. Both charge flipping and Monte Carlo-Simulated Annealing techniques are available; the former can be applied to (3+1) incommensurate structures as well as conventional 3D structures.« less

Ultra-high-resolution X-ray structure of proteins.

PubMed

Lecomte, C; Guillot, B; Muzet, N; Pichon-Pesme, V; Jelsch, C

2004-04-01

The constant advances in synchrotron radiation sources and crystallogenesis methods and the impulse of structural genomics projects have brought biocrystallography to a context favorable to subatomic resolution protein and nucleic acid structures. Thus, as soon as such precision can be frequently obtained, the amount of information available in the precise electron density should also be easily and naturally exploited, similarly to the field of small molecule charge density studies. Indeed, the use of a nonspherical model for the atomic electron density in the refinement of subatomic resolution protein structures allows the experimental description of their electrostatic properties. Some methods we have developed and implemented in our multipolar refinement program MoPro for this purpose are presented. Examples of successful applications to several subatomic resolution protein structures, including the 0.66 angstrom resolution human aldose reductase, are described.

Calcio-olivine {gamma}-Ca{sub 2}SiO{sub 4}: I. Rietveld refinement of the crystal structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gobechiya, E. R., E-mail: elgob@mail.ru; Yamnova, N. A.; Zadov, A. E.

2008-05-15

The structure of the natural mineral calcio-olivine ({gamma}-Ca{sub 2}SiO{sub 4}) found in skarn xenoliths in the region of the Lakargi Mountain (North Caucasus, Kabardino-Balkaria, Russia) is refined by the Rietveld method [a = 5.07389(7) A, b = 11.21128(14) A, c = 6.75340(9) A, V = 384.170(5) A{sup 3}, Z = 4, {rho}{sub calcd} = 2.98 g/cm{sup 3}, space group Pbnm]. The X-ray diffraction pattern of a powdered sample is recorded on a STOE STADI MP diffractometer [{lambda}CuK{sub {alpha}1}; Ge(111) primary monochromator; 6.00{sup o} < 2{theta} < 100.88{sup o}; step width, 2.5{sup o} in 2{theta}; number of reflections, 224]. All calculationsmore » are performed with the WYRIET (version 3.3) software package. The structural model is refined in the anisotropic approximation to R{sub p} = 6.44, R{sub wp} = 8.52, R{sub exp} = 5.85, R{sub B} = 4.98, R{sub F} = 6.90, and s = 1.46. It is shown that the sample under investigation is a mixture of several mineral phases, among which calcio-olivine (the natural analogue of the {gamma}-Ca{sub 2}SiO{sub 4} compound) (83%), hillebrandite (13%), and wadalite (4%) are dominant. Only the scale factors and the unit cell parameters are refined for hillebrandite Ca{sub 2}SiO{sub 3}(OH){sub 2} [a = 3.63472(16) A, b = 16.4140(10) A, c = 11.7914(8) A, space group Cmc2{sub 1}, Z = 6] and wadalite Ca{sub 6}Al{sub 5}Si{sub 2}O{sub 16}Cl{sub 3} (a = 12.0088 A, space group, I 4 bar 3d, Z = 4). The results of the structure refinement of the main component of the sample confirm that the mineral calcio-olivine is isostructural to the synthetic compound {gamma}-Ca{sub 2}SiO{sub 4}. The structure of this compound is formed by the heteropolyhedral framework composed of Ca octahedra joined together into olivine-like ribbons and isolated Si tetrahedra.« less

The comparison of approaches to the solid-state NMR-based structural refinement of vitamin B1 hydrochloride and of its monohydrate

NASA Astrophysics Data System (ADS)

Czernek, Jiří; Pawlak, Tomasz; Potrzebowski, Marek J.; Brus, Jiří

2013-01-01

The 13C and 15N CPMAS SSNMR measurements were accompanied by the proper theoretical description of the solid-phase environment, as provided by the density functional theory in the pseudopotential plane-wave scheme, and employed in refining the atomic coordinates of the crystal structures of thiamine chloride hydrochloride and of its monohydrate. Thus, using the DFT functionals PBE, PW91 and RPBE, the SSNMR-consistent solid-phase structures of these compounds are derived from the geometrical optimization, which is followed by an assessment of the fits of the GIPAW-predicted values of the chemical shielding parameters to their experimental counterparts.

Radiation Damage Workshop

NASA Technical Reports Server (NTRS)

Stella, P. M.

1984-01-01

The availability of data regarding the radiation behavior of GaAs and silicon solar cells is discussed as well as efforts to provide sufficient information. Other materials are considered too immature for reasonable radiation evaluation. The lack of concern over the possible catastrophic radiation degradation in cascade cells is a potentially serious problem. Lithium counterdoping shows potential for removing damage in irradiated P-type material, although initial efficiencies are not comparable to current state of the art. The possibility of refining the lithium doping method to maintain high initial efficiencies and combining it with radiation tolerant structures such as thin BSF cells or vertical junction cells could provide a substantial improvement in EOL efficiencies. Laser annealing of junctions, either those formed ion implantation or diffusion, may not only improve initial cell performance but might also reduce the radiation degradation rate.

Recrystallization and grain growth in NiAl

NASA Technical Reports Server (NTRS)

Haff, G. R.; Schulson, E. M.

1982-01-01

Aluminide intermetallics, because of their strength, microstructural stability, and oxidation resistance at elevated temperatures, represent potential structural materials for use in advanced energy conversion systems. This inherent potential of the intermetallics can currently not be realized in connection with the general brittleness of the materials under ambient conditions. It is pointed out, however, that brittleness is not an inherent characteristic. Single crystals are ductile and polycrystals may be, too, if their grains are fine enough. The present investigation is concerned with an approach for reducing material brittleness, taking into account thermal-mechanically induced grain refinement in NiAl, a B2 aluminide which melts at 1638 C and which retains complete order to its melting point. Attention is given to the kinetics of recrystallization and grain growth of warm-worked, nickel-rich material.

Rietveld analysis of the effect of annealing atmosphere on phase evolution of nanocrystalline TiO2 powders.

PubMed

Salari, M; Rezaee, M; Chidembo, A T; Konstantinov, K; Liu, H K

2012-06-01

The structural evolution of nanocrystalline TiO2 was studied by X-ray diffraction (XRD) and the Rietveld refinement method (RRM). TiO2 powders were prepared by the sol-gel technique. Post annealing of as-synthesized powders in the temperature range from 500 degrees C to 800 degrees C under air and argon atmospheres led to the formation of TiO2 nanoparticles with mean crystallite size in the range of 37-165 nm, based on the Rietveld refinement results. It was found that the phase structure, composition, and crystallite size of the resulting particles were dependent on not only the annealing temperature, but also the annealing atmosphere. Rietveld refinement of the XRD data showed that annealing the powders under argon atmosphere promoted the polymorphic phase transformation from anatase to rutile. Field emission scanning electron microscopy (FESEM) was employed to investigate the morphology and size of the annealed powders.

Figuring Out Gas in Galaxies In Enzo (FOGGIE): Resolving the Inner Circumgalactic Medium

NASA Astrophysics Data System (ADS)

Corlies, Lauren; Peeples, Molly; Tumlinson, Jason; O'Shea, Brian; Smith, Britton

2018-01-01

Cosmological hydrodynamical simulations using every common numerical method have struggled to reproduce the multiphase nature of the circumgalactic medium (CGM) revealed by recent observations. However, to date, resolution in these simulations has been aimed at dense regions — the galactic disk and in-falling satellites — while the diffuse CGM never reaches comparable levels of refinement. Taking advantage of the flexible grid structure of the adaptive mesh refinement code Enzo, we force refinement in a region of the CGM of a Milky Way-like galaxy to the same spatial resolution as that of the disk. In this talk, I will present how the physical and structural distributions of the circumgalactic gas change dramatically as a function of the resolution alone. I will also show the implications these changes have for the observational properties of the gas in the context of the observations.

Parallel Adaptive Mesh Refinement Library

NASA Technical Reports Server (NTRS)

Mac-Neice, Peter; Olson, Kevin

2005-01-01

Parallel Adaptive Mesh Refinement Library (PARAMESH) is a package of Fortran 90 subroutines designed to provide a computer programmer with an easy route to extension of (1) a previously written serial code that uses a logically Cartesian structured mesh into (2) a parallel code with adaptive mesh refinement (AMR). Alternatively, in its simplest use, and with minimal effort, PARAMESH can operate as a domain-decomposition tool for users who want to parallelize their serial codes but who do not wish to utilize adaptivity. The package builds a hierarchy of sub-grids to cover the computational domain of a given application program, with spatial resolution varying to satisfy the demands of the application. The sub-grid blocks form the nodes of a tree data structure (a quad-tree in two or an oct-tree in three dimensions). Each grid block has a logically Cartesian mesh. The package supports one-, two- and three-dimensional models.

Iterative feature refinement for accurate undersampled MR image reconstruction

NASA Astrophysics Data System (ADS)

Wang, Shanshan; Liu, Jianbo; Liu, Qiegen; Ying, Leslie; Liu, Xin; Zheng, Hairong; Liang, Dong

2016-05-01

Accelerating MR scan is of great significance for clinical, research and advanced applications, and one main effort to achieve this is the utilization of compressed sensing (CS) theory. Nevertheless, the existing CSMRI approaches still have limitations such as fine structure loss or high computational complexity. This paper proposes a novel iterative feature refinement (IFR) module for accurate MR image reconstruction from undersampled K-space data. Integrating IFR with CSMRI which is equipped with fixed transforms, we develop an IFR-CS method to restore meaningful structures and details that are originally discarded without introducing too much additional complexity. Specifically, the proposed IFR-CS is realized with three iterative steps, namely sparsity-promoting denoising, feature refinement and Tikhonov regularization. Experimental results on both simulated and in vivo MR datasets have shown that the proposed module has a strong capability to capture image details, and that IFR-CS is comparable and even superior to other state-of-the-art reconstruction approaches.

Neutron powder diffraction and molecular simulation study of the structural evolution of ammonia borane from 15 to 340 K.

PubMed

Hess, Nancy J; Schenter, Gregory K; Hartman, Michael R; Daemen, Luc L; Proffen, Thomas; Kathmann, Shawn M; Mundy, Christopher J; Hartl, Monika; Heldebrant, David J; Stowe, Ashley C; Autrey, Tom

2009-05-14

The structural behavior of (11)B-, (2)H-enriched ammonia borane, ND(3)(11)BD(3), over the temperature range from 15 to 340 K was investigated using a combination of neutron powder diffraction and ab initio molecular dynamics simulations. In the low temperature orthorhombic phase, the progressive displacement of the borane group under the amine group was observed leading to the alignment of the B-N bond near parallel to the c-axis. The orthorhombic to tetragonal structural phase transition at 225 K is marked by dramatic change in the dynamics of both the amine and borane group. The resulting hydrogen disorder is problematic to extract from the metrics provided by Rietveld refinement but is readily apparent in molecular dynamics simulation and in difference Fourier transform maps. At the phase transition, Rietveld refinement does indicate a disruption of one of two dihydrogen bonds that link adjacent ammonia borane molecules. Metrics determined by Rietveld refinement are in excellent agreement with those determined from molecular simulation. This study highlights the valuable insights added by coupled experimental and computational studies.

Simultaneous use of solution NMR and X-ray data in REFMAC5 for joint refinement/detection of structural differences.

PubMed

Rinaldelli, Mauro; Ravera, Enrico; Calderone, Vito; Parigi, Giacomo; Murshudov, Garib N; Luchinat, Claudio

2014-04-01

The program REFMAC5 from CCP4 was modified to allow the simultaneous use of X-ray crystallographic data and paramagnetic NMR data (pseudocontact shifts and self-orientation residual dipolar couplings) and/or diamagnetic residual dipolar couplings. Incorporation of these long-range NMR restraints in REFMAC5 can reveal differences between solid-state and solution conformations of molecules or, in their absence, can be used together with X-ray crystallographic data for structural refinement. Since NMR and X-ray data are complementary, when a single structure is consistent with both sets of data and still maintains reasonably `ideal' geometries, the reliability of the derived atomic model is expected to increase. The program was tested on five different proteins: the catalytic domain of matrix metalloproteinase 1, GB3, ubiquitin, free calmodulin and calmodulin complexed with a peptide. In some cases the joint refinement produced a single model consistent with both sets of observations, while in other cases it indicated, outside the experimental uncertainty, the presence of different protein conformations in solution and in the solid state.

Protein structure refinement using a quantum mechanics-based chemical shielding predictor.

PubMed

Bratholm, Lars A; Jensen, Jan H

2017-03-01

The accurate prediction of protein chemical shifts using a quantum mechanics (QM)-based method has been the subject of intense research for more than 20 years but so far empirical methods for chemical shift prediction have proven more accurate. In this paper we show that a QM-based predictor of a protein backbone and CB chemical shifts (ProCS15, PeerJ , 2016, 3, e1344) is of comparable accuracy to empirical chemical shift predictors after chemical shift-based structural refinement that removes small structural errors. We present a method by which quantum chemistry based predictions of isotropic chemical shielding values (ProCS15) can be used to refine protein structures using Markov Chain Monte Carlo (MCMC) simulations, relating the chemical shielding values to the experimental chemical shifts probabilistically. Two kinds of MCMC structural refinement simulations were performed using force field geometry optimized X-ray structures as starting points: simulated annealing of the starting structure and constant temperature MCMC simulation followed by simulated annealing of a representative ensemble structure. Annealing of the CHARMM structure changes the CA-RMSD by an average of 0.4 Å but lowers the chemical shift RMSD by 1.0 and 0.7 ppm for CA and N. Conformational averaging has a relatively small effect (0.1-0.2 ppm) on the overall agreement with carbon chemical shifts but lowers the error for nitrogen chemical shifts by 0.4 ppm. If an amino acid specific offset is included the ProCS15 predicted chemical shifts have RMSD values relative to experiments that are comparable to popular empirical chemical shift predictors. The annealed representative ensemble structures differ in CA-RMSD relative to the initial structures by an average of 2.0 Å, with >2.0 Å difference for six proteins. In four of the cases, the largest structural differences arise in structurally flexible regions of the protein as determined by NMR, and in the remaining two cases, the large structural change may be due to force field deficiencies. The overall accuracy of the empirical methods are slightly improved by annealing the CHARMM structure with ProCS15, which may suggest that the minor structural changes introduced by ProCS15-based annealing improves the accuracy of the protein structures. Having established that QM-based chemical shift prediction can deliver the same accuracy as empirical shift predictors we hope this can help increase the accuracy of related approaches such as QM/MM or linear scaling approaches or interpreting protein structural dynamics from QM-derived chemical shift.

Re-refinement of the spliceosomal U4 snRNP core-domain structure

PubMed Central

Li, Jade; Leung, Adelaine K.; Kondo, Yasushi; Oubridge, Chris; Nagai, Kiyoshi

2016-01-01

The core domain of small nuclear ribonucleoprotein (snRNP), comprised of a ring of seven paralogous proteins bound around a single-stranded RNA sequence, functions as the assembly nucleus in the maturation of U1, U2, U4 and U5 spliceosomal snRNPs. The structure of the human U4 snRNP core domain was initially solved at 3.6 Å resolution by experimental phasing using data with tetartohedral twinning. Molecular replacement from this model followed by density modification using untwinned data recently led to a structure of the minimal U1 snRNP at 3.3 Å resolution. With the latter structure providing a search model for molecular replacement, the U4 core-domain structure has now been re-refined. The U4 Sm site-sequence AAUUUUU has been shown to bind to the seven Sm proteins SmF–SmE–SmG–SmD3–SmB–SmD1–SmD2 in an identical manner as the U1 Sm-site sequence AAUUUGU, except in SmD1 where the bound U replaces G. The progression from the initial to the re-refined structure exemplifies a tortuous route to accuracy: where well diffracting crystals of complex assemblies are initially unavailable, the early model errors are rectified by exploiting preliminary interpretations in further experiments involving homologous structures. New insights are obtained from the more accurate model. PMID:26894541

Gyre and gimble: a maximum-likelihood replacement for Patterson correlation refinement.

PubMed

McCoy, Airlie J; Oeffner, Robert D; Millán, Claudia; Sammito, Massimo; Usón, Isabel; Read, Randy J

2018-04-01

Descriptions are given of the maximum-likelihood gyre method implemented in Phaser for optimizing the orientation and relative position of rigid-body fragments of a model after the orientation of the model has been identified, but before the model has been positioned in the unit cell, and also the related gimble method for the refinement of rigid-body fragments of the model after positioning. Gyre refinement helps to lower the root-mean-square atomic displacements between model and target molecular-replacement solutions for the test case of antibody Fab(26-10) and improves structure solution with ARCIMBOLDO_SHREDDER.

Solution structure of Syrian hamster prion protein rPrP(90-231).

PubMed

Liu, H; Farr-Jones, S; Ulyanov, N B; Llinas, M; Marqusee, S; Groth, D; Cohen, F E; Prusiner, S B; James, T L

1999-04-27

NMR has been used to refine the structure of Syrian hamster (SHa) prion protein rPrP(90-231), which is commensurate with the infectious protease-resistant core of the scrapie prion protein PrPSc. The structure of rPrP(90-231), refolded to resemble the normal cellular isoform PrPC spectroscopically and immunologically, has been studied using multidimensional NMR; initial results were published [James et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 10086-10091]. We now report refinement with better definition revealing important structural and dynamic features which can be related to biological observations pertinent to prion diseases. Structure refinement was based on 2778 unambiguously assigned nuclear Overhauser effect (NOE) connectivities, 297 ambiguous NOE restraints, and 63 scalar coupling constants (3JHNHa). The structure is represented by an ensemble of 25 best-scoring structures from 100 structures calculated using ARIA/X-PLOR and further refined with restrained molecular dynamics using the AMBER 4.1 force field with an explicit shell of water molecules. The rPrP(90-231) structure features a core domain (residues 125-228), with a backbone atomic root-mean-square deviation (RMSD) of 0.67 A, consisting of three alpha-helices (residues 144-154, 172-193, and 200-227) and two short antiparallel beta-strands (residues 129-131 and 161-163). The N-terminus (residues 90-119) is largely unstructured despite some sparse and weak medium-range NOEs implying the existence of bends or turns. The transition region between the core domain and flexible N-terminus, i.e., residues 113-128, consists of hydrophobic residues or glycines and does not adopt any regular secondary structure in aqueous solution. There are about 30 medium- and long-range NOEs within this hydrophobic cluster, so it clearly manifests structure. Multiple discrete conformations are evident, implying the possible existence of one or more metastable states, which may feature in conversion of PrPC to PrPSc. To obtain a more comprehensive picture of rPrP(90-231), dynamics have been studied using amide hydrogen-deuterium exchange and 15N NMR relaxation times (T1 and T2) and 15N{1H} NOE measurements. Comparison of the structure with previous reports suggests sequence-dependent features that may be reflected in a species barrier to prion disease transmission.

Internet pornography use: perceived addiction, psychological distress, and the validation of a brief measure.

PubMed

Grubbs, Joshua B; Volk, Fred; Exline, Julie J; Pargament, Kenneth I

2015-01-01

The authors aimed to validate a brief measure of perceived addiction to Internet pornography refined from the 32-item Cyber Pornography Use Inventory, report its psychometric properties, and examine how the notion of perceived addiction to Internet pornography might be related to other domains of psychological functioning. To accomplish this, 3 studies were conducted using a sample of undergraduate psychology students, a web-based adult sample, and a sample of college students seeking counseling at a university's counseling center. The authors developed and refined a short 9-item measure of perceived addiction to Internet pornography, confirmed its structure in multiple samples, examined its relatedness to hypersexuality more broadly, and demonstrated that the notion of perceived addiction to Internet pornography is very robustly related to various measures of psychological distress. Furthermore, the relation between psychological distress and the new measure persisted, even when other potential contributors (e.g., neuroticism, self-control, amount of time spent viewing pornography) were controlled for statistically, indicating the clinical relevance of assessing perceived addiction to Internet pornography.

Network structure and concentration fluctuations in a series of elemental, binary, and tertiary liquids and glasses.

PubMed

Soper, Alan K

2010-10-13

Liquids and glasses continue to produce a lively debate about the nature of the disordered structure in these materials, and whether it is driven by longer range concentration or density fluctuations. One factor often lacking in these studies is an overview of a wide range of structures from which common features of and differences between materials can be identified. Here I examine the structure of a wide range of chain and network, elemental, binary and tertiary liquids and glasses, using available x-ray and neutron diffraction data and combining them with empirical potential structure refinement. Calculation of the Bhatia-Thornton number-number and concentration-concentration structure factors and distribution functions highlights common structural motifs that run through many of the series. It is found that the greatest structural overlap occurs where the nearest-neighbour and second-neighbour coordination numbers are similar for different materials. As these coordination numbers increase, so the structures undergo a sequence of characteristic changes involving increasingly bent bond angle distributions and increased packing fractions. In these regards liquid and amorphous phosphorus appear to be in a structural class of their own, combining both chain-like and network-like characteristics.

Discovery of optimal zeolites for challenging separations and chemical transformations using predictive materials modeling

NASA Astrophysics Data System (ADS)

Bai, Peng; Jeon, Mi Young; Ren, Limin; Knight, Chris; Deem, Michael W.; Tsapatsis, Michael; Siepmann, J. Ilja

2015-01-01

Zeolites play numerous important roles in modern petroleum refineries and have the potential to advance the production of fuels and chemical feedstocks from renewable resources. The performance of a zeolite as separation medium and catalyst depends on its framework structure. To date, 213 framework types have been synthesized and >330,000 thermodynamically accessible zeolite structures have been predicted. Hence, identification of optimal zeolites for a given application from the large pool of candidate structures is attractive for accelerating the pace of materials discovery. Here we identify, through a large-scale, multi-step computational screening process, promising zeolite structures for two energy-related applications: the purification of ethanol from fermentation broths and the hydroisomerization of alkanes with 18-30 carbon atoms encountered in petroleum refining. These results demonstrate that predictive modelling and data-driven science can now be applied to solve some of the most challenging separation problems involving highly non-ideal mixtures and highly articulated compounds.

A Simplified Model of Local Structure in Aqueous Proline Amino Acid Revealed by First-Principles Molecular Dynamics Simulations

PubMed Central

Troitzsch, Raphael Z.; Tulip, Paul R.; Crain, Jason; Martyna, Glenn J.

2008-01-01

Aqueous proline solutions are deceptively simple as they can take on complex roles such as protein chaperones, cryoprotectants, and hydrotropic agents in biological processes. Here, a molecular level picture of proline/water mixtures is developed. Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations of aqueous proline amino acid at the B-LYP level of theory, performed using IBM's Blue Gene/L supercomputer and massively parallel software, reveal hydrogen-bonding propensities that are at odds with the predictions of the CHARMM22 empirical force field but are in better agreement with results of recent neutron diffraction experiments. In general, the CPAIMD (B-LYP) simulations predict a simplified structural model of proline/water mixtures consisting of fewer distinct local motifs. Comparisons of simulation results to experiment are made by direct evaluation of the neutron static structure factor S(Q) from CPAIMD (B-LYP) trajectories as well as to the results of the empirical potential structure refinement reverse Monte Carlo procedure applied to the neutron data. PMID:18790850

A simplified model of local structure in aqueous proline amino acid revealed by first-principles molecular dynamics simulations.

PubMed

Troitzsch, Raphael Z; Tulip, Paul R; Crain, Jason; Martyna, Glenn J

2008-12-01

Aqueous proline solutions are deceptively simple as they can take on complex roles such as protein chaperones, cryoprotectants, and hydrotropic agents in biological processes. Here, a molecular level picture of proline/water mixtures is developed. Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations of aqueous proline amino acid at the B-LYP level of theory, performed using IBM's Blue Gene/L supercomputer and massively parallel software, reveal hydrogen-bonding propensities that are at odds with the predictions of the CHARMM22 empirical force field but are in better agreement with results of recent neutron diffraction experiments. In general, the CPAIMD (B-LYP) simulations predict a simplified structural model of proline/water mixtures consisting of fewer distinct local motifs. Comparisons of simulation results to experiment are made by direct evaluation of the neutron static structure factor S(Q) from CPAIMD (B-LYP) trajectories as well as to the results of the empirical potential structure refinement reverse Monte Carlo procedure applied to the neutron data.

NASA Handbook for Spacecraft Structural Dynamics Testing

NASA Technical Reports Server (NTRS)

Kern, Dennis L.; Scharton, Terry D.

2005-01-01

Recent advances in the area of structural dynamics and vibrations, in both methodology and capability, have the potential to make spacecraft system testing more effective from technical, cost, schedule, and hardware safety points of view. However, application of these advanced test methods varies widely among the NASA Centers and their contractors. Identification and refinement of the best of these test methodologies and implementation approaches has been an objective of efforts by the Jet Propulsion Laboratory on behalf of the NASA Office of the Chief Engineer. But to develop the most appropriate overall test program for a flight project from the selection of advanced methodologies, as well as conventional test methods, spacecraft project managers and their technical staffs will need overall guidance and technical rationale. Thus, the Chief Engineer's Office has recently tasked JPL to prepare a NASA Handbook for Spacecraft Structural Dynamics Testing. An outline of the proposed handbook, with a synopsis of each section, has been developed and is presented herein. Comments on the proposed handbook are solicited from the spacecraft structural dynamics testing community.

NASA Handbook for Spacecraft Structural Dynamics Testing

NASA Technical Reports Server (NTRS)

Kern, Dennis L.; Scharton, Terry D.

2004-01-01

Recent advances in the area of structural dynamics and vibrations, in both methodology and capability, have the potential to make spacecraft system testing more effective from technical, cost, schedule, and hardware safety points of view. However, application of these advanced test methods varies widely among the NASA Centers and their contractors. Identification and refinement of the best of these test methodologies and implementation approaches has been an objective of efforts by the Jet Propulsion Laboratory on behalf of the NASA Office of the Chief Engineer. But to develop the most appropriate overall test program for a flight project from the selection of advanced methodologies, as well as conventional test methods, spacecraft project managers and their technical staffs will need overall guidance and technical rationale. Thus, the Chief Engineer's Office has recently tasked JPL to prepare a NASA Handbook for Spacecraft Structural Dynamics Testing. An outline of the proposed handbook, with a synopsis of each section, has been developed and is presented herein. Comments on the proposed handbook is solicited from the spacecraft structural dynamics testing community.

Binding of Amphipathic Cell Penetrating Peptide p28 to Wild Type and Mutated p53 as studied by Raman, Atomic Force and Surface Plasmon Resonance spectroscopies.

PubMed

Signorelli, Sara; Santini, Simona; Yamada, Tohru; Bizzarri, Anna Rita; Beattie, Craig W; Cannistraro, Salvatore

2017-04-01

Mutations within the DNA binding domain (DBD) of the tumor suppressor p53 are found in >50% of human cancers and may significantly modify p53 secondary structure impairing its function. p28, an amphipathic cell-penetrating peptide, binds to the DBD through hydrophobic interaction and induces a posttranslational increase in wildtype and mutant p53 restoring functionality. We use mutation analyses to explore which elements of secondary structure may be critical to p28 binding. Molecular modeling, Raman spectroscopy, Atomic Force Spectroscopy (AFS) and Surface Plasmon Resonance (SPR) were used to identify which secondary structure of site-directed and naturally occurring mutant DBDs are potentially altered by discrete changes in hydrophobicity and the molecular interaction with p28. We show that specific point mutations that alter hydrophobicity within non-mutable and mutable regions of the p53 DBD alter specific secondary structures. The affinity of p28 was positively correlated with the β-sheet content of a mutant DBD, and reduced by an increase in unstructured or random coil that resulted from a loss in hydrophobicity and redistribution of surface charge. These results help refine our knowledge of how mutations within p53-DBD alter secondary structure and provide insight on how potential structural alterations in p28 or similar molecules improve their ability to restore p53 function. Raman spectroscopy, AFS, SPR and computational modeling are useful approaches to characterize how mutations within the p53DBD potentially affect secondary structure and identify those structural elements prone to influence the binding affinity of agents designed to increase the functionality of p53. Copyright © 2017 Elsevier B.V. All rights reserved.

GeneBuilder: interactive in silico prediction of gene structure.

PubMed

Milanesi, L; D'Angelo, D; Rogozin, I B

1999-01-01

Prediction of gene structure in newly sequenced DNA becomes very important in large genome sequencing projects. This problem is complicated due to the exon-intron structure of eukaryotic genes and because gene expression is regulated by many different short nucleotide domains. In order to be able to analyse the full gene structure in different organisms, it is necessary to combine information about potential functional signals (promoter region, splice sites, start and stop codons, 3' untranslated region) together with the statistical properties of coding sequences (coding potential), information about homologous proteins, ESTs and repeated elements. We have developed the GeneBuilder system which is based on prediction of functional signals and coding regions by different approaches in combination with similarity searches in proteins and EST databases. The potential gene structure models are obtained by using a dynamic programming method. The program permits the use of several parameters for gene structure prediction and refinement. During gene model construction, selecting different exon homology levels with a protein sequence selected from a list of homologous proteins can improve the accuracy of the gene structure prediction. In the case of low homology, GeneBuilder is still able to predict the gene structure. The GeneBuilder system has been tested by using the standard set (Burset and Guigo, Genomics, 34, 353-367, 1996) and the performances are: 0.89 sensitivity and 0.91 specificity at the nucleotide level. The total correlation coefficient is 0.88. The GeneBuilder system is implemented as a part of the WebGene a the URL: http://www.itba.mi. cnr.it/webgene and TRADAT (TRAncription Database and Analysis Tools) launcher URL: http://www.itba.mi.cnr.it/tradat.

Effects of grain refinement on the biocorrosion and in vitro bioactivity of magnesium.

PubMed

Saha, Partha; Roy, Mangal; Datta, Moni Kanchan; Lee, Boeun; Kumta, Prashant N

2015-12-01

Magnesium is a new class of biodegradable metals potentially suitable for bone fracture fixation due to its suitable mechanical properties, high degradability and biocompatibility. However, rapid corrosion and loss in mechanical strength under physiological conditions render it unsuitable for load-bearing applications. In the present study, grain refinement was implemented to control bio-corrosion demonstrating improved in vitro bioactivity of magnesium. Pure commercial magnesium was grain refined using different amounts of zirconium (0.25 and 1.0 wt.%). Corrosion behavior was studied by potentiodynamic polarization (PDP) and mass loss immersion tests demonstrating corrosion rate decrease with grain size reduction. In vitro biocompatibility tests conducted by MC3T3-E1 pre-osteoblast cells and measured by DNA quantification demonstrate significant increase in cell proliferation for Mg-1 wt.% Zr at day 5. Similarly, alkaline phosphatase (ALP) activity was higher for grain refined Mg. Alloys were also tested for ability to support osteoclast differentiation using RAW264.7 monocytes with receptor activator of nuclear factor kappa-β ligand (RANKL) supplemented cell culture. Osteoclast differentiation process was observed to be severely restricted for smaller grained Mg. Overall, the results indicate grain refinement to be useful not only for improving corrosion resistance of Mg implants for bone fixation devices but also potentially modulate bone regeneration around the implant. Copyright © 2015 Elsevier B.V. All rights reserved.

Local structure of molten AuGa 2 under pressure: Evidence for coordination change and planetary implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalkan, Bora; Godwal, Budhiram; Raju, Selva Vennila

In situ x-ray diffraction measurements and inverse Monte Carlo simulations of pair distribution functions were used to characterize the local structure of molten AuGa 2 up to 16 GPa and 940 K. Our results document systematic changes in liquid structure due to a combination of bond compression and coordination increase. Empirical potential structure refinement shows the first-neighbor coordination of Ga around Au and of Au around Ga to increase from about 8 to 10 and 4 to 5, respectively between 0 and 16 GPa, and the inferred changes in liquid structure can explain the observed melting-point depression of AuGa2 upmore » to 5 GPa. As intermetallic AuGa 2 is an analogue for metallic SiO 2 at much higher pressures, our results imply that structural changes documented for non-metallic silicate melts below 100 GPa are followed by additional coordination changes in the metallic state at pressures in the 0.2–1 TPa range achieved inside large planets.« less

Local structure of molten AuGa 2 under pressure: Evidence for coordination change and planetary implications

DOE PAGES

Kalkan, Bora; Godwal, Budhiram; Raju, Selva Vennila; ...

2018-05-01

In situ x-ray diffraction measurements and inverse Monte Carlo simulations of pair distribution functions were used to characterize the local structure of molten AuGa 2 up to 16 GPa and 940 K. Our results document systematic changes in liquid structure due to a combination of bond compression and coordination increase. Empirical potential structure refinement shows the first-neighbor coordination of Ga around Au and of Au around Ga to increase from about 8 to 10 and 4 to 5, respectively between 0 and 16 GPa, and the inferred changes in liquid structure can explain the observed melting-point depression of AuGa2 upmore » to 5 GPa. As intermetallic AuGa 2 is an analogue for metallic SiO 2 at much higher pressures, our results imply that structural changes documented for non-metallic silicate melts below 100 GPa are followed by additional coordination changes in the metallic state at pressures in the 0.2–1 TPa range achieved inside large planets.« less

Crystal structure, quantum mechanical investigation, IR and NMR spectroscopy of two new organic salts: (C8H12NO)·[NO3] (I) and (C8H14N4)·[ClO4]2 (II)

NASA Astrophysics Data System (ADS)

Bayar, I.; Khedhiri, L.; Soudani, S.; Lefebvre, F.; Pereira da Silva, P. S.; Ben Nasr, C.

2018-06-01

Two new organic-inorganic hybrid materials, 4-methoxybenzylammonium nitrate, (C8H12NO)·[NO3] (I), and 2-(1-piperazinyl)pyrimidinium bis(perchlorate), (C8H14N4)·[ClO4]2(II), have been synthesized by an acid/base reaction at room temperature, their structures were determined by single crystal X-ray diffraction. Compound (I) crystallizes in the orthorhombic system and Pnma space group with a = 15.7908 (7), b = 6.8032 (3), c = 8.7091 (4) Å, V = 935.60 (7) Å3 with Z = 4. Full-matrix least-squares refinement converged at R = 0.038 and wR(F2) = 0.115. Compound (II) belongs to the monoclinic system, space group P21/c with the following parameters: a = 10.798(2), b = 7.330(1), c = 21.186(2) Å, β = 120.641 (4)°, V = 1442.7 (3) Å3and Z = 4. The structure was refined to R = 0.044, wR(F2) = 0.132. In the structures of (I) and (II), the anionic and cationic entities are interconnected by hydrogen bonding contacts forming three-dimensional networks. Intermolecular interactions were investigated by Hirshfeld surfaces and the contacts of the four different chloride atoms in (II) were compared. The Molecular Electrostatic Potential (MEP) maps and the HOMO and LUMO energy gaps of both compounds were computed. The vibrational absorption bands were identified by infrared spectroscopy. These compounds were also investigated by solid-state 13C, 35Cl and 15N NMR spectroscopy. DFT calculations allowed the attribution of the IR and NMR bands.

Structure determination of two modulated gamma-brass structures in the Zn-Pd System through a (3 + 1)-dimensional space description.

PubMed

Gourdon, Olivier; Izaola, Zunbeltz; Elcoro, Luis; Petricek, Vaclav; Miller, Gordon J

2009-10-19

The structure determination of two composite compounds in the Zn-Pd system with close relationships to the cubic gamma-brass structure Zn(11-delta)Pd(2+delta) is reported. Their structures have been solved from single crystal X-ray diffraction data within a (3 + 1)-dimensional [(3 + 1)D] formalism. Zn(75.7(7))Pd(24.3) and Zn(78.8(7))Pd(21.2) crystallize with orthorhombic symmetry, superspace group Xmmm(00gamma)0s0 (X = [(1/2,1/2,0,0); (0,1/2,1/2,1/2); (1/2,0,1/2,1/2)]), with the following lattice parameters, respectively: a(s) = 12.929(3) A, b(s) = 9.112(4) A, c(s) = 2.5631(7) A, q = 8/13 c* and V(s) = 302.1(3) A(3) and a(s) = 12.909(3) A, b(s) = 9.115(3) A, c(s) = 2.6052(6) A, q = 11/18 c* and V(s) = 306.4(2) A(3). Their structures may be considered as commensurate because they can be refined in the conventional 3D space groups (Cmce and Cmcm, respectively) using supercells, but they also refined within the (3 + 1)D formalism to residual factors R = 3.14% for 139 parameters and 1184 independent reflections for Zn(75.7(7))Pd(24.3) and R = 3.16% for 175 parameters and 1804 independent reflections for Zn(78.8(7))Pd(21.2). The use of the (3 + 1)D formalism improves the results of the refinement and leads to a better understanding of the complexity of the atomic arrangement through the various modulations (occupation waves and displacive waves). Our refinements emphasize a unique Pd/Zn occupancy modulation at the center of distorted icosahedra, a modulation which correlates with the distortion of these polyhedra.

Refined gradient theory of scale-dependent superthin rods

NASA Astrophysics Data System (ADS)

Lurie, S. A.; Kuznetsova, E. L.; Rabinskii, L. N.; Popova, E. I.

2015-03-01

A version of the refined nonclassical theory of thin beams whose thickness is comparable with the scale characteristic of the material structure is constructed on the basis of the gradient theory of elasticity which, in contrast to the classical theory, contains some additional physical characteristics depending on the structure scale parameters and is therefore most appropriate for modeling the strains of scale-dependent systems. The fundamental conditions for the well-posedness of the gradient theories are obtained for the first time, and it is shown that some of the known applied gradient theories do not generally satisfy the well-posedness criterion. A version of the well-posed gradient strain theory which satisfies the symmetry condition is proposed. The well-posed gradient theory is then used to implement the method of kinematic hypotheses for constructing a refined theory of scale-dependent beams. The equilibrium equations of the refined theory of scale-dependent Timoshenko and Bernoulli beams are obtained. It is shown that the scale effects are localized near the beam ends, and therefore, taking the scale effects into account does not give any correction to the bending rigidity of long beams as noted in the previously published papers dealing with the scale-dependent beams.

Refinement of the β-Sn Grains in Ni-Doped Sn-3.0Ag-0.5Cu Solder Joints with Cu-Based and Ni-Based Substrates

NASA Astrophysics Data System (ADS)

Chou, Tzu-Ting; Chen, Wei-Yu; Fleshman, Collin Jordon; Duh, Jenq-Gong

2018-03-01

A fine-grain structure with random orientations of lead-free solder joints was successfully obtained in this study. The Sn-Ag-Cu solder alloys doped with minor Ni were reflowed with Ni-based or Cu-based substrates to fabricate the joints containing different Ni content. Adding 0.1 wt.% Ni into the solder effectively promoted the formation of fine Sn grains, and reflowing with Ni-based substrates further enhanced the effects of β-Sn grain refinement. The crystallographic characteristics and the microstructures were analyzed to identify the solidification mechanism of different types of microstructure in the joints. The phase precipitating order in the joint altered as the solder composition were modified by elemental doping and changing substrate, which significantly affected the efficiency of grain refinement and the final grain structure. The formation mechanism of fine β-Sn grains in the Ni-doped joint with a Ni-based substrate is attributable to the heterogeneous nucleation by Ni, whereas the Ni in the joint using ChouCu-based substrate is consumed to form an intermetallic compound and thus retard the effect of grain refining.

Mars Aqueous Processing System

NASA Technical Reports Server (NTRS)

Berggren, Mark; Wilson, Cherie; Carrera, Stacy; Rose, Heather; Muscatello, Anthony; Kilgore, James; Zubrin, Robert

2012-01-01

The goal of the Mars Aqueous Processing System (MAPS) is to establish a flexible process that generates multiple products that are useful for human habitation. Selectively extracting useful components into an aqueous solution, and then sequentially recovering individual constituents, can obtain a suite of refined or semi-refined products. Similarities in the bulk composition (although not necessarily of the mineralogy) of Martian and Lunar soils potentially make MAPS widely applicable. Similar process steps can be conducted on both Mars and Lunar soils while tailoring the reaction extents and recoveries to the specifics of each location. The MAPS closed-loop process selectively extracts, and then recovers, constituents from soils using acids and bases. The emphasis on Mars involves the production of useful materials such as iron, silica, alumina, magnesia, and concrete with recovery of oxygen as a byproduct. On the Moon, similar chemistry is applied with emphasis on oxygen production. This innovation has been demonstrated to produce high-grade materials, such as metallic iron, aluminum oxide, magnesium oxide, and calcium oxide, from lunar and Martian soil simulants. Most of the target products exhibited purities of 80 to 90 percent or more, allowing direct use for many potential applications. Up to one-fourth of the feed soil mass was converted to metal, metal oxide, and oxygen products. The soil residue contained elevated silica content, allowing for potential additional refining and extraction for recovery of materials needed for photovoltaic, semiconductor, and glass applications. A high-grade iron oxide concentrate derived from lunar soil simulant was used to produce a metallic iron component using a novel, combined hydrogen reduction/metal sintering technique. The part was subsequently machined and found to be structurally sound. The behavior of the lunar-simulant-derived iron product was very similar to that produced using the same methods on a Michigan iron ore concentrate, which demonstrates that lunar-derived material can be used in a manner similar to conventional terrestrial iron. Metallic iron was also produced from the Mars soil simulant. The aluminum and magnesium oxide products produced by MAPS from lunar and Mars soil simulants exhibited excellent thermal stability, and were shown to be capable of use for refractory oxide structural materials, or insulation at temperatures far in excess of what could be achieved using unrefined soils. These materials exhibited the refractory characteristics needed to support iron casting and forming operations, as well as other thermal processing needs. Extraction residue samples contained up to 79 percent silica. Such samples were successfully fused into a glass that exhibited high light transmittance.

Leisure activities among older Germans - a qualitative study.

PubMed

Boggatz, Thomas

2013-05-01

Leisure activities contribute to well-being and health in old age. Community nurses should consequently promote such activities among older persons. To do so they need an understanding of older persons' interest in leisure activities. Social contacts, volunteering and pursuit of hobbies and interests constitute the main aspects of leisure. This study aimed to determine the attitudes of older Germans to these aspects to identify user types of leisure time facilities. A qualitative study was conducted within a community-based project in an industrial town in West Germany. Data were collected with semi-structured guideline interviews and evaluated with qualitative content analysis according to Mayring. With regard to social contacts attitudes ranged from limited need for contacts to being a reliable member in an older persons' club. Social engagement is only found among the latter. Pursuit of hobbies and interest ranged from being a minimal user of leisure time facilities to refined expectations. Inflexible group structures may prevent potential users from participation despite having a programme in accordance with target group needs. Attitudes to leisure activities can be described as a combination of two dimensions: the degree of social involvement and the desired refinement of hobbies and interest. Community nurses who organise social afternoons need to assess these attitudes and should steer social dynamics of in a way that facilitates access for newcomers. © 2012 Blackwell Publishing Ltd.

Testing the price and affordability of healthy and current (unhealthy) diets and the potential impacts of policy change in Australia.

PubMed

Lee, Amanda J; Kane, Sarah; Ramsey, Rebecca; Good, Elizabeth; Dick, Mathew

2016-04-12

Price and affordability of foods are important determinants of health. Targeted food pricing policies may help improve population diets. However, methods producing comparable data to inform relevant policy decisions are lacking in Australia and globally. The objective was to develop and pilot standardised methods to assess the price, relative price and affordability of healthy (recommended) and current (unhealthy) diets and test impacts of a potential policy change. Methods followed the optimal approach proposed by INFORMAS using recent Australian dietary intake data and guidelines. Draft healthy and current (unhealthy) diet baskets were developed for five household structures. Food prices were collected in stores in a high and low SES location in Brisbane, Australia. Diet prices were calculated and compared with household incomes, and with potential changes to the Australian Taxation System. Wilcoxen-signed rank tests were used to compare differences in price. The draft tools and protocols were deemed acceptable at household level, but methods could be refined. All households spend more on current (unhealthy) diets than required to purchase healthy (recommended) diets, with the majority (53-64 %) of the food budget being spent on 'discretionary' choices, including take-away foods and alcohol. A healthy diet presently costs between 20-31 % of disposable income of low income households, but would become unaffordable for these families under proposed changes to expand the GST to apply to all foods in Australia. Results confirmed that diet pricing methods providing meaningful, comparable data to inform potential fiscal and health policy actions can be developed, but draft tools should be refined. Results suggest that healthy diets can be more affordable than current (unhealthy) diets in Australia, but other factors may be as important as price in determining food choices.

NMR data-driven structure determination using NMR-I-TASSER in the CASD-NMR experiment

PubMed Central

Jang, Richard; Wang, Yan

2015-01-01

NMR-I-TASSER, an adaption of the I-TASSER algorithm combining NMR data for protein structure determination, recently joined the second round of the CASD-NMR experiment. Unlike many molecular dynamics-based methods, NMR-I-TASSER takes a molecular replacement-like approach to the problem by first threading the target through the PDB to identify structural templates which are then used for iterative NOE assignments and fragment structure assembly refinements. The employment of multiple templates allows NMR-I-TASSER to sample different topologies while convergence to a single structure is not required. Retroactive and blind tests of the CASD-NMR targets from Rounds 1 and 2 demonstrate that even without using NOE peak lists I-TASSER can generate correct structure topology with 15 of 20 targets having a TM-score above 0.5. With the addition of NOE-based distance restraints, NMR-I-TASSER significantly improved the I-TASSER models with all models having the TM-score above 0.5. The average RMSD was reduced from 5.29 to 2.14 Å in Round 1 and 3.18 to 1.71 Å in Round 2. There is no obvious difference in the modeling results with using raw and refined peak lists, indicating robustness of the pipeline to the NOE assignment errors. Overall, despite the low-resolution modeling the current NMR-I-TASSER pipeline provides a coarse-grained structure folding approach complementary to traditional molecular dynamics simulations, which can produce fast near-native frameworks for atomic-level structural refinement. PMID:25737244

Combined PDF and Rietveld studies of ADORable zeolites and the disordered intermediate IPC-1P.

PubMed

Morris, Samuel A; Wheatley, Paul S; Položij, Miroslav; Nachtigall, Petr; Eliášová, Pavla; Čejka, Jiří; Lucas, Tim C; Hriljac, Joseph A; Pinar, Ana B; Morris, Russell E

2016-09-28

The disordered intermediate of the ADORable zeolite UTL has been structurally confirmed using the pair distribution function (PDF) technique. The intermediate, IPC-1P, is a disordered layered compound formed by the hydrolysis of UTL in 0.1 M hydrochloric acid solution. Its structure is unsolvable by traditional X-ray diffraction techniques. The PDF technique was first benchmarked against high-quality synchrotron Rietveld refinements of IPC-2 (OKO) and IPC-4 (PCR) - two end products of IPC-1P condensation that share very similar structural features. An IPC-1P starting model derived from density functional theory was used for the PDF refinement, which yielded a final fit of Rw = 18% and a geometrically reasonable structure. This confirms the layers do stay intact throughout the ADOR process and shows PDF is a viable technique for layered zeolite structure determination.

An approach for prominent enhancement of the quality of konjac flour: dimethyl sulfoxide as medium.

PubMed

Ye, Ting; Wang, Ling; Xu, Wei; Liu, Jinjin; Wang, Yuntao; Zhu, Kunkun; Wang, Sujuan; Li, Bin; Wang, Chao

2014-01-01

In this paper, an approach to improve several konjac flour (KF) qualities by dimethyl sulfoxide (DMSO) addition using various concentrations at different temperature levels was proposed. Also, various properties of native and refined KF, including transparency, chemical composition and rheological properties have been investigated. The results showed that the KF refined by 75% DMSO achieved 27.7% improvement in transparency, 99.7% removal of starch, 99.4% removal of soluble sugar, and 98.2% removal of protein as well as more satisfactory viscosity stability. In addition, the morphology structure of refined KF showed a significant difference compared with the native one as observed using the SEM, which is promising for further industrial application. Furthermore, the rheological properties of both native and refined konjac sols were studied and the results showed that DMSO refinement is an effective and alternative approach to improve the qualities of KF in many aspects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Single-crystal growth, structure refinement and the properties of Bis(glycine) Strontium Chloride

NASA Astrophysics Data System (ADS)

Balaji, S. R.; Balu, T.; Rajasekaran, T. R.

2018-02-01

Single crystals of Bis (glycine) Strontium Chloride (BGSC) were grown by means of slow evaporation process by using analar grade Glycine and Strontium Chloride Hexahydrate as a parent compound from its aqueous solution at room temperature. The final chemical composition, [{{Sr}}{({{{C}}}2{{{H}}}5{{{NO}}}2)}2{{{Cl}}}2].{{{H}}}4{{{O}}}3+{{{H}}}8{{{O}}}3, formed were metallic light colorless block, about the size of 28 mm × 9 mm × 8 mm. A single-crystal x-ray diffraction study revealed an ordered superstructure with orthorhombic symmetry that could be assigned to the space group Pbcn. The structure in BGSC, revealed in the electron density distribution was analyzed by the direct methods (SHELXS-2014) and refined by least squares full matrix method (SHELXL-2014). The crystal structure, including anisotropic atomic displacement parameters for each atom and isotropic atomic displacement parameters for hydrogen atom, was refined to R1 = 0.0395, wR2 = 0.0776 using 1097 independent reflections. The FTIR spectrum of BGSC confirms the protonation of amino groups and the different molecular groups present in BGSC vibrate in different modes. Reverse Indentation Size Effect (RISE) was revealed in BGSC in the micro-hardness analysis using Vicker’s micro-hardness analysis. DTA and DSC results ruled out the possibility of structural change independent of mass change. The AFM studies shows fine nano size fiber like structure of the grown crystals.

Crystal Structure and Crystal Chemistry of Some Common REE Minerals and Nanpingite

NASA Astrophysics Data System (ADS)

Ni, Yunxiang

1995-01-01

Part I. Crystal structure and crystal chemistry of fluorocarbonate minerals. The crystal structure of bastnasite-(Ce) have been solved in P-62c and refined to R = 0.018. The structure is composed of (001) (CeF) layers interspersed with (CO_3) layers in a 1:1 ratio. The Ce atom is coordinated in rm CeO_6F_3 polyhedra. The atomic arrangement of synchysite-(Ce) has been solved and refined to R = 0.036 with a monoclinic space group C2/c. It possesses a (001) layer structure, with layers of (Ca) and (CeF) separated by layers of carbonate groups. The layers stack in a manner analogous to C2/c muscovite. Polytypism similar to the micas may exist in synchysite. The crystal structures of cordylite-(Ce) have been solved in P6 _3/mmc and refined to R = 0.023. The structure and chemical formula are different from those deduced by Oftedal. The formula is rm MBaCe_2(CO _3)_4F, where M is rm Na^+, Ca^{2+}_{1/2 }+ O_{1/2}, or any solution. The presence of (NaF) layer in the structure is the key difference from the Oftedal's structure. This redefinition of the chemical formula and crystal structure of cordylite will be proposed to IMA-CNMMN. Part II. Crystal structure and crystal chemistry of monazite-xenotime series. Monazite is monoclinic, P2 _1/n, and xenotime is isostructural with zircon (I4_1/amd). Both atomic arrangements are based on (001) chains of intervening phosphate tetrahedra and RE polyhedra, with a REO_8 polyhedron in xenotime that accommodates HRE (Tb - Lu) and a REO_9 polyhedron in monazite that preferentially incorporates LRE (La - Gd). As the structure "transforms" from xenotime to monazite, the crystallographic properties are comparable along the (001) chains, with structural adjustments of 2.2 A along (010) to accommodate the different size RE atoms. Part III. Crystal structure of nanpingite-2M _2, the Cs end-member of muscovite. The crystal structure of nanpingite has been refined to R = 0.058. Compared to K^+ in muscovite, the largest interlayer Cs^+ in nanpingite increases (001) separation between adjacent 2:1 layers, but has little effect on the dimensions in (001). The existence of rare 2M_2 polytype in nanpingite is attributed to this large layer separation, which minimizes the repulsion of the superimposed (along (001)) basal oxygens in neighboring tetrahedral layers.

Defect-Tolerant Diffusion Channels for Mg 2+ Ions in Ribbon-Type Borates: Structural Insights into Potential Battery Cathodes MgVBO 4 and Mg x Fe 2–xB 2O 5

DOE PAGES

Bo, Shou-Hang; Grey, Clare P.; Khalifah, Peter G.

2015-06-10

The reversible room temperature intercalation of Mg 2+ ions is difficult to achieve, but may offer substantial advantages in the design of next-generation batteries if this electrochemical process can be successfully realized. Two types of quadruple ribbon-type transition metal borates (Mg xFe 2-xB 2O 5 and MgVBO 4) with high theoretical capacities (186 mAh/g and 360 mAh/g) have been synthesized and structurally characterized through the combined Rietveld refinement of synchrotron and time-of-flight neutron diffraction data. Neither MgVBO 4 nor Mg xFe 2-xB 2O 5 can be chemically oxidized at room temperature, though Mg can be dynamically removed from themore » latter phase at elevated temperatures (approximately 200 - 500 °C). Findings show that Mg diffusion in the Mg xFe 2-xB 2O 5 structure is more facile for the inner two octahedral sites than for the two outer octahedral sites in the ribbons, a result supported by both the refined site occupancies after Mg removal and by bond valence sum difference map calculations of diffusion paths in the pristine material. Mg diffusion in this pyroborate Mg xFe 2-xB 2O 5 framework is also found to be tolerant to the presence of Mg/Fe disorder since Mg ions can diffuse through interstitial channels which bypass Fe-containing sites.« less

Stochastic and Deterministic Crystal Structure Solution Methods in GSAS-II: Monte Carlo/Simulated Annealing Versus Charge Flipping

DOE PAGES

Von Dreele, Robert

2017-08-29

One of the goals in developing GSAS-II was to expand from the capabilities of the original General Structure Analysis System (GSAS) which largely encompassed just structure refinement and post refinement analysis. GSAS-II has been written almost entirely in Python loaded with graphics, GUI and mathematical packages (matplotlib, pyOpenGL, wxpython, numpy and scipy). Thus, GSAS-II has a fully developed modern GUI as well as extensive graphical display of data and results. However, the structure and operation of Python has required new approaches to many of the algorithms used in crystal structure analysis. The extensions beyond GSAS include image calibration/integration as wellmore » as peak fitting and unit cell indexing for powder data which are precursors for structure solution. Structure solution within GSAS-II begins with either Pawley or LeBail extracted structure factors from powder data or those measured in a single crystal experiment. Both charge flipping and Monte Carlo-Simulated Annealing techniques are available; the former can be applied to (3+1) incommensurate structures as well as conventional 3D structures.« less

Grain Refinement by Authigenic Inoculation Inherited from the Medium-Range Order Structure of Ni-Cr-W Superalloy

NASA Astrophysics Data System (ADS)

Gao, Zhongtang; Hu, Rui; Guo, Wei; Zhang, Chuanwei

2018-04-01

The combination of liquidus casting and thermal control solidification furnace was applied to obtain a fine-grained ingot. A rapid quenching method and x-ray diffraction measurement were used to investigate the effect of authigenic inoculation on grain refinement. The structure factor S(Q) of liquid Ni-Cr-W superalloy at 1400 °C (Liquidus temperature) and bright-field image of the microstructures quenched from 1400 °C have been measured by the high-temperature x-ray diffractometer and the transmission electron microscopy (TEM), respectively. The results show that a pre-peak exists on a S(Q) curve at the liquidus temperature. The clusters of atom in rapidly quenched microstructures obtained by isothermal heat treatment at 1400 °C were studied using TEM. Meanwhile, the effect of isothermal different temperatures on rapidly quenched microstructures was studied. The results also show that there are only the globular, equiaxed grains distributed in the solidification structure. These particles are inherited from the medium-range order structure, which is beneficial for grain refinement. The normalized work-hardening rate-strain curve indicates the work-hardening rate of fine grain is higher than that of conventional grain at the same temperature and the same deformation.

Grain Refinement by Authigenic Inoculation Inherited from the Medium-Range Order Structure of Ni-Cr-W Superalloy

NASA Astrophysics Data System (ADS)

Gao, Zhongtang; Hu, Rui; Guo, Wei; Zhang, Chuanwei

2018-05-01

The combination of liquidus casting and thermal control solidification furnace was applied to obtain a fine-grained ingot. A rapid quenching method and x-ray diffraction measurement were used to investigate the effect of authigenic inoculation on grain refinement. The structure factor S( Q) of liquid Ni -Cr-W superalloy at 1400 °C (Liquidus temperature) and bright-field image of the microstructures quenched from 1400 °C have been measured by the high-temperature x-ray diffractometer and the transmission electron microscopy (TEM), respectively. The results show that a pre-peak exists on a S( Q) curve at the liquidus temperature. The clusters of atom in rapidly quenched microstructures obtained by isothermal heat treatment at 1400 °C were studied using TEM. Meanwhile, the effect of isothermal different temperatures on rapidly quenched microstructures was studied. The results also show that there are only the globular, equiaxed grains distributed in the solidification structure. These particles are inherited from the medium-range order structure, which is beneficial for grain refinement. The normalized work-hardening rate-strain curve indicates the work-hardening rate of fine grain is higher than that of conventional grain at the same temperature and the same deformation.

Bayesian refinement of protein structures and ensembles against SAXS data using molecular dynamics

PubMed Central

Shevchuk, Roman; Hub, Jochen S.

2017-01-01

Small-angle X-ray scattering is an increasingly popular technique used to detect protein structures and ensembles in solution. However, the refinement of structures and ensembles against SAXS data is often ambiguous due to the low information content of SAXS data, unknown systematic errors, and unknown scattering contributions from the solvent. We offer a solution to such problems by combining Bayesian inference with all-atom molecular dynamics simulations and explicit-solvent SAXS calculations. The Bayesian formulation correctly weights the SAXS data versus prior physical knowledge, it quantifies the precision or ambiguity of fitted structures and ensembles, and it accounts for unknown systematic errors due to poor buffer matching. The method further provides a probabilistic criterion for identifying the number of states required to explain the SAXS data. The method is validated by refining ensembles of a periplasmic binding protein against calculated SAXS curves. Subsequently, we derive the solution ensembles of the eukaryotic chaperone heat shock protein 90 (Hsp90) against experimental SAXS data. We find that the SAXS data of the apo state of Hsp90 is compatible with a single wide-open conformation, whereas the SAXS data of Hsp90 bound to ATP or to an ATP-analogue strongly suggest heterogenous ensembles of a closed and a wide-open state. PMID:29045407

Synthesis, structure refinement and chromate sorption characteristics of an Al-rich bayerite-based layered double hydroxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Britto, Sylvia, E-mail: sylviabritto11@gmail.com; Kamath, P. Vishnu

2014-07-01

“Imbibition” of Zn{sup 2+} ions into the cation vacancies of bayerite–Al(OH){sub 3} and NO{sub 3}{sup −} ions into the interlayer gallery yields an Al-rich layered double hydroxide with Al/Zn ratio ∼3. NO{sub 3}{sup −} ions are intercalated with their molecular planes inclined at an angle to the plane of the metal hydroxide slab and bonded to it by hydrogen bonds. Rietveld refinement of the structure shows that the monoclinic symmetry of the precursor bayerite is preserved in the product, showing that the imbibition is topochemical in nature. The nitrate ion is labile and is quantitatively replaced by CrO{sub 4}{sup 2−}more » ions from solution. The uptake of CrO{sub 4}{sup 2−} ions follows a Langmuir adsorption isotherm, thus showing that the hydroxide is a candidate material for green chemistry applications for the removal of CrO{sub 4}{sup 2−} ions from waste water. Rietveld refinement of the structure of the hydroxide after CrO{sub 4}{sup 2−} inclusion reveals that the CrO{sub 4}{sup 2−} ion is intercalated with one of its 2-fold axes parallel to the b-crystallographic axis of the crystal, also the principal 2 axis of the monoclinic cell. - Graphical abstract: The structure of the [Zn–Al4-nitrate] LDH viewed along the a-axis. - Highlights: • Synthesis of Al-rich layered double hydroxide with Al/Zn ratio ∼3. • Rietveld refinement indicates that the imbibition of Zn into Al(OH){sub 3} is topochemical in nature. • The uptake of CrO{sub 4}{sup 2−} ions follows a Langmuir adsorption isotherm.« less

Na 3Cr 2P 3S 12 and K 3Cr 2P 3S 12: Two New One-Dimensional Thiophosphate Compounds with a Novel Structure

NASA Astrophysics Data System (ADS)

Coste, S.; Kopnin, E.; Evain, M.; Jobic, S.; Payen, C.; Brec, R.

2001-12-01

Two new alkali metal chromium thiophosphates, Na3Cr2P3S12 and K3Cr2P3S12, have been synthesized and their structure determined from single-crystal or powder X-ray diffraction analyses. These isostructural compounds, which exhibit a novel structural arrangement, crystallize in the monoclinic system (space group P21/c) with the cell parameters a=17.4076(10) Å, b=11.1723(10) Å, c=19.2502(11) Å, β=149.731(3)° (V=1887.1(2) Å3, Z=4) and a=17.9690(14) Å, b=12.0607(5) Å, c=19.3109(16) Å, β=150.008(3)° (V=2091.98(16) Å3, Z=4) for Na3Cr2P3S12 (I) and K3Cr2P3S12 (II), respectively. For (I), the single-crystal refinement led to R/Rw(F2)=0.0417/0.0650 (for 4125 independent reflections and 182 refined parameters). For (II), the Rietveld refinement led to Rp/Rwp=0.0181/0.0233 (for 90 refined parameters). In both materials, the structures consist of 1∞[Cr2P3S12]3- chains built upon two edge-sharing [CrS6] octahedra capped by two [PS4] tetrahedra defining isolated [Cr2P2S12]-8 entities. These entities are linked to each other through an extra [PS4] tetrahedral group. Magnetic measurements evidence antiferromagnetic coupling between Cr3+ cations. The charge balance of the phase is MI3CrIII2PV3S-II12.

Participant and Public Involvement in Refining a Peer-Volunteering Active Aging Intervention: Project ACE (Active, Connected, Engaged).

PubMed

Withall, Janet; Thompson, Janice L; Fox, Kenneth R; Davis, Mark; Gray, Selena; de Koning, Jolanthe; Lloyd, Liz; Parkhurst, Graham; Stathi, Afroditi

2018-03-19

Evidence for the health benefits of a physically active lifestyle among older adults is strong, yet only a small proportion of older people meet physical activity recommendations. A synthesis of evidence identified "best bet" approaches, and this study sought guidance from end-user representatives and stakeholders to refine one of these, a peer-volunteering active aging intervention. Focus groups with 28 older adults and four professional volunteer managers were conducted. Semi-structured interviews were conducted with 9 older volunteers. Framework analysis was used to gauge participants' views on the ACE intervention. Motives for engaging in community groups and activities were almost entirely social. Barriers to participation were lack of someone to attend with, lack of confidence, fear of exclusion or "cliquiness" in established groups, bad weather, transport issues, inaccessibility of activities, ambivalence, and older adults being "set in their ways". Motives for volunteering included "something to do," avoiding loneliness, the need to feel needed, enjoyment, and altruism. Challenges included negative events between volunteer and recipient of volunteering support, childcare commitments, and high volunteering workload. Peer-volunteering approaches have great potential for promotion of active aging. The systematic multistakeholder approach adopted in this study led to important refinements of the original ACE intervention. The findings provide guidance for active aging community initiatives highlighting the importance of effective recruitment strategies and of tackling major barriers including lack of motivation, confidence, and readiness to change; transport issues; security concerns and cost; activity availability; and lack of social support.

Asymptotics for moist deep convection I: refined scalings and self-sustaining updrafts

NASA Astrophysics Data System (ADS)

Hittmeir, Sabine; Klein, Rupert

2018-04-01

Moist processes are among the most important drivers of atmospheric dynamics, and scale analysis and asymptotics are cornerstones of theoretical meteorology. Accounting for moist processes in systematic scale analyses therefore seems of considerable importance for the field. Klein and Majda (Theor Comput Fluid Dyn 20:525-551, 2006) proposed a scaling regime for the incorporation of moist bulk microphysics closures in multiscale asymptotic analyses of tropical deep convection. This regime is refined here to allow for mixtures of ideal gases and to establish consistency with a more general multiple scales modeling framework for atmospheric flows. Deep narrow updrafts, the so-called hot towers, constitute principal building blocks of larger scale storm systems. They are analyzed here in a sample application of the new scaling regime. A single quasi-one-dimensional upright columnar cloud is considered on the vertical advective (or tower life cycle) time scale. The refined asymptotic scaling regime is essential for this example as it reveals a new mechanism for the self-sustainance of such updrafts. Even for strongly positive convectively available potential energy, a vertical balance of buoyancy forces is found in the presence of precipitation. This balance induces a diagnostic equation for the vertical velocity, and it is responsible for the generation of self-sustained balanced updrafts. The time-dependent updraft structure is encoded in a Hamilton-Jacobi equation for the precipitation mixing ratio. Numerical solutions of this equation suggest that the self-sustained updrafts may strongly enhance hot tower life cycles.

Grain refinement of a nickel and manganese free austenitic stainless steel produced by pressurized solution nitriding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohammadzadeh, Roghayeh, E-mail: r_mohammadzadeh@sut.ac.ir; Akbari, Alireza, E-mail: akbari@sut.ac.ir

2014-07-01

Prolonged exposure at high temperatures during solution nitriding induces grain coarsening which deteriorates the mechanical properties of high nitrogen austenitic stainless steels. In this study, grain refinement of nickel and manganese free Fe–22.75Cr–2.42Mo–1.17N high nitrogen austenitic stainless steel plates was investigated via a two-stage heat treatment procedure. Initially, the coarse-grained austenitic stainless steel samples were subjected to an isothermal heating at 700 °C to be decomposed into the ferrite + Cr{sub 2}N eutectoid structure and then re-austenitized at 1200 °C followed by water quenching. Microstructure and hardness of samples were characterized using X-ray diffraction, optical and scanning electron microscopy, andmore » micro-hardness testing. The results showed that the as-solution-nitrided steel decomposes non-uniformly to the colonies of ferrite and Cr{sub 2}N nitrides with strip like morphology after isothermal heat treatment at 700 °C. Additionally, the complete dissolution of the Cr{sub 2}N precipitates located in the sample edges during re-austenitizing requires longer times than 1 h. In order to avoid this problem an intermediate nitrogen homogenizing heat treatment cycle at 1200 °C for 10 h was applied before grain refinement process. As a result, the initial austenite was uniformly decomposed during the first stage, and a fine grained austenitic structure with average grain size of about 20 μm was successfully obtained by re-austenitizing for 10 min. - Highlights: • Successful grain refinement of Fe–22.75Cr–2.42Mo–1.17N steel by heat treatment • Using the γ → α + Cr{sub 2}N reaction for grain refinement of a Ni and Mn free HNASS • Obtaining a single phase austenitic structure with average grain size of ∼ 20 μm • Incomplete dissolution of Cr{sub 2}N during re-austenitizing at 1200 °C for long times • Reducing re-austenitizing time by homogenizing treatment before grain refinement.« less

A new parallelization scheme for adaptive mesh refinement

DOE PAGES

Loffler, Frank; Cao, Zhoujian; Brandt, Steven R.; ...

2016-05-06

Here, we present a new method for parallelization of adaptive mesh refinement called Concurrent Structured Adaptive Mesh Refinement (CSAMR). This new method offers the lower computational cost (i.e. wall time x processor count) of subcycling in time, but with the runtime performance (i.e. smaller wall time) of evolving all levels at once using the time step of the finest level (which does more work than subcycling but has less parallelism). We demonstrate our algorithm's effectiveness using an adaptive mesh refinement code, AMSS-NCKU, and show performance on Blue Waters and other high performance clusters. For the class of problem considered inmore » this paper, our algorithm achieves a speedup of 1.7-1.9 when the processor count for a given AMR run is doubled, consistent with our theoretical predictions.« less

A new parallelization scheme for adaptive mesh refinement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loffler, Frank; Cao, Zhoujian; Brandt, Steven R.

Here, we present a new method for parallelization of adaptive mesh refinement called Concurrent Structured Adaptive Mesh Refinement (CSAMR). This new method offers the lower computational cost (i.e. wall time x processor count) of subcycling in time, but with the runtime performance (i.e. smaller wall time) of evolving all levels at once using the time step of the finest level (which does more work than subcycling but has less parallelism). We demonstrate our algorithm's effectiveness using an adaptive mesh refinement code, AMSS-NCKU, and show performance on Blue Waters and other high performance clusters. For the class of problem considered inmore » this paper, our algorithm achieves a speedup of 1.7-1.9 when the processor count for a given AMR run is doubled, consistent with our theoretical predictions.« less

Use of mechanical refining to improve the production of low-cost sugars from lignocellulosic biomass.

PubMed

Park, Junyeong; Jones, Brandon; Koo, Bonwook; Chen, Xiaowen; Tucker, Melvin; Yu, Ju-Hyun; Pschorn, Thomas; Venditti, Richard; Park, Sunkyu

2016-01-01

Mechanical refining is widely used in the pulp and paper industry to enhance the end-use properties of products by creating external fibrillation and internal delamination. This technology can be directly applied to biochemical conversion processes. By implementing mechanical refining technology, biomass recalcitrance to enzyme hydrolysis can be overcome and carbohydrate conversion can be enhanced with commercially attractive levels of enzymes. In addition, chemical and thermal pretreatment severity can be reduced to achieve the same level of carbohydrate conversion, which reduces pretreatment cost and results in lower concentrations of inhibitors. Refining is versatile and a commercially proven technology that can be operated at process flows of ∼ 1500 dry tons per day of biomass. This paper reviews the utilization of mechanical refining in the pulp and paper industry and summarizes the recent development in applications for biochemical conversion, which potentially make an overall biorefinery process more economically viable. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal dietary intakes of refined grains during pregnancy and growth through the first 7 y of life among children born to women with gestational diabetes.

PubMed

Zhu, Yeyi; Olsen, Sjurdur F; Mendola, Pauline; Halldorsson, Thorhallur I; Yeung, Edwina H; Granström, Charlotta; Bjerregaard, Anne A; Wu, Jing; Rawal, Shristi; Chavarro, Jorge E; Hu, Frank B; Zhang, Cuilin

2017-07-01

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking. Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM). Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors. Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P -trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth. Conclusions: Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with offspring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted. © 2017 American Society for Nutrition.

A multi-block adaptive solving technique based on lattice Boltzmann method

NASA Astrophysics Data System (ADS)

Zhang, Yang; Xie, Jiahua; Li, Xiaoyue; Ma, Zhenghai; Zou, Jianfeng; Zheng, Yao

2018-05-01

In this paper, a CFD parallel adaptive algorithm is self-developed by combining the multi-block Lattice Boltzmann Method (LBM) with Adaptive Mesh Refinement (AMR). The mesh refinement criterion of this algorithm is based on the density, velocity and vortices of the flow field. The refined grid boundary is obtained by extending outward half a ghost cell from the coarse grid boundary, which makes the adaptive mesh more compact and the boundary treatment more convenient. Two numerical examples of the backward step flow separation and the unsteady flow around circular cylinder demonstrate the vortex structure of the cold flow field accurately and specifically.

Adaptively-refined overlapping grids for the numerical solution of systems of hyperbolic conservation laws

NASA Technical Reports Server (NTRS)

Brislawn, Kristi D.; Brown, David L.; Chesshire, Geoffrey S.; Saltzman, Jeffrey S.

1995-01-01

Adaptive mesh refinement (AMR) in conjunction with higher-order upwind finite-difference methods have been used effectively on a variety of problems in two and three dimensions. In this paper we introduce an approach for resolving problems that involve complex geometries in which resolution of boundary geometry is important. The complex geometry is represented by using the method of overlapping grids, while local resolution is obtained by refining each component grid with the AMR algorithm, appropriately generalized for this situation. The CMPGRD algorithm introduced by Chesshire and Henshaw is used to automatically generate the overlapping grid structure for the underlying mesh.

A database of new zeolite-like materials.

PubMed

Pophale, Ramdas; Cheeseman, Phillip A; Deem, Michael W

2011-07-21

We here describe a database of computationally predicted zeolite-like materials. These crystals were discovered by a Monte Carlo search for zeolite-like materials. Positions of Si atoms as well as unit cell, space group, density, and number of crystallographically unique atoms were explored in the construction of this database. The database contains over 2.6 M unique structures. Roughly 15% of these are within +30 kJ mol(-1) Si of α-quartz, the band in which most of the known zeolites lie. These structures have topological, geometrical, and diffraction characteristics that are similar to those of known zeolites. The database is the result of refinement by two interatomic potentials that both satisfy the Pauli exclusion principle. The database has been deposited in the publicly available PCOD database and in www.hypotheticalzeolites.net/database/deem/. This journal is © the Owner Societies 2011

Integrative Approach for Computationally Inferring Interactions between the Alpha and Beta Subunits of the Calcium-Activated Potassium Channel (BK): a Docking Study

PubMed Central

González, Janneth; Gálvez, Angela; Morales, Ludis; Barreto, George E.; Capani, Francisco; Sierra, Omar; Torres, Yolima

2013-01-01

Three-dimensional models of the alpha- and beta-1 subunits of the calcium-activated potassium channel (BK) were predicted by threading modeling. A recursive approach comprising of sequence alignment and model building based on three templates was used to build these models, with the refinement of non-conserved regions carried out using threading techniques. The complex formed by the subunits was studied by means of docking techniques, using 3D models of the two subunits, and an approach based on rigid-body structures. Structural effects of the complex were analyzed with respect to hydrogen-bond interactions and binding-energy calculations. Potential interaction sites of the complex were determined by referencing a study of the difference accessible surface area (DASA) of the protein subunits in the complex. PMID:23492851

On the possibility of using polycrystalline material in the development of structure-based generic assays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allaire, Marc, E-mail: allaire@bnl.gov; Moiseeva, Natalia; Botez, Cristian E.

The correlation coefficients calculated between raw powder diffraction profiles can be used to identify ligand-bound/unbound states of lysozyme. The discovery of ligands that bind specifically to a targeted protein benefits from the development of generic assays for high-throughput screening of a library of chemicals. Protein powder diffraction (PPD) has been proposed as a potential method for use as a structure-based assay for high-throughput screening applications. Building on this effort, powder samples of bound/unbound states of soluble hen-egg white lysozyme precipitated with sodium chloride were compared. The correlation coefficients calculated between the raw diffraction profiles were consistent with the known bindingmore » properties of the ligands and suggested that the PPD approach can be used even prior to a full description using stereochemically restrained Rietveld refinement.« less

An investigation of squeeze-cast alloy 718

NASA Technical Reports Server (NTRS)

Gamwell, W. R.

1993-01-01

Alloy 718 billets produced by the squeeze-cast process have been evaluated for use as potential replacements for propulsion engine components which are normally produced from forgings. Alloy 718 billets were produced using various processing conditions. Structural characterizations were performed on 'as-cast' billets. As-cast billets were then homogenized and solution treated and aged according to conventional heat-treatment practices for this alloy. Mechanical property evaluations were performed on heat-treated billets. As-cast macrostructures and microstructures varied with squeeze-cast processing parameters. Mechanical properties varied with squeeze-cast processing parameters and heat treatments. One billet exhibited a defect free, refined microstructure, with mechanical properties approaching those of wrought alloy 718 bar, confirming the feasibility of squeeze-casting alloy 718. However, further process optimization is required, and further structural and mechanical property improvements are expected with process optimization.

Search for memory effects in methane hydrate: structure of water before hydrate formation and after hydrate decomposition.

PubMed

Buchanan, Piers; Soper, Alan K; Thompson, Helen; Westacott, Robin E; Creek, Jefferson L; Hobson, Greg; Koh, Carolyn A

2005-10-22

Neutron diffraction with HD isotope substitution has been used to study the formation and decomposition of the methane clathrate hydrate. Using this atomistic technique coupled with simultaneous gas consumption measurements, we have successfully tracked the formation of the sI methane hydrate from a water/gas mixture and then the subsequent decomposition of the hydrate from initiation to completion. These studies demonstrate that the application of neutron diffraction with simultaneous gas consumption measurements provides a powerful method for studying the clathrate hydrate crystal growth and decomposition. We have also used neutron diffraction to examine the water structure before the hydrate growth and after the hydrate decomposition. From the neutron-scattering curves and the empirical potential structure refinement analysis of the data, we find that there is no significant difference between the structure of water before the hydrate formation and the structure of water after the hydrate decomposition. Nor is there any significant change to the methane hydration shell. These results are discussed in the context of widely held views on the existence of memory effects after the hydrate decomposition.

Performance Comparison of Al-Ti Master Alloys with Different Microstructures in Grain Refinement of Commercial Purity Aluminum.

PubMed

Ding, Wanwu; Xia, Tiandong; Zhao, Wenjun

2014-05-07

Three types of Al-5Ti master alloys were synthesized by a method of thermal explosion reaction in pure molten aluminum. Performance comparison of Al-5Ti master alloy in grain refinement of commercial purity Al with different additions (0.6%, 1.0%, 1.6%, 2.0%, and 3.0%) and holding time (10, 30, 60 and 120 min) were investigated. The results show that Al-5Ti master alloy with blocky TiAl₃ particles clearly has better refining efficiency than the master alloy with mixed TiAl₃ particles and the master alloy with needle-like TiAl₃ particles. The structures of master alloys, differing by sizes, morphologies and quantities of TiAl₃ crystals, were found to affect the pattern of the grain refining properties with the holding time. The grain refinement effect was revealed to reduce markedly for master alloys with needle-like TiAl₃ crystals and to show the further significant improvement at a longer holding time for the master alloy containing both larger needle-like and blocky TiAl₃ particles. For the master alloy with finer blocky particles, the grain refining effect did not obviously decrease during the whole studied range of the holding time.

Detonation Product EOS Studies: Using ISLS to Refine Cheetah

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaug, J M; Howard, W M; Fried, L E

2001-08-08

Knowledge of an effective interatomic potential function underlies any effort to predict or rationalize the properties of solids and liquids. The experiments we undertake are directed towards determination of equilibrium and dynamic properties of simple fluids at densities sufficiently high that traditional computational methods and semi-empirical forms successful at ambient conditions may require reconsideration. In this paper we present high-pressure and temperature experimental sound speed data on a simple fluid, methanol. Impulsive Stimulated Light Scattering (ISLS) conducted on diamond-anvil cell (DAC) encapsulated samples offers an experimental approach to determine cross-pair potential interactions through equation of state determinations. In addition themore » kinetics of structural relaxation in fluids can be studied. We compare our experimental results with our thermochemical computational model Cheetah. Computational models are systematically improved with each addition of experimental data.« less

3-D geoelectrical modelling using finite-difference: a new boundary conditions improvement

NASA Astrophysics Data System (ADS)

Maineult, A.; Schott, J.-J.; Ardiot, A.

2003-04-01

Geoelectrical prospecting is a well-known and frequently used method for quantitative and non-destructive subsurface exploration until depths of a few hundreds metres. Thus archeological objects can be efficiently detected as their resistivities often contrast with those of the surrounding media. Nevertheless using the geoelectrical prospecting method has long been restricted due to inhability to model correctly arbitrarily-shaped structures. The one-dimensional modelling and inversion have long been classical, but are of no interest for the majority of field data, since the natural distribution of resistivity is rarely homogeneous or tabular. Since the 1970's some authors developed discrete methods in order to solve the two and three-dimensional problem, using mathematical tools such as finite-element or finite-difference. The finite-difference approach is quite simple, easily understandable and programmable. Since the work of Dey and Morrison (1979), this approach has become quite popular. Nevertheless, one of its major drawbacks is the difficulty to establish satisfying boundary conditions. Recently Lowry et al. (1989) and Zhao and Yedlin (1996) suggested some refinements on the improvement of the boundary problem. We propose a new betterment, based on the splitting of the potential into two terms, the potential due to a reference tabular medium and a secondary potential caused by a disturbance of this medium. The surface response of a tabular medium has long been known (see for example Koefoed 1979). Here we developed the analytical solution for the electrical tabular potential everywhere in the medium, in order to establish more satisfying boundary conditions. The response of the perturbation, that is to say the object of interest, is then solved using volume-difference and preconditioned conjugate gradient. Finally the grid is refined one or more times in the perturbed domain in order to ameliorate the precision. This method of modelling is easy to implement and numerical computations run very fast. Thanks to improved boundary conditions and refinement processes, edges effects are reduced. Moreover, one important conclusion of this work is the necessity to prefer three-dimensional prospecting, since in some cases a unique profile can lead to misinterpretation, as shown by the comparison of transverse profiles through a buried cylinder and through a buried sphere.

A new crystal form of Aspergillus oryzae catechol oxidase and evaluation of copper site structures in coupled binuclear copper enzymes.

PubMed

Penttinen, Leena; Rutanen, Chiara; Saloheimo, Markku; Kruus, Kristiina; Rouvinen, Juha; Hakulinen, Nina

2018-01-01

Coupled binuclear copper (CBC) enzymes have a conserved type 3 copper site that binds molecular oxygen to oxidize various mono- and diphenolic compounds. In this study, we found a new crystal form of catechol oxidase from Aspergillus oryzae (AoCO4) and solved two new structures from two different crystals at 1.8-Å and at 2.5-Å resolutions. These structures showed different copper site forms (met/deoxy and deoxy) and also differed from the copper site observed in the previously solved structure of AoCO4. We also analysed the electron density maps of all of the 56 CBC enzyme structures available in the protein data bank (PDB) and found that many of the published structures have vague copper sites. Some of the copper sites were then re-refined to find a better fit to the observed electron density. General problems in the refinement of metalloproteins and metal centres are discussed.

Testing hydrodynamics schemes in galaxy disc simulations

NASA Astrophysics Data System (ADS)

Few, C. G.; Dobbs, C.; Pettitt, A.; Konstandin, L.

2016-08-01

We examine how three fundamentally different numerical hydrodynamics codes follow the evolution of an isothermal galactic disc with an external spiral potential. We compare an adaptive mesh refinement code (RAMSES), a smoothed particle hydrodynamics code (SPHNG), and a volume-discretized mesh-less code (GIZMO). Using standard refinement criteria, we find that RAMSES produces a disc that is less vertically concentrated and does not reach such high densities as the SPHNG or GIZMO runs. The gas surface density in the spiral arms increases at a lower rate for the RAMSES simulations compared to the other codes. There is also a greater degree of substructure in the SPHNG and GIZMO runs and secondary spiral arms are more pronounced. By resolving the Jeans length with a greater number of grid cells, we achieve more similar results to the Lagrangian codes used in this study. Other alterations to the refinement scheme (adding extra levels of refinement and refining based on local density gradients) are less successful in reducing the disparity between RAMSES and SPHNG/GIZMO. Although more similar, SPHNG displays different density distributions and vertical mass profiles to all modes of GIZMO (including the smoothed particle hydrodynamics version). This suggests differences also arise which are not intrinsic to the particular method but rather due to its implementation. The discrepancies between codes (in particular, the densities reached in the spiral arms) could potentially result in differences in the locations and time-scales for gravitational collapse, and therefore impact star formation activity in more complex galaxy disc simulations.

Development in corrosion resistance by microstructural refinement in Zr-16 SS 304 alloy using suction casting technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, N., E-mail: nirupamd@barc.gov.in; Sengupta, P.; Abraham, G.

Highlights: • Grain refinement was made in Zr–16 wt.% SS alloy while prepared by suction casting process. • Distribution of Laves phase, e.g., Zr{sub 2}(Fe, Cr) was raised in suction cast (SC) Zr–16 wt.% SS. • Corrosion resistance was improved in SC alloy compared to that of arc-melt-cast alloy. • Grain refinement in SC alloy assisted for an increase in its corrosion resistance. - Abstract: Zirconium (Zr)-stainless steel (SS) hybrid alloys are being considered as baseline alloys for developing metallic-waste-form (MWF) with the motivation of disposing of Zr and SS base nuclear metallic wastes. Zr–16 wt.% SS, a MWF alloymore » optimized from previous studies, exhibit significant grain refinement and changes in phase assemblages (soft phase: Zr{sub 2}(Fe, Cr)/α-Zr vs. hard phase: Zr{sub 3}(Fe, Ni)) when prepared by suction casting (SC) technique in comparison to arc-cast-melt (AMC) route. Variation in Cr-distribution among different phases are found to be low in suction cast alloy, which along with grain refinement restricted Cr-depletion at the Zr{sub 2}(Fe, Cr)/Zr interfaces, prone to localized attack. Hence, SC alloy, compared to AMC alloy, showed lower current density, higher potential at the breakdown of passivity and higher corrosion potential during polarization experiments (carried out under possible geological repository environments, viz., pH 8, 5 and 1) indicating its superior corrosion resistance.« less

A dynamic structural model of expanded RNA CAG repeats: A refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations

PubMed Central

Yildirim, Ilyas; Park, Hajeung; Disney, Matthew D.; Schatz, George C.

2013-01-01

One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded r(CAG) repeats can cause Huntington’s and other disease through translation of toxic proteins. Herein, crystal structure of r[5ʹUUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that show both anti-anti and syn-anti orientations for 1×1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using Amber force field in explicit solvent were run for over 500 ns on model systems r(5ʹGCGCAGCGC)2 (MS1) and r(5ʹCCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti↔anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, over 800 ns explicit solvent MD simulation was run on r[5ʹGGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1×1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and develop small molecules that target RNA dynamic ensembles. PMID:23441937

Structural analysis of glycoproteins: building N-linked glycans with Coot.

PubMed

Emsley, Paul; Crispin, Max

2018-04-01

Coot is a graphics application that is used to build or manipulate macromolecular models; its particular forte is manipulation of the model at the residue level. The model-building tools of Coot have been combined and extended to assist or automate the building of N-linked glycans. The model is built by the addition of monosaccharides, placed by variation of internal coordinates. The subsequent model is refined by real-space refinement, which is stabilized with modified and additional restraints. It is hoped that these enhanced building tools will help to reduce building errors of N-linked glycans and improve our knowledge of the structures of glycoproteins.

A CPU benchmark for protein crystallographic refinement.

PubMed

Bourne, P E; Hendrickson, W A

1990-01-01

The CPU time required to complete a cycle of restrained least-squares refinement of a protein structure from X-ray crystallographic data using the FORTRAN codes PROTIN and PROLSQ are reported for 48 different processors, ranging from single-user workstations to supercomputers. Sequential, vector, VLIW, multiprocessor, and RISC hardware architectures are compared using both a small and a large protein structure. Representative compile times for each hardware type are also given, and the improvement in run-time when coding for a specific hardware architecture considered. The benchmarks involve scalar integer and vector floating point arithmetic and are representative of the calculations performed in many scientific disciplines.

Analysis of multicrystal pump–probe data sets. I. Expressions for the RATIO model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fournier, Bertrand; Coppens, Philip

2014-08-30

The RATIO method in time-resolved crystallography [Coppenset al.(2009).J. Synchrotron Rad.16, 226–230] was developed for use with Laue pump–probe diffraction data to avoid complex corrections due to wavelength dependence of the intensities. The application of the RATIO method in processing/analysis prior to structure refinement requires an appropriate ratio model for modeling the light response. The assessment of the accuracy of pump–probe time-resolved structure refinements based on the observed ratios was discussed in a previous paper. In the current paper, a detailed ratio model is discussed, taking into account both geometric and thermal light-induced changes.

Rietveld-refinement and optical study of the Fe doped ZnO thin film by RF magnetron sputtering

NASA Astrophysics Data System (ADS)

Kumar, Arun; Dhiman, Pooja; Singh, M.

2017-05-01

Fe Doped ZnO Dilute Magnetic Semiconductor thin film prepared by RF magnetron sputtering on glass substrate and Influence of 3% Fe-doping on structural and Optical properties has been studied. The Rietveld-refinement analysis shows that Fe doping has a significant effect on crystalline structure, grain size and strain in the thin film. Two dimensional and three-dimensional atom probe tomography of the thin film shows that Fe ions are randomly distributed which is supported by Xray Diffraction (XRD). Fe-doping is found to effectively modify the band gap energy up to 3.5 eV.

The effect of high pressure torsion on structural refinement and mechanical properties of an austenitic stainless steel.

PubMed

Krawczynska, Agnieszka Teresa; Lewandowska, Malgorzata; Pippan, Reinhard; Kurzydlowski, Krzysztof Jan

2013-05-01

In the present study, the high pressure torsion (HPT) was used to refine the grain structure down to the nanometer scale in an austenitic stainless steel. The principles of HPT lay on torsional deformation under simultaneous high pressure of the specimen, which results in substantial reduction in the grain size. Disks of the 316LVM austenitic stainless steel of 10 mm in diameter were subjected to equivalent strains epsilon of 32 at RT and 450 degrees C under the pressure of 4 GPa. Furthermore, two-stage HPT processes, i.e., deformation at room temperature followed by deformation at 450 degrees C, were performed. The resulting microstructures were investigated in TEM observations. The mechanical properties were measured in terms of the microhardness and in tensile tests. HPT performed at two-stage conditions (firstly at RT next at 450 degrees C) gives similar values of microhardness to the ones obtained after deforming only at 450 degrees C but performed to higher values of the overall equivalent strain epsilon. The effect of high pressure torsion on structural refinement and mechanical properties of an austenitic stainless steel was evaluated.

Protein structure refinement using a quantum mechanics-based chemical shielding predictor† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04344e Click here for additional data file.

PubMed Central

2017-01-01

The accurate prediction of protein chemical shifts using a quantum mechanics (QM)-based method has been the subject of intense research for more than 20 years but so far empirical methods for chemical shift prediction have proven more accurate. In this paper we show that a QM-based predictor of a protein backbone and CB chemical shifts (ProCS15, PeerJ, 2016, 3, e1344) is of comparable accuracy to empirical chemical shift predictors after chemical shift-based structural refinement that removes small structural errors. We present a method by which quantum chemistry based predictions of isotropic chemical shielding values (ProCS15) can be used to refine protein structures using Markov Chain Monte Carlo (MCMC) simulations, relating the chemical shielding values to the experimental chemical shifts probabilistically. Two kinds of MCMC structural refinement simulations were performed using force field geometry optimized X-ray structures as starting points: simulated annealing of the starting structure and constant temperature MCMC simulation followed by simulated annealing of a representative ensemble structure. Annealing of the CHARMM structure changes the CA-RMSD by an average of 0.4 Å but lowers the chemical shift RMSD by 1.0 and 0.7 ppm for CA and N. Conformational averaging has a relatively small effect (0.1–0.2 ppm) on the overall agreement with carbon chemical shifts but lowers the error for nitrogen chemical shifts by 0.4 ppm. If an amino acid specific offset is included the ProCS15 predicted chemical shifts have RMSD values relative to experiments that are comparable to popular empirical chemical shift predictors. The annealed representative ensemble structures differ in CA-RMSD relative to the initial structures by an average of 2.0 Å, with >2.0 Å difference for six proteins. In four of the cases, the largest structural differences arise in structurally flexible regions of the protein as determined by NMR, and in the remaining two cases, the large structural change may be due to force field deficiencies. The overall accuracy of the empirical methods are slightly improved by annealing the CHARMM structure with ProCS15, which may suggest that the minor structural changes introduced by ProCS15-based annealing improves the accuracy of the protein structures. Having established that QM-based chemical shift prediction can deliver the same accuracy as empirical shift predictors we hope this can help increase the accuracy of related approaches such as QM/MM or linear scaling approaches or interpreting protein structural dynamics from QM-derived chemical shift. PMID:28451325

Waste management of printed wiring boards: a life cycle assessment of the metals recycling chain from liberation through refining.

PubMed

Xue, Mianqiang; Kendall, Alissa; Xu, Zhenming; Schoenung, Julie M

2015-01-20

Due to economic and societal reasons, informal activities including open burning, backyard recycling, and landfill are still the prevailing methods used for electronic waste treatment in developing countries. Great efforts have been made, especially in China, to promote formal approaches for electronic waste management by enacting laws, developing green recycling technologies, initiating pilot programs, etc. The formal recycling process can, however, engender environmental impact and resource consumption, although information on the environmental loads and resource consumption is currently limited. To quantitatively assess the environmental impact of the processes in a formal printed wiring board (PWB) recycling chain, life cycle assessment (LCA) was applied to a formal recycling chain that includes the steps from waste liberation through materials refining. The metal leaching in the refining stage was identified as a critical process, posing most of the environmental impact in the recycling chain. Global warming potential was the most significant environmental impact category after normalization and weighting, followed by fossil abiotic depletion potential, and marine aquatic eco-toxicity potential. Scenario modeling results showed that variations in the power source and chemical reagents consumption had the greatest influence on the environmental performance. The environmental impact from transportation used for PWB collection was also evaluated. The results were further compared to conventional primary metals production processes, highlighting the environmental benefit of metal recycling from waste PWBs. Optimizing the collection mode, increasing the precious metals recovery efficiency in the beneficiation stage and decreasing the chemical reagents consumption in the refining stage by effective materials liberation and separation are proposed as potential improvement strategies to make the recycling chain more environmentally friendly. The LCA results provide environmental information for the improvement of future integrated technologies and electronic waste management.

Neutron diffraction study of a non-strichiometric Ni-Mn-Ga MSM alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ari-Gur, Pnina; Garlea, Vasile O

2013-01-01

The structure and chemical order of a Heusler alloy of non-stoichiometric composition Ni-Mn-Ga were studied using constant-wavelength (1.538 ) neutron diffraction at 363K and the diffraction pattern was refined using the FullProf software. At this temperature the structure is austenite (cubic) with Fm-3m space group and lattice constant of a = 5.83913(4) [ ]. The chemical order is of critical importance in these alloys, as Mn becomes antiferromagnetic when the atoms are closer than the radius of the 3d shell. In the studied alloy the refinement of the site occupancy showed that the 4b (Ga site) contained as much asmore » 22% Mn; that significantly alters the distances between the Mn atoms in the crystal and, as a result, also the exchange energy between some of the Mn atoms. Based on the refinement, the composition was determined to be Ni1.91Mn1.29Ga0.8« less

On the Hydrologic Adjustment of Climate-Model Projections: The Potential Pitfall of Potential Evapotranspiration

USGS Publications Warehouse

Milly, Paul C.D.; Dunne, Krista A.

2011-01-01

Hydrologic models often are applied to adjust projections of hydroclimatic change that come from climate models. Such adjustment includes climate-bias correction, spatial refinement ("downscaling"), and consideration of the roles of hydrologic processes that were neglected in the climate model. Described herein is a quantitative analysis of the effects of hydrologic adjustment on the projections of runoff change associated with projected twenty-first-century climate change. In a case study including three climate models and 10 river basins in the contiguous United States, the authors find that relative (i.e., fractional or percentage) runoff change computed with hydrologic adjustment more often than not was less positive (or, equivalently, more negative) than what was projected by the climate models. The dominant contributor to this decrease in runoff was a ubiquitous change in runoff (median -11%) caused by the hydrologic model’s apparent amplification of the climate-model-implied growth in potential evapotranspiration. Analysis suggests that the hydrologic model, on the basis of the empirical, temperature-based modified Jensen–Haise formula, calculates a change in potential evapotranspiration that is typically 3 times the change implied by the climate models, which explicitly track surface energy budgets. In comparison with the amplification of potential evapotranspiration, central tendencies of other contributions from hydrologic adjustment (spatial refinement, climate-bias adjustment, and process refinement) were relatively small. The authors’ findings highlight the need for caution when projecting changes in potential evapotranspiration for use in hydrologic models or drought indices to evaluate climate-change impacts on water.

GIRAF: a method for fast search and flexible alignment of ligand binding interfaces in proteins at atomic resolution

PubMed Central

Kinjo, Akira R.; Nakamura, Haruki

2012-01-01

Comparison and classification of protein structures are fundamental means to understand protein functions. Due to the computational difficulty and the ever-increasing amount of structural data, however, it is in general not feasible to perform exhaustive all-against-all structure comparisons necessary for comprehensive classifications. To efficiently handle such situations, we have previously proposed a method, now called GIRAF. We herein describe further improvements in the GIRAF protein structure search and alignment method. The GIRAF method achieves extremely efficient search of similar structures of ligand binding sites of proteins by exploiting database indexing of structural features of local coordinate frames. In addition, it produces refined atom-wise alignments by iterative applications of the Hungarian method to the bipartite graph defined for a pair of superimposed structures. By combining the refined alignments based on different local coordinate frames, it is made possible to align structures involving domain movements. We provide detailed accounts for the database design, the search and alignment algorithms as well as some benchmark results. PMID:27493524

Structural simplicity as a restraint on the structure of amorphous silicon

NASA Astrophysics Data System (ADS)

Cliffe, Matthew J.; Bartók, Albert P.; Kerber, Rachel N.; Grey, Clare P.; Csányi, Gábor; Goodwin, Andrew L.

2017-06-01

Understanding the structural origins of the properties of amorphous materials remains one of the most important challenges in structural science. In this study, we demonstrate that local "structural simplicity", embodied by the degree to which atomic environments within a material are similar to each other, is a powerful concept for rationalizing the structure of amorphous silicon (a -Si) a canonical amorphous material. We show, by restraining a reverse Monte Carlo refinement against pair distribution function (PDF) data to be simpler, that the simplest model consistent with the PDF is a continuous random network (CRN). A further effect of producing a simple model of a -Si is the generation of a (pseudo)gap in the electronic density of states, suggesting that structural homogeneity drives electronic homogeneity. That this method produces models of a -Si that approach the state-of-the-art without the need for chemically specific restraints (beyond the assumption of homogeneity) suggests that simplicity-based refinement approaches may allow experiment-driven structural modeling techniques to be developed for the wide variety of amorphous semiconductors with strong local order.

Assume-Guarantee Abstraction Refinement Meets Hybrid Systems

NASA Technical Reports Server (NTRS)

Bogomolov, Sergiy; Frehse, Goran; Greitschus, Marius; Grosu, Radu; Pasareanu, Corina S.; Podelski, Andreas; Strump, Thomas

2014-01-01

Compositional verification techniques in the assume- guarantee style have been successfully applied to transition systems to efficiently reduce the search space by leveraging the compositional nature of the systems under consideration. We adapt these techniques to the domain of hybrid systems with affine dynamics. To build assumptions we introduce an abstraction based on location merging. We integrate the assume-guarantee style analysis with automatic abstraction refinement. We have implemented our approach in the symbolic hybrid model checker SpaceEx. The evaluation shows its practical potential. To the best of our knowledge, this is the first work combining assume-guarantee reasoning with automatic abstraction-refinement in the context of hybrid automata.

Mesh Generation via Local Bisection Refinement of Triangulated Grids

DTIC Science & Technology

2015-06-01

Science and Technology Organisation DSTO–TR–3095 ABSTRACT This report provides a comprehensive implementation of an unstructured mesh generation method...and Technology Organisation 506 Lorimer St, Fishermans Bend, Victoria 3207, Australia Telephone: 1300 333 362 Facsimile: (03) 9626 7999 c© Commonwealth...their behaviour is critically linked to Maubach’s method and the data structures N and T . The top- level mesh refinement algorithm is also presented

Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10

PubMed Central

Zhang, Yang

2014-01-01

We develop and test a new pipeline in CASP10 to predict protein structures based on an interplay of I-TASSER and QUARK for both free-modeling (FM) and template-based modeling (TBM) targets. The most noteworthy observation is that sorting through the threading template pool using the QUARK-based ab initio models as probes allows the detection of distant-homology templates which might be ignored by the traditional sequence profile-based threading alignment algorithms. Further template assembly refinement by I-TASSER resulted in successful folding of two medium-sized FM targets with >150 residues. For TBM, the multiple threading alignments from LOMETS are, for the first time, incorporated into the ab initio QUARK simulations, which were further refined by I-TASSER assembly refinement. Compared with the traditional threading assembly refinement procedures, the inclusion of the threading-constrained ab initio folding models can consistently improve the quality of the full-length models as assessed by the GDT-HA and hydrogen-bonding scores. Despite the success, significant challenges still exist in domain boundary prediction and consistent folding of medium-size proteins (especially beta-proteins) for nonhomologous targets. Further developments of sensitive fold-recognition and ab initio folding methods are critical for solving these problems. PMID:23760925

Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10.

PubMed

Zhang, Yang

2014-02-01

We develop and test a new pipeline in CASP10 to predict protein structures based on an interplay of I-TASSER and QUARK for both free-modeling (FM) and template-based modeling (TBM) targets. The most noteworthy observation is that sorting through the threading template pool using the QUARK-based ab initio models as probes allows the detection of distant-homology templates which might be ignored by the traditional sequence profile-based threading alignment algorithms. Further template assembly refinement by I-TASSER resulted in successful folding of two medium-sized FM targets with >150 residues. For TBM, the multiple threading alignments from LOMETS are, for the first time, incorporated into the ab initio QUARK simulations, which were further refined by I-TASSER assembly refinement. Compared with the traditional threading assembly refinement procedures, the inclusion of the threading-constrained ab initio folding models can consistently improve the quality of the full-length models as assessed by the GDT-HA and hydrogen-bonding scores. Despite the success, significant challenges still exist in domain boundary prediction and consistent folding of medium-size proteins (especially beta-proteins) for nonhomologous targets. Further developments of sensitive fold-recognition and ab initio folding methods are critical for solving these problems. Copyright © 2013 Wiley Periodicals, Inc.

Benchmarking NLDAS-2 Soil Moisture and Evapotranspiration to Separate Uncertainty Contributions

NASA Technical Reports Server (NTRS)

Nearing, Grey S.; Mocko, David M.; Peters-Lidard, Christa D.; Kumar, Sujay V.; Xia, Youlong

2016-01-01

Model benchmarking allows us to separate uncertainty in model predictions caused 1 by model inputs from uncertainty due to model structural error. We extend this method with a large-sample approach (using data from multiple field sites) to measure prediction uncertainty caused by errors in (i) forcing data, (ii) model parameters, and (iii) model structure, and use it to compare the efficiency of soil moisture state and evapotranspiration flux predictions made by the four land surface models in the North American Land Data Assimilation System Phase 2 (NLDAS-2). Parameters dominated uncertainty in soil moisture estimates and forcing data dominated uncertainty in evapotranspiration estimates; however, the models themselves used only a fraction of the information available to them. This means that there is significant potential to improve all three components of the NLDAS-2 system. In particular, continued work toward refining the parameter maps and look-up tables, the forcing data measurement and processing, and also the land surface models themselves, has potential to result in improved estimates of surface mass and energy balances.

Benchmarking NLDAS-2 Soil Moisture and Evapotranspiration to Separate Uncertainty Contributions

PubMed Central

Nearing, Grey S.; Mocko, David M.; Peters-Lidard, Christa D.; Kumar, Sujay V.; Xia, Youlong

2018-01-01

Model benchmarking allows us to separate uncertainty in model predictions caused by model inputs from uncertainty due to model structural error. We extend this method with a “large-sample” approach (using data from multiple field sites) to measure prediction uncertainty caused by errors in (i) forcing data, (ii) model parameters, and (iii) model structure, and use it to compare the efficiency of soil moisture state and evapotranspiration flux predictions made by the four land surface models in the North American Land Data Assimilation System Phase 2 (NLDAS-2). Parameters dominated uncertainty in soil moisture estimates and forcing data dominated uncertainty in evapotranspiration estimates; however, the models themselves used only a fraction of the information available to them. This means that there is significant potential to improve all three components of the NLDAS-2 system. In particular, continued work toward refining the parameter maps and look-up tables, the forcing data measurement and processing, and also the land surface models themselves, has potential to result in improved estimates of surface mass and energy balances. PMID:29697706

Benchmarking NLDAS-2 Soil Moisture and Evapotranspiration to Separate Uncertainty Contributions.

PubMed

Nearing, Grey S; Mocko, David M; Peters-Lidard, Christa D; Kumar, Sujay V; Xia, Youlong

2016-03-01

Model benchmarking allows us to separate uncertainty in model predictions caused by model inputs from uncertainty due to model structural error. We extend this method with a "large-sample" approach (using data from multiple field sites) to measure prediction uncertainty caused by errors in (i) forcing data, (ii) model parameters, and (iii) model structure, and use it to compare the efficiency of soil moisture state and evapotranspiration flux predictions made by the four land surface models in the North American Land Data Assimilation System Phase 2 (NLDAS-2). Parameters dominated uncertainty in soil moisture estimates and forcing data dominated uncertainty in evapotranspiration estimates; however, the models themselves used only a fraction of the information available to them. This means that there is significant potential to improve all three components of the NLDAS-2 system. In particular, continued work toward refining the parameter maps and look-up tables, the forcing data measurement and processing, and also the land surface models themselves, has potential to result in improved estimates of surface mass and energy balances.

Refined sugar intake in Australian children.

PubMed

Somerset, Shawn M

2003-12-01

To estimate the intake of refined sugar in Australian children and adolescents, aged 2-18 years. Foods contributing to total sugar intake were identified using data from the National Nutrition Survey 1995 (NNS95), the most recent national dietary survey of the Australian population. The top 100 foods represented means of 85% (range 79-91%) and 82% (range 78-85%) of total sugar intake for boys and girls, respectively. Using published Australian food composition data (NUTTAB95), the proportion of total sugar being refined sugar was estimated for each food. Where published food composition data were not available, calculations from ingredients and manufacturer's information were used. The NNS95 assessed the dietary intake of a random sample of the Australian population, aged 2-18 years (n=3007). Mean daily intakes of refined sugar ranged from 26.9 to 78.3 g for 2-18-year-old girls, representing 6.6-14.8% of total energy intake. Corresponding figures for boys were 27.0 to 81.6 g and 8.0-14.0%, respectively. Of the 10 highest sources of refined sugar for each age group, sweetened beverages, especially cola-type beverages, were the most prominent. Refined sugar is an important contributor to dietary energy in Australian children. Sweetened beverages such as soft drinks and cordials were substantial sources of refined sugar and represent a potential target for campaigns to reduce refined sugar intake. Better access to information on the amounts of sugar added to processed food is essential for appropriate monitoring of this important energy source.

Semi-experimental equilibrium structure of pyrazinamide from gas-phase electron diffraction. How much experimental is it?

NASA Astrophysics Data System (ADS)

Tikhonov, Denis S.; Vishnevskiy, Yury V.; Rykov, Anatolii N.; Grikina, Olga E.; Khaikin, Leonid S.

2017-03-01

A semi-experimental equilibrium structure of free molecules of pyrazinamide has been determined for the first time using gas electron diffraction method. The refinement was carried using regularization of geometry by calculated quantum chemical parameters. It is discussed to which extent is the final structure experimental. A numerical approach for estimation of the amount of experimental information in the refined parameters is suggested. The following values of selected internuclear distances were determined (values are in Å with 1σ in the parentheses): re(Cpyrazine-Cpyrazine)av = 1.397(2), re(Npyrazine-Cpyrazine)av = 1.332(3), re(Cpyrazine-Camide) = 1.493(1), re(Namide-Camide) = 1.335(2), re(Oamide-Camide) = 1.219(1). The given standard deviations represent pure experimental uncertainties without the influence of regularization.

Structural design of the Sandia 34-M Vertical Axis Wind Turbine

NASA Astrophysics Data System (ADS)

Berg, D. E.

Sandia National Laboratories, as the lead DOE laboratory for Vertical Axis Wind Turbine (VAWT) development, is currently designing a 34-meter diameter Darrieus-type VAWT. This turbine will be a research test bed which provides a focus for advancing technology and validating design and fabrication techniques in a size range suitable for utility use. Structural data from this machine will allow structural modeling to be refined and verified for a turbine on which the gravity effects and stochastic wind loading are significant. Performance data from it will allow aerodynamic modeling to be refined and verified. The design effort incorporates Sandia's state-of-the-art analysis tools in the design of a complete machine. The analytic tools used in this design are discussed and the conceptual design procedure is described.

Discrete size optimization of steel trusses using a refined big bang-big crunch algorithm

NASA Astrophysics Data System (ADS)

Hasançebi, O.; Kazemzadeh Azad, S.

2014-01-01

This article presents a methodology that provides a method for design optimization of steel truss structures based on a refined big bang-big crunch (BB-BC) algorithm. It is shown that a standard formulation of the BB-BC algorithm occasionally falls short of producing acceptable solutions to problems from discrete size optimum design of steel trusses. A reformulation of the algorithm is proposed and implemented for design optimization of various discrete truss structures according to American Institute of Steel Construction Allowable Stress Design (AISC-ASD) specifications. Furthermore, the performance of the proposed BB-BC algorithm is compared to its standard version as well as other well-known metaheuristic techniques. The numerical results confirm the efficiency of the proposed algorithm in practical design optimization of truss structures.

Three-dimensional structure of photosystem II from Thermosynechococcus elongates in complex with terbutryn

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gabdulkhakov, A. G., E-mail: azat@vega.protes.ru; Dontsova, M. V.; Saenger, W.

Photosystem II is a key component of the photosynthetic pathway producing oxygen at the thylakoid membrane of cyanobacteria, green algae, and plants. The three-dimensional structure of photosystem II from the cyanobacterium Thermosynechococcus elongates in a complex with herbicide terbutryn (a photosynthesis inhibitor) was determined for the first time by X-ray diffraction and refined at 3.2 Angstrom-Sign resolution (R{sub factor} = 26.9%, R{sub free} = 29.9%, rmsd for bond lengths is 0.013 Angstrom-Sign , and rmsd for bond angles is 2.2 Degree-Sign ). The terbutryn molecule was located in the binding pocket of the mobile plastoquinone. The atomic coordinates of themore » refined structure of photosystem II in a complex with terbutryn were deposited in the Protein Data Bank.« less

3D magnetospheric parallel hybrid multi-grid method applied to planet–plasma interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leclercq, L., E-mail: ludivine.leclercq@latmos.ipsl.fr; Modolo, R., E-mail: ronan.modolo@latmos.ipsl.fr; Leblanc, F.

2016-03-15

We present a new method to exploit multiple refinement levels within a 3D parallel hybrid model, developed to study planet–plasma interactions. This model is based on the hybrid formalism: ions are kinetically treated whereas electrons are considered as a inertia-less fluid. Generally, ions are represented by numerical particles whose size equals the volume of the cells. Particles that leave a coarse grid subsequently entering a refined region are split into particles whose volume corresponds to the volume of the refined cells. The number of refined particles created from a coarse particle depends on the grid refinement rate. In order tomore » conserve velocity distribution functions and to avoid calculations of average velocities, particles are not coalesced. Moreover, to ensure the constancy of particles' shape function sizes, the hybrid method is adapted to allow refined particles to move within a coarse region. Another innovation of this approach is the method developed to compute grid moments at interfaces between two refinement levels. Indeed, the hybrid method is adapted to accurately account for the special grid structure at the interfaces, avoiding any overlapping grid considerations. Some fundamental test runs were performed to validate our approach (e.g. quiet plasma flow, Alfven wave propagation). Lastly, we also show a planetary application of the model, simulating the interaction between Jupiter's moon Ganymede and the Jovian plasma.« less

Structure of Escherichia coli RutC, a member of the YjgF family and putative aminoacrylate peracid reductase of the rut operon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knapik, Aleksandra Alicja; Petkowski, Janusz Jurand; Otwinowski, Zbyszek

2014-10-02

RutC is the third enzyme in the Escherichia coli rut pathway of uracil degradation. RutC belongs to the highly conserved YjgF family of proteins. The structure of the RutC protein was determined and refined to 1.95 Å resolution. This crystal belonged to space group P21212 and contained six molecules in the asymmetric unit. The structure was solved by SAD phasing and was refined to an Rwork of 19.3% (Rfree = 21.7%). Moreover, the final model revealed that this protein has a Bacillus chorismate mutase-like fold and forms a homotrimer with a hydrophobic cavity in the center of the structure andmore » ligand-binding clefts between two subunits. A likely function for RutC is the reduction of peroxy-aminoacrylate to aminoacrylate as a part of a detoxification process.« less

Refining the structure and content of clinical genomic reports.

PubMed

Dorschner, Michael O; Amendola, Laura M; Shirts, Brian H; Kiedrowski, Lesli; Salama, Joseph; Gordon, Adam S; Fullerton, Stephanie M; Tarczy-Hornoch, Peter; Byers, Peter H; Jarvik, Gail P

2014-03-01

To effectively articulate the results of exome and genome sequencing we refined the structure and content of molecular test reports. To communicate results of a randomized control trial aimed at the evaluation of exome sequencing for clinical medicine, we developed a structured narrative report. With feedback from genetics and non-genetics professionals, we developed separate indication-specific and incidental findings reports. Standard test report elements were supplemented with research study-specific language, which highlighted the limitations of exome sequencing and provided detailed, structured results, and interpretations. The report format we developed to communicate research results can easily be transformed for clinical use by removal of research-specific statements and disclaimers. The development of clinical reports for exome sequencing has shown that accurate and open communication between the clinician and laboratory is ideally an ongoing process to address the increasing complexity of molecular genetic testing. © 2014 Wiley Periodicals, Inc.

Refining the Structure and Content of Clinical Genomic Reports

PubMed Central

DORSCHNER, MICHAEL O.; AMENDOLA, LAURA M.; SHIRTS, BRIAN H.; KIEDROWSKI, LESLI; SALAMA, JOSEPH; GORDON, ADAM S.; FULLERTON, STEPHANIE M.; TARCZY-HORNOCH, PETER; BYERS, PETER H.; JARVIK, GAIL P.

2014-01-01

To effectively articulate the results of exome and genome sequencing we refined the structure and content of molecular test reports. To communicate results of a randomized control trial aimed at the evaluation of exome sequencing for clinical medicine, we developed a structured narrative report. With feedback from genetics and non-genetics professionals, we developed separate indication-specific and incidental findings reports. Standard test report elements were supplemented with research study-specific language, which highlighted the limitations of exome sequencing and provided detailed, structured results, and interpretations. The report format we developed to communicate research results can easily be transformed for clinical use by removal of research-specific statements and disclaimers. The development of clinical reports for exome sequencing has shown that accurate and open communication between the clinician and laboratory is ideally an ongoing process to address the increasing complexity of molecular genetic testing. PMID:24616401

Combining functional and structural genomics to sample the essential Burkholderia structome.

PubMed

Baugh, Loren; Gallagher, Larry A; Patrapuvich, Rapatbhorn; Clifton, Matthew C; Gardberg, Anna S; Edwards, Thomas E; Armour, Brianna; Begley, Darren W; Dieterich, Shellie H; Dranow, David M; Abendroth, Jan; Fairman, James W; Fox, David; Staker, Bart L; Phan, Isabelle; Gillespie, Angela; Choi, Ryan; Nakazawa-Hewitt, Steve; Nguyen, Mary Trang; Napuli, Alberto; Barrett, Lynn; Buchko, Garry W; Stacy, Robin; Myler, Peter J; Stewart, Lance J; Manoil, Colin; Van Voorhis, Wesley C

2013-01-01

The genus Burkholderia includes pathogenic gram-negative bacteria that cause melioidosis, glanders, and pulmonary infections of patients with cancer and cystic fibrosis. Drug resistance has made development of new antimicrobials critical. Many approaches to discovering new antimicrobials, such as structure-based drug design and whole cell phenotypic screens followed by lead refinement, require high-resolution structures of proteins essential to the parasite. We experimentally identified 406 putative essential genes in B. thailandensis, a low-virulence species phylogenetically similar to B. pseudomallei, the causative agent of melioidosis, using saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq). We selected 315 protein products of these genes based on structure-determination criteria, such as excluding very large and/or integral membrane proteins, and entered them into the Seattle Structural Genomics Center for Infection Disease (SSGCID) structure determination pipeline. To maximize structural coverage of these targets, we applied an "ortholog rescue" strategy for those producing insoluble or difficult to crystallize proteins, resulting in the addition of 387 orthologs (or paralogs) from seven other Burkholderia species into the SSGCID pipeline. This structural genomics approach yielded structures from 31 putative essential targets from B. thailandensis, and 25 orthologs from other Burkholderia species, yielding an overall structural coverage for 49 of the 406 essential gene families, with a total of 88 depositions into the Protein Data Bank. Of these, 25 proteins have properties of a potential antimicrobial drug target i.e., no close human homolog, part of an essential metabolic pathway, and a deep binding pocket. We describe the structures of several potential drug targets in detail. This collection of structures, solubility and experimental essentiality data provides a resource for development of drugs against infections and diseases caused by Burkholderia. All expression clones and proteins created in this study are freely available by request.

Fixed mesh refinement in the characteristic formulation of general relativity

NASA Astrophysics Data System (ADS)

Barreto, W.; de Oliveira, H. P.; Rodriguez-Mueller, B.

2017-08-01

We implement a spatially fixed mesh refinement under spherical symmetry for the characteristic formulation of General Relativity. The Courant-Friedrich-Levy condition lets us deploy an adaptive resolution in (retarded-like) time, even for the nonlinear regime. As test cases, we replicate the main features of the gravitational critical behavior and the spacetime structure at null infinity using the Bondi mass and the News function. Additionally, we obtain the global energy conservation for an extreme situation, i.e. in the threshold of the black hole formation. In principle, the calibrated code can be used in conjunction with an ADM 3+1 code to confirm the critical behavior recently reported in the gravitational collapse of a massless scalar field in an asymptotic anti-de Sitter spacetime. For the scenarios studied, the fixed mesh refinement offers improved runtime and results comparable to code without mesh refinement.

Petroleum mineral oil refining and evaluation of cancer hazard.

PubMed

Mackerer, Carl R; Griffis, Larry C; Grabowski, John S; Reitman, Fred A

2003-11-01

Petroleum base oils (petroleum mineral oils) are manufactured from crude oils by vacuum distillation to produce several distillates and a residual oil that are then further refined. Aromatics including alkylated polycyclic aromatic compounds (PAC) are undesirable constituents of base oils because they are deleterious to product performance and are potentially carcinogenic. In modern base oil refining, aromatics are reduced by solvent extraction, catalytic hydrotreating, or hydrocracking. Chronic exposure to poorly refined base oils has the potential to cause skin cancer. A chronic mouse dermal bioassay has been the standard test for estimating carcinogenic potential of mineral oils. The level of alkylated 3-7-ring PAC in raw streams from the vacuum tower must be greatly reduced to render the base oil noncarcinogenic. The processes that can reduce PAC levels are known, but the operating conditions for the processing units (e.g., temperature, pressure, catalyst type, residence time in the unit, unit engineering design, etc.) needed to achieve adequate PAC reduction are refinery specific. Chronic dermal bioassays provide information about whether conditions applied can make a noncarcinogenic oil, but cannot be used to monitor current production for quality control or for conducting research or developing new processes since this test takes at least 78 weeks to conduct. Three short-term, non-animal assays all involving extraction of oil with dimethylsulfoxide (DMSO) have been validated for predicting potential carcinogenic activity of petroleum base oils: a modified Ames assay of a DMSO extract, a gravimetric assay (IP 346) for wt. percent of oil extracted into DMSO, and a GC-FID assay measuring 3-7-ring PAC content in a DMSO extract of oil, expressed as percent of the oil. Extraction with DMSO concentrates PAC in a manner that mimics the extraction method used in the solvent refining of noncarcinogenic oils. The three assays are described, data demonstrating the validation of the assays are shown, and test results of currently manufactured base oils are summarized to illustrate the general lack of cancer hazard for the base oils now being manufactured.

Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network.

PubMed

Good, Jean-Marc; Mahoney, Michael; Miyazaki, Taisuke; Tanaka, Kenji F; Sakimura, Kenji; Watanabe, Masahiko; Kitamura, Kazuo; Kano, Masanobu

2017-11-21

Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Effect of TiC Nanoparticles Supported by Ti Powders on the Solidification Behavior and Microstructure of Pure Aluminum

NASA Astrophysics Data System (ADS)

Zhao, Bingyi; Cai, Qizhou; Li, Xinwei; Li, Bing; Cheng, Jingfan

2018-03-01

A novel grain refiner consisting of TiC nanoparticles (NPs) supported by Ti powders (abbr. TiC/Ti refiner) was prepared by high-energy milling. The addition of 0.5 wt% TiC/Ti refiner converted the structure of pure Al from coarse dendrites to fine equiaxed grains with the average grain size of 114.7 μm, and it also increased the nucleation temperature of α(Al) from 656.7 to 664.4 °C. When TiC/Ti refiner was introduced into Al melt, the heat released from the Al-Ti reaction promoted the uniform dispersion of TiC NPs. The dissolution of the reaction product TiAl3 released Ti atoms into the melt and thus formed a "Ti-rich transition region" around TiC NPs. The dispersive TiC NPs could act as the heterogeneous nuclei for α(Al) and the "Ti-rich transition region" further improved the lattice orientation relationship between Al (\\bar{1}1\\bar{1} ) and TiC (11\\bar{1} ) planes, which eventually resulted in the refining of α(Al).

Adaptive h -refinement for reduced-order models: ADAPTIVE h -refinement for reduced-order models

DOE PAGES

Carlberg, Kevin T.

2014-11-05

Our work presents a method to adaptively refine reduced-order models a posteriori without requiring additional full-order-model solves. The technique is analogous to mesh-adaptive h-refinement: it enriches the reduced-basis space online by ‘splitting’ a given basis vector into several vectors with disjoint support. The splitting scheme is defined by a tree structure constructed offline via recursive k-means clustering of the state variables using snapshot data. This method identifies the vectors to split online using a dual-weighted-residual approach that aims to reduce error in an output quantity of interest. The resulting method generates a hierarchy of subspaces online without requiring large-scale operationsmore » or full-order-model solves. Furthermore, it enables the reduced-order model to satisfy any prescribed error tolerance regardless of its original fidelity, as a completely refined reduced-order model is mathematically equivalent to the original full-order model. Experiments on a parameterized inviscid Burgers equation highlight the ability of the method to capture phenomena (e.g., moving shocks) not contained in the span of the original reduced basis.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callear, Samantha K.; Imberti, Silvia; Johnston, Andrew

The aqueous solution of dopamine hydrochloride has been investigated using neutron and X-ray total scattering data together with Monte-Carlo based modelling using Empirical Potential Structure Refinement. The conformation of the protonated dopamine molecule is presented and the results compared to the conformations found in crystal structures, dopamine-complexed protein crystal structures and predicted from theoretical calculations and pharmacophoric models. It is found that protonated dopamine adopts a range of conformations in solution, highlighting the low rotational energy barrier between different conformations, with the preferred conformation being trans-perpendicular. The interactions between each of the species present (protonated dopamine molecules, water molecules, andmore » chloride anions) have been determined and are discussed with reference to interactions observed in similar systems both in the liquid and crystalline state, and predicted from theoretical calculations. The expected strong hydrogen bonds between the strong hydrogen bond donors and acceptors are observed, together with evidence of weaker CH hydrogen bonds and π interactions also playing a significant role in determining the arrangement of adjacent molecules.« less

Structure of a bacterial RNA polymerase holoenzyme open promoter complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Brian; Feklistov, Andrey; Lass-Napiorkowska, Agnieszka

2015-09-08

Initiation of transcription is a primary means for controlling gene expression. In bacteria, the RNA polymerase (RNAP) holoenzyme binds and unwinds promoter DNA, forming the transcription bubble of the open promoter complex (RPo). We have determined crystal structures, refined to 4.14 Å-resolution, of RPo containing Thermus aquaticus RNAP holoenzyme and promoter DNA that includes the full transcription bubble. The structures, combined with biochemical analyses, reveal key features supporting the formation and maintenance of the double-strand/single-strand DNA junction at the upstream edge of the -10 element where bubble formation initiates. The results also reveal RNAP interactions with duplex DNA just upstreammore » of the -10 element and potential protein/DNA interactions that direct the DNA template strand into the RNAP active site. Addition of an RNA primer to yield a 4 base-pair post-translocated RNA:DNA hybrid mimics an initially transcribing complex at the point where steric clash initiates abortive initiation and σA dissociation.« less

Structure of a bacterial RNA polymerase holoenzyme open promoter complex

DOE PAGES

Bae, Brian; Feklistov, Andrey; Lass-Napiorkowska, Agnieszka; ...

2015-09-08

Initiation of transcription is a primary means for controlling gene expression. In bacteria, the RNA polymerase (RNAP) holoenzyme binds and unwinds promoter DNA, forming the transcription bubble of the open promoter complex (RPo). We have determined crystal structures, refined to 4.14 Å-resolution, of RPo containing Thermus aquaticus RNAP holoenzyme and promoter DNA that includes the full transcription bubble. The structures, combined with biochemical analyses, reveal key features supporting the formation and maintenance of the double-strand/single-strand DNA junction at the upstream edge of the -10 element where bubble formation initiates. The results also reveal RNAP interactions with duplex DNA just upstreammore » of the -10 element and potential protein/DNA interactions that direct the DNA template strand into the RNAP active site. Additionally a RNA primer to yield a 4 base-pair post-translocated RNA:DNA hybrid mimics an initially transcribing complex at the point where steric clash initiates abortive initiation and σ A dissociation.« less

Characterizing Aeroelastic Systems Using Eigenanalysis, Explicitly Retaining The Aerodynamic Degrees of Freedom

NASA Technical Reports Server (NTRS)

Heeg, Jennifer; Dowell, Earl H.

2001-01-01

Discrete time aeroelastic models with explicitly retained aerodynamic modes have been generated employing a time marching vortex lattice aerodynamic model. This paper presents analytical results from eigenanalysis of these models. The potential of these models to calculate the behavior of modes that represent damped system motion (noncritical modes) in addition to the simple harmonic modes is explored. A typical section with only structural freedom in pitch is examined. The eigenvalues are examined and compared to experimental data. Issues regarding the convergence of the solution with regard to refining the aerodynamic discretization are investigated. Eigenvector behavior is examined; the eigenvector associated with a particular eigenvalue can be viewed as the set of modal participation factors for that particular mode. For the present formulation of the equations of motion, the vorticity for each aerodynamic element appears explicitly as an element of each eigenvector in addition to the structural dynamic generalized coordinates. Thus, modal participation of the aerodynamic degrees of freedom can be assessed in M addition to participation of structural degrees of freedom.

On the solvation of the phosphocholine headgroup in an aqueous propylene glycol solution

NASA Astrophysics Data System (ADS)

Rhys, Natasha H.; Al-Badri, Mohamed Ali; Ziolek, Robert M.; Gillams, Richard J.; Collins, Louise E.; Lawrence, M. Jayne; Lorenz, Christian D.; McLain, Sylvia E.

2018-04-01

The atomic-scale structure of the phosphocholine (PC) headgroup in 30 mol. % propylene glycol (PG) in an aqueous solution has been investigated using a combination of neutron diffraction with isotopic substitution experiments and computer simulation techniques—molecular dynamics and empirical potential structure refinement. Here, the hydration of the PC headgroup remains largely intact compared with the hydration of this group in a bilayer and in a bulk water solution, with the PG molecules showing limited interactions with the headgroup. When direct PG interactions with PC do occur, they are most likely to coordinate to the 3+N (CH 3 ) motifs. Further, PG does not affect the bulk water structure and the addition of PC does not perturb the PG-solvent interactions. This suggests that the reason why PG is able to penetrate into membranes easily is that it does not form strong-hydrogen bonding or electrostatic interactions with the headgroup allowing it to easily move across the membrane barrier.

Prediction of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling

NASA Astrophysics Data System (ADS)

Bhakat, Soumendranath; Åberg, Emil; Söderhjelm, Pär

2018-01-01

Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge. The results show that the multiple-target docking protocol performs surprisingly well, with correct poses found for 21 of the ligands. MD simulations started on the docked structures are remarkably stable, but show almost no tendency of refining the structure closer to the experimentally found binding pose. Reconnaissance metadynamics enhances the exploration of new binding poses, but additional collective variables involving the protein are needed to exploit the full potential of the method.

Prediction of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling.

PubMed

Bhakat, Soumendranath; Åberg, Emil; Söderhjelm, Pär

2018-01-01

Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge. The results show that the multiple-target docking protocol performs surprisingly well, with correct poses found for 21 of the ligands. MD simulations started on the docked structures are remarkably stable, but show almost no tendency of refining the structure closer to the experimentally found binding pose. Reconnaissance metadynamics enhances the exploration of new binding poses, but additional collective variables involving the protein are needed to exploit the full potential of the method.

Coherent convergent-beam time-resolved X-ray diffraction

PubMed Central

Spence, John C. H.; Zatsepin, Nadia A.; Li, Chufeng

2014-01-01

The use of coherent X-ray lasers for structural biology allows the use of nanometre diameter X-ray beams with large beam divergence. Their application to the structure analysis of protein nanocrystals and single particles raises new challenges and opportunities. We discuss the form of these coherent convergent-beam (CCB) hard X-ray diffraction patterns and their potential use for time-resolved crystallography, normally achieved by Laue (polychromatic) diffraction, for which the monochromatic laser radiation of a free-electron X-ray laser is unsuitable. We discuss the possibility of obtaining single-shot, angle-integrated rocking curves from CCB patterns, and the dependence of the resulting patterns on the focused beam coordinate when the beam diameter is larger or smaller than a nanocrystal, or smaller than one unit cell. We show how structure factor phase information is provided at overlapping interfering orders and how a common phase origin between different shots may be obtained. Their use in refinement of the phase-sensitive intensity between overlapping orders is suggested. PMID:24914153

Two stage bioethanol refining with multi litre stacked microbial fuel cell and microbial electrolysis cell.

PubMed

Sugnaux, Marc; Happe, Manuel; Cachelin, Christian Pierre; Gloriod, Olivier; Huguenin, Gérald; Blatter, Maxime; Fischer, Fabian

2016-12-01

Ethanol, electricity, hydrogen and methane were produced in a two stage bioethanol refinery setup based on a 10L microbial fuel cell (MFC) and a 33L microbial electrolysis cell (MEC). The MFC was a triple stack for ethanol and electricity co-generation. The stack configuration produced more ethanol with faster glucose consumption the higher the stack potential. Under electrolytic conditions ethanol productivity outperformed standard conditions and reached 96.3% of the theoretically best case. At lower external loads currents and working potentials oscillated in a self-synchronized manner over all three MFC units in the stack. In the second refining stage, fermentation waste was converted into methane, using the scale up MEC stack. The bioelectric methanisation reached 91% efficiency at room temperature with an applied voltage of 1.5V using nickel cathodes. The two stage bioethanol refining process employing bioelectrochemical reactors produces more energy vectors than is possible with today's ethanol distilleries. Copyright © 2016 Elsevier Ltd. All rights reserved.

A User's Guide to AMR1D: An Instructional Adaptive Mesh Refinement Code for Unstructured Grids

NASA Technical Reports Server (NTRS)

deFainchtein, Rosalinda

1996-01-01

This report documents the code AMR1D, which is currently posted on the World Wide Web (http://sdcd.gsfc.nasa.gov/ESS/exchange/contrib/de-fainchtein/adaptive _mesh_refinement.html). AMR1D is a one-dimensional finite element fluid-dynamics solver, capable of adaptive mesh refinement (AMR). It was written as an instructional tool for AMR on unstructured mesh codes. It is meant to illustrate the minimum requirements for AMR on more than one dimension. For that purpose, it uses the same type of data structure that would be necessary on a two-dimensional AMR code (loosely following the algorithm described by Lohner).

Performance-Based Service Acquisition (PBSA) Study and Graduate Level Course Material

DTIC Science & Technology

2005-12-01

Realizing Marketplace Potential, Acquisition Solutions, Inc (Advisory), February 2001 Dickson, Bob, March 10, 2003. Federal 7 Contract Law : Feds...Management and Policy Federal Contract Law : Feds should use market research to refine IT plans Session 4: The Performance Requirements and...March 10, 2003. Federal Contract Law : Feds should use market research to refine IT plans, Post-Newsweek Media, Inchttp://appserv.gcn.com/cgi- bin/udt

Neutron protein crystallography: A complementary tool for locating hydrogens in proteins.

PubMed

O'Dell, William B; Bodenheimer, Annette M; Meilleur, Flora

2016-07-15

Neutron protein crystallography is a powerful tool for investigating protein chemistry because it directly locates hydrogen atom positions in a protein structure. The visibility of hydrogen and deuterium atoms arises from the strong interaction of neutrons with the nuclei of these isotopes. Positions can be unambiguously assigned from diffraction at resolutions typical of protein crystals. Neutrons have the additional benefit to structural biology of not inducing radiation damage in protein crystals. The same crystal could be measured multiple times for parametric studies. Here, we review the basic principles of neutron protein crystallography. The information that can be gained from a neutron structure is presented in balance with practical considerations. Methods to produce isotopically-substituted proteins and to grow large crystals are provided in the context of neutron structures reported in the literature. Available instruments for data collection and software for data processing and structure refinement are described along with technique-specific strategies including joint X-ray/neutron structure refinement. Examples are given to illustrate, ultimately, the unique scientific value of neutron protein crystal structures. Copyright © 2015 Elsevier Inc. All rights reserved.

Combining density functional theory (DFT) and pair distribution function (PDF) analysis to solve the structure of metastable materials: the case of metakaolin.

PubMed

White, Claire E; Provis, John L; Proffen, Thomas; Riley, Daniel P; van Deventer, Jannie S J

2010-04-07

Understanding the atomic structure of complex metastable (including glassy) materials is of great importance in research and industry, however, such materials resist solution by most standard techniques. Here, a novel technique combining thermodynamics and local structure is presented to solve the structure of the metastable aluminosilicate material metakaolin (calcined kaolinite) without the use of chemical constraints. The structure is elucidated by iterating between least-squares real-space refinement using neutron pair distribution function data, and geometry optimisation using density functional modelling. The resulting structural representation is both energetically feasible and in excellent agreement with experimental data. This accurate structural representation of metakaolin provides new insight into the local environment of the aluminium atoms, with evidence of the existence of tri-coordinated aluminium. By the availability of this detailed chemically feasible atomic description, without the need to artificially impose constraints during the refinement process, there exists the opportunity to tailor chemical and mechanical processes involving metakaolin and other complex metastable materials at the atomic level to obtain optimal performance at the macro-scale.

Assessment of land use impact on water-related ecosystem services capturing the integrated terrestrial-aquatic system.

PubMed

Maes, Wouter H; Heuvelmans, Griet; Muys, Bart

2009-10-01

Although the importance of green (evaporative) water flows in delivering ecosystem services has been recognized, most operational impact assessment methods still focus only on blue water flows. In this paper, we present a new model to evaluate the effect of land use occupation and transformation on water quantity. Conceptually based on the supply of ecosystem services by terrestrial and aquatic ecosystems, the model is developed for, but not limited to, land use impact assessment in life cycle assessment (LCA) and requires a minimum amount of input data. Impact is minimal when evapotranspiration is equal to that of the potential natural vegetation, and maximal when evapotranspiration is zero or when it exceeds a threshold value derived from the concept of environmental water requirement. Three refinements to the model, requiring more input data, are proposed. The first refinement considers a minimal impact over a certain range based on the boundary evapotranspiration of the potential natural vegetation. In the second refinement the effects of evaporation and transpiration are accounted for separately, and in the third refinement a more correct estimate of evaporation from a fully sealed surface is incorporated. The simplicity and user friendliness of the proposed impact assessment method are illustrated with two examples.

RNA2D3D: a program for generating, viewing, and comparing 3-dimensional models of RNA.

PubMed

Martinez, Hugo M; Maizel, Jacob V; Shapiro, Bruce A

2008-06-01

Using primary and secondary structure information of an RNA molecule, the program RNA2D3D automatically and rapidly produces a first-order approximation of a 3-dimensional conformation consistent with this information. Applicable to structures of arbitrary branching complexity and pseudoknot content, it features efficient interactive graphical editing for the removal of any overlaps introduced by the initial generating procedure and for making conformational changes favorable to targeted features and subsequent refinement. With emphasis on fast exploration of alternative 3D conformations, one may interactively add or delete base-pairs, adjacent stems can be coaxially stacked or unstacked, single strands can be shaped to accommodate special constraints, and arbitrary subsets can be defined and manipulated as rigid bodies. Compaction, whereby base stacking within stems is optimally extended into connecting single strands, is also available as a means of strategically making the structures more compact and revealing folding motifs. Subsequent refinement of the first-order approximation, of modifications, and for the imposing of tertiary constraints is assisted with standard energy refinement techniques. Previously determined coordinates for any part of the molecule are readily incorporated, and any part of the modeled structure can be output as a PDB or XYZ file. Illustrative applications in the areas of ribozymes, viral kissing loops, viral internal ribosome entry sites, and nanobiology are presented.

Lunar troilite: Crystallography

USGS Publications Warehouse

Evans, H.T.

1970-01-01

Fine, euhedral crystals of troilite from lunar sample 10050 show a hexagonal habit consistent with the high-temperature NiAs-type structure. Complete three-dimensional counter intensity data have been measured and used to confirm and refine Bertaut's proposed low-temperature crystal structure.

Advances in the REDCAT software package

PubMed Central

2013-01-01

Background Residual Dipolar Couplings (RDCs) have emerged in the past two decades as an informative source of experimental restraints for the study of structure and dynamics of biological macromolecules and complexes. The REDCAT software package was previously introduced for the analysis of molecular structures using RDC data. Here we report additional features that have been included in this software package in order to expand the scope of its analyses. We first discuss the features that enhance REDCATs user-friendly nature, such as the integration of a number of analyses into one single operation and enabling convenient examination of a structural ensemble in order to identify the most suitable structure. We then describe the new features which expand the scope of RDC analyses, performing exercises that utilize both synthetic and experimental data to illustrate and evaluate different features with regard to structure refinement and structure validation. Results We establish the seamless interaction that takes place between REDCAT, VMD, and Xplor-NIH in demonstrations that utilize our newly developed REDCAT-VMD and XplorGUI interfaces. These modules enable visualization of RDC analysis results on the molecular structure displayed in VMD and refinement of structures with Xplor-NIH, respectively. We also highlight REDCAT’s Error-Analysis feature in reporting the localized fitness of a structure to RDC data, which provides a more effective means of recognizing local structural anomalies. This allows for structurally sound regions of a molecule to be identified, and for any refinement efforts to be focused solely on locally distorted regions. Conclusions The newly engineered REDCAT software package, which is available for download via the WWW from http://ifestos.cse.sc.edu, has been developed in the Object Oriented C++ environment. Our most recent enhancements to REDCAT serve to provide a more complete RDC analysis suite, while also accommodating a more user-friendly experience, and will be of great interest to the community of researchers and developers since it hides the complications of software development. PMID:24098943

The crystal structure of calcite III

NASA Astrophysics Data System (ADS)

Smyth, Joseph R.; Ahrens, Thomas J.

The crystal structure of calcite III has been deduced from existing high pressure powder X-ray diffraction patterns, based on the assumption that it is a displacive modification of the calcite I structure. The structure is monoclinic with space group C2 and a Z of 6. There are two Ca and two C positions, and five O positions, and atom coordinates have been refined by distance-least-squares methods to give reasonable octahedral coordination for Ca and parallel, planar CO3 groups. Unit cell parameters refined from a published powder diffraction pattern at 4.1 GPa are: a = 8.746(8)Å b = 4.685(5)Å c = 8.275(8)Å and β= 94.4°. The structure has a calculated density of 2.949 Mg/m³ at 4.1 GPa which is less than that of aragonite at this pressure and consistent with early piston cylinder studies. This implies that calcite III is indeed a metastable intermediary between calcite I and aragonite.

Update on Bio-Refining and Nanocellulose Composite Materials Manufacturing.

PubMed

Postek, Michael T; Poster, Dianne L

2017-01-01

Nanocellulose is a high value material that has gained increasing attention because of its high strength, stiffness, unique photonic and piezoelectric properties, high stability and uniform structure. One of the factors limiting the potential of nanocellulose and the vast array of potential new products is the ability to produce high-volume quantities of this nano-material. However, recent research has demonstrated that nanocellulose can be efficently produced in large volumes from wood at relatively low cost by the incorporation of ionizing radiation in the process stream. Ionizing radiation causes significant break down of the polysaccharides and leads to the production of potentially useful gaseous products such as H 2 and CO. Ionizing radiation processing remains an open field, ripe for innovation and application. This presentation will review the strong collaboration between the National Institute of Standards and Technology (NIST) and its academic partners pursuing the demonstration of applied ionizing radiation processing to plant materials for the manufacturing and characterization of novel nanomaterials.

Update on Bio-Refining and Nanocellulose Composite Materials Manufacturing

PubMed Central

Postek, Michael T.; Poster, Dianne L.

2017-01-01

Nanocellulose is a high value material that has gained increasing attention because of its high strength, stiffness, unique photonic and piezoelectric properties, high stability and uniform structure. One of the factors limiting the potential of nanocellulose and the vast array of potential new products is the ability to produce high-volume quantities of this nano-material. However, recent research has demonstrated that nanocellulose can be efficently produced in large volumes from wood at relatively low cost by the incorporation of ionizing radiation in the process stream. Ionizing radiation causes significant break down of the polysaccharides and leads to the production of potentially useful gaseous products such as H2 and CO. Ionizing radiation processing remains an open field, ripe for innovation and application. This presentation will review the strong collaboration between the National Institute of Standards and Technology (NIST) and its academic partners pursuing the demonstration of applied ionizing radiation processing to plant materials for the manufacturing and characterization of novel nanomaterials. PMID:29225398

Update on bio-refining and nanocellulose composite materials manufacturing

NASA Astrophysics Data System (ADS)

Postek, Michael T.; Poster, Dianne L.

2017-08-01

Nanocellulose is a high value material that has gained increasing attention because of its high strength, stiffness, unique photonic and piezoelectric properties, high stability and uniform structure. One of the factors limiting the potential of nanocellulose and the vast array of potential new products is the ability to produce high-volume quantities of this nano-material. However, recent research has demonstrated that nanocellulose can be efficently produced in large volumes from wood at relatively low cost by the incorporation of ionizing radiation in the process stream. Ionizing radiation causes significant break down of the polysaccharides and leads to the production of potentially useful gaseous products such as H2 and CO. Ionizing radiation processing remains an open field, ripe for innovation and application. This presentation will review the strong collaboration between the National Institute of Standards and Technology (NIST) and its academic partners pursuing the demonstration of applied ionizing radiation processing to plant materials for the manufacturing and characterization of novel nanomaterials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leimkuhler, B.; Hermans, J.; Skeel, R.D.

A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

Analysis of Microstructure Refinement During Single-Pass and Multi-Pass Friction Stir Processing of Nial Propeller Bronze

DTIC Science & Technology

2010-09-01

on an Optical Micrograph of the Transverse View of Single-Pass NAB. After [5]............................................... 6 Figure 4 . Vertical...deformed and 6 elongated but does not see the same refinement that is seen inside the SZ [ 4 ]. The grain structure right outside the TMAZ will also...including grinding, polishing, and electropolishing . The first step was to grind the surface using a Buehler ECOMET 4 Variable Speed Grinder

The Processes Involved in Designing Software.

DTIC Science & Technology

1980-08-01

repeats Itself at the next level, terminating with a plan whose individual steps can be executed to solve the Initial problem. Hayes-Roth and Hayes-Roth...that the original design problem is decomposed into a collection of well structured subproblems under the control of some type of executive process...given element to refine further, the schema is assumed to execute to completion, developing a solution model for that element and refining it into a

Effect of Al Addition on Microstructure of AZ91D

NASA Astrophysics Data System (ADS)

Joshi, Utsavi; Babu, Nadendla Hari

Casting is a net shape or near net shape forming process so work-hardening will not be applicable for improving properties of magnesium cast alloys. Grain refinement, solid-solution strengthening, precipitation hardening and specially designed heat treatment are the techniques used to enhance the properties of these alloys. This research focusses on grain refinement of magnesium alloy AZ91D, which is a widely used commercial cast alloy. Recently, Al-B based master alloys have shown potential in grain refining AZ91D. A comparative study of the grain refinement of AZ91D by addition of 0.02wt%B, 0.04wt%B, 0.1wt%B, 0.5wt%B and 1.0wt%B of A1-5B master alloy and equivalent amount of solute element aluminium is described in this paper. Hardness profile of AZ91D alloyed with boron and aluminium is compared.

Design of Broad-Spectrum Inhibitors of Influenza A Virus M2 Proton Channels: A Molecular Modeling Approach.

PubMed

Klimochkin, Yuri N; Shiryaev, Vadim A; Petrov, Pavel V; Radchenko, Eugene V; Palyulin, Vladimir A; Zefirov, Nikolay S

2016-01-01

The influenza A virus M2 proton channel plays a critical role in its life cycle. However, known M2 inhibitors have lost their clinical efficacy due to the spread of resistant mutant channels. Thus, the search for broad-spectrum M2 channel inhibitors is of great importance. The goal of the present work was to develop a general approach supporting the design of ligands interacting with multiple labile targets and to propose on its basis the potential broad-spectrum inhibitors of the M2 proton channel. The dynamic dimer-of-dimers structures of the three primary M2 target variants, wild-type, S31N and V27A, were modeled by molecular dynamics and thoroughly analyzed in order to define the inhibitor binding sites. The potential inhibitor structures were identified by molecular docking and their binding was verified by molecular dynamics simulation. The binding sites of the M2 proton channel inhibitors were analyzed, a number of potential broad-spectrum inhibitors were identified and the binding modes and probable mechanisms of action of one promising compound were clarified. Using the molecular dynamics and molecular docking techniques, we have refined the dynamic dimer-ofdimers structures of the WT, S31N and V27A variants of the M2 proton channel of the influenza A virus, analyzed the inhibitor binding sites, identified a number of potential broad-spectrum inhibitor structures targeting them, and clarified the binding modes and probable mechanisms of action of one promising compound. The proposed approach is also suitable for the design of ligands interacting with other multiple labile targets.

How large B-factors can be in protein crystal structures.

PubMed

Carugo, Oliviero

2018-02-23

Protein crystal structures are potentially over-interpreted since they are routinely refined without any restraint on the upper limit of atomic B-factors. Consequently, some of their atoms, undetected in the electron density maps, are allowed to reach extremely large B-factors, even above 100 square Angstroms, and their final positions are purely speculative and not based on any experimental evidence. A strategy to define B-factors upper limits is described here, based on the analysis of protein crystal structures deposited in the Protein Data Bank prior 2008, when the tendency to allow B-factor to arbitrary inflate was limited. This B-factor upper limit (B_max) is determined by extrapolating the relationship between crystal structure average B-factor and percentage of crystal volume occupied by solvent (pcVol) to pcVol =100%, when, ab absurdo, the crystal contains only liquid solvent, the structure of which is, by definition, undetectable in electron density maps. It is thus possible to highlight structures with average B-factors larger than B_max, which should be considered with caution by the users of the information deposited in the Protein Data Bank, in order to avoid scientifically deleterious over-interpretations.

Probing the structure of heterogeneous diluted materials by diffraction tomography.

PubMed

Bleuet, Pierre; Welcomme, Eléonore; Dooryhée, Eric; Susini, Jean; Hodeau, Jean-Louis; Walter, Philippe

2008-06-01

The advent of nanosciences calls for the development of local structural probes, in particular to characterize ill-ordered or heterogeneous materials. Furthermore, because materials properties are often related to their heterogeneity and the hierarchical arrangement of their structure, different structural probes covering a wide range of scales are required. X-ray diffraction is one of the prime structural methods but suffers from a relatively poor detection limit, whereas transmission electron analysis involves destructive sample preparation. Here we show the potential of coupling pencil-beam tomography with X-ray diffraction to examine unidentified phases in nanomaterials and polycrystalline materials. The demonstration is carried out on a high-pressure pellet containing several carbon phases and on a heterogeneous powder containing chalcedony and iron pigments. The present method enables a non-invasive structural refinement with a weight sensitivity of one part per thousand. It enables the extraction of the scattering patterns of amorphous and crystalline compounds with similar atomic densities and compositions. Furthermore, such a diffraction-tomography experiment can be carried out simultaneously with X-ray fluorescence, Compton and absorption tomographies, enabling a multimodal analysis of prime importance in materials science, chemistry, geology, environmental science, medical science, palaeontology and cultural heritage.

Improving Protocols for Protein Mapping through Proper Comparison to Crystallography Data

PubMed Central

Lexa, Katrina W.; Carlson, Heather A.

2013-01-01

Computational approaches to fragment-based drug design (FBDD) can complement experiments and facilitate the identification of potential hot spots along the protein surface. However, the evaluation of computational methods for mapping binding sites frequently focuses upon the ability to reproduce crystallographic coordinates to within a low RMSD threshold. This dependency on the deposited coordinate data overlooks the original electron density from the experiment, thus techniques may be developed based upon subjective - or even erroneous - atomic coordinates. This can become a significant drawback in applications to systems where the location of hot spots is unknown. Based on comparison to crystallographic density, we previously showed that mixed-solvent molecular dynamics (MixMD) accurately identifies the active site for HEWL, with acetonitrile as an organic solvent. Here, we concentrated on the influence of protic solvent on simulation and refined the optimal MixMD approach for extrapolation of the method to systems without established sites. Our results establish an accurate approach for comparing simulations to experiment. We have outlined the most efficient strategy for MixMD, based on simulation length and number of runs. The development outlined here makes MixMD a robust method which should prove useful across a broad range of target structures. Lastly, our results with MixMD match experimental data so well that consistency between simulations and density may be a useful way to aid the identification of probes vs waters during the refinement of future MSCS crystallographic structures. PMID:23327200

A Proposed Intelligent Policy-Based Interface for a Mobile eHealth Environment

NASA Astrophysics Data System (ADS)

Tavasoli, Amir; Archer, Norm

Users of mobile eHealth systems are often novices, and the learning process for them may be very time consuming. In order for systems to be attractive to potential adopters, it is important that the interface should be very convenient and easy to learn. However, the community of potential users of a mobile eHealth system may be quite varied in their requirements, so the system must be able to adapt easily to suit user preferences. One way to accomplish this is to have the interface driven by intelligent policies. These policies can be refined gradually, using inputs from potential users, through intelligent agents. This paper develops a framework for policy refinement for eHealth mobile interfaces, based on dynamic learning from user interactions.

Bayesian ensemble refinement by replica simulations and reweighting.

PubMed

Hummer, Gerhard; Köfinger, Jürgen

2015-12-28

We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We show that the strength of the restraints should scale linearly with the number of replicas to ensure convergence to the optimal Bayesian result in the limit of infinitely many replicas. In the "Bayesian inference of ensembles" method, we combine the replica and EROS approaches to accelerate the convergence. An adaptive algorithm can be used to sample directly from the optimal ensemble, without replicas. We discuss the incorporation of single-molecule measurements and dynamic observables such as relaxation parameters. The theoretical analysis of different Bayesian ensemble refinement approaches provides a basis for practical applications and a starting point for further investigations.

Improved parallel image reconstruction using feature refinement.

PubMed

Cheng, Jing; Jia, Sen; Ying, Leslie; Liu, Yuanyuan; Wang, Shanshan; Zhu, Yanjie; Li, Ye; Zou, Chao; Liu, Xin; Liang, Dong

2018-07-01

The aim of this study was to develop a novel feature refinement MR reconstruction method from highly undersampled multichannel acquisitions for improving the image quality and preserve more detail information. The feature refinement technique, which uses a feature descriptor to pick up useful features from residual image discarded by sparsity constrains, is applied to preserve the details of the image in compressed sensing and parallel imaging in MRI (CS-pMRI). The texture descriptor and structure descriptor recognizing different types of features are required for forming the feature descriptor. Feasibility of the feature refinement was validated using three different multicoil reconstruction methods on in vivo data. Experimental results show that reconstruction methods with feature refinement improve the quality of reconstructed image and restore the image details more accurately than the original methods, which is also verified by the lower values of the root mean square error and high frequency error norm. A simple and effective way to preserve more useful detailed information in CS-pMRI is proposed. This technique can effectively improve the reconstruction quality and has superior performance in terms of detail preservation compared with the original version without feature refinement. Magn Reson Med 80:211-223, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Bayesian ensemble refinement by replica simulations and reweighting

NASA Astrophysics Data System (ADS)

Hummer, Gerhard; Köfinger, Jürgen

2015-12-01

We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We show that the strength of the restraints should scale linearly with the number of replicas to ensure convergence to the optimal Bayesian result in the limit of infinitely many replicas. In the "Bayesian inference of ensembles" method, we combine the replica and EROS approaches to accelerate the convergence. An adaptive algorithm can be used to sample directly from the optimal ensemble, without replicas. We discuss the incorporation of single-molecule measurements and dynamic observables such as relaxation parameters. The theoretical analysis of different Bayesian ensemble refinement approaches provides a basis for practical applications and a starting point for further investigations.

Implementing technical refinement in high-level athletics: exploring the knowledge schemas of coaches.

PubMed

Kearney, Philip E; Carson, Howie J; Collins, Dave

2018-05-01

This paper explores the approaches adopted by high-level field athletics coaches when attempting to refine an athlete's already well-established technique (long and triple jump and javelin throwing). Six coaches, who had all coached multiple athletes to multiple major championships, took part in semi-structured interviews focused upon a recent example of technique refinement. Data were analysed using a thematic content analysis. The coaching tools reported were generally consistent with those advised by the existing literature, focusing on attaining "buy-in", utilising part-practice, restoring movement automaticity and securing performance under pressure. Five of the six coaches reported using a systematic sequence of stages to implement the refinement, although the number and content of these stages varied between them. Notably, however, there were no formal sources of knowledge (e.g., coach education or training) provided to inform coaches' decision making. Instead, coaches' decisions were largely based on experience both within and outside the sporting domain. Data offer a useful stimulus for reflection amongst sport practitioners confronted by the problem of technique refinement. Certainly the limited awareness of existing guidelines on technique refinement expressed by the coaches emphasises a need for further collaborative work by researchers and coach educators to disseminate best practice.

Challenges of Representing Sub-Grid Physics in an Adaptive Mesh Refinement Atmospheric Model

NASA Astrophysics Data System (ADS)

O'Brien, T. A.; Johansen, H.; Johnson, J. N.; Rosa, D.; Benedict, J. J.; Keen, N. D.; Collins, W.; Goodfriend, E.

2015-12-01

Some of the greatest potential impacts from future climate change are tied to extreme atmospheric phenomena that are inherently multiscale, including tropical cyclones and atmospheric rivers. Extremes are challenging to simulate in conventional climate models due to existing models' coarse resolutions relative to the native length-scales of these phenomena. Studying the weather systems of interest requires an atmospheric model with sufficient local resolution, and sufficient performance for long-duration climate-change simulations. To this end, we have developed a new global climate code with adaptive spatial and temporal resolution. The dynamics are formulated using a block-structured conservative finite volume approach suitable for moist non-hydrostatic atmospheric dynamics. By using both space- and time-adaptive mesh refinement, the solver focuses computational resources only where greater accuracy is needed to resolve critical phenomena. We explore different methods for parameterizing sub-grid physics, such as microphysics, macrophysics, turbulence, and radiative transfer. In particular, we contrast the simplified physics representation of Reed and Jablonowski (2012) with the more complex physics representation used in the System for Atmospheric Modeling of Khairoutdinov and Randall (2003). We also explore the use of a novel macrophysics parameterization that is designed to be explicitly scale-aware.

Development and analysis of a twelfth degree and order gravity model for Mars

NASA Technical Reports Server (NTRS)

Christensen, E. J.; Balmino, G.

1979-01-01

Satellite geodesy techniques previously applied to artificial earth satellites have been extended to obtain a high-resolution gravity field for Mars. Two-way Doppler data collected by 10 Deep Space Network (DSN) stations during Mariner 9 and Viking 1 and 2 missions have been processed to obtain a twelfth degree and order spherical harmonic model for the martian gravitational potential. The quality of this model was evaluated by examining the rms residuals within the fit and the ability of the model to predict the spacecraft state beyond the fit. Both indicators show that more data and higher degree and order harmonics will be required to further refine our knowledge of the martian gravity field. The model presented shows much promise, since it resolves local gravity features which correlate highly with the martian topography. An isostatic analysis based on this model, as well as an error analysis, shows rather complete compensation on a global (long wavelength) scale. Though further model refinements are necessary to be certain, local (short wavelength) features such as the shield volcanos in Tharsis appear to be uncompensated. These are interpreted to place some bounds on the internal structure of Mars.

Surface layer protein characterization by small angle x-ray scattering and a fractal mean force concept: from protein structure to nanodisk assemblies.

PubMed

Horejs, Christine; Pum, Dietmar; Sleytr, Uwe B; Peterlik, Herwig; Jungbauer, Alois; Tscheliessnig, Rupert

2010-11-07

Surface layers (S-layers) are the most commonly observed cell surface structure of prokaryotic organisms. They are made up of proteins that spontaneously self-assemble into functional crystalline lattices in solution, on various solid surfaces, and interfaces. While classical experimental techniques failed to recover a complete structural model of an unmodified S-layer protein, small angle x-ray scattering (SAXS) provides an opportunity to study the structure of S-layer monomers in solution and of self-assembled two-dimensional sheets. For the protein under investigation we recently suggested an atomistic structural model by the use of molecular dynamics simulations. This structural model is now refined on the basis of SAXS data together with a fractal assembly approach. Here we show that a nondiluted critical system of proteins, which crystallize into monomolecular structures, might be analyzed by SAXS if protein-protein interactions are taken into account by relating a fractal local density distribution to a fractal local mean potential, which has to fulfill the Poisson equation. The present work demonstrates an important step into the elucidation of the structure of S-layers and offers a tool to analyze the structure of self-assembling systems in solution by means of SAXS and computer simulations.

Surface layer protein characterization by small angle x-ray scattering and a fractal mean force concept: From protein structure to nanodisk assemblies

NASA Astrophysics Data System (ADS)

Horejs, Christine; Pum, Dietmar; Sleytr, Uwe B.; Peterlik, Herwig; Jungbauer, Alois; Tscheliessnig, Rupert

2010-11-01

Surface layers (S-layers) are the most commonly observed cell surface structure of prokaryotic organisms. They are made up of proteins that spontaneously self-assemble into functional crystalline lattices in solution, on various solid surfaces, and interfaces. While classical experimental techniques failed to recover a complete structural model of an unmodified S-layer protein, small angle x-ray scattering (SAXS) provides an opportunity to study the structure of S-layer monomers in solution and of self-assembled two-dimensional sheets. For the protein under investigation we recently suggested an atomistic structural model by the use of molecular dynamics simulations. This structural model is now refined on the basis of SAXS data together with a fractal assembly approach. Here we show that a nondiluted critical system of proteins, which crystallize into monomolecular structures, might be analyzed by SAXS if protein-protein interactions are taken into account by relating a fractal local density distribution to a fractal local mean potential, which has to fulfill the Poisson equation. The present work demonstrates an important step into the elucidation of the structure of S-layers and offers a tool to analyze the structure of self-assembling systems in solution by means of SAXS and computer simulations.

Surface layer protein characterization by small angle x-ray scattering and a fractal mean force concept: From protein structure to nanodisk assemblies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horejs, Christine; Pum, Dietmar; Sleytr, Uwe B.

2010-11-07

Surface layers (S-layers) are the most commonly observed cell surface structure of prokaryotic organisms. They are made up of proteins that spontaneously self-assemble into functional crystalline lattices in solution, on various solid surfaces, and interfaces. While classical experimental techniques failed to recover a complete structural model of an unmodified S-layer protein, small angle x-ray scattering (SAXS) provides an opportunity to study the structure of S-layer monomers in solution and of self-assembled two-dimensional sheets. For the protein under investigation we recently suggested an atomistic structural model by the use of molecular dynamics simulations. This structural model is now refined on themore » basis of SAXS data together with a fractal assembly approach. Here we show that a nondiluted critical system of proteins, which crystallize into monomolecular structures, might be analyzed by SAXS if protein-protein interactions are taken into account by relating a fractal local density distribution to a fractal local mean potential, which has to fulfill the Poisson equation. The present work demonstrates an important step into the elucidation of the structure of S-layers and offers a tool to analyze the structure of self-assembling systems in solution by means of SAXS and computer simulations.« less

Grid refinement in Cartesian coordinates for groundwater flow models using the divergence theorem and Taylor's series.

PubMed

Mansour, M M; Spink, A E F

2013-01-01

Grid refinement is introduced in a numerical groundwater model to increase the accuracy of the solution over local areas without compromising the run time of the model. Numerical methods developed for grid refinement suffered certain drawbacks, for example, deficiencies in the implemented interpolation technique; the non-reciprocity in head calculations or flow calculations; lack of accuracy resulting from high truncation errors, and numerical problems resulting from the construction of elongated meshes. A refinement scheme based on the divergence theorem and Taylor's expansions is presented in this article. This scheme is based on the work of De Marsily (1986) but includes more terms of the Taylor's series to improve the numerical solution. In this scheme, flow reciprocity is maintained and high order of refinement was achievable. The new numerical method is applied to simulate groundwater flows in homogeneous and heterogeneous confined aquifers. It produced results with acceptable degrees of accuracy. This method shows the potential for its application to solving groundwater heads over nested meshes with irregular shapes. © 2012, British Geological Survey © NERC 2012. Ground Water © 2012, National GroundWater Association.

Nutrient and suspended solids removal from petrochemical wastewater via microalgal biofilm cultivation.

PubMed

Hodges, Alan; Fica, Zachary; Wanlass, Jordan; VanDarlin, Jessica; Sims, Ronald

2017-05-01

Wastewater derived from petroleum refining currently accounts for 33.6 million barrels per day globally. Few wastewater treatment strategies exist to produce value-added products from petroleum refining wastewater. In this study, mixed culture microalgal biofilm-based treatment of petroleum refining wastewater using rotating algae biofilm reactors (RABRs) was compared with suspended-growth open pond lagoon reactors for removal of nutrients and suspended solids. Triplicate reactors were operated for 12 weeks and were continuously fed with petroleum refining wastewater. Effluent wastewater was monitored for nitrogen, phosphorus, total suspended solids (TSS), and chemical oxygen demand (COD). RABR treatment demonstrated a statistically significant increase in removal of nutrients and suspended solids, and increase in biomass productivity, compared to the open pond lagoon treatment. These trends translate to a greater potential for the production of biomass-based fuels, feed, and fertilizer as value-added products. This study is the first demonstration of the cultivation of mixed culture biofilm microalgae on petroleum refining wastewater for the dual purposes of treatment and biomass production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Data acquisition instruments: Psychopharmacology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartley, D.S. III

This report contains the results of a Direct Assistance Project performed by Lockheed Martin Energy Systems, Inc., for Dr. K. O. Jobson. The purpose of the project was to perform preliminary analysis of the data acquisition instruments used in the field of psychiatry, with the goal of identifying commonalities of data and strategies for handling and using the data in the most advantageous fashion. Data acquisition instruments from 12 sources were provided by Dr. Jobson. Several commonalities were identified and a potentially useful data strategy is reported here. Analysis of the information collected for utility in performing diagnoses is recommended.more » In addition, further work is recommended to refine the commonalities into a directly useful computer systems structure.« less

Thermodynamically accessible titanium clusters TiN, N = 2-32.

PubMed

Lazauskas, Tomas; Sokol, Alexey A; Buckeridge, John; Catlow, C Richard A; Escher, Susanne G E T; Farrow, Matthew R; Mora-Fonz, David; Blum, Volker W; Phaahla, Tshegofatso M; Chauke, Hasani R; Ngoepe, Phuti E; Woodley, Scott M

2018-05-10

We have performed a genetic algorithm search on the tight-binding interatomic potential energy surface (PES) for small TiN (N = 2-32) clusters. The low energy candidate clusters were further refined using density functional theory (DFT) calculations with the PBEsol exchange-correlation functional and evaluated with the PBEsol0 hybrid functional. The resulting clusters were analysed in terms of their structural features, growth mechanism and surface area. The results suggest a growth mechanism that is based on forming coordination centres by interpenetrating icosahedra, icositetrahedra and Frank-Kasper polyhedra. We identify centres of coordination, which act as centres of bulk nucleation in medium sized clusters and determine the morphological features of the cluster.

Development of Simultaneous Corrosion Barrier and Optimized Microstructure in FeCrAl Heat-Resistant Alloy for Energy Applications. Part II: The Optimized Creep-Resistant Microstructure

NASA Astrophysics Data System (ADS)

Pimentel, G.; Aranda, M. M.; Chao, J.; González-Carrasco, J. L.; Capdevila, C.

2015-09-01

The first part of this two-part study reported the possibility of simultaneously generating a dense, self-healing α-alumina layer by thermal oxidation and a coarse-grained microstructure with a potential goodness for high-temperature creep resistance in a FeCrAl oxide dispersion-strengthened ferritic alloy that was cold deformed after hot rolling and extrusion. In this second part, the factors affecting the formation of the coarse-grained microstructure such as strain gradients induced during the rolling process are analyzed. It is concluded that larger strain gradients lead to more refined and more isotropic grain structures.

Configuration development study of the X-24C hypersonic research airplane, phase 2

NASA Technical Reports Server (NTRS)

Combs, H. G.

1977-01-01

The X-24C Hypersonic Research Vehicle, configured with a heat-sink structure, a launch mass limit of 31.75 Mg and powered by an LR-105 Rocket Engine plus 12 LR-101 Sustainer Engines, was found to be the more cost effective of the candidate configurations. In addition, the configuration provides the maximum off design growth potential capability and subsequently, was selected as the candidate configuration to be subjected to the design refinement study in the remaining segment of the study. Selection of this configuration was based on the analytical study conducted on the performance growth capabilities of the candidate configurations selected from the Phase 1 Study.

Effects of chemical, physical, and technological processes on the nature of food allergens.

PubMed

Poms, Roland E; Anklam, Elke

2004-01-01

A review is presented of studies of different processing techniques and their effect on the allergenicity and antigenicity of certain allergenic foods. An overview of investigated technologies is given with regard to their impact on the protein structure and their potential application in the production of hypoallergenic foods. The use of physical processes (such as heating, high pressure, microparticulation, ultrafiltration, and irradiation), chemical processes (such as proteolysis, fermentation, and refining by extraction), and biotechnological approaches, as well as the effects of these processes on individual allergenic foods, are included. Additionally, the implications of food processing for food allergen analysis with respect to food safety assessment and industrial quality control are briefly discussed.

A feature refinement approach for statistical interior CT reconstruction

NASA Astrophysics Data System (ADS)

Hu, Zhanli; Zhang, Yunwan; Liu, Jianbo; Ma, Jianhua; Zheng, Hairong; Liang, Dong

2016-07-01

Interior tomography is clinically desired to reduce the radiation dose rendered to patients. In this work, a new statistical interior tomography approach for computed tomography is proposed. The developed design focuses on taking into account the statistical nature of local projection data and recovering fine structures which are lost in the conventional total-variation (TV)—minimization reconstruction. The proposed method falls within the compressed sensing framework of TV minimization, which only assumes that the interior ROI is piecewise constant or polynomial and does not need any additional prior knowledge. To integrate the statistical distribution property of projection data, the objective function is built under the criteria of penalized weighed least-square (PWLS-TV). In the implementation of the proposed method, the interior projection extrapolation based FBP reconstruction is first used as the initial guess to mitigate truncation artifacts and also provide an extended field-of-view. Moreover, an interior feature refinement step, as an important processing operation is performed after each iteration of PWLS-TV to recover the desired structure information which is lost during the TV minimization. Here, a feature descriptor is specifically designed and employed to distinguish structure from noise and noise-like artifacts. A modified steepest descent algorithm is adopted to minimize the associated objective function. The proposed method is applied to both digital phantom and in vivo Micro-CT datasets, and compared to FBP, ART-TV and PWLS-TV. The reconstruction results demonstrate that the proposed method performs better than other conventional methods in suppressing noise, reducing truncated and streak artifacts, and preserving features. The proposed approach demonstrates its potential usefulness for feature preservation of interior tomography under truncated projection measurements.

A feature refinement approach for statistical interior CT reconstruction.

PubMed

Hu, Zhanli; Zhang, Yunwan; Liu, Jianbo; Ma, Jianhua; Zheng, Hairong; Liang, Dong

2016-07-21

Interior tomography is clinically desired to reduce the radiation dose rendered to patients. In this work, a new statistical interior tomography approach for computed tomography is proposed. The developed design focuses on taking into account the statistical nature of local projection data and recovering fine structures which are lost in the conventional total-variation (TV)-minimization reconstruction. The proposed method falls within the compressed sensing framework of TV minimization, which only assumes that the interior ROI is piecewise constant or polynomial and does not need any additional prior knowledge. To integrate the statistical distribution property of projection data, the objective function is built under the criteria of penalized weighed least-square (PWLS-TV). In the implementation of the proposed method, the interior projection extrapolation based FBP reconstruction is first used as the initial guess to mitigate truncation artifacts and also provide an extended field-of-view. Moreover, an interior feature refinement step, as an important processing operation is performed after each iteration of PWLS-TV to recover the desired structure information which is lost during the TV minimization. Here, a feature descriptor is specifically designed and employed to distinguish structure from noise and noise-like artifacts. A modified steepest descent algorithm is adopted to minimize the associated objective function. The proposed method is applied to both digital phantom and in vivo Micro-CT datasets, and compared to FBP, ART-TV and PWLS-TV. The reconstruction results demonstrate that the proposed method performs better than other conventional methods in suppressing noise, reducing truncated and streak artifacts, and preserving features. The proposed approach demonstrates its potential usefulness for feature preservation of interior tomography under truncated projection measurements.

The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.

PubMed

May, Eric R; Armen, Roger S; Mannan, Aristotle M; Brooks, Charles L

2010-08-01

The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. (c) 2010 Wiley-Liss, Inc.

The Flexible C-terminal Arm of the Lassa Arenavirus Z-Protein Mediates Interactions with Multiple Binding Partners

PubMed Central

May, Eric R.; Armen, Roger S.; Mannan, Aristotle M.; Brooks, Charles L.

2010-01-01

The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics were employed to refine the structures, which were then subsequently clustered. Population weighted ensembles of low energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was indentified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during molecular dynamics trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein binding recognition motifs for Tsg101 and eIF4E, and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. PMID:20544962

Mechanisms of amyloid formation revealed by solution NMR

PubMed Central

Karamanos, Theodoros K.; Kalverda, Arnout P.; Thompson, Gary S.; Radford, Sheena E.

2015-01-01

Amyloid fibrils are proteinaceous elongated aggregates involved in more than fifty human diseases. Recent advances in electron microscopy and solid state NMR have allowed the characterization of fibril structures to different extents of refinement. However, structural details about the mechanism of fibril formation remain relatively poorly defined. This is mainly due to the complex, heterogeneous and transient nature of the species responsible for assembly; properties that make them difficult to detect and characterize in structural detail using biophysical techniques. The ability of solution NMR spectroscopy to investigate exchange between multiple protein states, to characterize transient and low-population species, and to study high molecular weight assemblies, render NMR an invaluable technique for studies of amyloid assembly. In this article we review state-of-the-art solution NMR methods for investigations of: (a) protein dynamics that lead to the formation of aggregation-prone species; (b) amyloidogenic intrinsically disordered proteins; and (c) protein–protein interactions on pathway to fibril formation. Together, these topics highlight the power and potential of NMR to provide atomic level information about the molecular mechanisms of one of the most fascinating problems in structural biology. PMID:26282197

A nucleobase-centered coarse-grained representation for structure prediction of RNA motifs.

PubMed

Poblete, Simón; Bottaro, Sandro; Bussi, Giovanni

2018-02-28

We introduce the SPlit-and-conQueR (SPQR) model, a coarse-grained (CG) representation of RNA designed for structure prediction and refinement. In our approach, the representation of a nucleotide consists of a point particle for the phosphate group and an anisotropic particle for the nucleoside. The interactions are, in principle, knowledge-based potentials inspired by the $\\mathcal {E}$SCORE function, a base-centered scoring function. However, a special treatment is given to base-pairing interactions and certain geometrical conformations which are lost in a raw knowledge-based model. This results in a representation able to describe planar canonical and non-canonical base pairs and base-phosphate interactions and to distinguish sugar puckers and glycosidic torsion conformations. The model is applied to the folding of several structures, including duplexes with internal loops of non-canonical base pairs, tetraloops, junctions and a pseudoknot. For the majority of these systems, experimental structures are correctly predicted at the level of individual contacts. We also propose a method for efficiently reintroducing atomistic detail from the CG representation.

The Leptospiral Antigen Lp49 is a Two-Domain Protein with Putative Protein Binding Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oliveira Giuseppe,P.; Oliveira Neves, F.; Nascimento, A.

2008-01-01

Pathogenic Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. Currently available vaccines have limited effectiveness and therapeutic interventions are complicated by the difficulty in making an early diagnosis of leptospirosis. The genome of Leptospira interrogans was recently sequenced and comparative genomic analysis contributed to the identification of surface antigens, potential candidates for development of new vaccines and serodiagnosis. Lp49 is a membrane-associated protein recognized by antibodies present in sera from early and convalescent phases of leptospirosis patients. Its crystal structure was determined by single-wavelength anomalous diffraction using selenomethionine-labelled crystals and refined at 2.0 Angstromsmore » resolution. Lp49 is composed of two domains and belongs to the all-beta-proteins class. The N-terminal domain folds in an immunoglobulin-like beta-sandwich structure, whereas the C-terminal domain presents a seven-bladed beta-propeller fold. Structural analysis of Lp49 indicates putative protein-protein binding sites, suggesting a role in Leptospira-host interaction. This is the first crystal structure of a leptospiral antigen described to date.« less