Quantification of the impact of PSI:Biology according to the annotations of the determined structures.

PubMed

DePietro, Paul J; Julfayev, Elchin S; McLaughlin, William A

2013-10-21

Protein Structure Initiative:Biology (PSI:Biology) is the third phase of PSI where protein structures are determined in high-throughput to characterize their biological functions. The transition to the third phase entailed the formation of PSI:Biology Partnerships which are composed of structural genomics centers and biomedical science laboratories. We present a method to examine the impact of protein structures determined under the auspices of PSI:Biology by measuring their rates of annotations. The mean numbers of annotations per structure and per residue are examined. These are designed to provide measures of the amount of structure to function connections that can be leveraged from each structure. One result is that PSI:Biology structures are found to have a higher rate of annotations than structures determined during the first two phases of PSI. A second result is that the subset of PSI:Biology structures determined through PSI:Biology Partnerships have a higher rate of annotations than those determined exclusive of those partnerships. Both results hold when the annotation rates are examined either at the level of the entire protein or for annotations that are known to fall at specific residues within the portion of the protein that has a determined structure. We conclude that PSI:Biology determines structures that are estimated to have a higher degree of biomedical interest than those determined during the first two phases of PSI based on a broad array of biomedical annotations. For the PSI:Biology Partnerships, we see that there is an associated added value that represents part of the progress toward the goals of PSI:Biology. We interpret the added value to mean that team-based structural biology projects that utilize the expertise and technologies of structural genomics centers together with biological laboratories in the community are conducted in a synergistic manner. We show that the annotation rates can be used in conjunction with established metrics, i.e. the numbers of structures and impact of publication records, to monitor the progress of PSI:Biology towards its goals of examining structure to function connections of high biomedical relevance. The metric provides an objective means to quantify the overall impact of PSI:Biology as it uses biomedical annotations from external sources.

Quantification of the impact of PSI:Biology according to the annotations of the determined structures

PubMed Central

2013-01-01

Background Protein Structure Initiative:Biology (PSI:Biology) is the third phase of PSI where protein structures are determined in high-throughput to characterize their biological functions. The transition to the third phase entailed the formation of PSI:Biology Partnerships which are composed of structural genomics centers and biomedical science laboratories. We present a method to examine the impact of protein structures determined under the auspices of PSI:Biology by measuring their rates of annotations. The mean numbers of annotations per structure and per residue are examined. These are designed to provide measures of the amount of structure to function connections that can be leveraged from each structure. Results One result is that PSI:Biology structures are found to have a higher rate of annotations than structures determined during the first two phases of PSI. A second result is that the subset of PSI:Biology structures determined through PSI:Biology Partnerships have a higher rate of annotations than those determined exclusive of those partnerships. Both results hold when the annotation rates are examined either at the level of the entire protein or for annotations that are known to fall at specific residues within the portion of the protein that has a determined structure. Conclusions We conclude that PSI:Biology determines structures that are estimated to have a higher degree of biomedical interest than those determined during the first two phases of PSI based on a broad array of biomedical annotations. For the PSI:Biology Partnerships, we see that there is an associated added value that represents part of the progress toward the goals of PSI:Biology. We interpret the added value to mean that team-based structural biology projects that utilize the expertise and technologies of structural genomics centers together with biological laboratories in the community are conducted in a synergistic manner. We show that the annotation rates can be used in conjunction with established metrics, i.e. the numbers of structures and impact of publication records, to monitor the progress of PSI:Biology towards its goals of examining structure to function connections of high biomedical relevance. The metric provides an objective means to quantify the overall impact of PSI:Biology as it uses biomedical annotations from external sources. PMID:24139526

A preliminary structural analysis of space-base living quarters modules to verify a weight-estimating technique

NASA Technical Reports Server (NTRS)

Grissom, D. S.; Schneider, W. C.

1971-01-01

The determination of a base line (minimum weight) design for the primary structure of the living quarters modules in an earth-orbiting space base was investigated. Although the design is preliminary in nature, the supporting analysis is sufficiently thorough to provide a reasonably accurate weight estimate of the major components that are considered to comprise the structural weight of the space base.

Structure of Profiled Crystals Based on Solid Solutions of Bi2Te3 and Their X-Ray Diagnostics

NASA Astrophysics Data System (ADS)

Voronin, A. I.; Bublik, V. T.; Tabachkova, N. Yu.; Belov, Yu. M.

2011-05-01

In this work, we used x-ray structural diagnostic data to reveal the formation of structural regularities in profiled polycrystalline ingots based on Bi and Sb chalcogenide solid solutions. In Bi2Te3 lattice crystals, the solid phase grows such that the cleavage surfaces are perpendicular to the crystallization front. The crystallization singularity determines the nature of the growth texture. Because texture is an important factor determining the anisotropy of properties, which in turn determines the suitability of an ingot for production of modules and the possibility of figure of merit improvement, its diagnostics is an important issue for technology testing. Examples of texture analysis using the method of straight pole figure (SPF) construction for profiled crystals are provided. The structure of the surface layers in the profiled ingots was studied after electroerosion cutting. In addition, the method of estimation of the disturbed layer depth based on the nature of texture changes was used.

Automated protein NMR structure determination using wavelet de-noised NOESY spectra.

PubMed

Dancea, Felician; Günther, Ulrich

2005-11-01

A major time-consuming step of protein NMR structure determination is the generation of reliable NOESY cross peak lists which usually requires a significant amount of manual interaction. Here we present a new algorithm for automated peak picking involving wavelet de-noised NOESY spectra in a process where the identification of peaks is coupled to automated structure determination. The core of this method is the generation of incremental peak lists by applying different wavelet de-noising procedures which yield peak lists of a different noise content. In combination with additional filters which probe the consistency of the peak lists, good convergence of the NOESY-based automated structure determination could be achieved. These algorithms were implemented in the context of the ARIA software for automated NOE assignment and structure determination and were validated for a polysulfide-sulfur transferase protein of known structure. The procedures presented here should be commonly applicable for efficient protein NMR structure determination and automated NMR peak picking.

SCI model structure determination program (OSR) user's guide. [optimal subset regression

NASA Technical Reports Server (NTRS)

1979-01-01

The computer program, OSR (Optimal Subset Regression) which estimates models for rotorcraft body and rotor force and moment coefficients is described. The technique used is based on the subset regression algorithm. Given time histories of aerodynamic coefficients, aerodynamic variables, and control inputs, the program computes correlation between various time histories. The model structure determination is based on these correlations. Inputs and outputs of the program are given.

Automated batch fiducial-less tilt-series alignment in Appion using Protomo.

PubMed

Noble, Alex J; Stagg, Scott M

2015-11-01

The field of electron tomography has benefited greatly from manual and semi-automated approaches to marker-based tilt-series alignment that have allowed for the structural determination of multitudes of in situ cellular structures as well as macromolecular structures of individual protein complexes. The emergence of complementary metal-oxide semiconductor detectors capable of detecting individual electrons has enabled the collection of low dose, high contrast images, opening the door for reliable correlation-based tilt-series alignment. Here we present a set of automated, correlation-based tilt-series alignment, contrast transfer function (CTF) correction, and reconstruction workflows for use in conjunction with the Appion/Leginon package that are primarily targeted at automating structure determination with cryogenic electron microscopy. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanical impedance and acoustic mobility measurement techniques of specifying vibration environments

NASA Technical Reports Server (NTRS)

Kao, G. C.

1973-01-01

Method has been developed for predicting interaction between components and corresponding support structures subjected to acoustic excitations. Force environments determined in spectral form are called force spectra. Force-spectra equation is determined based on one-dimensional structural impedance model.

Exploiting the Synergy of Powder X-ray Diffraction and Solid-State NMR Spectroscopy in Structure Determination of Organic Molecular Solids

PubMed Central

2013-01-01

We report a strategy for structure determination of organic materials in which complete solid-state nuclear magnetic resonance (NMR) spectral data is utilized within the context of structure determination from powder X-ray diffraction (XRD) data. Following determination of the crystal structure from powder XRD data, first-principles density functional theory-based techniques within the GIPAW approach are exploited to calculate the solid-state NMR data for the structure, followed by careful scrutiny of the agreement with experimental solid-state NMR data. The successful application of this approach is demonstrated by structure determination of the 1:1 cocrystal of indomethacin and nicotinamide. The 1H and 13C chemical shifts calculated for the crystal structure determined from the powder XRD data are in excellent agreement with those measured experimentally, notably including the two-dimensional correlation of 1H and 13C chemical shifts for directly bonded 13C–1H moieties. The key feature of this combined approach is that the quality of the structure determined is assessed both against experimental powder XRD data and against experimental solid-state NMR data, thus providing a very robust validation of the veracity of the structure. PMID:24386493

Exploiting the Synergy of Powder X-ray Diffraction and Solid-State NMR Spectroscopy in Structure Determination of Organic Molecular Solids.

PubMed

Dudenko, Dmytro V; Williams, P Andrew; Hughes, Colan E; Antzutkin, Oleg N; Velaga, Sitaram P; Brown, Steven P; Harris, Kenneth D M

2013-06-13

We report a strategy for structure determination of organic materials in which complete solid-state nuclear magnetic resonance (NMR) spectral data is utilized within the context of structure determination from powder X-ray diffraction (XRD) data. Following determination of the crystal structure from powder XRD data, first-principles density functional theory-based techniques within the GIPAW approach are exploited to calculate the solid-state NMR data for the structure, followed by careful scrutiny of the agreement with experimental solid-state NMR data. The successful application of this approach is demonstrated by structure determination of the 1:1 cocrystal of indomethacin and nicotinamide. The 1 H and 13 C chemical shifts calculated for the crystal structure determined from the powder XRD data are in excellent agreement with those measured experimentally, notably including the two-dimensional correlation of 1 H and 13 C chemical shifts for directly bonded 13 C- 1 H moieties. The key feature of this combined approach is that the quality of the structure determined is assessed both against experimental powder XRD data and against experimental solid-state NMR data, thus providing a very robust validation of the veracity of the structure.

Crystal structures of ASK1-inhibtor complexes provide a platform for structure-based drug design

PubMed Central

Singh, Onkar; Shillings, Anthony; Craggs, Peter; Wall, Ian; Rowland, Paul; Skarzynski, Tadeusz; Hobbs, Clare I; Hardwick, Phil; Tanner, Rob; Blunt, Michelle; Witty, David R; Smith, Kathrine J

2013-01-01

ASK1, a member of the MAPK Kinase Kinase family of proteins has been shown to play a key role in cancer, neurodegeneration and cardiovascular diseases and is emerging as a possible drug target. Here we describe a ‘replacement-soaking’ method that has enabled the high-throughput X-ray structure determination of ASK1/ligand complexes. Comparison of the X-ray structures of five ASK1/ligand complexes from 3 different chemotypes illustrates that the ASK1 ATP binding site is able to accommodate a range of chemical diversity and different binding modes. The replacement-soaking system is also able to tolerate some protein flexibility. This crystal system provides a robust platform for ASK1/ligand structure determination and future structure based drug design. PMID:23776076

Structure-based Markov random field model for representing evolutionary constraints on functional sites.

PubMed

Jeong, Chan-Seok; Kim, Dongsup

2016-02-24

Elucidating the cooperative mechanism of interconnected residues is an important component toward understanding the biological function of a protein. Coevolution analysis has been developed to model the coevolutionary information reflecting structural and functional constraints. Recently, several methods have been developed based on a probabilistic graphical model called the Markov random field (MRF), which have led to significant improvements for coevolution analysis; however, thus far, the performance of these models has mainly been assessed by focusing on the aspect of protein structure. In this study, we built an MRF model whose graphical topology is determined by the residue proximity in the protein structure, and derived a novel positional coevolution estimate utilizing the node weight of the MRF model. This structure-based MRF method was evaluated for three data sets, each of which annotates catalytic site, allosteric site, and comprehensively determined functional site information. We demonstrate that the structure-based MRF architecture can encode the evolutionary information associated with biological function. Furthermore, we show that the node weight can more accurately represent positional coevolution information compared to the edge weight. Lastly, we demonstrate that the structure-based MRF model can be reliably built with only a few aligned sequences in linear time. The results show that adoption of a structure-based architecture could be an acceptable approximation for coevolution modeling with efficient computation complexity.

NMR-based automated protein structure determination.

PubMed

Würz, Julia M; Kazemi, Sina; Schmidt, Elena; Bagaria, Anurag; Güntert, Peter

2017-08-15

NMR spectra analysis for protein structure determination can now in many cases be performed by automated computational methods. This overview of the computational methods for NMR protein structure analysis presents recent automated methods for signal identification in multidimensional NMR spectra, sequence-specific resonance assignment, collection of conformational restraints, and structure calculation, as implemented in the CYANA software package. These algorithms are sufficiently reliable and integrated into one software package to enable the fully automated structure determination of proteins starting from NMR spectra without manual interventions or corrections at intermediate steps, with an accuracy of 1-2 Å backbone RMSD in comparison with manually solved reference structures. Copyright © 2017 Elsevier Inc. All rights reserved.

Progress in the Modeling of NiAl-Based Alloys Using the BFS Method

NASA Technical Reports Server (NTRS)

Bozzolo, Guillermo; Noebe, Ronald D.; Ferrante, John; Garg, Anita

1997-01-01

The BFS method has been applied to the study of NiAl-based materials to assess the effect of alloying additions on structure. Ternary, quaternary and even pent-alloys based on Ni-rich NiAl with additions of Ti, Cr and Cu were studied. Two approaches were used, Monte Carlo simulations to determine ground state structures and analytical calculations of high symmetry configurations which give physical insight into preferred bonding. Site occupancy energetics for ternary and the more complicated case of quaternary additions were determined, and solubility limits and precipitate formation with corresponding information concerning structure and lattice parameter were also 'observed' computationally. The method was also applied to determine the composition of alloy surfaces and interfaces. Overall, the results demonstrate that the BFS method for alloys is a powerful tool for alloy design and with its simplicity and obvious advantages can be used to complement any experimental alloy design program.

Adjusting protein graphs based on graph entropy.

PubMed

Peng, Sheng-Lung; Tsay, Yu-Wei

2014-01-01

Measuring protein structural similarity attempts to establish a relationship of equivalence between polymer structures based on their conformations. In several recent studies, researchers have explored protein-graph remodeling, instead of looking a minimum superimposition for pairwise proteins. When graphs are used to represent structured objects, the problem of measuring object similarity become one of computing the similarity between graphs. Graph theory provides an alternative perspective as well as efficiency. Once a protein graph has been created, its structural stability must be verified. Therefore, a criterion is needed to determine if a protein graph can be used for structural comparison. In this paper, we propose a measurement for protein graph remodeling based on graph entropy. We extend the concept of graph entropy to determine whether a graph is suitable for representing a protein. The experimental results suggest that when applied, graph entropy helps a conformational on protein graph modeling. Furthermore, it indirectly contributes to protein structural comparison if a protein graph is solid.

Adjusting protein graphs based on graph entropy

PubMed Central

2014-01-01

Measuring protein structural similarity attempts to establish a relationship of equivalence between polymer structures based on their conformations. In several recent studies, researchers have explored protein-graph remodeling, instead of looking a minimum superimposition for pairwise proteins. When graphs are used to represent structured objects, the problem of measuring object similarity become one of computing the similarity between graphs. Graph theory provides an alternative perspective as well as efficiency. Once a protein graph has been created, its structural stability must be verified. Therefore, a criterion is needed to determine if a protein graph can be used for structural comparison. In this paper, we propose a measurement for protein graph remodeling based on graph entropy. We extend the concept of graph entropy to determine whether a graph is suitable for representing a protein. The experimental results suggest that when applied, graph entropy helps a conformational on protein graph modeling. Furthermore, it indirectly contributes to protein structural comparison if a protein graph is solid. PMID:25474347

Analysis of large space structures assembly: Man/machine assembly analysis

NASA Technical Reports Server (NTRS)

1983-01-01

Procedures for analyzing large space structures assembly via three primary modes: manual, remote and automated are outlined. Data bases on each of the assembly modes and a general data base on the shuttle capabilities to support structures assembly are presented. Task element times and structure assembly component costs are given to provide a basis for determining the comparative economics of assembly alternatives. The lessons learned from simulations of space structures assembly are detailed.

76 FR 56156 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... materials for energy production. The experiments will involve structural and chemical analyses of materials... experiments will involve structural and chemical analyses of materials on the electron based nanometer scale... tissues, viruses, and bacteria, to determine the morphology of multiphase materials, determine the...

Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.

PubMed

Huang, Weiyun; Liu, Minhao; Yan, S Frank; Yan, Nieng

2017-06-01

Voltage-gated sodium (Na v ) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na v channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na v channels, with Na v 1.1 and Na v 1.5 each harboring more than 400 mutations. Na v channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na v channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca v ) channel Ca v 1.1 provides a template for homology-based structural modeling of the evolutionarily related Na v channels. In this Resource article, we summarized all the reported disease-related mutations in human Na v channels, generated a homologous model of human Na v 1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na v channels, the analysis presented here serves as the base framework for mechanistic investigation of Na v channelopathies and for potential structure-based drug discovery.

Application of Nuclear Magnetic Resonance and Hybrid Methods to Structure Determination of Complex Systems.

PubMed

Prischi, Filippo; Pastore, Annalisa

2016-01-01

The current main challenge of Structural Biology is to undertake the structure determination of increasingly complex systems in the attempt to better understand their biological function. As systems become more challenging, however, there is an increasing demand for the parallel use of more than one independent technique to allow pushing the frontiers of structure determination and, at the same time, obtaining independent structural validation. The combination of different Structural Biology methods has been named hybrid approaches. The aim of this review is to critically discuss the most recent examples and new developments that have allowed structure determination or experimentally-based modelling of various molecular complexes selecting them among those that combine the use of nuclear magnetic resonance and small angle scattering techniques. We provide a selective but focused account of some of the most exciting recent approaches and discuss their possible further developments.

Examination of Short- and Long-Range Atomic Order Nanocrystalline SiC and Diamond by Powder Diffraction Methods

NASA Technical Reports Server (NTRS)

Palosz, B.; Grzanka, E.; Stelmakh, S.; Gierlotka, S.; Weber, H.-P.; Proffen, T.; Palosz, W.

2002-01-01

The real atomic structure of nanocrystals determines unique, key properties of the materials. Determination of the structure presents a challenge due to inherent limitations of standard powder diffraction techniques when applied to nanocrystals. Alternate methodology of the structural analysis of nanocrystals (several nanometers in size) based on Bragg-like scattering and called the "apparent lattice parameter" (alp) is proposed. Application of the alp methodology to examination of the core-shell model of nanocrystals will be presented. The results of application of the alp method to structural analysis of several nanopowders were complemented by those obtained by determination of the Atomic Pair Distribution Function, PDF. Based on synchrotron and neutron diffraction data measured in a large diffraction vector of up to Q = 25 Angstroms(exp -1), the surface stresses in nanocrystalline diamond and SiC were evaluated.

Quantitative Evaluation of Delamination in Composites Using Lamb Waves

NASA Astrophysics Data System (ADS)

Michalcová, L.; Hron, R.

2018-03-01

Ultrasonic guided wave monitoring has become very popular in the area of structural health monitoring (SHM) of aerospace structures. Any possible type of damage must be reliably assessed. The paper deals with delamination length determination in DCB specimens using Lamb waves. An analytical equation based on the velocity dependence on variable thickness is utilized. The group velocity of the fundamental antisymmetric A0 mode rapidly changes in a particular range of the frequency-thickness product. Using the same actuation frequency the propagation velocity is different for delaminated structure. Lamb wave based delamination lengths were compared to the visually determined lengths. The method of the wave velocity determination proved to be essential. More accurate results were achieved by tracking the maximum amplitude of A0 mode than the first signal arrival. These findings are considered as the basis for the damage evaluation of complex structures.

In-service inspection methods for graphite-epoxy structures on commercial transport aircraft

NASA Technical Reports Server (NTRS)

Phelps, M. L.

1981-01-01

In-service inspection methods for graphite-epoxy composite structures on commercial transport aircraft are determined. Graphite/epoxy structures, service incurred defects, current inspection practices and concerns of the airline and manufacturers, and other related information were determind by survey. Based on this information, applicable inspection nondestructive inspection methods are evaluated and inspection techniques determined. Technology is developed primarily in eddy current inspection.

Influence of cross section variations on the structural behaviour of composite rotor blades

NASA Astrophysics Data System (ADS)

Rapp, Helmut; Woerndle, Rudolf

1991-09-01

A highly sophisticated structural analysis is required for helicopter rotor blades with nonhomogeneous cross sections made from nonisotropic material. Combinations of suitable analytical techniques with FEM-based techniques permit a cost effective and sufficiently accurate analysis of these complicated structures. It is determined that in general the 1D engineering theory of bending combined with 2D theories for determining the cross section properties is sufficient to describe the structural blade behavior.

Structural determination of intact proteins using mass spectrometry

DOEpatents

Kruppa, Gary [San Francisco, CA; Schoeniger, Joseph S [Oakland, CA; Young, Malin M [Livermore, CA

2008-05-06

The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

29 CFR 1926.701 - General requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... structure or portion of a concrete structure unless the employer determines, based on information received from a person who is qualified in structural design, that the structure or portion of the structure is capable of supporting the loads. (b) Reinforcing steel. All protruding reinforcing steel, onto and into...

29 CFR 1926.701 - General requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... structure or portion of a concrete structure unless the employer determines, based on information received from a person who is qualified in structural design, that the structure or portion of the structure is capable of supporting the loads. (b) Reinforcing steel. All protruding reinforcing steel, onto and into...

29 CFR 1926.701 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... structure or portion of a concrete structure unless the employer determines, based on information received from a person who is qualified in structural design, that the structure or portion of the structure is capable of supporting the loads. (b) Reinforcing steel. All protruding reinforcing steel, onto and into...

The feasibility of accommodating physically handicapped individuals on pedestrian over and undercrossing structures

DOT National Transportation Integrated Search

1980-09-01

The objective of this study was to determine the feasibility of accommodating the physically handicapped on over- and undercrossing structures. Based upon the evaluation of 124 crossing structures, 86 percent of these structures had at least one majo...

Fingerprint-Based Structure Retrieval Using Electron Density

PubMed Central

Yin, Shuangye; Dokholyan, Nikolay V.

2010-01-01

We present a computational approach that can quickly search a large protein structural database to identify structures that fit a given electron density, such as determined by cryo-electron microscopy. We use geometric invariants (fingerprints) constructed using 3D Zernike moments to describe the electron density, and reduce the problem of fitting of the structure to the electron density to simple fingerprint comparison. Using this approach, we are able to screen the entire Protein Data Bank and identify structures that fit two experimental electron densities determined by cryo-electron microscopy. PMID:21287628

Fingerprint-based structure retrieval using electron density.

PubMed

Yin, Shuangye; Dokholyan, Nikolay V

2011-03-01

We present a computational approach that can quickly search a large protein structural database to identify structures that fit a given electron density, such as determined by cryo-electron microscopy. We use geometric invariants (fingerprints) constructed using 3D Zernike moments to describe the electron density, and reduce the problem of fitting of the structure to the electron density to simple fingerprint comparison. Using this approach, we are able to screen the entire Protein Data Bank and identify structures that fit two experimental electron densities determined by cryo-electron microscopy. Copyright © 2010 Wiley-Liss, Inc.

Electronic structures of WAlO(y) and WAlO(y)(-) (y = 2-4) determined by anion photoelectron spectroscopy and density functional theory calculations.

PubMed

Mann, Jennifer E; Waller, Sarah E; Jarrold, Caroline Chick

2012-07-28

The anion photoelectron spectra of WAlO(y)(-) (y = 2-4) are presented and assigned based on results of density functional theory calculations. The WAlO(2)(-) and WAlO(3)(-) spectra are both broad, with partially resolved vibrational structure. In contrast, the WAlO(4)(-) spectrum features well-resolved vibrational structure with contributions from three modes. There is reasonable agreement between experiment and theory for all oxides, and calculations are in particular validated by the near perfect agreement between the WAlO(4)(-) photoelectron spectrum and a Franck-Condon simulation based on computationally determined spectroscopic parameters. The structures determined from this study suggest strong preferential W-O bond formation, and ionic bonding between Al(+) and WO(y)(-2) for all anions. Neutral species are similarly ionic, with WAlO(2) and WAlO(3) having electronic structure that suggests Al(+) ionically bound to WO(y)(-) and WAlO(4) being described as Al(+2) ionically bound to WO(4)(-2). The doubly-occupied 3sp hybrid orbital localized on the Al center is energetically situated between the bonding O-local molecular orbitals and the anti- or non-bonding W-local molecular orbitals. The structures determined in this study are very similar to structures recently determined for the analogous MoAlO(y)(-)/MoAlO(y) cluster series, with subtle differences found in the electronic structures [S. E. Waller, J. E. Mann, E. Hossain, M. Troyer, and C. C. Jarrold, J. Chem. Phys. 137, 024302 (2012)].

Surface similarity-based molecular query-retrieval

PubMed Central

Singh, Rahul

2007-01-01

Background Discerning the similarity between molecules is a challenging problem in drug discovery as well as in molecular biology. The importance of this problem is due to the fact that the biochemical characteristics of a molecule are closely related to its structure. Therefore molecular similarity is a key notion in investigations targeting exploration of molecular structural space, query-retrieval in molecular databases, and structure-activity modelling. Determining molecular similarity is related to the choice of molecular representation. Currently, representations with high descriptive power and physical relevance like 3D surface-based descriptors are available. Information from such representations is both surface-based and volumetric. However, most techniques for determining molecular similarity tend to focus on idealized 2D graph-based descriptors due to the complexity that accompanies reasoning with more elaborate representations. Results This paper addresses the problem of determining similarity when molecules are described using complex surface-based representations. It proposes an intrinsic, spherical representation that systematically maps points on a molecular surface to points on a standard coordinate system (a sphere). Molecular surface properties such as shape, field strengths, and effects due to field super-positioningcan then be captured as distributions on the surface of the sphere. Surface-based molecular similarity is subsequently determined by computing the similarity of the surface-property distributions using a novel formulation of histogram-intersection. The similarity formulation is not only sensitive to the 3D distribution of the surface properties, but is also highly efficient to compute. Conclusion The proposed method obviates the computationally expensive step of molecular pose-optimisation, can incorporate conformational variations, and facilitates highly efficient determination of similarity by directly comparing molecular surfaces and surface-based properties. Retrieval performance, applications in structure-activity modeling of complex biological properties, and comparisons with existing research and commercial methods demonstrate the validity and effectiveness of the approach. PMID:17634096

Auto-rickshaw: an automated crystal structure determination platform as an efficient tool for the validation of an X-ray diffraction experiment.

PubMed

Panjikar, Santosh; Parthasarathy, Venkataraman; Lamzin, Victor S; Weiss, Manfred S; Tucker, Paul A

2005-04-01

The EMBL-Hamburg Automated Crystal Structure Determination Platform is a system that combines a number of existing macromolecular crystallographic computer programs and several decision-makers into a software pipeline for automated and efficient crystal structure determination. The pipeline can be invoked as soon as X-ray data from derivatized protein crystals have been collected and processed. It is controlled by a web-based graphical user interface for data and parameter input, and for monitoring the progress of structure determination. A large number of possible structure-solution paths are encoded in the system and the optimal path is selected by the decision-makers as the structure solution evolves. The processes have been optimized for speed so that the pipeline can be used effectively for validating the X-ray experiment at a synchrotron beamline.

Application of the maximum entropy principle to determine ensembles of intrinsically disordered proteins from residual dipolar couplings.

PubMed

Sanchez-Martinez, M; Crehuet, R

2014-12-21

We present a method based on the maximum entropy principle that can re-weight an ensemble of protein structures based on data from residual dipolar couplings (RDCs). The RDCs of intrinsically disordered proteins (IDPs) provide information on the secondary structure elements present in an ensemble; however even two sets of RDCs are not enough to fully determine the distribution of conformations, and the force field used to generate the structures has a pervasive influence on the refined ensemble. Two physics-based coarse-grained force fields, Profasi and Campari, are able to predict the secondary structure elements present in an IDP, but even after including the RDC data, the re-weighted ensembles differ between both force fields. Thus the spread of IDP ensembles highlights the need for better force fields. We distribute our algorithm in an open-source Python code.

Reservoir and Source Rock Identification Based on Geologycal, Geophysics and Petrophysics Analysis Study Case: South Sumatra Basin

NASA Astrophysics Data System (ADS)

Anggit Maulana, Hiska; Haris, Abdul

2018-05-01

Reservoir and source rock Identification has been performed to deliniate the reservoir distribution of Talangakar Formation South Sumatra Basin. This study is based on integrated geophysical, geological and petrophysical data. The aims of study to determine the characteristics of the reservoir and source rock, to differentiate reservoir and source rock in same Talangakar formation, to find out the distribution of net pay reservoir and source rock layers. The method of geophysical included seismic data interpretation using time and depth structures map, post-stack inversion, interval velocity, geological interpretations included the analysis of structures and faults, and petrophysical processing is interpret data log wells that penetrating Talangakar formation containing hydrocarbons (oil and gas). Based on seismic interpretation perform subsurface mapping on Layer A and Layer I to determine the development of structures in the Regional Research. Based on the geological interpretation, trapping in the form of regional research is anticline structure on southwest-northeast trending and bounded by normal faults on the southwest-southeast regional research structure. Based on petrophysical analysis, the main reservoir in the field of research, is a layer 1,375 m of depth and a thickness 2 to 8.3 meters.

High-throughput determination of structural phase diagram and constituent phases using GRENDEL

NASA Astrophysics Data System (ADS)

Kusne, A. G.; Keller, D.; Anderson, A.; Zaban, A.; Takeuchi, I.

2015-11-01

Advances in high-throughput materials fabrication and characterization techniques have resulted in faster rates of data collection and rapidly growing volumes of experimental data. To convert this mass of information into actionable knowledge of material process-structure-property relationships requires high-throughput data analysis techniques. This work explores the use of the Graph-based endmember extraction and labeling (GRENDEL) algorithm as a high-throughput method for analyzing structural data from combinatorial libraries, specifically, to determine phase diagrams and constituent phases from both x-ray diffraction and Raman spectral data. The GRENDEL algorithm utilizes a set of physical constraints to optimize results and provides a framework by which additional physics-based constraints can be easily incorporated. GRENDEL also permits the integration of database data as shown by the use of critically evaluated data from the Inorganic Crystal Structure Database in the x-ray diffraction data analysis. Also the Sunburst radial tree map is demonstrated as a tool to visualize material structure-property relationships found through graph based analysis.

Thermostabilisation of membrane proteins for structural studies

PubMed Central

Magnani, Francesca; Serrano-Vega, Maria J.; Shibata, Yoko; Abdul-Hussein, Saba; Lebon, Guillaume; Miller-Gallacher, Jennifer; Singhal, Ankita; Strege, Annette; Thomas, Jennifer A.; Tate, Christopher G.

2017-01-01

The thermostability of an integral membrane protein in detergent solution is a key parameter that dictates the likelihood of obtaining well-diffracting crystals suitable for structure determination. However, many mammalian membrane proteins are too unstable for crystallisation. We developed a thermostabilisation strategy based on systematic mutagenesis coupled to a radioligand-binding thermostability assay that can be applied to receptors, ion channels and transporters. It takes approximately 6-12 months to thermostabilise a G protein-coupled receptor (GPCR) containing 300 amino acid residues. The resulting thermostabilised membrane proteins are more easily crystallised and result in high-quality structures. This methodology has facilitated structure-based drug design applied to GPCRs, because it is possible to determine multiple structures of the thermostabilised receptors bound to low affinity ligands. Protocols and advice are given on how to develop thermostability assays for membrane proteins and how to combine mutations to make an optimally stable mutant suitable for structural studies. PMID:27466713

Structural assessment of a Space Station solar dynamic heat receiver thermal energy storage canister

NASA Technical Reports Server (NTRS)

Tong, M. T.; Kerslake, T. W.; Thompson, R. L.

1988-01-01

This paper assesses the structural performance of a Space Station thermal energy storage (TES) canister subject to orbital solar flux variation and engine cold start-up operating conditions. The impact of working fluid temperature and salt-void distribution on the canister structure are assessed. Both analytical and experimental studies were conducted to determine the temperature distribution of the canister. Subsequent finite-element structural analyses of the canister were performed using both analytically and experimentally obtained temperatures. The Arrhenius creep law was incorporated into the procedure, using secondary creep data for the canister material, Haynes-188 alloy. The predicted cyclic creep strain accumulations at the hot spot were used to assess the structural performance of the canister. In addition, the structural performance of the canister based on the analytically-determined temperature was compared with that based on the experimentally-measured temperature data.

Structural assessment of a space station solar dynamic heat receiver thermal energy storage canister

NASA Technical Reports Server (NTRS)

Thompson, R. L.; Kerslake, T. W.; Tong, M. T.

1988-01-01

The structural performance of a space station thermal energy storage (TES) canister subject to orbital solar flux variation and engine cold start up operating conditions was assessed. The impact of working fluid temperature and salt-void distribution on the canister structure are assessed. Both analytical and experimental studies were conducted to determine the temperature distribution of the canister. Subsequent finite element structural analyses of the canister were performed using both analytically and experimentally obtained temperatures. The Arrhenius creep law was incorporated into the procedure, using secondary creep data for the canister material, Haynes 188 alloy. The predicted cyclic creep strain accumulations at the hot spot were used to assess the structural performance of the canister. In addition, the structural performance of the canister based on the analytically determined temperature was compared with that based on the experimentally measured temperature data.

Modelling the social and structural determinants of tuberculosis: opportunities and challenges

PubMed Central

Boccia, D.; Dodd, P. J.; Lönnroth, K.; Dowdy, D. W.; Siroka, A.; Kimerling, M. E.; White, R. G.; Houben, R. M. G. J.

2017-01-01

INTRODUCTION: Despite the close link between tuberculosis (TB) and poverty, most mathematical models of TB have not addressed underlying social and structural determinants. OBJECTIVE: To review studies employing mathematical modelling to evaluate the epidemiological impact of the structural determinants of TB. METHODS: We systematically searched PubMed and personal libraries to identify eligible articles. We extracted data on the modelling techniques employed, research question, types of structural determinants modelled and setting. RESULTS: From 232 records identified, we included eight articles published between 2008 and 2015; six employed population-based dynamic TB transmission models and two non-dynamic analytic models. Seven studies focused on proximal TB determinants (four on nutritional status, one on wealth, one on indoor air pollution, and one examined overcrowding, socioeconomic and nutritional status), and one focused on macro-economic influences. CONCLUSIONS: Few modelling studies have attempted to evaluate structural determinants of TB, resulting in key knowledge gaps. Despite the challenges of modelling such a complex system, models must broaden their scope to remain useful for policy making. Given the intersectoral nature of the interrelations between structural determinants and TB outcomes, this work will require multidisciplinary collaborations. A useful starting point would be to focus on developing relatively simple models that can strengthen our knowledge regarding the potential effect of the structural determinants on TB outcomes. PMID:28826444

Combining Vision with Voice: A Learning and Implementation Structure Promoting Teachers' Internalization of Practices Based on Self-Determination Theory

ERIC Educational Resources Information Center

Assor, Avi; Kaplan, Haya; Feinberg, Ofra; Tal, Karen

2009-01-01

We propose that self-determination theory's conceptualization of internalization may help school reformers overcome the recurrent problem of "the predictable failure of educational reform" (Sarason, 1993). Accordingly, we present a detailed learning and implementation structure to promote teachers' internalization and application of ideas and…

Document boundary determination using structural and lexical analysis

NASA Astrophysics Data System (ADS)

Taghva, Kazem; Cartright, Marc-Allen

2009-01-01

The document boundary determination problem is the process of identifying individual documents in a stack of papers. In this paper, we report on a classification system for automation of this process. The system employs features based on document structure and lexical content. We also report on experimental results to support the effectiveness of this system.

The analysis of cable forces based on natural frequency

NASA Astrophysics Data System (ADS)

Suangga, Made; Hidayat, Irpan; Juliastuti; Bontan, Darwin Julius

2017-12-01

A cable is a flexible structural member that is effective at resisting tensile forces. Cables are used in a variety of structures that employ their unique characteristics to create efficient design tension members. The condition of the cable forces in the cable supported structure is an important indication of judging whether the structure is in good condition. Several methods have been developed to measure on site cable forces. Vibration technique using correlation between natural frequency and cable forces is a simple method to determine in situ cable forces, however the method need accurate information on the boundary condition, cable mass, and cable length. The natural frequency of the cable is determined using FFT (Fast Fourier Transform) Technique to the acceleration record of the cable. Based on the natural frequency obtained, the cable forces then can be determine by analytical or by finite element program. This research is focus on the vibration techniques to determine the cable forces, to understand the physical parameter effect of the cable and also modelling techniques to the natural frequency and cable forces.

Rapid condition assessment of structural condition after a blast using state-space identification

NASA Astrophysics Data System (ADS)

Eskew, Edward; Jang, Shinae

2015-04-01

After a blast event, it is important to quickly quantify the structural damage for emergency operations. In order improve the speed, accuracy, and efficiency of condition assessments after a blast, the authors have previously performed work to develop a methodology for rapid assessment of the structural condition of a building after a blast. The method involved determining a post-event equivalent stiffness matrix using vibration measurements and a finite element (FE) model. A structural model was built for the damaged structure based on the equivalent stiffness, and inter-story drifts from the blast are determined using numerical simulations, with forces determined from the blast parameters. The inter-story drifts are then compared to blast design conditions to assess the structures damage. This method still involved engineering judgment in terms of determining significant frequencies, which can lead to error, especially with noisy measurements. In an effort to improve accuracy and automate the process, this paper will look into a similar method of rapid condition assessment using subspace state-space identification. The accuracy of the method will be tested using a benchmark structural model, as well as experimental testing. The blast damage assessments will be validated using pressure-impulse (P-I) diagrams, which present the condition limits across blast parameters. Comparisons between P-I diagrams generated using the true system parameters and equivalent parameters will show the accuracy of the rapid condition based blast assessments.

Development of a hybrid wave based-transfer matrix model for sound transmission analysis.

PubMed

Dijckmans, A; Vermeir, G

2013-04-01

In this paper, a hybrid wave based-transfer matrix model is presented that allows for the investigation of the sound transmission through finite multilayered structures placed between two reverberant rooms. The multilayered structure may consist of an arbitrary configuration of fluid, elastic, or poro-elastic layers. The field variables (structural displacements and sound pressures) are expanded in terms of structural and acoustic wave functions. The boundary and continuity conditions in the rooms determine the participation factors in the pressure expansions. The displacement of the multilayered structure is determined by the mechanical impedance matrix, which gives a relation between the pressures and transverse displacements at both sides of the structure. The elements of this matrix are calculated with the transfer matrix method. First, the hybrid model is numerically validated. Next a comparison is made with sound transmission loss measurements of a hollow brick wall and a sandwich panel. Finally, numerical simulations show the influence of structural damping, room dimensions and plate dimensions on the sound transmission loss of multilayered structures.

Adverse event detection (AED) system for continuously monitoring and evaluating structural health status

NASA Astrophysics Data System (ADS)

Yun, Jinsik; Ha, Dong Sam; Inman, Daniel J.; Owen, Robert B.

2011-03-01

Structural damage for spacecraft is mainly due to impacts such as collision of meteorites or space debris. We present a structural health monitoring (SHM) system for space applications, named Adverse Event Detection (AED), which integrates an acoustic sensor, an impedance-based SHM system, and a Lamb wave SHM system. With these three health-monitoring methods in place, we can determine the presence, location, and severity of damage. An acoustic sensor continuously monitors acoustic events, while the impedance-based and Lamb wave SHM systems are in sleep mode. If an acoustic sensor detects an impact, it activates the impedance-based SHM. The impedance-based system determines if the impact incurred damage. When damage is detected, it activates the Lamb wave SHM system to determine the severity and location of the damage. Further, since an acoustic sensor dissipates much less power than the two SHM systems and the two systems are activated only when there is an acoustic event, our system reduces overall power dissipation significantly. Our prototype system demonstrates the feasibility of the proposed concept.

Synthetic and structural studies on syringolin A and B reveal critical determinants of selectivity and potency of proteasome inhibition

PubMed Central

Clerc, Jérôme; Groll, Michael; Illich, Damir J.; Bachmann, André S.; Huber, Robert; Schellenberg, Barbara; Dudler, Robert; Kaiser, Markus

2009-01-01

Syrbactins, a family of natural products belonging either to the syringolin or glidobactin class, are highly potent proteasome inhibitors. Although sharing similar structural features, they differ in their macrocyclic lactam core structure and exocyclic side chain. These structural variations critically influence inhibitory potency and proteasome subsite selectivity. Here, we describe the total synthesis of syringolin A and B, which together with enzyme kinetic and structural studies, allowed us to elucidate the structural determinants underlying the proteasomal subsite selectivity and binding affinity of syrbactins. These findings were used successfully in the rational design and synthesis of a syringolin A-based lipophilic derivative, which proved to be the most potent syrbactin-based proteasome inhibitor described so far. With a Ki′ of 8.65 ± 1.13 nM for the chymotryptic activity, this syringolin A derivative displays a 100-fold higher potency than the parent compound syringolin A. In light of the medicinal relevance of proteasome inhibitors as anticancer compounds, the present findings may assist in the rational design and development of syrbactin-based chemotherapeutics. PMID:19359491

A new nanostructured Silicon biosensor for diagnostics of bovine leucosis

NASA Astrophysics Data System (ADS)

Luchenko, A. I.; Melnichenko, M. M.; Starodub, N. F.; Shmyryeva, O. M.

2010-08-01

In this report we propose a new instrumental method for the biochemical diagnostics of the bovine leucosis through the registration of the formation of the specific immune complex (antigen-antibody) with the help of biosensor based on the nano-structured silicon. The principle of the measurements is based on the determination of the photosensitivity of the surface. In spite of the existed traditional methods of the biochemical diagnostics of the bovine leucosis the proposed approach may provide the express control of the milk quality as direct on the farm and during the process raw materials. The proposed variant of the biosensor based on the nano-structured silicon may be applied for the determination of the concentration of different substances which may form the specific complex in the result of the bioaffine reactions. A new immune technique based on the nanostructured silicon and intended for the quantitative determination of some toxic substances is offered. The sensitivity of such biosensor allows determining T-2 mycotoxin at the concentration of 10 ng/ml during several minutes.

The Structures of Life

ERIC Educational Resources Information Center

National Institute of General Medical Sciences (NIGMS), 2007

2007-01-01

This booklet reveals how structural biology provides insight into health and disease and is useful in developing new medications. It contains a general introduction to proteins, coverage of the techniques used to determine protein structures, and a chapter on structure-based drug design. The booklet features "Student Snapshots," designed to…

SDSL-ESR-based protein structure characterization.

PubMed

Strancar, Janez; Kavalenka, Aleh; Urbancic, Iztok; Ljubetic, Ajasja; Hemminga, Marcus A

2010-03-01

As proteins are key molecules in living cells, knowledge about their structure can provide important insights and applications in science, biotechnology, and medicine. However, many protein structures are still a big challenge for existing high-resolution structure-determination methods, as can be seen in the number of protein structures published in the Protein Data Bank. This is especially the case for less-ordered, more hydrophobic and more flexible protein systems. The lack of efficient methods for structure determination calls for urgent development of a new class of biophysical techniques. This work attempts to address this problem with a novel combination of site-directed spin labelling electron spin resonance spectroscopy (SDSL-ESR) and protein structure modelling, which is coupled by restriction of the conformational spaces of the amino acid side chains. Comparison of the application to four different protein systems enables us to generalize the new method and to establish a general procedure for determination of protein structure.

Calorimetric Studies and Structural Aspects of Ionic Liquids in Designing Sorption Materials for Thermal Energy Storage.

PubMed

Brünig, Thorge; Krekić, Kristijan; Bruhn, Clemens; Pietschnig, Rudolf

2016-11-02

The thermal properties of a series of twenty-four ionic liquids (ILs) have been determined by isothermal titration calorimetry (ITC) with the aim of simulating processes involving water sorption. For eleven water-free ILs, the molecular structures have been determined by X-ray crystallography in the solid state, which have been used to derive the molecular volumes of the ionic components of the ILs. Moreover, the structures reveal a high prevalence of hydrogen bonding in these compounds. A relationship between the molecular volumes and the experimentally determined energies of dilution could be established. The highest energies of dilution observed in this series were obtained for the acetate-based ILs, which underlines their potential as working fluids in sorption-based thermal energy storage systems. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

G-LoSA for Prediction of Protein-Ligand Binding Sites and Structures.

PubMed

Lee, Hui Sun; Im, Wonpil

2017-01-01

Recent advances in high-throughput structure determination and computational protein structure prediction have significantly enriched the universe of protein structure. However, there is still a large gap between the number of available protein structures and that of proteins with annotated function in high accuracy. Computational structure-based protein function prediction has emerged to reduce this knowledge gap. The identification of a ligand binding site and its structure is critical to the determination of a protein's molecular function. We present a computational methodology for predicting small molecule ligand binding site and ligand structure using G-LoSA, our protein local structure alignment and similarity measurement tool. All the computational procedures described here can be easily implemented using G-LoSA Toolkit, a package of standalone software programs and preprocessed PDB structure libraries. G-LoSA and G-LoSA Toolkit are freely available to academic users at http://compbio.lehigh.edu/GLoSA . We also illustrate a case study to show the potential of our template-based approach harnessing G-LoSA for protein function prediction.

Modeling, estimation and identification methods for static shape determination of flexible structures. [for large space structure design

NASA Technical Reports Server (NTRS)

Rodriguez, G.; Scheid, R. E., Jr.

1986-01-01

This paper outlines methods for modeling, identification and estimation for static determination of flexible structures. The shape estimation schemes are based on structural models specified by (possibly interconnected) elliptic partial differential equations. The identification techniques provide approximate knowledge of parameters in elliptic systems. The techniques are based on the method of maximum-likelihood that finds parameter values such that the likelihood functional associated with the system model is maximized. The estimation methods are obtained by means of a function-space approach that seeks to obtain the conditional mean of the state given the data and a white noise characterization of model errors. The solutions are obtained in a batch-processing mode in which all the data is processed simultaneously. After methods for computing the optimal estimates are developed, an analysis of the second-order statistics of the estimates and of the related estimation error is conducted. In addition to outlining the above theoretical results, the paper presents typical flexible structure simulations illustrating performance of the shape determination methods.

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling

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

Kumar G.; Swaminathan S.; Kumaran, D.

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC{sub 50} of 0.9 {micro}M and a K{sub i} ofmore » 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.« less

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling.

PubMed

Kumar, Gyanendra; Kumaran, Desigan; Ahmed, S Ashraf; Swaminathan, Subramanyam

2012-05-01

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC(50) of 0.9 µM and a K(i) of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features. © 2012 International Union of Crystallography

Determination of the structural phase and octahedral rotation angle in halide perovskites

NASA Astrophysics Data System (ADS)

dos Reis, Roberto; Yang, Hao; Ophus, Colin; Ercius, Peter; Bizarri, Gregory; Perrodin, Didier; Shalapska, Tetiana; Bourret, Edith; Ciston, Jim; Dahmen, Ulrich

2018-02-01

A key to the unique combination of electronic and optical properties in halide perovskite materials lies in their rich structural complexity. However, their radiation sensitive nature limits nanoscale structural characterization requiring dose efficient microscopic techniques in order to determine their structures precisely. In this work, we determine the space-group and directly image the Br halide sites of CsPbBr3, a promising material for optoelectronic applications. Based on the symmetry of high-order Laue zone reflections of convergent-beam electron diffraction, we identify the tetragonal (I4/mcm) structural phase of CsPbBr3 at cryogenic temperature. Electron ptychography provides a highly sensitive phase contrast measurement of the halide positions under low electron-dose conditions, enabling imaging of the elongated Br sites originating from the out-of-phase octahedral rotation viewed along the [001] direction of I4/mcm persisting at room temperature. The measurement of these features and comparison with simulations yield an octahedral rotation angle of 6.5°(±1.5°). The approach demonstrated here opens up opportunities for understanding the atomic scale structural phenomena applying advanced characterization tools on a wide range of radiation sensitive halide-based all-inorganic and hybrid organic-inorganic perovskites.

Prediction of Ras-effector interactions using position energy matrices.

PubMed

Kiel, Christina; Serrano, Luis

2007-09-01

One of the more challenging problems in biology is to determine the cellular protein interaction network. Progress has been made to predict protein-protein interactions based on structural information, assuming that structural similar proteins interact in a similar way. In a previous publication, we have determined a genome-wide Ras-effector interaction network based on homology models, with a high accuracy of predicting binding and non-binding domains. However, for a prediction on a genome-wide scale, homology modelling is a time-consuming process. Therefore, we here successfully developed a faster method using position energy matrices, where based on different Ras-effector X-ray template structures, all amino acids in the effector binding domain are sequentially mutated to all other amino acid residues and the effect on binding energy is calculated. Those pre-calculated matrices can then be used to score for binding any Ras or effector sequences. Based on position energy matrices, the sequences of putative Ras-binding domains can be scanned quickly to calculate an energy sum value. By calibrating energy sum values using quantitative experimental binding data, thresholds can be defined and thus non-binding domains can be excluded quickly. Sequences which have energy sum values above this threshold are considered to be potential binding domains, and could be further analysed using homology modelling. This prediction method could be applied to other protein families sharing conserved interaction types, in order to determine in a fast way large scale cellular protein interaction networks. Thus, it could have an important impact on future in silico structural genomics approaches, in particular with regard to increasing structural proteomics efforts, aiming to determine all possible domain folds and interaction types. All matrices are deposited in the ADAN database (http://adan-embl.ibmc.umh.es/). Supplementary data are available at Bioinformatics online.

Thermosensitive chitosan gels containing calcium glycerophosphate.

PubMed

Skwarczynska, Agata L; Kuberski, Slawomir; Maniukiewicz, Waldemar; Modrzejewska, Zofia

2018-08-05

In this paper the properties of thermosensitive chitosan hydrogels, formulated with chitosan chloride with β-glycerophosphate disodium salt hydrate and chitosan chloride with β-glycerophosphate disodium salt hydrate enriched with calcium glycerophosphate, are presented. The study focused on the determination of the hydrogel structure after conditioning in water. The structure of the gels was investigated by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The crystallinity of the gel structure was determined by X-ray diffraction analysis (XRD) and the thermal effects were determined based on DSC thermograms. Copyright © 2018 Elsevier B.V. All rights reserved.

Cryo-EM structure of haemoglobin at 3.2 Å determined with the Volta phase plate

NASA Astrophysics Data System (ADS)

Khoshouei, Maryam; Radjainia, Mazdak; Baumeister, Wolfgang; Danev, Radostin

2017-06-01

With the advent of direct electron detectors, the perspectives of cryo-electron microscopy (cryo-EM) have changed in a profound way. These cameras are superior to previous detectors in coping with the intrinsically low contrast and beam-induced motion of radiation-sensitive organic materials embedded in amorphous ice, and hence they have enabled the structure determination of many macromolecular assemblies to atomic or near-atomic resolution. Nevertheless, there are still limitations and one of them is the size of the target structure. Here, we report the use of a Volta phase plate in determining the structure of human haemoglobin (64 kDa) at 3.2 Å. Our results demonstrate that this method can be applied to complexes that are significantly smaller than those previously studied by conventional defocus-based approaches. Cryo-EM is now close to becoming a fast and cost-effective alternative to crystallography for high-resolution protein structure determination.

Simple Approach for De Novo Structural Identification of Mannose Trisaccharides

NASA Astrophysics Data System (ADS)

Hsu, Hsu Chen; Liew, Chia Yen; Huang, Shih-Pei; Tsai, Shang-Ting; Ni, Chi-Kung

2018-03-01

Oligosaccharides have diverse functions in biological systems. However, the structural determination of oligosaccharides remains difficult and has created a bottleneck in carbohydrate research. In this study, a new approach for the de novo structural determination of underivatized oligosaccharides is demonstrated. A low-energy collision-induced dissociation (CID) of sodium ion adducts was used to facilitate the cleavage of desired chemical bonds during the dissociation. The selection of fragments for the subsequent CID was guided using a procedure that we built from the understanding of the saccharide dissociation mechanism. The linkages, anomeric configurations, and branch locations of oligosaccharides were determined by comparing the CID spectra of oligosaccharide with the fragmentation patterns based on the dissociation mechanism and our specially prepared disaccharide CID spectrum database. The usefulness of this method was demonstrated to determine the structures of several mannose trisaccharides. This method can also be applied in the structural determination of oligosaccharides larger than trisaccharides and containing hexose other than mannose if authentic standards are available. [Figure not available: see fulltext.

Simple Approach for De Novo Structural Identification of Mannose Trisaccharides

NASA Astrophysics Data System (ADS)

Hsu, Hsu Chen; Liew, Chia Yen; Huang, Shih-Pei; Tsai, Shang-Ting; Ni, Chi-Kung

2017-12-01

Oligosaccharides have diverse functions in biological systems. However, the structural determination of oligosaccharides remains difficult and has created a bottleneck in carbohydrate research. In this study, a new approach for the de novo structural determination of underivatized oligosaccharides is demonstrated. A low-energy collision-induced dissociation (CID) of sodium ion adducts was used to facilitate the cleavage of desired chemical bonds during the dissociation. The selection of fragments for the subsequent CID was guided using a procedure that we built from the understanding of the saccharide dissociation mechanism. The linkages, anomeric configurations, and branch locations of oligosaccharides were determined by comparing the CID spectra of oligosaccharide with the fragmentation patterns based on the dissociation mechanism and our specially prepared disaccharide CID spectrum database. The usefulness of this method was demonstrated to determine the structures of several mannose trisaccharides. This method can also be applied in the structural determination of oligosaccharides larger than trisaccharides and containing hexose other than mannose if authentic standards are available. [Figure not available: see fulltext.

Structure of 2,4-Diaminopyrimidine - Theobromine Alternate Base Pairs

NASA Technical Reports Server (NTRS)

Gengeliczki, Zsolt; Callahan, Michael P.; Kabelac, Martin; Rijs, Anouk M.; deVries, Mattanjah S.

2011-01-01

We report the structure of clusters of 2,4-diaminopyrimidine with 3,7-dimethylxanthine (theobromine) in the gas phase determined by IR-UV double resonance spectroscopy in both the near-IR and mid-IR regions in combination with ab initio computations. These clusters represent potential alternate nucleobase pairs, geometrically equivalent to guanine-cytosine. We have found the four lowest energy structures, which include the Watson-Crick base pairing motif. This Watson-Crick structure has not been observed by resonant two-photon ionization (R2PI) in the gas phase for the canonical DNA base pairs.

Mechanical Response Analysis of Long-life Asphalt Pavement Structure of Yunluo High-speed on the Semi-rigid Base

NASA Astrophysics Data System (ADS)

Liu, Feng; Wu, Chuanhai; Xu, Xinquan; Li, Hao; Wang, Zhixiang

2018-01-01

In order to grasp the rule of the strain change of the semi-rigid asphalt pavement structure under the FWD load and provide a reliable theoretical and practical basis for the design of the pavement structure, based on the test section of Guangdong Yunluo expressway, taking FWD as the loading tool, by using the finite element analysis software ANSYS, the internal variation rules of each pavement structural layer were obtained. Based on the results of the theoretical analysis, the measured strain sensor was set up in the corresponding layer of the pavement structure, and the strain test plan was determined. Based on the analysis of the strain data obtained from several structural layers and field monitoring, the rationality of the type pavement structure and the strain test scheme were verified, so as to provide useful help for the design and the maintenance of the pavement structure.

Studies of the structure-activity relationships of peptides and proteins involved in growth and development based on their three-dimensional structures.

PubMed

Nagata, Koji

2010-01-01

Peptides and proteins with similar amino acid sequences can have different biological functions. Knowledge of their three-dimensional molecular structures is critically important in identifying their functional determinants. In this review, I describe the results of our and other groups' structure-based functional characterization of insect insulin-like peptides, a crustacean hyperglycemic hormone-family peptide, a mammalian epidermal growth factor-family protein, and an intracellular signaling domain that recognizes proline-rich sequence.

Structural analysis of a highly glycosylated and unliganded gp120-based antigen using mass spectrometry†

PubMed Central

Wang, Liwen; Qin, Yali; Ilchenko, Serguei; Bohon, Jen; Shi, Wuxian; Cho, Michael W.; Takamoto, Keiji; Chance, Mark R.

2010-01-01

Structural characterization of the HIV envelope protein gp120 is very important to provide an understanding of the protein's immunogenicity and it's binding to cell receptors. So far, crystallographic structure determination of gp120 with an intact V3 loop (in the absence of CD4 co-receptor or antibody) has not been achieved. The third variable region (V3) of the gp120 is immunodominant and contains glycosylation signatures that are essential for co-receptor binding and viral entry to T-cells. In this study, we characterized the structure of the outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila S2 cells utilizing mass spectrometry-based approaches. We mapped the glycosylation sites and calculated glycosylation occupancy of gp120-OD8; eleven sites from fifteen glycosylation motifs were determined as having high mannose or hybrid glycosylation structures. The specific glycan moieties of nine glycosylation sites from eight unique glycopeptides were determined by a combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein footprinting coupled with mass spectrometry analysis was employed to provide detailed information on protein structure of gp120-OD8 by directly identifying accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120-OD8 experimental footprinting data with a homology model derived from the ligated CD4/ gp120-OD8 crystal structure revealed a flexible V3 loop structure where the V3 tip may provide contacts with the rest of the protein while residues in the V3 base remain solvent accessible. In addition, the data illustrate interactions between specific sugar moieties and amino acid side chains potentially important to the gp120-OD8 structure. PMID:20825246

[A quantitative approach to sports training-adapted social determinants concerning sport].

PubMed

Alvis-Gómez, Martina K; Neira-Tolosa, Nury A

2013-01-01

Identifying and quantitatively analysing social determinants affecting disabled teenagers' inclusion/exclusion in high-performance sports. This was a descriptive cross-sectional study involving 19 12- to 19-year-old athletes suffering physical and sensory disability and 17 staff from the District Institute of Recreation and Sport. Likert-type rating scales were used, based on four analysis categories, i.e. social structure, socio-economic, educational and living condition determinants. Social inequity pervades the national paralympic sports' system. This is because 74 % of individuals only become recognised as sportspeople when they have obtained meritorious results in set competition without appropriate conditions having been previously provided by such paralympic sports institution to enable them to overcome structural and intermediate barriers. The social structure imposed on district-based paralympic sport stigmatises individuals regarding their individual abilities, affects their empowerment and freedom due to the discrimination experienced by disabled teenagers regarding their competitive achievements.

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

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

In-plane chemical pressure essential for superconductivity in BiCh2-based (Ch: S, Se) layered structure

PubMed Central

Mizuguchi, Yoshikazu; Miura, Akira; Kajitani, Joe; Hiroi, Takafumi; Miura, Osuke; Tadanaga, Kiyoharu; Kumada, Nobuhiro; Magome, Eisuke; Moriyoshi, Chikako; Kuroiwa, Yoshihiro

2015-01-01

BiCh2-based compounds (Ch: S, Se) are a new series of layered superconductors, and the mechanisms for the emergence of superconductivity in these materials have not yet been elucidated. In this study, we investigate the relationship between crystal structure and superconducting properties of the BiCh2-based superconductor family, specifically, optimally doped Ce1−xNdxO0.5F0.5BiS2 and LaO0.5F0.5Bi(S1−ySey)2. We use powder synchrotron X-ray diffraction to determine the crystal structures. We show that the structure parameter essential for the emergence of bulk superconductivity in both systems is the in-plane chemical pressure, rather than Bi-Ch bond lengths or in-plane Ch-Bi-Ch bond angle. Furthermore, we show that the superconducting transition temperature for all REO0.5F0.5BiCh2 superconductors can be determined from the in-plane chemical pressure. PMID:26447333

Modeling Structure and Dynamics of Protein Complexes with SAXS Profiles

PubMed Central

Schneidman-Duhovny, Dina; Hammel, Michal

2018-01-01

Small-angle X-ray scattering (SAXS) is an increasingly common and useful technique for structural characterization of molecules in solution. A SAXS experiment determines the scattering intensity of a molecule as a function of spatial frequency, termed SAXS profile. SAXS profiles can be utilized in a variety of molecular modeling applications, such as comparing solution and crystal structures, structural characterization of flexible proteins, assembly of multi-protein complexes, and modeling of missing regions in the high-resolution structure. Here, we describe protocols for modeling atomic structures based on SAXS profiles. The first protocol is for comparing solution and crystal structures including modeling of missing regions and determination of the oligomeric state. The second protocol performs multi-state modeling by finding a set of conformations and their weights that fit the SAXS profile starting from a single-input structure. The third protocol is for protein-protein docking based on the SAXS profile of the complex. We describe the underlying software, followed by demonstrating their application on interleukin 33 (IL33) with its primary receptor ST2 and DNA ligase IV-XRCC4 complex. PMID:29605933

Accuracy Assessment in Determining the Location of Corners of Building Structures Using a Combination of Various Measurement Methods

NASA Astrophysics Data System (ADS)

Krzyżek, Robert; Przewięźlikowska, Anna

2017-12-01

When surveys of corners of building structures are carried out, surveyors frequently use a compilation of two surveying methods. The first one involves the determination of several corners with reference to a geodetic control using classical methods of surveying field details. The second method relates to the remaining corner points of a structure, which are determined in sequence from distance-distance intersection, using control linear values of the wall faces of the building, the so-called tie distances. This paper assesses the accuracy of coordinates of corner points of a building structure, determined using the method of distance-distance intersection, based on the corners which had previously been determined by the conducted surveys tied to a geodetic control. It should be noted, however, that such a method of surveying the corners of building structures from linear measures is based on the details of the first-order accuracy, while the regulations explicitly allow such measurement only for the details of the second- and third-order accuracy. Therefore, a question arises whether this legal provision is unfounded, or whether surveyors are acting not only against the applicable standards but also without due diligence while performing surveys? This study provides answers to the formulated problem. The main purpose of the study was to verify whether the actual method which is used in practice for surveying building structures allows to obtain the required accuracy of coordinates of the points being determined, or whether it should be strictly forbidden. The results of the conducted studies clearly demonstrate that the problem is definitely more complex. Eventually, however, it might be assumed that assessment of the accuracy in determining a location of corners of a building using a combination of two different surveying methods will meet the requirements of the regulation [MIA, 2011), subject to compliance with relevant baseline criteria, which have been presented in this study. Observance of the proposed boundary conditions would allow for frequent performance of surveys of building structures by surveyors (from tie distances), while maintaining the applicable accuracy criteria. This would allow for the inclusion of surveying documentation into the national geodetic and cartographic documentation center database pursuant to the legal bases.

Fiber optic monitoring methods for composite steel-concrete structures based on determination of neutral axis and deformed shape.

DOT National Transportation Integrated Search

2014-01-01

Structural Health Monitoring has great potential to provide valuable information about the actual structural condition and can help optimize the management activities. However, few effective and robust monitoring methods exist which hinders a nationw...

Structure of an E. coli integral membrane sulfurtransferase and its structural transition upon SCN- binding defined by EPR-based hybrid method

NASA Astrophysics Data System (ADS)

Ling, Shenglong; Wang, Wei; Yu, Lu; Peng, Junhui; Cai, Xiaoying; Xiong, Ying; Hayati, Zahra; Zhang, Longhua; Zhang, Zhiyong; Song, Likai; Tian, Changlin

2016-01-01

Electron paramagnetic resonance (EPR)-based hybrid experimental and computational approaches were applied to determine the structure of a full-length E. coli integral membrane sulfurtransferase, dimeric YgaP, and its structural and dynamic changes upon ligand binding. The solution NMR structures of the YgaP transmembrane domain (TMD) and cytosolic catalytic rhodanese domain were reported recently, but the tertiary fold of full-length YgaP was not yet available. Here, systematic site-specific EPR analysis defined a helix-loop-helix secondary structure of the YagP-TMD monomers using mobility, accessibility and membrane immersion measurements. The tertiary folds of dimeric YgaP-TMD and full-length YgaP in detergent micelles were determined through inter- and intra-monomer distance mapping and rigid-body computation. Further EPR analysis demonstrated the tight packing of the two YgaP second transmembrane helices upon binding of the catalytic product SCN-, which provides insight into the thiocyanate exportation mechanism of YgaP in the E. coli membrane.

Research on criticality analysis method of CNC machine tools components under fault rate correlation

NASA Astrophysics Data System (ADS)

Gui-xiang, Shen; Xian-zhuo, Zhao; Zhang, Ying-zhi; Chen-yu, Han

2018-02-01

In order to determine the key components of CNC machine tools under fault rate correlation, a system component criticality analysis method is proposed. Based on the fault mechanism analysis, the component fault relation is determined, and the adjacency matrix is introduced to describe it. Then, the fault structure relation is hierarchical by using the interpretive structure model (ISM). Assuming that the impact of the fault obeys the Markov process, the fault association matrix is described and transformed, and the Pagerank algorithm is used to determine the relative influence values, combined component fault rate under time correlation can obtain comprehensive fault rate. Based on the fault mode frequency and fault influence, the criticality of the components under the fault rate correlation is determined, and the key components are determined to provide the correct basis for equationting the reliability assurance measures. Finally, taking machining centers as an example, the effectiveness of the method is verified.

Structural, spectroscopic and DFT study of 4-methoxybenzohydrazide Schiff bases. A new series of polyfunctional ligands.

PubMed

Ferraresi-Curotto, Verónica; Echeverría, Gustavo A; Piro, Oscar E; Pis-Diez, Reinaldo; González-Baró, Ana C

2015-02-25

Five Schiff bases obtained from condensation of 4-methoxybenzohydrazide with related aldehydes, namely o-vanillin, vanillin, 5-bromovanillin, 5-chlorosalicylaldehyde and 5-bromosalicylaldehyde were prepared. A detailed structural and spectroscopic study is reported. The crystal structures of four members of the family were determined and compared with one another. The hydrazones obtained from 5-chlorosalicylaldehyde and 5-bromosalicylaldehyde resulted to be isomorphic to each other. The solid-state structures are stabilized by intra-molecular O-H⋯N interactions in salicylaldehyde derivatives between the O-H moiety from the aldehyde and the hydrazone nitrogen atom. All crystals are further stabilized by inter-molecular H-bonds mediated by the crystallization water molecule. A comparative analysis between experimental and theoretical results is presented. The conformational space was searched and geometries were optimized both in gas phase and including solvent effects. The structure is predicted for the compound for which the crystal structure was not determined. Infrared and electronic spectra were measured and assigned with the help of data obtained from computational methods based on the Density Functional Theory. Copyright © 2014 Elsevier B.V. All rights reserved.

Tomographic reconstruction of layered tissue structures

NASA Astrophysics Data System (ADS)

Hielscher, Andreas H.; Azeez-Jan, Mohideen; Bartel, Sebastian

2001-11-01

In recent years the interest in the determination of optical properties of layered tissue structure has resurfaced. Applications include, for example, studies on layered skin tissue and underlying muscles, imaging of the brain underneath layers of skin, skull, and meninges, and imaging of the fetal head in utero beneath the layered structures of the maternal abdomen. In this work we approach the problem of layered structures in the framework of model-based iterative image reconstruction schemes. These schemes are currently developed to determine the optical properties inside tissue from measurement on the surface. If applied to layered structure these techniques yield substantial improvements over currently available semi-analytical approaches.

1H and 13C-NMR studies on phenol-formaldehyde prepolymers for tannin-based adhesives

Treesearch

Gerald W. McGraw; Lawerence L. Lanucci; Seiji Ohara; Richard W. Hemingway

1989-01-01

The number average structure and the molecular weight distribution of phenol-formaldehyde prepolymers for use in synthesis of tannin-based adhesive resins were determined with 1H and 13C-NMR spectroscopy and gel permeation chromatography of acetylated resins. These methods were used to determine differences in phenol-...

Apparatus and method for determining microscale interactions based on compressive sensors such as crystal structures

DOEpatents

McAdams, Harley; AlQuraishi, Mohammed

2015-04-21

Techniques for determining values for a metric of microscale interactions include determining a mesoscale metric for a plurality of mesoscale interaction types, wherein a value of the mesoscale metric for each mesoscale interaction type is based on a corresponding function of values of the microscale metric for the plurality of the microscale interaction types. A plurality of observations that indicate the values of the mesoscale metric are determined for the plurality of mesoscale interaction types. Values of the microscale metric are determined for the plurality of microscale interaction types based on the plurality of observations and the corresponding functions and compressed sensing.

TAP score: torsion angle propensity normalization applied to local protein structure evaluation

PubMed Central

Tosatto, Silvio CE; Battistutta, Roberto

2007-01-01

Background Experimentally determined protein structures may contain errors and require validation. Conformational criteria based on the Ramachandran plot are mainly used to distinguish between distorted and adequately refined models. While the readily available criteria are sufficient to detect totally wrong structures, establishing the more subtle differences between plausible structures remains more challenging. Results A new criterion, called TAP score, measuring local sequence to structure fitness based on torsion angle propensities normalized against the global minimum and maximum is introduced. It is shown to be more accurate than previous methods at estimating the validity of a protein model in terms of commonly used experimental quality parameters on two test sets representing the full PDB database and a subset of obsolete PDB structures. Highly selective TAP thresholds are derived to recognize over 90% of the top experimental structures in the absence of experimental information. Both a web server and an executable version of the TAP score are available at . Conclusion A novel procedure for energy normalization (TAP) has significantly improved the possibility to recognize the best experimental structures. It will allow the user to more reliably isolate problematic structures in the context of automated experimental structure determination. PMID:17504537

Synthesis, crystal structure and redox properties of dihydropyrazole-bridged ferrocene-based derivatives

NASA Astrophysics Data System (ADS)

Li, Heng-Dong; Ma, Zai-He; Yang, Kun; Xie, Li-Li; Yuan, Yao-Feng

2012-09-01

Dihydropyrazole-bridged ferrocene-based derivatives were prepared by corresponding chalcones with hydrazine hydrate, then acylation with 3-(ethoxycarbonyl)propionyl chloride directly in high yields and purity. All of these compounds were characterized by MS, IR, 1H NMR, 13C NMR and elemental analysis. The relationship between the structure and redox properties was investigated based on the results of single crystal X-ray structure determinations and cyclic voltammetry. The mechanism of the electron transfer for representative compound 4b was verified by density functional theory (DFT) calculations.

Electrochemical Characterization of InP and GaAs Based Structures for Space Solar Cell Applications.

NASA Technical Reports Server (NTRS)

Faur, Maria; Faur, Mircea; Jenkins, Philip P.; Goradia, Manju; Wilt, David M.

1994-01-01

In this paper the emphasis is on accurate majority carrier concentration EC-V profiling of structures based on Indium Phosphide and Gallium Arsenide, using a newly developed electrolyte based on Hydrogen Flouride, Acetic Acid, Phosphoric Acid, 1-phenyl-2-propanamine and Ammonia Diflouride. Some preliminary data on the use of this electrolyte for determining the energy distribution of surface and deep states of these structures, applicable to fabrication process optimization and radiation induced defects studies of solar cells, are also provided.

Performance-based plastic design of earthquake resistant reinforced concrete moment frames

NASA Astrophysics Data System (ADS)

Liao, Wen-Cheng

Performance-Based Plastic Design (PBPD) method has been recently developed to achieve enhanced performance of earthquake resistant structures. The design concept uses pre-selected target drift and yield mechanism as performance criteria. The design base shear for selected hazard level is determined by equating the work needed to push the structure monotonically up to the target drift to the corresponding energy demand of an equivalent SDOF oscillator. This study presents development of the PBPD approach as applied to reinforced concrete special moment frame (RC SMF) structures. RC structures present special challenge because of their complex and degrading ("pinched") hysteretic behavior. In order to account for the degrading hysteretic behavior the 1-EMA 440 C2 factor approach was used in the process of determining the design base shear. Four baseline RC SMF (4, 8, 12 and 20-story) as used in the FEMA P695 were selected for this study. Those frames were redesigned by the PBPD approach. The baseline frames and the PBPD frames were subjected to extensive inelastic pushover and time-history analyses. The PBPD frames showed much improved response meeting all desired performance objectives, including the intended yield mechanisms and the target drifts. On the contrary, the baseline frames experienced large story drifts due to flexural yielding of the columns. The work-energy equation to determine design base shear can also be used to estimate seismic demands, called the energy spectrum method. In this approach the skeleton force-displacement (capacity) curve of the structure is converted into energy-displacement plot (Ec) which is superimposed over the corresponding energy demand plot ( Ed) for the specified hazard level to determine the expected peak displacement demands. In summary, this study shows that the PBPD approach can be successfully applied to RC moment frame structures as well, and that the responses of the example moment frames were much improved over those of the corresponding baseline frames. In addition, the drift demands of all study frames as computed by the energy spectrum method were in excellent agreement with those obtained from detailed inelastic dynamic analyses.

Study the effect of nitrogen flow rate on tribological properties of tantalum nitride based coatings

NASA Astrophysics Data System (ADS)

Chauhan, Dharmesh B.; Chauhan, Kamlesh V.; Sonera, Akshay L.; Makwana, Nishant S.; Dave, Divyeshkumar P.; Rawal, Sushant K.

2018-05-01

Tantalum Nitride (TaN) based coatings are well-known for their high temperature stability and chemical inertness. We have studied the effect of nitrogen flow rate variation on the structural and tribological properties of TaN based coating deposited by RF magnetron sputtering process. The nitrogen flow rate was varied from 5 to 30 sccm. X-ray diffractometer (XRD) and Atomic Force Microscopy (AFM) were used to determine structure and surface topography of coating. Pin on disc tribometer was used to determine tribological properties of coating. TaN coated brass and mild steel substrates shows higher wear resistance compared to uncoated substrates of brass and mild steel.

Advanced solid-state NMR techniques for characterization of membrane protein structure and dynamics: Application to Anabaena Sensory Rhodopsin

NASA Astrophysics Data System (ADS)

Ward, Meaghan E.; Brown, Leonid S.; Ladizhansky, Vladimir

2015-04-01

Studies of the structure, dynamics, and function of membrane proteins (MPs) have long been considered one of the main applications of solid-state NMR (SSNMR). Advances in instrumentation, and the plethora of new SSNMR methodologies developed over the past decade have resulted in a number of high-resolution structures and structural models of both bitopic and polytopic α-helical MPs. The necessity to retain lipids in the sample, the high proportion of one type of secondary structure, differential dynamics, and the possibility of local disorder in the loop regions all create challenges for structure determination. In this Perspective article we describe our recent efforts directed at determining the structure and functional dynamics of Anabaena Sensory Rhodopsin, a heptahelical transmembrane (7TM) protein. We review some of the established and emerging methods which can be utilized for SSNMR-based structure determination, with a particular focus on those used for ASR, a bacterial protein which shares its 7TM architecture with G-protein coupled receptors.

A study of concept-based similarity approaches for recommending program examples

NASA Astrophysics Data System (ADS)

Hosseini, Roya; Brusilovsky, Peter

2017-07-01

This paper investigates a range of concept-based example recommendation approaches that we developed to provide example-based problem-solving support in the domain of programming. The goal of these approaches is to offer students a set of most relevant remedial examples when they have trouble solving a code comprehension problem where students examine a program code to determine its output or the final value of a variable. In this paper, we use the ideas of semantic-level similarity-based linking developed in the area of intelligent hypertext to generate examples for the given problem. To determine the best-performing approach, we explored two groups of similarity approaches for selecting examples: non-structural approaches focusing on examples that are similar to the problem in terms of concept coverage and structural approaches focusing on examples that are similar to the problem by the structure of the content. We also explored the value of personalized example recommendation based on student's knowledge levels and learning goal of the exercise. The paper presents concept-based similarity approaches that we developed, explains the data collection studies and reports the result of comparative analysis. The results of our analysis showed better ranking performance of the personalized structural variant of cosine similarity approach.

Modeling complexes of modeled proteins.

PubMed

Anishchenko, Ivan; Kundrotas, Petras J; Vakser, Ilya A

2017-03-01

Structural characterization of proteins is essential for understanding life processes at the molecular level. However, only a fraction of known proteins have experimentally determined structures. This fraction is even smaller for protein-protein complexes. Thus, structural modeling of protein-protein interactions (docking) primarily has to rely on modeled structures of the individual proteins, which typically are less accurate than the experimentally determined ones. Such "double" modeling is the Grand Challenge of structural reconstruction of the interactome. Yet it remains so far largely untested in a systematic way. We present a comprehensive validation of template-based and free docking on a set of 165 complexes, where each protein model has six levels of structural accuracy, from 1 to 6 Å C α RMSD. Many template-based docking predictions fall into acceptable quality category, according to the CAPRI criteria, even for highly inaccurate proteins (5-6 Å RMSD), although the number of such models (and, consequently, the docking success rate) drops significantly for models with RMSD > 4 Å. The results show that the existing docking methodologies can be successfully applied to protein models with a broad range of structural accuracy, and the template-based docking is much less sensitive to inaccuracies of protein models than the free docking. Proteins 2017; 85:470-478. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Integrating NOE and RDC using sum-of-squares relaxation for protein structure determination.

PubMed

Khoo, Y; Singer, A; Cowburn, D

2017-07-01

We revisit the problem of protein structure determination from geometrical restraints from NMR, using convex optimization. It is well-known that the NP-hard distance geometry problem of determining atomic positions from pairwise distance restraints can be relaxed into a convex semidefinite program (SDP). However, often the NOE distance restraints are too imprecise and sparse for accurate structure determination. Residual dipolar coupling (RDC) measurements provide additional geometric information on the angles between atom-pair directions and axes of the principal-axis-frame. The optimization problem involving RDC is highly non-convex and requires a good initialization even within the simulated annealing framework. In this paper, we model the protein backbone as an articulated structure composed of rigid units. Determining the rotation of each rigid unit gives the full protein structure. We propose solving the non-convex optimization problems using the sum-of-squares (SOS) hierarchy, a hierarchy of convex relaxations with increasing complexity and approximation power. Unlike classical global optimization approaches, SOS optimization returns a certificate of optimality if the global optimum is found. Based on the SOS method, we proposed two algorithms-RDC-SOS and RDC-NOE-SOS, that have polynomial time complexity in the number of amino-acid residues and run efficiently on a standard desktop. In many instances, the proposed methods exactly recover the solution to the original non-convex optimization problem. To the best of our knowledge this is the first time SOS relaxation is introduced to solve non-convex optimization problems in structural biology. We further introduce a statistical tool, the Cramér-Rao bound (CRB), to provide an information theoretic bound on the highest resolution one can hope to achieve when determining protein structure from noisy measurements using any unbiased estimator. Our simulation results show that when the RDC measurements are corrupted by Gaussian noise of realistic variance, both SOS based algorithms attain the CRB. We successfully apply our method in a divide-and-conquer fashion to determine the structure of ubiquitin from experimental NOE and RDC measurements obtained in two alignment media, achieving more accurate and faster reconstructions compared to the current state of the art.

Sequence Determinants of Compaction in Intrinsically Disordered Proteins

PubMed Central

Marsh, Joseph A.; Forman-Kay, Julie D.

2010-01-01

Abstract Intrinsically disordered proteins (IDPs), which lack folded structure and are disordered under nondenaturing conditions, have been shown to perform important functions in a large number of cellular processes. These proteins have interesting structural properties that deviate from the random-coil-like behavior exhibited by chemically denatured proteins. In particular, IDPs are often observed to exhibit significant compaction. In this study, we have analyzed the hydrodynamic radii of a number of IDPs to investigate the sequence determinants of this compaction. Net charge and proline content are observed to be strongly correlated with increased hydrodynamic radii, suggesting that these are the dominant contributors to compaction. Hydrophobicity and secondary structure, on the other hand, appear to have negligible effects on compaction, which implies that the determinants of structure in folded and intrinsically disordered proteins are profoundly different. Finally, we observe that polyhistidine tags seem to increase IDP compaction, which suggests that these tags have significant perturbing effects and thus should be removed before any structural characterizations of IDPs. Using the relationships observed in this analysis, we have developed a sequence-based predictor of hydrodynamic radius for IDPs that shows substantial improvement over a simple model based upon chain length alone. PMID:20483348

Determination of the structural phase and octahedral rotation angle in halide perovskites

DOE PAGES

dos Reis, Roberto; Yang, Hao; Ophus, Colin; ...

2018-02-12

A key to the unique combination of electronic and optical properties in halide perovskite materials lies in their rich structural complexity. However, their radiation sensitive nature limits nanoscale structural characterization requiring dose efficient microscopic techniques in order to determine their structures precisely. In this work, we determine the space-group and directly image the Br halide sites of CsPbBr 3, a promising material for optoelectronic applications. Based on the symmetry of high-order Laue zone reflections of convergent-beam electron diffraction, we identify the tetragonal (I4/mcm) structural phase of CsPbBr 3 at cryogenic temperature. Electron ptychography provides a highly sensitive phase contrast measurementmore » of the halide positions under low electron-dose conditions, enabling imaging of the elongated Br sites originating from the out-of-phase octahedral rotation viewed along the [001] direction of I4/mcm persisting at room temperature. The measurement of these features and comparison with simulations yield an octahedral rotation angle of 6.5°(±1.5°). Finally, the approach demonstrated here opens up opportunities for understanding the atomic scale structural phenomena applying advanced characterization tools on a wide range of radiation sensitive halide-based all-inorganic and hybrid organic-inorganic perovskites.« less

Structural features of microRNA (miRNA) precursors and their relevance to miRNA biogenesis and small interfering RNA/short hairpin RNA design.

PubMed

Krol, Jacek; Sobczak, Krzysztof; Wilczynska, Urszula; Drath, Maria; Jasinska, Anna; Kaczynska, Danuta; Krzyzosiak, Wlodzimierz J

2004-10-01

We have established the structures of 10 human microRNA (miRNA) precursors using biochemical methods. Eight of these structures turned out to be different from those that were computer-predicted. The differences localized in the terminal loop region and at the opposite side of the precursor hairpin stem. We have analyzed the features of these structures from the perspectives of miRNA biogenesis and active strand selection. We demonstrated the different thermodynamic stability profiles for pre-miRNA hairpins harboring miRNAs at their 5'- and 3'-sides and discussed their functional implications. Our results showed that miRNA prediction based on predicted precursor structures may give ambiguous results, and the success rate is significantly higher for the experimentally determined structures. On the other hand, the differences between the predicted and experimentally determined structures did not affect the stability of termini produced through "conceptual dicing." This result confirms the value of thermodynamic analysis based on mfold as a predictor of strand section by RNAi-induced silencing complex (RISC).

NMR Structure of Francisella tularensis Virulence Determinant Reveals Structural Homology to Bet v1 Allergen Proteins.

PubMed

Zook, James; Mo, Gina; Sisco, Nicholas J; Craciunescu, Felicia M; Hansen, Debra T; Baravati, Bobby; Cherry, Brian R; Sykes, Kathryn; Wachter, Rebekka; Van Horn, Wade D; Fromme, Petra

2015-06-02

Tularemia is a potentially fatal bacterial infection caused by Francisella tularensis, and is endemic to North America and many parts of northern Europe and Asia. The outer membrane lipoprotein, Flpp3, has been identified as a virulence determinant as well as a potential subunit template for vaccine development. Here we present the first structure for the soluble domain of Flpp3 from the highly infectious Type A SCHU S4 strain, derived through high-resolution solution nuclear magnetic resonance (NMR) spectroscopy; the first structure of a lipoprotein from the genus Francisella. The Flpp3 structure demonstrates a globular protein with an electrostatically polarized surface containing an internal cavity-a putative binding site based on the structurally homologous Bet v1 protein family of allergens. NMR-based relaxation studies suggest loop regions that potentially modulate access to the internal cavity. The Flpp3 structure may add to the understanding of F. tularensis virulence and contribute to the development of effective vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multi-target parallel processing approach for gene-to-structure determination of the influenza polymerase PB2 subunit.

PubMed

Armour, Brianna L; Barnes, Steve R; Moen, Spencer O; Smith, Eric; Raymond, Amy C; Fairman, James W; Stewart, Lance J; Staker, Bart L; Begley, Darren W; Edwards, Thomas E; Lorimer, Donald D

2013-06-28

Pandemic outbreaks of highly virulent influenza strains can cause widespread morbidity and mortality in human populations worldwide. In the United States alone, an average of 41,400 deaths and 1.86 million hospitalizations are caused by influenza virus infection each year (1). Point mutations in the polymerase basic protein 2 subunit (PB2) have been linked to the adaptation of the viral infection in humans (2). Findings from such studies have revealed the biological significance of PB2 as a virulence factor, thus highlighting its potential as an antiviral drug target. The structural genomics program put forth by the National Institute of Allergy and Infectious Disease (NIAID) provides funding to Emerald Bio and three other Pacific Northwest institutions that together make up the Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is dedicated to providing the scientific community with three-dimensional protein structures of NIAID category A-C pathogens. Making such structural information available to the scientific community serves to accelerate structure-based drug design. Structure-based drug design plays an important role in drug development. Pursuing multiple targets in parallel greatly increases the chance of success for new lead discovery by targeting a pathway or an entire protein family. Emerald Bio has developed a high-throughput, multi-target parallel processing pipeline (MTPP) for gene-to-structure determination to support the consortium. Here we describe the protocols used to determine the structure of the PB2 subunit from four different influenza A strains.

Strain-Based Damage Determination Using Finite Element Analysis for Structural Health Management

NASA Technical Reports Server (NTRS)

Hochhalter, Jacob D.; Krishnamurthy, Thiagaraja; Aguilo, Miguel A.

2016-01-01

A damage determination method is presented that relies on in-service strain sensor measurements. The method employs a gradient-based optimization procedure combined with the finite element method for solution to the forward problem. It is demonstrated that strains, measured at a limited number of sensors, can be used to accurately determine the location, size, and orientation of damage. Numerical examples are presented to demonstrate the general procedure. This work is motivated by the need to provide structural health management systems with a real-time damage characterization. The damage cases investigated herein are characteristic of point-source damage, which can attain critical size during flight. The procedure described can be used to provide prognosis tools with the current damage configuration.

Determination of CME 3D parameters based on a new full ice-cream cone model

NASA Astrophysics Data System (ADS)

Na, Hyeonock; Moon, Yong-Jae

2017-08-01

In space weather forecast, it is important to determine three-dimensional properties of CMEs. Using 29 limb CMEs, we examine which cone type is close to a CME three-dimensional structure. We find that most CMEs have near full ice-cream cone structure which is a symmetrical circular cone combined with a hemisphere. We develop a full ice-cream cone model based on a new methodology that the full ice-cream cone consists of many flat cones with different heights and angular widths. By applying this model to 12 SOHO/LASCO halo CMEs, we find that 3D parameters from our method are similar to those from other stereoscopic methods (i.e., a triangulation method and a Graduated Cylindrical Shell model). In addition, we derive CME mean density (ρmean=Mtotal/Vcone) based on the full ice-cream cone structure. For several limb events, we determine CME mass by applying the Solarsoft procedure (e.g., cme_mass.pro) to SOHO/LASCO C3 images. CME volumes are estimated from the full ice-cream cone structure. From the power-law relationship between CME mean density and its height, we estimate CME mean densities at 20 solar radii (Rs). We will compare the CME densities at 20 Rs with their corresponding ICME densities.

Structure of Lmaj006129AAA, a hypothetical protein from Leishmania major

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

Arakaki, Tracy; Le Trong, Isolde; Structural Genomics of Pathogenic Protozoa

2006-03-01

The crystal structure of a conserved hypothetical protein from L. major, Pfam sequence family PF04543, structural genomics target ID Lmaj006129AAA, has been determined at a resolution of 1.6 Å. The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD)more » using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (R{sub free} = 0.229) at 1.60 Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif.« less

Method for Real-Time Model Based Structural Anomaly Detection

NASA Technical Reports Server (NTRS)

Urnes, James M., Sr. (Inventor); Smith, Timothy A. (Inventor); Reichenbach, Eric Y. (Inventor)

2015-01-01

A system and methods for real-time model based vehicle structural anomaly detection are disclosed. A real-time measurement corresponding to a location on a vehicle structure during an operation of the vehicle is received, and the real-time measurement is compared to expected operation data for the location to provide a modeling error signal. A statistical significance of the modeling error signal to provide an error significance is calculated, and a persistence of the error significance is determined. A structural anomaly is indicated, if the persistence exceeds a persistence threshold value.

Photoelectron diffraction from single oriented molecules: Towards ultrafast structure determination of molecules using x-ray free-electron lasers

NASA Astrophysics Data System (ADS)

Kazama, Misato; Fujikawa, Takashi; Kishimoto, Naoki; Mizuno, Tomoya; Adachi, Jun-ichi; Yagishita, Akira

2013-06-01

We provide a molecular structure determination method, based on multiple-scattering x-ray photoelectron diffraction (XPD) calculations. This method is applied to our XPD data on several molecules having different equilibrium geometries. Then it is confirmed that, by our method, bond lengths and bond angles can be determined with a resolution of less than 0.1 Å and 10∘, respectively. Differently from any other scenario of ultrafast structure determination, we measure the two- or three-dimensional XPD of aligned or oriented molecules in the energy range from 100 to 200 eV with a 4π detection velocity map imaging spectrometer. Thanks to the intense and ultrashort pulse properties of x-ray free-electron lasers, our approach exhibits the most probable method for obtaining ultrafast real-time structural information on small to medium-sized molecules consisting of light elements, i.e., a “molecular movie.”

Structural characterization/correlation of calorimetric properties of coal fluids. First annual report, September 1, 1985-August 31, 1986

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

Starling, K.E.; Mallinson, R.G.; Li, M.H.

The objective of this research is to examine the relationship between the calorimetric properties of coal liquids and their molecular functional group composition. Coal liquid samples which have had their calorimetric properties measured are characterized using proton NMR, ir and elemental analysis. These characterizations are then used in a chemical structural model to determine the composition of the coal liquid in terms of the important molecular functional groups. These functional groups are particularly important in determining the intramolecular based properties of a fluid, such as ideal gas heat capacities. Correlational frameworks for heat capacities will then be examined within anmore » existing equation of state methodology to determine an optimal correlation. Also, the optimal recipe for obtaining the characterization/chemical structure information and the sensitivity of the correlation to the characterization and structural model will be examined and determined. 7 refs.« less

Ozonation of wastewater: removal and transformation products of drugs of abuse.

PubMed

Rodayan, Angela; Segura, Pedro Alejandro; Yargeau, Viviane

2014-07-15

In this study amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), cocaine (COC), benzoylecgonine (BE), ketamine (KET) and oxycodone (OXY) in wastewater at concentrations of 100 μgL(-1) were subjected to ozone to determine their removals as a function of ozone dose and to identify significant oxidation transformation products (OTPs) produced as a result of ozonation. A method based on high resolution mass spectrometry and differential analysis was used to facilitate and accelerate the identification and structural elucidation of the transformation products. The drug removal ranged from 3 to 50% depending on the complexity of the matrix and whether a mixture or individual drugs were ozonated. Both transient and persistent oxidation transformation products were identified for MDMA, COC and OXY and their chemical formulae were determined. Three possible structures of the persistent transformation product of MDMA (OTP-213) with chemical formula C10H16O4N, were determined based on MS(n) mass spectra and the most plausible structure (OTP-213a) was determined based on the chemistry of ozone. These results indicate that ozone is capable of removing drugs of abuse from wastewater to varying extents and that persistent transformation products are produced as a result of treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Teaching Three-Dimensional Structural Chemistry Using Crystal Structure Databases. 4. Examples of Discovery-Based Learning Using the Complete Cambridge Structural Database

ERIC Educational Resources Information Center

Battle, Gary M.; Allen, Frank H.; Ferrence, Gregory M.

2011-01-01

Parts 1 and 2 of this series described the educational value of experimental three-dimensional (3D) chemical structures determined by X-ray crystallography and retrieved from the crystallographic databases. In part 1, we described the information content of the Cambridge Structural Database (CSD) and discussed a representative teaching subset of…

Protein secondary structure determination by constrained single-particle cryo-electron tomography.

PubMed

Bartesaghi, Alberto; Lecumberry, Federico; Sapiro, Guillermo; Subramaniam, Sriram

2012-12-05

Cryo-electron microscopy (cryo-EM) is a powerful technique for 3D structure determination of protein complexes by averaging information from individual molecular images. The resolutions that can be achieved with single-particle cryo-EM are frequently limited by inaccuracies in assigning molecular orientations based solely on 2D projection images. Tomographic data collection schemes, however, provide powerful constraints that can be used to more accurately determine molecular orientations necessary for 3D reconstruction. Here, we propose "constrained single-particle tomography" as a general strategy for 3D structure determination in cryo-EM. A key component of our approach is the effective use of images recorded in tilt series to extract high-resolution information and correct for the contrast transfer function. By incorporating geometric constraints into the refinement to improve orientational accuracy of images, we reduce model bias and overrefinement artifacts and demonstrate that protein structures can be determined at resolutions of ∼8 Å starting from low-dose tomographic tilt series. Copyright © 2012 Elsevier Ltd. All rights reserved.

Modeling helical proteins using residual dipolar couplings, sparse long-range distance constraints and a simple residue-based force field

PubMed Central

Eggimann, Becky L.; Vostrikov, Vitaly V.; Veglia, Gianluigi; Siepmann, J. Ilja

2013-01-01

We present a fast and simple protocol to obtain moderate-resolution backbone structures of helical proteins. This approach utilizes a combination of sparse backbone NMR data (residual dipolar couplings and paramagnetic relaxation enhancements) or EPR data with a residue-based force field and Monte Carlo/simulated annealing protocol to explore the folding energy landscape of helical proteins. By using only backbone NMR data, which are relatively easy to collect and analyze, and strategically placed spin relaxation probes, we show that it is possible to obtain protein structures with correct helical topology and backbone RMS deviations well below 4 Å. This approach offers promising alternatives for the structural determination of proteins in which nuclear Overha-user effect data are difficult or impossible to assign and produces initial models that will speed up the high-resolution structure determination by NMR spectroscopy. PMID:24639619

Hall Determination of Atomic Radii of Alkali Metals

ERIC Educational Resources Information Center

Houari, Ahmed

2008-01-01

I will propose here an alternative method for determining atomic radii of alkali metals based on the Hall measurements of their free electron densities and the knowledge of their crystal structure. (Contains 2 figures.)

Optimization of fluorimetric lipid membrane biosensor sensitivity through manipulation of membrane structure and nitrobenzoxadiazole dipalmitoylphosphatidylethanolamine concentration

NASA Astrophysics Data System (ADS)

Shrive, Jason D. A.; Krull, Ulrich J.

1995-01-01

In the work reported here, surface concentrations of 0.027 and 0.073 molecules nm-2 of the fluorescent membrane probe molecule nitrobenzoxadiazole dipalmitoylphosphatidylethanolamine (NBD-PE) were shown to yield optimum sensitivity for fluorimetric transduction of membrane structural perturbations for lipid membrane-based biosensor development. These optima were obtained through correlation of experimental data with theoretical predictions of optimum surface concentrations based on a model for NBD-PE self quenching previously published by our group. It was also determined that membrane structural heterogeneity improves the sensitivity of NBD-PE labeled membrane transducers. Together with fluorescence microscopy, observations of surface potential change upon compression or expansion of phosphatidylcholine (PC)/phosphatidic acid (PA) monolayers were used to qualitatively indicate the degree of structural heterogeneity in these membranes. It was determined that sub-microscopic domains must exist in microscopically homogeneous egg PC/egg PA membranes in order to facilitate the observed NBD-PE self-quenching responses upon alteration of bulk pH and therefore, membrane surface electrostatics and structure.

Structure-guided statistical textural distinctiveness for salient region detection in natural images.

PubMed

Scharfenberger, Christian; Wong, Alexander; Clausi, David A

2015-01-01

We propose a simple yet effective structure-guided statistical textural distinctiveness approach to salient region detection. Our method uses a multilayer approach to analyze the structural and textural characteristics of natural images as important features for salient region detection from a scale point of view. To represent the structural characteristics, we abstract the image using structured image elements and extract rotational-invariant neighborhood-based textural representations to characterize each element by an individual texture pattern. We then learn a set of representative texture atoms for sparse texture modeling and construct a statistical textural distinctiveness matrix to determine the distinctiveness between all representative texture atom pairs in each layer. Finally, we determine saliency maps for each layer based on the occurrence probability of the texture atoms and their respective statistical textural distinctiveness and fuse them to compute a final saliency map. Experimental results using four public data sets and a variety of performance evaluation metrics show that our approach provides promising results when compared with existing salient region detection approaches.

Camps 2.0: exploring the sequence and structure space of prokaryotic, eukaryotic, and viral membrane proteins.

PubMed

Neumann, Sindy; Hartmann, Holger; Martin-Galiano, Antonio J; Fuchs, Angelika; Frishman, Dmitrij

2012-03-01

Structural bioinformatics of membrane proteins is still in its infancy, and the picture of their fold space is only beginning to emerge. Because only a handful of three-dimensional structures are available, sequence comparison and structure prediction remain the main tools for investigating sequence-structure relationships in membrane protein families. Here we present a comprehensive analysis of the structural families corresponding to α-helical membrane proteins with at least three transmembrane helices. The new version of our CAMPS database (CAMPS 2.0) covers nearly 1300 eukaryotic, prokaryotic, and viral genomes. Using an advanced classification procedure, which is based on high-order hidden Markov models and considers both sequence similarity as well as the number of transmembrane helices and loop lengths, we identified 1353 structurally homogeneous clusters roughly corresponding to membrane protein folds. Only 53 clusters are associated with experimentally determined three-dimensional structures, and for these clusters CAMPS is in reasonable agreement with structure-based classification approaches such as SCOP and CATH. We therefore estimate that ∼1300 structures would need to be determined to provide a sufficient structural coverage of polytopic membrane proteins. CAMPS 2.0 is available at http://webclu.bio.wzw.tum.de/CAMPS2.0/. Copyright © 2011 Wiley Periodicals, Inc.

Method to control residual stress in a film structure and a system thereof

DOEpatents

Parthum, Sr., Michael J.

2008-12-30

A method for controlling residual stress in a structure in a MEMS device and a structure thereof includes selecting a total thickness and an overall equivalent stress for the structure. A thickness for each of at least one set of alternating first and second layers is determined to control an internal stress with respect to a neutral axis for each of the at least alternating first and second layers and to form the structure based on the selected total thickness and the selected overall equivalent stress. Each of the at least alternating first and second layers is deposited to the determined thickness for each of the at least alternating first and second layers to form the structure.

NMR in structural genomics to increase structural coverage of the protein universe: Delivered by Prof. Kurt Wüthrich on 7 July 2013 at the 38th FEBS Congress in St. Petersburg, Russia.

PubMed

Serrano, Pedro; Dutta, Samit K; Proudfoot, Andrew; Mohanty, Biswaranjan; Susac, Lukas; Martin, Bryan; Geralt, Michael; Jaroszewski, Lukasz; Godzik, Adam; Elsliger, Marc; Wilson, Ian A; Wüthrich, Kurt

2016-11-01

For more than a decade, the Joint Center for Structural Genomics (JCSG; www.jcsg.org) worked toward increased three-dimensional structure coverage of the protein universe. This coordinated quest was one of the main goals of the four high-throughput (HT) structure determination centers of the Protein Structure Initiative (PSI; www.nigms.nih.gov/Research/specificareas/PSI). To achieve the goals of the PSI, the JCSG made use of the complementarity of structure determination by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy to increase and diversify the range of targets entering the HT structure determination pipeline. The overall strategy, for both techniques, was to determine atomic resolution structures for representatives of large protein families, as defined by the Pfam database, which had no structural coverage and could make significant contributions to biological and biomedical research. Furthermore, the experimental structures could be leveraged by homology modeling to further expand the structural coverage of the protein universe and increase biological insights. Here, we describe what could be achieved by this structural genomics approach, using as an illustration the contributions from 20 NMR structure determinations out of a total of 98 JCSG NMR structures, which were selected because they are the first three-dimensional structure representations of the respective Pfam protein families. The information from this small sample is representative for the overall results from crystal and NMR structure determination in the JCSG. There are five new folds, which were classified as domains of unknown functions (DUF), three of the proteins could be functionally annotated based on three-dimensional structure similarity with previously characterized proteins, and 12 proteins showed only limited similarity with previous deposits in the Protein Data Bank (PDB) and were classified as DUFs. © 2016 Federation of European Biochemical Societies.

Management of the aging of critical safety-related concrete structures in light-water reactor plants

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

Naus, D.J.; Oland, C.B.; Arndt, E.G.

1990-01-01

The Structural Aging Program has the overall objective of providing the USNRC with an improved basis for evaluating nuclear power plant safety-related structures for continued service. The program consists of a management task and three technical tasks: materials property data base, structural component assessment/repair technology, and quantitative methodology for continued-service determinations. Objectives, accomplishments, and planned activities under each of these tasks are presented. Major program accomplishments include development of a materials property data base for structural materials as well as an aging assessment methodology for concrete structures in nuclear power plants. Furthermore, a review and assessment of inservice inspection techniquesmore » for concrete materials and structures has been complete, and work on development of a methodology which can be used for performing current as well as reliability-based future condition assessment of concrete structures is well under way. 43 refs., 3 tabs.« less

Structural Analysis of Chemokine Receptor–Ligand Interactions

PubMed Central

2017-01-01

This review focuses on the construction and application of structural chemokine receptor models for the elucidation of molecular determinants of chemokine receptor modulation and the structure-based discovery and design of chemokine receptor ligands. A comparative analysis of ligand binding pockets in chemokine receptors is presented, including a detailed description of the CXCR4, CCR2, CCR5, CCR9, and US28 X-ray structures, and their implication for modeling molecular interactions of chemokine receptors with small-molecule ligands, peptide ligands, and large antibodies and chemokines. These studies demonstrate how the integration of new structural information on chemokine receptors with extensive structure–activity relationship and site-directed mutagenesis data facilitates the prediction of the structure of chemokine receptor–ligand complexes that have not been crystallized. Finally, a review of structure-based ligand discovery and design studies based on chemokine receptor crystal structures and homology models illustrates the possibilities and challenges to find novel ligands for chemokine receptors. PMID:28165741

Transfer Learning to Accelerate Interface Structure Searches

NASA Astrophysics Data System (ADS)

Oda, Hiromi; Kiyohara, Shin; Tsuda, Koji; Mizoguchi, Teruyasu

2017-12-01

Interfaces have atomic structures that are significantly different from those in the bulk, and play crucial roles in material properties. The central structures at the interfaces that provide properties have been extensively investigated. However, determination of even one interface structure requires searching for the stable configuration among many thousands of candidates. Here, a powerful combination of machine learning techniques based on kriging and transfer learning (TL) is proposed as a method for unveiling the interface structures. Using the kriging+TL method, thirty-three grain boundaries were systematically determined from 1,650,660 candidates in only 462 calculations, representing an increase in efficiency over conventional all-candidate calculation methods, by a factor of approximately 3,600.

Structural characterisation of some vanillic Mannich bases: Experimental and theoretical study

NASA Astrophysics Data System (ADS)

Petrović, Vladimir P.; Simijonović, Dušica; Novaković, Sladjana B.; Bogdanović, Goran A.; Marković, Svetlana; Petrović, Zorica D.

2015-10-01

In this paper, synthesis and structural determination of 2-[1-(N-4-fluorophenylamino)-1-(4-hydroxy-3-methoxyphenyl)]methylcyclohexanone (MB-F) is presented. To determine the structure of this new compound, IR and NMR spectral characterisation was performed experimentally and theoretically. Simulation of spectral data was carried out using three functionals: B3LYP, B3LYP-D2, and M06-2X. The results obtained for MB-F were compared to those attained for similar, known compound 2-[1-(N-phenylamino)-1-(4-hydroxy-3-methoxyphenyl)]methylcyclohexanone (MB-H), whose crystal structure is presented here. Taking into account all experimental and theoretical findings, the structure of MB-F was proposed.

Mechanical properties and the electronic structure of transition of metal alloys

NASA Technical Reports Server (NTRS)

Arsenault, R. J.; Drew, H. D.

1977-01-01

This interdiscipline research program was undertaken in an effort to investigate the relationship between the mechanical strength of Mo based alloys with their electronic structure. Electronic properties of these alloys were examined through optical studies, and the classical solid solution strengthening mechanisms were considered, based on size and molecular differences to determine if these mechanisms could explain the hardness data.

Mobility power flow analysis of an L-shaped plate structure subjected to distributed loading

NASA Technical Reports Server (NTRS)

Cuschieri, J. M.; Cimmerman, B.

1990-01-01

An analytical investigation based in the Mobility Power Flow (MPF) method is presented for the determination of the vibrational response and power flow for two coupled flat plate structures in an L-shaped configuration, subjected to distributed excitation. The principle of the MPF method consists of dividing the global structure into a series of subsystems coupled together using mobility functions. Each separate subsystem is analyzed independently to determine the structural mobility functions for the junction and excitation locations. The mobility functions, together with the characteristics of the junction between the subsystems, are then used to determine the response of the global structure and the MPF. In the considered coupled plate structure, MPF expressions are derived for distributed mechanical excitation which is independent of the structure response. However using a similar approach with some modifications excitation by an acoustic plane wave can be considered. Some modifications are required to deal with the latter case are necessary because the forces (acoustic pressure) acting on the structure are dependent on the response of the structure due to the presence of the scattered pressure.

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

Wu, Hong; Zeng, Hong; Lam, Robert

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in theMLH1gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. Lastly, the structure shares a high degree of similarity with previously determined prokaryoticMLH1homologs; however, this structure affords a more accurate platform for the classification ofMLH1variants.

Unusual monosaccharides: components of O-antigenic polysaccharides of microorganisms

NASA Astrophysics Data System (ADS)

Kochetkov, Nikolai K.

1996-09-01

The data on new monosaccharides detected in O-antigenic polysaccharides of Gram-negative bacteria have been surveyed. The results of isolation and structure determination of these unusual monosaccharides have been arranged and described systematically. The NMR spectroscopy techniques are shown to be promising for the O-antigenic polysaccharides structure determination. The information about fine structure of monosaccharides which constitute the base of important class of microbial polysaccharides, is of great significance for applied studies, first of all, the design and synthesis of biologically active substances. The bibliography includes 216 references.

Phenetic Comparison of Prokaryotic Genomes Using k-mers

PubMed Central

Déraspe, Maxime; Raymond, Frédéric; Boisvert, Sébastien; Culley, Alexander; Roy, Paul H.; Laviolette, François; Corbeil, Jacques

2017-01-01

Abstract Bacterial genomics studies are getting more extensive and complex, requiring new ways to envision analyses. Using the Ray Surveyor software, we demonstrate that comparison of genomes based on their k-mer content allows reconstruction of phenetic trees without the need of prior data curation, such as core genome alignment of a species. We validated the methodology using simulated genomes and previously published phylogenomic studies of Streptococcus pneumoniae and Pseudomonas aeruginosa. We also investigated the relationship of specific genetic determinants with bacterial population structures. By comparing clusters from the complete genomic content of a genome population with clusters from specific functional categories of genes, we can determine how the population structures are correlated. Indeed, the strain clustering based on a subset of k-mers allows determination of its similarity with the whole genome clusters. We also applied this methodology on 42 species of bacteria to determine the correlational significance of five important bacterial genomic characteristics. For example, intrinsic resistance is more important in P. aeruginosa than in S. pneumoniae, and the former has increased correlation of its population structure with antibiotic resistance genes. The global view of the pangenome of bacteria also demonstrated the taxa-dependent interaction of population structure with antibiotic resistance, bacteriophage, plasmid, and mobile element k-mer data sets. PMID:28957508

40 CFR 745.86 - Recordkeeping and reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Residential... certifying that a determination had been made that lead-based paint was not present on the components...

40 CFR 745.86 - Recordkeeping and reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Residential... certifying that a determination had been made that lead-based paint was not present on the components...

40 CFR 745.86 - Recordkeeping and reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Residential... certifying that a determination had been made that lead-based paint was not present on the components...

40 CFR 745.86 - Recordkeeping and reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SUBSTANCES CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Residential... certifying that a determination had been made that lead-based paint was not present on the components...

Explaining gender differences in ill-health in South Korea: the roles of socio-structural, psychosocial, and behavioral factors.

PubMed

Chun, Heeran; Khang, Young-Ho; Kim, Il-Ho; Cho, Sung-Il

2008-09-01

This study examines and explains the gender disparity in health despite rapid modernization in South Korea where the social structure is still based on traditional gender relations. A nationally representative sample of 2897 men and 3286 women aged 25-64 from the 2001 Korean National Health and Nutrition Examination Survey was analyzed. Health indicators included self rated health and chronic disease. Age-adjusted prevalence was computed according to a gender and odds ratios (OR) derived from logistic regression. Percentage changes in OR by inclusion of determinant variables (socio-structural, psychosocial, and behavioral) into the base logistic regression model were used to estimate the contributions to the gender gap in two morbidity measures. Results showed a substantial female excess in ill-health in both measures, revealing an increasing disparity in the older age group. Group-specific age-adjusted prevalence of ill-health showed an inverse relationship to socioeconomic position. When adjusting for each determinant, employment status, education, and depression contributed the greatest to the gender gap. After adjusting for all suggested determinants, 78% for self rated health and 86% for chronic disease in excess OR could be explained. After stratifying for age, the full model provided a complete explanation for the female excess in chronic illness, but for self rated health a female excess was still evident for the younger age group. Socio-structural factors played a crucial role in accounting for female excess in ill-health. This result calls for greater attention to gender-based health inequality stemming from socio-structural determinants in South Korea. Cross-cultural validation studies are suggested for further discussion of the link between changing gender relations and the gender health gap in morbidity in diverse settings.

Construction patterns of birds' nests provide insight into nest-building behaviours.

PubMed

Biddle, Lucia; Goodman, Adrian M; Deeming, D Charles

2017-01-01

Previous studies have suggested that birds and mammals select materials needed for nest building based on their thermal or structural properties, although the amounts or properties of the materials used have been recorded for only a very small number of species. Some of the behaviours underlying the construction of nests can be indirectly determined by careful deconstruction of the structure and measurement of the biomechanical properties of the materials used. Here we examined this idea in an investigation of Bullfinch ( Pyrrhula pyrrhula ) nests as a model for open-nesting songbird species that construct a "twig" nest, and tested the hypothesis that materials in different parts of nests serve different functions. The quantities of materials present in the nest base, sides and cup were recorded before structural analysis. Structural analysis showed that the base of the outer nests were composed of significantly thicker, stronger and more rigid materials compared to the side walls, which in turn were significantly thicker, stronger and more rigid than materials used in the cup. These results suggest that the placement of particular materials in nests may not be random, but further work is required to determine if the final structure of a nest accurately reflects the construction process.

Racemic & quasi-racemic protein crystallography enabled by chemical protein synthesis.

PubMed

Kent, Stephen Bh

2018-04-04

A racemic protein mixture can be used to form centrosymmetric crystals for structure determination by X-ray diffraction. Both the unnatural d-protein and the corresponding natural l-protein are made by total chemical synthesis based on native chemical ligation-chemoselective condensation of unprotected synthetic peptide segments. Racemic protein crystallography is important for structure determination of the many natural protein molecules that are refractory to crystallization. Racemic mixtures facilitate the crystallization of recalcitrant proteins, and give diffraction-quality crystals. Quasi-racemic crystallization, using a single d-protein molecule, can facilitate the determination of the structures of a series of l-protein analog molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

Phospholipid component volumes: determination and application to bilayer structure calculations.

PubMed

Armen, R S; Uitto, O D; Feller, S E

1998-08-01

We present a new method for the determination of bilayer structure based on a combination of computational studies and laboratory experiments. From molecular dynamics simulations, the volumes of submolecular fragments of saturated and unsaturated phosphatidylcholines in the liquid crystalline state have been extracted with a precision not available experimentally. Constancy of component volumes, both among different lipids and as a function of membrane position for a given lipid, have been examined. The component volumes were then incorporated into the liquid crystallographic method described by Wiener and White (1992. Biophys. J. 61:434-447, and references therein) for determining the structure of a fluid-phase dioleoylphosphatidylcholine bilayer from x-ray and neutron diffraction experiments.

Phospholipid component volumes: determination and application to bilayer structure calculations.

PubMed Central

Armen, R S; Uitto, O D; Feller, S E

1998-01-01

We present a new method for the determination of bilayer structure based on a combination of computational studies and laboratory experiments. From molecular dynamics simulations, the volumes of submolecular fragments of saturated and unsaturated phosphatidylcholines in the liquid crystalline state have been extracted with a precision not available experimentally. Constancy of component volumes, both among different lipids and as a function of membrane position for a given lipid, have been examined. The component volumes were then incorporated into the liquid crystallographic method described by Wiener and White (1992. Biophys. J. 61:434-447, and references therein) for determining the structure of a fluid-phase dioleoylphosphatidylcholine bilayer from x-ray and neutron diffraction experiments. PMID:9675175

Structural classification of CDR-H3 revisited: a lesson in antibody modeling.

PubMed

Kuroda, Daisuke; Shirai, Hiroki; Kobori, Masato; Nakamura, Haruki

2008-11-15

Among the six complementarity-determining regions (CDRs) in the variable domains of an antibody, the third CDR of the heavy chain (CDR-H3), which lies in the center of the antigen-binding site, plays a particularly important role in antigen recognition. CDR-H3 shows significant variability in its length, sequence, and structure. Although difficult, model building of this segment is the most critical step in antibody modeling. Since our first proposal of the "H3-rules," which classify CDR-H3 structure based on amino acid sequence, the number of experimentally determined antibody structures has increased. Here, we revise these H3-rules and propose an improved classification scheme for CDR-H3 structure modeling. In addition, we determine the common features of CDR-H3 in antibody drugs as well as discuss the concept of "antibody druggability," which can be applied as an indicator of antibody evaluation during drug discovery.

Mixing and Matching Detergents for Membrane Protein NMR Structure Determination

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

Columbus, Linda; Lipfert, Jan; Jambunathan, Kalyani

2009-10-21

One major obstacle to membrane protein structure determination is the selection of a detergent micelle that mimics the native lipid bilayer. Currently, detergents are selected by exhaustive screening because the effects of protein-detergent interactions on protein structure are poorly understood. In this study, the structure and dynamics of an integral membrane protein in different detergents is investigated by nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy and small-angle X-ray scattering (SAXS). The results suggest that matching of the micelle dimensions to the protein's hydrophobic surface avoids exchange processes that reduce the completeness of the NMR observations. Based onmore » these dimensions, several mixed micelles were designed that improved the completeness of NMR observations. These findings provide a basis for the rational design of mixed micelles that may advance membrane protein structure determination by NMR.« less

Covering complete proteomes with X-ray structures: A current snapshot

DOE PAGES

Mizianty, Marcin J.; Fan, Xiao; Yan, Jing; ...

2014-10-23

Structural genomics programs have developed and applied structure-determination pipelines to a wide range of protein targets, facilitating the visualization of macromolecular interactions and the understanding of their molecular and biochemical functions. The fundamental question of whether three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography is investigated. A first-of-its-kind large-scale analysis of crystallization propensity for all proteins encoded in 1953 fully sequenced genomes was performed. It is shown that current X-ray crystallographic knowhow combined with homology modeling can provide structures for 25% of modeling families (protein clusters for which structural models can be obtainedmore » through homology modeling), with at least one structural model produced for each Gene Ontology functional annotation. The coverage varies between superkingdoms, with 19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of viruses following the coverage values of their hosts. It is shown that the crystallization propensities of proteomes from the taxonomic superkingdoms are distinct. The use of knowledge-based target selection is shown to substantially increase the ability to produce X-ray structures. It is demonstrated that the human proteome has one of the highest attainable coverage values among eukaryotes, and GPCR membrane proteins suitable for X-ray structure determination were determined.« less

Linear-hall sensor based force detecting unit for lower limb exoskeleton

NASA Astrophysics Data System (ADS)

Li, Hongwu; Zhu, Yanhe; Zhao, Jie; Wang, Tianshuo; Zhang, Zongwei

2018-04-01

This paper describes a knee-joint human-machine interaction force sensor for lower-limb force-assistance exoskeleton. The structure is designed based on hall sensor and series elastic actuator (SEA) structure. The work we have done includes the structure design, the parameter determination and dynamic simulation. By converting the force signal into macro displacement and output voltage, we completed the measurement of man-machine interaction force. And it is proved by experiments that the design is simple, stable and low-cost.

Role of structural barriers for carotenoid bioaccessibility upon high pressure homogenization.

PubMed

Palmero, Paola; Panozzo, Agnese; Colle, Ines; Chigwedere, Claire; Hendrickx, Marc; Van Loey, Ann

2016-05-15

A specific approach to investigate the effect of high pressure homogenization on the carotenoid bioaccessibility in tomato-based products was developed. Six different tomato-based model systems were reconstituted in order to target the specific role of the natural structural barriers (chromoplast substructure/cell wall) and of the phases (soluble/insoluble) in determining the carotenoid bioaccessibility and viscosity changes upon high pressure homogenization. Results indicated that in the absence of natural structural barriers (carotenoid enriched oil), the soluble and insoluble phases determined the carotenoid bioaccessibility upon processing whereas, in their presence, these barriers governed the bioaccessibility. Furthermore, it was shown that the increment of the viscosity upon high pressure homogenization is determined by the presence of insoluble phase, however, this result was related to the initial ratio of the soluble:insoluble phases in the system. In addition, no relationship between the changes in viscosity and carotenoid bioaccessibility upon high pressure homogenization was found. Copyright © 2015 Elsevier Ltd. All rights reserved.

The special features of the crystal structure and properties of oxides with mixed conductivity based on lanthanum gallate

NASA Astrophysics Data System (ADS)

Politova, E. D.; Ivanov, S. A.; Kaleva, G. M.; Mosunov, A. V.; Rusakov, V. S.

2008-10-01

The paper presents a review of works on the synthesis, structural composition effects, phase transitions, and electrical conductivity properties of multicomponent solid solutions based on heterosubstituted lanthanum gallate (La,A)(Ga,M)O3 - y . High-temperature phase transitions and structural and charge ordering effects were studied. The presence of iron cations in different valence states was proved; the relative contents of these cations depended on the x parameter and nonstoichiometry parameter y of the base composition. For M = Fe, antiferromagnetic ordering was observed; its temperature interval was determined by the concentration of iron cations in the high-spin state. The total conductivity was found to increase as the concentration of transition metal cations grew because of an increase in the electronic conductivity component. The data on structural parameters and dc and ac conductivity substantiated the conclusion that the highest ionic conductivity and permeability to oxygen were characteristic of iron-containing oxides. The results obtained are evidence that crystal chemical factors play a determining role in the formation of the ion-conducting properties of anion-deficient perovskite-like oxides.

Structure and properties of microporous titanosilicate determined by first-principles calculations

NASA Astrophysics Data System (ADS)

Ching, W. Y.; Xu, Yong-Nian; Gu, Zong-Quan

1996-12-01

The structure of EST-10, a member of synthetic microporous titanosilicates, was recently determined by an ingenious combination of experimental and simulational techniques. However, the locations of the alkali atoms in the framework remain elusive and its electronic structure is totally unknown. Based on first-principles local density calculations, the possible locations of the alkali atoms are identified and its electronic structure and bonding fully elucidated. ETS-10 is a semiconductor with a direct band gap of 2.33 eV. The Na atoms are likely to locate inside the seven-member ring pore adjacent to the one-dimensional Ti-O-Ti-O- chain.

Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

DOE PAGES

Wu, Hong; Zeng, Hong; Lam, Robert; ...

2015-08-01

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in theMLH1gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. Lastly, the structure shares a high degree of similarity with previously determined prokaryoticMLH1homologs; however, this structure affords a more accurate platform for the classification ofMLH1variants.

Structure of an E. coli integral membrane sulfurtransferase and its structural transition upon SCN− binding defined by EPR-based hybrid method

PubMed Central

Ling, Shenglong; Wang, Wei; Yu, Lu; Peng, Junhui; Cai, Xiaoying; Xiong, Ying; Hayati, Zahra; Zhang, Longhua; Zhang, Zhiyong; Song, Likai; Tian, Changlin

2016-01-01

Electron paramagnetic resonance (EPR)-based hybrid experimental and computational approaches were applied to determine the structure of a full-length E. coli integral membrane sulfurtransferase, dimeric YgaP, and its structural and dynamic changes upon ligand binding. The solution NMR structures of the YgaP transmembrane domain (TMD) and cytosolic catalytic rhodanese domain were reported recently, but the tertiary fold of full-length YgaP was not yet available. Here, systematic site-specific EPR analysis defined a helix-loop-helix secondary structure of the YagP-TMD monomers using mobility, accessibility and membrane immersion measurements. The tertiary folds of dimeric YgaP-TMD and full-length YgaP in detergent micelles were determined through inter- and intra-monomer distance mapping and rigid-body computation. Further EPR analysis demonstrated the tight packing of the two YgaP second transmembrane helices upon binding of the catalytic product SCN−, which provides insight into the thiocyanate exportation mechanism of YgaP in the E. coli membrane. PMID:26817826

High-Resolution Crystal Structure of a Silver(I)-RNA Hybrid Duplex Containing Watson-Crick-like C-Silver(I)-C Metallo-Base Pairs.

PubMed

Kondo, Jiro; Tada, Yoshinari; Dairaku, Takenori; Saneyoshi, Hisao; Okamoto, Itaru; Tanaka, Yoshiyuki; Ono, Akira

2015-11-02

Metallo-base pairs have been extensively studied for applications in nucleic acid-based nanodevices and genetic code expansion. Metallo-base pairs composed of natural nucleobases are attractive because nanodevices containing natural metallo-base pairs can be easily prepared from commercially available sources. Previously, we have reported a crystal structure of a DNA duplex containing T-Hg(II)-T base pairs. Herein, we have determined a high-resolution crystal structure of the second natural metallo-base pair between pyrimidine bases C-Ag(I)-C formed in an RNA duplex. One Ag(I) occupies the center between two cytosines and forms a C-Ag(I)-C base pair through N3-Ag(I)-N3 linear coordination. The C-Ag(I)-C base pair formation does not disturb the standard A-form conformation of RNA. Since the C-Ag(I)-C base pair is structurally similar to the canonical Watson-Crick base pairs, it can be a useful building block for structure-based design and fabrication of nucleic acid-based nanodevices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mobility power flow analysis of an L-shaped plate structure subjected to acoustic excitation

NASA Technical Reports Server (NTRS)

Cuschieri, J. M.

1989-01-01

An analytical investigation based on the Mobility Power Flow method is presented for the determination of the vibrational response and power flow for two coupled flat plate structures in an L-shaped configuration, subjected to acoustical excitation. The principle of the mobility power flow method consists of dividing the global structure into a series of subsystems coupled together using mobility functions. Each separate subsystem is analyzed independently to determine the structural mobility functions for the junction and excitation locations. The mobility functions, together with the characteristics of the junction between the subsystems, are then used to determine the response of the global structure and the power flow. In the coupled plate structure considered here, mobility power flow expressions are derived for excitation by an incident acoustic plane wave. In this case, the forces (acoustic pressures) acting on the structure are dependent on the response of the structure because of the scattered pressure component. The interaction between the structure and the fluid leads to the derivation of a corrected mode shape for the plates' normal surface velocity and also for the structure mobility functions. The determination of the scattered pressure components in the expressions for the power flow represents an additional component in the power flow balance for the source plate and the receiver plate. This component represents the radiated acoustical power from the plate structure.

nextPARS: parallel probing of RNA structures in Illumina

PubMed Central

Saus, Ester; Willis, Jesse R.; Pryszcz, Leszek P.; Hafez, Ahmed; Llorens, Carlos; Himmelbauer, Heinz

2018-01-01

RNA molecules play important roles in virtually every cellular process. These functions are often mediated through the adoption of specific structures that enable RNAs to interact with other molecules. Thus, determining the secondary structures of RNAs is central to understanding their function and evolution. In recent years several sequencing-based approaches have been developed that allow probing structural features of thousands of RNA molecules present in a sample. Here, we describe nextPARS, a novel Illumina-based implementation of in vitro parallel probing of RNA structures. Our approach achieves comparable accuracy to previous implementations, while enabling higher throughput and sample multiplexing. PMID:29358234

TOPSAN: a dynamic web database for structural genomics.

PubMed

Ellrott, Kyle; Zmasek, Christian M; Weekes, Dana; Sri Krishna, S; Bakolitsa, Constantina; Godzik, Adam; Wooley, John

2011-01-01

The Open Protein Structure Annotation Network (TOPSAN) is a web-based collaboration platform for exploring and annotating structures determined by structural genomics efforts. Characterization of those structures presents a challenge since the majority of the proteins themselves have not yet been characterized. Responding to this challenge, the TOPSAN platform facilitates collaborative annotation and investigation via a user-friendly web-based interface pre-populated with automatically generated information. Semantic web technologies expand and enrich TOPSAN's content through links to larger sets of related databases, and thus, enable data integration from disparate sources and data mining via conventional query languages. TOPSAN can be found at http://www.topsan.org.

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit

PubMed Central

Moen, Spencer O.; Smith, Eric; Raymond, Amy C.; Fairman, James W.; Stewart, Lance J.; Staker, Bart L.; Begley, Darren W.; Edwards, Thomas E.; Lorimer, Donald D.

2013-01-01

Pandemic outbreaks of highly virulent influenza strains can cause widespread morbidity and mortality in human populations worldwide. In the United States alone, an average of 41,400 deaths and 1.86 million hospitalizations are caused by influenza virus infection each year 1. Point mutations in the polymerase basic protein 2 subunit (PB2) have been linked to the adaptation of the viral infection in humans 2. Findings from such studies have revealed the biological significance of PB2 as a virulence factor, thus highlighting its potential as an antiviral drug target. The structural genomics program put forth by the National Institute of Allergy and Infectious Disease (NIAID) provides funding to Emerald Bio and three other Pacific Northwest institutions that together make up the Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is dedicated to providing the scientific community with three-dimensional protein structures of NIAID category A-C pathogens. Making such structural information available to the scientific community serves to accelerate structure-based drug design. Structure-based drug design plays an important role in drug development. Pursuing multiple targets in parallel greatly increases the chance of success for new lead discovery by targeting a pathway or an entire protein family. Emerald Bio has developed a high-throughput, multi-target parallel processing pipeline (MTPP) for gene-to-structure determination to support the consortium. Here we describe the protocols used to determine the structure of the PB2 subunit from four different influenza A strains. PMID:23851357

Probabilistic Structural Evaluation of Uncertainties in Radiator Sandwich Panel Design

NASA Technical Reports Server (NTRS)

Kuguoglu, Latife; Ludwiczak, Damian

2006-01-01

The Jupiter Icy Moons Orbiter (JIMO) Space System is part of the NASA's Prometheus Program. As part of the JIMO engineering team at NASA Glenn Research Center, the structural design of the JIMO Heat Rejection Subsystem (HRS) is evaluated. An initial goal of this study was to perform sensitivity analyses to determine the relative importance of the input variables on the structural responses of the radiator panel. The desire was to let the sensitivity analysis information identify the important parameters. The probabilistic analysis methods illustrated here support this objective. The probabilistic structural performance evaluation of a HRS radiator sandwich panel was performed. The radiator panel structural performance was assessed in the presence of uncertainties in the loading, fabrication process variables, and material properties. The stress and displacement contours of the deterministic structural analysis at mean probability was performed and results presented. It is followed by a probabilistic evaluation to determine the effect of the primitive variables on the radiator panel structural performance. Based on uncertainties in material properties, structural geometry and loading, the results of the displacement and stress analysis are used as an input file for the probabilistic analysis of the panel. The sensitivity of the structural responses, such as maximum displacement and maximum tensile and compressive stresses of the facesheet in x and y directions and maximum VonMises stresses of the tube, to the loading and design variables is determined under the boundary condition where all edges of the radiator panel are pinned. Based on this study, design critical material and geometric parameters of the considered sandwich panel are identified.

ARPES investigations of parent compounds of 122 Fe-based superconductors and their 3d transition metal cousins

NASA Astrophysics Data System (ADS)

Richard, Pierre; Zhang, W.-L.; Wu, S.-F.; van Roekeghem, A.; Zhang, P.; Miao, H.; Qian, T.; Nie, S.-M.; Chen, G.-F.; Ding, H.; Xu, N.; Biermann, S.; Capan, C.; Fisk, Z.; Saparov, B. I.; Sefat, A. S.

2015-03-01

It is widely believed that the key ingredients for high-temperature superconductivity are already present in the non-superconducting parent compounds. With its ability to probe the single-particle electronic structure directly in the momentum space, ARPES is a very powerful tool to determine which parameters of the electronic structure are possibly relevant for promoting superconductivity. Here we report ARPES studies on the parent compounds of the 122 family of Fe-based superconductors and their 3 d transition metal pnictide cousins. In particular, we show that the Fe-compound exhibits the largest electronic correlations, possibly a determining factor for unconventional superconductivity.

Analysis of factors affecting satisfaction level on problem based learning approach using structural equation modeling

NASA Astrophysics Data System (ADS)

Hussain, Nur Farahin Mee; Zahid, Zalina

2014-12-01

Nowadays, in the job market demand, graduates are expected not only to have higher performance in academic but they must also be excellent in soft skill. Problem-Based Learning (PBL) has a number of distinct advantages as a learning method as it can deliver graduates that will be highly prized by industry. This study attempts to determine the satisfaction level of engineering students on the PBL Approach and to evaluate their determinant factors. The Structural Equation Modeling (SEM) was used to investigate how the factors of Good Teaching Scale, Clear Goals, Student Assessment and Levels of Workload affected the student satisfaction towards PBL approach.

Solution structure of a DNA decamer containing the antiviral drug ganciclovir: combined use of NMR, restrained molecular dynamics, and full relaxation matrix refinement.

PubMed

Foti, M; Marshalko, S; Schurter, E; Kumar, S; Beardsley, G P; Schweitzer, B I

1997-05-06

The nucleoside analog 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir, DHPG) is an antiviral drug that is used in the treatment of a variety of herpes viruses in immunocompromised patients and in a gene therapy protocol that has shown promising activity for the treatment of cancer. To probe the structural effects of ganciclovir when incorporated into DNA, we determined and compared the solution structure of a modified ganciclovir-containing decamer duplex [d(CTG)(ganciclovir)d(ATCCAG)]2 and a control duplex d[(CTGGATCCAG)]2 using nuclear magnetic resonance techniques. 1H and 31P resonances in both duplexes were assigned using a combination of 2-D 1H and 31P NMR experiments. Proton-proton distances determined from NOESY data and dihedral angles determined from DQF-COSY data were used in restrained molecular dynamics simulations starting from canonical A- and B-form DNA models. Both the control and ganciclovir sets of simulations converged to B-type structures. These structures were subjected to full relaxation matrix refinement to produce final structures that were in excellent agreement with the observed NOE intensities. Examination of the final ganciclovir-containing structures reveals that the base of the ganciclovir residue is hydrogen bonded to its complementary dC and is stacked in the helix; in fact, the base of ganciclovir exhibits increased stacking with the 5' base relative to the control. Interestingly, some of the most significant distortions in the structures occur 3' to the lesion site, including a noticeable kink in the sugar-phosphate backbone at this position. Further examination reveals that the backbone conformation, sugar pucker, and glycosidic torsion angle of the residue 3' to the lesion site all indicate an A-type conformation at this position. A possible correlation of these structural findings with results obtained from earlier biochemical studies will be discussed.

Eukaryotic major facilitator superfamily transporter modeling based on the prokaryotic GlpT crystal structure.

PubMed

Lemieux, M Joanne

2007-01-01

The major facilitator superfamily (MFS) of transporters represents the largest family of secondary active transporters and has a diverse range of substrates. With structural information for four MFS transporters, we can see a strong structural commonality suggesting, as predicted, a common architecture for MFS transporters. The rate for crystal structure determination of MFS transporters is slow, making modeling of both prokaryotic and eukaryotic transporters more enticing. In this review, models of eukaryotic transporters Glut1, G6PT, OCT1, OCT2 and Pho84, based on the crystal structures of the prokaryotic GlpT, based on the crystal structure of LacY are discussed. The techniques used to generate the different models are compared. In addition, the validity of these models and the strategy of using prokaryotic crystal structures to model eukaryotic proteins are discussed. For comparison, E. coli GlpT was modeled based on the E. coli LacY structure and compared to the crystal structure of GlpT demonstrating that experimental evidence is essential for accurate modeling of membrane proteins.

Dimensions of vegetable parenting practices among preschoolers

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine the factor structure of 31 effective and ineffective vegetable parenting practices used by parents of preschool children based on three theoretically proposed factors: responsiveness, control, and structure. The methods employed included both corrected it...

Observations of the global structure of the stratosphere and mesosphere with sounding rockets and with remote sensing techniques from satellites

NASA Technical Reports Server (NTRS)

Heath, D. F.; Hilsenrath, E.; Krueger, A. J.; Nordberg, W.; Prabhakara, C.; Theon, J. S.

1972-01-01

Brief descriptions are given of the techniques involved in determining the global structure of the mesosphere and stratosphere based on sounding rocket observations and satellite remotely sensed measurements.

Model-based Approaches for the Determination of Lipid Bilayer Structure from Small-Angle Neutron and X-ray Scattering Data

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

Heberle, Frederick A; Pan, Jianjun; Standaert, Robert F

2012-01-01

Some of our recent work has resulted in the detailed structures of fully hydrated, fluid phase phosphatidylcholine (PC) and phosphatidylglycerol (PG) bilayers. These structures were obtained from the joint refinement of small-angle neutron and X-ray data using the scattering density profile (SDP) models developed by Ku erka et al. (Ku erka et al. 2012; Ku erka et al. 2008). In this review, we first discuss models for the standalone analysis of neutron or X-ray scattering data from bilayers, and assess the strengths and weaknesses inherent in these models. In particular, it is recognized that standalone data do not contain enoughmore » information to fully resolve the structure of inherently disordered fluid bilayers, and therefore may not provide a robust determination of bilayer structural parameters, including the much sought after area per lipid. We then discuss the development of matter density-based models (including the SDP model) that allow for the joint refinement of different contrast neutron and X-ray data sets, as well as the implementation of local volume conservation in the unit cell (i.e., ideal packing). Such models provide natural definitions of bilayer thicknesses (most importantly the hydrophobic and Luzzati thicknesses) in terms of Gibbs dividing surfaces, and thus allow for the robust determination of lipid areas through equivalent slab relationships between bilayer thickness and lipid volume. In the final section of this review, we discuss some of the significant findings/features pertaining to structures of PC and PG bilayers as determined from SDP model analyses.« less

NMR and computational methods applied to the 3- dimensional structure determination of DNA and ligand-DNA complexes in solution

NASA Astrophysics Data System (ADS)

Smith, Jarrod Anson

2D homonuclear 1H NMR methods and restrained molecular dynamics (rMD) calculations have been applied to determining the three-dimensional structures of DNA and minor groove-binding ligand-DNA complexes in solution. The structure of the DNA decamer sequence d(GCGTTAACGC)2 has been solved both with a distance-based rMD protocol and an NOE relaxation matrix backcalculation-based protocol in order to probe the relative merits of the different refinement methods. In addition, three minor groove binding ligand-DNA complexes have been examined. The solution structure of the oligosaccharide moiety of the antitumor DNA scission agent calicheamicin γ1I has been determined in complex with a decamer duplex containing its high affinity 5'-TCCT- 3' binding sequence. The structure of the complex reinforces the belief that the oligosaccharide moiety is responsible for the sequence selective minor-groove binding activity of the agent, and critical intermolecular contacts are revealed. The solution structures of both the (+) and (-) enantiomers of the minor groove binding DNA alkylating agent duocarmycin SA have been determined in covalent complex with the undecamer DNA duplex d(GACTAATTGTC).d(GAC AATTAGTC). The results support the proposal that the alkylation activity of the duocarmycin antitumor antibiotics is catalyzed by a binding-induced conformational change in the ligand which activates the cyclopropyl group for reaction with the DNA. Comparisons between the structures of the two enantiomers covalently bound to the same DNA sequence at the same 5'-AATTA-3 ' site have provided insight into the binding orientation and site selectivity, as well as the relative rates of reactivity of these two agents.

Structures-propulsion interactions and requirements. [large space structures

NASA Technical Reports Server (NTRS)

Coyner, J. V.

1982-01-01

The effects of low-thrust primary propulsion system characteristics on the mass, area, and orbit transfer characteristics of large space systems (LSS) were determined. Three general structural classes of LSS were considered, each with a broad range of diameters and nonstructural surface densities. While transferring the deployed structure from LEO and to GEO, an acceleration range of 0.02 to 0.1 g's was found to maximize deliverable payload based on structural mass impact. After propulsion system parametric analyses considering four propellant combinations produced values for available payload mass, length and volume, a thrust level range which maximizes deliverable LSS diameter was determined corresponding to a structure and propulsion vehicle. The engine start and/or shutdown thrust transients on the last orbit transfer (apogee) burn can impose transient loads which would be greater than the steady-state loads at the burnout acceleration. The effect of the engine thrust transients on the LSS was determined from the dynamic models upon which various engine ramps were imposed.

Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs

PubMed Central

2017-01-01

Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package. PMID:29107980

Computational approaches for identification of conserved/unique binding pockets in the A chain of ricin

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

Ecale Zhou, C L; Zemla, A T; Roe, D

2005-01-29

Specific and sensitive ligand-based protein detection assays that employ antibodies or small molecules such as peptides, aptamers, or other small molecules require that the corresponding surface region of the protein be accessible and that there be minimal cross-reactivity with non-target proteins. To reduce the time and cost of laboratory screening efforts for diagnostic reagents, we developed new methods for evaluating and selecting protein surface regions for ligand targeting. We devised combined structure- and sequence-based methods for identifying 3D epitopes and binding pockets on the surface of the A chain of ricin that are conserved with respect to a set ofmore » ricin A chains and unique with respect to other proteins. We (1) used structure alignment software to detect structural deviations and extracted from this analysis the residue-residue correspondence, (2) devised a method to compare corresponding residues across sets of ricin structures and structures of closely related proteins, (3) devised a sequence-based approach to determine residue infrequency in local sequence context, and (4) modified a pocket-finding algorithm to identify surface crevices in close proximity to residues determined to be conserved/unique based on our structure- and sequence-based methods. In applying this combined informatics approach to ricin A we identified a conserved/unique pocket in close proximity (but not overlapping) the active site that is suitable for bi-dentate ligand development. These methods are generally applicable to identification of surface epitopes and binding pockets for development of diagnostic reagents, therapeutics, and vaccines.« less

DNA Nanotubes for NMR Structure Determination of Membrane Proteins

PubMed Central

Bellot, Gaëtan; McClintock, Mark A.; Chou, James J; Shih, William M.

2013-01-01

Structure determination of integral membrane proteins by solution NMR represents one of the most important challenges of structural biology. A Residual-Dipolar-Coupling-based refinement approach can be used to solve the structure of membrane proteins up to 40 kDa in size, however, a weak-alignment medium that is detergent-resistant is required. Previously, availability of media suitable for weak alignment of membrane proteins was severely limited. We describe here a protocol for robust, large-scale synthesis of detergent-resistant DNA nanotubes that can be assembled into dilute liquid crystals for application as weak-alignment media in solution NMR structure determination of membrane proteins in detergent micelles. The DNA nanotubes are heterodimers of 400nm-long six-helix bundles each self-assembled from a M13-based p7308 scaffold strand and >170 short oligonucleotide staple strands. Compatibility with proteins bearing considerable positive charge as well as modulation of molecular alignment, towards collection of linearly independent restraints, can be introduced by reducing the negative charge of DNA nanotubes via counter ions and small DNA binding molecules. This detergent-resistant liquid-crystal media offers a number of properties conducive for membrane protein alignment, including high-yield production, thermal stability, buffer compatibility, and structural programmability. Production of sufficient nanotubes for 4–5 NMR experiments can be completed in one week by a single individual. PMID:23518667

3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships.

PubMed

Dhar, T G Murali; Shen, Zhongqi; Gu, Henry H; Chen, Ping; Norris, Derek; Watterson, Scott H; Ballentine, Shelley K; Fleener, Catherine A; Rouleau, Katherine A; Barrish, Joel C; Townsend, Robert; Hollenbaugh, Diane L; Iwanowicz, Edwin J

2003-10-20

A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SAR), derived from in vitro studies, for this new series of inhibitors is given.

Characterizing structural transitions using localized free energy landscape analysis.

PubMed

Banavali, Nilesh K; Mackerell, Alexander D

2009-01-01

Structural changes in molecules are frequently observed during biological processes like replication, transcription and translation. These structural changes can usually be traced to specific distortions in the backbones of the macromolecules involved. Quantitative energetic characterization of such distortions can greatly advance the atomic-level understanding of the dynamic character of these biological processes. Molecular dynamics simulations combined with a variation of the Weighted Histogram Analysis Method for potential of mean force determination are applied to characterize localized structural changes for the test case of cytosine (underlined) base flipping in a GTCAGCGCATGG DNA duplex. Free energy landscapes for backbone torsion and sugar pucker degrees of freedom in the DNA are used to understand their behavior in response to the base flipping perturbation. By simplifying the base flipping structural change into a two-state model, a free energy difference of upto 14 kcal/mol can be attributed to the flipped state relative to the stacked Watson-Crick base paired state. This two-state classification allows precise evaluation of the effect of base flipping on local backbone degrees of freedom. The calculated free energy landscapes of individual backbone and sugar degrees of freedom expectedly show the greatest change in the vicinity of the flipping base itself, but specific delocalized effects can be discerned upto four nucleotide positions away in both 5' and 3' directions. Free energy landscape analysis thus provides a quantitative method to pinpoint the determinants of structural change on the atomic scale and also delineate the extent of propagation of the perturbation along the molecule. In addition to nucleic acids, this methodology is anticipated to be useful for studying conformational changes in all macromolecules, including carbohydrates, lipids, and proteins.

Mobile communications satellite antenna flight experiment definition

NASA Technical Reports Server (NTRS)

Freeland, Robert E.

1987-01-01

Results of a NASA-sponsored study to determine the technical feasibility and cost of a Shuttle-based flight experiment specifically intended for the MSAT commercial user community are presented. The experiment will include demonstrations of technology in the areas of radio frequency, sensing and control, and structures. The results of the structural subsystem study summarized here include experiment objective and technical approach, experiment structural description, structure/environment interactions, structural characterization, thermal characterization, structural measurement system, and experiment functional description.

Improved in-cell structure determination of proteins at near-physiological concentration

PubMed Central

Ikeya, Teppei; Hanashima, Tomomi; Hosoya, Saori; Shimazaki, Manato; Ikeda, Shiro; Mishima, Masaki; Güntert, Peter; Ito, Yutaka

2016-01-01

Investigating three-dimensional (3D) structures of proteins in living cells by in-cell nuclear magnetic resonance (NMR) spectroscopy opens an avenue towards understanding the structural basis of their functions and physical properties under physiological conditions inside cells. In-cell NMR provides data at atomic resolution non-invasively, and has been used to detect protein-protein interactions, thermodynamics of protein stability, the behavior of intrinsically disordered proteins, etc. in cells. However, so far only a single de novo 3D protein structure could be determined based on data derived only from in-cell NMR. Here we introduce methods that enable in-cell NMR protein structure determination for a larger number of proteins at concentrations that approach physiological ones. The new methods comprise (1) advances in the processing of non-uniformly sampled NMR data, which reduces the measurement time for the intrinsically short-lived in-cell NMR samples, (2) automatic chemical shift assignment for obtaining an optimal resonance assignment, and (3) structure refinement with Bayesian inference, which makes it possible to calculate accurate 3D protein structures from sparse data sets of conformational restraints. As an example application we determined the structure of the B1 domain of protein G at about 250 μM concentration in living E. coli cells. PMID:27910948

High-throughput determination of RNA structure by proximity ligation.

PubMed

Ramani, Vijay; Qiu, Ruolan; Shendure, Jay

2015-09-01

We present an unbiased method to globally resolve RNA structures through pairwise contact measurements between interacting regions. RNA proximity ligation (RPL) uses proximity ligation of native RNA followed by deep sequencing to yield chimeric reads with ligation junctions in the vicinity of structurally proximate bases. We apply RPL in both baker's yeast (Saccharomyces cerevisiae) and human cells and generate contact probability maps for ribosomal and other abundant RNAs, including yeast snoRNAs, the RNA subunit of the signal recognition particle and the yeast U2 spliceosomal RNA homolog. RPL measurements correlate with established secondary structures for these RNA molecules, including stem-loop structures and long-range pseudoknots. We anticipate that RPL will complement the current repertoire of computational and experimental approaches in enabling the high-throughput determination of secondary and tertiary RNA structures.

Dynamic control of spin states in interacting magnetic elements

DOEpatents

Jain, Shikha; Novosad, Valentyn

2014-10-07

A method for the control of the magnetic states of interacting magnetic elements comprising providing a magnetic structure with a plurality of interacting magnetic elements. The magnetic structure comprises a plurality of magnetic states based on the state of each interacting magnetic element. The desired magnetic state of the magnetic structure is determined. The active resonance frequency and amplitude curve of the desired magnetic state is determined. Each magnetic element of the magnetic structure is then subjected to an alternating magnetic field or electrical current having a frequency and amplitude below the active resonance frequency and amplitude curve of said desired magnetic state and above the active resonance frequency and amplitude curve of the current state of the magnetic structure until the magnetic state of the magnetic structure is at the desired magnetic state.

NIAS-Server: Neighbors Influence of Amino acids and Secondary Structures in Proteins.

PubMed

Borguesan, Bruno; Inostroza-Ponta, Mario; Dorn, Márcio

2017-03-01

The exponential growth in the number of experimentally determined three-dimensional protein structures provide a new and relevant knowledge about the conformation of amino acids in proteins. Only a few of probability densities of amino acids are publicly available for use in structure validation and prediction methods. NIAS (Neighbors Influence of Amino acids and Secondary structures) is a web-based tool used to extract information about conformational preferences of amino acid residues and secondary structures in experimental-determined protein templates. This information is useful, for example, to characterize folds and local motifs in proteins, molecular folding, and can help the solution of complex problems such as protein structure prediction, protein design, among others. The NIAS-Server and supplementary data are available at http://sbcb.inf.ufrgs.br/nias .

Co-extinction in a host-parasite network: identifying key hosts for network stability.

PubMed

Dallas, Tad; Cornelius, Emily

2015-08-17

Parasites comprise a substantial portion of total biodiversity. Ultimately, this means that host extinction could result in many secondary extinctions of obligate parasites and potentially alter host-parasite network structure. Here, we examined a highly resolved fish-parasite network to determine key hosts responsible for maintaining parasite diversity and network structure (quantified here as nestedness and modularity). We evaluated four possible host extinction orders and compared the resulting co-extinction dynamics to random extinction simulations; including host removal based on estimated extinction risk, parasite species richness and host level contributions to nestedness and modularity. We found that all extinction orders, except the one based on realistic extinction risk, resulted in faster declines in parasite diversity and network structure relative to random biodiversity loss. Further, we determined species-level contributions to network structure were best predicted by parasite species richness and host family. Taken together, we demonstrate that a small proportion of hosts contribute substantially to network structure and that removal of these hosts results in rapid declines in parasite diversity and network structure. As network stability can potentially be inferred through measures of network structure, our findings may provide insight into species traits that confer stability.

RNA 3D Structure Modeling by Combination of Template-Based Method ModeRNA, Template-Free Folding with SimRNA, and Refinement with QRNAS.

PubMed

Piatkowski, Pawel; Kasprzak, Joanna M; Kumar, Deepak; Magnus, Marcin; Chojnowski, Grzegorz; Bujnicki, Janusz M

2016-01-01

RNA encompasses an essential part of all known forms of life. The functions of many RNA molecules are dependent on their ability to form complex three-dimensional (3D) structures. However, experimental determination of RNA 3D structures is laborious and challenging, and therefore, the majority of known RNAs remain structurally uncharacterized. To address this problem, computational structure prediction methods were developed that either utilize information derived from known structures of other RNA molecules (by way of template-based modeling) or attempt to simulate the physical process of RNA structure formation (by way of template-free modeling). All computational methods suffer from various limitations that make theoretical models less reliable than high-resolution experimentally determined structures. This chapter provides a protocol for computational modeling of RNA 3D structure that overcomes major limitations by combining two complementary approaches: template-based modeling that is capable of predicting global architectures based on similarity to other molecules but often fails to predict local unique features, and template-free modeling that can predict the local folding, but is limited to modeling the structure of relatively small molecules. Here, we combine the use of a template-based method ModeRNA with a template-free method SimRNA. ModeRNA requires a sequence alignment of the target RNA sequence to be modeled with a template of the known structure; it generates a model that predicts the structure of a conserved core and provides a starting point for modeling of variable regions. SimRNA can be used to fold small RNAs (<80 nt) without any additional structural information, and to refold parts of models for larger RNAs that have a correctly modeled core. ModeRNA can be either downloaded, compiled and run locally or run through a web interface at http://genesilico.pl/modernaserver/ . SimRNA is currently available to download for local use as a precompiled software package at http://genesilico.pl/software/stand-alone/simrna and as a web server at http://genesilico.pl/SimRNAweb . For model optimization we use QRNAS, available at http://genesilico.pl/qrnas .

PONDEROSA-C/S: client-server based software package for automated protein 3D structure determination.

PubMed

Lee, Woonghee; Stark, Jaime L; Markley, John L

2014-11-01

Peak-picking Of Noe Data Enabled by Restriction Of Shift Assignments-Client Server (PONDEROSA-C/S) builds on the original PONDEROSA software (Lee et al. in Bioinformatics 27:1727-1728. doi: 10.1093/bioinformatics/btr200, 2011) and includes improved features for structure calculation and refinement. PONDEROSA-C/S consists of three programs: Ponderosa Server, Ponderosa Client, and Ponderosa Analyzer. PONDEROSA-C/S takes as input the protein sequence, a list of assigned chemical shifts, and nuclear Overhauser data sets ((13)C- and/or (15)N-NOESY). The output is a set of assigned NOEs and 3D structural models for the protein. Ponderosa Analyzer supports the visualization, validation, and refinement of the results from Ponderosa Server. These tools enable semi-automated NMR-based structure determination of proteins in a rapid and robust fashion. We present examples showing the use of PONDEROSA-C/S in solving structures of four proteins: two that enable comparison with the original PONDEROSA package, and two from the Critical Assessment of automated Structure Determination by NMR (Rosato et al. in Nat Methods 6:625-626. doi: 10.1038/nmeth0909-625 , 2009) competition. The software package can be downloaded freely in binary format from http://pine.nmrfam.wisc.edu/download_packages.html. Registered users of the National Magnetic Resonance Facility at Madison can submit jobs to the PONDEROSA-C/S server at http://ponderosa.nmrfam.wisc.edu, where instructions, tutorials, and instructions can be found. Structures are normally returned within 1-2 days.

Detecting Structural Failures Via Acoustic Impulse Responses

NASA Technical Reports Server (NTRS)

Bayard, David S.; Joshi, Sanjay S.

1995-01-01

Advanced method of acoustic pulse reflectivity testing developed for use in determining sizes and locations of failures within structures. Used to detect breaks in electrical transmission lines, detect faults in optical fibers, and determine mechanical properties of materials. In method, structure vibrationally excited with acoustic pulse (a "ping") at one location and acoustic response measured at same or different location. Measured acoustic response digitized, then processed by finite-impulse-response (FIR) filtering algorithm unique to method and based on acoustic-wave-propagation and -reflection properties of structure. Offers several advantages: does not require training, does not require prior knowledge of mathematical model of acoustic response of structure, enables detection and localization of multiple failures, and yields data on extent of damage at each location.

Structure determination and total synthesis of a novel antibacterial substance, AB0022A, produced by a cellular slime mold.

PubMed

Sawada, T; Aono, M; Asakawa, S; Ito, A; Awano, K

2000-09-01

A novel antibacterial substance, AB0022A, was isolated from the cellular slime mold Dictyostelium purpureum K1001. It inhibited the growth of Gram-positive bacteria, and its MICs ranged from 0.39 to 50 microg/ml. Because AB0022A was a highly substituted aromatic compound, we could not determine its structure based on only its physico-chemical and spectral data. We therefore used a dehalogenated derivative from AB0022A and deduced that its structure was 1,9-dihydroxy-3,7-dimethoxy-2-hexanoyl-4,6,8-trichlorodibenzofuran . To confirm this structure, we synthesized the compound having the deduced structure. The synthetic compound was identical to naturally occurring AB0022A.

Towards a true protein movie: a perspective on the potential impact of the ensemble-based structure determination using exact NOEs.

PubMed

Vögeli, Beat; Orts, Julien; Strotz, Dean; Chi, Celestine; Minges, Martina; Wälti, Marielle Aulikki; Güntert, Peter; Riek, Roland

2014-04-01

Confined by the Boltzmann distribution of the energies of the states, a multitude of structural states are inherent to biomolecules. For a detailed understanding of a protein's function, its entire structural landscape at atomic resolution and insight into the interconversion between all the structural states (i.e. dynamics) are required. Whereas dedicated trickery with NMR relaxation provides aspects of local dynamics, and 3D structure determination by NMR is well established, only recently have several attempts been made to formulate a more comprehensive description of the dynamics and the structural landscape of a protein. Here, a perspective is given on the use of exact NOEs (eNOEs) for the elucidation of structural ensembles of a protein describing the covered conformational space. Copyright © 2013 Elsevier Inc. All rights reserved.

Lattice and Valence Electronic Structures of Crystalline Octahedral Molybdenum Halide Clusters-Based Compounds, Cs2[Mo6X14] (X = Cl, Br, I), Studied by Density Functional Theory Calculations.

PubMed

Saito, Norio; Cordier, Stéphane; Lemoine, Pierric; Ohsawa, Takeo; Wada, Yoshiki; Grasset, Fabien; Cross, Jeffrey S; Ohashi, Naoki

2017-06-05

The electronic and crystal structures of Cs 2 [Mo 6 X 14 ] (X = Cl, Br, I) cluster-based compounds were investigated by density functional theory (DFT) simulations and experimental methods such as powder X-ray diffraction, ultraviolet-visible spectroscopy, and X-ray photoemission spectroscopy (XPS). The experimentally determined lattice parameters were in good agreement with theoretically optimized ones, indicating the usefulness of DFT calculations for the structural investigation of these clusters. The calculated band gaps of these compounds reproduced those experimentally determined by UV-vis reflectance within an error of a few tenths of an eV. Core-level XPS and effective charge analyses indicated bonding states of the halogens changed according to their sites. The XPS valence spectra were fairly well reproduced by simulations based on the projected electron density of states weighted with cross sections of Al K α , suggesting that DFT calculations can predict the electronic properties of metal-cluster-based crystals with good accuracy.

Electronic origin of structural transition in 122 Fe based superconductors

NASA Astrophysics Data System (ADS)

Ghosh, Haranath; Sen, Smritijit; Ghosh, Abyay

2017-03-01

Direct quantitative correlations between the orbital order and orthorhombicity is achieved in a number of Fe-based superconductors of 122 family. The former (orbital order) is calculated from first principles simulations using experimentally determined doping and temperature dependent structural parameters while the latter (the orthorhombicity) is taken from already established experimental studies; when normalized, both the above quantities quantitatively corresponds to each other in terms of their doping as well as temperature variations. This proves that the structural transition in Fe-based materials is electronic in nature due to orbital ordering. An universal correlations among various structural parameters and electronic structure are also obtained. Most remarkable among them is the mapping of two Fe-Fe distances in the low temperature orthorhombic phase, with the band energies Edxz, Edyz of Fe at the high symmetry points of the Brillouin zone. The fractional co-ordinate zAs of As which essentially determines anion height is inversely (directly) proportional to Fe-As bond distances (with exceptions of K doped BaFe2As2) for hole (electron) doped materials as a function of doping. On the other hand, Fe-As bond-distance is found to be inversely (directly) proportional to the density of states at the Fermi level for hole (electron) doped systems. Implications of these results to current issues of Fe based superconductivity are discussed.

Sequence-similar, structure-dissimilar protein pairs in the PDB.

PubMed

Kosloff, Mickey; Kolodny, Rachel

2008-05-01

It is often assumed that in the Protein Data Bank (PDB), two proteins with similar sequences will also have similar structures. Accordingly, it has proved useful to develop subsets of the PDB from which "redundant" structures have been removed, based on a sequence-based criterion for similarity. Similarly, when predicting protein structure using homology modeling, if a template structure for modeling a target sequence is selected by sequence alone, this implicitly assumes that all sequence-similar templates are equivalent. Here, we show that this assumption is often not correct and that standard approaches to create subsets of the PDB can lead to the loss of structurally and functionally important information. We have carried out sequence-based structural superpositions and geometry-based structural alignments of a large number of protein pairs to determine the extent to which sequence similarity ensures structural similarity. We find many examples where two proteins that are similar in sequence have structures that differ significantly from one another. The source of the structural differences usually has a functional basis. The number of such proteins pairs that are identified and the magnitude of the dissimilarity depend on the approach that is used to calculate the differences; in particular sequence-based structure superpositioning will identify a larger number of structurally dissimilar pairs than geometry-based structural alignments. When two sequences can be aligned in a statistically meaningful way, sequence-based structural superpositioning provides a meaningful measure of structural differences. This approach and geometry-based structure alignments reveal somewhat different information and one or the other might be preferable in a given application. Our results suggest that in some cases, notably homology modeling, the common use of nonredundant datasets, culled from the PDB based on sequence, may mask important structural and functional information. We have established a data base of sequence-similar, structurally dissimilar protein pairs that will help address this problem (http://luna.bioc.columbia.edu/rachel/seqsimstrdiff.htm).

Temperature and Pressure Sensors Based on Spin-Allowed Broadband Luminescence of Doped Orthorhombic Perovskite Structures

NASA Technical Reports Server (NTRS)

Eldridge, Jeffrey I. (Inventor); Chambers, Matthew D. (Inventor)

2014-01-01

Systems and methods that are capable of measuring pressure or temperature based on luminescence are discussed herein. These systems and methods are based on spin-allowed broadband luminescence of sensors with orthorhombic perovskite structures of rare earth aluminates doped with chromium or similar transition metals, such as chromium-doped gadolinium aluminate. Luminescence from these sensors can be measured to determine at least one of temperature or pressure, based on either the intense luminescence of these sensors, even at high temperatures, or low temperature techniques discussed herein.

Synthesis, characterization, spectroscopic and theoretical studies of new zinc(II), copper(II) and nickel(II) complexes based on imine ligand containing 2-aminothiophenol moiety

NASA Astrophysics Data System (ADS)

Shafaatian, Bita; Mousavi, S. Sedighe; Afshari, Sadegh

2016-11-01

New dimer complexes of zinc(II), copper(II) and nickel(II) were synthesized using the Schiff base ligand which was formed by the condensation of 2-aminothiophenol and 2-hydroxy-5-methyl benzaldehyde. This tridentate Schiff base ligand was coordinated to the metal ions through the NSO donor atoms. In order to prevent the oxidation of the thiole group during the formation of Schiff base and its complexes, all of the reactions were carried out under an inert atmosphere of argon. The X-ray structure of the Schiff base ligand showed that in the crystalline form the SH groups were oxidized to produce a disulfide Schiff base as a new double Schiff base ligand. The molar conductivity values of the complexes in dichloromethane implied the presence of non-electrolyte species. The fluorescence properties of the Schiff base ligand and its complexes were also studied in dichloromethane. The products were characterized by FT-IR, 1H NMR, UV/Vis spectroscopies, elemental analysis, and conductometry. The crystal structure of the double Schiff base was determined by single crystal X-ray diffraction. Furthermore, the density functional theory (DFT) calculations were performed at the B3LYP/6-31G(d,p) level of theory for the determination of the optimized structures of Schiff base complexes.

Damage of composite structures: Detection technique, dynamic response and residual strength

NASA Astrophysics Data System (ADS)

Lestari, Wahyu

2001-10-01

Reliable and accurate health monitoring techniques can prevent catastrophic failures of structures. Conventional damage detection methods are based on visual or localized experimental methods and very often require prior information concerning the vicinity of the damage or defect. The structure must also be readily accessible for inspections. The techniques are also labor intensive. In comparison to these methods, health-monitoring techniques that are based on the structural dynamic response offers unique information on failure of structures. However, systematic relations between the experimental data and the defect are not available and frequently, the number of vibration modes needed for an accurate identification of defects is much higher than the number of modes that can be readily identified in the experiment. These motivated us to develop an experimental data based detection method with systematic relationships between the experimentally identified information and the analytical or mathematical model representing the defective structures. The developed technique use changes in vibrational curvature modes and natural frequencies. To avoid misinterpretation of the identified information, we also need to understand the effects of defects on the structural dynamic response prior to developing health-monitoring techniques. In this thesis work we focus on two type of defects in composite structures, namely delamination and edge notch like defect. Effects of nonlinearity due to the presence of defect and due to the axial stretching are studied for beams with delamination. Once defects are detected in a structure, next concern is determining the effects of the defects on the strength of the structure and its residual stiffness under dynamic loading. In this thesis, energy release rate due to dynamic loading in a delaminated structure is studied, which will be a foundation toward determining the residual strength of the structure.

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold

PubMed Central

Huber, Roland G.; Bond, Peter J.

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners. PMID:29016650

New strategy for protein interactions and application to structure-based drug design

NASA Astrophysics Data System (ADS)

Zou, Xiaoqin

One of the greatest challenges in computational biophysics is to predict interactions between biological molecules, which play critical roles in biological processes and rational design of therapeutic drugs. Biomolecular interactions involve delicate interplay between multiple interactions, including electrostatic interactions, van der Waals interactions, solvent effect, and conformational entropic effect. Accurate determination of these complex and subtle interactions is challenging. Moreover, a biological molecule such as a protein usually consists of thousands of atoms, and thus occupies a huge conformational space. The large degrees of freedom pose further challenges for accurate prediction of biomolecular interactions. Here, I will present our development of physics-based theory and computational modeling on protein interactions with other molecules. The major strategy is to extract microscopic energetics from the information embedded in the experimentally-determined structures of protein complexes. I will also present applications of the methods to structure-based therapeutic design. Supported by NSF CAREER Award DBI-0953839, NIH R01GM109980, and the American Heart Association (Midwest Affiliate) [13GRNT16990076].

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.

PubMed

Ivanov, Stefan M; Cawley, Andrew; Huber, Roland G; Bond, Peter J; Warwicker, Jim

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.

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.

Study of Cr/Sc-based multilayer reflecting mirrors using soft x-ray reflectivity and standing wave-enhanced x-ray fluorescence

NASA Astrophysics Data System (ADS)

Wu, Meiyi; Burcklen, Catherine; André, Jean-Michel; Guen, Karine Le; Giglia, Angelo; Koshmak, Konstantin; Nannarone, Stefano; Bridou, Françoise; Meltchakov, Evgueni; Rossi, Sébastien de; Delmotte, Franck; Jonnard, Philippe

2017-11-01

We study Cr/Sc-based multilayer mirrors designed to work in the water window range using hard and soft x-ray reflectivity as well as x-ray fluorescence enhanced by standing waves. Samples differ by the elemental composition of the stack, the thickness of each layer, and the order of deposition. This paper mainly consists of two parts. In the first part, the optical performances of different Cr/Sc-based multilayers are reported, and in the second part, we extend further the characterization of the structural parameters of the multilayers, which can be extracted by comparing the experimental data with simulations. The methodology is detailed in the case of Cr/B4C/Sc sample for which a three-layer model is used. Structural parameters determined by fitting reflectivity curve are then introduced as fixed parameters to plot the x-ray standing wave curve, to compare with the experiment, and confirm the determined structure of the stack.

Total-energy Assisted Tight-binding Method Based on Local Density Approximation of Density Functional Theory

NASA Astrophysics Data System (ADS)

Fujiwara, Takeo; Nishino, Shinya; Yamamoto, Susumu; Suzuki, Takashi; Ikeda, Minoru; Ohtani, Yasuaki

2018-06-01

A novel tight-binding method is developed, based on the extended Hückel approximation and charge self-consistency, with referring the band structure and the total energy of the local density approximation of the density functional theory. The parameters are so adjusted by computer that the result reproduces the band structure and the total energy, and the algorithm for determining parameters is established. The set of determined parameters is applicable to a variety of crystalline compounds and change of lattice constants, and, in other words, it is transferable. Examples are demonstrated for Si crystals of several crystalline structures varying lattice constants. Since the set of parameters is transferable, the present tight-binding method may be applicable also to molecular dynamics simulations of large-scale systems and long-time dynamical processes.

Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei

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

Begley, Darren W.; Hartley, Robert C.; Davies, Douglas R.

As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification ofmore » several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme.« less

Integrated Structural Biology for α-Helical Membrane Protein Structure Determination.

PubMed

Xia, Yan; Fischer, Axel W; Teixeira, Pedro; Weiner, Brian; Meiler, Jens

2018-04-03

While great progress has been made, only 10% of the nearly 1,000 integral, α-helical, multi-span membrane protein families are represented by at least one experimentally determined structure in the PDB. Previously, we developed the algorithm BCL::MP-Fold, which samples the large conformational space of membrane proteins de novo by assembling predicted secondary structure elements guided by knowledge-based potentials. Here, we present a case study of rhodopsin fold determination by integrating sparse and/or low-resolution restraints from multiple experimental techniques including electron microscopy, electron paramagnetic resonance spectroscopy, and nuclear magnetic resonance spectroscopy. Simultaneous incorporation of orthogonal experimental restraints not only significantly improved the sampling accuracy but also allowed identification of the correct fold, which is demonstrated by a protein size-normalized transmembrane root-mean-square deviation as low as 1.2 Å. The protocol developed in this case study can be used for the determination of unknown membrane protein folds when limited experimental restraints are available. Copyright © 2018 Elsevier Ltd. All rights reserved.

Upper-crustal structure of the inner Continental Borderland near Long Beach, California

USGS Publications Warehouse

Baher, S.; Fuis, G.; Sliter, R.; Normark, W.R.

2005-01-01

A new P-wave velocity/structural model for the inner Continental Borderland (ICB) region was developed for the area near Long Beach, California. It combines controlled-source seismic reflection and refraction data collected during the 1994 Los Angeles Region Seismic Experiment (LARSE), multichannel seismic reflection data collected by the U.S. Geological Survey (1998-2000), and nearshore borehole stratigraphy. Based on lateral velocity contrasts and stratigraphic variation determined from borehole data, we are able to locate major faults such as the Cabrillo, Palos Verdes, THUMS-Huntington Beach, and Newport Inglewood fault zones, along with minor faults such as the slope fault, Avalon knoll, and several other yet unnamed faults. Catalog seismicity (1975-2002) plotted on our preferred velocity/structural model shows recent seismicity is located on 16 out of our 24 faults, providing evidence for continuing concern with respect to the existing seismic-hazard estimates. Forward modeling of P-wave arrival times on the LARSE line 1 resulted in a four-layer model that better resolves the stratigraphy and geologic structures of the ICB and also provides tighter constraints on the upper-crustal velocity structure than previous modeling of the LARSE data. There is a correlation between the structural horizons identified in the reflection data with the velocity interfaces determined from forward modeling of refraction data. The strongest correlation is between the base of velocity layer 1 of the refraction model and the base of the planar sediment beneath the shelf and slope determined by the reflection model. Layers 2 and 3 of the velocity model loosely correlate with the diffractive crust layer, locally interpreted as Catalina Schist.

Hybrid approach to structure modeling of the histamine H3 receptor: Multi-level assessment as a tool for model verification.

PubMed

Jończyk, Jakub; Malawska, Barbara; Bajda, Marek

2017-01-01

The crucial role of G-protein coupled receptors and the significant achievements associated with a better understanding of the spatial structure of known receptors in this family encouraged us to undertake a study on the histamine H3 receptor, whose crystal structure is still unresolved. The latest literature data and availability of different software enabled us to build homology models of higher accuracy than previously published ones. The new models are expected to be closer to crystal structures; and therefore, they are much more helpful in the design of potential ligands. In this article, we describe the generation of homology models with the use of diverse tools and a hybrid assessment. Our study incorporates a hybrid assessment connecting knowledge-based scoring algorithms with a two-step ligand-based docking procedure. Knowledge-based scoring employs probability theory for global energy minimum determination based on information about native amino acid conformation from a dataset of experimentally determined protein structures. For a two-step docking procedure two programs were applied: GOLD was used in the first step and Glide in the second. Hybrid approaches offer advantages by combining various theoretical methods in one modeling algorithm. The biggest advantage of hybrid methods is their intrinsic ability to self-update and self-refine when additional structural data are acquired. Moreover, the diversity of computational methods and structural data used in hybrid approaches for structure prediction limit inaccuracies resulting from theoretical approximations or fuzziness of experimental data. The results of docking to the new H3 receptor model allowed us to analyze ligand-receptor interactions for reference compounds.

Cryo-electron microscopy and cryo-electron tomography of nanoparticles.

PubMed

Stewart, Phoebe L

2017-03-01

Cryo-transmission electron microscopy (cryo-TEM or cryo-EM) and cryo-electron tomography (cryo-ET) offer robust and powerful ways to visualize nanoparticles. These techniques involve imaging of the sample in a frozen-hydrated state, allowing visualization of nanoparticles essentially as they exist in solution. Cryo-TEM grid preparation can be performed with the sample in aqueous solvents or in various organic and ionic solvents. Two-dimensional (2D) cryo-TEM provides a direct way to visualize the polydispersity within a nanoparticle preparation. Fourier transforms of cryo-TEM images can confirm the structural periodicity within a sample. While measurement of specimen parameters can be performed with 2D TEM images, determination of a three-dimensional (3D) structure often facilitates more spatially accurate quantization. 3D structures can be determined in one of two ways. If the nanoparticle has a homogeneous structure, then 2D projection images of different particles can be averaged using a computational process referred to as single particle reconstruction. Alternatively, if the nanoparticle has a heterogeneous structure, then a structure can be generated by cryo-ET. This involves collecting a tilt-series of 2D projection images for a defined region of the grid, which can be used to generate a 3D tomogram. Occasionally it is advantageous to calculate both a single particle reconstruction, to reveal the regular portions of a nanoparticle structure, and a cryo-electron tomogram, to reveal the irregular features. A sampling of 2D cryo-TEM images and 3D structures are presented for protein based, DNA based, lipid based, and polymer based nanoparticles. WIREs Nanomed Nanobiotechnol 2017, 9:e1417. doi: 10.1002/wnan.1417 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis

PubMed Central

2012-01-01

Introduction Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. Methods Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environment-based or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). Results 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. Conclusions The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities. PMID:22889402

Determinants of community structure of zooplankton in heavily polluted river ecosystems

NASA Astrophysics Data System (ADS)

Xiong, Wei; Li, Jie; Chen, Yiyong; Shan, Baoqing; Wang, Weimin; Zhan, Aibin

2016-02-01

River ecosystems are among the most affected habitats globally by human activities, such as the release of chemical pollutants. However, it remains largely unknown how and to what extent many communities such as zooplankton are affected by these environmental stressors in river ecosystems. Here, we aim to determine major factors responsible for shaping community structure of zooplankton in heavily polluted river ecosystems. Specially, we use rotifers in the Haihe River Basin (HRB) in North China as a case study to test the hypothesis that species sorting (i.e. species are “filtered” by environmental factors and occur at environmental suitable sites) plays a key role in determining community structure at the basin level. Based on an analysis of 94 sites across the plain region of HRB, we found evidence that both local and regional factors could affect rotifer community structure. Interestingly, further analyses indicated that local factors played a more important role in determining community structure. Thus, our results support the species sorting hypothesis in highly polluted rivers, suggesting that local environmental constraints, such as environmental pollution caused by human activities, can be stronger than dispersal limitation caused by regional factors to shape local community structure of zooplankton at the basin level.

Social determinants of disability-based disadvantage in Solomon islands.

PubMed

Gartrell, Alexandra; Jennaway, Megan; Manderson, Lenore; Fangalasuu, Judy; Dolaiano, Simon

2018-04-01

Development discourse widely recognises that disability is the result of economic and social processes and structures that fail to accommodate persons with disabilities. Empirical work on the relationship between disability and poverty however, conceptualize poverty through an economic resource lens in high-income countries. To address this conceptual gap this article uses a social determinants of health perspective to examine how socio-cultural, economic and political contexts shape disability-based disadvantage. This article draws upon ethnographic research and supplementary data collected using rapid assessment techniques in Solomon Islands. Findings suggest that the disability-poverty nexus and inequalities in health, wellbeing and quality of life must be understood within broader patterns of social vulnerability that are institutionalised in landownership and patterns of descent, gendered power relations and disability specific stigmas that preclude social and productive engagement . This article demonstrates how a social determinant of health perspective that closely examines lived experiences of disability provides critical analytical insights into the structural mechanisms that constitute disability-based disadvantage. This article provides foundation knowledge on which policies and further research to promote disability-inclusion and equity can be based.

Is better beautiful or is beautiful better? Exploring the relationship between beauty and category structure.

PubMed

Sanders, Megan; Davis, Tyler; Love, Bradley C

2013-06-01

We evaluate two competing accounts of the relationship between beauty and category structure. According to the similarity-based view, beauty arises from category structure such that central items are favored due to their increased fluency. In contrast, the theory-based view holds that people's theories of beauty shape their perceptions of categories. In the present study, subjects learned to categorize abstract paintings into meaningfully labeled categories and rated the paintings' beauty, value, and typicality. Inconsistent with the similarity-based view, beauty ratings were highly correlated across conditions despite differences in fluency and assigned category structure. Consistent with the theory-based view, beautiful paintings were treated as central members for categories expected to contain beautiful paintings (e.g., art museum pieces), but not in others (e.g., student show pieces). These results suggest that the beauty of complex, real-world stimuli is not determined by fluency within category structure but, instead, interacts with people's prior knowledge to structure categories.

Structure and properties of microporous titanosilicate determined by first-principles calculations

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

Ching, W.Y.; Xu, Y.; Gu, Z.

1996-12-01

The structure of EST-10, a member of synthetic microporous titanosilicates, was recently determined by an ingenious combination of experimental and simulational techniques. However, the locations of the alkali atoms in the framework remain elusive and its electronic structure is totally unknown. Based on first-principles local density calculations, the possible locations of the alkali atoms are identified and its electronic structure and bonding fully elucidated. ETS-10 is a semiconductor with a direct band gap of 2.33 eV. The Na atoms are likely to locate inside the seven-member ring pore adjacent to the one-dimensional Ti-O-Ti-O- chain. {copyright} {ital 1996 The American Physicalmore » Society.}« less

Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.

PubMed

Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

2013-11-01

The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation. © 2013 FEBS.

Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination

PubMed Central

Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

2014-01-01

The number of macromolecular structures deposited in the Protein Data Bank now approaches 100 000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation. PMID:24034303

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

Photogrammetric Modeling and Image-Based Rendering for Rapid Virtual Environment Creation

DTIC Science & Technology

2004-12-01

area and different methods have been proposed. Pertinent methods include: Camera Calibration , Structure from Motion, Stereo Correspondence, and Image...Based Rendering 1.1.1 Camera Calibration Determining the 3D structure of a model from multiple views becomes simpler if the intrinsic (or internal...can introduce significant nonlinearities into the image. We have found that camera calibration is a straightforward process which can simplify the

Clustering of Tuberculosis Cases Based on Variable-Number Tandem-Repeat Typing in Relation to the Population Structure of Mycobacterium tuberculosis in the Netherlands

PubMed Central

Sloot, Rosa; Borgdorff, Martien W.; de Beer, Jessica L.; van Ingen, Jakko; Supply, Philip

2013-01-01

The population structure of 3,776 Mycobacterium tuberculosis isolates was determined using variable-number tandem-repeat (VNTR) typing. The degree of clonality was so high that a more relaxed definition of clustering cannot be applied. Among recent immigrants with non-Euro-American isolates, transmission is overestimated if based on identical VNTR patterns. PMID:23658260

Seismic Structural Considerations for the Stern and Base of Retaining Walls Subjected to Earthquake Ground Motions

DTIC Science & Technology

2005-05-01

CONTRACT NUMBER 5b. GRANT NUMBER 4. TITLE AND SUBTITLE Seismic Structural Considerations for the Stem and Base of Retaining Walls...as represented by response spectra are determined. Several modes of vibration are considered. The number of modes included in the analysis is that...response spectrum- modal analysis procedure. Especially important is the number of excursions beyond acceptable displacement. As with the response

Fourier-based classification of protein secondary structures.

PubMed

Shu, Jian-Jun; Yong, Kian Yan

2017-04-15

The correct prediction of protein secondary structures is one of the key issues in predicting the correct protein folded shape, which is used for determining gene function. Existing methods make use of amino acids properties as indices to classify protein secondary structures, but are faced with a significant number of misclassifications. The paper presents a technique for the classification of protein secondary structures based on protein "signal-plotting" and the use of the Fourier technique for digital signal processing. New indices are proposed to classify protein secondary structures by analyzing hydrophobicity profiles. The approach is simple and straightforward. Results show that the more types of protein secondary structures can be classified by means of these newly-proposed indices. Copyright © 2017 Elsevier Inc. All rights reserved.

HBNG: Graph theory based visualization of hydrogen bond networks in protein structures.

PubMed

Tiwari, Abhishek; Tiwari, Vivek

2007-07-09

HBNG is a graph theory based tool for visualization of hydrogen bond network in 2D. Digraphs generated by HBNG facilitate visualization of cooperativity and anticooperativity chains and rings in protein structures. HBNG takes hydrogen bonds list files (output from HBAT, HBEXPLORE, HBPLUS and STRIDE) as input and generates a DOT language script and constructs digraphs using freeware AT and T Graphviz tool. HBNG is useful in the enumeration of favorable topologies of hydrogen bond networks in protein structures and determining the effect of cooperativity and anticooperativity on protein stability and folding. HBNG can be applied to protein structure comparison and in the identification of secondary structural regions in protein structures. Program is available from the authors for non-commercial purposes.

Map showing structure contours on the top of the upper Jurassic Morrison Formation, Powder River basin, Wyoming and Montana

USGS Publications Warehouse

Crysdale, B.L.

1991-01-01

This map is one in a series of U.S. Geological Survey Miscellaneous Field Studies (MF) maps showing computer-generated structure contours, isopachs, and cross sections of selected formations in the Powder River basin, Wyoming and Montana. The map and cross sections were constructed from information stored in a U.S. Geological Survey Evolution of Sedimentary Basins data base. This data base contains picks of geologic formation and (or) unit tops and bases determined from electric resistivity and gamma-ray logs of 8,592 wells penetrating Tertiary and older rocks in the Powder River basin. Well completion cards (scout tickets) were reviewed and compared with copies of all logs, and formation or unit contacts determined by N. M. Denson, D.L. Macke, R. R. Schumann and others. This isopach map is based on information from 2,429 of these wells that penetrate the Minnelusa Formation and equivalents.

Q factor of megahertz LC circuits based on thin films of YBaCuO high-temperature superconductor

NASA Astrophysics Data System (ADS)

Masterov, D. V.; Pavlov, S. A.; Parafin, A. E.

2008-05-01

High-frequency properties of resonant structures based on thin films of YBa2Cu3O7 δ high-temperature superconductor are studied experimentally in the frequency range 30 100 MHz. The structures planar induction coils with a self-capacitance fabricated on neodymium gallate and lanthanum aluminate substrates. The unloaded Q factor of the circuits exceeds 2 × 105 at 77 K and 40 MHz. Possible loss mechanisms that determine the Q factor of the superconducting resonant structures in the megahertz range are considered.

26 CFR 1.509(a)-3 - Broadly, publicly supported organizations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... this paragraph, if applicable, the basic consideration is whether its organizational structure... paragraph in determining whether the organizational structure, programs or activities, and method of... subparagraph based on a computation period of taxable years 1971 through 1974 or 1972 through 1975, such an...

A nonlinear viscoelastic approach to durability predictions for polymer based composite structures

NASA Technical Reports Server (NTRS)

Brinson, Hal F.

1991-01-01

Current industry approaches for the durability assessment of metallic structures are briefly reviewed. For polymer based composite structures, it is suggested that new approaches must be adopted to include memory or viscoelastic effects which could lead to delayed failures that might not be predicted using current techniques. A durability or accelerated life assessment plan for fiber reinforced plastics (FRP) developed and documented over the last decade or so is reviewed and discussed. Limitations to the plan are outlined and suggestions to remove the limitations are given. These include the development of a finite element code to replace the previously used lamination theory code and the development of new specimen geometries to evaluate delamination failures. The new DCB model is reviewed and results are presented. Finally, it is pointed out that new procedures are needed to determine interfacial properties and current efforts underway to determine such properties are reviewed. Suggestions for additional efforts to develop a consistent and accurate durability predictive approach for FRP structures are outlined.

A nonlinear viscoelastic approach to durability predictions for polymer based composite structures

NASA Technical Reports Server (NTRS)

Brinson, Hal F.; Hiel, C. C.

1990-01-01

Current industry approaches for the durability assessment of metallic structures are briefly reviewed. For polymer based composite structures, it is suggested that new approaches must be adopted to include memory or viscoelastic effects which could lead to delayed failures that might not be predicted using current techniques. A durability or accelerated life assessment plan for fiber reinforced plastics (FRP) developed and documented over the last decade or so is reviewed and discussed. Limitations to the plan are outlined and suggestions to remove the limitations are given. These include the development of a finite element code to replace the previously used lamination theory code and the development of new specimen geometries to evaluate delamination failures. The new DCB model is reviewed and results are presented. Finally, it is pointed out that new procedures are needed to determine interfacial properties and current efforts underway to determine such properties are reviewed. Suggestions for additional efforts to develop a consistent and accurate durability predictive approach for FRP structures is outlined.

The Researches on Damage Detection Method for Truss Structures

NASA Astrophysics Data System (ADS)

Wang, Meng Hong; Cao, Xiao Nan

2018-06-01

This paper presents an effective method to detect damage in truss structures. Numerical simulation and experimental analysis were carried out on a damaged truss structure under instantaneous excitation. The ideal excitation point and appropriate hammering method were determined to extract time domain signals under two working conditions. The frequency response function and principal component analysis were used for data processing, and the angle between the frequency response function vectors was selected as a damage index to ascertain the location of a damaged bar in the truss structure. In the numerical simulation, the time domain signal of all nodes was extracted to determine the location of the damaged bar. In the experimental analysis, the time domain signal of a portion of the nodes was extracted on the basis of an optimal sensor placement method based on the node strain energy coefficient. The results of the numerical simulation and experimental analysis showed that the damage detection method based on the frequency response function and principal component analysis could locate the damaged bar accurately.

GNSS-based multi-sensor system for structural monitoring applications

NASA Astrophysics Data System (ADS)

Bogusz, Janusz; Figurski, Mariusz; Nykiel, Grzegorz; Szolucha, Marcin; Wrona, Maciej

2012-03-01

In 2007 the Centre of Applied Geomatics of the Military University of Technology started measurements aimed at the monitoring of the dynamic state of the engineering structures using GNSS. The complexity of the problem forced us to apply an integrated system architecture. This concept is based on simultaneous measuring some selected elements of the structure using various types of sensors. Measurement information from numerous instruments is numerically integrated for determining the investigated parameter, e.g., the displacement vector. The CAG team performed the tests using such a system on the two permanent 500-meters long bridges, the temporary bridge crossing for military purposes and the 300-meters high chimney of the CHP station. The information about displacement vector together with the characteristic frequencies of the structure were determined using different techniques for increasing of its reliability. This paper presents the results of such tests, gives description of the integrated system designed in the CAG and brings forward with the plans for the future.

Development of an embedded thin-film strain-gauge-based SHM network into 3D-woven composite structure for wind turbine blades

NASA Astrophysics Data System (ADS)

Zhao, Dongning; Rasool, Shafqat; Forde, Micheal; Weafer, Bryan; Archer, Edward; McIlhagger, Alistair; McLaughlin, James

2017-04-01

Recently, there has been increasing demand in developing low-cost, effective structure health monitoring system to be embedded into 3D-woven composite wind turbine blades to determine structural integrity and presence of defects. With measuring the strain and temperature inside composites at both in-situ blade resin curing and in-service stages, we are developing a novel scheme to embed a resistive-strain-based thin-metal-film sensory into the blade spar-cap that is made of composite laminates to determine structural integrity and presence of defects. Thus, with fiberglass, epoxy, and a thinmetal- film sensing element, a three-part, low-cost, smart composite laminate is developed. Embedded strain sensory inside composite laminate prototype survived after laminate curing process. The internal strain reading from embedded strain sensor under three-point-bending test standard is comparable. It proves that our proposed method will provide another SHM alternative to reduce sensing costs during the renewable green energy generation.

Mechanical Deformation Mechanisms and Properties of Prion Fibrils Probed by Atomistic Simulations

NASA Astrophysics Data System (ADS)

Choi, Bumjoon; Kim, Taehee; Ahn, Eue Soo; Lee, Sang Woo; Eom, Kilho

2017-03-01

Prion fibrils, which are a hallmark for neurodegenerative diseases, have recently been found to exhibit the structural diversity that governs disease pathology. Despite our recent finding concerning the role of the disease-specific structure of prion fibrils in determining their elastic properties, the mechanical deformation mechanisms and fracture properties of prion fibrils depending on their structures have not been fully characterized. In this work, we have studied the tensile deformation mechanisms of prion and non-prion amyloid fibrils by using steered molecular dynamics simulations. Our simulation results show that the elastic modulus of prion fibril, which is formed based on left-handed β-helical structure, is larger than that of non-prion fibril constructed based on right-handed β-helix. However, the mechanical toughness of prion fibril is found to be less than that of non-prion fibril, which indicates that infectious prion fibril is more fragile than non-infectious (non-prion) fibril. Our study sheds light on the role of the helical structure of amyloid fibrils, which is related to prion infectivity, in determining their mechanical deformation mechanisms and properties.

Construction patterns of birds’ nests provide insight into nest-building behaviours

PubMed Central

Goodman, Adrian M.

2017-01-01

Previous studies have suggested that birds and mammals select materials needed for nest building based on their thermal or structural properties, although the amounts or properties of the materials used have been recorded for only a very small number of species. Some of the behaviours underlying the construction of nests can be indirectly determined by careful deconstruction of the structure and measurement of the biomechanical properties of the materials used. Here we examined this idea in an investigation of Bullfinch (Pyrrhula pyrrhula) nests as a model for open-nesting songbird species that construct a “twig” nest, and tested the hypothesis that materials in different parts of nests serve different functions. The quantities of materials present in the nest base, sides and cup were recorded before structural analysis. Structural analysis showed that the base of the outer nests were composed of significantly thicker, stronger and more rigid materials compared to the side walls, which in turn were significantly thicker, stronger and more rigid than materials used in the cup. These results suggest that the placement of particular materials in nests may not be random, but further work is required to determine if the final structure of a nest accurately reflects the construction process. PMID:28265501

Structural Mechanism behind Distinct Efficiency of Oct4/Sox2 Proteins in Differentially Spaced DNA Complexes

PubMed Central

Yesudhas, Dhanusha; Anwar, Muhammad Ayaz; Panneerselvam, Suresh; Durai, Prasannavenkatesh; Shah, Masaud; Choi, Sangdun

2016-01-01

The octamer-binding transcription factor 4 (Oct4) and sex-determining region Y (SRY)-box 2 (Sox2) proteins induce various transcriptional regulators to maintain cellular pluripotency. Most Oct4/Sox2 complexes have either 0 base pairs (Oct4/Sox20bp) or 3 base pairs (Oct4/Sox23bp) separation between their DNA-binding sites. Results from previous biochemical studies have shown that the complexes separated by 0 base pairs are associated with a higher pluripotency rate than those separated by 3 base pairs. Here, we performed molecular dynamics (MD) simulations and calculations to determine the binding free energy and per-residue free energy for the Oct4/Sox20bp and Oct4/Sox23bp complexes to identify structural differences that contribute to differences in induction rate. Our MD simulation results showed substantial differences in Oct4/Sox2 domain movements, as well as secondary-structure changes in the Oct4 linker region, suggesting a potential reason underlying the distinct efficiencies of these complexes during reprogramming. Moreover, we identified key residues and hydrogen bonds that potentially facilitate protein-protein and protein-DNA interactions, in agreement with previous experimental findings. Consequently, our results confess that differential spacing of the Oct4/Sox2 DNA binding sites can determine the magnitude of transcription of the targeted genes during reprogramming. PMID:26790000

The Proposal of a Evolutionary Strategy Generating the Data Structures Based on a Horizontal Tree for the Tests

NASA Astrophysics Data System (ADS)

Żukowicz, Marek; Markiewicz, Michał

2016-09-01

The aim of the article is to present a mathematical definition of the object model, that is known in computer science as TreeList and to show application of this model for design evolutionary algorithm, that purpose is to generate structures based on this object. The first chapter introduces the reader to the problem of presenting data using the TreeList object. The second chapter describes the problem of testing data structures based on TreeList. The third one shows a mathematical model of the object TreeList and the parameters, used in determining the utility of structures created through this model and in evolutionary strategy, that generates these structures for testing purposes. The last chapter provides a brief summary and plans for future research related to the algorithm presented in the article.

From picture to porosity of river bed material using Structure-from-Motion with Multi-View-Stereo

NASA Astrophysics Data System (ADS)

Seitz, Lydia; Haas, Christian; Noack, Markus; Wieprecht, Silke

2018-04-01

Common methods for in-situ determination of porosity of river bed material are time- and effort-consuming. Although mathematical predictors can be used for estimation, they do not adequately represent porosities. The objective of this study was to assess a new approach for the determination of porosity of frozen sediment samples. The method is based on volume determination by applying Structure-from-Motion with Multi View Stereo (SfM-MVS) to estimate a 3D volumetric model based on overlapping imagery. The method was applied on artificial sediment mixtures as well as field samples. In addition, the commonly used water replacement method was applied to determine porosities in comparison with the SfM-MVS method. We examined a range of porosities from 0.16 to 0.46 that are representative of the wide range of porosities found in rivers. SfM-MVS performed well in determining volumes of the sediment samples. A very good correlation (r = 0.998, p < 0.0001) was observed between the SfM-MVS and the water replacement method. Results further show that the water replacement method underestimated total sample volumes. A comparison with several mathematical predictors showed that for non-uniform samples the calculated porosity based on the standard deviation performed better than porosities based on the median grain size. None of the predictors were effective at estimating the porosity of the field samples.

USAKA Long Range Planning Study

DTIC Science & Technology

1990-03-01

effects. Thus, the additional metric potential of RV imaging is not being realized. 3.3.2 Location Determination The location determination function...deceleration), and radiometric measurements allowing determination of object thermal dynamics and modulation by e.g., tumbling. Key issues involved in these... imaging mode, which is based on ISAR principles, allows determination of object structure and free-body and reentry dynamics, while the metric mode again

Determination of the fine structure constant based on BLOCH oscillations of ultracold atoms in a vertical optical lattice.

PubMed

Cladé, Pierre; de Mirandes, Estefania; Cadoret, Malo; Guellati-Khélifa, Saïda; Schwob, Catherine; Nez, François; Julien, Lucile; Biraben, François

2006-01-27

We report an accurate measurement of the recoil velocity of 87Rb atoms based on Bloch oscillations in a vertical accelerated optical lattice. We transfer about 900 recoil momenta with an efficiency of 99.97% per recoil. A set of 72 measurements of the recoil velocity, each one with a relative uncertainty of about 33 ppb in 20 min integration time, leads to a determination of the fine structure constant with a statistical relative uncertainty of 4.4 ppb. The detailed analysis of the different systematic errors yields to a relative uncertainty of 6.7 ppb. The deduced value of alpha-1 is 137.035 998 78(91).

Structural characterization/correlation of calorimetric properties of coal fluids: Final report, September 1, 1985--August 31, 1988

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

Starling, K.E.; Mallinson, R.G.; Li, M.H.

The objective of this research is to examine the relationship between the calorimetric properties of coal fluids and their molecular functional group composition. Coal fluid samples which have had their calorimetric properties measured are characterized using proton NMR, IR, and elemental analysis. These characterizations are then used in a chemical structural model to determine the composition of the coal fluid in terms of the important molecular functional groups. These functional groups are particularly important in determining the intramolecular based properties of a fluid, such as ideal gas heat capacities. Correlational frameworks for ideal gas heat capacities are then examined withinmore » an existing equation of state methodology to determine an optimal correlation. The optimal correlation for obtaining the characterization/chemical structure information and the sensitivity of the correlation to the characterization and structural model is examined. 8 refs.« less

Structural characterization/correlation of calorimetric properties of coal fluids: Second annual report, September 1, 1986-August 31, 1987

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

Starling, K.E.; Mallinson, R.G.; Li, M.H.

The objective of this research is to examine the relationship between the calorimetric properties of coal fluids and their molecular functional group composition. Coal fluid samples which have had their calorimetric properties measured are characterized using proton NMR, ir, and elemental analysis. These characterizations are then used in a chemical structural model to determine the composition of the coal fluid in terms of the important molecular functional groups. These functional groups are particularly important in determining the intramolecular based properties of a fluid, such as ideal gas heat capacities. Correlational frameworks for ideal gas heat capacities are then examined withinmore » an existing equation of state methodology to determine an optimal correlation. The optimal correlation for obtaining the characterization/chemical structure information and the sensitivity of the correlation to the characterization and structural model is examined.« less

RNA Characterization by Solid-State NMR Spectroscopy.

PubMed

Yang, Yufei; Wang, Shenlin

2018-06-21

The structures of RNAs, which play critical roles in various biological processes, provide important clues and insights into the biological functions of these molecules. However, RNA structure determination remains a challenging topic. In recent years, magic-angle-spinning solid-state NMR (MAS SSNMR) has emerged as an alternative technique for structural and dynamic characterization of RNA. MAS SSNMR has been successfully applied to provide atomic-level structural information about several RNA molecules and RNA-protein complexes. In this Minireview, we give an overview of recent progress in the field of MAS SSNMR based RNA structural characterization, and introduce sample preparation strategies and SSNMR spectroscopic techniques that have been incorporated to identify RNA structural elements. We also highlight a few impressive examples of RNAs that have been investigated extensively by SSNMR. Finally, we briefly discuss future technical trends in the use of MAS SSNMR to facilitate RNA structure determination. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Accelerating calculations of RNA secondary structure partition functions using GPUs

PubMed Central

2013-01-01

Background RNA performs many diverse functions in the cell in addition to its role as a messenger of genetic information. These functions depend on its ability to fold to a unique three-dimensional structure determined by the sequence. The conformation of RNA is in part determined by its secondary structure, or the particular set of contacts between pairs of complementary bases. Prediction of the secondary structure of RNA from its sequence is therefore of great interest, but can be computationally expensive. In this work we accelerate computations of base-pair probababilities using parallel graphics processing units (GPUs). Results Calculation of the probabilities of base pairs in RNA secondary structures using nearest-neighbor standard free energy change parameters has been implemented using CUDA to run on hardware with multiprocessor GPUs. A modified set of recursions was introduced, which reduces memory usage by about 25%. GPUs are fastest in single precision, and for some hardware, restricted to single precision. This may introduce significant roundoff error. However, deviations in base-pair probabilities calculated using single precision were found to be negligible compared to those resulting from shifting the nearest-neighbor parameters by a random amount of magnitude similar to their experimental uncertainties. For large sequences running on our particular hardware, the GPU implementation reduces execution time by a factor of close to 60 compared with an optimized serial implementation, and by a factor of 116 compared with the original code. Conclusions Using GPUs can greatly accelerate computation of RNA secondary structure partition functions, allowing calculation of base-pair probabilities for large sequences in a reasonable amount of time, with a negligible compromise in accuracy due to working in single precision. The source code is integrated into the RNAstructure software package and available for download at http://rna.urmc.rochester.edu. PMID:24180434

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

Wu, Hong; Zeng, Hong; Lam, Robert

The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree ofmore » similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.« less

Determination of the structure of lecithins via the formation of acetylated 1,2-diglycerides.

PubMed

Privett, O S; Nutter, L J

1967-03-01

A detailed procedure for quantitative determinations of molecular species of lecithins is described and applied to several lecithins isolated from natural sources. The method is based on the conversion of lecithin to acetylated 1,2-diglycerides and analysis of these compounds by methodology used for the determination of triglyceride structure.The preparation of the acetylated 1,2-diglycerides was carried out via hydrolysis with phospholipase C and acetylation of the resultant, 1,2-diglycerides with pyridine-acetic anhydride. Preparation of acetylated 1,2-diglycerides from lecithin by acetolysis with acetic acid-acetic anhydride was shown to be accompanied by intermolecular as well as intramolecular rearrangement of the fatty acids.The structure of the acetylated 1,2-diglycerides was determined by a combination of argentation-TLC and pancreatic lipase hydrolysis using internal standards for quantification. The method was applied to lecithins isolated from milk serum, egg, soybean, safflower seed and wheat germ lipids.

Investigation into adamantane-based M2 inhibitors with FB-QSAR.

PubMed

Wei, Hang; Wang, Cheng-Hua; Du, Qi-Shi; Meng, Jianzong; Chou, Kuo-Chen

2009-07-01

Because of their high resistance rate to the existing drugs, influenza A viruses have become a threat to human beings. It is known that the replication of influenza A viruses needs a pH-gated proton channel, the so-called M2 channel. Therefore, to develop effective drugs against influenza A, the most logic strategy is to inhibit the M2 channel. Recently, the atomic structure of the M2 channel was determined by NMR spectroscopy (Schnell, J.R. and Chou, J.J., Nature, 2008, 451, 591-595). The high-resolution NMR structure has provided a solid basis for structure-based drug design approaches. In this study, a benchmark dataset has been constructed that contains 34 newly-developed adamantane-based M2 inhibitors and covers considerable structural diversities and wide range of bioactivities. Based on these compounds, an in-depth analysis was performed with the newly developed fragment-based quantitative structure-activity relationship (FB-QSAR) algorithm. The results thus obtained provide useful insights for dealing with the drug-resistant problem and designing effective adamantane-based antiflu drugs.

FEDS - An experiment with a microprocessor-based orbit determination system using TDRS data

NASA Technical Reports Server (NTRS)

Shank, D.; Pajerski, R.

1986-01-01

An experiment in microprocessor-based onboard orbit determination has been conducted at NASA's Goddard Space Flight Center. The experiment collected forward-link observation data in real time from a prototype transponder and performed orbit estimation on a typical low-earth scientific satellite. This paper discusses the hardware and organizational configurations of the experiment, the structure of the onboard software, the mathematical models, and the experiment results.

Effects of porosity distribution and porosity volume fraction on the electromechanical properties of 3-3 piezoelectric foams

NASA Astrophysics Data System (ADS)

Nguyen, B. V.; Challagulla, K. S.; Venkatesh, T. A.; Hadjiloizi, D. A.; Georgiades, A. V.

2016-12-01

Unit-cell based finite element models are developed to completely characterize the role of porosity distribution and porosity volume fraction in determining the elastic, dielectric and piezoelectric properties as well as relevant figures of merit of 3-3 type piezoelectric foam structures. Eight classes of foam structures which represent structures with different types and degrees of uniformity of porosity distribution are identified; a Base structure (Class I), two H-type foam structures (Classes II, and III), a Cross-type foam structure (Class IV) and four Line-type foam structures (Classes V, VI, VII, and VIII). Three geometric factors that influence the electromechanical properties are identified: (i) the number of pores per face, pore size and the distance between the pores; (ii) pore orientation with respect to poling direction; (iii) the overall symmetry of the pore distribution with respect to the center of the face of the unit cell. To assess the suitability of these structures for such applications as hydrophones, bone implants, medical imaging and diagnostic devices, five figures of merit are determined via the developed finite element model; the piezoelectric coupling constant (K t ), the acoustic impedance (Z), the piezoelectric charge coefficient (d h ), the hydrostatic voltage coefficient (g h ), and the hydrostatic figure of merit (d h g h ). At high material volume fractions, foams with non-uniform Line-type porosity (Classes V and VII) where the pores are preferentially distributed perpendicular to poling direction, are found to exhibit the best combination of desirable piezoelectric figures of merit. For example, at about 50% volume fraction, the d h , g h , and d h g h figures of merit are 55%, 1600% and 2500% higher, respectively, for Classes V and VII of Line-like foam structures compared with the Base structure.

DNA nanotubes for NMR structure determination of membrane proteins.

PubMed

Bellot, Gaëtan; McClintock, Mark A; Chou, James J; Shih, William M

2013-04-01

Finding a way to determine the structures of integral membrane proteins using solution nuclear magnetic resonance (NMR) spectroscopy has proved to be challenging. A residual-dipolar-coupling-based refinement approach can be used to resolve the structure of membrane proteins up to 40 kDa in size, but to do this you need a weak-alignment medium that is detergent-resistant and it has thus far been difficult to obtain such a medium suitable for weak alignment of membrane proteins. We describe here a protocol for robust, large-scale synthesis of detergent-resistant DNA nanotubes that can be assembled into dilute liquid crystals for application as weak-alignment media in solution NMR structure determination of membrane proteins in detergent micelles. The DNA nanotubes are heterodimers of 400-nm-long six-helix bundles, each self-assembled from a M13-based p7308 scaffold strand and >170 short oligonucleotide staple strands. Compatibility with proteins bearing considerable positive charge as well as modulation of molecular alignment, toward collection of linearly independent restraints, can be introduced by reducing the negative charge of DNA nanotubes using counter ions and small DNA-binding molecules. This detergent-resistant liquid-crystal medium offers a number of properties conducive for membrane protein alignment, including high-yield production, thermal stability, buffer compatibility and structural programmability. Production of sufficient nanotubes for four or five NMR experiments can be completed in 1 week by a single individual.

Population structure of rice varieties used in Turkish rice breeding programs determined using simple-sequence repeat and inter-primer binding site-retrotransposon data.

PubMed

Cömertpay, G; Baloch, F S; Derya, M; Andeden, E E; Alsaleh, A; Sürek, H; Özkan, H

2016-02-19

Effective breeding programs based on genetic diversity are needed to broaden the genetic basis of rice (Oryza sativa L.) in Turkey. In this study, 81 commercial varieties from seven countries were studied in order to estimate the genomic relationships among them using nine inter-primer binding site (iPBS)-retrotransposon and 17 simple-sequence repeat (SSR) markers. A total of 59 alleles for the SSR markers and 96 bands for the iPBS-retrotransposon markers were detected, with an average of 3.47 and 10.6 per locus, respectively. Each of the varieties could be unequivocally identified by the SSR and iPBS-retrotransposon profiles. The iPBS-retrotransposon- and SSR-based clustering were identical and closely mirrored each other, with a significantly high correlation (r = 0.73). A neighbor-joining cluster based on the combined SSR and iPBS-retrotransposon data divided the rice varieties into three clusters. The population structure was determined using the STRUCTURE software, and three populations (K = 3) were identified among the varieties studied, showing that the diversity harbored by Turkish rice varieties is low. The results indicate that iPBS-retrotransposon markers are a very powerful technique to determine the genetic diversity of rice varieties.

Crystal and molecular structures of 3-amino-4-hydroxy benzenesulfonamide and its hydrochloride: Quantum-chemical study of their tautomerism

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

Kovalchukova, O. V., E-mail: okovalchukova@mail.ru; Strashnova, S. B.; Romashkina, E. P.

2013-03-15

3-amino-4-hydroxy benzenesulfonamide and its hydrochloride have been isolated in the crystalline state. Their crystal and molecular structures are determined by X-ray diffraction. The equilibrium between neutral tautomeric forms of the 3-amino-4-hydroxy benzenesulfonamide molecule is studied within the approximation of density functional theory (B3LYP/aug-cc-pVDZ). The constants of acid-base equilibrium of 3-amino-4-hydroxy benzenesulfonamide are deter-mined using spectrophotometry.

RNAHelix: computational modeling of nucleic acid structures with Watson-Crick and non-canonical base pairs.

PubMed

Bhattacharyya, Dhananjay; Halder, Sukanya; Basu, Sankar; Mukherjee, Debasish; Kumar, Prasun; Bansal, Manju

2017-02-01

Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN. The program can regenerate duplexes using the dinucleotide step and base pair orientation parameters for a given double helical DNA or RNA sequence with defined Watson-Crick or non-Watson-Crick base pairs. The original structure and the corresponding regenerated structure of double helices were found to be very close, as indicated by the small RMSD values between positions of the corresponding atoms. Structures of several usual and unusual double helices have been regenerated and compared with their original structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes.

Structure-based drug design: aiming for a perfect fit

PubMed Central

van Montfort, Rob L.M.; Workman, Paul

2017-01-01

Knowledge of the three-dimensional structure of therapeutically relevant targets has informed drug discovery since the first protein structures were determined using X-ray crystallography in the 1950s and 1960s. In this editorial we provide a brief overview of the powerful impact of structure-based drug design (SBDD), which has its roots in computational and structural biology, with major contributions from both academia and industry. We describe advances in the application of SBDD for integral membrane protein targets that have traditionally proved very challenging. We emphasize the major progress made in fragment-based approaches for which success has been exemplified by over 30 clinical drug candidates and importantly three FDA-approved drugs in oncology. We summarize the articles in this issue that provide an excellent snapshot of the current state of the field of SBDD and fragment-based drug design and which offer key insights into exciting new developments, such as the X-ray free-electron laser technology, cryo-electron microscopy, open science approaches and targeted protein degradation. We stress the value of SBDD in the design of high-quality chemical tools that are used to interrogate biology and disease pathology, and to inform target validation. We emphasize the need to maintain the scientific rigour that has been traditionally associated with structural biology and extend this to other methods used in drug discovery. This is particularly important because the quality and robustness of any form of contributory data determines its usefulness in accelerating drug design, and therefore ultimately in providing patient benefit. PMID:29118091

24 CFR 35.925 - Examples of determining applicable requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES... for a dwelling is $2,000, and the hard costs of rehabilitation are $10,000, the lead-based paint... costs of rehabilitation are $2,000, the lead-based paint requirements would be those described in § 35...

24 CFR 35.925 - Examples of determining applicable requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES... for a dwelling is $2,000, and the hard costs of rehabilitation are $10,000, the lead-based paint... costs of rehabilitation are $2,000, the lead-based paint requirements would be those described in § 35...

24 CFR 35.925 - Examples of determining applicable requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES... for a dwelling is $2,000, and the hard costs of rehabilitation are $10,000, the lead-based paint... costs of rehabilitation are $2,000, the lead-based paint requirements would be those described in § 35...

24 CFR 35.925 - Examples of determining applicable requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES... for a dwelling is $2,000, and the hard costs of rehabilitation are $10,000, the lead-based paint... costs of rehabilitation are $2,000, the lead-based paint requirements would be those described in § 35...

24 CFR 35.925 - Examples of determining applicable requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES... for a dwelling is $2,000, and the hard costs of rehabilitation are $10,000, the lead-based paint... costs of rehabilitation are $2,000, the lead-based paint requirements would be those described in § 35...

Analysis of Physicochemical and Structural Properties Determining HIV-1 Coreceptor Usage

PubMed Central

Bozek, Katarzyna; Lengauer, Thomas; Sierra, Saleta; Kaiser, Rolf; Domingues, Francisco S.

2013-01-01

The relationship of HIV tropism with disease progression and the recent development of CCR5-blocking drugs underscore the importance of monitoring virus coreceptor usage. As an alternative to costly phenotypic assays, computational methods aim at predicting virus tropism based on the sequence and structure of the V3 loop of the virus gp120 protein. Here we present a numerical descriptor of the V3 loop encoding its physicochemical and structural properties. The descriptor allows for structure-based prediction of HIV tropism and identification of properties of the V3 loop that are crucial for coreceptor usage. Use of the proposed descriptor for prediction results in a statistically significant improvement over the prediction based solely on V3 sequence with 3 percentage points improvement in AUC and 7 percentage points in sensitivity at the specificity of the 11/25 rule (95%). We additionally assessed the predictive power of the new method on clinically derived ‘bulk’ sequence data and obtained a statistically significant improvement in AUC of 3 percentage points over sequence-based prediction. Furthermore, we demonstrated the capacity of our method to predict therapy outcome by applying it to 53 samples from patients undergoing Maraviroc therapy. The analysis of structural features of the loop informative of tropism indicates the importance of two loop regions and their physicochemical properties. The regions are located on opposite strands of the loop stem and the respective features are predominantly charge-, hydrophobicity- and structure-related. These regions are in close proximity in the bound conformation of the loop potentially forming a site determinant for the coreceptor binding. The method is available via server under http://structure.bioinf.mpi-inf.mpg.de/. PMID:23555214

Automatic building of a web-like structure based on thermoplastic adhesive.

PubMed

Leach, Derek; Wang, Liyu; Reusser, Dorothea; Iida, Fumiya

2014-09-01

Animals build structures to extend their control over certain aspects of the environment; e.g., orb-weaver spiders build webs to capture prey, etc. Inspired by this behaviour of animals, we attempt to develop robotics technology that allows a robot to automatically builds structures to help it accomplish certain tasks. In this paper we show automatic building of a web-like structure with a robot arm based on thermoplastic adhesive (TPA) material. The material properties of TPA, such as elasticity, adhesiveness, and low melting temperature, make it possible for a robot to form threads across an open space by an extrusion-drawing process and then combine several of these threads into a web-like structure. The problems addressed here are discovering which parameters determine the thickness of a thread and determining how web-like structures may be used for certain tasks. We first present a model for the extrusion and the drawing of TPA threads which also includes the temperature-dependent material properties. The model verification result shows that the increasing relative surface area of the TPA thread as it is drawn thinner increases the heat loss of the thread, and that by controlling how quickly the thread is drawn, a range of diameters can be achieved from 0.2-0.75 mm. We then present a method based on a generalized nonlinear finite element truss model. The model was validated and could predict the deformation of various web-like structures when payloads are added. At the end, we demonstrate automatic building of a web-like structure for payload bearing.

Structure solution of DNA-binding proteins and complexes with ARCIMBOLDO libraries

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

Pröpper, Kevin; Instituto de Biologia Molecular de Barcelona; Meindl, Kathrin

2014-06-01

The structure solution of DNA-binding protein structures and complexes based on the combination of location of DNA-binding protein motif fragments with density modification in a multi-solution frame is described. Protein–DNA interactions play a major role in all aspects of genetic activity within an organism, such as transcription, packaging, rearrangement, replication and repair. The molecular detail of protein–DNA interactions can be best visualized through crystallography, and structures emphasizing insight into the principles of binding and base-sequence recognition are essential to understanding the subtleties of the underlying mechanisms. An increasing number of high-quality DNA-binding protein structure determinations have been witnessed despite themore » fact that the crystallographic particularities of nucleic acids tend to pose specific challenges to methods primarily developed for proteins. Crystallographic structure solution of protein–DNA complexes therefore remains a challenging area that is in need of optimized experimental and computational methods. The potential of the structure-solution program ARCIMBOLDO for the solution of protein–DNA complexes has therefore been assessed. The method is based on the combination of locating small, very accurate fragments using the program Phaser and density modification with the program SHELXE. Whereas for typical proteins main-chain α-helices provide the ideal, almost ubiquitous, small fragments to start searches, in the case of DNA complexes the binding motifs and DNA double helix constitute suitable search fragments. The aim of this work is to provide an effective library of search fragments as well as to determine the optimal ARCIMBOLDO strategy for the solution of this class of structures.« less

Applications of molecular modeling in coal research

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

Carlson, G.A.; Faulon, J.L.

Over the past several years, molecular modeling has been applied to study various characteristics of coal molecular structures. Powerful workstations coupled with molecular force-field-based software packages have been used to study coal and coal-related molecules. Early work involved determination of the minimum-energy three-dimensional conformations of various published coal structures (Given, Wiser, Solomon and Shinn), and the dominant role of van der Waals and hydrogen bonding forces in defining the energy-minimized structures. These studies have been extended to explore various physical properties of coal structures, including density, microporosity, surface area, and fractal dimension. Other studies have related structural characteristics to cross-linkmore » density and have explored small molecule interactions with coal. Finally, recent studies using a structural elucidation (molecular builder) technique have constructed statistically diverse coal structures based on quantitative and qualitative data on coal and its decomposition products. This technique is also being applied to study coalification processes based on postulated coalification chemistry.« less

Determining the semantic similarities among Gene Ontology terms.

PubMed

Taha, Kamal

2013-05-01

We present in this paper novel techniques that determine the semantic relationships among GeneOntology (GO) terms. We implemented these techniques in a prototype system called GoSE, which resides between user application and GO database. Given a set S of GO terms, GoSE would return another set S' of GO terms, where each term in S' is semantically related to each term in S. Most current research is focused on determining the semantic similarities among GO ontology terms based solely on their IDs and proximity to one another in the GO graph structure, while overlooking the contexts of the terms, which may lead to erroneous results. The context of a GO term T is the set of other terms, whose existence in the GO graph structure is dependent on T. We propose novel techniques that determine the contexts of terms based on the concept of existence dependency. We present a stack-based sort-merge algorithm employing these techniques for determining the semantic similarities among GO terms.We evaluated GoSE experimentally and compared it with three existing methods. The results of measuring the semantic similarities among genes in KEGG and Pfam pathways retrieved from the DBGET and Sanger Pfam databases, respectively, have shown that our method outperforms the other three methods in recall and precision.

A Quantitative Measure of Conformational Changes in Apo, Holo and Ligand-Bound Forms of Enzymes.

PubMed

Singh, Satendra; Singh, Atul Kumar; Wadhwa, Gulshan; Singh, Dev Bukhsh; Dwivedi, Seema; Gautam, Budhayash; Ramteke, Pramod W

2016-06-01

Determination of the native geometry of the enzymes and ligand complexes is a key step in the process of structure-based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in the presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in apo, holo and ligand-bound forms is selected. Enzyme data set was retrieved from protein data bank. Fifteen triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in the presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer-aided drug designing.

Solution structure of a DNA complex with the fluorescent bis-intercalator TOTO determined by NMR spectroscopy.

PubMed

Spielmann, H P; Wemmer, D E; Jacobsen, J P

1995-07-11

We have used two-dimensional 1H NMR spectroscopy to determine the solution structure of the DNA oligonucleotide d(5'-CGCTAGCG-3')2 complexed with the bis-intercalating dye 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)bis[4-(3-methyl -2,3- dihydrobenzo-1,3-thiazolyl-2-methylidene)qui nolinium] tetraiodide (TOTO). The determination of the structure was based on total relaxation matrix analysis of the NOESY cross-peak intensities using the program MARDIGRAS. Improved procedures to consider the experimental "noise" in NOESY spectra during these calculations have been employed. The NOE-derived distance restraints were applied in restrained molecular dynamics calculations. Twenty final structures each were generated for the TOTO complex from both A-form and B-form dsDNA starting structures. The root-mean-square (rms) deviation of the coordinates for the 40 structures of the complex was 1.45 A. The local DNA structure is distorted in the complex. The helix is unwound by 60 degrees and has an overall helical repeat of 12 base pairs, caused by bis-intercalation of TOTO. The poly(propylenamine) linker chain is located in the minor groove of dsDNA. Calculations indicate that the benzothiazole ring system is twisted relative to the quinoline in the uncomplexed TOTO molecule. The site selectivity of TOTO for the CTAG-CTAG site is explained by its ability to adapt to the base pair propeller twist of dsDNA to optimize stacking and the hydrophobic interaction between the thymidine methyl group and the benzothiazole ring. There is a 3000-fold fluorescence enhancement upon binding of TOTO to dsDNA. Rotation about the cyanine methine bonds is possible in free TOTO, allowing relaxation nonradiatively. When bound to dsDNA, the benzothiazole ring and the quinolinium ring are clamped by the nucleobases preventing this rotation, and the chromophore loses excitation energy by fluorescence instead.

Determination of phosphate phases in sewage sludge ash-based fertilizers by Raman microspectroscopy.

PubMed

Vogel, Christian; Adam, Christian; McNaughton, Don

2013-09-01

The chemical form of phosphate phases in sewage sludge ash (SSA)-based fertilizers was determined by Raman microspectroscopy. Raman mapping with a lateral resolution of 5 × 5 μm(2) easily detected different compounds present in the fertilizers with the help of recorded reference spectra of pure substances. Quartz and aluminosilicates showed Raman bands in the range of 450-520 cm(-1). Phosphates with apatite structure and magnesium triphosphate were determined at around 960 and 980 cm(-1), respectively. Furthermore, calcium/magnesium pyrophosphates were detected in some samples.

Training in Structured Diagnostic Assessment Using DSM-IV Criteria

ERIC Educational Resources Information Center

Ponniah, Kathryn; Weissman, Myrna M.; Bledsoe, Sarah E.; Verdeli, Helen; Gameroff, Marc J.; Mufson, Laura; Fitterling, Heidi; Wickramaratne, Priya

2011-01-01

Objectives: Determining a patient's psychiatric diagnosis is an important first step for the selection of empirically supported treatments and a critical component of evidence-based practice. Structured diagnostic assessment covers the range of psychiatric diagnoses and is usually more complete and accurate than unstructured assessment. Method: We…

PRELIMINARY ANALYSIS OF COMMON LOON GENETIC STRUCTURE IN NORTH AMERICA BASED ON FIVE MICROSATELLITE LOCI

EPA Science Inventory

This study seeks to determine fine-scale genetic structure of Common Loon breeding populations in order to link wintering birds with their breeding regions. Common Loons are large piscivorous birds that breed in lakes of northern North America and Iceland. Loons are highly phil...

The procedure for determining the residual life of high-temperature aggregates

NASA Astrophysics Data System (ADS)

Nikiforov, A. S.; Prihodko, E. V.; Kinzhibekova, A. K.; Karmanov, A. E.

2018-01-01

One of the main reasons for the withdrawal of high-temperature aggregates for repairs is the destruction of enclosing structures due to the occurrence of temperature stresses. A wide range of refractory materials used, a large number of product names, a difference in the operation of even the same aggregates makes it impossible to apply general principles for determining the residual resource of high-temperature aggregates, which is based, as a rule, on the determination of temperature stresses. In the article there is suggested a technique based on the method of simulation modeling, allowing to estimate the remaining resource and reliability of the operating equipment. There are given data on the calculation of these indicators for a 25-ton steel-casting ladle. The values obtained make it possible to evaluate the rationality of the further operation of the high-temperature unit by the condition of reliability of the enclosing structures.

Determination of mechanical properties for cement-treated aggregate base : final report.

DOT National Transportation Integrated Search

2017-06-01

The Virginia Department of Transportation (VDOT) currently follows pavement design procedures for all new and rehabilitated pavements based on the 1993 AASHTO Guide for Design of Pavement Structures. VDOTs Materials Division is in the process of i...

Effect of chloride-based deicers on reinforced concrete structures.

DOT National Transportation Integrated Search

2012-07-01

We conducted an extensive literature review and performed laboratory tests to assess the effect of chloride-based deicers on the rebars and dowel bars in concrete and to determine whether or not deicer corrosion inhibitors help preserve the transport...

Hydration sites of unpaired RNA bases: a statistical analysis of the PDB structures.

PubMed

Kirillova, Svetlana; Carugo, Oliviero

2011-10-19

Hydration is crucial for RNA structure and function. X-ray crystallography is the most commonly used method to determine RNA structures and hydration and, therefore, statistical surveys are based on crystallographic results, the number of which is quickly increasing. A statistical analysis of the water molecule distribution in high-resolution X-ray structures of unpaired RNA nucleotides showed that: different bases have the same penchant to be surrounded by water molecules; clusters of water molecules indicate possible hydration sites, which, in some cases, match those of the major and minor grooves of RNA and DNA double helices; complex hydrogen bond networks characterize the solvation of the nucleotides, resulting in a significant rigidity of the base and its surrounding water molecules. Interestingly, the hydration sites around unpaired RNA bases do not match, in general, the positions that are occupied by the second nucleotide when the base-pair is formed. The hydration sites around unpaired RNA bases were found. They do not replicate the atom positions of complementary bases in the Watson-Crick pairs.

Hydration sites of unpaired RNA bases: a statistical analysis of the PDB structures

PubMed Central

2011-01-01

Background Hydration is crucial for RNA structure and function. X-ray crystallography is the most commonly used method to determine RNA structures and hydration and, therefore, statistical surveys are based on crystallographic results, the number of which is quickly increasing. Results A statistical analysis of the water molecule distribution in high-resolution X-ray structures of unpaired RNA nucleotides showed that: different bases have the same penchant to be surrounded by water molecules; clusters of water molecules indicate possible hydration sites, which, in some cases, match those of the major and minor grooves of RNA and DNA double helices; complex hydrogen bond networks characterize the solvation of the nucleotides, resulting in a significant rigidity of the base and its surrounding water molecules. Interestingly, the hydration sites around unpaired RNA bases do not match, in general, the positions that are occupied by the second nucleotide when the base-pair is formed. Conclusions The hydration sites around unpaired RNA bases were found. They do not replicate the atom positions of complementary bases in the Watson-Crick pairs. PMID:22011380

Dynamic Analyses Including Joints Of Truss Structures

NASA Technical Reports Server (NTRS)

Belvin, W. Keith

1991-01-01

Method for mathematically modeling joints to assess influences of joints on dynamic response of truss structures developed in study. Only structures with low-frequency oscillations considered; only Coulomb friction and viscous damping included in analysis. Focus of effort to obtain finite-element mathematical models of joints exhibiting load-vs.-deflection behavior similar to measured load-vs.-deflection behavior of real joints. Experiments performed to determine stiffness and damping nonlinearities typical of joint hardware. Algorithm for computing coefficients of analytical joint models based on test data developed to enable study of linear and nonlinear effects of joints on global structural response. Besides intended application to large space structures, applications in nonaerospace community include ground-based antennas and earthquake-resistant steel-framed buildings.

Synthesis of regional crust and upper-mantle structure from seismic and gravity data

NASA Technical Reports Server (NTRS)

Alexander, S. S.; Lavin, P. M.

1979-01-01

Available seismic and ground based gravity data are combined to infer the three dimensional crust and upper mantle structure in selected regions. This synthesis and interpretation proceeds from large-scale average models suitable for early comparison with high-altitude satellite potential field data to more detailed delineation of structural boundaries and other variations that may be significant in natural resource assessment. Seismic and ground based gravity data are the primary focal point, but other relevant information (e.g. magnetic field, heat flow, Landsat imagery, geodetic leveling, and natural resources maps) is used to constrain the structure inferred and to assist in defining structural domains and boundaries. The seismic data consists of regional refraction lines, limited reflection coverage, surface wave dispersion, teleseismic P and S wave delay times, anelastic absorption, and regional seismicity patterns. The gravity data base consists of available point gravity determinations for the areas considered.

A New Method for Determining Structure Ensemble: Application to a RNA Binding Di-Domain Protein.

PubMed

Liu, Wei; Zhang, Jingfeng; Fan, Jing-Song; Tria, Giancarlo; Grüber, Gerhard; Yang, Daiwen

2016-05-10

Structure ensemble determination is the basis of understanding the structure-function relationship of a multidomain protein with weak domain-domain interactions. Paramagnetic relaxation enhancement has been proven a powerful tool in the study of structure ensembles, but there exist a number of challenges such as spin-label flexibility, domain dynamics, and overfitting. Here we propose a new (to our knowledge) method to describe structure ensembles using a minimal number of conformers. In this method, individual domains are considered rigid; the position of each spin-label conformer and the structure of each protein conformer are defined by three and six orthogonal parameters, respectively. First, the spin-label ensemble is determined by optimizing the positions and populations of spin-label conformers against intradomain paramagnetic relaxation enhancements with a genetic algorithm. Subsequently, the protein structure ensemble is optimized using a more efficient genetic algorithm-based approach and an overfitting indicator, both of which were established in this work. The method was validated using a reference ensemble with a set of conformers whose populations and structures are known. This method was also applied to study the structure ensemble of the tandem di-domain of a poly (U) binding protein. The determined ensemble was supported by small-angle x-ray scattering and nuclear magnetic resonance relaxation data. The ensemble obtained suggests an induced fit mechanism for recognition of target RNA by the protein. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Implication of the cause of differences in 3D structures of proteins with high sequence identity based on analyses of amino acid sequences and 3D structures.

PubMed

Matsuoka, Masanari; Sugita, Masatake; Kikuchi, Takeshi

2014-09-18

Proteins that share a high sequence homology while exhibiting drastically different 3D structures are investigated in this study. Recently, artificial proteins related to the sequences of the GA and IgG binding GB domains of human serum albumin have been designed. These artificial proteins, referred to as GA and GB, share 98% amino acid sequence identity but exhibit different 3D structures, namely, a 3α bundle versus a 4β + α structure. Discriminating between their 3D structures based on their amino acid sequences is a very difficult problem. In the present work, in addition to using bioinformatics techniques, an analysis based on inter-residue average distance statistics is used to address this problem. It was hard to distinguish which structure a given sequence would take only with the results of ordinary analyses like BLAST and conservation analyses. However, in addition to these analyses, with the analysis based on the inter-residue average distance statistics and our sequence tendency analysis, we could infer which part would play an important role in its structural formation. The results suggest possible determinants of the different 3D structures for sequences with high sequence identity. The possibility of discriminating between the 3D structures based on the given sequences is also discussed.

Simultaneous determination of micellar structure and drag reduction in a surfactant solution flow using the fluorescence probe method

NASA Astrophysics Data System (ADS)

Wakimoto, Tatsuro; Araga, Koichi; Katoh, Kenji

2018-03-01

As widely known, the addition of a specific type of surfactant to water reduces drag in a pipe flow. This effect is considered to be a result of the suppression of turbulent transition caused by the ordered structure of rod-like micelles that is referred to as a shear-induced structure (SIS). However, it is typically difficult to determine the SIS since it is necessary to noninvasively detect the SIS with several hundred nanometers in the actual moving flow. In this study, we used the fluorescence probe method to locally determine the SIS in a pipe flow. When hydrophobic fluorescence molecules are added to the surfactant solution, the fluorescence molecules are trapped in micelles. Thus, fluorescence intensity varies based on the change in the micellar structure. We verified the applicability of the fluorescence probe method to the SIS detection and determined the relationship between the micellar structure and the drag reduction in the pipe flow by simultaneously measuring the fluorescence intensity and pipe friction factor. The experimental result demonstrates that the SIS formation in the near-wall region is closely correlated with the drag reduction and suggests that the near-wall SIS suppresses the turbulent transition.

Determining the Views and Adequacy of the Preschool Teachers Related to Science Activities

ERIC Educational Resources Information Center

Akçay, Nilüfer Okur

2016-01-01

In this study, it is aimed to determine the views and adequacy of the preschool teachers related to science activities. The study is based on descriptive survey model. The sample of the study consists of 47 preschool teachers working in Agri city center. Personal information form, semi-structured interview form to determine the views of the…

Structural Evolution of central part of the Tuzgolu (Salt Lake) Basin, Central Anatolia, Turkey

NASA Astrophysics Data System (ADS)

Ada, M.; Cemen, I.; Çaptuğ, A.; Demirci, M.; Engin, C.

2017-12-01

The Tuzgolu Basin in Central Anatolia, Turkey, covers low-relief areas located between the Pontide Mountains to the North and Tauride Mountains to the South. The basin started to form as a rift basin during the Late Maastrichtian. The main Tuzgolu-Aksaray fault zone on the eastern margin of the basin and the northwest trending Yeniceoba and Cihanbeyli fault zones on the western margin of the basin were probably developed during that time. The basin has also experienced westward extension in response to westward escape of the Anatolian plate since Late Miocene. Several geologic studies have been conducted in the Tuz Gölü (Salt Lake) Basin and surrounding areas to determine structural and tectono-stratigraphic development of the basin. However, there are still many questions regarding the structural evolution of the basin. The main purpose of this study is to investigate the structural evolution of the central Tuzgolu Basin based on the structural interpretation of available 2-D seismic reflection profiles, well log analysis and construction of structural cross sections. The cross-sections will be based on depth converted seismic lines to determine structural geometry of the faults and folds. A preliminary Petrel project has been prepared using available seismic profiles. Our preliminary structural interpretations suggest that a well-developed rollover anticline was developed with respect to the westward extension in Central Anatolia. The rollover anticline is faulted in its crest area by both down-to-the west and down-to-the east normal faults. The geometry of the main boundary fault at depth still remains in question. We anticipate that this question will be resolved based on depth converted structural cross-sections and their restoration.

The universal scissor component: Optimization of a reconfigurable component for deployable scissor structures

NASA Astrophysics Data System (ADS)

Alegria Mira, Lara; Thrall, Ashley P.; De Temmerman, Niels

2016-02-01

Deployable scissor structures are well equipped for temporary and mobile applications since they are able to change their form and functionality. They are structural mechanisms that transform from a compact state to an expanded, fully deployed configuration. A barrier to the current design and reuse of scissor structures, however, is that they are traditionally designed for a single purpose. Alternatively, a universal scissor component (USC)-a generalized element which can achieve all traditional scissor types-introduces an opportunity for reuse in which the same component can be utilized for different configurations and spans. In this article, the USC is optimized for structural performance. First, an optimized length for the USC is determined based on a trade-off between component weight and structural performance (measured by deflections). Then, topology optimization, using the simulated annealing algorithm, is implemented to determine a minimum weight layout of beams within a single USC component.

Atomic structure of a toxic, oligomeric segment of SOD1 linked to amyotrophic lateral sclerosis (ALS)

PubMed Central

Sangwan, Smriti; Zhao, Anni; Adams, Katrina L.; Jayson, Christina K.; Sawaya, Michael R.; Guenther, Elizabeth L.; Pan, Albert C.; Ngo, Jennifer; Moore, Destaye M.; Soriaga, Angela B.; Do, Thanh D.; Goldschmidt, Lukasz; Nelson, Rebecca; Bowers, Michael T.; Koehler, Carla M.; Shaw, David E.; Novitch, Bennett G.; Eisenberg, David S.

2017-01-01

Fibrils and oligomers are the aggregated protein agents of neuronal dysfunction in ALS diseases. Whereas we now know much about fibril architecture, atomic structures of disease-related oligomers have eluded determination. Here, we determine the corkscrew-like structure of a cytotoxic segment of superoxide dismutase 1 (SOD1) in its oligomeric state. Mutations that prevent formation of this structure eliminate cytotoxicity of the segment in isolation as well as cytotoxicity of the ALS-linked mutants of SOD1 in primary motor neurons and in a Danio rerio (zebrafish) model of ALS. Cytotoxicity assays suggest that toxicity is a property of soluble oligomers, and not large insoluble aggregates. Our work adds to evidence that the toxic oligomeric entities in protein aggregation diseases contain antiparallel, out-of-register β-sheet structures and identifies a target for structure-based therapeutics in ALS. PMID:28760994

Structured Uncertainty Bound Determination From Data for Control and Performance Validation

NASA Technical Reports Server (NTRS)

Lim, Kyong B.

2003-01-01

This report attempts to document the broad scope of issues that must be satisfactorily resolved before one can expect to methodically obtain, with a reasonable confidence, a near-optimal robust closed loop performance in physical applications. These include elements of signal processing, noise identification, system identification, model validation, and uncertainty modeling. Based on a recently developed methodology involving a parameterization of all model validating uncertainty sets for a given linear fractional transformation (LFT) structure and noise allowance, a new software, Uncertainty Bound Identification (UBID) toolbox, which conveniently executes model validation tests and determine uncertainty bounds from data, has been designed and is currently available. This toolbox also serves to benchmark the current state-of-the-art in uncertainty bound determination and in turn facilitate benchmarking of robust control technology. To help clarify the methodology and use of the new software, two tutorial examples are provided. The first involves the uncertainty characterization of a flexible structure dynamics, and the second example involves a closed loop performance validation of a ducted fan based on an uncertainty bound from data. These examples, along with other simulation and experimental results, also help describe the many factors and assumptions that determine the degree of success in applying robust control theory to practical problems.

Advanced glycation end products induce differential structural modifications and fibrillation of albumin

NASA Astrophysics Data System (ADS)

Awasthi, Saurabh; Sankaranarayanan, Kamatchi; Saraswathi, N. T.

2016-06-01

Glycation induced amyloid fibrillation is fundamental to the development of many neurodegenerative and cardiovascular complications. Excessive non-enzymatic glycation in conditions such as hyperglycaemia results in the increased accumulation of advanced glycation end products (AGEs). AGEs are highly reactive pro-oxidants, which can lead to the activation of inflammatory pathways and development of oxidative stress. Recently, the effect of non-enzymatic glycation on protein structure has been the major research area, but the role of specific AGEs in such structural alteration and induction of fibrillation remains undefined. In this study, we determined the specific AGEs mediated structural modifications in albumin mainly considering carboxymethyllysine (CML), carboxyethyllysine (CEL), and argpyrimidine (Arg-P) which are the major AGEs formed in the body. We studied the secondary structural changes based on circular dichroism (CD) and spectroscopic analysis. The AGEs induced fibrillation was determined by Congo red binding and examination of scanning and transmission electron micrographs. The amyloidogenic regions in the sequence of BSA were determined using FoldAmyloid. It was observed that CEL modification of BSA leads to the development of fibrillar structures, which was evident from both secondary structure changes and TEM analysis.

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase.

PubMed

Zemla, Adam T; Lang, Dorothy M; Kostova, Tanya; Andino, Raul; Ecale Zhou, Carol L

2011-06-02

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.

F2Dock: Fast Fourier Protein-Protein Docking

PubMed Central

Bajaj, Chandrajit; Chowdhury, Rezaul; Siddavanahalli, Vinay

2009-01-01

The functions of proteins is often realized through their mutual interactions. Determining a relative transformation for a pair of proteins and their conformations which form a stable complex, reproducible in nature, is known as docking. It is an important step in drug design, structure determination and understanding function and structure relationships. In this paper we extend our non-uniform fast Fourier transform docking algorithm to include an adaptive search phase (both translational and rotational) and thereby speed up its execution. We have also implemented a multithreaded version of the adaptive docking algorithm for even faster execution on multicore machines. We call this protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated F2Dock based on an extensive experimental study on a list of benchmark complexes and conclude that F2Dock works very well in practice. Though all docking results reported in this paper use shape complementarity and Coulombic potential based scores only, F2Dock is structured to incorporate Lennard-Jones potential and re-ranking docking solutions based on desolvation energy. PMID:21071796

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

MOTIVATION INTERNALIZATION AND SIMPLEX STRUCTURE IN SELF-DETERMINATION THEORY.

PubMed

Ünlü, Ali; Dettweiler, Ulrich

2015-12-01

Self-determination theory, as proposed by Deci and Ryan, postulated different types of motivation regulation. As to the introjected and identified regulation of extrinsic motivation, their internalizations were described as "somewhat external" and "somewhat internal" and remained undetermined in the theory. This paper introduces a constrained regression analysis that allows these vaguely expressed motivations to be estimated in an "optimal" manner, in any given empirical context. The approach was even generalized and applied for simplex structure analysis in self-determination theory. The technique was exemplified with an empirical study comparing science teaching in a classical school class versus an expeditionary outdoor program. Based on a sample of 84 German pupils (43 girls, 41 boys, 10 to 12 years old), data were collected using the German version of the Academic Self-Regulation Questionnaire. The science-teaching format was seen to not influence the pupils' internalization of identified regulation. The internalization of introjected regulation differed and shifted more toward the external pole in the outdoor teaching format. The quantification approach supported the simplex structure of self-determination theory, whereas correlations may disconfirm the simplex structure.

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

Lentine, Anthony L.; Cox, Jonathan Albert

Methods and systems for stabilizing a resonant modulator include receiving pre-modulation and post-modulation portions of a carrier signal, determining the average power from these portions, comparing an average input power to the average output power, and operating a heater coupled to the modulator based on the comparison. One system includes a pair of input structures, one or more processing elements, a comparator, and a control element. The input structures are configured to extract pre-modulation and post-modulation portions of a carrier signal. The processing elements are configured to determine average powers from the extracted portions. The comparator is configured to comparemore » the average input power and the average output power. The control element operates a heater coupled to the modulator based on the comparison.« less

Determination of nasal and oropharyngeal microbiomes in a multicenter population-based study - findings from Pretest 1 of the German National Cohort.

PubMed

Akmatov, Manas K; Koch, Nadine; Vital, Marius; Ahrens, Wolfgang; Flesch-Janys, Dieter; Fricke, Julia; Gatzemeier, Anja; Greiser, Halina; Günther, Kathrin; Illig, Thomas; Kaaks, Rudolf; Krone, Bastian; Kühn, Andrea; Linseisen, Jakob; Meisinger, Christine; Michels, Karin; Moebus, Susanne; Nieters, Alexandra; Obi, Nadia; Schultze, Anja; Six-Merker, Julia; Pieper, Dietmar H; Pessler, Frank

2017-05-12

We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.

Crystal structure prediction supported by incomplete experimental data

NASA Astrophysics Data System (ADS)

Tsujimoto, Naoto; Adachi, Daiki; Akashi, Ryosuke; Todo, Synge; Tsuneyuki, Shinji

2018-05-01

We propose an efficient theoretical scheme for structure prediction on the basis of the idea of combining methods, which optimize theoretical calculation and experimental data simultaneously. In this scheme, we formulate a cost function based on a weighted sum of interatomic potential energies and a penalty function which is defined with partial experimental data totally insufficient for conventional structure analysis. In particular, we define the cost function using "crystallinity" formulated with only peak positions within the small range of the x-ray-diffraction pattern. We apply this method to well-known polymorphs of SiO2 and C with up to 108 atoms in the simulation cell and show that it reproduces the correct structures efficiently with very limited information of diffraction peaks. This scheme opens a new avenue for determining and predicting structures that are difficult to determine by conventional methods.

Integral equation model for warm and hot dense mixtures.

PubMed

Starrett, C E; Saumon, D; Daligault, J; Hamel, S

2014-09-01

In a previous work [C. E. Starrett and D. Saumon, Phys. Rev. E 87, 013104 (2013)] a model for the calculation of electronic and ionic structures of warm and hot dense matter was described and validated. In that model the electronic structure of one atom in a plasma is determined using a density-functional-theory-based average-atom (AA) model and the ionic structure is determined by coupling the AA model to integral equations governing the fluid structure. That model was for plasmas with one nuclear species only. Here we extend it to treat plasmas with many nuclear species, i.e., mixtures, and apply it to a carbon-hydrogen mixture relevant to inertial confinement fusion experiments. Comparison of the predicted electronic and ionic structures with orbital-free and Kohn-Sham molecular dynamics simulations reveals excellent agreement wherever chemical bonding is not significant.

SAD phasing of a structure based on cocrystallized iodides using an in-house Cu Kalpha X-ray source: effects of data redundancy and completeness on structure solution.

PubMed

Yogavel, Manickam; Gill, Jasmita; Mishra, Prakash Chandra; Sharma, Amit

2007-08-01

Superoxide dismutase (SOD) from Potentilla atrosanguinea (Wall. ex. Lehm.) was crystallized using 20% PEG 3350 and 0.2 M ammonium iodide and diffraction data were collected to 2.36 A resolution using an in-house Cu Kalpha X-ray source. Analyses show that data with a redundancy of 3.2 were sufficient to determine the structure by the SAD technique using the iodine anomalous signal. This redundancy is lower than that in previous cases in which protein structures were determined using iodines for phasing and in-house copper X-ray sources. Cocrystallization of proteins with halide salts such as ammonium iodide in combination with copper-anode X-ray radiation can therefore serve as a powerful and easy avenue for structure solution.

Does Organizational Forgetting Matter? Organizational Survival for Life Coaching Companies

ERIC Educational Resources Information Center

Aydin, Erhan; Gormus, Alparslan Sahin

2015-01-01

Purpose: The purposes of this paper are to determine the role of organizational forgetting in different type of coaching companies and to determine organizational survival based on both knowledge structure of coaching companies and organizational forgetting with core features of organizations. Design/methodology/approach: Within the context of…

Influence of professional preparation and class structure on sexuality topics taught in middle and high schools.

PubMed

Rhodes, Darson L; Kirchofer, Gregg; Hammig, Bart J; Ogletree, Roberta J

2013-05-01

This study examined the impact of professional preparation and class structure on sexuality topics taught and use of practice-based instructional strategies in US middle and high school health classes. Data from the classroom-level file of the 2006 School Health Policies and Programs were used. A series of multivariable logistic regression models were employed to determine if sexuality content taught was dependent on professional preparation and /or class structure (HE only versus HE/another subject combined). Additional multivariable logistic regression models were employed to determine if use of practice-based instructional strategies was dependent upon professional preparation and/or class structure. Years of teaching health topics and size of the school district were included as covariates in the multivariable logistic regression models. Findings indicated professionally prepared health educators were significantly more likely to teach 7 of the 13 sexuality topics as compared to nonprofessionally prepared health educators. There was no statistically significant difference in the instructional strategies used by professionally prepared and nonprofessionally prepared health educators. Exclusively health education classes versus combined classes were significantly more likely to have included 6 of the 13 topics and to have incorporated practice-based instructional strategies in the curricula. This study indicated professional preparation and class structure impacted sexuality content taught. Class structure also impacted whether opportunities for students to practice skills were made available. Results support the need for continued advocacy for professionally prepared health educators and health only courses. © 2013, American School Health Association.

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.

Group-theoretical approach to the construction of bases in 2{sup n}-dimensional Hilbert space

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

Garcia, A.; Romero, J. L.; Klimov, A. B., E-mail: klimov@cencar.udg.mx

2011-06-15

We propose a systematic procedure to construct all the possible bases with definite factorization structure in 2{sup n}-dimensional Hilbert space and discuss an algorithm for the determination of basis separability. The results are applied for classification of bases for an n-qubit system.

Ligand Binding Site Detection by Local Structure Alignment and Its Performance Complementarity

PubMed Central

Lee, Hui Sun; Im, Wonpil

2013-01-01

Accurate determination of potential ligand binding sites (BS) is a key step for protein function characterization and structure-based drug design. Despite promising results of template-based BS prediction methods using global structure alignment (GSA), there is a room to improve the performance by properly incorporating local structure alignment (LSA) because BS are local structures and often similar for proteins with dissimilar global folds. We present a template-based ligand BS prediction method using G-LoSA, our LSA tool. A large benchmark set validation shows that G-LoSA predicts drug-like ligands’ positions in single-chain protein targets more precisely than TM-align, a GSA-based method, while the overall success rate of TM-align is better. G-LoSA is particularly efficient for accurate detection of local structures conserved across proteins with diverse global topologies. Recognizing the performance complementarity of G-LoSA to TM-align and a non-template geometry-based method, fpocket, a robust consensus scoring method, CMCS-BSP (Complementary Methods and Consensus Scoring for ligand Binding Site Prediction), is developed and shows improvement on prediction accuracy. The G-LoSA source code is freely available at http://im.bioinformatics.ku.edu/GLoSA. PMID:23957286

RNA secondary structure prediction with pseudoknots: Contribution of algorithm versus energy model.

PubMed

Jabbari, Hosna; Wark, Ian; Montemagno, Carlo

2018-01-01

RNA is a biopolymer with various applications inside the cell and in biotechnology. Structure of an RNA molecule mainly determines its function and is essential to guide nanostructure design. Since experimental structure determination is time-consuming and expensive, accurate computational prediction of RNA structure is of great importance. Prediction of RNA secondary structure is relatively simpler than its tertiary structure and provides information about its tertiary structure, therefore, RNA secondary structure prediction has received attention in the past decades. Numerous methods with different folding approaches have been developed for RNA secondary structure prediction. While methods for prediction of RNA pseudoknot-free structure (structures with no crossing base pairs) have greatly improved in terms of their accuracy, methods for prediction of RNA pseudoknotted secondary structure (structures with crossing base pairs) still have room for improvement. A long-standing question for improving the prediction accuracy of RNA pseudoknotted secondary structure is whether to focus on the prediction algorithm or the underlying energy model, as there is a trade-off on computational cost of the prediction algorithm versus the generality of the method. The aim of this work is to argue when comparing different methods for RNA pseudoknotted structure prediction, the combination of algorithm and energy model should be considered and a method should not be considered superior or inferior to others if they do not use the same scoring model. We demonstrate that while the folding approach is important in structure prediction, it is not the only important factor in prediction accuracy of a given method as the underlying energy model is also as of great value. Therefore we encourage researchers to pay particular attention in comparing methods with different energy models.

RaptorX server: a resource for template-based protein structure modeling.

PubMed

Källberg, Morten; Margaryan, Gohar; Wang, Sheng; Ma, Jianzhu; Xu, Jinbo

2014-01-01

Assigning functional properties to a newly discovered protein is a key challenge in modern biology. To this end, computational modeling of the three-dimensional atomic arrangement of the amino acid chain is often crucial in determining the role of the protein in biological processes. We present a community-wide web-based protocol, RaptorX server ( http://raptorx.uchicago.edu ), for automated protein secondary structure prediction, template-based tertiary structure modeling, and probabilistic alignment sampling.Given a target sequence, RaptorX server is able to detect even remotely related template sequences by means of a novel nonlinear context-specific alignment potential and probabilistic consistency algorithm. Using the protocol presented here it is thus possible to obtain high-quality structural models for many target protein sequences when only distantly related protein domains have experimentally solved structures. At present, RaptorX server can perform secondary and tertiary structure prediction of a 200 amino acid target sequence in approximately 30 min.

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

dos Reis, Roberto; Yang, Hao; Ophus, Colin

A key to the unique combination of electronic and optical properties in halide perovskite materials lies in their rich structural complexity. However, their radiation sensitive nature limits nanoscale structural characterization requiring dose efficient microscopic techniques in order to determine their structures precisely. In this work, we determine the space-group and directly image the Br halide sites of CsPbBr 3, a promising material for optoelectronic applications. Based on the symmetry of high-order Laue zone reflections of convergent-beam electron diffraction, we identify the tetragonal (I4/mcm) structural phase of CsPbBr 3 at cryogenic temperature. Electron ptychography provides a highly sensitive phase contrast measurementmore » of the halide positions under low electron-dose conditions, enabling imaging of the elongated Br sites originating from the out-of-phase octahedral rotation viewed along the [001] direction of I4/mcm persisting at room temperature. The measurement of these features and comparison with simulations yield an octahedral rotation angle of 6.5°(±1.5°). Finally, the approach demonstrated here opens up opportunities for understanding the atomic scale structural phenomena applying advanced characterization tools on a wide range of radiation sensitive halide-based all-inorganic and hybrid organic-inorganic perovskites.« less

Regional atrophy of the basal ganglia and thalamus in idiopathic generalized epilepsy.

PubMed

Du, Hanjian; Zhang, Yuanchao; Xie, Bing; Wu, Nan; Wu, Guocai; Wang, Jian; Jiang, Tianzi; Feng, Hua

2011-04-01

To determine the regional changes in the shapes of subcortical structures in idiopathic generalized epilepsy using a vertex-based analysis method. Earlier studies found that gray matter volume in the frontal, parietal, and temporal lobes is significantly altered in idiopathic generalized epilepsy (IGE). Research has indicated that a relationship exists between the brain's subcortical structures and epilepsy. However, little is known about possible changes in the subcortical structures in IGE. This study aims to determine the changes in the shape of subcortical structures in IGE using vertex analysis. Fourteen male patients with IGE and 28 age- and sex-matched healthy controls were included in this study, which used high-resolution magnetic resonance imaging. We performed a vertex-based shape analysis, in which we compared patients with IGE with the controls, on the subcortical structures that we had obtained from the MRI data. Statistical analysis showed significant regional atrophy in the left thalamus, left putamen and bilateral globus pallidus in patients with IGE. These results indicate that regional atrophy of the basal ganglia and the thalamus may be related to seizure disorder. In the future, these findings may prove useful for choosing new therapeutic regimens. Copyright © 2011 Wiley-Liss, Inc.

Influence of the Compositional Grading on Concentration of Majority Charge Carriers in Near-Surface Layers of n(p)-HgCdTe Grown by Molecular Beam Epitaxy

NASA Astrophysics Data System (ADS)

Voitsekhovskii, A. V.; Nesmelov, S. N.; Dzyadukh, S. M.

2018-02-01

The capacitive characteristics of metal-insulator-semiconductor (MIS) structures based on the compositionally graded Hg1-xCdxTe created by molecular beam epitaxy have been experimentally investigated in a wide temperature range (8-77 K). A program has been developed for numerical simulation of ideal capacitance-voltage (C-V) characteristics in the low-frequency and high-frequency approximations. The concentrations of the majority carriers in the near-surface semiconductor layer are determined from the values of the capacitances in the minima of low-frequency C-V curves. For MIS structures based on p-Hg1-xCdxTe, the effect of the presence of the compositionally graded layer on the hole concentration in the near-surface semiconductor layer, determined from capacitive measurements, has not been established. Perhaps this is due to the fact that the concentration of holes in the near-surface layer largely depends on the type of dielectric coating and the regimes of its application. For MIS structures based on n-Hg1-x Cd x Te (x = 0.22-0.23) without a graded-gap layer, the electron concentration determined by the proposed method is close to the average concentration determined by the Hall measurements. The electron concentration in the near-surface semiconductor layer of the compositionally graded n-Hg1-x Cd x Te (x = 0.22-0.23) found from the minimum capacitance value is much higher than the average electron concentration determined by the Hall measurements. The results are qualitatively explained by the creation of additional intrinsic donor-type defects in the near-surface compositionally graded layer of n-Hg1-x Cd x Te.

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

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

Zemla, A; Lang, D; Kostova, T

2010-11-29

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory - still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could overcome these difficulties and facilitatemore » the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV, a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus and demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique or that shared structural similarity with structures that are distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position.« less

Analytical calculation on the determination of steep side wall angles from far field measurements

NASA Astrophysics Data System (ADS)

Cisotto, Luca; Pereira, Silvania F.; Urbach, H. Paul

2018-06-01

In the semiconductor industry, the performance and capabilities of the lithographic process are evaluated by measuring specific structures. These structures are often gratings of which the shape is described by a few parameters such as period, middle critical dimension, height, and side wall angle (SWA). Upon direct measurement or retrieval of these parameters, the determination of the SWA suffers from considerable inaccuracies. Although the scattering effects that steep SWAs have on the illumination can be obtained with rigorous numerical simulations, analytical models constitute a very useful tool to get insights into the problem we are treating. In this paper, we develop an approach based on analytical calculations to describe the scattering of a cliff and a ridge with steep SWAs. We also propose a detection system to determine the SWAs of the structures.

Maintenance of polygenic sex determination in a fluctuating environment: an individual-based model.

PubMed

Bateman, A W; Anholt, B R

2017-05-01

R. A. Fisher predicted that individuals should invest equally in offspring of both sexes, and that the proportion of males and females produced (the primary sex ratio) should evolve towards 1:1 when unconstrained. For many species, sex determination is dependent on sex chromosomes, creating a strong tendency for balanced sex ratios, but in other cases, multiple autosomal genes interact to determine sex. In such cases, the maintenance of multiple sex-determining alleles at multiple loci and the consequent among-family variability in sex ratios presents a puzzle, as theory predicts that such systems should be unstable. Theory also predicts that environmental influences on sex can complicate outcomes of genetic sex determination, and that population structure may play a role. Tigriopus californicus, a copepod that lives in splash-pool metapopulations and exhibits polygenic and environment-dependent sex determination, presents a test case for relevant theory. We use this species as a model for parameterizing an individual-based simulation to investigate conditions that could maintain polygenic sex determination. We find that metapopulation structure can delay the degradation of polygenic sex determination and that periods of alternating frequency-dependent selection, imposed by seasonal fluctuations in environmental conditions, can maintain polygenic sex determination indefinitely. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Alcohol sensor based on u-bent hetero-structured fiber optic

NASA Astrophysics Data System (ADS)

Patrialova, Sefi N.; Hatta, Agus M.; Sekartedjo, Sekartedjo

2016-11-01

A sensor based on a fiber optic hetero-structure to determine the concentration of alcohol has been proposed. The structure of the sensing probe in this research is a singlemode-multimode-singlemode (SMS) which bent into Ushaped and soon called as SMS u-bent. The SMS structure was chosen to get a higher sensitivity. This research utilizes the principle of multimode interference and evanescent field by modifying the cladding with various alcohol concentration. Testing of the sensor's performance has been done by measuring the sensor's power output response to the length of the SMS fiber optic, bending diameter, and alcohol concentration. Based on the experiment result, the ubent SMS fiber optic with 50 mm bending diameter and 63 mm MMF lenght has the highest sensitivity, 3.87 dB/% and the minimum resolution, 0.26 x 10-3 %.

Teacher Need-Structure and Instructional Preference in Reading: A Pilot Study.

ERIC Educational Resources Information Center

Duncan, Patricia H.

Thirty-one experienced teachers enrolled in graduate reading courses served as subjects in a study conducted to determine whether simple instruments could be developed to assess teacher need structure, frequency of teacher behaviors related to reading, and the relationship between the two. A 25-item instrument was developed based on Abraham…

Novel fatty acid binding protein 4 (FABP4) inhibitors: virtual screening, synthesis and crystal structure determination.

PubMed

Cai, Haiyan; Liu, Qiufeng; Gao, Dingding; Wang, Ting; Chen, Tiantian; Yan, Guirui; Chen, Kaixian; Xu, Yechun; Wang, Heyao; Li, Yingxia; Zhu, Weiliang

2015-01-27

Fatty acid binding protein 4 (FABP4) is a potential drug target for diabetes and atherosclerosis. For discovering new chemical entities as FABP4 inhibitors, structure-based virtual screening (VS) was performed, bioassay demonstrated that 16 of 251 tested compounds are FABP4 inhibitors, among which compound m1 are more active than endogenous ligand linoleic acid (LA). Based on the structure of m1, new derivatives were designed and prepared, leading to the discovery of two more potent inhibitors, compounds 9 and 10. To further explore the binding mechanisms of these new inhibitors, we determined the X-ray structures of the complexes of FABP4-9 and FABP4-10, which revealed similar binding conformations of the two compounds. Residue Ser53 and Arg126 formed direct hydrogen bonding with the ligands. We also found that 10 could significantly reduce the levels of lipolysis on mouse 3T3-L1 adipocytes. Taken together, in silico, in vitro and crystallographic data provide useful hints for future development of novel inhibitors against FABP4. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A voxel-based asymmetry study of the relationship between hemispheric asymmetry and language dominance in Wada tested patients.

PubMed

Keller, Simon S; Roberts, Neil; Baker, Gus; Sluming, Vanessa; Cezayirli, Enis; Mayes, Andrew; Eldridge, Paul; Marson, Anthony G; Wieshmann, Udo C

2018-03-23

Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole-brain voxel-based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10 (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty-four controls were also studied. Right-handed controls and right-handed patients with left HLD had comparable structural brain asymmetries in cortical, subcortical, and cerebellar regions that have previously been documented in healthy people. However, these patients and controls differed in structural asymmetry of the mesial temporal lobe and a circumscribed region in the superior temporal gyrus, suggesting that only asymmetries of these regions were due to brain alterations caused by epilepsy. Additional comparisons between patients with left and right HLD, matched for type and location of epilepsy, revealed that structural asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal cortex, ventral temporo-occipital cortex, mesial somatosensory cortex, and mesial cerebellum were significantly associated with the side of HLD. Patients with right HLD and bilateral language representation were significantly less right-handed. These results suggest that structural asymmetries of an insular-fronto-temporal network may be related to HLD. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Quantitative analysis of voids in percolating structures in two-dimensional N-body simulations

NASA Technical Reports Server (NTRS)

Harrington, Patrick M.; Melott, Adrian L.; Shandarin, Sergei F.

1993-01-01

We present in this paper a quantitative method for defining void size in large-scale structure based on percolation threshold density. Beginning with two-dimensional gravitational clustering simulations smoothed to the threshold of nonlinearity, we perform percolation analysis to determine the large scale structure. The resulting objective definition of voids has a natural scaling property, is topologically interesting, and can be applied immediately to redshift surveys.

Data Mining of Macromolecular Structures.

PubMed

van Beusekom, Bart; Perrakis, Anastassis; Joosten, Robbie P

2016-01-01

The use of macromolecular structures is widespread for a variety of applications, from teaching protein structure principles all the way to ligand optimization in drug development. Applying data mining techniques on these experimentally determined structures requires a highly uniform, standardized structural data source. The Protein Data Bank (PDB) has evolved over the years toward becoming the standard resource for macromolecular structures. However, the process selecting the data most suitable for specific applications is still very much based on personal preferences and understanding of the experimental techniques used to obtain these models. In this chapter, we will first explain the challenges with data standardization, annotation, and uniformity in the PDB entries determined by X-ray crystallography. We then discuss the specific effect that crystallographic data quality and model optimization methods have on structural models and how validation tools can be used to make informed choices. We also discuss specific advantages of using the PDB_REDO databank as a resource for structural data. Finally, we will provide guidelines on how to select the most suitable protein structure models for detailed analysis and how to select a set of structure models suitable for data mining.

To have or to be? A comparison of materialism-based theories and self-determination theory as explanatory frameworks of prejudice.

PubMed

Van Hiel, Alain; Cornelis, Ilse; Roets, Arne

2010-06-01

The present study aimed to delineate the psychological structure of materialism and intrinsic and extrinsic value pursuit. Moreover, we compared models based on self-determination theory (SDT), Fromm's marketing character, and Inglehart's theory of social change to account for racial prejudice. In a sample of undergraduate students (n=131) and adults (n=176) it was revealed that the extrinsic value pursuit Financial Success/Materialism could be distinguished from the extrinsic value scales Physical Appeal and Social Recognition, and Community Concern could be distinguished from the intrinsic value pursuit scales Self-acceptance and Affiliation. Moreover, Financial Success/Materialism and Community Concern were consistently and significantly related to prejudice, whereas the other SDT facet scales yielded weaker relationships with prejudice. Structural models based on SDT and Inglehart were not corroborated, but instead the present data supported a mediation model based on Fromm's work in which the effect of Community Concern was mediated by Financial Success/Materialism. Broader implications for SDT are critically assessed.

Amino Acid Distribution Rules Predict Protein Fold: Protein Grammar for Beta-Strand Sandwich-Like Structures

PubMed Central

Kister, Alexander

2015-01-01

We present an alternative approach to protein 3D folding prediction based on determination of rules that specify distribution of “favorable” residues, that are mainly responsible for a given fold formation, and “unfavorable” residues, that are incompatible with that fold, in polypeptide sequences. The process of determining favorable and unfavorable residues is iterative. The starting assumptions are based on the general principles of protein structure formation as well as structural features peculiar to a protein fold under investigation. The initial assumptions are tested one-by-one for a set of all known proteins with a given structure. The assumption is accepted as a “rule of amino acid distribution” for the protein fold if it holds true for all, or near all, structures. If the assumption is not accepted as a rule, it can be modified to better fit the data and then tested again in the next step of the iterative search algorithm, or rejected. We determined the set of amino acid distribution rules for a large group of beta sandwich-like proteins characterized by a specific arrangement of strands in two beta sheets. It was shown that this set of rules is highly sensitive (~90%) and very specific (~99%) for identifying sequences of proteins with specified beta sandwich fold structure. The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure. So long as the query protein satisfies residue distribution rules, it can be confidently assigned to its respective protein fold. Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation. It may, therefore, facilitate rational protein engineering design. PMID:25625198

Text Mining for Protein Docking

PubMed Central

Badal, Varsha D.; Kundrotas, Petras J.; Vakser, Ilya A.

2015-01-01

The rapidly growing amount of publicly available information from biomedical research is readily accessible on the Internet, providing a powerful resource for predictive biomolecular modeling. The accumulated data on experimentally determined structures transformed structure prediction of proteins and protein complexes. Instead of exploring the enormous search space, predictive tools can simply proceed to the solution based on similarity to the existing, previously determined structures. A similar major paradigm shift is emerging due to the rapidly expanding amount of information, other than experimentally determined structures, which still can be used as constraints in biomolecular structure prediction. Automated text mining has been widely used in recreating protein interaction networks, as well as in detecting small ligand binding sites on protein structures. Combining and expanding these two well-developed areas of research, we applied the text mining to structural modeling of protein-protein complexes (protein docking). Protein docking can be significantly improved when constraints on the docking mode are available. We developed a procedure that retrieves published abstracts on a specific protein-protein interaction and extracts information relevant to docking. The procedure was assessed on protein complexes from Dockground (http://dockground.compbio.ku.edu). The results show that correct information on binding residues can be extracted for about half of the complexes. The amount of irrelevant information was reduced by conceptual analysis of a subset of the retrieved abstracts, based on the bag-of-words (features) approach. Support Vector Machine models were trained and validated on the subset. The remaining abstracts were filtered by the best-performing models, which decreased the irrelevant information for ~ 25% complexes in the dataset. The extracted constraints were incorporated in the docking protocol and tested on the Dockground unbound benchmark set, significantly increasing the docking success rate. PMID:26650466

Antifungal Indole and Pyrrolidine-2,4-Dione Derivative Peptidomimetic Lead Design Based on In Silico Study of Bioactive Peptide Families

PubMed Central

Moradi, Shoeib; Azerang, Parisa; Khalaj, Vahid; Sardari, Soroush

2013-01-01

Background The rise of opportunistic fungal infections highlights the need for development of new antimicrobial agents. Antimicrobial Peptides (AMPs) and Antifungal Peptides (AFPs) are among the agents with minimal resistance being developed against them, therefore they can be used as structural templates for design of new antimicrobial agents. Methods In the present study four antifungal peptidomimetic structures named C1 to C4 were designed based on plant defensin of Pisum sativum. Minimum inhibitory concentrations (MICs) for these structures were determined against Aspergillus niger N402, Candida albicans ATCC 10231, and Saccharomyces cerevisiae PTCC 5052. Results C1 and C2 showed more potent antifungal activity against these fungal strains compared to C3 and C4. The structure C2 demonstrated a potent antifungal activity among them and could be used as a template for future study on antifungal peptidomemetics design. Sequences alignments led to identifying antifungal decapeptide (KTCENLADTY) named KTC-Y, which its MIC was determined on fungal protoplast showing 25 (µg/ml) against Aspergillus fumigatus Af293. Conclusion The present approach to reach the antifungal molecules seems to be a powerful approach in design of bioactive agents based on AMP mimetic identification. PMID:23626876

A semi-supervised learning approach for RNA secondary structure prediction.

PubMed

Yonemoto, Haruka; Asai, Kiyoshi; Hamada, Michiaki

2015-08-01

RNA secondary structure prediction is a key technology in RNA bioinformatics. Most algorithms for RNA secondary structure prediction use probabilistic models, in which the model parameters are trained with reliable RNA secondary structures. Because of the difficulty of determining RNA secondary structures by experimental procedures, such as NMR or X-ray crystal structural analyses, there are still many RNA sequences that could be useful for training whose secondary structures have not been experimentally determined. In this paper, we introduce a novel semi-supervised learning approach for training parameters in a probabilistic model of RNA secondary structures in which we employ not only RNA sequences with annotated secondary structures but also ones with unknown secondary structures. Our model is based on a hybrid of generative (stochastic context-free grammars) and discriminative models (conditional random fields) that has been successfully applied to natural language processing. Computational experiments indicate that the accuracy of secondary structure prediction is improved by incorporating RNA sequences with unknown secondary structures into training. To our knowledge, this is the first study of a semi-supervised learning approach for RNA secondary structure prediction. This technique will be useful when the number of reliable structures is limited. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamic Camouflage in Benthic and Pelagic Cephalopods: An Interdisciplinary Approach to Crypsis Based on Color, Reflection, and Bioluminescence

DTIC Science & Technology

2012-09-30

display a currently valid OMB control number. 1. REPORT DATE 2012 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Dynamic...2. To determine the visual abilities of several species of cephalopod and model both the shallow and deep-water world from the animals’ points...ultrastructure of the reflectin-based structures using transmission electron microscopy and model their optical effects to determine what aspects of

Small-angle x-ray scattering study of polymer structure: Carbosilane dendrimers in hexane solution

NASA Astrophysics Data System (ADS)

Shtykova, E. V.; Feigin, L. A.; Volkov, V. V.; Malakhova, Yu. N.; Streltsov, D. R.; Buzin, A. I.; Chvalun, S. N.; Katarzhanova, E. Yu.; Ignatieva, G. M.; Muzafarov, A. M.

2016-09-01

The three-dimensional organization of monodisperse hyper-branched macromolecules of regular structure—carbosilane dendrimers of zero, third, and sixth generations—has been studied by small-angle X-ray scattering (SAXS) in solution. The use of modern methods of SAXS data interpretation, including ab initio modeling, has made it possible to determine the internal architecture of the dendrimers in dependence of the generation number and the number of cyclosiloxane end groups (forming the shell of dendritic macromolecules) and show dendrimers to be spherical. The structural results give grounds to consider carbosilane dendrimers promising objects for forming crystals with subsequent structural analysis and determining their structure with high resolution, as well as for designing new materials to be used in various dendrimer-based technological applications.

Report of the panel on earth structure and dynamics, section 6

NASA Technical Reports Server (NTRS)

Dziewonski, Adam M.; Mcadoo, David C.; Oconnell, Richard J.; Smylie, Douglas E.; Yoder, Charles F.

1991-01-01

The panel identified problems related to the dynamics of the core and mantle that should be addressed by NASA programs. They include investigating the geodynamo based on observations of the Earth's magnetic field, determining the rheology of the mantle from geodetic observations of post-glacial vertical motions and changes in the gravity field, and determining the coupling between plate motions and mantle flow from geodetic observations of plate deformation. Also emphasized is the importance of support for interdisciplinary research to combine various data sets with models which couple rheology, structure and dynamics.

Carbon Nanostructure Examined by Lattice Fringe Analysis of High Resolution Transmission Electron Microscopy Images

NASA Technical Reports Server (NTRS)

VanderWal, Randy L.; Tomasek, Aaron J.; Street, Kenneth; Thompson, William K.

2002-01-01

The dimensions of graphitic layer planes directly affect the reactivity of soot towards oxidation and growth. Quantification of graphitic structure could be used to develop and test correlations between the soot nanostructure and its reactivity. Based upon transmission electron microscopy images, this paper provides a demonstration of the robustness of a fringe image analysis code for determining the level of graphitic structure within nanoscale carbon, i.e. soot. Results, in the form of histograms of graphitic layer plane lengths, are compared to their determination through Raman analysis.

Carbon Nanostructure Examined by Lattice Fringe Analysis of High Resolution Transmission Electron Microscopy Images

NASA Technical Reports Server (NTRS)

VanderWal, Randy L.; Tomasek, Aaron J.; Street, Kenneth; Thompson, William K.; Hull, David R.

2003-01-01

The dimensions of graphitic layer planes directly affect the reactivity of soot towards oxidation and growth. Quantification of graphitic structure could be used to develop and test correlations between the soot nanostructure and its reactivity. Based upon transmission electron microscopy images, this paper provides a demonstration of the robustness of a fringe image analysis code for determining the level of graphitic structure within nanoscale carbon, i.e., soot. Results, in the form of histograms of graphitic layer plane lengths, are compared to their determination through Raman analysis.

Global search in photoelectron diffraction structure determination using genetic algorithms

NASA Astrophysics Data System (ADS)

Viana, M. L.; Díez Muiño, R.; Soares, E. A.; Van Hove, M. A.; de Carvalho, V. E.

2007-11-01

Photoelectron diffraction (PED) is an experimental technique widely used to perform structural determinations of solid surfaces. Similarly to low-energy electron diffraction (LEED), structural determination by PED requires a fitting procedure between the experimental intensities and theoretical results obtained through simulations. Multiple scattering has been shown to be an effective approach for making such simulations. The quality of the fit can be quantified through the so-called R-factor. Therefore, the fitting procedure is, indeed, an R-factor minimization problem. However, the topography of the R-factor as a function of the structural and non-structural surface parameters to be determined is complex, and the task of finding the global minimum becomes tough, particularly for complex structures in which many parameters have to be adjusted. In this work we investigate the applicability of the genetic algorithm (GA) global optimization method to this problem. The GA is based on the evolution of species, and makes use of concepts such as crossover, elitism and mutation to perform the search. We show results of its application in the structural determination of three different systems: the Cu(111) surface through the use of energy-scanned experimental curves; the Ag(110)-c(2 × 2)-Sb system, in which a theory-theory fit was performed; and the Ag(111) surface for which angle-scanned experimental curves were used. We conclude that the GA is a highly efficient method to search for global minima in the optimization of the parameters that best fit the experimental photoelectron diffraction intensities to the theoretical ones.

Survey of large protein complexes D. vulgaris reveals great structural diversity

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

Han, B.-G.; Dong, M.; Liu, H.

2009-08-15

An unbiased survey has been made of the stable, most abundant multi-protein complexes in Desulfovibrio vulgaris Hildenborough (DvH) that are larger than Mr {approx} 400 k. The quaternary structures for 8 of the 16 complexes purified during this work were determined by single-particle reconstruction of negatively stained specimens, a success rate {approx}10 times greater than that of previous 'proteomic' screens. In addition, the subunit compositions and stoichiometries of the remaining complexes were determined by biochemical methods. Our data show that the structures of only two of these large complexes, out of the 13 in this set that have recognizable functions,more » can be modeled with confidence based on the structures of known homologs. These results indicate that there is significantly greater variability in the way that homologous prokaryotic macromolecular complexes are assembled than has generally been appreciated. As a consequence, we suggest that relying solely on previously determined quaternary structures for homologous proteins may not be sufficient to properly understand their role in another cell of interest.« less

Model-based local density sharpening of cryo-EM maps

PubMed Central

Jakobi, Arjen J; Wilmanns, Matthias

2017-01-01

Atomic models based on high-resolution density maps are the ultimate result of the cryo-EM structure determination process. Here, we introduce a general procedure for local sharpening of cryo-EM density maps based on prior knowledge of an atomic reference structure. The procedure optimizes contrast of cryo-EM densities by amplitude scaling against the radially averaged local falloff estimated from a windowed reference model. By testing the procedure using six cryo-EM structures of TRPV1, β-galactosidase, γ-secretase, ribosome-EF-Tu complex, 20S proteasome and RNA polymerase III, we illustrate how local sharpening can increase interpretability of density maps in particular in cases of resolution variation and facilitates model building and atomic model refinement. PMID:29058676

Using a two-phase evolutionary framework to select multiple network spreaders based on community structure

NASA Astrophysics Data System (ADS)

Fu, Yu-Hsiang; Huang, Chung-Yuan; Sun, Chuen-Tsai

2016-11-01

Using network community structures to identify multiple influential spreaders is an appropriate method for analyzing the dissemination of information, ideas and infectious diseases. For example, data on spreaders selected from groups of customers who make similar purchases may be used to advertise products and to optimize limited resource allocation. Other examples include community detection approaches aimed at identifying structures and groups in social or complex networks. However, determining the number of communities in a network remains a challenge. In this paper we describe our proposal for a two-phase evolutionary framework (TPEF) for determining community numbers and maximizing community modularity. Lancichinetti-Fortunato-Radicchi benchmark networks were used to test our proposed method and to analyze execution time, community structure quality, convergence, and the network spreading effect. Results indicate that our proposed TPEF generates satisfactory levels of community quality and convergence. They also suggest a need for an index, mechanism or sampling technique to determine whether a community detection approach should be used for selecting multiple network spreaders.

Predictive and Experimental Approaches for Elucidating Protein–Protein Interactions and Quaternary Structures

PubMed Central

Nealon, John Oliver; Philomina, Limcy Seby

2017-01-01

The elucidation of protein–protein interactions is vital for determining the function and action of quaternary protein structures. Here, we discuss the difficulty and importance of establishing protein quaternary structure and review in vitro and in silico methods for doing so. Determining the interacting partner proteins of predicted protein structures is very time-consuming when using in vitro methods, this can be somewhat alleviated by use of predictive methods. However, developing reliably accurate predictive tools has proved to be difficult. We review the current state of the art in predictive protein interaction software and discuss the problem of scoring and therefore ranking predictions. Current community-based predictive exercises are discussed in relation to the growth of protein interaction prediction as an area within these exercises. We suggest a fusion of experimental and predictive methods that make use of sparse experimental data to determine higher resolution predicted protein interactions as being necessary to drive forward development. PMID:29206185

Surveying hospital network structure in New York State: how are they structured?

PubMed

Nauenberg, E; Brewer, C S

2000-01-01

We determine the most common network structures in New York state. The taxonomy employed uses three structural dimensions: integration, complexity, and risk-sharing between organizations. Based on a survey conducted in 1996, the most common type of network (26.4 percent) had medium levels of integration, medium or high levels of complexity, and some risk-sharing. Also common were networks with low levels of integration, low levels of complexity, and no risk-sharing (22.1 percent).

Methods for combining payload parameter variations with input environment. [calculating design limit loads compatible with probabilistic structural design criteria

NASA Technical Reports Server (NTRS)

Merchant, D. H.

1976-01-01

Methods are presented for calculating design limit loads compatible with probabilistic structural design criteria. The approach is based on the concept that the desired limit load, defined as the largest load occurring in a mission, is a random variable having a specific probability distribution which may be determined from extreme-value theory. The design limit load, defined as a particular of this random limit load, is the value conventionally used in structural design. Methods are presented for determining the limit load probability distributions from both time-domain and frequency-domain dynamic load simulations. Numerical demonstrations of the method are also presented.

Assessment of PIV-based unsteady load determination of an airfoil with actuated flap

NASA Astrophysics Data System (ADS)

Sterenborg, J. J. H. M.; Lindeboom, R. C. J.; Simão Ferreira, C. J.; van Zuijlen, A. H.; Bijl, H.

2014-02-01

For complex experimental setups involving movable structures it is not trivial to directly measure unsteady loads. An alternative is to deduce unsteady loads indirectly from measured velocity fields using Noca's method. The ultimate aim is to use this method in future work to determine unsteady loads for fluid-structure interaction problems. The focus in this paper is first on the application and assessment of Noca's method for an airfoil with an oscillating trailing edge flap. To our best knowledge Noca's method has not been applied yet to airfoils with moving control surfaces or fluid-structure interaction problems. In addition, wind tunnel corrections for this type of unsteady flow problem are considered.

Ab initio simulations of the dynamic ion structure factor of warm dense lithium

DOE PAGES

Witte, B. B. L.; Shihab, M.; Glenzer, S. H.; ...

2017-04-06

Here, we present molecular dynamics simulations based on finite-temperature density functional theory that determine self-consistently the dynamic ion structure factor and the electronic form factor in lithium. Our comprehensive data set allows for the calculation of the dispersion relation for collective excitations, the calculation of the sound velocity, and the determination of the ion feature from the total electronic form factor and the ion structure factor. The results are compared with available experimental x-ray and neutron scattering data. Good agreement is found for both the liquid metal and warm dense matter domain. Finally, we study the impact of possible targetmore » inhomogeneities on x-ray scattering spectra.« less

Ab initio simulations of the dynamic ion structure factor of warm dense lithium

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

Witte, B. B. L.; Shihab, M.; Glenzer, S. H.

Here, we present molecular dynamics simulations based on finite-temperature density functional theory that determine self-consistently the dynamic ion structure factor and the electronic form factor in lithium. Our comprehensive data set allows for the calculation of the dispersion relation for collective excitations, the calculation of the sound velocity, and the determination of the ion feature from the total electronic form factor and the ion structure factor. The results are compared with available experimental x-ray and neutron scattering data. Good agreement is found for both the liquid metal and warm dense matter domain. Finally, we study the impact of possible targetmore » inhomogeneities on x-ray scattering spectra.« less

Conformational Transitions upon Ligand Binding: Holo-Structure Prediction from Apo Conformations

PubMed Central

Seeliger, Daniel; de Groot, Bert L.

2010-01-01

Biological function of proteins is frequently associated with the formation of complexes with small-molecule ligands. Experimental structure determination of such complexes at atomic resolution, however, can be time-consuming and costly. Computational methods for structure prediction of protein/ligand complexes, particularly docking, are as yet restricted by their limited consideration of receptor flexibility, rendering them not applicable for predicting protein/ligand complexes if large conformational changes of the receptor upon ligand binding are involved. Accurate receptor models in the ligand-bound state (holo structures), however, are a prerequisite for successful structure-based drug design. Hence, if only an unbound (apo) structure is available distinct from the ligand-bound conformation, structure-based drug design is severely limited. We present a method to predict the structure of protein/ligand complexes based solely on the apo structure, the ligand and the radius of gyration of the holo structure. The method is applied to ten cases in which proteins undergo structural rearrangements of up to 7.1 Å backbone RMSD upon ligand binding. In all cases, receptor models within 1.6 Å backbone RMSD to the target were predicted and close-to-native ligand binding poses were obtained for 8 of 10 cases in the top-ranked complex models. A protocol is presented that is expected to enable structure modeling of protein/ligand complexes and structure-based drug design for cases where crystal structures of ligand-bound conformations are not available. PMID:20066034

Accurate anharmonic zero-point energies for some combustion-related species from diffusion Monte Carlo

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

Harding, Lawrence B.; Georgievskii, Yuri; Klippenstein, Stephen J.

Full dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ calculations have been determined for 48 small combustion related molecules. The analytic surfaces have been used in Diffusion Monte Carlo calculations of the anharmonic, zero point energies. Here, the resulting anharmonicity corrections are compared to vibrational perturbation theory results based both on the same level of electronic structure theory and on lower level electronic structure methods (B3LYP and MP2).

Program structure-based blocking

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

Bertolli, Carlo; Eichenberger, Alexandre E.; O'Brien, John K.

2017-09-26

Embodiments relate to program structure-based blocking. An aspect includes receiving source code corresponding to a computer program by a compiler of a computer system. Another aspect includes determining a prefetching section in the source code by a marking module of the compiler. Yet another aspect includes performing, by a blocking module of the compiler, blocking of instructions located in the prefetching section into instruction blocks, such that the instruction blocks of the prefetching section only contain instructions that are located in the prefetching section.

Accurate Anharmonic Zero-Point Energies for Some Combustion-Related Species from Diffusion Monte Carlo.

PubMed

Harding, Lawrence B; Georgievskii, Yuri; Klippenstein, Stephen J

2017-06-08

Full-dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ calculations have been determined for 48 small combustion-related molecules. The analytic surfaces have been used in Diffusion Monte Carlo calculations of the anharmonic zero-point energies. The resulting anharmonicity corrections are compared to vibrational perturbation theory results based both on the same level of electronic structure theory and on lower-level electronic structure methods (B3LYP and MP2).

Accurate anharmonic zero-point energies for some combustion-related species from diffusion Monte Carlo

DOE PAGES

Harding, Lawrence B.; Georgievskii, Yuri; Klippenstein, Stephen J.

2017-05-17

Full dimensional analytic potential energy surfaces based on CCSD(T)/cc-pVTZ calculations have been determined for 48 small combustion related molecules. The analytic surfaces have been used in Diffusion Monte Carlo calculations of the anharmonic, zero point energies. Here, the resulting anharmonicity corrections are compared to vibrational perturbation theory results based both on the same level of electronic structure theory and on lower level electronic structure methods (B3LYP and MP2).

VoroMQA: Assessment of protein structure quality using interatomic contact areas.

PubMed

Olechnovič, Kliment; Venclovas, Česlovas

2017-06-01

In the absence of experimentally determined protein structure many biological questions can be addressed using computational structural models. However, the utility of protein structural models depends on their quality. Therefore, the estimation of the quality of predicted structures is an important problem. One of the approaches to this problem is the use of knowledge-based statistical potentials. Such methods typically rely on the statistics of distances and angles of residue-residue or atom-atom interactions collected from experimentally determined structures. Here, we present VoroMQA (Voronoi tessellation-based Model Quality Assessment), a new method for the estimation of protein structure quality. Our method combines the idea of statistical potentials with the use of interatomic contact areas instead of distances. Contact areas, derived using Voronoi tessellation of protein structure, are used to describe and seamlessly integrate both explicit interactions between protein atoms and implicit interactions of protein atoms with solvent. VoroMQA produces scores at atomic, residue, and global levels, all in the fixed range from 0 to 1. The method was tested on the CASP data and compared to several other single-model quality assessment methods. VoroMQA showed strong performance in the recognition of the native structure and in the structural model selection tests, thus demonstrating the efficacy of interatomic contact areas in estimating protein structure quality. The software implementation of VoroMQA is freely available as a standalone application and as a web server at http://bioinformatics.lt/software/voromqa. Proteins 2017; 85:1131-1145. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Salient object detection: manifold-based similarity adaptation approach

NASA Astrophysics Data System (ADS)

Zhou, Jingbo; Ren, Yongfeng; Yan, Yunyang; Gao, Shangbing

2014-11-01

A saliency detection algorithm based on manifold-based similarity adaptation is proposed. The proposed algorithm is divided into three steps. First, we segment an input image into superpixels, which are represented as the nodes in a graph. Second, a new similarity measurement is used in the proposed algorithm. The weight matrix of the graph, which indicates the similarities between the nodes, uses a similarity-based method. It also captures the manifold structure of the image patches, in which the graph edges are determined in a data adaptive manner in terms of both similarity and manifold structure. Then, we use local reconstruction method as a diffusion method to obtain the saliency maps. The objective function in the proposed method is based on local reconstruction, with which estimated weights capture the manifold structure. Experiments on four bench-mark databases demonstrate the accuracy and robustness of the proposed method.

Prediction of nanofluids properties: the density and the heat capacity

NASA Astrophysics Data System (ADS)

Zhelezny, V. P.; Motovoy, I. V.; Ustyuzhanin, E. E.

2017-11-01

The results given in this report show that the additives of Al2O3 nanoparticles lead to increase the density and decrease the heat capacity of isopropanol. Based on the experimental data the excess molar volume and the excess molar heat capacity were calculated. The report suggests new method for predicting the molar volume and molar heat capacity of nanofluids. It is established that the values of the excess thermodynamic functions are determined by the properties and the volume of the structurally oriented layers of the base fluid molecules near the surface of nanoparticles. The heat capacity of the structurally oriented layers of the base fluid is less than the heat capacity of the base fluid for given parameters due to the greater regulation of its structure. It is shown that information on the geometric dimensions of the structured layers of the base fluid near nanoparticles can be obtained from data on the nanofluids density and at ambient temperature - by the dynamic light scattering method. For calculations of the nanofluids heat capacity over a wide range of temperatures a new correlation based on the extended scaling is proposed.

Unraveling the meaning of chemical shifts in protein NMR.

PubMed

Berjanskii, Mark V; Wishart, David S

2017-11-01

Chemical shifts are among the most informative parameters in protein NMR. They provide wealth of information about protein secondary and tertiary structure, protein flexibility, and protein-ligand binding. In this report, we review the progress in interpreting and utilizing protein chemical shifts that has occurred over the past 25years, with a particular focus on the large body of work arising from our group and other Canadian NMR laboratories. More specifically, this review focuses on describing, assessing, and providing some historical context for various chemical shift-based methods to: (1) determine protein secondary and super-secondary structure; (2) derive protein torsion angles; (3) assess protein flexibility; (4) predict residue accessible surface area; (5) refine 3D protein structures; (6) determine 3D protein structures and (7) characterize intrinsically disordered proteins. This review also briefly covers some of the methods that we previously developed to predict chemical shifts from 3D protein structures and/or protein sequence data. It is hoped that this review will help to increase awareness of the considerable utility of NMR chemical shifts in structural biology and facilitate more widespread adoption of chemical-shift based methods by the NMR spectroscopists, structural biologists, protein biophysicists, and biochemists worldwide. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

Thermodynamic heuristics with case-based reasoning: combined insights for RNA pseudoknot secondary structure.

PubMed

Al-Khatib, Ra'ed M; Rashid, Nur'Aini Abdul; Abdullah, Rosni

2011-08-01

The secondary structure of RNA pseudoknots has been extensively inferred and scrutinized by computational approaches. Experimental methods for determining RNA structure are time consuming and tedious; therefore, predictive computational approaches are required. Predicting the most accurate and energy-stable pseudoknot RNA secondary structure has been proven to be an NP-hard problem. In this paper, a new RNA folding approach, termed MSeeker, is presented; it includes KnotSeeker (a heuristic method) and Mfold (a thermodynamic algorithm). The global optimization of this thermodynamic heuristic approach was further enhanced by using a case-based reasoning technique as a local optimization method. MSeeker is a proposed algorithm for predicting RNA pseudoknot structure from individual sequences, especially long ones. This research demonstrates that MSeeker improves the sensitivity and specificity of existing RNA pseudoknot structure predictions. The performance and structural results from this proposed method were evaluated against seven other state-of-the-art pseudoknot prediction methods. The MSeeker method had better sensitivity than the DotKnot, FlexStem, HotKnots, pknotsRG, ILM, NUPACK and pknotsRE methods, with 79% of the predicted pseudoknot base-pairs being correct.

Determinants of Literacy Proficiency: A Lifelong-Lifewide Learning Perspective

ERIC Educational Resources Information Center

Desjardins, Richard

2003-01-01

The aim of this article is to investigate the predictive capacity of major determinants of literacy proficiency that are associated with a variety of contexts including school, home, work, community and leisure. An identical structural model based on previous research is fitted to data for 18 countries. The results show that even after accounting…

Mapping the nomological network of employee self-determined safety motivation: A preliminary measure in China.

PubMed

Jiang, Li; Tetrick, Lois E

2016-09-01

The present study introduced a preliminary measure of employee safety motivation based on the definition of self-determination theory from Fleming (2012) research and validated the structure of self-determined safety motivation (SDSM) by surveying 375 employees in a Chinese high-risk organization. First, confirmatory factor analysis (CFA) was used to examine the factor structure of SDSM, and indices of five-factor model CFA met the requirements. Second, a nomological network was examined to provide evidence of the construct validity of SDSM. Beyond construct validity, the analysis also produced some interesting results concerning the relationship between leadership antecedents and safety motivation, and between safety motivation and safety behavior. Autonomous motivation was positively related to transformational leadership, negatively related to abusive supervision, and positively related to safety behavior. Controlled motivation with the exception of introjected regulation was negatively related to transformational leadership, positively related to abusive supervision, and negatively related to safety behavior. The unique role of introjected regulation and future research based on self-determination theory were discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

All-atom four-body knowledge-based statistical potential to distinguish native tertiary RNA structures from nonnative folds.

PubMed

Masso, Majid

2018-09-14

Scientific breakthroughs in recent decades have uncovered the capability of RNA molecules to fulfill a wide array of structural, functional, and regulatory roles in living cells, leading to a concomitantly significant increase in both the number and diversity of experimentally determined RNA three-dimensional (3D) structures. Atomic coordinates from a representative training set of solved RNA structures, displaying low sequence and structure similarity, facilitate derivation of knowledge-based energy functions. Here we develop an all-atom four-body statistical potential and evaluate its capacity to distinguish native RNA 3D structures from nonnative folds based on calculated free energy scores. Atomic four-body nearest-neighbors are objectively identified by their occurrence as tetrahedral vertices in the Delaunay tessellations of RNA structures, and rates of atomic quadruplet interactions expected by chance are obtained from a multinomial reference distribution. Our four-body energy function, referred to as RAMP (ribonucleic acids multibody potential), is subsequently derived by applying the inverted Boltzmann principle to the frequency data, yielding an energy score for each type of atomic quadruplet interaction. Several well-known benchmark datasets reveal that RAMP is comparable with, and often outperforms, existing knowledge- and physics-based energy functions. To the best of our knowledge, this is the first study detailing an RNA tertiary structure-based multibody statistical potential and its comparative evaluation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography

DOE PAGES

Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius; ...

2015-05-07

We report that angiotensin II type 1 receptor (AT 1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT 1R blockers (ARBs), the structural basis for AT 1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT 1R in complex with its selective antagonist ZD7155 atmore » 2.9 Å resolution. The AT 1R-ZD7155 complex structure revealed key structural features ofAT 1R and critical interactions for ZD7155 binding. Finally, docking simulations of the clinically used ARBs into the AT 1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT 1R structure-function relationship and structure-based drug design.« less

Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography

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

Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius

We report that angiotensin II type 1 receptor (AT 1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT 1R blockers (ARBs), the structural basis for AT 1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT 1R in complex with its selective antagonist ZD7155 atmore » 2.9 Å resolution. The AT 1R-ZD7155 complex structure revealed key structural features ofAT 1R and critical interactions for ZD7155 binding. Finally, docking simulations of the clinically used ARBs into the AT 1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT 1R structure-function relationship and structure-based drug design.« less

Determination of the structure of lecithins.

PubMed

Blank, M L; Nutter, L J; Privett, O S

1966-03-01

A method is described for the determination of the classes of lecithins in terms of unsaturated and saturated fatty acids based on a total fatty acid composition, the composition of the fatty acids in the beta-position, and the amount of disaturated class determined via mercuric acetate adduct formation. The accuracy of the method was determined on lecithins of known composition and the method was applied to lecithins isolated from milk serum and egg lipids, safflower and soybean oils.

Comparative studies of industrial grade carbon black powders

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

Chawla, Komal, E-mail: komalchawla.rs@gmail.com; Chauhan, Alok P. S., E-mail: chauhan.alok@gmail.com, E-mail: alok.chauhan@alumni.stonybrook.edu

Comparative studies of two dissimilar industrial grade Carbon Black (CB) powders (N375 and N405) were conducted. The structure, surface area and particle size are the three important characteristics of CB powder that determine their processability and application as filler in preparing rubber compounds. The powders were characterized for their structure using dibutyl phthalate absorption (DBPA), particle size via laser particle size analyzer and surface area by nitrogen adsorption method. The structural characterization showed that N405 had lower DBPA in comparison to N375, confirming low structure of N405 grade CB powder. It was observed from the particle size analysis that N375more » was coarser than N405 grade CB. The total surface area values were determined by the BET method based on the cross sectional area of the nitrogen molecule. N375, a coarse grade CB powder with high structure, depicted less surface area as compared to N405.« less

Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

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

Ghosh, Arun K.; Brindisi, Margherita; Nyalapatla, Prasanth R.

Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 Å resolution. These structures revealed important molecular insight into the inhibitor–HIV-1 protease interactions in the active site.

Theoretical and experimental studies of the current–voltage and capacitance–voltage of HEMT structures and field-effect transistors

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

Tarasova, E. A.; Obolenskaya, E. S., E-mail: obolensk@rf.unn.ru; Hananova, A. V.

The sensitivity of classical n{sup +}/n{sup –} GaAs and AlGaN/GaN structures with a 2D electron gas (HEMT) and field-effect transistors based on these structures to γ-neutron exposure is studied. The levels of their radiation hardness were determined. A method for experimental study of the structures on the basis of a differential analysis of their current–voltage characteristics is developed. This method makes it possible to determine the structure of the layers in which radiation-induced defects accumulate. A procedure taking into account changes in the plate area of the experimentally measured barrier-contact capacitance associated with the emergence of clusters of radiation-induced defectsmore » that form dielectric inclusions in the 2D-electron-gas layer is presented for the first time.« less

Sample-based synthesis of two-scale structures with anisotropy

DOE PAGES

Liu, Xingchen; Shapiro, Vadim

2017-05-19

A vast majority of natural or synthetic materials are characterized by their anisotropic properties, such as stiffness. Such anisotropy is effected by the spatial distribution of the fine-scale structure and/or anisotropy of the constituent phases at a finer scale. In design, proper control of the anisotropy may greatly enhance the efficiency and performance of synthesized structures. In this paper, we propose a sample-based two-scale structure synthesis approach that explicitly controls anisotropic effective material properties of the structure on the coarse scale by orienting sampled material neighborhoods at the fine scale. We first characterize the non-uniform orientations distribution of the samplemore » structure by showing that the principal axes of an orthotropic material may be determined by the eigenvalue decomposition of its effective stiffness tensor. Such effective stiffness tensors can be efficiently estimated based on the two-point correlation functions of the fine-scale structures. Then we synthesize the two-scale structure by rotating fine-scale structures from the sample to follow a given target orientation field. Finally, the effectiveness of the proposed approach is demonstrated through examples in both 2D and 3D.« less

Sample-based synthesis of two-scale structures with anisotropy

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

Liu, Xingchen; Shapiro, Vadim

A vast majority of natural or synthetic materials are characterized by their anisotropic properties, such as stiffness. Such anisotropy is effected by the spatial distribution of the fine-scale structure and/or anisotropy of the constituent phases at a finer scale. In design, proper control of the anisotropy may greatly enhance the efficiency and performance of synthesized structures. In this paper, we propose a sample-based two-scale structure synthesis approach that explicitly controls anisotropic effective material properties of the structure on the coarse scale by orienting sampled material neighborhoods at the fine scale. We first characterize the non-uniform orientations distribution of the samplemore » structure by showing that the principal axes of an orthotropic material may be determined by the eigenvalue decomposition of its effective stiffness tensor. Such effective stiffness tensors can be efficiently estimated based on the two-point correlation functions of the fine-scale structures. Then we synthesize the two-scale structure by rotating fine-scale structures from the sample to follow a given target orientation field. Finally, the effectiveness of the proposed approach is demonstrated through examples in both 2D and 3D.« less

Density functional theory calculations of III-N based semiconductors with mBJLDA

NASA Astrophysics Data System (ADS)

Gürel, Hikmet Hakan; Akıncı, Özden; Ünlü, Hilmi

2017-02-01

In this work, we present first principles calculations based on a full potential linear augmented plane-wave method (FP-LAPW) to calculate structural and electronic properties of III-V based nitrides such as GaN, AlN, InN in a zinc-blende cubic structure. First principles calculation using the local density approximation (LDA) and generalized gradient approximation (GGA) underestimate the band gap. We proposed a new potential called modified Becke-Johnson local density approximation (MBJLDA) that combines modified Becke-Johnson exchange potential and the LDA correlation potential to get better band gap results compared to experiment. We compared various exchange-correlation potentials (LSDA, GGA, HSE, and MBJLDA) to determine band gaps and structural properties of semiconductors. We show that using MBJLDA density potential gives a better agreement with experimental data for band gaps III-V nitrides based semiconductors.

Towards a First-Principles Determination of Effective Coulomb Interactions in Correlated Electron Materials: Role of Intershell Interactions

NASA Astrophysics Data System (ADS)

Seth, Priyanka; Hansmann, Philipp; van Roekeghem, Ambroise; Vaugier, Loig; Biermann, Silke

2017-08-01

The determination of the effective Coulomb interactions to be used in low-energy Hamiltonians for materials with strong electronic correlations remains one of the bottlenecks for parameter-free electronic structure calculations. We propose and benchmark a scheme for determining the effective local Coulomb interactions for charge-transfer oxides and related compounds. Intershell interactions between electrons in the correlated shell and ligand orbitals are taken into account in an effective manner, leading to a reduction of the effective local interactions on the correlated shell. Our scheme resolves inconsistencies in the determination of effective interactions as obtained by standard methods for a wide range of materials, and allows for a conceptual understanding of the relation of cluster model and dynamical mean field-based electronic structure calculations.

Towards a First-Principles Determination of Effective Coulomb Interactions in Correlated Electron Materials: Role of Intershell Interactions.

PubMed

Seth, Priyanka; Hansmann, Philipp; van Roekeghem, Ambroise; Vaugier, Loig; Biermann, Silke

2017-08-04

The determination of the effective Coulomb interactions to be used in low-energy Hamiltonians for materials with strong electronic correlations remains one of the bottlenecks for parameter-free electronic structure calculations. We propose and benchmark a scheme for determining the effective local Coulomb interactions for charge-transfer oxides and related compounds. Intershell interactions between electrons in the correlated shell and ligand orbitals are taken into account in an effective manner, leading to a reduction of the effective local interactions on the correlated shell. Our scheme resolves inconsistencies in the determination of effective interactions as obtained by standard methods for a wide range of materials, and allows for a conceptual understanding of the relation of cluster model and dynamical mean field-based electronic structure calculations.

[Structural and Dipole Structure Peculiarities of Hoogsteen Base Pairs Formed in Complementary Nucleobases according to ab initio Quantum Mechanics Studies].

PubMed

Petrenko, Y M

2015-01-01

Ab initio quantum mechanics studies for the detection of structure and dipole structure peculiarities of Hoogsteen base pairs relative to Watson-Crick base pairs, were performed during our work. These base pairs are formed as a result of complementary interactions. It was revealed, that adenine-thymine Hoogsteen base pair and adenine-thymine Watson-Crick base pairs can be formed depending on initial configuration. Cytosine-guanine Hoogsteen pairs are formed only when cytosine was originally protonated. Both types of Hoogsteen pairs have noticeable difference in the bond distances and angles. These differences appeared in purine as well as in pyrimidine parts of the pairs. Hoogsteen pairs have mostly shorter hydrogen bond lengths and significantly larger angles of hydrogen bonds and larger angles between the hydrogen bonds than Watson-Crick base pairs. Notable differences are also observed with respect to charge distribution and dipole moment. Quantitative data on these differences are shown in our work. It is also reported that the values of local parameters (according to Cambridge classification of the parameters which determine DNA properties) in Hoogsteen base pairs, are greatly different from Watson-Crick ones.

pKa shifting in double-stranded RNA is highly dependent upon nearest neighbors and bulge positioning.

PubMed

Wilcox, Jennifer L; Bevilacqua, Philip C

2013-10-22

Shifting of pKa's in RNA is important for many biological processes; however, the driving forces responsible for shifting are not well understood. Herein, we determine how structural environments surrounding protonated bases affect pKa shifting in double-stranded RNA (dsRNA). Using (31)P NMR, we determined the pKa of the adenine in an A(+)·C base pair in various sequence and structural environments. We found a significant dependence of pKa on the base pairing strength of nearest neighbors and the location of a nearby bulge. Increasing nearest neighbor base pairing strength shifted the pKa of the adenine in an A(+)·C base pair higher by an additional 1.6 pKa units, from 6.5 to 8.1, which is well above neutrality. The addition of a bulge two base pairs away from a protonated A(+)·C base pair shifted the pKa by only ~0.5 units less than a perfectly base paired hairpin; however, positioning the bulge just one base pair away from the A(+)·C base pair prohibited formation of the protonated base pair as well as several flanking base pairs. Comparison of data collected at 25 °C and 100 mM KCl to biological temperature and Mg(2+) concentration revealed only slight pKa changes, suggesting that similar sequence contexts in biological systems have the potential to be protonated at biological pH. We present a general model to aid in the determination of the roles protonated bases may play in various dsRNA-mediated processes including ADAR editing, miRNA processing, programmed ribosomal frameshifting, and general acid-base catalysis in ribozymes.

Population structure of humpback whales in the western and central South Pacific Ocean as determined by vocal exchange among populations.

PubMed

Garland, Ellen C; Goldizen, Anne W; Lilley, Matthew S; Rekdahl, Melinda L; Garrigue, Claire; Constantine, Rochelle; Hauser, Nan Daeschler; Poole, M Michael; Robbins, Jooke; Noad, Michael J

2015-08-01

For cetaceans, population structure is traditionally determined by molecular genetics or photographically identified individuals. Acoustic data, however, has provided information on movement and population structure with less effort and cost than traditional methods in an array of taxa. Male humpback whales (Megaptera novaeangliae) produce a continually evolving vocal sexual display, or song, that is similar among all males in a population. The rapid cultural transmission (the transfer of information or behavior between conspecifics through social learning) of different versions of this display between distinct but interconnected populations in the western and central South Pacific region presents a unique way to investigate population structure based on the movement dynamics of a song (acoustic) display. Using 11 years of data, we investigated an acoustically based population structure for the region by comparing stereotyped song sequences among populations and years. We used the Levenshtein distance technique to group previously defined populations into (vocally based) clusters based on the overall similarity of their song display in space and time. We identified the following distinct vocal clusters: western cluster, 1 population off eastern Australia; central cluster, populations around New Caledonia, Tonga, and American Samoa; and eastern region, either a single cluster or 2 clusters, one around the Cook Islands and the other off French Polynesia. These results are consistent with the hypothesis that each breeding aggregation represents a distinct population (each occupied a single, terminal node) in a metapopulation, similar to the current understanding of population structure based on genetic and photo-identification studies. However, the central vocal cluster had higher levels of song-sharing among populations than the other clusters, indicating that levels of vocal connectivity varied within the region. Our results demonstrate the utility and value of using culturally transmitted vocal patterns as a way of defining connectivity to infer population structure. We suggest vocal patterns be incorporated by the International Whaling Commission in conjunction with traditional methods in the assessment of structure. © 2015, Society for Conservation Biology.

Measures of motivation for psychiatric treatment based on self-determination theory: psychometric properties in Dutch psychiatric outpatients.

PubMed

Jochems, Eline C; Mulder, Cornelis L; Duivenvoorden, Hugo J; van der Feltz-Cornelis, Christina M; van Dam, Arno

2014-08-01

Self-determination theory is potentially useful for understanding reasons why individuals with mental illness do or do not engage in psychiatric treatment. The current study examined the psychometric properties of three questionnaires based on self-determination theory-The Treatment Entry Questionnaire (TEQ), Health Care Climate Questionnaire (HCCQ), and the Short Motivation Feedback List (SMFL)-in a sample of 348 Dutch adult outpatients with primary diagnoses of mood, anxiety, psychotic, and personality disorders. Structural equation modeling showed that the empirical factor structures of the TEQ and SMFL were adequately represented by a model with three intercorrelated factors. These were interpreted as identified, introjected, and external motivation. The reliabilities of the Dutch TEQ, HCCQ, and SMFL were found to be acceptable but can be improved on; congeneric estimates ranged from 0.66 to 0.94 depending on the measure and patient subsample. Preliminary support for the construct validities of the questionnaires was found in the form of theoretically expected associations with other scales, including therapist-rated motivation and treatment engagement and with legally mandated treatment. Additionally, the study provides insights into the relations between measures of motivation based on self-determination theory, the transtheoretical model and the integral model of treatment motivation in psychiatric outpatients with severe mental illness. © The Author(s) 2013.

A statistical physics perspective on alignment-independent protein sequence comparison.

PubMed

Chattopadhyay, Amit K; Nasiev, Diar; Flower, Darren R

2015-08-01

Within bioinformatics, the textual alignment of amino acid sequences has long dominated the determination of similarity between proteins, with all that implies for shared structure, function and evolutionary descent. Despite the relative success of modern-day sequence alignment algorithms, so-called alignment-free approaches offer a complementary means of determining and expressing similarity, with potential benefits in certain key applications, such as regression analysis of protein structure-function studies, where alignment-base similarity has performed poorly. Here, we offer a fresh, statistical physics-based perspective focusing on the question of alignment-free comparison, in the process adapting results from 'first passage probability distribution' to summarize statistics of ensemble averaged amino acid propensity values. In this article, we introduce and elaborate this approach. © The Author 2015. Published by Oxford University Press.

Effects of a finite outer scale on the measurement of atmospheric-turbulence statistics with a Hartmann wave-front sensor.

PubMed

Feng, Shen; Wenhan, Jiang

2002-06-10

Phase-structure and aperture-averaged slope-correlated functions with a finite outer scale are derived based on the Taylor hypothesis and a generalized spectrum, such as the von Kármán modal. The effects of the finite outer scale on measuring and determining the character of atmospheric-turbulence statistics are shown especially for an approximately 4-m class telescope and subaperture. The phase structure function and atmospheric coherent length based on the Kolmogorov model are approximations of the formalism we have derived. The analysis shows that it cannot be determined whether the deviation from the power-law parameter of Kolmogorov turbulence is caused by real variations of the spectrum or by the effect of the finite outer scale.

Analytical Fuselage and Wing Weight Estimation of Transport Aircraft

NASA Technical Reports Server (NTRS)

Chambers, Mark C.; Ardema, Mark D.; Patron, Anthony P.; Hahn, Andrew S.; Miura, Hirokazu; Moore, Mark D.

1996-01-01

A method of estimating the load-bearing fuselage weight and wing weight of transport aircraft based on fundamental structural principles has been developed. This method of weight estimation represents a compromise between the rapid assessment of component weight using empirical methods based on actual weights of existing aircraft, and detailed, but time-consuming, analysis using the finite element method. The method was applied to eight existing subsonic transports for validation and correlation. Integration of the resulting computer program, PDCYL, has been made into the weights-calculating module of the AirCraft SYNThesis (ACSYNT) computer program. ACSYNT has traditionally used only empirical weight estimation methods; PDCYL adds to ACSYNT a rapid, accurate means of assessing the fuselage and wing weights of unconventional aircraft. PDCYL also allows flexibility in the choice of structural concept, as well as a direct means of determining the impact of advanced materials on structural weight. Using statistical analysis techniques, relations between the load-bearing fuselage and wing weights calculated by PDCYL and corresponding actual weights were determined.

Matching algorithm of missile tail flame based on back-propagation neural network

NASA Astrophysics Data System (ADS)

Huang, Da; Huang, Shucai; Tang, Yidong; Zhao, Wei; Cao, Wenhuan

2018-02-01

This work presents a spectral matching algorithm of missile plume detection that based on neural network. The radiation value of the characteristic spectrum of the missile tail flame is taken as the input of the network. The network's structure including the number of nodes and layers is determined according to the number of characteristic spectral bands and missile types. We can get the network weight matrixes and threshold vectors through training the network using training samples, and we can determine the performance of the network through testing the network using the test samples. A small amount of data cause the network has the advantages of simple structure and practicality. Network structure composed of weight matrix and threshold vector can complete task of spectrum matching without large database support. Network can achieve real-time requirements with a small quantity of data. Experiment results show that the algorithm has the ability to match the precise spectrum and strong robustness.

A combination of spin diffusion methods for the determination of protein-ligand complex structural ensembles.

PubMed

Pilger, Jens; Mazur, Adam; Monecke, Peter; Schreuder, Herman; Elshorst, Bettina; Bartoschek, Stefan; Langer, Thomas; Schiffer, Alexander; Krimm, Isabelle; Wegstroth, Melanie; Lee, Donghan; Hessler, Gerhard; Wendt, K-Ulrich; Becker, Stefan; Griesinger, Christian

2015-05-26

Structure-based drug design (SBDD) is a powerful and widely used approach to optimize affinity of drug candidates. With the recently introduced INPHARMA method, the binding mode of small molecules to their protein target can be characterized even if no spectroscopic information about the protein is known. Here, we show that the combination of the spin-diffusion-based NMR methods INPHARMA, trNOE, and STD results in an accurate scoring function for docking modes and therefore determination of protein-ligand complex structures. Applications are shown on the model system protein kinase A and the drug targets glycogen phosphorylase and soluble epoxide hydrolase (sEH). Multiplexing of several ligands improves the reliability of the scoring function further. The new score allows in the case of sEH detecting two binding modes of the ligand in its binding site, which was corroborated by X-ray analysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distributed ice accretion sensor for smart aircraft structures

NASA Technical Reports Server (NTRS)

Gerardi, J. J.; Hickman, G. A.

1989-01-01

A distributed ice accretion sensor is presented, based on the concept of smart structures. Ice accretion is determined using spectral techniques to process signals from piezoelectric sensors integral to the airfoil skin. Frequency shifts in the leading edge structural skin modes are correlated to ice thickness. It is suggested that this method may be used to detect ice over large areas with minimal hardware. Results are presented from preliminary tests to measure simulated ice growth.

Identifying Configurations of Perceived Teacher Autonomy Support and Structure: Associations with Self-Regulated Learning, Motivation and Problem Behavior

ERIC Educational Resources Information Center

Vansteenkiste, Maarten; Sierens, Eline; Goossens, Luc; Soenens, Bart; Dochy, Filip; Mouratidis, Athanasios; Aelterman, Nathalie; Haerens, Leen; Beyers, Wim

2012-01-01

Grounded in self-determination theory, the aim of this study was (a) to examine naturally occurring configurations of perceived teacher autonomy support and clear expectations (i.e., a central aspect of teacher structure), and (b) to investigate associations with academic motivation, self-regulated learning, and problem behavior. Based on…

Stories and Gossip in English: The Macro-Structure of Casual Talk.

ERIC Educational Resources Information Center

Slade, Diana

1997-01-01

A discussion of two text-types commonly occurring in casual conversation, stories and gossip, (1) details four kinds of stories told in casual talk, (2) demonstrates that gossip is a culturally-determined process with a distinctive structure, and (3) considers implications for teaching English-as-a- Second-Language. Analysis is based on over three…

Analyzing Pre-Service Primary Teachers' Fraction Knowledge Structures through Problem Posing

ERIC Educational Resources Information Center

Kilic, Cigdem

2015-01-01

In this study it was aimed to determine pre-service primary teachers' knowledge structures of fraction through problem posing activities. A total of 90 pre-service primary teachers participated in this study. A problem posing test consisting of two questions was used and the participants were asked to generate as many as problems based on the…

The Relative Costs of American Men, Skills, and Machines: A Long View.

ERIC Educational Resources Information Center

Williamson, Jeffrey G.

The document is based on a premise that mid-twentieth century experience with income distribution cannot be adequately understood without a better knowledge of the long-term macroeconomic forces that have endogenously determined the wage structure. The secular performance of the price of skills and the occupational wage structure are important to…

Research Team Engineers a Better Plastic-Degrading Enzyme | News | NREL

Science.gov Websites

polyethylene terephthalate, or PET. While working to solve the crystal structure of PETase-a recently determine its structure to aid in protein engineering, but we ended up going a step further and accidentally discovery that PETase can also degrade polyethylene furandicarboxylate, or PEF, a bio-based substitute for

Prospective mathematics teachers' understanding of the base concept

NASA Astrophysics Data System (ADS)

Horzum, Tuğba; Ertekin, Erhan

2018-02-01

The purpose of this study is to analyze what kind of conceptions prospective mathematics teachers(PMTs) have about the base concept(BC). One-hundred and thirty-nine PMTs participated in the study. In this qualitative research, data were obtained through open-ended questions, the semi-structured interviews and pictures of geometric figures drawn by PMTs. As a result, it was determined that PMTs dealt with the BC in a broad range of seven different images. It was also determined that the base perception of PMTs was limited mostly to their usage in daily life and in this context, they have position-dependent and word-dependent images. It was also determined that PMTs named the base to explain the BC or paid attention to the naming of three-dimensional geometric figures through the statement: 'objects are named according to their bases'. At the same time, it was also determined that PMTs had more than one concept imageswhich were contradicting with each other. According to these findings, potential explanations and advices were given.

Spatial Statistics for Segmenting Histological Structures in H&E Stained Tissue Images.

PubMed

Nguyen, Luong; Tosun, Akif Burak; Fine, Jeffrey L; Lee, Adrian V; Taylor, D Lansing; Chennubhotla, S Chakra

2017-07-01

Segmenting a broad class of histological structures in transmitted light and/or fluorescence-based images is a prerequisite for determining the pathological basis of cancer, elucidating spatial interactions between histological structures in tumor microenvironments (e.g., tumor infiltrating lymphocytes), facilitating precision medicine studies with deep molecular profiling, and providing an exploratory tool for pathologists. This paper focuses on segmenting histological structures in hematoxylin- and eosin-stained images of breast tissues, e.g., invasive carcinoma, carcinoma in situ, atypical and normal ducts, adipose tissue, and lymphocytes. We propose two graph-theoretic segmentation methods based on local spatial color and nuclei neighborhood statistics. For benchmarking, we curated a data set of 232 high-power field breast tissue images together with expertly annotated ground truth. To accurately model the preference for histological structures (ducts, vessels, tumor nets, adipose, etc.) over the remaining connective tissue and non-tissue areas in ground truth annotations, we propose a new region-based score for evaluating segmentation algorithms. We demonstrate the improvement of our proposed methods over the state-of-the-art algorithms in both region- and boundary-based performance measures.

Evaluation of the effectiveness of elastomeric mount using vibration power flow and transmissibility methods

NASA Astrophysics Data System (ADS)

Arib Rejab, M. N.; Shukor, S. A. Abdul; Sofian, M. R. Mohd; Inayat-Hussain, J. I.; Nazirah, A.; Asyraf, I.

2017-10-01

This paper presents the results of an experimental work to determine the dynamic stiffness and loss factor of elastomeric mounts. It also presents the results of theoretical analysis to determine the transmissibility and vibration power flow of these mounts, which are associated with their contribution to structure-borne noise. Four types of elastomeric mounts were considered, where three of them were made from green natural rubber material (SMR CV60, Ekoprena and Pureprena) and one made from petroleum based synthetic rubber (EPDM). In order to determine the dynamic stiffness and loss factor of these elastomeric mounts, dynamic tests were conducted using MTS 830 Elastomer Test System. Dynamic stiffness and loss factor of these mounts were measured for a range of frequency between 5 Hz and 150 Hz, and with a dynamic amplitude of 0.2 mm (p-p). The transmissibility and vibration power flow were determined based on a simple 2-Degree-of-Freedom model representing a vibration isolation system with a flexible receiver. This model reprsents the three main parts of a vehicle, which are the powertrain and engine mounting, the flexible structure and the floor of the vehicle. The results revealed that synthetic rubber (EPDM) was only effective at high frequency region. Natural rubber (Ekoprena), on the other hand, was found to be effective at both low and high frequency regions due to its low transmissibility at resonant frequency and its ability to damp the resonance. The estimated structure-borne noise emission showed that Ekoprena has a lower contribution to structure-borne noise as compared to the other types of elastomeric mounts.

Divergence of Structure and Function in the Haloacid Dehalogenase Enzyme Superfamily: Bacteroides thetaiotaomicron BT2127 is an Inorganic Pyrophosphatase+

PubMed Central

Huang, Hua; Yury, Patskovsky; Toro, Rafael; Farelli, Jeremiah D.; Pandya, Chetanya; Almo, Steven C.; Allen, Karen N.; Dunaway-Mariano, Debra

2012-01-01

The explosion of protein sequence information requires that current strategies for function assignment must evolve to complement experimental approaches with computationally-based function prediction. This necessitates the development of strategies based on the identification of sequence markers in the form of specificity determinants and a more informed definition of orthologues. Herein, we have undertaken the function assignment of the unknown Haloalkanoate Dehalogenase superfamily member BT2127 (Uniprot accession # Q8A5V9) from Bacteroides thetaiotaomicron using an integrated bioinformatics/structure/mechanism approach. The substrate specificity profile and steady-state rate constants of BT2127 (with kcat/Km value for pyrophosphate of ∼1 × 105 M−1 s−1), together with the gene context, supports the assigned in vivo function as an inorganic pyrophosphatase. The X-ray structural analysis of the wild-type BT2127 and several variants generated by site-directed mutagenesis shows that substrate discrimination is based, in part, on active site space restrictions imposed by the cap domain (specifically by residues Tyr76 and Glu47). Structure guided site directed mutagenesis coupled with kinetic analysis of the mutant enzymes identified the residues required for catalysis, substrate binding, and domain-domain association. Based on this structure-function analysis, the catalytic residues Asp11, Asp13, Thr113, and Lys147 as well the metal binding residues Asp171, Asn172 and Glu47 were used as markers to confirm BT2127 orthologues identified via sequence searches. This bioinformatic analysis demonstrated that the biological range of BT2127 orthologue is restricted to the phylum Bacteroidetes/Chlorobi. The key structural determinants in the divergence of BT2127 and its closest homologue β-phosphoglucomutase control the leaving group size (phosphate vs. glucose-phosphate) and the position of the Asp acid/base in the open vs. closed conformations. HADSF pyrophosphatases represent a third mechanistic and fold type for bacterial pyrophosphatases. PMID:21894910

A fading-based method for checking the presence of closely overlapping peaks in thermoluminescent (TL) materials

NASA Astrophysics Data System (ADS)

Furetta, C.

The paper describes a method, based on fading experiment, for determining the presence of a complex structure in the thermoluminescent glow curve emission from herbs, e.g. oregano and nopal. Because of the polymineral content of the inorganic part of these herbs, the emitted glow curve is the result of several overlapping glow peaks, each one corresponding to another mineral. The initial rise method is also used for determining the activation energy of each component.

Transformation of BCC and B2 High Temperature Phases to HCP and Orthorhombic Structures in the Ti-Al-Nb System. Part I: Microstructural Predictions Based on a Subgroup Relation Between Phases

PubMed Central

Bendersky, L. A.; Roytburd, A.; Boettinger, W. J.

1993-01-01

Possible paths for the constant composition coherent transformation of BCC or B2 high temperature phases to low temperature HCP or Orthorhombic phases in the Ti-Al-Nb system are analyzed using a sequence of ciystallographic structural relationships developed from subgroup symmetry relations. Symmetry elements lost in each step of the sequence determine the possibilities for variants of the low symmetry phase and domains that can be present in the microstructure. The orientation of interdomain interfaces is determined by requiring the existence of a strain-free interface between the domains. Polydomain structures are also determined that minimize elastic energy. Microstructural predictions are made for comparison to experimental results given by Benderslcy and Boettinger [J. Res. Natl. Inst. Stand. Technol. 98, 585 (1993)]. PMID:28053487

Neutron and X-ray total scattering study of hydrogen disorder in fully hydrated hydrogrossular, Ca3Al2(O4H4)3

NASA Astrophysics Data System (ADS)

Keen, David A.; Keeble, Dean S.; Bennett, Thomas D.

2018-04-01

The structure of fully hydrated grossular, or katoite, contains an unusual arrangement of four O-H bonds within each O4 tetrahedra. Neutron and X-ray total scattering from a powdered deuterated sample have been measured to investigate the local arrangement of this O4D4 cluster. The O-D bond length determined directly from the pair distribution function is 0.954 Å, although the Rietveld-refined distance between average O and D positions was slightly smaller. Reverse Monte Carlo refinement of supercell models to the total scattering data show that other than the consequences of this correctly determined O-D bond length, there is little to suggest that the O4D4 structure is locally significantly different from that expected based on the average structure determined solely from Bragg diffraction.

Identification of Extracellular Segments by Mass Spectrometry Improves Topology Prediction of Transmembrane Proteins.

PubMed

Langó, Tamás; Róna, Gergely; Hunyadi-Gulyás, Éva; Turiák, Lilla; Varga, Julia; Dobson, László; Várady, György; Drahos, László; Vértessy, Beáta G; Medzihradszky, Katalin F; Szakács, Gergely; Tusnády, Gábor E

2017-02-13

Transmembrane proteins play crucial role in signaling, ion transport, nutrient uptake, as well as in maintaining the dynamic equilibrium between the internal and external environment of cells. Despite their important biological functions and abundance, less than 2% of all determined structures are transmembrane proteins. Given the persisting technical difficulties associated with high resolution structure determination of transmembrane proteins, additional methods, including computational and experimental techniques remain vital in promoting our understanding of their topologies, 3D structures, functions and interactions. Here we report a method for the high-throughput determination of extracellular segments of transmembrane proteins based on the identification of surface labeled and biotin captured peptide fragments by LC/MS/MS. We show that reliable identification of extracellular protein segments increases the accuracy and reliability of existing topology prediction algorithms. Using the experimental topology data as constraints, our improved prediction tool provides accurate and reliable topology models for hundreds of human transmembrane proteins.

Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks.

PubMed

Falzone, Tobias T; Lenz, Martin; Kovar, David R; Gardel, Margaret L

2012-05-29

The actin cytoskeleton is organized into diverse meshworks and bundles that support many aspects of cell physiology. Understanding the self-assembly of these actin-based structures is essential for developing predictive models of cytoskeletal organization. Here we show that the competing kinetics of bundle formation with the onset of dynamic arrest arising from filament entanglements and crosslinking determine the architecture of reconstituted actin networks formed with α-actinin crosslinks. Crosslink-mediated bundle formation only occurs in dilute solutions of highly mobile actin filaments. As actin polymerization proceeds, filament mobility and bundle formation are arrested concomitantly. By controlling the onset of dynamic arrest, perturbations to actin assembly kinetics dramatically alter the architecture of biochemically identical samples. Thus, the morphology of reconstituted F-actin networks is a kinetically determined structure similar to those formed by physical gels and glasses. These results establish mechanisms controlling the structure and mechanics in diverse semiflexible biopolymer networks.

The emerging role of native mass spectrometry in characterizing the structure and dynamics of macromolecular complexes

PubMed Central

Boeri Erba, Elisabetta; Petosa, Carlo

2015-01-01

Mass spectrometry (MS) is a powerful tool for determining the mass of biomolecules with high accuracy and sensitivity. MS performed under so-called “native conditions” (native MS) can be used to determine the mass of biomolecules that associate noncovalently. Here we review the application of native MS to the study of protein−ligand interactions and its emerging role in elucidating the structure of macromolecular assemblies, including soluble and membrane protein complexes. Moreover, we discuss strategies aimed at determining the stoichiometry and topology of subunits by inducing partial dissociation of the holo-complex. We also survey recent developments in "native top-down MS", an approach based on Fourier Transform MS, whereby covalent bonds are broken without disrupting non-covalent interactions. Given recent progress, native MS is anticipated to play an increasingly important role for researchers interested in the structure of macromolecular complexes. PMID:25676284

Purely Structural Protein Scoring Functions Using Support Vector Machine and Ensemble Learning.

PubMed

Mirzaei, Shokoufeh; Sidi, Tomer; Keasar, Chen; Crivelli, Silvia

2016-08-24

The function of a protein is determined by its structure, which creates a need for efficient methods of protein structure determination to advance scientific and medical research. Because current experimental structure determination methods carry a high price tag, computational predictions are highly desirable. Given a protein sequence, computational methods produce numerous 3D structures known as decoys. However, selection of the best quality decoys is challenging as the end users can handle only a few ones. Therefore, scoring functions are central to decoy selection. They combine measurable features into a single number indicator of decoy quality. Unfortunately, current scoring functions do not consistently select the best decoys. Machine learning techniques offer great potential to improve decoy scoring. This paper presents two machine-learning based scoring functions to predict the quality of proteins structures, i.e., the similarity between the predicted structure and the experimental one without knowing the latter. We use different metrics to compare these scoring functions against three state-of-the-art scores. This is a first attempt at comparing different scoring functions using the same non-redundant dataset for training and testing and the same features. The results show that adding informative features may be more significant than the method used.

Sequence-specific bias correction for RNA-seq data using recurrent neural networks.

PubMed

Zhang, Yao-Zhong; Yamaguchi, Rui; Imoto, Seiya; Miyano, Satoru

2017-01-25

The recent success of deep learning techniques in machine learning and artificial intelligence has stimulated a great deal of interest among bioinformaticians, who now wish to bring the power of deep learning to bare on a host of bioinformatical problems. Deep learning is ideally suited for biological problems that require automatic or hierarchical feature representation for biological data when prior knowledge is limited. In this work, we address the sequence-specific bias correction problem for RNA-seq data redusing Recurrent Neural Networks (RNNs) to model nucleotide sequences without pre-determining sequence structures. The sequence-specific bias of a read is then calculated based on the sequence probabilities estimated by RNNs, and used in the estimation of gene abundance. We explore the application of two popular RNN recurrent units for this task and demonstrate that RNN-based approaches provide a flexible way to model nucleotide sequences without knowledge of predetermined sequence structures. Our experiments show that training a RNN-based nucleotide sequence model is efficient and RNN-based bias correction methods compare well with the-state-of-the-art sequence-specific bias correction method on the commonly used MAQC-III data set. RNNs provides an alternative and flexible way to calculate sequence-specific bias without explicitly pre-determining sequence structures.

Anharmonic Normal Mode Analysis of Elastic Network Model Improves the Modeling of Atomic Fluctuations in Protein Crystal Structures

PubMed Central

Zheng, Wenjun

2010-01-01

Abstract Protein conformational dynamics, despite its significant anharmonicity, has been widely explored by normal mode analysis (NMA) based on atomic or coarse-grained potential functions. To account for the anharmonic aspects of protein dynamics, this study proposes, and has performed, an anharmonic NMA (ANMA) based on the Cα-only elastic network models, which assume elastic interactions between pairs of residues whose Cα atoms or heavy atoms are within a cutoff distance. The key step of ANMA is to sample an anharmonic potential function along the directions of eigenvectors of the lowest normal modes to determine the mean-squared fluctuations along these directions. ANMA was evaluated based on the modeling of anisotropic displacement parameters (ADPs) from a list of 83 high-resolution protein crystal structures. Significant improvement was found in the modeling of ADPs by ANMA compared with standard NMA. Further improvement in the modeling of ADPs is attained if the interactions between a protein and its crystalline environment are taken into account. In addition, this study has determined the optimal cutoff distances for ADP modeling based on elastic network models, and these agree well with the peaks of the statistical distributions of distances between Cα atoms or heavy atoms derived from a large set of protein crystal structures. PMID:20550915

The Influence of the Support Structure on Residual Stress and Distortion in SLM Inconel 718 Parts

NASA Astrophysics Data System (ADS)

Mishurova, Tatiana; Cabeza, Sandra; Thiede, Tobias; Nadammal, Naresh; Kromm, Arne; Klaus, Manuela; Genzel, Christoph; Haberland, Christoph; Bruno, Giovanni

2018-07-01

The effect of support structure and of removal from the base plate on the residual stress state in selective laser melted IN718 parts was studied by means of synchrotron X-ray diffraction. The residual stresses in subsurface region of two elongated prisms in as-built condition and after removal from the base plate were determined. One sample was directly built on a base plate and another one on a support structure. Also, the distortion on the top surface due to stress release was measured by contact profilometry. High tensile residual stress values were found, with pronounced stress gradient along the hatching direction. In the sample on support, stress redistribution took place after removal from the base plate, as opposed to simple stress relaxation for the sample without support. The sample on support structure showed larger distortion compared to sample without support. We conclude that the use of a support decreases stress values but stress-relieving heat treatments are still needed.

The Influence of the Support Structure on Residual Stress and Distortion in SLM Inconel 718 Parts

NASA Astrophysics Data System (ADS)

Mishurova, Tatiana; Cabeza, Sandra; Thiede, Tobias; Nadammal, Naresh; Kromm, Arne; Klaus, Manuela; Genzel, Christoph; Haberland, Christoph; Bruno, Giovanni

2018-05-01

The effect of support structure and of removal from the base plate on the residual stress state in selective laser melted IN718 parts was studied by means of synchrotron X-ray diffraction. The residual stresses in subsurface region of two elongated prisms in as-built condition and after removal from the base plate were determined. One sample was directly built on a base plate and another one on a support structure. Also, the distortion on the top surface due to stress release was measured by contact profilometry. High tensile residual stress values were found, with pronounced stress gradient along the hatching direction. In the sample on support, stress redistribution took place after removal from the base plate, as opposed to simple stress relaxation for the sample without support. The sample on support structure showed larger distortion compared to sample without support. We conclude that the use of a support decreases stress values but stress-relieving heat treatments are still needed.

Distributed friction damping of travelling wave vibration in rods.

PubMed

Tangpong, Xiangqing W; Wickert, Jonathan A; Akay, Adnan

2008-03-13

A ring damper can be affixed to a rotating base structure such as a gear, an automotive brake rotor or a gas turbine's labyrinth air seal. Depending on the frequency range, wavenumber and level of preload, vibration of the base structure can be effectively and passively attenuated by friction that develops along the interface between it and the damper. The assembly is modelled as two rods that couple in longitudinal vibration through spatially distributed hysteretic friction, with each rod having periodic boundary conditions in a manner analogous to an unwrapped ring and disc. As is representative of rotating machinery applications, the system is driven by a travelling wave disturbance, and for that form of excitation, the base structure's and the damper's responses are determined without the need for computationally intensive simulation. The damper's performance can be optimized with respect to normal preload, and its effectiveness is insensitive to variations in preload or the excitation's magnitude when its natural frequency is substantially lower than the base structure's in the absence of contact.

Fold independent structural comparisons of protein-ligand binding sites for exploring functional relationships.

PubMed

Gold, Nicola D; Jackson, Richard M

2006-02-03

The rapid growth in protein structural data and the emergence of structural genomics projects have increased the need for automatic structure analysis and tools for function prediction. Small molecule recognition is critical to the function of many proteins; therefore, determination of ligand binding site similarity is important for understanding ligand interactions and may allow their functional classification. Here, we present a binding sites database (SitesBase) that given a known protein-ligand binding site allows rapid retrieval of other binding sites with similar structure independent of overall sequence or fold similarity. However, each match is also annotated with sequence similarity and fold information to aid interpretation of structure and functional similarity. Similarity in ligand binding sites can indicate common binding modes and recognition of similar molecules, allowing potential inference of function for an uncharacterised protein or providing additional evidence of common function where sequence or fold similarity is already known. Alternatively, the resource can provide valuable information for detailed studies of molecular recognition including structure-based ligand design and in understanding ligand cross-reactivity. Here, we show examples of atomic similarity between superfamily or more distant fold relatives as well as between seemingly unrelated proteins. Assignment of unclassified proteins to structural superfamiles is also undertaken and in most cases substantiates assignments made using sequence similarity. Correct assignment is also possible where sequence similarity fails to find significant matches, illustrating the potential use of binding site comparisons for newly determined proteins.

Investigating energy-based pool structure selection in the structure ensemble modeling with experimental distance constraints: The example from a multidomain protein Pub1.

PubMed

Zhu, Guanhua; Liu, Wei; Bao, Chenglong; Tong, Dudu; Ji, Hui; Shen, Zuowei; Yang, Daiwen; Lu, Lanyuan

2018-05-01

The structural variations of multidomain proteins with flexible parts mediate many biological processes, and a structure ensemble can be determined by selecting a weighted combination of representative structures from a simulated structure pool, producing the best fit to experimental constraints such as interatomic distance. In this study, a hybrid structure-based and physics-based atomistic force field with an efficient sampling strategy is adopted to simulate a model di-domain protein against experimental paramagnetic relaxation enhancement (PRE) data that correspond to distance constraints. The molecular dynamics simulations produce a wide range of conformations depicted on a protein energy landscape. Subsequently, a conformational ensemble recovered with low-energy structures and the minimum-size restraint is identified in good agreement with experimental PRE rates, and the result is also supported by chemical shift perturbations and small-angle X-ray scattering data. It is illustrated that the regularizations of energy and ensemble-size prevent an arbitrary interpretation of protein conformations. Moreover, energy is found to serve as a critical control to refine the structure pool and prevent data overfitting, because the absence of energy regularization exposes ensemble construction to the noise from high-energy structures and causes a more ambiguous representation of protein conformations. Finally, we perform structure-ensemble optimizations with a topology-based structure pool, to enhance the understanding on the ensemble results from different sources of pool candidates. © 2018 Wiley Periodicals, Inc.

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.

Factors within University-Based Teacher Education Relating to Preservice Teachers' Professional Vision

ERIC Educational Resources Information Center

Stürmer, Kathleen; Könings, Karen D.; Seidel, Tina

2015-01-01

Preservice teachers' professional vision is an important indicator of their initial acquisition of integrated knowledge structures within university-based teacher education. To date, empirical research investigating which factors contribute to explaining preservice teachers' professional vision is scarce. This study aims to determine which factors…

Biophysics of cadherin adhesion.

PubMed

Leckband, Deborah; Sivasankar, Sanjeevi

2012-01-01

Since the identification of cadherins and the publication of the first crystal structures, the mechanism of cadherin adhesion, and the underlying structural basis have been studied with a number of different experimental techniques, different classical cadherin subtypes, and cadherin fragments. Earlier studies based on biophysical measurements and structure determinations resulted in seemingly contradictory findings regarding cadherin adhesion. However, recent experimental data increasingly reveal parallels between structures, solution binding data, and adhesion-based biophysical measurements that are beginning to both reconcile apparent differences and generate a more comprehensive model of cadherin-mediated cell adhesion. This chapter summarizes the functional, structural, and biophysical findings relevant to cadherin junction assembly and adhesion. We emphasize emerging parallels between findings obtained with different experimental approaches. Although none of the current models accounts for all of the available experimental and structural data, this chapter discusses possible origins of apparent discrepancies, highlights remaining gaps in current knowledge, and proposes challenges for further study.

The Effects of Reducing the Structural Mass of the Transit Habitat on the Cryogenic Propellant Required for a Human Phobos Mission

NASA Technical Reports Server (NTRS)

Zipay, John Joseph

2016-01-01

A technique for rapidly determining the relationship between the pressurized volume, structural mass and the cryogenic propellant required to be delivered to Earth orbit for a Mars Transit Habitat is provided. This technique is based on assumptions for the required delta-V's, the Exploration Upper Stage performance and the historical structural masses for human spacecraft from Mercury Program through the International Space Station. If the Mars Transit Habitat is constructed from aluminum, structural mass estimates based on the habitat pressurized volume are accurate to within 15%. Other structural material options for the Mars Transit Habitat are also evaluated. The results show that small, achievable reductions in the structural mass of the Transit Habitat can save tens of thousands of pounds of cryogenic propellant that need to be delivered to Earth orbit for a human Phobos Mission.

The Effects of Reducing the Structural Mass of the Transit Habitat on the Cryogenic Propellant Required for a Human Phobos Mission

NASA Technical Reports Server (NTRS)

Zipay, John J.

2016-01-01

A technique for rapidly determining the relationship between the pressurized volume, structural mass and the cryogenic propellant required to be delivered to Earth orbit for a Mars Transit Habitat is provided. This technique is based on assumptions for the required delta-V's, the Exploration Upper Stage performance and the historical structural masses for human spacecraft from Mercury Program through the International Space Station. If the Mars Transit Habitat is constructed from aluminum, structural mass estimates based on the habitat pressurized volume are accurate to within 15 percent. Other structural material options for the Mars Transit Habitat are also evaluated. The results show that small, achievable reductions in the structural mass of the Transit Habitat can save tens of thousands of pounds of cryogenic propellant that need to be delivered to Earth orbit for a human Phobos Mission.

A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere.

PubMed

Rutenber, E E; McPhee, F; Kaplan, A P; Gallion, S L; Hogan, J C; Craik, C S; Stroud, R M

1996-09-01

The essential role of HIV-1 protease (HIV-1 PR) in the viral life cycle makes it an attractive target for the development of substrate-based inhibitors that may find efficacy as anti-AIDS drugs. However, resistance has arisen to potent peptidomimetic drugs necessitating the further development of novel chemical backbones for diversity based chemistry focused on probing the active site for inhibitor interactions and binding modes that evade protease resistance. AQ148 is a potent inhibitor of HIV-1 PR and represents a new class of transition state analogues incorporating an aminimide peptide isostere. A 3-D crystallographic structure of AQ148, a tetrapeptide isostere, has been determined in complex with its target HIV-1 PR to a resolution of 2.5 A and used to evaluate the specific structural determinants of AQ148 potency and to correlate structure-activity relationships within the class of related compounds. AQ148 is a competitive inhibitor of HIV-1 PR with a Ki value of 137 nM. Twenty-nine derivatives have been synthesized and chemical modifications have been made at the P1, P2, P1', and P2' sites. The atomic resolution structure of AQ148 bound to HIV-1 PR reveals both an inhibitor binding mode that closely resembles that of other peptidomimetic inhibitors and specific protein/inhibitor interactions that correlate with structure-activity relationships. The structure provides the basis for the design, synthesis and evaluation of the next generation of hydroxyethyl aminimide inhibitors. The aminimide peptide isostere is a scaffold with favorable biological properties well suited to both the combinatorial methods of peptidomimesis and the rational design of potent and specific substrate-based analogues.

Analysis of the Seismic Performance of Isolated Buildings according to Life-Cycle Cost

PubMed Central

Dang, Yu; Han, Jian-ping; Li, Yong-tao

2015-01-01

This paper proposes an indicator of seismic performance based on life-cycle cost of a building. It is expressed as a ratio of lifetime damage loss to life-cycle cost and determines the seismic performance of isolated buildings. Major factors are considered, including uncertainty in hazard demand and structural capacity, initial costs, and expected loss during earthquakes. Thus, a high indicator value indicates poor building seismic performance. Moreover, random vibration analysis is conducted to measure structural reliability and evaluate the expected loss and life-cycle cost of isolated buildings. The expected loss of an actual, seven-story isolated hospital building is only 37% of that of a fixed-base building. Furthermore, the indicator of the structural seismic performance of the isolated building is much lower in value than that of the structural seismic performance of the fixed-base building. Therefore, isolated buildings are safer and less risky than fixed-base buildings. The indicator based on life-cycle cost assists owners and engineers in making investment decisions in consideration of structural design, construction, and expected loss. It also helps optimize the balance between building reliability and building investment. PMID:25653677

Analysis of the seismic performance of isolated buildings according to life-cycle cost.

PubMed

Dang, Yu; Han, Jian-Ping; Li, Yong-Tao

2015-01-01

This paper proposes an indicator of seismic performance based on life-cycle cost of a building. It is expressed as a ratio of lifetime damage loss to life-cycle cost and determines the seismic performance of isolated buildings. Major factors are considered, including uncertainty in hazard demand and structural capacity, initial costs, and expected loss during earthquakes. Thus, a high indicator value indicates poor building seismic performance. Moreover, random vibration analysis is conducted to measure structural reliability and evaluate the expected loss and life-cycle cost of isolated buildings. The expected loss of an actual, seven-story isolated hospital building is only 37% of that of a fixed-base building. Furthermore, the indicator of the structural seismic performance of the isolated building is much lower in value than that of the structural seismic performance of the fixed-base building. Therefore, isolated buildings are safer and less risky than fixed-base buildings. The indicator based on life-cycle cost assists owners and engineers in making investment decisions in consideration of structural design, construction, and expected loss. It also helps optimize the balance between building reliability and building investment.

Graphene-insulator-semiconductor capacitors as superior test structures for photoelectric determination of semiconductor devices band diagrams

NASA Astrophysics Data System (ADS)

Piskorski, K.; Passi, V.; Ruhkopf, J.; Lemme, M. C.; Przewlocki, H. M.

2018-05-01

We report on the advantages of using Graphene-Insulator-Semiconductor (GIS) instead of Metal-Insulator-Semiconductor (MIS) structures in reliable and precise photoelectric determination of the band alignment at the semiconductor-insulator interface and of the insulator band gap determination. Due to the high transparency to light of the graphene gate in GIS structures large photocurrents due to emission of both electrons and holes from the substrate and negligible photocurrents due to emission of carriers from the gate can be obtained, which allows reliable determination of barrier heights for both electrons, Ee and holes, Eh from the semiconductor substrate. Knowing the values of both Ee and Eh allows direct determination of the insulator band gap EG(I). Photoelectric measurements were made of a series of Graphene-SiO2-Si structures and an example is shown of the results obtained in sequential measurements of the same structure giving the following barrier height values: Ee = 4.34 ± 0.01 eV and Eh = 4.70 ± 0.03 eV. Based on this result and results obtained for other structures in the series we conservatively estimate the maximum uncertainty of both barrier heights estimations at ± 0.05 eV. This sets the SiO2 band gap estimation at EG(I) = 7.92 ± 0.1 eV. It is shown that widely different SiO2 band gap values were found by research groups using various determination methods. We hypothesize that these differences are due to different sensitivities of measurement methods used to the existence of the SiO2 valence band tail.

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.

Using 1H and 13C NMR chemical shifts to determine cyclic peptide conformations: a combined molecular dynamics and quantum mechanics approach.

PubMed

Nguyen, Q Nhu N; Schwochert, Joshua; Tantillo, Dean J; Lokey, R Scott

2018-05-10

Solving conformations of cyclic peptides can provide insight into structure-activity and structure-property relationships, which can help in the design of compounds with improved bioactivity and/or ADME characteristics. The most common approaches for determining the structures of cyclic peptides are based on NMR-derived distance restraints obtained from NOESY or ROESY cross-peak intensities, and 3J-based dihedral restraints using the Karplus relationship. Unfortunately, these observables are often too weak, sparse, or degenerate to provide unequivocal, high-confidence solution structures, prompting us to investigate an alternative approach that relies only on 1H and 13C chemical shifts as experimental observables. This method, which we call conformational analysis from NMR and density-functional prediction of low-energy ensembles (CANDLE), uses molecular dynamics (MD) simulations to generate conformer families and density functional theory (DFT) calculations to predict their 1H and 13C chemical shifts. Iterative conformer searches and DFT energy calculations on a cyclic peptide-peptoid hybrid yielded Boltzmann ensembles whose predicted chemical shifts matched the experimental values better than any single conformer. For these compounds, CANDLE outperformed the classic NOE- and 3J-coupling-based approach by disambiguating similar β-turn types and also enabled the structural elucidation of the minor conformer. Through the use of chemical shifts, in conjunction with DFT and MD calculations, CANDLE can help illuminate conformational ensembles of cyclic peptides in solution.

C-glucosidic ellagitannins from Lythri herba (European Pharmacopoeia): chromatographic profile and structure determination.

PubMed

Piwowarski, Jakub P; Kiss, Anna K

2013-01-01

Lythri herba, a pharmacopoeial plant material (European Pharmacopoea), is obtained from flowering parts of purple loosestrife (Lythrum salicaria L.). Although extracts from this plant material have been proven to possess some interesting biological activities and its pharmacopoeial standardisation is based on total tannin content determination, the phytochemical characterisation of this main group of compounds has not yet been fully conducted. To isolate ellagitannins from Lythri herba, determine their structures and develop chromatographic methods for their qualitative analysis. Five C-glucosidic ellagitannins - monomeric- vescalagin and castalagin together with new dimeric structures - salicarinins A-C, composed of vescalagin and stachyurin, vescalagin and casuarinin, castalagin and casuarinin units connected via formation of valoneoyl group, were isolated using column chromatography and preparative HPLC. Structures were determined according to (1) H and (13) C-NMR (one- and two-dimensional), electrospray ionisation-time of flight (ESI-TOF), electrospray ionisation-ion trap (ESI-MS(n) ) and circular dichroism (CD) spectra, together with acidic hydrolysis products analysis. HPTLC on RP-18 modified plates and HPLC-DAD-MS(n) on RP-18 column methods were developed for separation of the five main ellagitannins. Copyright © 2012 John Wiley & Sons, Ltd.

HRTEM and neutron diffraction study of Li{sub x}Mo{sub 5}O{sub 17}: From the ribbon (x=5) structure to the rock salt (x=12) structure

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

Lebedev, O.I.; Caignaert, V.; Raveau, B.

2011-04-15

Structure determination of the fully intercalated phase Li{sub 12}Mo{sub 5}O{sub 17} and of the deintercalated oxide Li{sub 5}Mo{sub 5}O{sub 17} has been carried out by electron microscopy and neutron powder diffraction. The reversible topotactic transformation between the ordered rock salt structure of the former and the ribbon structure of the latter (closely related to that of Li{sub 4}Mo{sub 5}O{sub 17}) is explained on the following basis: both structures can be described as strips built up as an assembly of infinite ribbons of MoO{sub 6} octahedra that are five octahedra thick, and that differ by slight displacements of the octahedral ribbons.more » We show that the electrochemical behavior of the Li{sub x}Mo{sub 5}O{sub 17} system is based on two sorts of Li{sup +} sites; those that are located within the strips between the ribbons, and those that are located at the border of the strips. The high rate of Li intercalation in this oxide and its reversibility are discussed in terms of its peculiar structure. -- Graphical abstract: Structure determination of the fully intercalated phase Li{sub 12}Mo{sub 5}O{sub 17} and of the deintercalated oxide Li{sub 5}Mo{sub 5}O{sub 17} has been carried out by electron microscopy and neutron powder diffraction. The reversible topotactic transformation between the ordered rock salt structure of the former and the ribbon structure of the latter is explained on the following basis: both structures can be described as strips built up as an assembly of infinite ribbons of MoO{sub 6} octahedra that are five octahedra thick, and that differ by slight displacements of the octahedral ribbons. We show that the electrochemical behavior of the Li{sub x}Mo{sub 5}O{sub 17} system is based on two sorts of Li{sup +} sites; those that are located within the strips between the ribbons, and those that are located at the border of the strips. The high rate of Li intercalation in this oxide and its reversibility are discussed in terms of its peculiar structure. Research highlights: {yields} Electron microscopy and neutron powder diffraction structure determination {yields} We have explained the reversible topotactic transformation between an ordered rock salt structure and a ribbon structure {yields} We show that the electrochemical behavior of the Li{sub x}Mo{sub 5}O{sub 17} system is based on two sorts of Li{sup +} sites {yields} The high rate of Li intercalation in this oxide and its reversibility are discussed in terms of its peculiar structure.« less

A determinant-based criterion for working correlation structure selection in generalized estimating equations.

PubMed

Jaman, Ajmery; Latif, Mahbub A H M; Bari, Wasimul; Wahed, Abdus S

2016-05-20

In generalized estimating equations (GEE), the correlation between the repeated observations on a subject is specified with a working correlation matrix. Correct specification of the working correlation structure ensures efficient estimators of the regression coefficients. Among the criteria used, in practice, for selecting working correlation structure, Rotnitzky-Jewell, Quasi Information Criterion (QIC) and Correlation Information Criterion (CIC) are based on the fact that if the assumed working correlation structure is correct then the model-based (naive) and the sandwich (robust) covariance estimators of the regression coefficient estimators should be close to each other. The sandwich covariance estimator, used in defining the Rotnitzky-Jewell, QIC and CIC criteria, is biased downward and has a larger variability than the corresponding model-based covariance estimator. Motivated by this fact, a new criterion is proposed in this paper based on the bias-corrected sandwich covariance estimator for selecting an appropriate working correlation structure in GEE. A comparison of the proposed and the competing criteria is shown using simulation studies with correlated binary responses. The results revealed that the proposed criterion generally performs better than the competing criteria. An example of selecting the appropriate working correlation structure has also been shown using the data from Madras Schizophrenia Study. Copyright © 2015 John Wiley & Sons, Ltd.

A Bayesian Approach for Determining Protein Side-Chain Rotamer Conformations Using Unassigned NOE Data

PubMed Central

Zeng, Jianyang; Roberts, Kyle E.; Zhou, Pei

2011-01-01

Abstract A major bottleneck in protein structure determination via nuclear magnetic resonance (NMR) is the lengthy and laborious process of assigning resonances and nuclear Overhauser effect (NOE) cross peaks. Recent studies have shown that accurate backbone folds can be determined using sparse NMR data, such as residual dipolar couplings (RDCs) or backbone chemical shifts. This opens a question of whether we can also determine the accurate protein side-chain conformations using sparse or unassigned NMR data. We attack this question by using unassigned nuclear Overhauser effect spectroscopy (NOESY) data, which records the through-space dipolar interactions between protons nearby in three-dimensional (3D) space. We propose a Bayesian approach with a Markov random field (MRF) model to integrate the likelihood function derived from observed experimental data, with prior information (i.e., empirical molecular mechanics energies) about the protein structures. We unify the side-chain structure prediction problem with the side-chain structure determination problem using unassigned NMR data, and apply the deterministic dead-end elimination (DEE) and A* search algorithms to provably find the global optimum solution that maximizes the posterior probability. We employ a Hausdorff-based measure to derive the likelihood of a rotamer or a pairwise rotamer interaction from unassigned NOESY data. In addition, we apply a systematic and rigorous approach to estimate the experimental noise in NMR data, which also determines the weighting factor of the data term in the scoring function derived from the Bayesian framework. We tested our approach on real NMR data of three proteins: the FF Domain 2 of human transcription elongation factor CA150 (FF2), the B1 domain of Protein G (GB1), and human ubiquitin. The promising results indicate that our algorithm can be applied in high-resolution protein structure determination. Since our approach does not require any NOE assignment, it can accelerate the NMR structure determination process. PMID:21970619

Crystal structure of the toxin Msmeg_6760, the structural homolog of Mycobacterium tuberculosis Rv2035, a novel type II toxin involved in the hypoxic response

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

Bajaj, R. Alexandra; Arbing, Mark A.; Shin, Annie

The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin–antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate–latch mechanism. The function of the Msmeg_6760 toxin is unknown, but structure-based predictions revealed that Msmeg_6760 and Msmeg_6762 are homologous to Rv2034 and Rv2035, a predicted novelmore » TA system involved inMycobacterium tuberculosislatency during macrophage infection. The Msmeg_6760 toxin fold has not been previously described for bacterial toxins and its unique structural features suggest that toxin activation is likely to be mediated by a novel mechanism.« less

Investigation of the adhesive bonding technology for the insulator structure of EAST neutral beam injector

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

Wei, Jiang-Long, E-mail: jlwei@ipp.ac.cn; Li, Jun; Hu, Chun-Dong

A key issue on the development of EAST ion source was the junction design of insulator structure, which consists of three insulators and four supporting flanges of electrode grid. Because the ion source is installed on the vertical plane, the insulator structure has to withstand large bending and shear stress due to the gravity of whole ion source. Through a mechanical analysis, it was calculated that the maximum bending normal stress was 0.34 MPa and shear stress was 0.23 MPa on the insulator structure. Due to the advantages of simplicity and high strength, the adhesive bonding technology was applied tomore » the junction of insulator structure. A tensile testing campaign of different junction designs between insulator and supporting flange was performed, and a junction design of stainless steel and fiber enhanced epoxy resin with epoxy adhesive was determined. The insulator structure based on the determined design can satisfy both the requirements of high-voltage holding and mechanical strength.« less

Testing Strategies for Model-Based Development

NASA Technical Reports Server (NTRS)

Heimdahl, Mats P. E.; Whalen, Mike; Rajan, Ajitha; Miller, Steven P.

2006-01-01

This report presents an approach for testing artifacts generated in a model-based development process. This approach divides the traditional testing process into two parts: requirements-based testing (validation testing) which determines whether the model implements the high-level requirements and model-based testing (conformance testing) which determines whether the code generated from a model is behaviorally equivalent to the model. The goals of the two processes differ significantly and this report explores suitable testing metrics and automation strategies for each. To support requirements-based testing, we define novel objective requirements coverage metrics similar to existing specification and code coverage metrics. For model-based testing, we briefly describe automation strategies and examine the fault-finding capability of different structural coverage metrics using tests automatically generated from the model.

Intervention mapping protocol for developing a theory-based diabetes self-management education program.

PubMed

Song, Misoon; Choi, Suyoung; Kim, Se-An; Seo, Kyoungsan; Lee, Soo Jin

2015-01-01

Development of behavior theory-based health promotion programs is encouraged with the paradigm shift from contents to behavior outcomes. This article describes the development process of the diabetes self-management program for older Koreans (DSME-OK) using intervention mapping (IM) protocol. The IM protocol includes needs assessment, defining goals and objectives, identifying theory and determinants, developing a matrix to form change objectives, selecting strategies and methods, structuring the program, and planning for evaluation and pilot testing. The DSME-OK adopted seven behavior objectives developed by the American Association of Diabetes Educators as behavioral outcomes. The program applied an information-motivation-behavioral skills model, and interventions were targeted to 3 determinants to change health behaviors. Specific methods were selected to achieve each objective guided by IM protocol. As the final step, program evaluation was planned including a pilot test. The DSME-OK was structured as the 3 determinants of the IMB model were intervened to achieve behavior objectives in each session. The program has 12 weekly 90-min sessions tailored for older adults. Using the IM protocol in developing a theory-based self-management program was beneficial in terms of providing a systematic guide to developing theory-based and behavior outcome-focused health education programs.

Structural determinants of ubiquitin-CXC chemokine receptor 4 interaction.

PubMed

Saini, Vikas; Marchese, Adriano; Tang, Wei-Jen; Majetschak, Matthias

2011-12-23

Ubiquitin, a post-translational protein modifier inside the cell, functions as a CXC chemokine receptor (CXCR) 4 agonist outside the cell. However, the structural determinants of the interaction between extracellular ubiquitin and CXCR4 remain unknown. Utilizing C-terminal truncated ubiquitin and ubiquitin mutants, in which surface residues that are known to interact with ubiquitin binding domains in interacting proteins are mutated (Phe-4, Leu-8, Ile-44, Asp-58, Val-70), we provide evidence that the ubiquitin-CXCR4 interaction follows a two-site binding mechanism in which the hydrophobic surfaces surrounding Phe-4 and Val-70 are important for receptor binding, whereas the flexible C terminus facilitates receptor activation. Based on these findings and the available crystal structures, we then modeled the ubiquitin-CXCR4 interface with the RosettaDock software followed by small manual adjustments, which were guided by charge complementarity and anticipation of a conformational switch of CXCR4 upon activation. This model suggests three residues of CXCR4 (Phe-29, Phe-189, Lys-271) as potential interaction sites. Binding studies with HEK293 cells overexpressing wild type and CXCR4 after site-directed mutagenesis confirm that these residues are important for ubiquitin binding but that they do not contribute to the binding of stromal cell-derived factor 1α. Our findings suggest that the structural determinants of the CXCR4 agonist activity of ubiquitin mimic the typical structure-function relationship of chemokines. Furthermore, we provide evidence for separate and specific ligand binding sites on CXCR4. As exogenous ubiquitin has been shown to possess therapeutic potential, our findings are expected to facilitate the structure-based design of new compounds with ubiquitin-mimetic actions on CXCR4.

Biferrocene-Based Diphosphine Ligands: Synthesis and Application of Walphos Analogues in Asymmetric Hydrogenations

PubMed Central

2013-01-01

A total of four biferrocene-based Walphos-type ligands have been synthesized, structurally characterized, and tested in the rhodium-, ruthenium- and iridium-catalyzed hydrogenation of alkenes and ketones. Negishi coupling conditions allowed the biferrocene backbone of these diphosphine ligands to be built up diastereoselectively from the two nonidentical and nonracemic ferrocene fragments (R)-1-(N,N-dimethylamino)ethylferrocene and (SFc)-2-bromoiodoferrocene. The molecular structures of (SFc)-2-bromoiodoferrocene, the coupling product, two ligands, and the two complexes ([PdCl2(L)] and [RuCl(p-cymene)(L)]PF6) were determined by X-ray diffraction. The structural features of complexes and the catalysis results obtained with the newly synthesized biferrocene-based ligands were compared with those of the corresponding Walphos ligands. PMID:23457421

Volumetric three-dimensional intravascular ultrasound visualization using shape-based nonlinear interpolation

PubMed Central

2013-01-01

Background Intravascular ultrasound (IVUS) is a standard imaging modality for identification of plaque formation in the coronary and peripheral arteries. Volumetric three-dimensional (3D) IVUS visualization provides a powerful tool to overcome the limited comprehensive information of 2D IVUS in terms of complex spatial distribution of arterial morphology and acoustic backscatter information. Conventional 3D IVUS techniques provide sub-optimal visualization of arterial morphology or lack acoustic information concerning arterial structure due in part to low quality of image data and the use of pixel-based IVUS image reconstruction algorithms. In the present study, we describe a novel volumetric 3D IVUS reconstruction algorithm to utilize IVUS signal data and a shape-based nonlinear interpolation. Methods We developed an algorithm to convert a series of IVUS signal data into a fully volumetric 3D visualization. Intermediary slices between original 2D IVUS slices were generated utilizing the natural cubic spline interpolation to consider the nonlinearity of both vascular structure geometry and acoustic backscatter in the arterial wall. We evaluated differences in image quality between the conventional pixel-based interpolation and the shape-based nonlinear interpolation methods using both virtual vascular phantom data and in vivo IVUS data of a porcine femoral artery. Volumetric 3D IVUS images of the arterial segment reconstructed using the two interpolation methods were compared. Results In vitro validation and in vivo comparative studies with the conventional pixel-based interpolation method demonstrated more robustness of the shape-based nonlinear interpolation algorithm in determining intermediary 2D IVUS slices. Our shape-based nonlinear interpolation demonstrated improved volumetric 3D visualization of the in vivo arterial structure and more realistic acoustic backscatter distribution compared to the conventional pixel-based interpolation method. Conclusions This novel 3D IVUS visualization strategy has the potential to improve ultrasound imaging of vascular structure information, particularly atheroma determination. Improved volumetric 3D visualization with accurate acoustic backscatter information can help with ultrasound molecular imaging of atheroma component distribution. PMID:23651569

Damage tolerance modeling and validation of a wireless sensory composite panel for a structural health monitoring system

NASA Astrophysics Data System (ADS)

Talagani, Mohamad R.; Abdi, Frank; Saravanos, Dimitris; Chrysohoidis, Nikos; Nikbin, Kamran; Ragalini, Rose; Rodov, Irena

2013-05-01

The paper proposes the diagnostic and prognostic modeling and test validation of a Wireless Integrated Strain Monitoring and Simulation System (WISMOS). The effort verifies a hardware and web based software tool that is able to evaluate and optimize sensorized aerospace composite structures for the purpose of Structural Health Monitoring (SHM). The tool is an extension of an existing suite of an SHM system, based on a diagnostic-prognostic system (DPS) methodology. The goal of the extended SHM-DPS is to apply multi-scale nonlinear physics-based Progressive Failure analyses to the "as-is" structural configuration to determine residual strength, remaining service life, and future inspection intervals and maintenance procedures. The DPS solution meets the JTI Green Regional Aircraft (GRA) goals towards low weight, durable and reliable commercial aircraft. It will take advantage of the currently developed methodologies within the European Clean sky JTI project WISMOS, with the capability to transmit, store and process strain data from a network of wireless sensors (e.g. strain gages, FBGA) and utilize a DPS-based methodology, based on multi scale progressive failure analysis (MS-PFA), to determine structural health and to advice with respect to condition based inspection and maintenance. As part of the validation of the Diagnostic and prognostic system, Carbon/Epoxy ASTM coupons were fabricated and tested to extract the mechanical properties. Subsequently two composite stiffened panels were manufactured, instrumented and tested under compressive loading: 1) an undamaged stiffened buckling panel; and 2) a damaged stiffened buckling panel including an initial diamond cut. Next numerical Finite element models of the two panels were developed and analyzed under test conditions using Multi-Scale Progressive Failure Analysis (an extension of FEM) to evaluate the damage/fracture evolution process, as well as the identification of contributing failure modes. The comparisons between predictions and test results were within 10% accuracy.

A method for the on-site determination of prestressing forces using long-gauge fiber optic strain sensors

NASA Astrophysics Data System (ADS)

Abdel-Jaber, H.; Glisic, B.

2014-07-01

Structural health monitoring (SHM) consists of the continuous or periodic measurement of structural parameters and their analysis with the aim of deducing information about the performance and health condition of a structure. The significant increase in the construction of prestressed concrete bridges motivated this research on an SHM method for the on-site determination of the distribution of prestressing forces along prestressed concrete beam structures. The estimation of the distribution of forces is important as it can give information regarding the overall performance and structural integrity of the bridge. An inadequate transfer of the designed prestressing forces to the concrete cross-section can lead to a reduced capacity of the bridge and consequently malfunction or failure at lower loads than predicted by design. This paper researches a universal method for the determination of the distribution of prestressing forces along concrete beam structures at the time of transfer of the prestressing force (e.g., at the time of prestressing or post-tensioning). The method is based on the use of long-gauge fiber optic sensors, and the sensor network is similar (practically identical) to the one used for damage identification. The method encompasses the determination of prestressing forces at both healthy and cracked cross-sections, and for the latter it can yield information about the condition of the cracks. The method is validated on-site by comparison to design forces through the application to two structures: (1) a deck-stiffened arch and (2) a curved continuous girder. The uncertainty in the determination of prestressing forces was calculated and the comparison with the design forces has shown very good agreement in most of the structures’ cross-sections, but also helped identify some unusual behaviors. The method and its validation are presented in this paper.

Bridging quantum mechanics and structure-based drug design.

PubMed

De Vivo, Marco

2011-01-01

The last decade has seen great advances in the use of quantum mechanics (QM) to solve biological problems of pharmaceutical relevance. For instance, enzymatic catalysis is often investigated by means of the so-called QM/MM approach, which uses QM and molecular mechanics (MM) methods to determine the (free) energy landscape of the enzymatic reaction mechanism. Here, I will discuss a few representative examples of QM and QM/MM studies of important metalloenzymes of pharmaceutical interest (i.e. metallophosphatases and metallo-beta-lactamases). This review article aims to show how QM-based methods can be used to elucidate ligand-receptor interactions. The challenge is then to exploit this knowledge for the structure-based design of new and potent inhibitors, such as transition state (TS) analogues that resemble the structure and physicochemical properties of the enzymatic TS. Given the results and potential expressed to date by QM-based methods in studying biological problems, the application of QM in structure-based drug design will likely increase, making of these once-prohibitive computations a routinely used tool for drug design.

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

Kirouac, Kevin N.; Ling, Hong; UWO)

Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP andmore » dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity.« less

A broadband vibro-impacting power harvester with symmetrical piezoelectric bimorph-stops

NASA Astrophysics Data System (ADS)

Moss, S.; Barry, A.; Powlesland, I.; Galea, S.; Carman, G. P.

2011-04-01

The certification of retrofitted structural health monitoring (SHM) systems for use on aircraft raises a number of challenges. One critical issue is determining the optimal means of supplying power to these systems, given that access to the existing aircraft power system is often problematic. Previously, the Australian Defence Science and Technology Organisation has shown that a structural strain-based energy harvesting approach can be used to power a device for SHM of aircraft structure. Acceleration-based power harvesting from airframes can be more demanding than a strain-based approach because the vibration spectrum of an aircraft structure can vary dynamically with flight conditions. A vibration spectrum with varying frequency may severely limit the energy harvested by a single-degree-of-freedom resonance-based device, and hence a frequency agile or (relatively) broadband device is often required to maximize the energy harvested. This paper reports on an investigation into the use of a vibro-impact approach to construct a piezoelectric-based kinetic power harvester that can operate in the approximate frequency range of 29-63 Hz.

44 CFR 65.5 - Revision to special hazard area boundaries with no change to base flood elevation determinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... flood elevation. Scientific and technical information to support a request to gain exclusion from an... hazard. (4) Written assurance by the participating community that they have complied with the appropriate... participating community has determined that the land and any existing or proposed structures to be removed from...

Autonomy, Competence, and Intrinsic Motivation in Science Education: A Self- Determination Theory Perspective

ERIC Educational Resources Information Center

Painter, Jason

2011-01-01

The purpose of this study was to examine a proposed motivational model of science achievement based on self-determination theory. The study relied on U.S. eighth-grade science data from the 2007 Third International Mathematics and Science Study to examine a structural model that hypothesized how perceived autonomy support, perceived competence in…

How an Inquiry-Based Classroom Lesson Intervenes in Science Efficacy, Career-Orientation and Self-Determination

ERIC Educational Resources Information Center

Schmid, S.; Bogner, F. X.

2017-01-01

Three subscales of the "Science Motivation Questionnaire II" (SMQII; motivational components: career motivation, self-efficacy and self-determination), with 4 items each, were applied to a sample of 209 secondary school students to monitor the impact of a 3-hour structured inquiry lesson. Four testing points (before, immediately after, 6…

Determination of ethylenic residues in wood and TMP of spruce by FT-Raman spectroscopy

Treesearch

Umesh P. Agarwal; Sally A. Ralph

2008-01-01

A method based on FT-Raman spectroscopy is proposed for determining in situ concentrations of ethylenic residues in softwood lignin. Raman contributions at 1133 and 1654 cm-1, representing coniferaldehyde and coniferyl alcohol structures, respectively, were used in quantifying these units in spruce wood with subsequent conversion to concentrations in lignin. For...

Tutorial for Collecting and Processing Images of Composite Structures to Determine the Fiber Volume Fraction

NASA Technical Reports Server (NTRS)

Conklin, Lindsey

2017-01-01

Fiber-reinforced composite structures have become more common in aerospace components due to their light weight and structural efficiency. In general, the strength and stiffness of a composite structure are directly related to the fiber volume fraction, which is defined as the fraction of fiber volume to total volume of the composite. The most common method to measure the fiber volume fraction is acid digestion, which is a useful method when the total weight of the composite, the fiber weight, and the total weight can easily be obtained. However, acid digestion is a destructive test, so the material will no longer be available for additional characterization. Acid digestion can also be difficult to machine out specific components of a composite structure with complex geometries. These disadvantages of acid digestion led the author to develop a method to calculate the fiber volume fraction. The developed method uses optical microscopy to calculate the fiber area fraction based on images of the cross section of the composite. The fiber area fraction and fiber volume fraction are understood to be the same, based on the assumption that the shape and size of the fibers are consistent in the depth of the composite. This tutorial explains the developed method for optically determining fiber area fraction performed at NASA Langley Research Center.

Conductance based characterization of structure and hopping site density in 2D molecule-nanoparticle arrays

NASA Astrophysics Data System (ADS)

McCold, Cliff E.; Fu, Qiang; Howe, Jane Y.; Hihath, Joshua

2015-09-01

Composite molecule-nanoparticle hybrid systems have recently emerged as important materials for applications ranging from chemical sensing to nanoscale electronics. However, creating reproducible and repeatable composite materials with precise properties has remained one of the primary challenges to the implementation of these technologies. Understanding the sources of variation that dominate the assembly and transport behavior is essential for the advancement of nanoparticle-array based devices. In this work, we use a combination of charge-transport measurements, electron microscopy, and optical characterization techniques to determine the role of morphology and structure on the charge transport properties of 2-dimensional monolayer arrays of molecularly-interlinked Au nanoparticles. Using these techniques we are able to determine the role of both assembly-dependent and particle-dependent defects on the conductivities of the films. These results demonstrate that assembly processes dominate the dispersion of conductance values, while nanoparticle and ligand features dictate the mean value of the conductance. By performing a systematic study of the conductance of these arrays as a function of nanoparticle size we are able to extract the carrier mobility for specific molecular ligands. We show that nanoparticle polydispersity correlates with the void density in the array, and that because of this correlation it is possible to accurately determine the void density within the array directly from conductance measurements. These results demonstrate that conductance-based measurements can be used to accurately and non-destructively determine the morphological and structural properties of these hybrid arrays, and thus provide a characterization platform that helps move 2-dimensional nanoparticle arrays toward robust and reproducible electronic systems.Composite molecule-nanoparticle hybrid systems have recently emerged as important materials for applications ranging from chemical sensing to nanoscale electronics. However, creating reproducible and repeatable composite materials with precise properties has remained one of the primary challenges to the implementation of these technologies. Understanding the sources of variation that dominate the assembly and transport behavior is essential for the advancement of nanoparticle-array based devices. In this work, we use a combination of charge-transport measurements, electron microscopy, and optical characterization techniques to determine the role of morphology and structure on the charge transport properties of 2-dimensional monolayer arrays of molecularly-interlinked Au nanoparticles. Using these techniques we are able to determine the role of both assembly-dependent and particle-dependent defects on the conductivities of the films. These results demonstrate that assembly processes dominate the dispersion of conductance values, while nanoparticle and ligand features dictate the mean value of the conductance. By performing a systematic study of the conductance of these arrays as a function of nanoparticle size we are able to extract the carrier mobility for specific molecular ligands. We show that nanoparticle polydispersity correlates with the void density in the array, and that because of this correlation it is possible to accurately determine the void density within the array directly from conductance measurements. These results demonstrate that conductance-based measurements can be used to accurately and non-destructively determine the morphological and structural properties of these hybrid arrays, and thus provide a characterization platform that helps move 2-dimensional nanoparticle arrays toward robust and reproducible electronic systems. Electronic supplementary information (ESI) available: Temperature dependent measurements, activation energies, particle size distributions, void density-polydispersity relation, and DLS data. See DOI: 10.1039/c5nr04460j

Accurate Structural Correlations from Maximum Likelihood Superpositions

PubMed Central

Theobald, Douglas L; Wuttke, Deborah S

2008-01-01

The cores of globular proteins are densely packed, resulting in complicated networks of structural interactions. These interactions in turn give rise to dynamic structural correlations over a wide range of time scales. Accurate analysis of these complex correlations is crucial for understanding biomolecular mechanisms and for relating structure to function. Here we report a highly accurate technique for inferring the major modes of structural correlation in macromolecules using likelihood-based statistical analysis of sets of structures. This method is generally applicable to any ensemble of related molecules, including families of nuclear magnetic resonance (NMR) models, different crystal forms of a protein, and structural alignments of homologous proteins, as well as molecular dynamics trajectories. Dominant modes of structural correlation are determined using principal components analysis (PCA) of the maximum likelihood estimate of the correlation matrix. The correlations we identify are inherently independent of the statistical uncertainty and dynamic heterogeneity associated with the structural coordinates. We additionally present an easily interpretable method (“PCA plots”) for displaying these positional correlations by color-coding them onto a macromolecular structure. Maximum likelihood PCA of structural superpositions, and the structural PCA plots that illustrate the results, will facilitate the accurate determination of dynamic structural correlations analyzed in diverse fields of structural biology. PMID:18282091

Methods for Combining Payload Parameter Variations with Input Environment

NASA Technical Reports Server (NTRS)

Merchant, D. H.; Straayer, J. W.

1975-01-01

Methods are presented for calculating design limit loads compatible with probabilistic structural design criteria. The approach is based on the concept that the desired limit load, defined as the largest load occuring in a mission, is a random variable having a specific probability distribution which may be determined from extreme-value theory. The design limit load, defined as a particular value of this random limit load, is the value conventionally used in structural design. Methods are presented for determining the limit load probability distributions from both time-domain and frequency-domain dynamic load simulations. Numerical demonstrations of the methods are also presented.

Macromolecular structure of coals. 6. Mass spectroscopic analysis of coal-derived liquids

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

Hooker, D.T.; Lucht, L.M.; Peppas, N.A.

1986-02-01

The macromolecular structure of coal networks was analyzed by depolymerizing coal samples using the Sternberg reductive alkylation and the Miyake alkylation techniques. Electron impact mass spectra showed peaks of greater abundance of 125-132, 252-260, 383-391, and 511-520 m/z ratios. Based on analysis of the patterns of the spectra, the cluster size of the cross-linked structure of bituminous coals was determined as 126-130. Various chemical species were identified.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

PubMed

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

PubMed Central

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. PMID:28243062

Solution structure of a DNA duplex containing a cis-diammineplatinum(II) 1,3-d(GTG) intrastrand cross-link, a major adduct in cells treated with the anticancer drug carboplatin.

PubMed

Teuben, J M; Bauer, C; Wang, A H; Reedijk, J

1999-09-21

The platinum 1,3-d(GXG) intrastrand cross-link is one of the adducts formed in the reaction of the antitumor drug cisplatin with DNA, and in fact the major adduct found in cells treated with the cisplatin analogue carboplatin. To determine the 3D structure of this adduct, the duplex d(CTCTGTGTCTC).d(GAGACACAGAG)], where GTG denotes a platinum 1,3-intrastrand cross-link, was prepared and studied with high-resolution (1)H NMR. The solution structure was determined using the SPEDREF protocol, which includes an iterative NOE-restrained refinement procedure. Calculated and recorded NOE spectra were found to be in good agreement (NMR R factor 22%). The studied duplex is more distorted from B-DNA than previously determined structures of the 1,2-d(GG) intrastrand adducts. The base pairing is lost for the 5'G-C and the central T-A base pair in the GTG lesion, and the central thymine is extruded from the minor groove. To accommodate this lesion, the minor groove is widened, and the 5'-guanine ribose adopts an N-type conformation. The helix is unwound locally and is significantly bent toward the major groove. Significant difference between the structural distortion of the 1, 3-d(GTG) cross-link and other Pt-DNA cross-links sheds new light on the observed differences in protein recognition of these lesions, and thus on the possible differences in mechanisms of action of the various Pt-DNA adducts formed in treatment with platinum anticancer complexes.

Swellix: a computational tool to explore RNA conformational space.

PubMed

Sloat, Nathan; Liu, Jui-Wen; Schroeder, Susan J

2017-11-21

The sequence of nucleotides in an RNA determines the possible base pairs for an RNA fold and thus also determines the overall shape and function of an RNA. The Swellix program presented here combines a helix abstraction with a combinatorial approach to the RNA folding problem in order to compute all possible non-pseudoknotted RNA structures for RNA sequences. The Swellix program builds on the Crumple program and can include experimental constraints on global RNA structures such as the minimum number and lengths of helices from crystallography, cryoelectron microscopy, or in vivo crosslinking and chemical probing methods. The conceptual advance in Swellix is to count helices and generate all possible combinations of helices rather than counting and combining base pairs. Swellix bundles similar helices and includes improvements in memory use and efficient parallelization. Biological applications of Swellix are demonstrated by computing the reduction in conformational space and entropy due to naturally modified nucleotides in tRNA sequences and by motif searches in Human Endogenous Retroviral (HERV) RNA sequences. The Swellix motif search reveals occurrences of protein and drug binding motifs in the HERV RNA ensemble that do not occur in minimum free energy or centroid predicted structures. Swellix presents significant improvements over Crumple in terms of efficiency and memory use. The efficient parallelization of Swellix enables the computation of sequences as long as 418 nucleotides with sufficient experimental constraints. Thus, Swellix provides a practical alternative to free energy minimization tools when multiple structures, kinetically determined structures, or complex RNA-RNA and RNA-protein interactions are present in an RNA folding problem.

Relations between benthic community structure and metals concentrations in aquatic macroinvertebrates: Clark Fork River, Montana

USGS Publications Warehouse

1995-01-01

We sampled macroinvertebrate communities at six sites on the upper Clark Fork River, Montana, to determine relations between macroinvertebrate community structure and metals in invertebrates and the best benthic community metrics to use for ranking sites based on the relative severity of the effects of metals. Concentrations (μg/g) of six metals in invertebrates were determined: Al (range = 591–4193), As (2.7–34.1), Cd (0.13–8.38), Cu (26–1382), Pb (0.54–67.1), and Zn (212–1665). Concentrations of As, Cd, Cu, Pb, and total metals were significantly correlated with at least one benthic metric. Copper (r = 0.88–0.94) and total metals (r = 0.90–0.97) provided the most highly significant correlations. Based on longitudinal site comparisons of metals in invertebrates, benthic community structure, and differences between proportionally scaled ranks, five benthic metrics provided the best indicators of relative impact: taxa richness, Ephemeroptera-Plecoptera-Trichoptera (EPT) richness, chironomid richness, percentage of the most dominant taxon, and density. The two sites with the highest accumulations of invertebrate metals also demonstrated the greatest relative degree of impact based on these parameters. The most meaningful combinations of metrics indicate that the benthic community at the most upstream site is being severely impacted by metals. Two sites demonstrated little or no negative impact, and three sites demonstrated low or moderate levels of negative impacts, which may be due to a combination of metals and other factors such as organic enrichment. We recommend that benthic community structure and metals in invertebrates collected from riffle habitats be used to determine relative impacts in metals-contaminated river systems, owing to their close relation to metal availability and transfer to higher trophic levels.

Overcoming barriers to membrane protein structure determination.

PubMed

Bill, Roslyn M; Henderson, Peter J F; Iwata, So; Kunji, Edmund R S; Michel, Hartmut; Neutze, Richard; Newstead, Simon; Poolman, Bert; Tate, Christopher G; Vogel, Horst

2011-04-01

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

A Critical Assessment of the Performance of Protein-ligand Scoring Functions Based on NMR Chemical Shift Perturbations

PubMed Central

Wang, Bing; Westerhoff, Lance M.; Merz, Kenneth M.

2008-01-01

We have generated docking poses for the FKBP-GPI complex using eight docking programs, and compared their scoring functions with scoring based on NMR chemical shift perturbations (NMRScore). Because the chemical shift perturbation (CSP) is exquisitely sensitive on the orientation of ligand inside the binding pocket, NMRScore offers an accurate and straightforward approach to score different poses. All scoring functions were inspected by their abilities to highly rank the native-like structures and separate them from decoy poses generated for a protein-ligand complex. The overall performance of NMRScore is much better than that of energy-based scoring functions associated with docking programs in both aspects. In summary, we find that the combination of docking programs with NMRScore results in an approach that can robustly determine the binding site structure for a protein-ligand complex, thereby, providing a new tool facilitating the structure-based drug discovery process. PMID:17867664

Progress in multirate digital control system design

NASA Technical Reports Server (NTRS)

Berg, Martin C.; Mason, Gregory S.

1991-01-01

A new methodology for multirate sampled-data control design based on a new generalized control law structure, two new parameter-optimization-based control law synthesis methods, and a new singular-value-based robustness analysis method are described. The control law structure can represent multirate sampled-data control laws of arbitrary structure and dynamic order, with arbitrarily prescribed sampling rates for all sensors and update rates for all processor states and actuators. The two control law synthesis methods employ numerical optimization to determine values for the control law parameters. The robustness analysis method is based on the multivariable Nyquist criterion applied to the loop transfer function for the sampling period equal to the period of repetition of the system's complete sampling/update schedule. The complete methodology is demonstrated by application to the design of a combination yaw damper and modal suppression system for a commercial aircraft.

[Using fractional polynomials to estimate the safety threshold of fluoride in drinking water].

PubMed

Pan, Shenling; An, Wei; Li, Hongyan; Yang, Min

2014-01-01

To study the dose-response relationship between fluoride content in drinking water and prevalence of dental fluorosis on the national scale, then to determine the safety threshold of fluoride in drinking water. Meta-regression analysis was applied to the 2001-2002 national endemic fluorosis survey data of key wards. First, fractional polynomial (FP) was adopted to establish fixed effect model, determining the best FP structure, after that restricted maximum likelihood (REML) was adopted to estimate between-study variance, then the best random effect model was established. The best FP structure was first-order logarithmic transformation. Based on the best random effect model, the benchmark dose (BMD) of fluoride in drinking water and its lower limit (BMDL) was calculated as 0.98 mg/L and 0.78 mg/L. Fluoride in drinking water can only explain 35.8% of the variability of the prevalence, among other influencing factors, ward type was a significant factor, while temperature condition and altitude were not. Fractional polynomial-based meta-regression method is simple, practical and can provide good fitting effect, based on it, the safety threshold of fluoride in drinking water of our country is determined as 0.8 mg/L.

Objective identification of residue ranges for the superposition of protein structures

PubMed Central

2011-01-01

Background The automation of objectively selecting amino acid residue ranges for structure superpositions is important for meaningful and consistent protein structure analyses. So far there is no widely-used standard for choosing these residue ranges for experimentally determined protein structures, where the manual selection of residue ranges or the use of suboptimal criteria remain commonplace. Results We present an automated and objective method for finding amino acid residue ranges for the superposition and analysis of protein structures, in particular for structure bundles resulting from NMR structure calculations. The method is implemented in an algorithm, CYRANGE, that yields, without protein-specific parameter adjustment, appropriate residue ranges in most commonly occurring situations, including low-precision structure bundles, multi-domain proteins, symmetric multimers, and protein complexes. Residue ranges are chosen to comprise as many residues of a protein domain that increasing their number would lead to a steep rise in the RMSD value. Residue ranges are determined by first clustering residues into domains based on the distance variance matrix, and then refining for each domain the initial choice of residues by excluding residues one by one until the relative decrease of the RMSD value becomes insignificant. A penalty for the opening of gaps favours contiguous residue ranges in order to obtain a result that is as simple as possible, but not simpler. Results are given for a set of 37 proteins and compared with those of commonly used protein structure validation packages. We also provide residue ranges for 6351 NMR structures in the Protein Data Bank. Conclusions The CYRANGE method is capable of automatically determining residue ranges for the superposition of protein structure bundles for a large variety of protein structures. The method correctly identifies ordered regions. Global structure superpositions based on the CYRANGE residue ranges allow a clear presentation of the structure, and unnecessary small gaps within the selected ranges are absent. In the majority of cases, the residue ranges from CYRANGE contain fewer gaps and cover considerably larger parts of the sequence than those from other methods without significantly increasing the RMSD values. CYRANGE thus provides an objective and automatic method for standardizing the choice of residue ranges for the superposition of protein structures. PMID:21592348

Synthesis and crystal structure analysis of uranyl triple acetates

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

Klepov, Vladislav V., E-mail: vladislavklepov@gmail.com; Department of Chemistry, Samara National Research University, 443086 Samara; Serezhkina, Larisa B.

2016-12-15

Single crystals of triple acetates NaR[UO{sub 2}(CH{sub 3}COO){sub 3}]{sub 3}·6H{sub 2}O (R=Mg, Co, Ni, Zn), well-known for their use as reagents for sodium determination, were grown from aqueous solutions and their structural and spectroscopic properties were studied. Crystal structures of the mentioned phases are based upon (Na[UO{sub 2}(CH{sub 3}COO){sub 3}]{sub 3}){sup 2–} clusters and [R(H{sub 2}O){sub 6}]{sup 2+} aqua-complexes. The cooling of a single crystal of NaMg[UO{sub 2}(CH{sub 3}COO){sub 3}]{sub 3}·6H{sub 2}O from 300 to 100 K leads to a phase transition from trigonal to monoclinic crystal system. Intermolecular interactions between the structural units and their mutual packing were studiedmore » and compared from the point of view of the stereoatomic model of crystal structures based on Voronoi-Dirichlet tessellation. Using this method we compared the crystal structures of the triple acetates with Na[UO{sub 2}(CH{sub 3}COO){sub 3}] and [R(H{sub 2}O){sub 6}][UO{sub 2}(CH{sub 3}COO){sub 3}]{sub 2} and proposed reasons of triple acetates stability. Infrared and Raman spectra were collected and their bands were assigned. - Graphical abstract: Single crystals of uranium based triple acetates, analytical reagents for sodium determination, were synthesized and structurally, spectroscopically and topologically characterized. The structures were compared with the structures of compounds from preceding families [M(H{sub 2}O){sub 6})][UO{sub 2}(CH{sub 3}COO){sub 3}]{sub 2} (M = Mg, Co, Ni, Zn) and Na[UO{sub 2}(CH{sub 3}COO){sub 3}]. Analysis was performed with the method of molecular Voronoi-Dirichlet polyhedra to reveal a large contribution of the hydrogen bonds into intermolecular interactions which can be a reason of low solubility of studied complexes.« less

Mass spectrometry based structural analysis and systems immunoproteomics strategies for deciphering the host response to endotoxin.

PubMed

Khan, Mohd M; Ernst, Orna; Sun, Jing; Fraser, Iain D C; Ernst, Robert K; Goodlett, David R; Nita-Lazar, Aleksandra

2018-06-24

One cause of sepsis is systemic maladaptive immune response of the host to bacteria and specifically, to Gram-negative bacterial outer membrane glycolipid lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS activates the innate immune system via Toll-like receptor-4 (TLR4)/myeloid differentiation factor-2 (MD2) complex. Intracellularly, LPS is also sensed by the noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The minimal functional determinant for innate immune activation is the membrane anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold can enable, diminish, or abolish immune activation. Bacteria are known to modify their LPS structure during environmental stress, and infection of hosts to alter cellular immune phenotypes. In this review, we describe how mass spectrometry (MS)-based structural analysis of endotoxin helped uncover major determinations of molecular pathogenesis. Through characterization of LPS modifications, we now better understand resistance to antibiotics and cationic antimicrobial peptides, as well as how the environment impacts overall endotoxin structure. In addition, MS-based systems immunoproteomics approaches can assist in elucidating the immune response against LPS. Many regulatory proteins have been characterized through proteomics and global/targeted analysis of protein modifications, enabling the discovery and characterization of novel endotoxin-mediated protein translational modifications (PTMs). Copyright © 2018. Published by Elsevier Ltd.

Elastic theory of origami-based metamaterials

NASA Astrophysics Data System (ADS)

Brunck, V.; Lechenault, F.; Reid, A.; Adda-Bedia, M.

2016-03-01

Origami offers the possibility for new metamaterials whose overall mechanical properties can be programed by acting locally on each crease. Starting from a thin plate and having knowledge about the properties of the material and the folding procedure, one would like to determine the shape taken by the structure at rest and its mechanical response. In this article, we introduce a vector deformation field acting on the imprinted network of creases that allows us to express the geometrical constraints of rigid origami structures in a simple and systematic way. This formalism is then used to write a general covariant expression of the elastic energy of n -creases meeting at a single vertex. Computations of the equilibrium states are then carried out explicitly in two special cases: the generalized waterbomb base and the Miura-Ori. For the waterbomb, we show a generic bistability for any number of creases. For the Miura folding, however, we uncover a phase transition from monostable to bistable states that explains the efficient deployability of this structure for a given range of geometrical and mechanical parameters. Moreover, the analysis shows that geometric frustration induces residual stresses in origami structures that should be taken into account in determining their mechanical response. This formalism can be extended to a general crease network, ordered or otherwise, and so opens new perspectives for the mechanics and the physics of origami-based metamaterials.

The Association Between Family Violence and Adolescent Dating Violence Onset: Does it Vary by Race, Socioeconomic Status, and Family Structure?

ERIC Educational Resources Information Center

Foshee, Vangie A.; Ennett, Susan T.; Bauman, Karl E.; Benefield, Thad; Suchindran, Chirayath

2005-01-01

The authors determine if the associations between family violence (corporal punishment, violence against the child with the intention of harm, and witnessing violence between parents) and adolescent dating violence vary by subgroups based on race, socioeconomic status, and family structure. This study is guided by the theoretical propositions of…

1983 Home Study Survey. A Report on Current Course Structure and Educational Practices in NHSC Member Institutions.

ERIC Educational Resources Information Center

National Home Study Council, Washington, DC.

A study examined the course structure and educational practices used by National Home Study Council (NHSC) member institutions. To gather data for the study, researchers mailed questionnaires to 60 members of the NHSC. Based on data from the 51 usable responses, the researchers determined that the average age of students enrolled in programs…

The Most Important Concept of Transport and Circulatory Systems: Turkish Biology Student Teachers' Cognitive Structure

ERIC Educational Resources Information Center

Kurt, Hakan; Ekici, Gulay; Aksu, Ozlem; Aktas, Murat

2013-01-01

The purpose of this study is to determine biology student teachers' cognitive structure with regard to "Blood". Qualitative research method has been used. The free word association test and the draw-write technique have been used in collection of data. The data obtained have been evaluated and divided into categories based on content…

Vegetation structure of plantain-based agrosystems determines numerical dominance in community of ground-dwelling ants

PubMed Central

Dassou, Anicet Gbéblonoudo; Tixier, Philippe; Dépigny, Sylvain

2017-01-01

In tropics, ants can represent an important part of animal biomass and are known to be involved in ecosystem services, such as pest regulation. Understanding the mechanisms underlying the structuring of local ant communities is therefore important in agroecology. In the humid tropics of Africa, plantains are cropped in association with many other annual and perennial crops. Such agrosystems differ greatly in vegetation diversity and structure and are well-suited for studying how habitat-related factors affect the ant community. We analysed abundance data for the six numerically dominant ant taxa in 500 subplots located in 20 diversified, plantain-based fields. We found that the density of crops with foliage at intermediate and high canopy strata determined the numerical dominance of species. We found no relationship between the numerical dominance of each ant taxon with the crop diversity. Our results indicate that the manipulation of the densities of crops with leaves in the intermediate and high strata may help maintain the coexistence of ant species by providing different habitat patches. Further research in such agrosystems should be performed to assess if the effect of vegetation structure on ant abundance could result in efficient pest regulation. PMID:29152414

A comparison of viscoelastic damping models

NASA Technical Reports Server (NTRS)

Slater, Joseph C.; Belvin, W. Keith; Inman, Daniel J.

1993-01-01

Modern finite element methods (FEM's) enable the precise modeling of mass and stiffness properties in what were in the past overwhelmingly large and complex structures. These models allow the accurate determination of natural frequencies and mode shapes. However, adequate methods for modeling highly damped and high frequency dependent structures did not exist until recently. The most commonly used method, Modal Strain Energy, does not correctly predict complex mode shapes since it is based on the assumption that the mode shapes of a structure are real. Recently, many techniques have been developed which allow the modeling of frequency dependent damping properties of materials in a finite element compatible form. Two of these methods, the Golla-Hughes-McTavish method and the Lesieutre-Mingori method, model the frequency dependent effects by adding coordinates to the existing system thus maintaining the linearity of the model. The third model, proposed by Bagley and Torvik, is based on the Fractional Calculus method and requires fewer empirical parameters to model the frequency dependence at the expense of linearity of the governing equations. This work examines the Modal Strain Energy, Golla-Hughes-McTavish and Bagley and Torvik models and compares them to determine the plausibility of using them for modeling viscoelastic damping in large structures.

Determination of a refractive index and an extinction coefficient of standard production of CVD-graphene.

PubMed

Ochoa-Martínez, Efraín; Gabás, Mercedes; Barrutia, Laura; Pesquera, Amaia; Centeno, Alba; Palanco, Santiago; Zurutuza, Amaia; Algora, Carlos

2015-01-28

The refractive index and extinction coefficient of chemical vapour deposition grown graphene are determined by ellipsometry analysis. Graphene films were grown on copper substrates and transferred as both monolayers and bilayers onto SiO2/Si substrates by using standard manufacturing procedures. The chemical nature and thickness of residual debris formed after the transfer process were elucidated using photoelectron spectroscopy. The real layered structure so deduced has been used instead of the nominal one as the input in the ellipsometry analysis of monolayer and bilayer graphene, transferred onto both native and thermal silicon oxide. The effect of these contamination layers on the optical properties of the stacked structure is noticeable both in the visible and the ultraviolet spectral regions, thus masking the graphene optical response. Finally, the use of heat treatment under a nitrogen atmosphere of the graphene-based stacked structures, as a method to reduce the water content of the sample, and its effect on the optical response of both graphene and the residual debris layer are presented. The Lorentz-Drude model proposed for the optical response of graphene fits fairly well the experimental ellipsometric data for all the analysed graphene-based stacked structures.

Vegetation structure of plantain-based agrosystems determines numerical dominance in community of ground-dwelling ants.

PubMed

Dassou, Anicet Gbéblonoudo; Tixier, Philippe; Dépigny, Sylvain; Carval, Dominique

2017-01-01

In tropics, ants can represent an important part of animal biomass and are known to be involved in ecosystem services, such as pest regulation. Understanding the mechanisms underlying the structuring of local ant communities is therefore important in agroecology. In the humid tropics of Africa, plantains are cropped in association with many other annual and perennial crops. Such agrosystems differ greatly in vegetation diversity and structure and are well-suited for studying how habitat-related factors affect the ant community. We analysed abundance data for the six numerically dominant ant taxa in 500 subplots located in 20 diversified, plantain-based fields. We found that the density of crops with foliage at intermediate and high canopy strata determined the numerical dominance of species. We found no relationship between the numerical dominance of each ant taxon with the crop diversity. Our results indicate that the manipulation of the densities of crops with leaves in the intermediate and high strata may help maintain the coexistence of ant species by providing different habitat patches. Further research in such agrosystems should be performed to assess if the effect of vegetation structure on ant abundance could result in efficient pest regulation.

Design and Optimization of Composite Automotive Hatchback Using Integrated Material-Structure-Process-Performance Method

NASA Astrophysics Data System (ADS)

Yang, Xudong; Sun, Lingyu; Zhang, Cheng; Li, Lijun; Dai, Zongmiao; Xiong, Zhenkai

2018-03-01

The application of polymer composites as a substitution of metal is an effective approach to reduce vehicle weight. However, the final performance of composite structures is determined not only by the material types, structural designs and manufacturing process, but also by their mutual restrict. Hence, an integrated "material-structure-process-performance" method is proposed for the conceptual and detail design of composite components. The material selection is based on the principle of composite mechanics such as rule of mixture for laminate. The design of component geometry, dimension and stacking sequence is determined by parametric modeling and size optimization. The selection of process parameters are based on multi-physical field simulation. The stiffness and modal constraint conditions were obtained from the numerical analysis of metal benchmark under typical load conditions. The optimal design was found by multi-discipline optimization. Finally, the proposed method was validated by an application case of automotive hatchback using carbon fiber reinforced polymer. Compared with the metal benchmark, the weight of composite one reduces 38.8%, simultaneously, its torsion and bending stiffness increases 3.75% and 33.23%, respectively, and the first frequency also increases 44.78%.

Finite element study of scaffold architecture design and culture conditions for tissue engineering.

PubMed

Olivares, Andy L; Marsal, Elia; Planell, Josep A; Lacroix, Damien

2009-10-01

Tissue engineering scaffolds provide temporary mechanical support for tissue regeneration and transfer global mechanical load to mechanical stimuli to cells through its architecture. In this study the interactions between scaffold pore morphology, mechanical stimuli developed at the cell microscopic level, and culture conditions applied at the macroscopic scale are studied on two regular scaffold structures. Gyroid and hexagonal scaffolds of 55% and 70% porosity were modeled in a finite element analysis and were submitted to an inlet fluid flow or compressive strain. A mechanoregulation theory based on scaffold shear strain and fluid shear stress was applied for determining the influence of each structures on the mechanical stimuli on initial conditions. Results indicate that the distribution of shear stress induced by fluid perfusion is very dependent on pore distribution within the scaffold. Gyroid architectures provide a better accessibility of the fluid than hexagonal structures. Based on the mechanoregulation theory, the differentiation process in these structures was more sensitive to inlet fluid flow than axial strain of the scaffold. This study provides a computational approach to determine the mechanical stimuli at the cellular level when cells are cultured in a bioreactor and to relate mechanical stimuli with cell differentiation.

Crystal structure and sequence-dependent conformation of the A.G mispaired oligonucleotide d(CGCAAGCTGGCG).

PubMed Central

Webster, G D; Sanderson, M R; Skelly, J V; Neidle, S; Swann, P F; Li, B F; Tickle, I J

1990-01-01

The crystal structure of the dodecanucleotide d(CGCAAGCTGGCG) has been determined to a resolution of 2.5 A and refined to an R factor of 19.3% for 1710 reflections. The sequence crystallizes as a B-type double helix, with two G(anti).A(syn) base pairs. These are stabilized by three-center hydrogen bonds to pyrimidines that induce perturbations in base-pair geometry. The central AGCT region of the helix has a wide (greater than 6 A) minor groove. PMID:2395870

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.

Microgravity

NASA Image and Video Library

2004-04-15

A semiconductor's usefulness is determined by how atoms are ordered within the crystal's underlying three-dimensional structure. While this mercury telluride and cadmium telluride alloy sample mixes completely in Earth -based laboratories, convective flows prevent them from mixing uniformly.

Position specific interaction dependent scoring technique for virtual screening based on weighted protein--ligand interaction fingerprint profiles.

PubMed

Nandigam, Ravi K; Kim, Sangtae; Singh, Juswinder; Chuaqui, Claudio

2009-05-01

The desire to exploit structural information to aid structure based design and virtual screening led to the development of the interaction fingerprint for analyzing, mining, and filtering the binding patterns underlying the complex 3D data. In this paper we introduce a new approach, weighted SIFt (or w-SIFt), extending the concept of SIFt to capture the relative importance of different binding interactions. The methodology presented here for determining the weights in w-SIFt involves utilizing a dimensionality reduction technique for eliminating linear redundancies in the data followed by a stochastic optimization. We find that the relative weights of the fingerprint bits provide insight into what interactions are critical in determining inhibitor potency. Moreover, the weighted interaction fingerprint can serve as an interpretable position dependent scoring function for ligand protein interactions.

Polarized Raman Spectroscopy for Determining the Orientation of di-D-phenylalanine Molecules in a Nanotube.

PubMed

Sereda, Valentin; Ralbovsky, Nicole M; Vasudev, Milana C; Naik, Rajesh R; Lednev, Igor K

2016-09-01

Self-assembly of short peptides into nanostructures has become an important strategy for the bottom-up fabrication of nanomaterials. Significant interest to such peptide-based building blocks is due to the opportunity to control the structure and properties of well-structured nanotubes, nanofibrils, and hydrogels. X-ray crystallography and solution NMR, two major tools of structural biology, have significant limitations when applied to peptide nanotubes because of their non-crystalline structure and large weight. Polarized Raman spectroscopy was utilized for structural characterization of well-aligned D-Diphenylalanine nanotubes. The orientation of selected chemical groups relative to the main axis of the nanotube was determined. Specifically, the C-N bond of CNH 3 + groups is oriented parallel to the nanotube axis, the peptides' carbonyl groups are tilted at approximately 54° from the axis and the COO - groups run perpendicular to the axis. The determined orientation of chemical groups allowed the understanding of the orientation of D-diphenylalanine molecule that is consistent with its equilibrium conformation. The obtained data indicate that there is only one orientation of D-diphenylalanine molecules with respect to the nanotube main axis.

New method for determining central axial orientation of flux rope embedded within current sheet using multipoint measurements

NASA Astrophysics Data System (ADS)

Li, ZhaoYu; Chen, Tao; Yan, GuangQing

2016-10-01

A new method for determining the central axial orientation of a two-dimensional coherent magnetic flux rope (MFR) via multipoint analysis of the magnetic-field structure is developed. The method is devised under the following geometrical assumptions: (1) on its cross section, the structure is left-right symmetric; (2) the projected structure velocity is vertical to the line of symmetry. The two conditions can be naturally satisfied for cylindrical MFRs and are expected to be satisfied for MFRs that are flattened within current sheets. The model test demonstrates that, for determining the axial orientation of such structures, the new method is more efficient and reliable than traditional techniques such as minimum-variance analysis of the magnetic field, Grad-Shafranov (GS) reconstruction, and the more recent method based on the cylindrically symmetric assumption. A total of five flux transfer events observed by Cluster are studied using the proposed approach, and the application results indicate that the observed structures, regardless of their actual physical properties, fit the assumed geometrical model well. For these events, the inferred axial orientations are all in excellent agreement with those obtained using the multi-GS reconstruction technique.

Characterization of the planetary boundary layer height and structure by Raman lidar: comparison of different approaches

NASA Astrophysics Data System (ADS)

Summa, D.; Di Girolamo, P.; Stelitano, D.; Cacciani, M.

2013-12-01

The planetary boundary layer (PBL) includes the portion of the atmosphere which is directly influenced by the presence of the earth's surface. Aerosol particles trapped within the PBL can be used as tracers to study the boundary-layer vertical structure and time variability. As a result of this, elastic backscatter signals collected by lidar systems can be used to determine the height and the internal structure of the PBL. The present analysis considers three different methods to estimate the PBL height. The first method is based on the determination of the first-order derivative of the logarithm of the range-corrected elastic lidar signals. Estimates of the PBL height for specific case studies obtained through this approach are compared with simultaneous estimates from the potential temperature profiles measured by radiosondes launched simultaneously to lidar operation. Additional estimates of the boundary layer height are based on the determination of the first-order derivative of the range-corrected rotational Raman lidar signals. This latter approach results to be successfully applicable also in the afternoon-evening decaying phase of the PBL, when the effectiveness of the approach based on the elastic lidar signals may be compromised or altered by the presence of the residual layer. Results from these different approaches are compared and discussed in the paper, with a specific focus on selected case studies collected by the University of Basilicata Raman lidar system BASIL during the Convective and Orographically-induced Precipitation Study (COPS).

Characterization of the planetary boundary layer height and structure by Raman lidar: comparison of different approaches

NASA Astrophysics Data System (ADS)

Summa, D.; Di Girolamo, P.; Stelitano, D.; Cacciani, M.

2013-06-01

The Planetary Boundary Layer (PBL) includes the portion of the atmosphere which is directly influenced by the presence of the Earth's surface. Aerosol particles trapped within the PBL can be used as tracers to study the boundary-layer vertical structure and time variability. As a result of this, elastic backscatter signals collected by lidar systems can be used to determine the height and the internal structure of the PBL. The present analysis considers three different methods to estimate the PBL height. A first method is based on the determination of the first order derivative of the logarithm of the range-corrected elastic lidar signals. Estimates of the PBL height for specific case studies obtained from this approach are compared with simultaneous estimates from the potential temperature profiles measured by radiosondes launched simultaneously to lidar operation. Additional estimates of the boundary layer height are based on the determination of the first order derivative of the range-corrected rotational Raman lidar signals. This latter approach results to be successfully applicable also in the afternoon-evening decaying phase of the PBL, when the effectiveness of the approach based on the elastic lidar signals may be compromised or altered by the presence of the residual layer. Results from these different approaches are compared and discussed in the paper, with a specific focus on selected case studies collected by the University of Basilicata Raman lidar system BASIL during the Convective and Orographically-induced Precipitation Study (COPS).

Biomotor structures in elite female handball players.

PubMed

Katić, Ratko; Cavala, Marijana; Srhoj, Vatromir

2007-09-01

In order to identify biomotor structures in elite female handball players, factor structures of morphological characteristics and basic motor abilities of elite female handball players (N = 53) were determined first, followed by determination of relations between the morphological-motor space factors obtained and the set of criterion variables evaluating situation motor abilities in handball. Factor analysis of 14 morphological measures produced three morphological factors, i.e. factor of absolute voluminosity (mesoendomorph), factor of longitudinal skeleton dimensionality, and factor of transverse hand dimensionality. Factor analysis of 15 motor variables yielded five basic motor dimensions, i.e. factor of agility, factor of jumping explosive strength, factor of throwing explosive strength, factor of movement frequency rate, and factor of running explosive strength (sprint). Four significant canonic correlations, i.e. linear combinations, explained the correlation between the set of eight latent variables of the morphological and basic motor space and five variables of situation motoricity. First canonic linear combination is based on the positive effect of the factors of agility/coordination on the ability of fast movement without ball. Second linear combination is based on the effect of jumping explosive strength and transverse hand dimensionality on ball manipulation, throw precision, and speed of movement with ball. Third linear combination is based on the running explosive strength determination by the speed of movement with ball, whereas fourth combination is determined by throwing and jumping explosive strength, and agility on ball pass. The results obtained were consistent with the model of selection in female handball proposed (Srhoj et al., 2006), showing the speed of movement without ball and the ability of ball manipulation to be the predominant specific abilities, as indicated by the first and second linear combination.

Research on connection structure of aluminumbody bus using multi-objective topology optimization

NASA Astrophysics Data System (ADS)

Peng, Q.; Ni, X.; Han, F.; Rhaman, K.; Ulianov, C.; Fang, X.

2018-01-01

For connecting Aluminum Alloy bus body aluminum components often occur the problem of failure, a new aluminum alloy connection structure is designed based on multi-objective topology optimization method. Determining the shape of the outer contour of the connection structure with topography optimization, establishing a topology optimization model of connections based on SIMP density interpolation method, going on multi-objective topology optimization, and improving the design of the connecting piece according to the optimization results. The results show that the quality of the aluminum alloy connector after topology optimization is reduced by 18%, and the first six natural frequencies are improved and the strength performance and stiffness performance are obviously improved.

Fast iodide-SAD phasing for high-throughput membrane protein structure determination

PubMed Central

Melnikov, Igor; Polovinkin, Vitaly; Kovalev, Kirill; Gushchin, Ivan; Shevtsov, Mikhail; Shevchenko, Vitaly; Mishin, Alexey; Alekseev, Alexey; Rodriguez-Valera, Francisco; Borshchevskiy, Valentin; Cherezov, Vadim; Leonard, Gordon A.; Gordeliy, Valentin; Popov, Alexander

2017-01-01

We describe a fast, easy, and potentially universal method for the de novo solution of the crystal structures of membrane proteins via iodide–single-wavelength anomalous diffraction (I-SAD). The potential universality of the method is based on a common feature of membrane proteins—the availability at the hydrophobic-hydrophilic interface of positively charged amino acid residues with which iodide strongly interacts. We demonstrate the solution using I-SAD of four crystal structures representing different classes of membrane proteins, including a human G protein–coupled receptor (GPCR), and we show that I-SAD can be applied using data collection strategies based on either standard or serial x-ray crystallography techniques. PMID:28508075

Fast iodide-SAD phasing for high-throughput membrane protein structure determination.

PubMed

Melnikov, Igor; Polovinkin, Vitaly; Kovalev, Kirill; Gushchin, Ivan; Shevtsov, Mikhail; Shevchenko, Vitaly; Mishin, Alexey; Alekseev, Alexey; Rodriguez-Valera, Francisco; Borshchevskiy, Valentin; Cherezov, Vadim; Leonard, Gordon A; Gordeliy, Valentin; Popov, Alexander

2017-05-01

We describe a fast, easy, and potentially universal method for the de novo solution of the crystal structures of membrane proteins via iodide-single-wavelength anomalous diffraction (I-SAD). The potential universality of the method is based on a common feature of membrane proteins-the availability at the hydrophobic-hydrophilic interface of positively charged amino acid residues with which iodide strongly interacts. We demonstrate the solution using I-SAD of four crystal structures representing different classes of membrane proteins, including a human G protein-coupled receptor (GPCR), and we show that I-SAD can be applied using data collection strategies based on either standard or serial x-ray crystallography techniques.

Comparison of benthic bacterial community composition in nine streams

Treesearch

Xueqing Gao; Ola A. Olapade; Laura G. Leff

2005-01-01

In this study, the abundance of major bacterial taxa (based on fluorescent in situ hybridization, FISH) and the structure of the bacterial community (based on denaturing gradient gel electrophoresis, DGGE) were determined in the benthos of 9 streams in the southeastern and midwestern United States and related to differences in environmental...

Camparison of benthic bacterial community composition in nine streams

Treesearch

Xuqing Gao; Ola A. Olapade; Laura G. Leff

2005-01-01

In this study, the abundance of major bacterial taxa (based on fluorescent in situ hybridization, FISH) and the structure of the bacterial community (based on denaturing gradient gel electrophoresis, DGGE) were determined in the benthos of 9 streams in the southeastern and midwestern United States and related to differences in environmental conditions. Taxa examined...

Competency-Based Hiring Interviews and University Teaching Performance

ERIC Educational Resources Information Center

Ellis, Jerald K.

2014-01-01

The purpose of this study was to determine if a pre-hire structured interview with competency-based behavioral questions can be linked to the teaching performance ratings of faculty at member institutions of the Florida State University System (SUS). Insights gained from this investigation can support the initiative for a proactive Human Resource…

Pure Perceptual-Based Sequence Learning: A Role for Visuospatial Attention

ERIC Educational Resources Information Center

Remillard, Gilbert

2009-01-01

Learning the structure of a sequence of target locations when target location is not the response dimension and the sequence of target locations is uncorrelated with the sequence of responses is called pure perceptual-based sequence learning. The paradigm introduced by G. Remillard (2003) was used to determine whether orienting of visuospatial…

English Language Teacher Educators' Pedagogical Knowledge Base: The Macro and Micro Categories

ERIC Educational Resources Information Center

Moradkhani, Shahab; Akbari, Ramin; Samar, Reza Ghafar; Kiany, Gholam Reza

2013-01-01

The aim of this study was to determine the major categories of English language teacher educators' pedagogical knowledge base. To this end, semi-structured interviews were conducted with 5 teachers, teacher educators, and university professors (15 participants in total). The results of data analysis indicated that teacher educators' pedagogical…

Understanding Player Activity in a Game-Based Virtual Learning Environment

ERIC Educational Resources Information Center

Boyer, David Matthew

2011-01-01

This study examines player activity in a game-based virtual learning environment as a means toward evaluating instructional and game design. By determining the goals embedded in project development and the availability and structure of in-game activities, the first part of this research highlights opportunities for players to engage with learning…

DNA-based approach to aging martens (Martes americana and M. caurina)

Treesearch

Jonathan N. Pauli; John P. Whiteman; Bruce G. Marcot; Terry M. McClean; Merav Ben-David

2011-01-01

Demographic structure is central to understanding the dynamics of animal populations. However, determining the age of free-ranging mammals is difficult, and currently impossible when sampling with noninvasive, genetic-based approaches. We present a method to estimate age class by combining measures of telomere lengths with other biologically meaningful covariates in a...

Traffic model for advanced satellite designs and experiments for ISDN services

NASA Technical Reports Server (NTRS)

Pepin, Gerard R.; Hager, E. Paul

1991-01-01

The data base structure and fields for categorizing and storing Integrated Services Digital Network (ISDN) user characteristics is outlined. This traffic model data base will be used to exercise models of the ISDN Advanced Communication Satellite to determine design parameters and performance for the NASA Satellite Communications Applications Research (SCAR) Program.

Structure of the 30 kDa HIV-1 RNA Dimerization Signal by a Hybrid Cryo-EM, NMR, and Molecular Dynamics Approach.

PubMed

Zhang, Kaiming; Keane, Sarah C; Su, Zhaoming; Irobalieva, Rossitza N; Chen, Muyuan; Van, Verna; Sciandra, Carly A; Marchant, Jan; Heng, Xiao; Schmid, Michael F; Case, David A; Ludtke, Steven J; Summers, Michael F; Chiu, Wah

2018-03-06

Cryoelectron microscopy (cryo-EM) and nuclear magnetic resonance (NMR) spectroscopy are routinely used to determine structures of macromolecules with molecular weights over 65 and under 25 kDa, respectively. We combined these techniques to study a 30 kDa HIV-1 dimer initiation site RNA ([DIS] 2 ; 47 nt/strand). A 9 Å cryo-EM map clearly shows major groove features of the double helix and a right-handed superhelical twist. Simulated cryo-EM maps generated from time-averaged molecular dynamics trajectories (10 ns) exhibited levels of detail similar to those in the experimental maps, suggesting internal structural flexibility limits the cryo-EM resolution. Simultaneous inclusion of the cryo-EM map and 2 H-edited NMR-derived distance restraints during structure refinement generates a structure consistent with both datasets and supporting a flipped-out base within a conserved purine-rich bulge. Our findings demonstrate the power of combining global and local structural information from these techniques for structure determination of modest-sized RNAs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular dynamics of bacteriorhodopsin.

PubMed

Lupo, J A; Pachter, R

1997-02-01

A model of bacteriorhodopsin (bR), with a retinal chromophore attached, has been derived for a molecular dynamics simulation. A method for determining atomic coordinates of several ill-defined strands was developed using a structure prediction algorithm based on a sequential Kalman filter technique. The completed structure was minimized using the GROMOS force field. The structure was then heated to 293 K and run for 500 ps at constant temperature. A comparison with the energy-minimized structure showed a slow increase in the all-atom RMS deviation over the first 200 ps, leveling off to approximately 2.4 A relative to the starting structure. The final structure yielded a backbone-atom RMS deviation from the crystallographic structure of 2.8 A. The residue neighbors of the chromophore atoms were followed as a function of time. The set of persistent near-residue neighbors supports the theory that differences in pKa values control access to the Schiff base proton, rather than formation of a counterion complex.

Development and applications of two computational procedures for determining the vibration modes of structural systems. [aircraft structures - aerospaceplanes

NASA Technical Reports Server (NTRS)

Kvaternik, R. G.

1975-01-01

Two computational procedures for analyzing complex structural systems for their natural modes and frequencies of vibration are presented. Both procedures are based on a substructures methodology and both employ the finite-element stiffness method to model the constituent substructures. The first procedure is a direct method based on solving the eigenvalue problem associated with a finite-element representation of the complete structure. The second procedure is a component-mode synthesis scheme in which the vibration modes of the complete structure are synthesized from modes of substructures into which the structure is divided. The analytical basis of the methods contains a combination of features which enhance the generality of the procedures. The computational procedures exhibit a unique utilitarian character with respect to the versatility, computational convenience, and ease of computer implementation. The computational procedures were implemented in two special-purpose computer programs. The results of the application of these programs to several structural configurations are shown and comparisons are made with experiment.

A holistic approach to determine tree structural complexity based on laser scanning data and fractal analysis.

PubMed

Seidel, Dominik

2018-01-01

The three-dimensional forest structure affects many ecosystem functions and services provided by forests. As forests are made of trees it seems reasonable to approach their structure by investigating individual tree structure. Based on three-dimensional point clouds from laser scanning, a newly developed holistic approach is presented that enables to calculate the box dimension as a measure of structural complexity of individual trees using fractal analysis. It was found that the box dimension of trees was significantly different among the tested species, among trees belonging to the same species but exposed to different growing conditions (at gap vs. forest interior) or to different kinds of competition (intraspecific vs. interspecific). Furthermore, it was shown that the box dimension is positively related to the trees' growth rate. The box dimension was identified as an easy to calculate measure that integrates the effect of several external drivers of tree structure, such as competition strength and type, while simultaneously providing information on structure-related properties, like tree growth.

Multilayer photosensitive structures based on porous silicon and rare-earth-element compounds: Study of spectral characteristics

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

Kirsanov, N. Yu.; Latukhina, N. V., E-mail: natalat@yandex.ru; Lizunkova, D. A.

2017-03-15

The spectral characteristics of the specular reflectance, photosensitivity, and photoluminescence (PL) of multilayer structures based on porous silicon with rare-earth-element (REE) ions are investigated. It is shown that the photosensitivity of these structures in the wavelength range of 0.4–1.0 μm is higher than in structures free of REEs. The structures with Er{sup 3+} ions exhibit a luminescence response at room temperature in the spectral range from 1.1 to 1.7 μm. The PL spectrum of the erbium impurity is characterized by a fine line structure, which is determined by the splitting of the {sup 4}I{sub 15/2} multiplet of the Er{sup 3+}more » ion. It is shown that the structures with a porous layer on the working surface have a much lower reflectance in the entire spectral range under study (0.2–1.0 μm).« less

Waveform Based Acoustic Emission Detection and Location of Matrix Cracking in Composites

NASA Technical Reports Server (NTRS)

Prosser, W. H.

1995-01-01

The operation of damage mechanisms in a material or structure under load produces transient acoustic waves. These acoustic waves are known as acoustic emission (AE). In composites they can be caused by a variety of sources including matrix cracking, fiber breakage, and delamination. AE signals can be detected and analyzed to determine the location of the acoustic source by triangulation. Attempts are also made to analyze the signals to determine the type and severity of the damage mechanism. AE monitoring has been widely used for both laboratory studies of materials, and for testing the integrity of structures in the field. In this work, an advanced, waveform based AE system was used in a study of transverse matrix cracking in cross-ply graphite/epoxy laminates. This AE system featured broad band, high fidelity sensors, and high capture rate digital acquisition and storage of acoustic signals. In addition, analysis techniques based on plate wave propagation models were employed. These features provided superior source location and noise rejection capabilities.

A technique for measurement of material damping in metals. [absorption of structural vibration

NASA Technical Reports Server (NTRS)

Heine, J. C.

1976-01-01

The paper outlines the theory, design, and application of an apparatus based on the single beam resonant dwell technique to determine the damping capacity of metallic materials by measuring the response of a structural element to excitation at a modal frequency. In this apparatus, a cantilever beam specimen of a test material is clamped to a bar which is connected at one end to an electromagnetic shaker and at the other to a heavy base. The thickness of the bar at the base end is reduced by two saw cuts to provide a pivot around which the remainder of the bar can rotate when excited by the shaker which is connected to the bar by a rod passing through a hole in the base. The response of the supporting system to shaker excitation is measured with an accelerometer mounted on the bar at the root of the specimen. Specimen response is measured optically with a low-power microscope with a reticle. Specimen loss factor is determined in terms of acceleration at the beam root, beam tip displacement, and the beam natural frequency.

A transversal approach for patch-based label fusion via matrix completion

PubMed Central

Sanroma, Gerard; Wu, Guorong; Gao, Yaozong; Thung, Kim-Han; Guo, Yanrong; Shen, Dinggang

2015-01-01

Recently, multi-atlas patch-based label fusion has received an increasing interest in the medical image segmentation field. After warping the anatomical labels from the atlas images to the target image by registration, label fusion is the key step to determine the latent label for each target image point. Two popular types of patch-based label fusion approaches are (1) reconstruction-based approaches that compute the target labels as a weighted average of atlas labels, where the weights are derived by reconstructing the target image patch using the atlas image patches; and (2) classification-based approaches that determine the target label as a mapping of the target image patch, where the mapping function is often learned using the atlas image patches and their corresponding labels. Both approaches have their advantages and limitations. In this paper, we propose a novel patch-based label fusion method to combine the above two types of approaches via matrix completion (and hence, we call it transversal). As we will show, our method overcomes the individual limitations of both reconstruction-based and classification-based approaches. Since the labeling confidences may vary across the target image points, we further propose a sequential labeling framework that first labels the highly confident points and then gradually labels more challenging points in an iterative manner, guided by the label information determined in the previous iterations. We demonstrate the performance of our novel label fusion method in segmenting the hippocampus in the ADNI dataset, subcortical and limbic structures in the LONI dataset, and mid-brain structures in the SATA dataset. We achieve more accurate segmentation results than both reconstruction-based and classification-based approaches. Our label fusion method is also ranked 1st in the online SATA Multi-Atlas Segmentation Challenge. PMID:26160394

From protein structure to function via single crystal optical spectroscopy

PubMed Central

Ronda, Luca; Bruno, Stefano; Bettati, Stefano; Storici, Paola; Mozzarelli, Andrea

2015-01-01

The more than 100,000 protein structures determined by X-ray crystallography provide a wealth of information for the characterization of biological processes at the molecular level. However, several crystallographic “artifacts,” including conformational selection, crystallization conditions and radiation damages, may affect the quality and the interpretation of the electron density maps, thus limiting the relevance of structure determinations. Moreover, for most of these structures, no functional data have been obtained in the crystalline state, thus posing serious questions on their validity in infereing protein mechanisms. In order to solve these issues, spectroscopic methods have been applied for the determination of equilibrium and kinetic properties of proteins in the crystalline state. These methods are UV-vis spectrophotometry, spectrofluorimetry, IR, EPR, Raman, and resonance Raman spectroscopy. Some of these approaches have been implemented with on-line instruments at X-ray synchrotron beamlines. Here, we provide an overview of investigations predominantly carried out in our laboratory by single crystal polarized absorption UV-vis microspectrophotometry, the most applied technique for the functional characterization of proteins in the crystalline state. Studies on hemoglobins, pyridoxal 5′-phosphate dependent enzymes and green fluorescent protein in the crystalline state have addressed key biological issues, leading to either straightforward structure-function correlations or limitations to structure-based mechanisms. PMID:25988179

ATOMIC RESOLUTION CRYO ELECTRON MICROSCOPY OF MACROMOLECULAR COMPLEXES

PubMed Central

ZHOU, Z. HONG

2013-01-01

Single-particle cryo electron microscopy (cryoEM) is a technique for determining three-dimensional (3D) structures from projection images of molecular complexes preserved in their “native,” noncrystalline state. Recently, atomic or near-atomic resolution structures of several viruses and protein assemblies have been determined by single-particle cryoEM, allowing ab initio atomic model building by following the amino acid side chains or nucleic acid bases identifiable in their cryoEM density maps. In particular, these cryoEM structures have revealed extended arms contributing to molecular interactions that are otherwise not resolved by the conventional structural method of X-ray crystallography at similar resolutions. High-resolution cryoEM requires careful consideration of a number of factors, including proper sample preparation to ensure structural homogeneity, optimal configuration of electron imaging conditions to record high-resolution cryoEM images, accurate determination of image parameters to correct image distortions, efficient refinement and computation to reconstruct a 3D density map, and finally appropriate choice of modeling tools to construct atomic models for functional interpretation. This progress illustrates the power of cryoEM and ushers it into the arsenal of structural biology, alongside conventional techniques of X-ray crystallography and NMR, as a major tool (and sometimes the preferred one) for the studies of molecular interactions in supramolecular assemblies or machines. PMID:21501817

NMR studies of protein-nucleic acid interactions.

PubMed

Varani, Gabriele; Chen, Yu; Leeper, Thomas C

2004-01-01

Protein-DNA and protein-RNA complexes play key functional roles in every living organism. Therefore, the elucidation of their structure and dynamics is an important goal of structural and molecular biology. Nuclear magnetic resonance (NMR) studies of protein and nucleic acid complexes have common features with studies of protein-protein complexes: the interaction surfaces between the molecules must be carefully delineated, the relative orientation of the two species needs to be accurately and precisely determined, and close intermolecular contacts defined by nuclear Overhauser effects (NOEs) must be obtained. However, differences in NMR properties (e.g., chemical shifts) and biosynthetic pathways for sample productions generate important differences. Chemical shift differences between the protein and nucleic acid resonances can aid the NMR structure determination process; however, the relatively limited dispersion of the RNA ribose resonances makes the process of assigning intermolecular NOEs more difficult. The analysis of the resulting structures requires computational tools unique to nucleic acid interactions. This chapter summarizes the most important elements of the structure determination by NMR of protein-nucleic acid complexes and their analysis. The main emphasis is on recent developments (e.g., residual dipolar couplings and new Web-based analysis tools) that have facilitated NMR studies of these complexes and expanded the type of biological problems to which NMR techniques of structural elucidation can now be applied.

Direct methods in protein crystallography.

PubMed

Karle, J

1989-11-01

It is pointed out that the 'direct methods' of phase determination for small-structure crystallography do not have immediate applicability to macromolecular structures. The term 'direct methods in macromolecular crystallography' is suggested to categorize a spectrum of approaches to macromolecular structure determination in which the analyses are characterized by the use of two-phase and higher-order-phase invariants. The evaluation of the invariants is generally obtained by the use of heavy-atom techniques. The results of a number of the more recent algebraic and probabilistic studies involving isomorphous replacement and anomalous dispersion thus become valid subjects for discussion here. These studies are described and suggestions are also presented concerning future applicability. Additional discussion concerns the special techniques of filtering, the use of non-crystallographic symmetry, some features of maximum entropy and attempts to apply phase-determining formulas to the refinement of macromolecular structure. It is noted that, in addition to the continuing remarkable progress in macromolecular crystallography based on the traditional applications of isomorphous replacement and anomalous dispersion, recent valuable advances have been made in the application of non-crystallographic symmetry, in particular, to virus structures and in applications of filtering. Good progress has also been reported in the application of exact linear algebra to multiple-wavelength anomalous-dispersion investigations of structures containing anomalous scatterers of only moderate scattering power.

Ab initio structure determination and quantitative disorder analysis on nanoparticles by electron diffraction tomography.

PubMed

Krysiak, Yaşar; Barton, Bastian; Marler, Bernd; Neder, Reinhard B; Kolb, Ute

2018-03-01

Nanoscaled porous materials such as zeolites have attracted substantial attention in industry due to their catalytic activity, and their performance in sorption and separation processes. In order to understand the properties of such materials, current research focuses increasingly on the determination of structural features beyond the averaged crystal structure. Small particle sizes, various types of disorder and intergrown structures render the description of structures at atomic level by standard crystallographic methods difficult. This paper reports the characterization of a strongly disordered zeolite structure, using a combination of electron exit-wave reconstruction, automated diffraction tomography (ADT), crystal disorder modelling and electron diffraction simulations. Zeolite beta was chosen for a proof-of-principle study of the techniques, because it consists of two different intergrown polymorphs that are built from identical layer types but with different stacking sequences. Imaging of the projected inner Coulomb potential of zeolite beta crystals shows the intergrowth of the polymorphs BEA and BEB. The structures of BEA as well as BEB could be extracted from one single ADT data set using direct methods. A ratio for BEA/BEB = 48:52 was determined by comparison of the reconstructed reciprocal space based on ADT data with simulated electron diffraction data for virtual nanocrystals, built with different ratios of BEA/BEB. In this way, it is demonstrated that this smart interplay of the above-mentioned techniques allows the elaboration of the real structures of functional materials in detail - even if they possess a severely disordered structure.

In-flight investigation of a rotating cylinder-based structural excitation system for flutter testing

NASA Technical Reports Server (NTRS)

Vernon, Lura

1993-01-01

A research excitation system was test flown at the NASA Dryden Flight Research Facility on the two-seat F-16XL aircraft. The excitation system is a wingtip-mounted vane with a rotating slotted cylinder at the trailing edge. As the cylinder rotates during flight, the flow is alternately deflected upward and downward through the slot, resulting in a periodic lift force at twice the cylinder's rotational frequency. Flight testing was conducted to determine the excitation system's effectiveness in the subsonic and transonic flight regimes. Primary research objectives were to determine the system's ability to develop adequate force levels to excite the aircraft's structure and to determine the frequency range over which the system could excite structural modes of the aircraft. The results from the exciter were compared with results from atmospheric turbulence excitation at the same flight conditions. The results from the forced excitation were of higher quality and had less variation than the results from atmospheric turbulence. The forced excitation data also invariably yielded higher structural damping values than those from the atmospheric turbulence data.

Vibration-based health monitoring and model refinement of civil engineering structures

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

Farrar, C.R.; Doebling, S.W.

1997-10-01

Damage or fault detection, as determined by changes in the dynamic properties of structures, is a subject that has received considerable attention in the technical literature beginning approximately 30 years ago. The basic idea is that changes in the structure`s properties, primarily stiffness, will alter the dynamic properties of the structure such as resonant frequencies and mode shapes, and properties derived from these quantities such as modal-based flexibility. Recently, this technology has been investigated for applications to health monitoring of large civil engineering structures. This presentation will discuss such a study undertaken by engineers from New Mexico Sate University, Sandiamore » National Laboratory and Los Alamos National Laboratory. Experimental modal analyses were performed in an undamaged interstate highway bridge and immediately after four successively more severe damage cases were inflicted in the main girder of the structure. Results of these tests provide insight into the abilities of modal-based damage ID methods to identify damage and the current limitations of this technology. Closely related topics that will be discussed are the use of modal properties to validate computer models of the structure, the use of these computer models in the damage detection process, and the general lack of experimental investigation of large civil engineering structures.« less

Structural Health Monitoring Using Textile Reinforcement Structures with Integrated Optical Fiber Sensors

PubMed Central

Bremer, Kort; Weigand, Frank; Zheng, Yulong; Alwis, Lourdes Shanika; Helbig, Reinhard; Roth, Bernhard

2017-01-01

Optical fiber-based sensors “embedded” in functionalized carbon structures (FCSs) and textile net structures (TNSs) based on alkaline-resistant glass are introduced for the purpose of structural health monitoring (SHM) of concrete-based structures. The design aims to monitor common SHM parameters such as strain and cracks while at the same time acting as a structural strengthening mechanism. The sensor performances of the two systems are characterized in situ using Mach-Zehnder interferometric (MZI) and optical attenuation measurement techniques, respectively. For this purpose, different FCS samples were subjected to varying elongation using a tensile testing machine by carefully incrementing the applied force, and good correlation between the applied force and measured length change was observed. For crack detection, the functionalized TNSs were embedded into a concrete block which was then exposed to varying load using the three-point flexural test until destruction. Promising results were observed, identifying that the location of the crack can be determined using the conventional optical time domain reflectometry (OTDR) technique. The embedded sensors thus evaluated show the value of the dual achievement of the schemes proposed in obtaining strain/crack measurement while being utilized as strengthening agents as well. PMID:28208636

Quantification of Soil Pore Structure Based on Minkowski-Functions

NASA Astrophysics Data System (ADS)

Vogel, H.; Weller, U.; Schlüter, S.

2009-05-01

The porous structure in soils and other geologic media is typically a complex 3-dimensional object. Most of the physical material properties including mechanical and hydraulic characteristics are immediately linked to this structure which can be directly observed using non-invasive techniques as e.g. X-ray tomography. It is an old dream and still a formidable challenge to related structural features of porous media to their physical properties. In this contribution we present a scale-invariant concept to quantify pore structure based on a limited set of meaningful morphological functions. They are based on d+1 Minkowski functionals as defined for d-dimensional bodies. These basic quantities are determined as a function of pore size obtained by filter procedures using mathematical morphology. The resulting Minkowski functions provide valuable information on pore size, pore surface area and pore topology having the potential to be linked to physical properties. The theoretical background and the related algorithms are presented and the approach is demonstrated for the structure of an arable topsoil obtained by X-ray micro tomography. We also discuss the fundamental problem of limited resolution which is critical for any attempt to quantify structural features at any scale.

Detection and Alignment of 3D Domain Swapping Proteins Using Angle-Distance Image-Based Secondary Structural Matching Techniques

PubMed Central

Wang, Hsin-Wei; Hsu, Yen-Chu; Hwang, Jenn-Kang; Lyu, Ping-Chiang; Pai, Tun-Wen; Tang, Chuan Yi

2010-01-01

This work presents a novel detection method for three-dimensional domain swapping (DS), a mechanism for forming protein quaternary structures that can be visualized as if monomers had “opened” their “closed” structures and exchanged the opened portion to form intertwined oligomers. Since the first report of DS in the mid 1990s, an increasing number of identified cases has led to the postulation that DS might occur in a protein with an unconstrained terminus under appropriate conditions. DS may play important roles in the molecular evolution and functional regulation of proteins and the formation of depositions in Alzheimer's and prion diseases. Moreover, it is promising for designing auto-assembling biomaterials. Despite the increasing interest in DS, related bioinformatics methods are rarely available. Owing to a dramatic conformational difference between the monomeric/closed and oligomeric/open forms, conventional structural comparison methods are inadequate for detecting DS. Hence, there is also a lack of comprehensive datasets for studying DS. Based on angle-distance (A-D) image transformations of secondary structural elements (SSEs), specific patterns within A-D images can be recognized and classified for structural similarities. In this work, a matching algorithm to extract corresponding SSE pairs from A-D images and a novel DS score have been designed and demonstrated to be applicable to the detection of DS relationships. The Matthews correlation coefficient (MCC) and sensitivity of the proposed DS-detecting method were higher than 0.81 even when the sequence identities of the proteins examined were lower than 10%. On average, the alignment percentage and root-mean-square distance (RMSD) computed by the proposed method were 90% and 1.8Å for a set of 1,211 DS-related pairs of proteins. The performances of structural alignments remain high and stable for DS-related homologs with less than 10% sequence identities. In addition, the quality of its hinge loop determination is comparable to that of manual inspection. This method has been implemented as a web-based tool, which requires two protein structures as the input and then the type and/or existence of DS relationships between the input structures are determined according to the A-D image-based structural alignments and the DS score. The proposed method is expected to trigger large-scale studies of this interesting structural phenomenon and facilitate related applications. PMID:20976204

Aromatic claw: A new fold with high aromatic content that evades structural prediction: Aromatic Claw

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

Sachleben, Joseph R.; Adhikari, Aashish N.; Gawlak, Grzegorz

2016-11-10

We determined the NMR structure of a highly aromatic (13%) protein of unknown function, Aq1974 from Aquifex aeolicus (PDB ID: 5SYQ). The unusual sequence of this protein has a tryptophan content five times the normal (six tryptophan residues of 114 or 5.2% while the average tryptophan content is 1.0%) with the tryptophans occurring in a WXW motif. It has no detectable sequence homology with known protein structures. Although its NMR spectrum suggested that the protein was rich in β-sheet, upon resonance assignment and solution structure determination, the protein was found to be primarily α-helical with a small two-stranded β-sheet withmore » a novel fold that we have termed an Aromatic Claw. As this fold was previously unknown and the sequence unique, we submitted the sequence to CASP10 as a target for blind structural prediction. At the end of the competition, the sequence was classified a hard template based model; the structural relationship between the template and the experimental structure was small and the predictions all failed to predict the structure. CSRosetta was found to predict the secondary structure and its packing; however, it was found that there was little correlation between CSRosetta score and the RMSD between the CSRosetta structure and the NMR determined one. This work demonstrates that even in relatively small proteins, we do not yet have the capacity to accurately predict the fold for all primary sequences. The experimental discovery of new folds helps guide the improvement of structural prediction methods.« less

A 'periodic table' for protein structures.

PubMed

Taylor, William R

2002-04-11

Current structural genomics programs aim systematically to determine the structures of all proteins coded in both human and other genomes, providing a complete picture of the number and variety of protein structures that exist. In the past, estimates have been made on the basis of the incomplete sample of structures currently known. These estimates have varied greatly (between 1,000 and 10,000; see for example refs 1 and 2), partly because of limited sample size but also owing to the difficulties of distinguishing one structure from another. This distinction is usually topological, based on the fold of the protein; however, in strict topological terms (neglecting to consider intra-chain cross-links), protein chains are open strings and hence are all identical. To avoid this trivial result, topologies are determined by considering secondary links in the form of intra-chain hydrogen bonds (secondary structure) and tertiary links formed by the packing of secondary structures. However, small additions to or loss of structure can make large changes to these perceived topologies and such subjective solutions are neither robust nor amenable to automation. Here I formalize both secondary and tertiary links to allow the rigorous and automatic definition of protein topology.

Crystal structure of product-bound complex of UDP-N-acetyl-D-mannosamine dehydrogenase from Pyrococcus horikoshii OT3

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

Pampa, K.J., E-mail: sagarikakj@gmail.com; Lokanath, N.K.; Girish, T.U.

Highlights: • Determined the structure of UDP-D-ManNAcADH to a resolution of 1.55 Å. • First complex structure of PhUDP-D-ManNAcADH with UDP-D-ManMAcA. • The monomeric structure consists of three distinct domains. • Cys258 acting as catalytic nucleophilic and Lys204 acts as acid/base catalyst. • Oligomeric state plays an important role for the catalytic function. - Abstract: UDP-N-acetyl-D-mannosamine dehydrogenase (UDP-D-ManNAcDH) belongs to UDP-glucose/GDP-mannose dehydrogenase family and catalyzes Uridine-diphospho-N-acetyl-D-mannosamine (UDP-D-ManNAc) to Uridine-diphospho-N-acetyl-D-mannosaminuronic acid (UDP-D-ManNAcA) through twofold oxidation of NAD{sup +}. In order to reveal the structural features of the Pyrococcus horikoshii UDP-D-ManNAcADH, we have determined the crystal structure of the product-bound enzyme bymore » X-ray diffraction to resolution of 1.55 Å. The protomer folds into three distinct domains; nucleotide binding domain (NBD), substrate binding domain (SBD) and oligomerization domain (OD, involved in the dimerization). The clear electron density of the UDP-D-ManNAcA is observed and the residues binding are identified for the first time. Crystal structures reveal a tight dimeric polymer chains with product-bound in all the structures. The catalytic residues Cys258 and Lys204 are conserved. The Cys258 acts as catalytic nucleophile and Lys204 as acid/base catalyst. The product is directly interacts with residues Arg211, Thr249, Arg244, Gly255, Arg289, Lys319 and Arg398. In addition, the structural parameters responsible for thermostability and oligomerization of the three dimensional structure are analyzed.« less

Structure determination of a major facilitator peptide transporter: Inward facing PepTSt from Streptococcus thermophilus crystallized in space group P3121

PubMed Central

Quistgaard, Esben M.; Martinez Molledo, Maria

2017-01-01

Major facilitator superfamily (MFS) peptide transporters (typically referred to as PepT, POT or PTR transporters) mediate the uptake of di- and tripeptides, and so play an important dietary role in many organisms. In recent years, a better understanding of the molecular basis for this process has emerged, which is in large part due to a steep increase in structural information. Yet, the conformational transitions underlying the transport mechanism are still not fully understood, and additional data is therefore needed. Here we report in detail the detergent screening, crystallization, experimental MIRAS phasing, and refinement of the peptide transporter PepTSt from Streptococcus thermophilus. The space group is P3121, and the protein is crystallized in a monomeric inward facing form. The binding site is likely to be somewhat occluded, as the lobe encompassing transmembrane helices 10 and 11 is markedly bent towards the central pore of the protein, but the extent of this potential occlusion could not be determined due to disorder at the apex of the lobe. Based on structural comparisons with the seven previously determined P212121 and C2221 structures of inward facing PepTSt, the structural flexibility as well as the conformational changes mediating transition between the inward open and inward facing occluded states are discussed. In conclusion, this report improves our understanding of the structure and conformational cycle of PepTSt, and can furthermore serve as a case study, which may aid in supporting future structure determinations of additional MFS transporters or other integral membrane proteins. PMID:28264013

Optimization of Cost of Building with Concrete Slabs Based on the Maturity Method

NASA Astrophysics Data System (ADS)

Skibicki, Szymon

2017-10-01

The maturity method is a well-known technique for determination of mechanical properties of the concrete (e.g. compressive strength) based on the development of temperature during hardening. The compressive strength of concrete can be used to determine necessary striking time of the formwork. Use of this method for this purpose is economically effective and provides necessary safety measures. This method is used in many construction sites. Time of formwork striking depends on many factors e. g. class of concrete, grade of cement, type of cement, temperature, size of the element and air humidity. The existing technical Standards and scientific research on the striking of formwork present different estimated for the striking time. Striking time for the main structural elements ranges from 14 to 21 days. For structura elements such as slabs or beams with a span of more than 6 m need to reach the minimum of 70-85% of their designed strength to remove the formwork depend on the Standards. During the construction of the buildings in summer concrete acquires the required strength for striking of the formwork faster due to the higher ambient temperature. Knowing the maturity method, we are able to estimate the compressive strength of concrete. If concrete have the required strength, the striking time can be shortened. This allows to reduce the overall costs of construction. The more concrete works are done during the construction phase the bigger the generated savings. In this article formwork striking time for concrete slabs in building based on maturity method was determined. The structure was subjected to 10 different simulated weather conditions typical for the Central and Western Europe that varied by localization of the construction. Based on simulated weather conditions the temperature in structural elements was established. The results allowed to determine the formwork striking time using the maturity method. Presented analysis shows that use of the maturity method on construction site can result in lower overall costs due to shorter time of constructing.

Update of the equations of the limit state of the structural material with the realization of their deformation

NASA Astrophysics Data System (ADS)

Zenkov, E. V.

2018-01-01

Two methods are given in the article by considering the type of stressed-Deformed state (SDS) based on equations limit condition and analyzing the results of laboratory tests of special specimens for mechanical testing, focus having destruction thereof in the same view of SDS as in focus possible destruction of the structural member. The considered limited use of these methods in terms of considering physically consistent strength criterion type Pisarenko-Lebedev. A revised design-experimental procedure for determining the strength of the material of the structure, combining therein the elements of these two methods, consisting in determining the strength parameters of construction material, entering criterion equation Pisarenko-Lebedev, considering the actual appearance of the region-of-interest SDS structure. The implementation of the procedure is performed on the basis of the selection of the respective experimental laboratory specimens for mechanical testing, plan SDS in working zone coinciding with a SDS: structure whose strength is evaluated. The refinement process limit state equations demonstrated in determining 50CrV4 steel strength parameters, being in a state of biaxial stretching. Design-experimentally determined by, that steel for a given voltage limit value is almost a quarter of its value is reduced compared to the conventional tensile strength. value is reduced compared to the conventional tensile strength.

Attenuation Tomography Based on Strong Motion Data: Case Study of Central Honshu Region, Japan

NASA Astrophysics Data System (ADS)

Kumar, Parveen; Joshi, A.; Verma, O. P.

2013-12-01

Three-dimensional frequency dependent S-wave quality factor (Qβ(f)) value for the central Honshu region of Japan has been determined in this paper using an algorithm based on inversion of strong motion data. The method of inversion for determination of three-dimensional attenuation coefficients is proposed by H ashida and S himazaki (J Phys Earth. 32, 299-316, 1984) and has been used and modified by J oshi (Curr Sci. 90, 581-585, 2006; Nat Hazards. 43, 129-146, 2007) and J oshi et al. (J. Seismol. 14, 247-272, 2010). Twenty-one earthquakes digitally recorded on strong motion stations of Kik-net network have been used in this work. The magnitude of these earthquake ranges from 3.1 to 4.2 and depth ranging from 5 to 20 km, respectively. The borehole data having high signal to noise ratio and minimum site effect is used in the present work. The attenuation structure is determined by dividing the entire area into twenty-five three-dimensional blocks of uniform thickness having different frequency-dependent shear wave quality factor. Shear wave quality factor values have been determined at frequencies of 2.5, 7.0 and 10 Hz from record in a rectangular grid defined by 35.4°N to 36.4°N and 137.2°E to 138.2°E. The obtained attenuation structure is compared with the available geological features in the region and comparison shows that the obtained structure is capable of resolving important tectonic features present in the area. The proposed attenuation structure is compared with the probabilistic seismic hazard map of the region and shows that it bears some remarkable similarity in the patterns seen in seismic hazard map.

Extending existing structural identifiability analysis methods to mixed-effects models.

PubMed

Janzén, David L I; Jirstrand, Mats; Chappell, Michael J; Evans, Neil D

2018-01-01

The concept of structural identifiability for state-space models is expanded to cover mixed-effects state-space models. Two methods applicable for the analytical study of the structural identifiability of mixed-effects models are presented. The two methods are based on previously established techniques for non-mixed-effects models; namely the Taylor series expansion and the input-output form approach. By generating an exhaustive summary, and by assuming an infinite number of subjects, functions of random variables can be derived which in turn determine the distribution of the system's observation function(s). By considering the uniqueness of the analytical statistical moments of the derived functions of the random variables, the structural identifiability of the corresponding mixed-effects model can be determined. The two methods are applied to a set of examples of mixed-effects models to illustrate how they work in practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Two-dimensional nuclear magnetic resonance structure determination module for introductory biochemistry: synthesis and structural characterization of lyso-glycerophospholipids.

PubMed

Garrett, Teresa A; Rose, Rebecca L; Bell, Sidney M

2013-01-01

In this laboratory module, introductory biochemistry students are exposed to two-dimensional (1) H-nuclear magnetic resonance of glycerophospholipids (GPLs). Working in groups of three, students enzymatically synthesized and purified a variety of 2-acyl lyso GPLs. The structure of the 2-acyl lyso GPL was verified using (1) H-correlation spectroscopy. Students scored significantly higher on an assessment of NMR knowledge after having participated in this lab module and in comparison to a similar cohort who did not participate. Inaddition, student confidence in their NMR knowledge and abilities increased 62% following the module and correlated with their ability to apply their NMR knowledge. Based on these results, the laboratory module was very effective at providing students with a more extensive understanding of the underlying concepts of NMR as a tool for structural determination. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

ROCOPT: A user friendly interactive code to optimize rocket structural components

NASA Technical Reports Server (NTRS)

Rule, William K.

1989-01-01

ROCOPT is a user-friendly, graphically-interfaced, microcomputer-based computer program (IBM compatible) that optimizes rocket components by minimizing the structural weight. The rocket components considered are ring stiffened truncated cones and cylinders. The applied loading is static, and can consist of any combination of internal or external pressure, axial force, bending moment, and torque. Stress margins are calculated by means of simple closed form strength of material type equations. Stability margins are determined by approximate, orthotropic-shell, closed-form equations. A modified form of Powell's method, in conjunction with a modified form of the external penalty method, is used to determine the minimum weight of the structure subject to stress and stability margin constraints, as well as user input constraints on the structural dimensions. The graphical interface guides the user through the required data prompts, explains program options and graphically displays results for easy interpretation.

Halo Nuclei

NASA Astrophysics Data System (ADS)

Al-Khalili, Jim

2017-10-01

While neutron halos were discovered 30 years ago, this is the first book written on the subject of this exotic form of nuclei that typically contain many more neutrons than stable isotopes of those elements. It provides an introductory description of the halo and outlines the discovery and evidence for its existence. It also discusses different theoretical models of the halo's structure as well as models and techniques in reaction theory that have allowed us to study the halo. This is written at the graduate student (starting at PhD) level. The author of the book, Jim Al-Khalili, is a theoretician who published some of the key papers on the structure of the halo in the mid and late 90s and was the first to determine its true size. This monograph is based on review articles he has written on the mathematical models used to determine the halo structure and the reactions used to model that structure.

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

NASA Astrophysics Data System (ADS)

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-Ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-02-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT.

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

PubMed Central

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-01-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator–activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT. PMID:25687586

Parasite infracommunities of a specialized marine fish species in a compound community dominated by generalist parasites.

PubMed

Lanfranchi, A L; Rossin, M A; Timi, J T

2009-12-01

The structure and composition of parasite communities of Mullus argentinae were analysed under two alternative hypotheses in a sample of 75 specimens caught off Mar del Plata, Argentina (38 degrees 27'S, 57 degrees 90'W). The first, based on the dominance of trophically transmitted larval parasites of low host-specificity among fish species in the region, predicts that infracommunities will be random subsets of regionally available species. The second, based on previous studies on other mullids, predicts that infracommunities will be dominated by adult digeneans. The parasite fauna of goatfishes was mainly composed of endoparasites, with metacercariae of Prosorhynchus australis accounting for most individual parasites and greatly affecting infracommunity descriptors. Its importance was reinforced by the low number of trophically transmitted larval parasites. Both hypotheses were refuted; parasite communities were not dominated either by trophically transmitted larval parasites of low host-specificity or by adult digeneans. Prosorhynchus australis was the only species displaying any degree of phylogenetic specificity. Therefore, the influence of phylogenetic factors seems to exceed that of ecological ones in determining the observed structure of infracommunities. However, it is precisely host ecology that allows P. australis to become the determinant of infracommunity structure by constraining the acquisition of other parasites. Studies aiming to determine the relative importance of evolutionary and ecological processes as structuring forces of parasite communities should take into account not only the identity and specificity of their component parasites, but also their availability in the compound community.

Effect of breed and sperm concentration on the changes in structural, functional and motility parameters of ram-lamb spermatozoa during storage at 4 degrees C.

PubMed

Kasimanickam, Ramanathan; Kasimanickam, Vanmathy; Pelzer, Kevin D; Dascanio, John J

2007-09-01

The objectives of this study were (1) to determine the changes in structural, functional and motility parameters of ram-lamb semen stored at two different concentrations at 4 degrees C for 8 days in egg-yolk based extender and (2) to determine the effect of breed of ram-lambs on the changes in structural, functional and motility parameters of ram-lamb semen from different breeds stored at two different concentrations at 4 degrees C for 8 days in egg-yolk based extender. Two different concentrations suitable for laparoscopic and cervical insemination were employed in this experiment. A total of 14 ram-lambs (Polled Dorset-5, Suffolk-5, Katahdin-4) with satisfactory breeding potential were selected. Semen samples were collected by electro-ejaculation. Semen samples were extended to 50 and 200 million sperm per ml with a commercial egg yolk based extender (Triladyl, Minitube of America, Verona, WI, USA) at room temperature and were stored at 4 degrees C. The sperm DNA fragmentation index (DFI), percentages of high mitochondrial membrane potential (hMMP) and plasma membrane integrity (PMI) were assessed using flow cytometry as part of structural and functional parameters on Days 0, 1, 4, 6, and 8. A computer assisted sperm analyser (HTM-IVOS, Version 10.8, Hamilton Thorne Research, Beverly, MA, USA) was used to assess the sperm motility parameters on Days 0, 1, 4, 6, and 8. PROC MIXED procedure was used to determine the effect of days of storage, concentration and breed. The concentration and days of storage significantly affected the sperm structural, functional and motility parameters (P<0.0001). Significant concentration x days of storage interaction was found for all structural and functional parameters. There was a significant concentration x days of storage interaction for average path velocity, curvilinear velocity, straightness and linearity. Overall changes in the sperm structural, functional and sperm motility parameters over the storage period were less dramatic in the 200 x 10(6) ml(-1) concentration when compared to 50 x 10(6) ml(-1) concentration. The hMMP and total progressive motility were influenced by breed. In conclusion, the quality of structural, functional and motility parameters declined as days of storage were increased and the magnitude of changes in the parameters was less dramatic at the higher concentration.

An improved wavelet-Galerkin method for dynamic response reconstruction and parameter identification of shear-type frames

NASA Astrophysics Data System (ADS)

Bu, Haifeng; Wang, Dansheng; Zhou, Pin; Zhu, Hongping

2018-04-01

An improved wavelet-Galerkin (IWG) method based on the Daubechies wavelet is proposed for reconstructing the dynamic responses of shear structures. The proposed method flexibly manages wavelet resolution level according to excitation, thereby avoiding the weakness of the wavelet-Galerkin multiresolution analysis (WGMA) method in terms of resolution and the requirement of external excitation. IWG is implemented by this work in certain case studies, involving single- and n-degree-of-freedom frame structures subjected to a determined discrete excitation. Results demonstrate that IWG performs better than WGMA in terms of accuracy and computation efficiency. Furthermore, a new method for parameter identification based on IWG and an optimization algorithm are also developed for shear frame structures, and a simultaneous identification of structural parameters and excitation is implemented. Numerical results demonstrate that the proposed identification method is effective for shear frame structures.

Structure-based inhibitors of tau aggregation

NASA Astrophysics Data System (ADS)

Seidler, P. M.; Boyer, D. R.; Rodriguez, J. A.; Sawaya, M. R.; Cascio, D.; Murray, K.; Gonen, T.; Eisenberg, D. S.

2018-02-01

Aggregated tau protein is associated with over 20 neurological disorders, which include Alzheimer's disease. Previous work has shown that tau's sequence segments VQIINK and VQIVYK drive its aggregation, but inhibitors based on the structure of the VQIVYK segment only partially inhibit full-length tau aggregation and are ineffective at inhibiting seeding by full-length fibrils. Here we show that the VQIINK segment is the more powerful driver of tau aggregation. Two structures of this segment determined by the cryo-electron microscopy method micro-electron diffraction explain its dominant influence on tau aggregation. Of practical significance, the structures lead to the design of inhibitors that not only inhibit tau aggregation but also inhibit the ability of exogenous full-length tau fibrils to seed intracellular tau in HEK293 biosensor cells into amyloid. We also raise the possibility that the two VQIINK structures represent amyloid polymorphs of tau that may account for a subset of prion-like strains of tau.

Protein-ligand complex structure from serial femtosecond crystallography using soaked thermolysin microcrystals and comparison with structures from synchrotron radiation.

PubMed

Naitow, Hisashi; Matsuura, Yoshinori; Tono, Kensuke; Joti, Yasumasa; Kameshima, Takashi; Hatsui, Takaki; Yabashi, Makina; Tanaka, Rie; Tanaka, Tomoyuki; Sugahara, Michihiro; Kobayashi, Jun; Nango, Eriko; Iwata, So; Kunishima, Naoki

2017-08-01

Serial femtosecond crystallography (SFX) with an X-ray free-electron laser is used for the structural determination of proteins from a large number of microcrystals at room temperature. To examine the feasibility of pharmaceutical applications of SFX, a ligand-soaking experiment using thermolysin microcrystals has been performed using SFX. The results were compared with those from a conventional experiment with synchrotron radiation (SR) at 100 K. A protein-ligand complex structure was successfully obtained from an SFX experiment using microcrystals soaked with a small-molecule ligand; both oil-based and water-based crystal carriers gave essentially the same results. In a comparison of the SFX and SR structures, clear differences were observed in the unit-cell parameters, in the alternate conformation of side chains, in the degree of water coordination and in the ligand-binding mode.

Vibration suppression and slewing control of a flexible structure

NASA Technical Reports Server (NTRS)

Inman, Daniel J.; Garcia, Ephrahim; Pokines, Brett

1991-01-01

Examined here are the effects of motor dynamics and secondary piezoceramic actuators on vibration suppression during the slewing of flexible structures. The approach focuses on the interaction between the structure, the actuators, and the choice of control law. The results presented here are all simulated, but are based on experimentally determined parameters for the motor, structure, piezoceramic actuators, and piezofilm sensors. The simulation results clearly illustrate that the choice of motor inertia relative to beam inertia makes a critical difference in the performance of the system. In addition, the use of secondary piezoelectric actuators reduces the load requirements on the motor and also reduces the overshoot of the tip deflection. The structures considered here are a beam and a frame. The majority of results are based on a Euler Bernoulli beam model. The slewing frame introduces substantial torsional modes and a more realistic model. The slewing frame results are incomplete and represent work in progress.

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

Jones, T.P.

Sensors for the determination of pH have been developed which are based on the immobilization of direct dyes at hydrolyzed cellulosic films. The performance and structural characteristics of the sensors were investigated by a variety of spectroscopic methods, and applications for remote sensing were developed. Films of cellulose acetate were base hydrolyzed in 0.07 M KOH to yield a porous support structure. The structural changes resulting from the hydrolysis on cellulose acetate were probed with infrared internal reflectance spectroscopy. The progress of the hydrolysis reaction was monitored by the changes in vibrational modes of the acetyl group, and other spectralmore » changes indicated changes in film thickness as a result of solvent incorporation. Direct dyes, including Congo Red and C. I. Direct Blue 8, were then immobilized at these porous cellulosic films. The optical response characteristics of the Congo Red pH sensor were characterized, including the UV-visible absorption spectra as a function of pH, the response time as a function of ionic strength and ionic size of electrolyte, the long-term stability of the sensor, the effects of metal-ion interference, and the concentration of Congo Red in the polymer film. The structural characteristics of the sensor were investigated by internal reflectance spectroscopy and resonance-enhanced Raman spectroscopy, and the protonation sites were identified as the two azo groups of Congo Red. Infrared internal reflection spectra of immobilized Congo Red led to the development of a sensor for pH based on infrared spectroscopy. Finally, a two-wavelength fiber-optic photometer, which is based on solid-state sources and detectors, and a fiber-optic photometer, which is based on solid-state sources and detectors, and a fiber-optic probe were developed for pH determinations using Congo Red and C. I. Direct Blue 8 pH sensors.« less

Effectiveness of a Computer-Based Syntax Program in Improving the Morphosyntax of Students Who Are Deaf/Hard of Hearing

ERIC Educational Resources Information Center

Cannon, Joanna E.

2010-01-01

The purpose of this study was to determine if the frequent use of LanguageLinks: Syntax Assessment and Intervention (LL), produced by Laureate Learning Systems, Inc., as a supplemental classroom activity, affected morphosyntax structures (determiners, tense, and complementizers) in participants who are Deaf/Hard of Hearing (DHH) and use American…